Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome.

AIM: To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome [LADD (MIM 149730)] showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene. METHODS: Ophthalmological examinations, including slit-lamp biomicroscopy and lacrimal duct probing, and computed tomography dacryocystography (CT-DCG) were performed for all participants. The family pedigree was drawn, genetic features were analyzed, and the genomic DNA of the subjects was extracted. Pathogenic genes were screened via whole exome sequencing (WES) and confirmed using Sanger sequencing. RESULTS: Six patients belonged to this three-generation family, and their clinical manifestations included congenital nasolacrimal duct obstruction, congenital absence of lacrimal puncta and canaliculi, lacrimal fistulae, and limb deformities. This pattern indicates autosomal dominant inheritance. Diagnosis was based on the clinical characteristics of LADD syndrome, which presented in all the patients in this family. A novel frameshift mutation in the FGF10 gene (NM_004465.1), c.234dupC (p.Trp79Leus*15), was identified in all patients via WES. The variant was confirmed by Sanger sequencing and classified as a "pathogenic mutation" according to the American College of Medical Genetics and Genomics (ACMG) variant interpretation guidelines. CONCLUSION: A novel frameshift mutation in the FGF10 gene is found in all patients. This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.

Genome-wide methylation profiling of early colorectal cancer using an Illumina Infinium Methylation EPIC BeadChip.

BACKGROUND: DNA methylation is a part of epigenetic modification, that is closely related to the growth and development of colorectal cancer (CRC). Specific methylated genes and methylated diagnostic models of tumors have become current research focuses. The methylation status of circulating DNA in plasma might serve as a potential biomarker for CRC. AIM: To investigate genome-wide methylation pattern in early CRC using the Illumina Infinium Human Methylation 850K BeadChip. METHODS: The 850K Methylation BeadChip was used to analyze the genome-wide methylation status of early CRC patients (n = 5) and colorectal adenoma patients (n = 5). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were performed on the selected differentially methylated sites to further discover candidate methylation biomarkers in plasma. RESULTS: A total of 1865 methylated CpG sites with significant differences were detected, including 676 hypermethylated sites and 1189 hypomethylated sites. The distribution of these sites covered from the 1st to 22nd chromosomes and are mainly distributed on the gene body and gene promoter region. GO and KEGG enrichment analysis showed that the functions of these genes were related to biological regulation, molecular binding, transcription factor activity and signal transduction pathway. CONCLUSION: The study demonstrated that the Illumina Infinium Human Methylation 850K BeadChip can be used to investigate genome-wide methylation status of plasma DNA in early CRC and colorectal adenoma patients.

The predictive value of selected serum microRNAs for acute GVHD by TaqMan MicroRNA arrays.

Currently, the diagnosis of acute graft-versus-host disease (aGVHD) is mainly based on clinical symptoms and biopsy results. This study was designed to further explore new no noninvasive biomarkers for aGVHD prediction/diagnosis. We profiled miRNAs in serum pools from patients with aGVHD (grades II-IV) (n = 9) and non-aGVHD controls (n = 9) by real-time qPCR-based TaqMan MicroRNA arrays. Then, predictive models were established using related miRNAs (n = 38) and verified by a double-blind trial (n = 54). We found that miR-411 was significantly down regulated when aGVHD developed and recovered when aGVHD was controlled, which demonstrated that miR-411 has potential as an indicator for aGVHD monitoring. We developed and validated a predictive model and a diagnostic model for aGVHD. The predictive model included two miRNAs (miR-26b and miR-374a), which could predict an increased risk for aGVHD 1 or 2 weeks in advance, with an AUC, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of 0.722, 76.19 %, and 69.70 %, respectively. The diagnostic model included three miRNAs (miR-28-5p, miR-489, and miR-671-3p) with an AUC, PPV, and NPV of 0.841, 85.71 % and 83.33 %, respectively. Our results show that circulating miRNAs (miR-26b and miR-374a, miR-28-5p, miR-489 and miR-671-3p) may serve as biomarkers for the prediction and diagnosis of grades II-IV aGVHD.

Identifying joint biomarker panel from multiple level dataset by an optimization model.

AIM: Joint biomarker panel takes advantage of coherence across multiple level datasets and holds the promise to improve disease diagnosis accuracy. METHODS: We collected 101 colorectal cancer and 95 benign samples, measured the molecular concentrations by serum assays and mass spectra, and developed LPGLO (Linear Programming based on Group Lasso Optimization) to identify the joint biomarker panel. RESULTS: A joint biomarker panel, with ten serum biomarkers and six mass spectra peaks, achieves LOOCV accuracy 0.8724, which is better than the optimal panels identified from separate datasets (LOOCV = 0.7551 for mass spectra only or 0.8265 for serum assay only) and the simply merged dataset (LOOCV = 0.8622). CONCLUSION: LPGLO is useful to identify joint biomarker panel to help tumor diagnosis.

Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer.

AIM: To investigate the relationship of serum levels of polyunsaturated fatty acid (PUFA) with kinds of cytokines in colorectal cancer (CRC). METHODS: Serum samples of 100 CRC patients were collected. The concentration of total n-3 PUFA which included C18:3 n-3, C20:5 n-3, C22:5 n-3, C22:6 n-3 and the total n-6 PUFA included C18:2 n-6, C18:3 n-6, C20:3 n-6, C20:4 n-6, and C22:5 n-6 were detected on GC-2010 Plus Gas Chromatograph with a OmegawaxTM 250 column. Cytokines were detected by MagPlexTM-C microspheres. P values for the trend were estimated by creating a continuous variable using the median value within quartiles. RESULTS: Interleukin-6 (IL-6) showed significantly positive association with the C20:4 n-6 (P for trend = 0.004). Interferon gamma (IFN-γ) showed significant positive association with the C22:5 n-3 (P for trend = 0.035). IL-8 and matrix metalloproteinase-9 (MMP-9) showed significant inverse association with the C22:6 n-3 (P for trend = 0.049, and 0.021). MMP-2 showed significant inverse association with the C20:5 n-3 (P for trend = 0.008). MMP-7 showed significantly positive association with the ratio of n-6 PUFA and n-3 PUFA (P for trend = 0.008). MMP-7 also showed significantly inverse association with the ratio of C20:4 n-6 and (n-6 PUFA + n-3 PUFA) (P for trend = 0.024). IL-10 (P for trend = 0.023) and IL-6 (P for trend = 0.036) showed significantly positive association with the ratio of C20:4 n-6 and C20:5 n-3. CONCLUSION: Our data suggested that serum levels of PUFA is related to the inflammation of CRC, and also play different role in regulation of immune response.

A novel mixed integer programming for multi-biomarker panel identification by distinguishing malignant from benign colorectal tumors.

Multi-biomarker panels can capture the nonlinear synergy among biomarkers and they are important to aid in the early diagnosis and ultimately battle complex diseases. However, identification of these multi-biomarker panels from case and control data is challenging. For example, the exhaustive search method is computationally infeasible when the data dimension is high. Here, we propose a novel method, MILP_k, to identify serum-based multi-biomarker panel to distinguish colorectal cancers (CRC) from benign colorectal tumors. Specifically, the multi-biomarker panel detection problem is modeled by a mixed integer programming to maximize the classification accuracy. Then we measured the serum profiling data for 101 CRC patients and 95 benign patients. The 61 biomarkers were analyzed individually and further their combinations by our method. We discovered 4 biomarkers as the optimal small multi-biomarker panel, including known CRC biomarkers CEA and IL-10 as well as novel biomarkers IMA and NSE. This multi-biomarker panel obtains leave-one-out cross-validation (LOOCV) accuracy to 0.7857 by nearest centroid classifier. An independent test of this panel by support vector machine (SVM) with threefold cross validation gets an AUC 0.8438. This greatly improves the predictive accuracy by 20% over the single best biomarker. Further extension of this 4-biomarker panel to a larger 13-biomarker panel improves the LOOCV to 0.8673 with independent AUC 0.8437. Comparison with the exhaustive search method shows that our method dramatically reduces the searching time by 1000-fold. Experiments on the early cancer stage samples reveal two panel of biomarkers and show promising accuracy. The proposed method allows us to select the subset of biomarkers with best accuracy to distinguish case and control samples given the number of selected biomarkers. Both receiver operating characteristic curve and precision-recall curve show our method's consistent performance gain in accuracy. Our method also shows its advantage in capturing synergy among selected biomarkers. The multi-biomarker panel far outperforms the simple combination of best single features. Close investigation of the multi-biomarker panel illustrates that our method possesses the ability to remove redundancy and reveals complementary biomarker combinations. In addition, our method is efficient and can select multi-biomarker panel with more than 5 biomarkers, for which the exhaustive methods fail. In conclusion, we propose a promising model to improve the clinical data interpretability and to serve as a useful tool for other complex disease studies. Our small multi-biomarker panel, CEA, IL-10, IMA, and NSE, may provide insights on the disease status of colorectal diseases. The implementation of our method in MATLAB is available via the website: http://doc.aporc.org/wiki/MILP_k.

Identification and characterization of novel serum microRNA candidates from deep sequencing in cervical cancer patients.

Small non-coding microRNAs (miRNAs) are involved in cancer development and progression, and serum profiles of cervical cancer patients may be useful for identifying novel miRNAs. We performed deep sequencing on serum pools of cervical cancer patients and healthy controls with 3 replicates and constructed a small RNA library. We used MIREAP to predict novel miRNAs and identified 2 putative novel miRNAs between serum pools of cervical cancer patients and healthy controls after filtering out pseudo-pre-miRNAs using Triplet-SVM analysis. The 2 putative novel miRNAs were validated by real time PCR and were significantly decreased in cervical cancer patients compared with healthy controls. One novel miRNA had an area under curve (AUC) of 0.921 (95% CI: 0.883, 0.959) with a sensitivity of 85.7% and a specificity of 88.2% when discriminating between cervical cancer patients and healthy controls. Our results suggest that characterizing serum profiles of cervical cancers by Solexa sequencing may be a good method for identifying novel miRNAs and that the validated novel miRNAs described here may be cervical cancer-associated biomarkers.

Clinical value of serum tumor markers CA19-9, CA125 and CA72-4 in the diagnosis of pancreatic carcinoma.

CA125 and CA72-4 are members of a family of high-molecular weight glycosylated proteins and are commonly considered as biomarkers in the diagnosis of ovarian and gastric cancer, respectively. However, recent studies have revealed that these two markers may be of clinical value in the diagnosis of pancreatic cancer. As the availability of data regarding CA72-4 and CA125 in the diagnosis of pancreatic cancer is limited, the aim of this study was to investigate the clinical value of serum tumor markers CA19-9, CA125 and CA72-4 in the diagnosis of pancreatic carcinoma according to logistic regression analysis and receiver operating characteristic (ROC) curves and to investigate the correlation of these markers with tumor TNM stage and location. An immunoradiometric assay was used to measure pre-operative serum CA19-9, CA125 and CA72-4 levels in 75 patients with pancreatic carcinoma and 70 patients with benign pancreatic diseases. The concentrations of serum CA19-9, CA125 and CA72-4 in patients with pancreatic carcinoma were found to be significantly higher (P<0.05) compared with those with benign pancreatic diseases. The combined detection of two serum markers (CA19-9 + CA72-4) yielded a ROC value of 0.895 that was significantly higher compared to others (P<0.05) in distinguishing pancreatic cancer from benign pancreatic diseases. At optimal cut-off, the sensitivity and specificity of combined detection (CA19-9 + CA72-4) were 70.6 and 92.8%, respectively. The concentrations of CA125 and CA19-9 in patients with pancreatic adenocarcinoma were found to be significantly higher (P<0.05) compared with those of pancreatic neuroendocrine carcinoma. In conclusion, the combined detection of CA19-9 and CA72-4) may significantly improve the diagnostic specificity and the serum concentrations of CA125 and CA19-9 are correlated with tumor histological type.

A novel differential predict model based on matrix-assisted laser ionization time-of-flight mass spectrometry and serum ferritin for acute graft-versus-host disease.

Clinical diagnosis of acute graft-versus-host disease (aGVHD) mainly depends on clinical manifestation and tissue biopsies, leading to a delayed diagnosis and treatment for aGVHD patients when the early symptom is insignificant. Our objective was to investigate the possibility of prewarning the risk of aGVHD before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by serum protein profiling combined with serum ferritin. The difference in polypeptide expression before and after transplantation had been compared by using CLINPROT technology, and serum ferritin levels have been analyzed simultaneously. Through combining serum ferritin and MS spectral data, the diagnosis sensitivity and specificity of our model for prewarning severe aGVHD (III~IV°aGVHD) before transplant all increased to 90.0%, while after transplant, the sensitivity and specificity are 78.3% and 86.4%. Our joint prewarning model could predict the risk of aGVHD, especially severe aGVHD before and after transplant, which also provides a reliable method to the continuous monitoring of the condition of patients.

Prognostic value of combined serum biomarkers in predicting outcomes in cervical cancer patients.

BACKGROUND: We evaluated the prognostic value of pretreatment serum biomarkers in predicting outcomes in cervical cancer patients subjected to treatment. METHODS: Serum samples collected from 60 cervical cancer patients and 60 age-matched healthy individuals were used for the detection of 22 biomarkers, prior to therapy. Cox multivariate analysis and classification and regression tree analysis (CART) were performed to evaluate the prognostic factors. RESULTS: Cox multivariate analysis disclosed that carbohydrate antigen 153 (CA153), squamous cell carcinoma antigen (SCC) and tumor necrosis factor-α (TNF-α) are associated with prognosis in cervical cancer. CART analysis led to the stratification of patients into 3 groups: (1) serum concentrations of CA153 ≥17.60 µg/l, (2) serum concentrations of CA153 <17.60 µg/l and TNF-α ≥10.60 pg/ml, and (3) serum concentrations of CA153 <17.60 µg/l and TNF-α <10.60 pg/ml. The 2-y overall survival rates for Groups 1, 2 and 3 were 33.3%, 60.0% and 93.9%, respectively. CONCLUSIONS: Higher serum concentrations of TNF-α, SCC and CA153 before therapy are independently associated with poor prognosis in patients with stage I and II disease. Combined usage of these three biomarkers allows efficient evaluation of outcomes in cervical cancer patients.

hTERT rs2736098 genetic variants and susceptibility of hepatocellular carcinoma in the Chinese population: a case-control study.

BACKGROUND: The human telomerase reverse transcriptase (hTERT) gene encodes the catalytic subunit of telomerase, which mediates pleiotropic effects, including the regulation of senescence and proliferation and plays an important role in carcinogenesis. This study attempts to clarify the genetic predisposition to hepatocellular carcinoma (HCC), focusing on the hTERT gene rs2736098 polymorphism. METHOD: Four hundred patients with HCC and 400 non-cancer controls were genotyped to elucidate the potential association between hTERT rs2736098 polymorphism and HCC risks. RESULTS: Compared with the controls, the patients with HCC had a lower frequency of G/G genotype (33.3% vs 44.3%, P=0.001) and a higher frequency of G/A (51.5% vs 39.5%, P=0.001). Allele genotypic frequencies in the patients differed from those of the controls (P=0.040). The data of this study rs2736098[A] allele contributed significantly to HCC risk in female patients (OR=1.78, 95% CI, 1.17-2.72, P=0.007), patients with HCV infection (OR=2.89, 95% CI, 1.08-7.70, P=0.031), non-drinker patients (OR=1.32, 95% CI, 1.06-1.65, P=0.015), and patients not affected by HBV (OR=1.77, 95% CI, 1.30-2.40, P<0.001). CONCLUSIONS: rs2736098[A] may be an independent hereditary parameter in HCC, but some risk factors would cover up the association by more powerful hepatocarcinogenesis. These results are important guidance for further studies in detecting HCC-associated single nucleotide polymorphisms.

Clinical evaluation of the levels of 12 cytokines in serum/plasma under various storage conditions using evidence biochip arrays.

Cytokines are a group of peptides which form a sophisticated network to modulate multiple cellular events. Within such a network, and through complex feedback mechanisms, cytokine functions are largely interdependent and closely associated with a number of pathological processes. In the present study, the EVIDENCE 180 system was used to study the effects of storage temperature and repeated freeze/thaw cycles on the concentration of 12 cytokines in various sample types. Samples were collected from 9 healthy volunteers and stored by 3 methods: gel, glass and lithium heparin (LH) tubes. Immediately following collection, the concentration of each cytokine in the samples was measured. Cytokine concentrations of the 3 sample types that did not undergo repeated freeze/thaw cycles were compared with those subjected to 1­10 freeze/thaw cycles. In addition, the dynamic changes of 6 sample types which were stored at 4˚C for 6 h to 6 days was analyzed. In addition, the within­ and between­run precision of 12 cytokines on the biochip array was evaluated. Interleukin (IL)­8, vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) concentrations were lower in plasma compared with serum. Cytokine levels in serum and plasma were affected by several freeze/thaw cycles with IL­1ß, ­4 and ­10 increasing significantly following 1 freeze/thaw cycle and remaining at stable increased levels for the duration of the additional 9 cycles. In separated serum samples in gel and glass tubes stored at 4˚C for 6 days, no difference in concentration of the 12 cytokines was identified. In the other 4 sample types, IL­8, VEGF, tumor necrosis factor α and EGF levels were altered when stored at 4˚C. Results indicate that the EVIDENCE 180 system is stable and plasma was observed as the best sample type to determine concentration of the 12 cytokines using this biochip array. Repeated freeze/thaw cycles and storage at 4˚C was identified to affect the concentration of the 12 cytokines. The current study demonstrates that repeated freeze/thaw cycles of samples must be avoid. In addition, results indicate that plasma or serum must be separated immediately following centrifugation and sample concentration should be measured as soon as possible.

Impact of chronic kidney disease on serum tumor markers concentrations.

BACKGROUND: Serum tumor markers have always been of clinical importance in the diagnosis, monitoring disease progression and therapy efficacy for patients with malignant diseases. However, elevated serum tumor markers are found in some benign conditions, especially in chronic kidney disease (CKD). The elevation of them in CKD might cause confusion and misuse of these tumor markers. We conducted this retrospective study to investigate which of the five widely used tumor markers including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), squamous cell carcinoma antigen (SCC) and neuron specific enolase (NSE) are affected markedly by CKD, in order to use them more effectively. METHODS: Serum tumor marker concentrations, biochemical, hematological parameters, and urinalysis were measured in CKD patients and healthy controls. The positive rate and median tumor markers' level in CKD patients and controls, and those in CKD patients stratified by CKD grade were compared using nonparametric rank tests. Correlation analysis of serum tumor markers and other parameters in CKD patients were performed using the Spearman correlation coefficient. Multivariate Logistic regression analysis was used to estimate the important variables that caused elevated serum concentrations of these markers in CKD patients. RESULTS: The overall positive rates and serum concentrations of Cyfra21-1, SCC, CEA in CKD group were significantly higher than those in control group. Positive rate and serum concentrations of those tumor markers increased as kidney function decreased. Both univariate analysis and multivariate regression analysis showed that the elevations of those tumor markers were not only associated with kidney function, but also with nutritional status. CONCLUSIONS: Serum concentrations of Cyfra21-1, SCC, CEA are significantly influenced by kidney function, as well as nutritional status. Therefore, in clinical work, the indices of kidney function and nutritional status could be simultaneously measured to improve interpretation of the results of those tumor marker concentrations.

Genes expression profiling of peripheral blood cells of patients with hepatocellular carcinoma.

HCC (hepatocellular carcinoma) is often diagnosed at an advanced stage with poor prognosis. Peripheral blood may be useful in cancer classification, and therefore we investigated the gene expression found by Affymetrix HG-U133 Plus2.0 microarray, with samples from nine HCC patients and five healthy NC (normal controls). A total of 726 probe sets showed significant differences based on the criteria of P<0.05 and absolute fold change >2. The genes were related to many biological functions, including immune response, transcription regulation and metabolism processes. Ten genes [IL-8 (interleukin 8), GOS2 (G0 /G1 switch gene 2), CXCR4 (CXC chemokine receptor 4), FOS, RPS24 (40S ribosomal protein S24), HAP90AA1, PFDN5, RPL27, GZMA and PFN1] showing significant differences were confirmed by real-time PCR in 54 HCC patients and 56 healthy NC. Seven genes [IL-8, GOS2, CXCR4, FOS, RPS24, HSP90AA1 (heat shock protein 90AA1) and PFN1] showed significant difference both in RT-PCR (reverse transcription-PCR) and microarray. Expression of IL-8 and FOS proteins was up-regulated in HCC compared with healthy controls. A gene signature in peripheral blood which can distinguish HCC patients and healthy controls may have been identified.

The identification of miR-375 as a potential biomarker in distal gastric adenocarcinoma.

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level and play an important role in carcinogenesis. Herein, we characterized the global expression of miRNA in distal gastric adenocarcinomas and determined if circulating miRNAs could be used as biomarkers for distal gastric adenocarcinoma. We used a microarray screening system to detect dysregulated miRNAs in distal gastric adenocarcinoma tissues. The expression of a subset of five aberrantly expressed miRNAs (miR-375, -196b, -204, -18b, and -93) were further quantified in an independent set of clinical samples of distal gastric adenocarcinoma by real-time quantitative RT-PCR (rt-qRT-PCR). We also used rt-qRT-PCR to investigate the expression levels of putative miRNA biomarkers in serum and tumor cell lines. In our study, the expression of a subset of microRNAs was altered in distal gastric adenocarcinoma compared to normal tissue, miR-375 was significantly downregulated in distal gastric adenocarcinoma tissues, to a level that was significantly lower than cardia adenocarcinoma (p < 0.05). The circulating serum levels of miR-375 in patients who had distal gastric adenocarcinoma were also much lower than normal controls (p < 0.001). As a biomarker, miR-375 yielded a receiver operating characteristic area under the curve of 0.835. The specificity and sensitivity was 80% and 85%, respectively, in the discrimination of distal gastric adenocarcinoma from control, at a normalized cutoff of 0.218. The expression of miR-375 was downregulated both in distal gastric adenocarcinoma tissues and serum of patients with distal gastric adenocarcinoma. These data suggest miR-375 is a potential biomarker for distal gastric adenocarcinoma.

[Feasibility of peptide mass fingerprinting for differential diagnosis of IgA and non-IgA nephropathy].

OBJECTIVE: To investigate the feasibility of peptide mass fingerprinting for non-invasive differential diagnosis of IgA nephropathy (IgAN) from the non-IgA nephropathy (IgAN).? METHODS: According to the results of renal biopsy, 56 patients were divided into IgAN group (n=28) and non-IgAN group (n=28), and peptide mass fingerprints were acquired from these patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: Nine different peptides were identified between IgAN and non-IgAN. The two most distinctive differentially expressed peptides, with peptide peak values of 4476.46 and 1968.10, showed area under curve values of 86.18% and 79.77%. Principal component analysis demonstrated that the accumulated explained variance of the first 8 differential peptides reached 95%, suggesting the feasibility of differential diagnosis of IgAN from non-IgAN. Comparison with the Matrix protein database identified the peptide with a relative molecular mass of 5338.08 as a fragment of mucin 4 inform and the 2082.77 peptide as fragment of α1-II type collagen inform. CONCLUSION: MALDI-TOF MS is feasible for differential diagnosis of IgAN and non-IgAN and also has great potentials in the classification of the subtypes of other systemic diseases.

Infant sporotrichosis in northeast China: a report of 15 cases.

BACKGROUND: Sporotrichosis is a deep mycosis caused by Sporothrix schenckii. It is not uncommon in adults and children but is very rare in infants. METHODS: We collated a series of case reports. Clinical data and laboratory and therapeutic results in 15 infants with cutaneous sporotrichosis were analyzed. RESULTS: A total of 15 cases of sporotrichosis in infants aged <10 months (mean age: 5.2 months; 10 male, five female) were diagnosed at the Department of Dermatology and Venereology, First Hospital of Jilin University, Changchun, Jilin, China, between May 2007 and May 2009. The mean duration of the disease was 2.07 months (range: 1-4 months). All the patients had facial involvement. Fixed cutaneous and lymphocutaneous sporotrichosis were seen in 11 (73.3%) and four (26.7%) patients, respectively. All patients lived in rural areas and had not experienced prior trauma or had contact with soil, plants, animals, or other sporotrichosis patients. Sporothrix schenckii was isolated in all cases, and pathological findings showed suppurative granuloma, tuberculoid granuloma, or mixed inflammatory reaction. One of the 15 patients achieved a spontaneous resolution after biopsy. Fourteen were treated with oral agents, including potassium iodide (KI) alone in two cases, itraconazole alone in three cases, terbinafine alone in four cases, and a combination of KI and terbinafine in five cases. Twelve cases were followed for 4-24 months and were cured with a mean of 2.96 months of treatment (range: 2-4 months) without adverse effects. CONCLUSIONS: Infant sporotrichosis usually presents as a solitary lesion on the face. This is the largest series of infant sporotrichosis to be reported in the literature.

[hTERT single nucleotide polymorphism is associated with increased risks of hepatocellular carcinoma and tumor metastasis].

OBJECTIVE: To investigate the effect of hTERT single nucleotide polymorphisms on the development and metastasis of hepatocellular carcinoma. METHODS: A total of 290 male patients were divided into hepatitis-induced primary hepatocellular carcinoma (HCC) group (n%162), metastatic HCC group (n%22), and control group (n%106). hTERT gene was amplified and hTERT single nucleotide polymorphisms (SNPs) were tested in these subjects. RESULTS: Significant differences were found in rs2853690 and rs10069690 distribution, but the difference in rs6554743 remained uncertain. The C and T alleles of rs10069690 and rs6554743 showed significant differences between the 3 groups; the carriers of non-T allele of rs10069690 had higher frequencies in both primary and metastatic HCC groups. CONCLUSION: Some of the polymorphisms of hTERT may increase the risks of development and metastasis of hepatocellular carcinoma.

Protective effects of total glucosides of paeony and the underlying mechanisms in carbon tetrachloride-induced experimental liver injury.

INTRODUCTION: We explored the protective effects of total glucosides of paeony (TGP) and the underlying mechanisms in carbon tetrachloride (CCl(4))-induced experimental liver injury in mice. MATERIAL AND METHODS: Chronic liver damage was induced by intraperitoneal injection of CCl(4) (0.5 µl/g) three times per week for 8 weeks. Mice also received 25, 50 or 100 mg/kg TGP. Liver sections were stained with haematoxylin/eosin. Serum amino transferases, lipid peroxidation and tumour necrosis factor-α (TNF-α) levels were determined using commercial assays. Quantitative real-time polymerase chain reaction was used to determine the changes in hepatic TNF-α, COX-2, iNOS and HO-1 expression. Protein levels of nitric oxide synthase, cyclooxygenase-2, haem oxygenase-1 and cytochrome P450 2E1 were determined by western blotting. RESULTS: Histological results showed that TGP improved the CCl(4)-induced changes in liver structure and alleviated lobular necrosis. The increases in serum protein and hepatic mRNA expression of TNF-α induced by CCl(4) treatment were suppressed by TGP. Total glucosides of paeony also attenuated the increase the expression in iNOS and CYP2E1 but augmented the increase in HO-1.The mRNA and protein expression levels of inducible HO-1 increased significantly after CCl(4) treatment. CONCLUSIONS: Total glucosides of paeony protects hepatocytes from oxidative damage induced by CCl(4). Total glucosides of paeony may achieve these effects by enhancing HO-1 expression and inhibiting the expression of proinflammatory mediators.