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1.  Clinical and oncological outcomes in Chinese patients with renal cell carcinoma and venous tumor thrombus extension: single-center experience 
To evaluate the clinical and oncological outcomes and to identify prognostic factors for survival in Chinese patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT).
A total of 86 patients who underwent nephrectomy and tumor thrombectomy for RCC and venous tumor thrombus extension from 2003 to 2013 were included in this retrospective study. The records of these patients were reviewed. Kaplan-Meier analysis was used to determine cancer-specific survival (CSS). Prognostic factors for CSS were identified by univariate and multivariate analyses using the Cox proportional hazards regression mode.
All patients in this cohort received radical nephrectomy and tumor thrombectomy. Median follow-up period was 27.0 months (range 3–111). No patients died intraoperatively, and the complication rate was 36.0%. The 1-, 3-, and 5-year CSS rates for all patients were 93.0%, 70.9%, and 58.1%, respectively, and those for patients without distant metastasis at presentation were 95.3%, 82.6%, and 68.6%, respectively. Multivariate Cox regression analysis showed that lymph node invasion, distant metastasis at presentation, and invasion of the inferior vena cava (IVC) wall were the independent prognostic factors for CSS in all patients. For patients without distant metastasis, tumor grade, lymph node invasion, and perinephric fat invasion were significantly associated with CSS on multivariate analysis.
Survival rates for patients with RCC and VTT were still poor. Our results indicated that lymph node invasion, distant metastasis at presentation, and invasion of the IVC wall were independent negative prognostic factors.
PMCID: PMC4332967  PMID: 25650039
Renal cell carcinoma; Venous tumor thrombus; Cancer-specific survival; Prognostic factors
2.  Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis 
Scientific Reports  2015;5:8191.
Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i) systematically review the evidence regarding the long-term efficacy of omalizumab in patients with persistent uncontrolled allergic asthma, and to (ii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A comprehensive search for randomized controlled trials (RCTs; ≥52 weeks) was performed, and six studies met our final inclusion criteria (n = 2,749). Omalizumab was associated with significant improvements in quality of life and the Global Evaluation of Treatment Effectiveness. Omalizumab also allowed patients to completely withdraw from inhaled corticosteroid therapy and did not increase the overall incidence of adverse events. However, there was insufficient evidence that omalizumab reduced the incidence of exacerbations, and the cost-effectiveness of omalizumab varied across studies. Our data indicated that omalizumab use for at least 52 weeks in patients with persistent uncontrolled allergic asthma was accompanied by an acceptable safety profile, but it lacked effect on the asthma exacerbations. Use of omalizumab was associated with a higher cost than conventional therapy, but these increases may be cost-effective if the medication is used in patients with severe allergic asthma.
PMCID: PMC4314644  PMID: 25645133
3.  The Novel Quantitative Technique for Assessment of Gait Symmetry Using Advanced Statistical Learning Algorithm 
BioMed Research International  2015;2015:528971.
The accurate identification of gait asymmetry is very beneficial to the assessment of at-risk gait in the clinical applications. This paper investigated the application of classification method based on statistical learning algorithm to quantify gait symmetry based on the assumption that the degree of intrinsic change in dynamical system of gait is associated with the different statistical distributions between gait variables from left-right side of lower limbs; that is, the discrimination of small difference of similarity between lower limbs is considered the reorganization of their different probability distribution. The kinetic gait data of 60 participants were recorded using a strain gauge force platform during normal walking. The classification method is designed based on advanced statistical learning algorithm such as support vector machine algorithm for binary classification and is adopted to quantitatively evaluate gait symmetry. The experiment results showed that the proposed method could capture more intrinsic dynamic information hidden in gait variables and recognize the right-left gait patterns with superior generalization performance. Moreover, our proposed techniques could identify the small significant difference between lower limbs when compared to the traditional symmetry index method for gait. The proposed algorithm would become an effective tool for early identification of the elderly gait asymmetry in the clinical diagnosis.
PMCID: PMC4332467
4.  Aspiration dynamics in structured population acts as if in a well-mixed one 
Scientific Reports  2015;5:8014.
Understanding the evolution of human interactive behaviors is important. Recent experimental results suggest that human cooperation in spatial structured population is not enhanced as predicted in previous works, when payoff-dependent imitation updating rules are used. This constraint opens up an avenue to shed light on how humans update their strategies in real life. Studies via simulations show that, instead of comparison rules, self-evaluation driven updating rules may explain why spatial structure does not alter the evolutionary outcome. Though inspiring, there is a lack of theoretical result to show the existence of such evolutionary updating rule. Here we study the aspiration dynamics, and show that it does not alter the evolutionary outcome in various population structures. Under weak selection, by analytical approximation, we find that the favored strategy in regular graphs is invariant. Further, we show that this is because the criterion under which a strategy is favored is the same as that of a well-mixed population. By simulation, we show that this holds for random networks. Although how humans update their strategies is an open question to be studied, our results provide a theoretical foundation of the updating rules that may capture the real human updating rules.
PMCID: PMC4306144  PMID: 25619664
5.  Successful en bloc resection of recurrent hepatocellular carcinoma directly invading the abdominal wall: a case report 
Repeat hepatic resection has previously been reported as the most effective treatment for recurrence of intrahepatic carcinoma. To the best of our knowledge, en bloc resection of recurrent hepatocellular carcinoma directly invading the abdominal wall has not been previously reported.
Case presentation
In September 2012, a 64-year-old Chinese male patient was referred to our hospital because of primary hepatocellular carcinoma located in Couinaud’s segments III and V. Our patient first had a hepatectomy of the liver. Ten months later, he presented with an abdominal wall mass and upper abdominal pain. Computed tomography and magnetic resonance imaging scans demonstrated a 10cm tumor in his left liver with extrahepatic metastases in his abdominal wall. It was determined that he had recurrent hepatocellular carcinoma associated with direct invasion into his abdominal wall. He had an en bloc left hepatectomy with resection of the tumor in his abdominal wall. A pathological examination of the resected specimen confirmed the diagnosis of hepatocellular carcinoma involving the abdominal wall. Disease-free margins of resection were achieved. Our patient’s postoperative course was uneventful. Eight months after the last surgery, our patient died owing to recurrence and distal metastasis.
Direct invasion of hepatocellular carcinoma into the abdominal wall is rarely encountered. Complete surgical resection should be considered in patients with an appropriate hepatic functional reserve, with consideration of the technical difficulty relating to tumor involvement with surrounding tissues.
PMCID: PMC4333836  PMID: 25609080
Hepatectomy; Hepatocellular carcinoma; Recurrence
6.  Preoperative Oral Carbohydrate Improved Postoperative Insulin Resistance in Rats through the PI3K/AKT/mTOR Pathway 
Preoperative oral carbohydrate (OCH) improves postoperative insulin resistance (PIR) and insulin sensitivity. However, the exact mechanisms involved in the improvement of PIR with respect to preoperative OCH are still not clear. The aim of this study was to investigate the involvement of preoperative OCH and PI3K/AKT/mTOR pathway in reducing PIR in rats.
Forty male Sprague-Dawley rats were randomly assigned to PreOp, glucose, saline, and fasting groups. Rats in the PreOp, glucose, and saline groups received OCH, 5% glucose solution, and saline, respectively. Rats in the fasting group did not receive anything but were fasted 3 h before surgery. Blood glucose, insulin and leucine levels, and insulin resistance, secretion, and sensitivity indexes were measured before and after surgery. mRNA and protein (total and phosphorylated) levels of mTOR, IRS-1, PI3K, PKB/AKT, and GlUT4 were measured using real-time polymerase chain reaction and Western blot in skeletal muscles.
In the PIR experiment, blood glucose, serum insulin, insulin resistance, and serum leucine levels were all significantly lower in the PreOp group than in the other 3 groups (P<0.05) after surgery. HOMA-ISI were higher in the PreOp group vs the other 3 groups after surgery (P<0.05), and HOMA-β in the PreOp group was higher than that in the other 3 groups at 30 and 120 min after surgery. Additionally, post-operative phosphorylated IRS-1, PI3K, and AKT protein levels were significantly higher in the PreOp group than in the other 3 groups (P<0.05), but no significant differences were observed in their respective protein levels (P>0.05).
OCH decreases postoperative insulin resistance and improves postoperative insulin sensitivity in skeletal muscles through the PI3K/AKT/mTOR pathway.
PMCID: PMC4288420  PMID: 25553410
Leucine; Insulin Resistance; Perioperative Care; Phosphoinositide Phospholipase C; TOR Serine-Threonine Kinases
7.  Preparative Separation of Sulfur-Containing Diketopiperazines from Marine Fungus Cladosporium sp. Using High-Speed Counter-Current Chromatography in Stepwise Elution Mode 
Marine Drugs  2015;13(1):354-365.
High-speed counter-current chromatography (HSCCC) was successively applied to the separation of three sulfur-containing diketopiperazines (DKPs) (including two new compounds cladosporin A (1) and cladosporin B (3), and a known compound haematocin (2)) from a marine fungus Cladosporium sp. The two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water at (1:1:1:1, v/v) and (2:1:2:1, v/v), in stepwise elution mode, was used for HSCCC. The preparative HSCCC separation was performed on 300 mg of crude sample yielding 26.7 mg of compound 3 at a purity of over 95%, 53.6 mg of a mixture of compounds 1 and 2, which was further separated by preparative-HPLC yielding 14.3 mg of compound 1 and 25.4 mg of compound 2 each at a purity of over 95%. Their structures were established by spectroscopic methods. The sulfur-containing DKPs suppressed the proliferation of hepatocellular carcinoma cell line HepG2. The present work represents the first application of HSCCC in the efficient preparation of marine fungal natural products.
PMCID: PMC4306941  PMID: 25584683
Cladosporium; high-speed counter-current chromatography; marine fungus; sulfur-containing diketopiperazines
8.  Cost-effectiveness analysis of adjuvant chemotherapies in patients presenting with gastric cancer after D2 gastrectomy 
BMC Cancer  2014;14(1):984.
To analyze and compare the economic outcomes of adjuvant chemotherapy with capecitabine plus oxaliplatin (referred to as the XELOX strategy) and of S-1 (the S-1 strategy) for gastric cancer patients after D2 gastrectomy.
A Markov model was developed to simulate the lifetime disease course associated with stage II or III gastric cancer after D2 gastrectomy. The lifetime quality-adjusted life years (QALYs), associated costs, and incremental cost-effectiveness ratios (ICERs) were estimated. The clinical data were derived from the results of pilot studies. Direct costs were estimated from the perspective of the Chinese healthcare system, and the utility data were measured from end-point observations of Chinese patients. Sensitivity analyses were used to explore the impact of uncertainty on the model’s outcomes.
The combined adjuvant chemotherapy strategy with XELOX yielded the greatest increase in QALYs over the course of the disease (8.1 QALYs compared with 7.8 QALYs for the S-1 strategy and 6.2 for surgery alone). The incremental cost per QALY gained using the XELOX strategy was significantly lower than that for the S-1 strategy ($3,502 vs. $6,837, respectively). The results were sensitive to the costs of oxaliplatin and the hazard ratio of relapse-free survival.
The observations reported herein suggest that adjuvant therapy with capecitabine plus oxaliplatin is a highly cost-effective strategy and more favorable treatment option than the S-1 strategy in patients with stage II or III gastric cancer who have undergone D2 gastrectomy.
PMCID: PMC4301844  PMID: 25526802
Gastric cancer; Adjuvant chemotherapy; Economic analysis; Cost-effectiveness
9.  Cascade N-Alkylation/Hemiacetalization for Facile Construction of the Spiroketal Skeleton of Acortatarin Alkaloids with Therapeutic Potentiality in Diabetic Nephropathy 
The concise building of the spiroketal core of acortatarin-type alkaloids as potential therapeutic agents in diabetic nephropathy was established in four steps, through a tandem N-alkylation/hemiacetalization between pyrrole units and the corresponding halo alcohols generated by convenient halomethylation of chiral lactones from natural aldoses.
Graphical Abstract
The Acortatarin alkaloids exhibit a promising perspective against diabetic nephropathy and other ROS-linked diseases. Facile construction of the dioxaspirocycle motif was realized through tandem N-alkylation/hemiacetalization between pyrrole units and the corresponding halo alcohols, which were derived in turn from convenient halomethylation of chiral lactones in natural carbohydrates pool.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0049-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4327998  PMID: 25511450
Acortatarin alkaloids; Diabetic nephropathy; N-alkylation/hemiacetalization; Halomethylation; Chiral lactones
10.  Cascade N-Alkylation/Hemiacetalization for Facile Construction of the Spiroketal Skeleton of Acortatarin Alkaloids with Therapeutic Potentiality in Diabetic Nephropathy 
The concise building of the spiroketal core of acortatarin-type alkaloids as potential therapeutic agents in diabetic nephropathy was established in four steps, through a tandem N-alkylation/hemiacetalization between pyrrole units and the corresponding halo alcohols generated by convenient halomethylation of chiral lactones from natural aldoses.
Graphical Abstract
The Acortatarin alkaloids exhibit a promising perspective against diabetic nephropathy and other ROS-linked diseases. Facile construction of the dioxaspirocycle motif was realized through tandem N-alkylation/hemiacetalization between pyrrole units and the corresponding halo alcohols, which were derived in turn from convenient halomethylation of chiral lactones in natural carbohydrates pool.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0049-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4327998  PMID: 25511450
Acortatarin alkaloids; Diabetic nephropathy; N-alkylation/hemiacetalization; Halomethylation; Chiral lactones
11.  Computational Identification and Systematic Classification of Novel Cytochrome P450 Genes in Salvia miltiorrhiza 
PLoS ONE  2014;9(12):e115149.
Salvia miltiorrhiza is one of the most economically important medicinal plants. Cytochrome P450 (CYP450) genes have been implicated in the biosynthesis of its active components. However, only a dozen full-length CYP450 genes have been described, and there is no systematic classification of CYP450 genes in S. miltiorrhiza. We obtained 77,549 unigenes from three tissue types of S. miltiorrhiza using RNA-Seq technology. Combining our data with previously identified CYP450 sequences and scanning with the CYP450 model from Pfam resulted in the identification of 116 full-length and 135 partial-length CYP450 genes. The 116 genes were classified into 9 clans and 38 families using standard criteria. The RNA-Seq results showed that 35 CYP450 genes were co-expressed with CYP76AH1, a marker gene for tanshinone biosynthesis, using r≥0.9 as a cutoff. The expression profiles for 16 of 19 randomly selected CYP450 obtained from RNA-Seq were validated by qRT-PCR. Comparing against the KEGG database, 10 CYP450 genes were found to be associated with diterpenoid biosynthesis. Considering all the evidence, 3 CYP450 genes were identified to be potentially involved in terpenoid biosynthesis. Moreover, we found that 15 CYP450 genes were possibly regulated by antisense transcripts (r≥0.9 or r≤–0.9). Lastly, a web resource (SMCYP450, was set up, which allows users to browse, search, retrieve and compare CYP450 genes and can serve as a centralized resource.
PMCID: PMC4262458  PMID: 25493946
12.  High-temperature continuous-wave laser realized in hollow microcavities 
Scientific Reports  2014;4:7180.
Recently, an urgent requirement of ultraviolet (UV) semiconductor laser with lower cost and higher performance has motivated our intensive research in zinc oxide (ZnO) material owing to its wide direct band gap and large exciton binding energy. Here, we demonstrate for the first time continuous-wave laser in electrically-pumped hollow polygonal microcavities based on epitaxial ZnO/MgO-core/shell nanowall networks structures, and whispering gallery type resonant modes are responsible for the lasing action. The laser diodes exhibit an ultralow threshold current density (0.27 A/cm2), two or three orders of magnitude smaller than other reported UV-light semiconductor laser diodes to our knowledge. More importantly, the continuous-current-driven diode can achieve lasing up to ~430 K, showing a good temperature tolerance. This study indicates that nano-size injection lasers can be made from epitaxial semiconductor microcavities, which is a considerable advance towards the realization of practical UV coherent light sources, facilitating the existing applications and suggesting new potentials.
PMCID: PMC4241518  PMID: 25417966
13.  Inactivation of SAM-Methyltransferase is the Mechanism of Attenuation of a Historic Louse Borne Typhus Vaccine Strain 
PLoS ONE  2014;9(11):e113285.
Louse borne typhus (also called epidemic typhus) was one of man's major scourges, and epidemics of the disease can be reignited when social, economic, or political systems are disrupted. The fear of a bioterrorist attack using the etiologic agent of typhus, Rickettsia prowazekii, was a reality. An attenuated typhus vaccine, R. prowazekii Madrid E strain, was observed to revert to virulence as demonstrated by isolation of the virulent revertant Evir strain from animals which were inoculated with Madrid E strain. The mechanism of the mutation in R. prowazekii that affects the virulence of the vaccine was not known. We sequenced the genome of the virulent revertant Evir strain and compared its genome sequence with the genome sequences of its parental strain, Madrid E. We found that only a single nucleotide in the entire genome was different between the vaccine strain Madrid E and its virulent revertant strain Evir. The mutation is a single nucleotide insertion in the methyltransferase gene (also known as PR028) in the vaccine strain that inactivated the gene. We also confirmed that the vaccine strain E did not cause fever in guinea pigs and the virulent revertant strain Evir caused fever in guinea pigs. We concluded that a single nucleotide insertion in the methyltransferase gene of R. prowazekii attenuated the R. prowazekii vaccine strain E. This suggested that an irreversible insertion or deletion mutation in the methyl transferase gene of R. prowazekii is required for Madrid E to be considered a safe vaccine.
PMCID: PMC4239044  PMID: 25412248
14.  Endoscopic variceal ligation caused massive bleeding due to laceration of an esophageal varicose vein with tissue glue emboli 
World Journal of Gastroenterology : WJG  2014;20(42):15937-15940.
Endoscopic variceal obturation of gastric varices with tissue glue is considered the first choice for management of gastric varices, and is usually safe and effective. However, there is still a low incidence of complications and some are even fatal. Here, we present a case in which endoscopic variceal ligation caused laceration of the esophageal varicose vein with tissue glue emboli and massive bleeding after 3 mo. Cessation of bleeding was achieved via variceal sclerotherapy using a cap-fitted gastroscope. Methods of recognizing an esophageal varicose vein with tissue glue plug are discussed.
PMCID: PMC4229563  PMID: 25400482
Gastroesophageal varices; Variceal bleeding; Laceration; Varices ligation; Tissue glue injection
15.  Acute diarrhea and metabolic acidosis caused by tuberculous vesico-rectal fistula 
World Journal of Gastroenterology : WJG  2014;20(41):15462-15466.
Acquired vesico-rectal fistula is an uncommon complication of pelvic malignant tumors, surgical injury, inflammatory disorders such as tuberculosis infection, radiotherapy and less commonly diverticulum of the urinary tract. The fistula is often identified by urinary tract abnormalities such as dysuria, recurrent urinary tract infection, pneumaturia, and fecaluria. Here, we report an unusual case of a patient with a vesico-rectal fistula of tuberculous origin, presenting with severe acute diarrhea, metabolic acidosis, hyperchloremia and hypokalemia while with only mild urinary tract symptoms. The patient was cured by tuberculostatic therapy.
PMCID: PMC4223281  PMID: 25386096
Vesico-rectal fistula; Tuberculous; Diarrhea; Acidosis; Hyperchloremia; Hypokalemia
16.  The complex jujube genome provides insights into fruit tree biology 
Nature Communications  2014;5:5315.
The jujube (Ziziphus jujuba Mill.), a member of family Rhamnaceae, is a major dry fruit and a traditional herbal medicine for more than one billion people. Here we present a high-quality sequence for the complex jujube genome, the first genome sequence of Rhamnaceae, using an integrated strategy. The final assembly spans 437.65 Mb (98.6% of the estimated) with 321.45 Mb anchored to the 12 pseudo-chromosomes and contains 32,808 genes. The jujube genome has undergone frequent inter-chromosome fusions and segmental duplications, but no recent whole-genome duplication. Further analyses of the jujube-specific genes and transcriptome data from 15 tissues reveal the molecular mechanisms underlying some specific properties of the jujube. Its high vitamin C content can be attributed to a unique high level expression of genes involved in both biosynthesis and regeneration. Our study provides insights into jujube-specific biology and valuable genomic resources for the improvement of Rhamnaceae plants and other fruit trees.
The jujube is a major dry fruit crop in China and is commonly used for medicinal purposes. Here the authors sequence the genome and transcriptome of the most widely cultivated jujube cultivar, Dongzao, and highlight the genetic and molecular basis of agronomically important jujube traits, such as vitamin C content.
PMCID: PMC4220462  PMID: 25350882
17.  Expression profiling and clinicopathological significance of DNA methyltransferase 1, 3A and 3B in sporadic human renal cell carcinoma 
Purpose: This study aimed to evaluate the expression of DNA methyltransferase (DNMT) family proteins in renal cell carcinoma (RCC) and to assess the clinical significance and prognostic value of their expression patterns. Methods: A total of 97 renal cell carcinoma and 52 no-tumor tissues were recruited for immunohistochemical analysis of their expression. Results: DNMT1, DNMT3A and DNMT3B proteins were highly expressed in clear cell RCC, papillary RCC and chromophobe RCC tissues than that of no-tumor tissues (all P < 0.05). DNMT1, DNMT3A and DNMT3B expression was significantly associated with tumor size (P=0.003, 0.001 and 0.003, respectively), tumor pathology stage (P=0.039, 0.034 and 0.037, respectively), histopathological grading (P=0.042, 0.026 and 0.031, respectively), lymph node metastasis (P=0.022, 0.030 and 0.020, respectively) and vascular invasion (P=0.042, 0.031 and 0.044, respectively). The Kaplan-Meier survival analysis demonstrated that expression of DNMTs protein in RCC was significantly associated with shorter over all survival and disease-free survival (all P < 0.05). Furthermore, multivariate analysis showed that the expression of DNMT1 was an independent prognostic factor for overall survival (OS) (P=0.036), and the expression of DNMT3A or DNMT3B was an independent prognostic factor for disease-free survival (DFS) in the patients (P=0.031 and P=0.023, respectively). Conclusions: DNMTs were higher expressed in RCC than no-tumor tissues, and the expression of DNMTs were strongly associated with RCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence, and prognosis. DNMTs may thus serve as prognostic markers and novel therapeutic targets for RCC patients.
PMCID: PMC4270597  PMID: 25550796
Renal cell carcinoma; DNA methyltransferase; progression; prognosis
18.  Study of liver cirrhosis over ten consecutive years in Southern China 
World Journal of Gastroenterology : WJG  2014;20(37):13546-13555.
AIM: To investigate the etiology and complications of liver cirrhosis (LC) in Southern China.
METHODS: In this retrospective, cross-sectional study, we identified cases of liver cirrhosis admitted between January 2001 to December 2010 and reviewed the medical records. Patient demographics, etiologies and complications were collected, and etiological changes were illustrated by consecutive years and within two time periods (2001-2005 and 2006-2010). All results were expressed as the mean ± SD or as a percentage. The χ2 test or Student’s t-test was used to analyze the differences in age, gender, and etiological distribution, and one-way analysis of variance was applied to estimate the trends in etiological changes. We analyzed the relationship between the etiologies and complications using unconditioned logistic regression, and the risk of upper gastrointestinal bleeding (UGIB) and hepatocellular carcinoma (HCC) in the major etiological groups was evaluated as ORs. A P value less than 0.05 was considered significant. Statistical computation was performed using SPSS 17.0 software.
RESULTS: In this study, we identified 6719 (83.16%) male patients and 1361 (16.84%) female patients. The average age of all of the patients was 50.5 years at the time of diagnosis. The distribution of etiological agents was as follows: viral hepatitis, 80.62% [hepatitis B virus (HBV) 77.22%, hepatitis C virus (HCV) 2.80%, (HBV + HCV) 0.58%]; alcohol, 5.68%; mixed etiology, 4.95%; cryptogenic, 2.93%; and autoimmune hepatitis, 2.03%; whereas the other included etiologies accounted for less than 4% of the total. Infantile hepatitis syndrome LC patients were the youngest (2.5 years of age), followed by the metabolic LC group (27.2 years of age). Viral hepatitis, alcohol, and mixed etiology were more prevalent in the male group, whereas autoimmune diseases, cryptogenic cirrhosis, and metabolic diseases were more prevalent in the female group. When comparing the etiological distribution in 2001-2005 with that in 2006-2010, the proportion of viral hepatitis decreased from 84.7% to 78.3% (P < 0.001), and the proportion of HBV-induced LC also decreased from 81.9% to 74.6% (P < 0.001). The incidence of mixed etiology, cryptogenic cirrhosis, and autoimmune diseases increased by 3.1% (P < 0.001), 0.5% (P = 0.158), and 1.3% (P < 0.001), respectively. Alcohol-induced LC remained relatively steady over the 10-year period. The ORs of the development of UGIB between HBV and other major etiologies were as follows: HCV, 1.07; alcohol, 1.89; autoimmune, 0.90; mixed etiology, 0.83; and cryptogenic, 1.76. The ORs of the occurrence of HCC between HBV and other major etiologies were as follows: HCV, 0.54; alcohol, 0.16; autoimmune, 0.05; mixed etiology, 0.58; and cryptogenic, 0.60.
CONCLUSION: The major etiology of liver cirrhosis in Southern China is viral hepatitis. However, the proportions of viral hepatitis and HBV are gradually decreasing. Alcoholic LC patients exhibit a greater risk of experiencing UGIB, and HBV LC patients may have a greater risk of HCC.
PMCID: PMC4188906  PMID: 25309085
Liver cirrhosis; Epidemiology; Etiology; Complication; Hepatocellular carcinoma; Southern China
19.  Diagnostic and prognostic value of a disintegrin and metalloproteinase-17 in patients with gliomas 
Oncology Letters  2014;8(6):2616-2620.
A disintegrin and metalloproteinase-17 (ADAM17) has been shown to regulate numerous proteins involved in the cell cycle, as well as tumor oncogenes. The expression pattern of ADAM17 in glioma patients, however, is unclear. In the present study, the expression pattern and prognostic significance of ADAM17 was investigated in patients with glioma. A total of 60 glioma specimens and eight normal control samples were obtained. Immunohistochemical and western blot analyses were used to examine the expression of ADAM17. In addition, the association of ADAM17 expression with the clinicopathological parameters and the survival rates of the glioma patients was analyzed. The results showed that ADAM17 was upregulated in the high-grade glioma tissues compared with that in the low-grade and normal brain tissues of the glioma patients, and that the level increased with ascending World Health Organization tumor grade (P<0.05). Furthermore, the survival rate of the patients with ADAM17-positive tumors was lower compared with the patients with ADAM17-negative tumors. These results indicated that the overexpression of ADAM17 was correlated with a high tumor grade and a poor prognosis in patients with glioma. ADAM17 may have an important oncogenic function in glioma progression, and is a potential diagnostic and therapeutic target.
PMCID: PMC4214486  PMID: 25364437
ADAM17; expression; prognostic value; glioma
20.  Intestinal obstruction caused by extramedullary hematopoiesis and ascites in primary myelofibrosis 
World Journal of Gastroenterology : WJG  2014;20(33):11921-11926.
Primary myelofibrosis (PMF) is a clonal hematopoietic stem cell disorder. It is characterized by bone marrow fibrosis, extramedullary hematopoiesis with hepatosplenomegaly and leukoerythroblastosis in the peripheral blood. The main clinical manifestations of PMF are anemia, bleeding, hepatosplenomegaly, fatigue, and fever. Here we report a rare case of PMF with anemia, small bowel obstruction and ascites due to extramedullary hematopoiesis and portal hypertension. The diagnosis was difficult to establish before surgery and the differential diagnosis is discussed.
PMCID: PMC4155387  PMID: 25206301
Primary myelofibrosis; Intestinal obstruction; Ascites; Extramedullary hematopoiesis
21.  Time-Integrated Fluorescence Cumulant Analysis and Its Application in Living Cells 
Methods in enzymology  2013;518:99-119.
Time-integrated fluorescence cumulant analysis (TIFCA) is a data analysis technique for fluorescence fluctuation spectroscopy (FFS) that extracts information from the cumulants of the integrated fluorescence intensity. It is the first exact theory that describes the effect of sampling time on FFS experiment. Rebinning of data to longer sampling times helps to increase the signal/noise ratio of the experimental cumulants of the photon counts. The sampling time dependence of the cumulants encodes both brightness and diffusion information of the sample. TIFCA analysis extracts this formation by fitting the cumulants to model functions. Generalization of TIFCA to multicolor FFS experiment is straightforward. Here, we present an overview of the theory, its implementation, as well as the benefits and requirements of TIFCA. The questions of why, when, and how to use TIFCA will be discussed. We give several examples of practical applications of TIFCA, particularly focused on measuring molecular interaction in living cells.
PMCID: PMC4152916  PMID: 23276537
22.  CLDN3 inhibits cancer aggressiveness via Wnt-EMT signaling and is a potential prognostic biomarker for hepatocellular carcinoma 
Oncotarget  2014;5(17):7663-7676.
Hepatocellular carcinoma (HCC) is one of the most common fatal malignancies but the molecular genetic basis of this disease remains unclear. By using genome-wide methylation profiling analysis, we identified CLDN3 as an epigenetically regulated gene in cancer. Here, we investigated its function and clinical relevance in human HCC. CLDN3 downregulation occurred in 87/114 (76.3%) of primary HCCs, where it was correlated significantly with shorter survival of HCC patients (P=0.021). Moreover, multivariate cyclooxygenase regression analysis showed that CLDN3 was an independent prognostic factor for overall survival (P=0.014). Absent expression of CLDN3 was also detected in 67% of HCC cell lines, which was significantly associated with its promoter hypermethylation. Ectopic expression of CLDN3 in HCC cells could inhibit cell motility, cell invasiveness, and tumor formation in nude mice. Mechanistic investigations suggested through downregulation of GSK3B, CTNNB1, SNAI2, and CDH2, CLDN3 could significantly suppress metastasis by inactivating the Wnt/β-catenin-epithelial mesenchymal transition (EMT) axis in HCC cells. Collectively, our findings demonstrated that CLDN3 is an epigenetically silenced metastasis suppressor gene in HCC. A better understanding of the molecular mechanism of CLDN3 in inhibiting liver cancer cell metastasis may lead to a more effective management of HCC patients with the inactivation of CLDN3.
PMCID: PMC4202152  PMID: 25277196
CLDN3; hepatocellular carcinoma; metastasis; survival
23.  Comprehensive Analysis of Alternative Splicing in Digitalis purpurea by Strand-Specific RNA-Seq 
PLoS ONE  2014;9(8):e106001.
Digitalis purpurea (D. purpurea) is one of the most important medicinal plants and is well known in the treatment of heart failure because of the cardiac glycosides that are its main active compounds. However, in the absence of strand specific sequencing information, the post-transcriptional mechanism of gene regulation in D. purpurea thus far remains unknown. In this study, a strand-specific RNA-Seq library was constructed and sequenced using Illumina HiSeq platforms to characterize the transcriptome of D. purpurea with a focus on alternative splicing (AS) events and the effect of AS on protein domains. De novo RNA-Seq assembly resulted in 48,475 genes. Based on the assembled transcripts, we reported a list of 3,265 AS genes, including 5,408 AS events in D. purpurea. Interestingly, both glycosyltransferases and monooxygenase, which were involved in the biosynthesis of cardiac glycosides, are regulated by AS. A total of 2,422 AS events occurred in coding regions, and 959 AS events were located in the regions of 882 unique protein domains, which could affect protein function. This D. purpurea transcriptome study substantially increased the expressed sequence resource and presented a better understanding of post-transcriptional regulation to further facilitate the medicinal applications of D. purpurea for human health.
PMCID: PMC4148352  PMID: 25167195
24.  TolC Promotes ExPEC Biofilm Formation and Curli Production in Response to Medium Osmolarity 
BioMed Research International  2014;2014:574274.
While a high osmolarity medium activates Cpx signaling and causes CpxR to repress csgD expression, and efflux protein TolC protein plays an important role in biofilm formation in Escherichia coli, whether TolC also responds to an osmolarity change to regulate biofilm formation in extraintestinal pathogenic E. coli (ExPEC) remains unknown. In this study, we constructed ΔtolC mutant and complement ExPEC strains to investigate the role of TolC in the retention of biofilm formation and curli production capability under different osmotic conditions. The ΔtolC mutant showed significantly decreased biofilm formation and lost the ability to produce curli fimbriae compared to its parent ExPEC strain PPECC42 when cultured in M9 medium or 1/2 M9 medium of increased osmolarity with NaCl or sucrose at 28°C. However, biofilm formation and curli production levels were restored to wild-type levels in the ΔtolC mutant in 1/2 M9 medium. We propose for the first time that TolC protein is able to form biofilm even under high osmotic stress. Our findings reveal an interplay between the role of TolC in ExPEC biofilm formation and the osmolarity of the surrounding environment, thus providing guidance for the development of a treatment for ExPEC biofilm formation.
PMCID: PMC4163439  PMID: 25243151
25.  Androgenic regulation of beta-defensins in the mouse epididymis 
The majority of beta-defensin family members are exclusively expressed in the epididymis, and some members have been shown to play essential roles in sperm maturation and fertility in rats, mice and humans. Therefore, beta-defensins are hypothesized to be potential targets for contraception and infertility diagnosis and treatment. Clarifying the regulatory mechanisms for the expression of these genes is necessary. Androgen/androgen receptor (AR) signaling plays an important regulatory role in epididymal structure and function. However, very little is known about the androgenic regulation on the production and secretion of the epididymal beta-defensins.
The expression of beta-defensins was detected by quantitative RT-PCR. The androgen dependence of beta-defensins was determined by bilateral orchiectomy and androgen supplementation. The androgen response elements (AREs) in the promoters of beta-defensins were identified using the MatInspector software. The binding of AR to AREs was assayed by ChIP-PCR/qPCR.
We demonstrated that 23 mouse caput epididymal beta-defensins were differentially regulated by androgen/androgen receptor. Six genes, Defb18, 19, 20, 39, 41, and 42, showed full regulation by androgens. Ten genes, Defb15, 30, 34, 37, 40, 45, 51, 52, 22 and Spag11a, were partially regulated by androgens. Defb15, 18, 19, 20, 30, 34, 37, 39, 41, 42, 22 and Spag11a were associated with androgen receptor binding sites in their promoter or intronic regions, indicating direct regulation of AR. Six genes, Defb1, 12, 13, 29, 35, and spag11b/c, exhibited an androgen-independent expression pattern. One gene, Defb25, was highly dependent on testicular factors rather on androgens.
The present study provides novel insights into the mechanisms of androgen regulation on epididymal beta-defensins, enabling a better understanding of the function of beta-defensins in sperm maturation and fertility.
PMCID: PMC4127520  PMID: 25099571
Androgen; Androgen receptor; Epididymis; Beta-defensins

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