Cell-free microRNAs stably and abundantly exist in body fluids and emerging evidence suggests cell-free microRNAs as novel and non-invasive disease biomarker. Deregulation of miR-29 is involved in the pathogenesis of diabetic nephropathy and insulin resistance thus may be implicated in diabetic vascular complication. Therefore, we investigated the possibility of urinary miR-29 as biomarker for diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.
83 patients with type 2 diabetes were enrolled in this study, miR-29a, miR-29b and miR-29c levels in urine supernatant was determined by TaqMan qRT-PCR, and a synthetic cel-miR-39 was added to the urine as a spike-in control before miRNAs extraction. Urinary albumin excretion rate and urine albumin/creatinine ratio, funduscopy and carotid ultrasound were used for evaluation of diabetic vascular complication. The laboratory parameters indicating blood glucose level, renal function and serum lipids were also collected.
Patients with albuminuria (n = 42, age 60.62±12.00yrs) showed significantly higher comorbidity of diabetic retinopathy (p = 0.015) and higher levels of urinary miR-29a (p = 0.035) compared with those with normoalbuminuria (n = 41, age 58.54±14.40yrs). There was no significant difference in urinary miR-29b (p = 0.148) or miR-29c level (p = 0.321) between groups. Urinary albumin excretion rate significantly correlated with urinary miR-29a level (r = 0.286, p = 0.016), while urinary miR-29b significantly correlated with carotid intima-media thickness (cIMT) (r = 0.286, p = 0.046).
Urinary miR-29a correlated with albuminuria while urinary miR-29b correlated with carotid intima-media thickness (cIMT) in patients with type 2 diabetes. Therefore, they may have the potential to serve as alternative biomarker for diabetic nephropathy and atherosclerosis in type 2 diabetes.
The ambulatory arterial stiffness index (AASI) can be used to predict cardiovascular morbidity and mortality in hypertensive patients. However, data on AASI in Chinese patients with chronic kidney disease (CKD) is not available.
This cross-sectional study enrolled 583 CKD patients. Univariate and multivariate analyses were used to evaluate the relationship between AASI and renal function and parameters of cardiovascular injury.
Patients with a higher AASI had a higher systolic blood pressure, a lower estimated glomerular filtration rate (eGFR), a higher serum cystatin C, a higher left ventricular mass index (LVMI) and carotid intima-media thickness (cIMT). Univariate analyses showed that AASI was positively correlated with serum cystatin C (r=0.296, P < 0.001), serum creatinine (r=0.182, P < 0.001), and LVMI (r = 0.205, P < 0.001) and negatively correlated with the eGFR (r = –0.200, P < 0.001). Multivariate analyses revealed that serum cystatin C, eGFR, serum creatinine and LVMI were independently correlated with AASI.
These data suggest that AASI was closely correlated with renal function and parameters of cardiovascular injury in Chinese CKD patients. Good quality, long-term, large longitudinal trials to validate the role of AASI in clinical practice for Chinese CKD patients.
Ambulatory arterial stiffness index; Chronic kidney disease; Renal function; Left ventricular mass index
Endothelial dysfunction is an early sign of diabetic cardiovascular disease and may contribute to progressive diabetic nephropathy (DN). There is increasing evidence that dysfunction of the endothelial tight junction is a crucial step in the development of endothelial hyperpermeability, but it is unknown whether this occurs in glomerular endothelial cells (GEnCs) during the progression of DN. We examined tight junction dysfunction of GEnCs during early-stage DN and the potential underlying mechanisms. We also examined the effect of simvastatin (3-Hydroxy-3-methylglutaryl CoA reductase inhibitor) on dysfunction of the tight junctions of cultured GEnCs and in db/db mice with early-stage DN.
We assessed the expression of occludin and ZO-1, two major components of the tight junction complex, in cultured rat GEnCs treated with high glucose and in 12 week-old db/db mice with early-stage DN. We also investigated activation of RhoA/ROCK1 signaling, GEnC permeability, and renal function of the mice.
High glucose suppresses occludin expression and disrupts occludin/ZO-1 translocation in GEnCs. These changes were associated with increased permeability to albumin and activation of RhoA/ROCK1 signaling. Occludin and ZO-1 dysregulation also occurred in the glomeruli of mice with early-stage DN, and these abnormalities were accompanied by albuminuria and activation of RhoA/ROCK1 in isolated glomeruli. Simvastatin prevented high glucose or hyperglycemia-induced dysregulation of occludin and ZO-1 by inhibition of RhoA/ROCK1 signaling in cultured GEnCs and in db/db mice with early-stage DN.
Our results indicate that activation of RhoA/ROCK1 by high glucose disrupts the expression and translocation of occludin/ZO-1 and that simvastatin alleviates occludin/ZO-1 dysregulation and albuminuria by suppressing RhoA/ROCK1 signaling during early-stage DN. These results suggest a potential therapeutic strategy for preventing the onset of albuminuria in early-stage DN.
We sought to develop a new equation to estimate glomerular filtration rate (GFR) in Chinese elderly population.
A total of 668 Chinese elderly participants, including the development cohort (n = 433), the validation cohort (n = 235) were enrolled. The new equation using the generalized additive model, and age, gender, serum creatinine as predictor variables was developed and the performances was compared with the CKD-EPI equation.
In the validation data set, both bias and precision were improved with the new equation, as compared with the CKD-EPI equation (median difference, −1.5 ml/min/1.73 m2 vs. 7.4 ml/min/1.73 m2 for the new equation and the CKD-EPI equation, [P<0.001]; interquartile range [IQR] for the difference, 16.2 ml/min/1.73 m2 vs. 19.0 ml/min/1.73 m2 [P<0.001]), as were accuracies (15% accuracy, 40.4% vs. 30.6% [P = 0.02]; 30% accuracy, 71.1% vs. 47.2%, [P<0.001]; 50% accuracy, 90.2% vs. 75.7%, [P<0.001]), allowing improvement in GFR categorization (GFR category misclassification rate, 37.4% vs. 53.2% [P = <0.001]).
A new equation was developed in Chinese elderly population. In the validation data set, the new equation performed better than the original CKD-EPI equation. The new equation needs further external validations. Calibration of the GFR referent standard to a more accurate one should be an useful way to improve the performance of GFR estimating equations.
Recent studies have indicated that circulating microRNAs (miRNAs) in serum and plasma are stable and can serve as biomarkers of many human diseases. Measurement of circulating miRNAs with sufficient sensitivity and precision, however, faces some special challenges, among which proper normalization is the most critical but often an underappreciated issue. The primary aim of this study was to identify endogenous reference genes that maintain consistent levels under various conditions to serve as an internal control for quantification of serum miRNAs. We developed a strategy combining Illumina’s sequencing by synthesis (SBS) technology, reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay, literature screening and statistical analysis to screen and validate the most suitable reference genes. A combination of let-7d, let-7g and let-7i is selected as a reference for the normalization of serum miRNAs and it is statistically superior to the commonly used reference genes U6, RNU44, RNU48 and miR-16. This has important implications for proper experimental design and accurate data interpretation.
We aimed to evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine–cystatin C equation in a cohort of elderly Chinese participants.
Materials and methods
Glomerular filtration rate (GFR) was measured in 431 elderly Chinese participants by the technetium-99m diethylene-triamine-penta-acetic acid (99mTc-DTPA) renal dynamic imaging method, and was calibrated equally to the dual plasma sample 99mTc-DTPA-GFR. Performance of the CKD-EPI creatinine–cystatin C equation was compared with the Cockcroft–Gault equation, the re-expressed 4-variable Modification of Diet in Renal Disease (MDRD) equation, and the CKD-EPI creatinine equation.
Although the bias of the CKD-EPI creatinine–cystatin C equation was greater than with the other equations (median difference, 5.7 mL/minute/1.73 m2 versus a range from 0.4–2.5 mL/minute/1.73 m2; P<0.001 for all), the precision was improved with the CKD-EPI creatinine–cystatin C equation (interquartile range for the difference, 19.5 mL/minute/1.73 m2 versus a range from 23.0–23.6 mL/minute/1.73 m2; P<0.001 for all comparisons), leading to slight improvement in accuracy (median absolute difference, 10.5 mL/minute/1.73 m2 versus 12.2 and 11.4 mL/minute/1.73 m2 for the Cockcroft–Gault equation and the re-expressed 4-variable MDRD equation, P=0.04 for both; 11.6 mL/minute/1.73 m2 for the CKD-EPI creatinine equation, P=0.11), as the optimal scores of performance (6.0 versus a range from 1.0–2.0 for the other equations). Higher GFR category and diabetes were independent factors that negatively correlated with the accuracy of the CKD-EPI creatinine–cystatin C equation (β=−0.184 and −0.113, P<0.001 and P=0.02, respectively).
Compared with the creatinine-based equations, the CKD-EPI creatinine–cystatin C equation is more suitable for the elderly Chinese population. However, the cost-effectiveness of the CKD-EPI creatinine–cystatin C equation for clinical use should be considered.
elderly; equation; glomerular filtration rate; serum creatinine; cystatin C
Soybean is an important crop that provides valuable proteins and oils for human use. Because soybean growth and development is extremely sensitive to water deficit, quality and crop yields are severely impacted by drought stress. In the face of limited water resources, drought-responsive genes are therefore of interest. Identification and analysis of dehydration- and rehydration-inducible differentially expressed genes (DEGs) would not only aid elucidation of molecular mechanisms of stress response, but also enable improvement of crop stress tolerance via gene transfer. Using Digital Gene Expression Tag profiling (DGE), a new technique based on Illumina sequencing, we analyzed expression profiles between two soybean genotypes to identify drought-responsive genes.
Two soybean genotypes—drought-tolerant Jindou21 and drought-sensitive Zhongdou33—were subjected to dehydration and rehydration conditions. For analysis of DEGs under dehydration conditions, 20 cDNA libraries were generated from roots and leaves at two different time points under well-watered and dehydration conditions. We also generated eight libraries for analysis under rehydration conditions. Sequencing of the 28 libraries produced 25,000–33,000 unambiguous tags, which were mapped to reference sequences for annotation of expressed genes. Many genes exhibited significant expression differences among the libraries. DEGs in the drought-tolerant genotype were identified by comparison of DEGs among treatments and genotypes. In Jindou21, 518 and 614 genes were differentially expressed under dehydration in leaves and roots, respectively, with 24 identified both in leaves and roots. The main functional categories enriched in these DEGs were metabolic process, response to stresses, plant hormone signal transduction, protein processing, and plant-pathogen interaction pathway; the associated genes primarily encoded transcription factors, protein kinases, and other regulatory proteins. The seven most significantly expressed (|log2 ratio| ≥ 8) genes— Glyma15g03920, Glyma05g02470, Glyma15g15010, Glyma05g09070, Glyma06g35630, Glyma08g12590, and Glyma11g16000—are more likely to determine drought stress tolerance. The expression patterns of eight randomly-selected genes were confirmed by quantitative RT-PCR; the results of QRT-PCR analysis agreed with transcriptional profile data for 96 out of 128 (75%) data points.
Many soybean genes were differentially expressed between drought-tolerant and drought-sensitive genotypes. Based on GO functional annotation and pathway enrichment analysis, some of these genes encoded transcription factors, protein kinases, and other regulatory proteins. The seven most significant DEGs are candidates for improving soybean drought tolerance. These findings will be helpful for analysis and elucidation of molecular mechanisms of drought tolerance; they also provide a basis for cultivating new varieties of drought-tolerant soybean.
Soybean; Dehydration; Digital gene expression tag profile; Rehydration; Differentially expressed genes; Quantitative RT-PCR; Transcription factors; Protein kinases; Regulatory proteins
Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning.
Neurons have the ability to engage in selective pruning that eliminates unnecessary axons/dendrites. This process is crucial for sculpting the nervous system during development. During Drosophila development, dendrite arborization sensory neurons (ddaCs) selectively prune their larval dendrites in response to the molting steroid hormone ecdysone, whereas mushroom body γ neurons eliminate their axon branches. However, the underlying molecular mechanisms for both of these modes of pruning were not well understood. Here, we conduct a genome-wide screen and identify a conserved E3 ubiquitin ligase that is critical for pruning both ddaC dendrites and mushroom body γ axons. This ligase complex has four core components—Cullin1, Roc1a, SkpA, and Slimb—that promote ddaC dendrite pruning in response to ecdysone. We show that this ligase facilitates ddaC dendrite pruning through regulation of the InR/PI3K/TOR pathway. The substrate-recognition protein Slimb promotes ubiquitination of Akt, an activator of the InR/PI3K/TOR pathway. Akt ubiquitination leads to its degradation and inactivation of the InR/PI3K/TOR pathway, which is required for dendritic pruning. Consistent with this, ddaC dendrite pruning is inhibited when the InR/PI3K/TOR pathway is activated. Thus, we identify a link between the Cullin1-based E3 ligase and the InR/PI3K/TOR pathway in regulating dendrite pruning. This work represents the first link between neuronal pruning and the insulin signaling pathway, raising interesting questions about how metabolic states may influence the control of such developmental processes.
Near-duplicate image retrieval is a classical research problem in computer vision toward many applications such as image annotation and content-based image retrieval. On the web, near-duplication is more prevalent in queries for celebrities and historical figures which are of particular interest to the end users. Existing methods such as bag-of-visual-words (BoVW) solve this problem mainly by exploiting purely visual features. To overcome this limitation, this paper proposes a novel text-based data-driven reranking framework, which utilizes textual features and is combined with state-of-art BoVW schemes. Under this framework, the input of the retrieval procedure is still only a query image. To verify the proposed approach, a dataset of 2 million images of 1089 different celebrities together with their accompanying texts is constructed. In addition, we comprehensively analyze the different categories of near duplication observed in our constructed dataset. Experimental results on this dataset show that the proposed framework can achieve higher mean average precision (mAP) with an improvement of 21% on average in comparison with the approaches based only on visual features, while does not notably prolong the retrieval time.
Lung cancer is one of the leading causes of cancer-related mortality worldwide. Gastrointestinal metastasis from primary lung cancer is rare. Only a few reports have been published and the majority of described metastatic sites involved the small intestine. In the present study, we report the first case of primary lung adenocarcinoma with both gastric and colonic metastases. We also review the published literature of primary lung cancer with gastrointestinal metastasis.
lung cancer; gastrointestinal metastasis
Herpes simplex virus 2 (HSV-2) infection is still one of the common causes of sexually transmitted diseases worldwide. The prevalence of HSV strains resistant to traditional nucleoside antiviral agents has led to the development of novel antiviral drugs. Human alpha-defensin 5 (HD5), a kind of endogenous antimicrobial peptide expressed in the epithelia of the small intestine and urogenital tract, displays natural antiviral activity. Based on arginine-rich features and adaptive evolution characteristics of vertebrate defensins, we conducted a screen for HD5 derivatives with enhanced anti-HSV-2 activity by a single arginine substitution at the adaptive evolution sites. Cell protection assay and temporal antiviral studies showed that HD5 and its mutants displayed affirmatory but differential anti-HSV-2 effects in vitro by inhibiting viral adhesion and entry. Inspiringly, the E21R-HD5 mutant had significantly higher antiviral activity than natural HD5, which is possibly attributed to the stronger binding affinity of the E21R-HD5 mutant with HSV-2 capsid protein gD, indicating that E21R mutation can increase the anti-HSV-2 potency of HD5. In a mouse model of lethal HSV-2 infection, prophylactic and/or therapeutic treatment with E21R-HD5 via intravaginal instillation remarkably alleviated the symptoms and delayed disease progress and resulted in about a 1.5-fold-higher survival rate than in the HD5 group. Furthermore, the E21R variant exhibited a 2-fold-higher antiviral potency against HIV-1 over parental HD5 in vitro. This study demonstrates that arginine mutagenesis at appropriate evolution sites may significantly enhance the antiviral activity of HD5, which also paves a facile way to search for potent antiviral drugs based on natural antimicrobial peptides.
To determine the prevalence and correlates of syphilis among pregnant women in rural areas of South China.
Point-of-care syphilis testing was provided at 71 health facilities in less developed, rural areas of Guangdong Province. Positive samples were confirmed at a local referral center by toluidine red unheated serum tests (TRUST) and Treponema pallidum particle agglutination (TPPA) tests.
Altogether 27,150 pregnant women in rural Guangdong were screened for syphilis. 106 (0.39%) syphilis cases were diagnosed, of which 78 (73.6%) received treatment for syphilis. Multivariate analysis revealed that older pregnant women (31–35 years old, aOR 2.7, 95% CI 0.99–7.32; older than 35 years old, aOR 5.9, 95% CI 2.13–16.34) and those with a history of adverse pregnant outcomes (aOR 3.64, 95% CI 2.30–5.76) were more likely to be infected with syphilis.
A high prevalence of syphilis exists among pregnant women living in rural areas of South China. Enhanced integration of syphilis screening with other routine women's health services (OB GYN, family planning) may be useful for controlling China's syphilis epidemic.
Accurate and precise estimates of glomerular filtration rate (GFR) are essential for clinical assessments, and many methods of estimation are available. We developed a radial basis function (RBF) network and assessed the performance of this method in the estimation of the GFRs of 207 patients with type-2 diabetes and CKD.
Standard GFR (sGFR) was determined by 99mTc-DTPA renal dynamic imaging and GFR was also estimated by the 6-variable MDRD equation and the 4-variable MDRD equation.
Bland-Altman analysis indicated that estimates from the RBF network were more precise than those from the other two methods for some groups of patients. However, the median difference of RBF network estimates from sGFR was greater than those from the other two estimates, indicating greater bias. For patients with stage I/II CKD, the median absolute difference of the RBF network estimate from sGFR was significantly lower, and the P50 of the RBF network estimate (n = 56, 87.5%) was significantly higher than that of the MDRD-4 estimate (n = 49, 76.6%) (p < 0.0167), indicating that the RBF network estimate provided greater accuracy for these patients.
In patients with type-2 diabetes mellitus, estimation of GFR by our RBF network provided better precision and accuracy for some groups of patients than the estimation by the traditional MDRD equations. However, the RBF network estimates of GFR tended to have greater bias and higher than those indicated by sGFR determined by 99mTc-DTPA renal dynamic imaging.
Type 2 diabetes; Chronic kidney disease; Glomerular filtration rate; Artificial neural network
Three new bicyclic depsipeptides, which are related to the previously reported thailandepsins A (1), B (2) and C (3), were discovered from the culture broth of Burkholderia thailandensis E264 when supplemented with amino acid precursors, and were subsequently named as thailandepsins D (4), E (5) and F (6), respectively. Enzyme assays showed that 1–6 are potent histone deacetylase (HDAC) inhibitors, particularly toward HDAC1 which represents class I human HDACs.
Cellular reprogramming of somatic cells to patient-specific induced pluripotent stem cells (iPSCs) enables in-vitro modelling of human genetic disorders for pathogenic investigations and therapeutic screens1–7. However, using iPSC-derived cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains challenging due to the uncertainty regarding the ability of relatively immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart disease characterized by pathological fatty infiltration and cardiomyocyte loss predominantly in the right ventricle (RV)8, which is associated with life-threatening ventricular arrhythmias. Over 50% of affected individuals have desmosome gene mutations, most commonly in PKP2 encoding plakophilin-29. The median age at presentation of ARVD/C is 26 years8. We used Yamanaka’s methods1,10 to generate iPSC lines from fibroblasts of two patients with ARVD/C and PKP2 mutations11,12. Mutant PKP2 iPSC-CMs demonstrate abnormal plakoglobin nuclear translocation and decreased β-catenin activity13 in cardiogenic conditions; yet these abnormal features are insufficient to reproduce the pathological phenotypes of ARVD/C in standard cardiogenic conditions. Here we show that induction of adult-like metabolic energetics from an embryonic/glycolytic state and abnormal peroxisome proliferator-activated receptor-gamma (PPARγ) activation underlie the pathogenesis of ARVD/C. By coactivating normal PPAR-alpha (PPARα)-dependent metabolism and abnormal PPARγ pathway in beating embryoid bodies (EBs) with defined media, we established an efficient ARVD/C in-vitro model within two months. This model manifests exaggerated lipogenesis and apoptosis in mutant PKP2 iPSC-CMs. iPSC-CMs with a homozygous PKP2 mutation also displayed calcium-handling deficits. Our study is the first to demonstrate that induction of adult-like metabolism plays a critical role in establishing an adult-onset disease model using patient-specific iPSCs. Using this model, we revealed crucial pathogenic insights that metabolic derangement in adult-like metabolic milieu underlies ARVD/C pathologies, enabling us to propose novel disease-modifying therapeutic strategies.
The purpose of our study is to investigate whether diffusion-weighted imaging (DWI) is useful for monitoring the therapeutic response after neoadjuvant chemotherapy in osteosarcoma of long bones.
Materials and methods
Conventional magnetic resonance imaging (MRI) and DWI were obtained from 35 patients with histologically proven osteosarcomas. MR examinations were performed in all patients before and after 4 courses of preoperative neoadjuvant chemotherapy. Apparent diffusion coefficients (ADC) were measured. The degree of tumor necrosis was assessed macroscopically and histologically by two experienced pathologists after operation. Student’s t test was performed for testing changes in ADC value. Pearson’s correlation coefficient was used to estimate the correlation between necrosis rate and post- neoadjuvant chemotherapy ADC values. P<0.05 was considered to denote a significant difference.
The difference of the whole osteosarcoma between pre- neoadjuvant chemotherapy ADC value (1.24±0.17×10−3 mm2/s) and post- (1.93±0.39×10−3 mm2/s) was significant difference (P<0.01). Regarding in patients with good response, the post- neoadjuvant chemotherapy values were significantly higher than the pre- neoadjuvant chemotherapy values (P<0.01). The post- neoadjuvant chemotherapy ADC value in patients with good response was higher than that of poor response (t = 8.995, P<0.01). The differences in post- neoadjuvant chemotherapy ADC between viable (1.03±0.17×10−3 mm2/s) and necrotic (2.38±0.25×10−3 mm2/s) tumor was highly significant (t = 23.905, P<0.01). A positive correlation between necrosis rates and the whole tumor ADC values (r = 0.769, P<0.01) was noted, but necrosis rates were not correlated with the ADC values of necrotic (r = −0.191, P = 0.272) and viable tumor areas (r = 0.292, P = 0.089).
DWI can identify residual viable tumor tissues and tumor necrosis induced by neoadjuvant chemotherapy in osteosarcoma. The ADC value can directly reflect the degree of tumor necrosis, and it is useful to evaluate the preoperative neoadjuvant chemotherapy response in patients with osteosarcoma.
Background. The prognostic significance of ERG expression in prostate cancer (PCA) has generated mixed results. We sought to investigate the prognostic significance of ERG expression in a localized cohort of men with PCA. Material and Methods. We investigated ERG protein expression in a cohort of 198 men with localized PCA. ERG expression was correlated with patients' clinical outcome and several pathological parameters, including Gleason score (GS), pathological stage, surgical margin, and extra-capsular extension. Results. ERG expression was detected in 86/198 (43.4%) patients exclusively in neoplastic epithelium. Overall, ERG mean expression intensity was 1.01 ± 1.27 versus 0.37 ± 0.83 in acinar PCA compared to foamy type PCA (P < 0.001). In HGPIN, ERG intensity levels were comparable to those in foamy type PCA (0.13 ± 0.56) but significantly lower than those in acinar PCA (P < 0.001). ERG expression was significantly associated with extra-prostatic extension and higher pathological stage and showed a trend toward seminal vesicle invasion. Herein, ERG expression was documented in 50/131 (38.1%) patients with pT2 versus 30/55 (54.5%) patients with pT3 (P = 0.04). ERG association with higher pathological stage was more pronounced in patients with GS > 7. Grouping patients into those with GS ≤ 7 versus >7, there was no significant association between ERG expression and GS. Similarly, no association was present in relation to either surgical margins or postsurgical serum PSA levels. Conclusion. We report significant association between ERG protein levels and extra-prostatic extension and higher pathological stage. ERG expression is not associated with adverse clinical outcome and is of limited prognostic value in localized PCA.
Female sex workers have been the target of numerous sexually transmitted infection (STI) prevention strategies in China, but their male clients have attracted considerably less public health attention and resources. We sought to systematically assess the prevalence of HIV, syphilis, gonorrhea, and chlamydia among heterosexual male clients of female sex workers in China.
Original research manuscripts were identified by searching Chinese and English language databases, and 37 studies analyzing 26,552 male clients were included in the review. Client STI prevalence across studies was heterogeneous. Pooled prevalence estimates and 95% confidence intervals were 0.68% (0.36–1.28%) for HIV, 2.91% (2.17–3.89%) for syphilis, 2.16% (1.46–3.17%) for gonorrhea, and 8.01% (4.94–12.72%) for chlamydia.
The pooled prevalence estimates of HIV, syphilis, gonorrhea, and chlamydia among clients in this review exceed the prevalences previously reported among population-representative samples and low-risk groups in China. However, heterogeneity across studies and sampling limitations prevent definitive conclusions about how the prevalence of STIs in this population compares to the general population. These findings suggest a need for greater attention to clients’ sexual risk and disease prevalence in China’s STI research agenda in order to inform effective prevention policies.
Baylisascaris schroederi is one of the most common nematodes of the giant panda, and can cause severe baylisascarosis in both wild and captive giant pandas. Previous studies of the giant pandas indicated that this population is genetically distinct, implying the presence of a new subspecies. Based on the co-evolution between the parasite and the host, the aim of this study was to investigate the genetic differentiation in the B. schroederi population collected from giant pandas inhabiting different mountain ranges, and further to identify whether the evolution of this parasite correlates with the evolution of giant pandas.
In this study, 48 B. schroederi were collected from 28 wild giant pandas inhabiting the Qinling, Minshan and Qionglai mountain ranges in China. The complete sequence of the mitochondrial cytochrome b (mtCytb) gene was amplified by PCR, and the corresponding population genetic diversity of the three mountain populations was determined. In addition, we discussed the evolutionary relationship between B. schroederi and its host giant panda.
For the DNA dataset, insignificant Fst values and a significant, high level of gene flow were detected among the three mountain populations of B. schroederi, and high genetic variation within populations and a low genetic distance were observed. Both phylogenetic analyses and network mapping of the 16 haplotypes revealed a dispersed pattern and an absence of branches strictly corresponding to the three mountain range sampling sites. Neutrality tests and mismatch analysis indicated that B. schroederi experienced a population expansion in the past.
Taken together, the dispersed haplotype map, extremely high gene flow among the three populations of B. schroederi, low genetic structure and rapid evolutionary rate suggest that the B. schroederi populations did not follow a pattern of isolation by distance, indicating the existence of physical connections before these populations became geographically separated.
Giant panda; Baylisascaris schroederi; Mountain ranges; Genetic diversity; Genetic structure; Phylogeography
MicroRNA deregulation is a critical event in head and neck squamous cell carcinoma (HNSCC). Several microRNA profiling studies aimed at deciphering the microRNA signatures of HNSCC have been reported, but there tends to be poor agreement among studies. The objective of this study was to survey the published microRNA profiling studies on HNSCC, and to assess the commonly deregulated microRNAs in an independent sample set.
Materials and Methods
Meta-analysis of 13 published microRNA profiling studies was performed to define microRNA signatures in HNSCC. Selected microRNAs (including members of miR-99 family) were evaluated in an independent set of HNSCC cases. The potential contributions of miR-99 family to the tumorigenesis of HNSCC were assessed by in vitro assays.
We identified 67 commonly deregulated microRNAs. The up-regulation of miR-21, miR-155, miR-130b, miR-223 and miR-31, and the down-regulation of miR-100, miR-99a and miR-375 were further validated in an independent set of HNSCC cases with quantitative RT-PCR. Among these validated microRNAs, miR-100 and miR-99a belong to the miR-99 family. Our in vitro study demonstrated that restoration of miR-100 to the HNSCC cell lines suppressed cell proliferation and migration, and enhanced apoptosis. Furthermore, ectopic transfection of miR-99 family members down-regulated the expression of insulin-like growth factor 1 receptor (IGF1R) and mechanistic target of rapamycin (mTOR) genes.
In summary, we described a panel of frequently deregulated microRNAs in HNSCC, including members of miR-99 family. The deregulation of miR-99 family contributes to the tumorigenesis of HNSCC, in part by targeting IGF1R and mTOR signaling pathways.
meta-analysis; HNSCC; microRNA profiling; miR-99 family; miR-100; IGF1R; mTOR; tumor suppressor
The aim of the present study was to evaluate modified glomerular filtration rate (GFR) prediction formulae in an elderly Chinese population with chronic kidney disease (CKD).
A total of 378 elderly Chinese patients with CKD were enrolled. The GFR was estimated with six modified GFR prediction formulae. The performances of the estimated GFRs were compared with those of the standard GFRs measured by technetium-99m diethyl-enetraminepentaacetic acid.
Biases were similar for Chinese formula 1, the Asian formula, and Chinese formula 2 (median difference, 2.22 mL/min/1.73 m2 and 2.59 mL/min/1.73 m2 for Chinese formula 1 and the Asian formula, respectively, versus (vs) 3.69 mL/min/1.73 m2 for Chinese formula 2 [P = 0.298 and P = 0.913, respectively]). Precision was improved with the Japanese formula (interquartile range of the difference, 3.14 mL/min/1.73 m2 of the Japanese formula versus 15.53–23.06 mL/min/1.73 m2 of the other formulae). The accuracy of Chinese formula 2 was the highest (30% accuracy, 59.3% vs range 37.8–54.0% [P < 0.05 for all comparisons]). However, none of the modified formulae surpassed the acceptable tolerance (>70%), and the GFR category misclassification rates for all the formulae exceeded 50%.
Our findings suggest that all six modified formulae developed in Asian populations may show great bias in elderly Chinese patients with CKD. Also, our study suggests the need for uniform measures for the assessment of CKD in the elderly to guarantee better sensitivity and specificity.
formula; CKD; Asian; GFR
Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII) were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50–75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1β in TCL-loaded DCs and downregulated the expression of TGF-β1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines.
Aims. To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods and Results. Participants (n = 808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87; P = 0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72; P = 0.002). No major bleeding events were observed in any participant. Conclusion. Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding.