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1.  Fibroblast growth factor receptor 4 protein expression and clinicopathological features in gastric cancer 
AIM: To investigate fibroblast growth factor receptor 4 (FGFR4) protein expression in Chinese patients with resectable gastric cancer (GC) and the association with clinicopathological characteristics and survival.
METHODS: One hundred and seventy-five GC patients who underwent curative surgical procedures were enrolled in this study. The protein expression of FGFR4 in formalin-fixed, paraffin-embedded (FFPE) GC tissues was determined by immunohistochemical (IHC) analysis. Patient clinicopathological data and survival information were also collected and χ2 statistical analysis was performed to analyze FGFR4 protein expression in the subgroups with differing clinicopathological characteristics including; gender, age, tumor location, differentiation, tumor-node-metastasis stage, macroscopic type, depth of invasion, lymph node metastases, distant metastasis, neural invasion and vascular invasion. Furthermore, some common molecular markers of GC in our cancer center, including p53, p27, topoisomerase IIα (Topo IIα) were also determined by IHC and their association with FGFR4 protein expression evaluated. The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using the log rank test.
RESULTS: Seventy seven cases (44%) were found to have high expression of FGFR4 protein. Significantly different FGFR4 expression was observed between gastric cancers with differing expression of Topo IIα (log rank χ2 = 9.4760, P = 0.0236). No significant differences were observed between subgroups defined by any of the other clinicopathological characteristics. The median survival time of the FGFR4 high expression (77 cases) and low expression groups (98 cases) was 27 mo and 39 mo, respectively. The five-year survival rates and median survival times of gastric cancers with high FGFR4 expression were worse than those with low expression (30.8% vs 39.2%, 27 mo vs 39 mo), respectively, however, no significant difference was observed in survival time (log rank χ2 = 1.0477, P = 0.3060). Survival analysis revealed that high expression of FGFR4 was a predictor of poor outcome in GC patients if the tumor was small (less than or equal to 3 cm in size) (log rank χ2 = 5.5033, P = 0.0190), well differentiated (log rank χ2 = 7.9757, P = 0.0047), and of T1 or T2 stage invasion depth (log rank χ2 = 4.8827, P = 0.0271).
CONCLUSION: Our results suggest that high tumor expression of FGFR4 protein is not an independent risk factor for GC cancer initiation, but is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or in the early stages of invasion.
PMCID: PMC4323460
Gastric cancer; Fibroblast growth factor receptor 4; Protein expression; Clinicopathological characteristics; Prognosis
2.  Effects of Ferulic Acid and γ-Oryzanol on High-Fat and High-Fructose Diet-Induced Metabolic Syndrome in Rats 
PLoS ONE  2015;10(2):e0118135.
The high morbidity of metabolic dysfunction diseases has heightened interest in seeking natural and safe compounds to maintain optimal health. γ-Oryzanol (OZ), the ferulic acid (FA) ester with phytosterols, mainly present in rice bran has been shown to improve markers of metabolic syndrome. This study investigates the effects of FA and OZ on alleviating high-fat and high-fructose diet (HFFD)-induced metabolic syndrome parameters.
Male SD rats were fed with a regular rodent diet, HFFD, or HFFD supplemented with 0.05% FA or 0.16% OZ (equimolar concentrations) for 13 weeks. Food intake, organ indices, serum lipid profiles, glucose metabolism, insulin resistance (IR) index and cytokine levels were analyzed. The mechanisms were further investigated in oleic acid-stimulated HepG2 cells by analyzing triglyceride (TG) content and lipogenesis-related gene expressions.
In the in vivo study, FA and OZ exhibited similar effects in alleviating HFFD-induced obesity, hyperlipidemia, hyperglycemia, and IR. However, only OZ treatment significantly decreased liver index and hepatic TG content, lowered serum levels of C-reactive protein and IL-6, and increased serum concentration of adiponectin. In the in vitro assay, only OZ administration significantly inhibited intracellular TG accumulation and down-regulated expression of stearoyl coenzyme-A desaturase-1, which might facilitate OZ to enhance its hepatoprotective effect.
OZ is more effective than FA in inhibiting hepatic fat accumulation and inflammation. Thus, FA and OZ could be used as dietary supplements to alleviate the deleterious effects of HFFD.
PMCID: PMC4315454  PMID: 25646799
3.  Correlation between Serum Levels of High Mobility Group Box-1 Protein and Pancreatitis: A Meta-Analysis 
BioMed Research International  2015;2015:430185.
Background. Aberrant expression of high mobility group box-1 protein (HMGB1) contributes to the progression of various inflammatory diseases. This meta-analysis focused on the clinical significance of serum HMGB1 levels in pancreatitis patients, with the goal of building a novel diagnostic score model. Method. We conducted a meta-analysis by searching in the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases without any language restrictions. Studies were pooled and standard mean difference (SMD) and its corresponding 95% confidence intervals (95% CIs) were calculated. Version 12.0 STATA software was used for statistical analysis. Results. We performed a final analysis of 841 subjects from 12 clinical case-control studies. The meta-analysis results showed a positive association between serum HMGB1 levels and the progression of pancreatitis. In the subgroup analysis by country, high serum level of HMGB1 may be related to pancreatitis progression in China, Korea, Hungary, and Japan populations (all P < 0.05). Conclusion. The present meta-analysis indicated that serum HMGB1 level was statistically elevated in patients with pancreatitis, and thus serum levels of HMGB1 could be determined to be a useful biomarker for pancreatitis patients.
PMCID: PMC4324490
4.  Tumor-targeting novel manganese complex induces ROS-mediated apoptotic and autophagic cancer cell death 
In this study, the antitumor activity of the novel manganese (II) compound, Adpa-Mn {[(Adpa)Mn(Cl)(H2O)] (Adpa=bis(2-pyridylmethyl)amino-2-propionic acid)}, and its possible mechanisms of action were investigated. In vitro, the growth inhibitory effects of Adpa-Mn (with IC50 values lower than 15 μM) on tumor cell lines were examined by MTT assay. We found that this compound was more selective against cancer cells than the popular chemotherapeutic reagent, cisplatin. We then found that Adpa-Mn achieved its selectivity against cancer cells through the transferrin (Tf)-transferrin receptor (TfR) system, which is highly expressed in tumor cells. Furthermore, Adpa-Mn induced both apoptosis and autophagy, as indicated by chromatin condensation, the activation of poly(ADP-ribose) polymerase (PARP), Annexin V/prop-idium iodide staining, an enhanced fluorescence intensity of monodansylcadaverine (MDC), as well as the elevated expression of the autophagy-related protein, microtubule-associated protein 1 light chain 3 (LC3). In addition, Adpa-Mn induced the generation of intracellular reactive oxygen species (ROS) and its anticancer effects were significantly reduced following pre-treatment with the antioxidant, N-acetyl cysteine, indicating that ROS triggered cell death. In vivo, the induction of apoptosis and autophagy in tumor tissue was confirmed following treatment with Adpa-Mn, which contributed to its significant antitumor activity against hepatocellular carcinoma (Hep-A cell) xenografts at 10 mg/kg. Taken together, these data suggest the possible use of Adpa-Mn as a novel anticancer drug.
PMCID: PMC4314420  PMID: 25604962
manganese complex; anticancer; autophagy; apoptosis; reactive oxygen species
5.  Co-barcoded sequence reads from long DNA fragments: a cost-effective solution for “perfect genome” sequencing 
Frontiers in Genetics  2015;5:466.
Next generation sequencing (NGS) technologies, primarily based on massively parallel sequencing, have touched and radically changed almost all aspects of research worldwide. These technologies have allowed for the rapid analysis, to date, of the genomes of more than 2,000 different species. In humans, NGS has arguably had the largest impact. Over 100,000 genomes of individual humans (based on various estimates) have been sequenced allowing for deep insights into what makes individuals and families unique and what causes disease in each of us. Despite all of this progress, the current state of the art in sequence technology is far from generating a “perfect genome” sequence and much remains to be understood in the biology of human and other organisms’ genomes. In the article that follows, we outline why the “perfect genome” in humans is important, what is lacking from current human whole genome sequences, and a potential strategy for achieving the “perfect genome” in a cost effective manner.
PMCID: PMC4294197  PMID: 25642240
WGS; whole genome sequencing; haplotyping; NGS; MPS; “perfect genome; ” LFR; de novo assembly
6.  Complete Genome Sequence of the Fish Pathogen Yersinia ruckeri Strain SC09, Isolated from Diseased Ictalurus punctatus in China 
Genome Announcements  2015;3(1):e01327-14.
Yersinia ruckeri SC09 is a Gram-negative bacterium isolated from a moribund Ictalurus punctatus collected in Jianyang, China. Here, we report the complete genome sequence of this microorganism to facilitate the investigation of its pathogenicity and to reevaluate its taxonomic position.
PMCID: PMC4290980  PMID: 25573927
7.  Autoantibodies in Chinese patients with chronic hepatitis B: Prevalence and clinical associations 
AIM: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinese patients with chronic hepatitis B (CHB).
METHODS: A total of 325 Chinese patients with CHB were enrolled in this retrospective, hospital-based study. Patients with chronic hepatitis C (CHC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC) were included, with healthy donors acting as controls. A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay. The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies (ANA-H), smooth-muscle antibodies, anti-liver kidney microsome type 1, anti-liver cytosolic antigen type 1, and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rim-like, anti-mitochondrial antibodies-M2 (AMA-M2), anti-BPO (recombinant antigen targeted by AMA-M2), anti-Sp100, anti-promyelocytic leukemia protein (anti-PML), and anti-gp210. The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case. Anti-Ro52 antibodies were also tested.
RESULTS: The prevalence of any autoantibody in CHB amounted to 58.2%, which was similar to the 66.2% prevalence in CHC, significantly higher than the 6.7% in the healthy controls (P < 0.001), and lower than the 100% found in AIH and PBC (P = 0.004 and P < 0.001, respectively). There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients (11.1% vs 0%, P = 0.003; 12.6% vs 0%, P < 0.001, respectively). The prevalence and titer of AMA, anti-BPO, anti-PML, and anti-gp210 were higher in PBC than in those with CHB. Among the CHB patients, the prevalence of ANA, especially ANA-H, was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis. Thirty-eight cases of hepatocellular carcinoma (HCC) in CHB showed a significant difference compared with non-HCC patients in the prevalence of anti-PML (0% vs 12.5%, P = 0.013). Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC, and that it was strongly correlated with both compensated and decompensated cirrhosis. In contrast, the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis (18.5% vs 8.2%, P = 0.039). Moreover, the AIH profile was also closely associated with hepatitis B e-antigen positivity.
CONCLUSION: ANA-H could be an indicator of early-stage CHB. Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.
PMCID: PMC4284347  PMID: 25574103
Autoantibodies; Chronic hepatitis B; Autoimmune hepatitis; Primary biliary cirrhosis; Cirrhosis; Hepatocellular carcinoma
8.  Insulin Resistance Is an Important Risk Factor for Cognitive Impairment in Elderly Patients with Primary Hypertension 
Yonsei Medical Journal  2014;56(1):89-94.
Insulin resistance plays a role in the development of dementia and hypertension. We investigated a possible relationship between cognitive impairment and insulin resistance in elderly Chinese patients with primary hypertension.
Materials and Methods
One hundred and thirty-two hypertensive elderly patients (>60 years) were enrolled in this study, and assigned into either the cognitive impairment group (n=61) or the normal cognitive group (n=71). Gender, age, education, body mass index (BMI), waist hip ratio (WHR), total cholesterol (TC), triglyceride (TG), C-reactive protein (CRP), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), creatinine (Cr), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model of assessment for insulin resistance index (HOMA-IR), systolic blood pressure, diastolic blood pressure, smoking history, atherosclerosis and the proportion of uncontrolled hypertension were compared between the two groups. Multi-factorial logistic regression analysis was performed.
No significant differences were found in gender, age, TC, CRP, HDL-C, LDL-C, Cr, BP, smoking history, atherosclerosis and the proportion of uncontrolled hypertension between the two groups. The cognitive impairment group had lower education levels, and higher BMI, WHR, TG, FPG, FINS, and HOMA-IR levels than the control group. Logistic regression analysis revealed the levels of education, BMI, WHR, and HOMA-IR as independent factors that predict cognitive impairment in patients.
Our study demonstrates that poor education and increased BMI, WHR, and HOMA-IR are independent risk factors for cognitive impairment in elderly patients with hypertension. Insulin resistance plays an important role in the development of cognitive impairment in primary elderly hypertensive patients.
PMCID: PMC4276782  PMID: 25510751
Hypertension; insulin resistance; cognitive impairment; elderly; risk factor
9.  Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck 
Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model.
PMCID: PMC4305085  PMID: 25535101
Chronic hepatitis B; Hepatitis B virus; Woodchuck hepatitis virus; Immunotherapy; Gene therapy; Therapeutic vaccination; Immunomodulation
10.  Non-alcoholic fatty liver disease associated with gallstones in females rather than males: a longitudinal cohort study in Chinese urban population 
BMC Gastroenterology  2014;14(1):213.
Whether non-alcoholic fatty liver disease (NAFLD) is a risk factor for gallstones remains uncertain. Few longitudinal or cohort studies have been used to identify this relationship. The aim of this study was to confirm the association between NAFLD and gallstones in a longitudinal cohort of urban dwellers in China.
To elucidate the association between NAFLD and gallstones, we fitted a generalized estimating equation (GEE) model in a large-scale longitudinal cohort over 6 years, which included 11,200 participants with at least three regular health check-ups.
A total of 498 cases of gallstones occurred during the 6-year follow-up, which resulted in a total incidence density of 12.73 per 1000 person-years (498/39, 135.5 person-years). The GEE analyses confirmed and clarified the association between NAFLD and gallstones (relative risk (RR) = 1.2381, 95% confidence interval (CI) = 1.003–1.528, P = 0.047) after adjusting for other potential confounding factors, especially in females (RR = 1.707, 95% CI = 1.245–2.341, P = 0.001).
NAFLD is associated with gallstones in an urban Chinese population from the middle to upper socioeconomic strata. Moreover, this association is more strongly apparent in females than in males. Further cohort studies must be conducted to confirm this association in the general population.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-014-0213-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4273434  PMID: 25496394
Gallstones; Non-alcoholic fatty liver disease (NAFLD); Longitudinal cohort study; Generalized estimated equation (GEE)
11.  Hyperthyroid and Hypothyroid Status Was Strongly Associated with Gout and Weakly Associated with Hyperuricaemia 
PLoS ONE  2014;9(12):e114579.
The aim of this study was to estimate the risk of hyperuricaemia and gout in people with hypothyroid or hyperthyroid status.
This study analyzed data from individuals who participated in health screening programs at Chang Gung Memorial Hospital in northern Taiwan (2000–2010). Participants were categorized as having euthyroid, hypothyroid, or hyperthyroid status according to their thyroid-stimulating hormone (TSH) levels. Multinomial logistic regression models were used to calculate the odds ratios (95% CI) for hyperuricaemia and gout in participants with thyroid dysfunction compared to euthyroid participants.
A total of 87,813 (euthyroid, 83,502; hypothyroid, 1,460; hyperthyroid, 2,851) participants were included. The prevalence of hyperuricaemia was higher in hyperthyroid subjects (19.4%) than in euthyroid subjects (17.8%) but not in hypothyroid subjects (19.3%). The prevalence of gout was significantly higher in both hypothyroid (6.0%) and hyperthyroid (5.3%) subjects than in euthyroid subjects (4.3%). In men, hypothyroid or hyperthyroid status was not associated with hyperuricaemia. However, hypothyroid or hyperthyroid status was associated with ORs (95% CI) of 1.47 (1.10–1.97) and 1.37 (1.10–1.69), respectively, for gout. In women, hypothyroid status was not associated with hyperuricaemia or gout. However, hyperthyroid status was associated with ORs (95% CI) of 1.42 (1.24–1.62) for hyperuricaemia and 2.13 (1.58–2.87) for gout.
Both hyperthyroid and hypothyroid status were significantly associated with gout and weakly associated with hyperuricaemia. A thyroid function test for gout patients may by warranted.
PMCID: PMC4259336  PMID: 25486420
12.  Deep brain light stimulation effects on glutamate and dopamine concentration 
Biomedical Optics Express  2014;6(1):23-31.
Compared to deep brain electrical stimulation, which has been applied to treating pathological brain diseases, little work has been done on the effect of deep brain light stimulation. A fiber-coupled laser stimulator at 840 nm wavelength and 130 Hz pulse repetition rate is developed in this work for deep brain light stimulation in a rat model. Concentration changes in glutamate and dopamine in the striatum are observed using a microdialysis probe when the subthalamic nucleus (STN) is stimulated at various optical power levels. Experimental results show that light stimulation causes the concentration of glutamate to decrease while that of dopamine is increased. This suggests that deep brain light stimulation of the STN is a promising therapeutic strategy for dopamine-related diseases such as Parkinson’s disease. The stimulator developed for this work is useful for deep brain light stimulation in biomedical research.
PMCID: PMC4317125  PMID: 25657871
(170.5180) Photodynamic therapy; (170.3660) Light propagation in tissues; (170.3890) Medical optics instrumentation; (170.1420) Biology; (170.1610) Clinical applications; (170.0170) Medical optics and biotechnology
13.  Hierarchical Macro-meso-microporous ZSM-5 Zeolite Hollow Fibers With Highly Efficient Catalytic Cracking Capability 
Scientific Reports  2014;4:7276.
Zeolite fibers have attracted growing interest for a range of new applications because of their structural particularity while maintaining the intrinsic performances of the building blocks of zeolites. The fabrication of uniform zeolite fibers with tunable hierarchical porosity and further exploration of their catalytic potential are of great importance. Here, we present a versatile and facile method for the fabrication of hierarchical ZSM-5 zeolite fibers with macro-meso-microporosity by coaxial electrospinning. Due to the synergistic integration of the suitable acidity and the hierarchical porosity, high yield of propylene and excellent anti-coking stability were demonstrated on the as-prepared ZSM-5 hollow fibers in the catalytic cracking reaction of iso-butane. This work may also provide good model catalysts with uniform wall thickness and tunable porosity for studying a series of important catalytic reactions.
PMCID: PMC4250908  PMID: 25450726
14.  Cocirculation of Three Hemagglutinin and Two Neuraminidase Subtypes of Avian Influenza Viruses in Huzhou, China, April 2013: Implication for the Origin of the Novel H7N9 Virus 
Journal of Virology  2014;88(11):6506-6511.
We detected three avian influenza hemagglutinin (HA) subtypes (H7, H9, and H5) and two neuraminidase (NA) subtypes (N9 and N2), as well as H7N9-related H9N9 reassortant intermediates, cocirculating among poultry in Huzhou, China, during April 2013. The results of our study reveal not only that Huzhou is one of the geographic origins of the novel H7N9 virus but also that cocirculation poses a potential threat to humans in the future.
PMCID: PMC4093899  PMID: 24623437
15.  Impact of Diabetes Mellitus on the Prognosis of Patients with Hepatocellular Carcinoma after Curative Hepatectomy 
PLoS ONE  2014;9(12):e113858.
Background: The influence of diabetes mellitus (DM) on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. Here we investigated the impact of DM on the prognosis of such patients after curative hepatectomy.
Methods: A consecutive cohort of 505 patients with HCC (134 with DM, 371 without) underwent curative hepatectomy were retrospectively evaluated. Postoperative morbidity and mortality, overall survival (OS) and disease-free survival (DFS) were compared between patients with or without DM. Independent prognostic predictors were identified using the Cox proportional hazards model.
Results: Patients with or without DM showed similar morbidity and 30- and 90- day mortality after curative hepatectomy (all P>0.05), as well as similar DFS at 1, 3, 5 years (P = 0.781). However, the group of patients with DM showed significantly lower OS at 1, 3, 5 years than the group without DM (P = 0.038). Similar results were obtained in the propensity-matched cohort. Cox multivariate analysis identified DM as an independent predictor of poor OS, but not of poor DFS. We repeat compared OS and DFS for DM and non-DM subgroups defined according to the presence or absence of hepatitis B virus infection and cirrhosis. Similar results were obtained in all subgroups except the non-cirrhotic subgroup which showed patients with and without DM had similar OS.
Conclusions: DM does not significantly affect the postoperative morbidity or mortality or the DFS of patients with HCC after curative hepatectomy. It is, however, associated with significantly lower OS, especially in patients with cirrhosis.
PMCID: PMC4250061  PMID: 25436613
16.  Comparison of three mathematical prediction models in patients with a solitary pulmonary nodule 
Effective methods for managing patients with solitary pulmonary nodules (SPNs) depend critically on the predictive probability of malignancy.
Between July 2009 and June 2011, data on gender, age, cancer history, tumor familial history, smoking status, tumor location, nodule size, spiculation, calcification, the tumor border, and the final pathological diagnosis were collected retrospectively from 154 surgical patients with an SPN measuring 3-30 mm. Each final diagnosis was compared with the probability calculated by three predicted models—the Mayo, VA, and Peking University (PU) models. The accuracy of each model was assessed using area under the receiver operating characteristics (ROC) and calibration curves.
The area under the ROC curve of the PU model [0.800; 95% confidence interval (CI): 0.708-0.891] was higher than that of the Mayo model (0.753; 95% CI: 0.650-0.857) or VA model (0.728; 95% CI: 0.623-0.833); however, this finding was not statistically significant. To varying degrees, calibration curves showed that all three models overestimated malignancy.
The three predicted models have similar accuracy for prediction of SPN malignancy, although the accuracy is not sufficient. For Chinese patients, the PU model may has greater predictive power.
PMCID: PMC4279199  PMID: 25561761
Solitary pulmonary nodule (SPN); benign and malignant; model; comparison
17.  Clinical value of calcium load test in differential diagnosis of different types of hyperparathyroidism 
Objective: To investigate the clinical value of calcium load test in the differentiation of various types of hyperparathyroidism (HPT). Methods: A total of 56 healthy subjects (Control) and 68 patients with different types of HPT hyperparathyroidism were recruited into this study. Results: In primary HPT (PHPT) group, the inhibition rate of PTH (PTH-IR) was significantly smaller than those in Control, SHPT1 and CuHPT group (all P = 0.000). There was no significant difference in the PTH-IR among Control, mild secondary HPT (SHPT1) and cause-unknown HPT (CuHPT) group. In severe secondary HPT (SHPT2) group, the PTH-IR was significantly smaller than those in Control (P = 0.005), SHPT1 (P = 0.001) and CuHPT group (P = 0.002), but was similar to that in tertiary HPT (THPT) group (P = 0.644). ROC curve showed PTH-IR of < 71.26% could differentiate PHPT patients from controls; PTH-IR of < 82.26% could differentiate PHPT patients from SHPT1 patients; PTH-IR of < 82.60% could differentiate SHPT1 patients from SHPT2 patients. Conclusion: Calcium load test could effectively differentiate mild PHPT patients from mild SHPT patients and healthy subjects. In SHPT patients, the autonomous tendency of the parathyroid gland gradually increases with the deterioration of impaired renal function, resulting in similar parathyroid response to calcium between severe SHPT and THPT. The autonomous property of the parathyroid gland may become one of the indications for parathyroidectomy in SHPT patients.
PMCID: PMC4307501  PMID: 25664054
Hyperparathyroidism; calcium load test; differentiation
18.  Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel 
Scientific Reports  2014;4:7064.
Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.
PMCID: PMC4238302  PMID: 25412301
19.  Expression of P-gp in acute myeloid leukemia and the reversal function of As2O3 on drug resistance 
Oncology Letters  2014;9(1):177-182.
To study the expression of P-glycoprotein (P-gp) and the reversal function of As2O3, the active ingredient of arsenic, on drug resistance in acute myeloid leukemia (AML) patients, P-gp and cluster of differentiation 34 (CD34) were examined in primary mononuclear and resistant cells, with or without As2O3. In addition, multidrug resistance gene 1 (MDR1) mRNA expression was investigated in K562/D cells and AML patients. In total, 28.6% of newly-treated (NT) patients and 59.1% of relapsed/refractory (RR) patients were P-gpfunction+, and 31.7% of NT patients and 59.1% of RR patients were CD34+. The positivity rate of P-gpfunction and CD34+ expression in the RR group were significantly higher compared with that in the NT group (P<0.05). In addition, higher CD34+, P-gpexpression+ and P-gpfunction+ values were observed in older patients compared with younger patients. MDR1 expression was downregulated in certain patients following treatment with AS2O3. In the present study, the overexpression of P-gp was the primary cause of drug resistance in the AML patients, and MDR1 expression was downregulated by As2O3 in primary leukemia and drug-resistant cells.
PMCID: PMC4247107  PMID: 25435954
acute myeloid leukemia; P-gp; As2O3; MDR1
20.  Isolation and Characterization of Marine Brevibacillus sp. S-1 Collected from South China Sea and a Novel Antitumor Peptide Produced by the Strain 
PLoS ONE  2014;9(11):e111270.
A Gram-positive, rod-shaped bacterium, designated as S-1, was isolated from a marine sediment sample collected from South China Sea. Phylogenetic analysis based on 16S rRNA gene sequence showed that S-1 belongs to the genus Brevibacillus. A novel cytotoxic peptide was isolated from the fermentation broth of the marine-derived bacterium Brevibacillus sp. S-1, using ion-exchange chromatography and reverse-phase HPLC chromatography. The molecular weight of this peptide was determined as 1570 Da by MALDI-TOF mass spectrometry, and its structure was proposed as a cyclic peptide elucidated by MALDI-TOF/TOF mass spectrometry and de novo sequencing. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay showed that this peptide exhibited cytotoxicity against BEL-7402 human hepatocellular carcinoma cells, RKO human colon carcinoma cells, A549 human lung carcinoma cells, U251 human glioma cells and MCF-7 human breast carcinoma cells. Additionally, SBP exhibited low cytotoxicity against HFL1 human normal fibroblast lung cells. The result suggested that the cytotoxic effect of the peptide is specific to tumor cells.
PMCID: PMC4220994  PMID: 25372839
21.  Brain grey matter volume alterations in late-life depression 
Voxel-based morphometry (VBM) studies have demonstrated that grey matter abnormalities are involved in the pathophysiology of late-life depression (LLD), but the findings are inconsistent and have not been quantitatively reviewed. The aim of the present study was to conduct a meta-analysis that integrated the reported VBM studies, to determine consistent grey matter alterations in individuals with LLD.
A systematic search was conducted to identify VBM studies that compared patients with LLD and healthy controls. We performed a meta-analysis using the effect size signed differential mapping method to quantitatively estimate regional grey matter abnormalities in patients with LLD.
We included 9 studies with 11 data sets comprising 292 patients with LLD and 278 healthy controls in our meta-analysis. The pooled and subgroup meta-analyses showed robust grey matter reductions in the right lentiform nucleus extending into the parahippocampus, the hippocampus and the amygdala, the bilateral medial frontal gyrus and the right subcallosal gyrus as well as a grey matter increase in the right lingual gyrus. Meta-regression analyses showed that mean age and the percentage of female patients with LLD were not significantly related to grey matter changes.
The analysis techniques, patient characteristics and clinical variables of the studies included were heterogeneous, and most participants were medicated.
The present meta-analysis is, to our knowledge, the first to overcome previous inconsistencies in the VBM studies of LLD and provide robust evidence for grey matter alterations within fronto–striatal–limbic networks, thereby implicating them in the pathophysiology of LLD. The mean age and the percentage of female patients with LLD did not appear to have a measurable impact on grey matter changes, although we cannot rule out the contributory effects of medication.
PMCID: PMC4214874  PMID: 24949867
22.  Acute incarcerated external abdominal hernia 
External abdominal hernia occurs when abdominal organs or tissues leave their normal anatomic site and protrude outside the skin through the congenital or acquired weakness, defects or holes on the abdominal wall, including inguinal hernia, umbilical hernia, femoral hernia and so on. Acute incarcerated hernia is a common surgical emergency. With advances in minimally invasive devices and techniques, the diagnosis and treatment have witnessed major changes, such as the use of laparoscopic surgery in some cases to achieve minimally invasive treatment. However, strict adherence to the indications and contraindications is still required.
PMCID: PMC4245506  PMID: 25489584
Hernia; abdominal; inguinal; umbilical; laparoscopy
23.  13C NMR Metabolomic Evaluation of Immediate and Delayed Mild Hypothermia in Cerebrocortical Slices After Oxygen-Glucose Deprivation 
Anesthesiology  2013;119(5):1120-1136.
Mild brain hypothermia (32°C–34°C) after human neonatal asphyxia improves neurodevelopmental outcomes. Astrocytes but not neurons have pyruvate carboxylase (PC) and an acetate uptake transporter. 13C NMR spectroscopy of rodent brain extracts after administering [1-13C]glucose and [1,2-13C]acetate can distinguish metabolic differences between glia and neurons, and tricarboxylic acid cycle (TCA cycle) entry via pyruvate dehydrogenase (PDH) and PC.
Neonatal rat cerebrocortical slices receiving a 13C-acetate/glucose mixture underwent a 45-min asphyxia simulation via oxygen-glucose-deprivation (OGD) followed by 6 h of recovery. Protocols in three groups of N = 3 experiments were identical except for temperature management. The three temperature groups were: normothermia (37°C), hypothermia (32°C for 3.75 h beginning at OGD start), and delayed hypothermia (32°C for 3.75 h, beginning 15 min after OGD start). Multivariate analysis of nuclear magnetic resonance metabolite quantifications included principal component analyses and the L1-Penalized Regularized Regression algorithm known as the Least Absolute Shrinkage and Selection Operator (LASSO).
The most significant metabolite difference (p < 0.0056) was [2-13C]glutamine’s higher final/control ratio for the Hypothermia group (1.75 ± 0.12) compared to ratios for the Delayed (1.12 ± 0.12) and Normothermia group (0.94 ± 0.06), implying a higher PC/PDH ratio for glutamine formation. LASSO found the most important metabolites associated with adenosine triphosphate preservation: [3,4-13C]glutamate—produced via PDH entry, [2-13C]taurine--an important osmolyte, and phosphocreatine. Final principal component analyses scores plots suggested separate cluster formation for the hypothermia group, but with insufficient data for statistical significance.
Starting mild hypothermia simultaneously with OGD, compared with delayed starting or no hypothermia, has higher PC throughput, suggesting that better glial integrity is one important neuroprotection mechanism of earlier hypothermia.
PMCID: PMC3890426  PMID: 23748856
24.  Neuroacanthocytosis in China: A Review of Published Reports 
Neuroacanthocytosis (NA) syndromes are a group of rare diseases characterized by the presence of acanthocytes and neuronal multisystem pathology, including chorea-acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington's disease-like 2 (HDL-2), and pantothenate kinase-associated neurodegeneration (PKAN). China has the largest population in the world, which makes it a good location for investigating rare diseases like NA.
We searched Medline, ISI Proceedings, China National Knowledge Infrastructure, and Wanfang Data for literature published through December 31, 2013 for all the published Chinese NA case reports and extracted the clinical and laboratory findings.
A total of 42 studies describing 66 cases were found to be eligible for inclusion. Age of symptom onset ranged from 5 to 74 years. The most common findings included hyperkinetic movements (88%), orofacial dyskinesia (80%), dystonia (67%), and dysarthria (68%), as well as caudate atrophy or enlarged lateral ventricles on neuroimaging (64%), and elevated creatine kinase (52%). Most cases were not confirmed by any specific molecular tests. Only two cases were genetically studied and diagnosed as ChAc or MLS.
In view of the prevalence of NA syndromes in other countries, the number of patients in China appears to be underestimated. Chinese NA patients may benefit from the establishment of networks that offer specific diagnoses and care for rare diseases.
PMCID: PMC4219110  PMID: 25374764
Neuroacanthocytosis; chorea-acanthocytosis; McLeod syndrome; neurodegeneration with brain iron accumulation; China
25.  iBrick: A New Standard for Iterative Assembly of Biological Parts with Homing Endonucleases 
PLoS ONE  2014;9(10):e110852.
The BioBricks standard has made the construction of DNA modules easier, quicker and cheaper. So far, over 100 BioBricks assembly schemes have been developed and many of them, including the original standard of BBF RFC 10, are now widely used. However, because the restriction endonucleases employed by these standards usually recognize short DNA sequences that are widely spread among natural DNA sequences, and these recognition sites must be removed before the parts construction, there is much inconvenience in dealing with large-size DNA parts (e.g., more than couple kilobases in length) with the present standards. Here, we introduce a new standard, namely iBrick, which uses two homing endonucleases of I-SceI and PI-PspI. Because both enzymes recognize long DNA sequences (>18 bps), their sites are extremely rare in natural DNA sources, thus providing additional convenience, especially in handling large pieces of DNA fragments. Using the iBrick standard, the carotenoid biosynthetic cluster (>4 kb) was successfully assembled and the actinorhodin biosynthetic cluster (>20 kb) was easily cloned and heterologously expressed. In addition, a corresponding nomenclature system has been established for the iBrick standard.
PMCID: PMC4203835  PMID: 25329380

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