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1.  Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro 
Scientific Reports  2014;4:4619.
Basal cells in nasal epithelium have stemness/progenitor characters and play essential roles in the epithelial remodeling in nasal polyps (NP). We investigate whether the human nasal epithelial stem/progenitor cells (hNESPCs) from patients with NP are inherently distinct from those obtained from healthy controls. Epithelial basal cells were isolated and cultured for four passages from NP tissues and control nasal mucosa. hNESPCs from controls were stained positively with stem cell marker p63 and KRT5 and presented a consistent high Ki67 expression level over four passages. In contrast, hNESPCs from NP patients showed: i). a reduced growth and proliferation rate at each passage by evaluating colony-forming efficiency and doubling time; ii). a lower percentage of Ki67+ cells among p63+ cells in the colonies in late passages, which was also confirmed by immunostaining in the NP tissues. Thus reduced growth/proliferation dynamics in hNESPCs from NP could be an important pathological phenomenon in NP development.
PMCID: PMC3980221  PMID: 24714674
2.  Microscale separation of heparosan, heparan sulfate and heparin 
Analytical biochemistry  2012;434(2):215-217.
The separation and quantification of glycosaminoglycan (GAG) chains, with different levels of sulfation, from cells, media and prepared through chemoenzymatic synthesis or metabolic engineering, poses a major challenge in glycomics analysis. A method for microscale separation and quantification of heparin, heparan sulfate and heparosan from cells is reported. This separation relies on a mini-strong anion exchange spin column eluted stepwise with different concentrations of sodium chloride. Disaccharide analysis by LC-MS was used to monitor the chemical structure of the different GAG chains that were recovered.
PMCID: PMC3572195  PMID: 23262074
heparosan; heparan sulfate; heparin; glycosaminoglycan; anion exchange chromatography; disaccharide analysis
3.  Variations in the MHC Region Confer Risk to Esophageal Squamous Cell Carcinoma on the Subjects from High-Incidence Area in Northern China 
PLoS ONE  2014;9(3):e90438.
The human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population.
Conditional logistic regression analysis (CLRA) was performed on 24 single nucleotide polymorphisms (SNPs) within the MHC region, which were obtained from the genetically matched 937 cases and 692 controls of Chinese Han population. The identified promising SNPs were further correlated with clinical and clinicopathology characteristics. Immunohistochemistry was performed to explore the protein expression pattern of the related genes in ESCC and neighboring normal tissues.
Of the 24 promising SNPs analyzed, we identified three independent SNPs in the MHC region associated with ESCC: rs35399661 (P = 6.07E-06, OR = 1.71, 95%CI = 1.36–2.17), rs3763338 (P = 1.62E-05, OR = 0.63, 95%CI = 0.50–0.78) and rs2844695 (P = 7.60E-05, OR = 0.74, 95%CI = 0.64–0.86). These three SNPs were located at the genes of HLA-DQA1, TRIM27, and DPCR1, respectively. Further analyses showed that rs2844695 was preferentially associated with younger ESCC cases (P = 0.009). The positive immunostaining rates both for HLA-DQA1 and TRIM27 were much higher in ESCC tissues than in neighboring normal tissues (69.4% vs. 26.8% for HLA-DQA1 and 77.6% vs. 47.8% for TRIM27, P<0.001). Furthermore, the overexpression of HLA-DQA1 is correlated significantly with age (P = 0.001) and family history (P<0.001).
This study for the first time provides evidence that multiple genetic factors within the MHC region confer risk to ESCC on the subjects from high-risk area in northern China.
PMCID: PMC3942432  PMID: 24595008
4.  Co-Circulation of Multiple Hemorrhagic Fever Diseases with Distinct Clinical Characteristics in Dandong, China 
PLoS ONE  2014;9(2):e89896.
Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011–2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.
PMCID: PMC3937409  PMID: 24587107
5.  Multiple embolisms resulted from a huge fishbone piercing the left atrium 
Intensive Care Medicine  2014;40:621-622.
PMCID: PMC3969516  PMID: 24519573
6.  Decreased Peripheral Natural Killer Cells Activity in the Immune Activated Stage of Chronic Hepatitis B 
PLoS ONE  2014;9(2):e86927.
Background & Aims
The natural course of chronic hepatitis B virus (HBV) infection is characterized by different immune responses, ranging from immune tolerant (IT) to immune activated (IA) stages. In our study, we investigated the natural killer (NK) cells activity in patients at different immunological stages of chronic HBV infection.
Blood samples obtained from 57 HBeAg positive patients with chronic hepatitis B (CHB), including 15 patients in the immune tolerant (IT) stage, 42 patients in the immune activated (IA) stage, and 18 healthy individuals (HI). The analyses included flow cytometry to detect NK cells, the determination of cytokine levels as well as of surface receptor expression and cytotoxicity.
NK cells in peripheral blood were significantly lower in patients in the IA stage of CHB compared to HI (p<0.05). Patients in the IA stage of CHB had lower levels of NK cells activating receptor NKp30 and NKG2D expression, cytokine interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, as compared to patients in the IT stage and HI, respectively (p<0.05). Cytotoxicity of NK cells was lower in patients in the IA stage of CHB compared to patients in the IT stage and HI, respectively (p<0.05). The level of IFN-γ but not level of TNF-α and cytotoxicity of NK cells was inversely correlated with serum HBV load in patients with CHB. Peripheral NK cells activity did not correlate with ALT level.
NK cells activity was lower in CHB patients, especially in those in the IA stage.
PMCID: PMC3919705  PMID: 24520324
7.  Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury 
Patients with colorectal cancer (CRC) often develop liver metastases, in which case surgery is considered the only potentially curative treatment option. However, liver surgery is associated with a risk of ischemia-reperfusion (IR) injury, which is thought to promote the growth of colorectal liver metastases. The influence of IR-induced tumor necrosis factor alpha (TNF-α) elevation in the process still is unknown. To investigate the role of TNF-α in the growth of pre-existing micrometastases in the liver following IR, we used a mouse model of colorectal liver metastases. In this model, mice received IR treatment seven days after intrasplenic injections of colorectal CT26 cells. Prior to IR treatment, either TNF-α blocker Enbrel or low-dose TNF-α, which could inhibit IR-induced TNF-α elevation, was administered by intraperitoneal injection.
Hepatic IR treatment significantly promoted CT26 tumor growth in the liver, but either Enbrel or low-dose TNF-α pretreatment reversed this trend. Further studies showed that the CT26 + IR group prominently increased the levels of ALT and AST, liver necrosis, inflammatory infiltration and the expressions of hepatic IL-6, MMP9 and E-selectin compared to those of CT26 group. Inhibition of TNF-α elevation remarkably attenuated the increases of these liver inflammatory damage indicators and tumor-promoting factors.
These findings suggested that inhibition of TNF-α elevation delayed the IR-enhanced outgrowth of colorectal liver metastases by reducing IR-induced inflammatory damage and the formation of tumor-promoting microenvironments. Both Enbrel and low-dose TNF-α represented the potential therapeutic approaches for the protection of colorectal liver metastatic patients against IR injury-induced growth of liver micrometastases foci.
PMCID: PMC3902418  PMID: 24397824
Colorectal cancer; Liver metastases; Ischemia-reperfusion; TNF-α; Enbrel
8.  Aluminium tolerance in rice is antagonistic with nitrate preference and synergistic with ammonium preference 
Annals of Botany  2012;111(1):69-77.
Background and Aims
Acidic soils are dominated chemically by more ammonium and more available, so more potentially toxic, aluminium compared with neutral to calcareous soils, which are characterized by more nitrate and less available, so less toxic, aluminium. However, it is not known whether aluminium tolerance and nitrogen source preference are linked in plants.
This question was investigated by comparing the responses of 30 rice (Oryza sativa) varieties (15 subsp. japonica cultivars and 15 subsp. indica cultivars) to aluminium, various ammonium/nitrate ratios and their combinations under acidic solution conditions.
Key Results
indica rice plants were generally found to be aluminium-sensitive and nitrate-preferring, while japonica cultivars were aluminium-tolerant and relatively ammonium-preferring. Aluminium tolerance of different rice varieties was significantly negatively correlated with their nitrate preference. Furthermore, aluminium enhanced ammonium-fed rice growth but inhibited nitrate-fed rice growth.
The results suggest that aluminium tolerance in rice is antagonistic with nitrate preference and synergistic with ammonium preference under acidic solution conditions. A schematic diagram summarizing the interactions of aluminium and nitrogen in soil–plant ecosystems is presented and provides a new basis for the integrated management of acidic soils.
PMCID: PMC3523647  PMID: 23118122
Aluminium; ammonium; correlation; Indica; Japonica; nitrate; rice
9.  Biomechanical Comparison of Different Stabilization Constructs for Unstable Posterior Wall Fractures of Acetabulum. A Cadaveric Study 
PLoS ONE  2013;8(12):e82993.
Operative treatment of unstable posterior wall fractures of acetabulum has been widely recommended. This laboratory study was undertaken to evaluate static fixation strength of three common fixation constructs: interfragmentary screws alone, in combination with conventional reconstruction plate, or locking reconstruction plate.
Six formalin-preserved cadaveric pelvises were used for this investigation. A posterior wall fracture was created along an arc of 40–90 degree about the acetabular rim. Three groups of different fixation constructs (two interfragmentary screws alone; two interfragmentary screws and a conventional reconstruction plate; two interfragmentary screws and a locking reconstruction) were compared. Pelvises were axial loaded with six cycles of 1500 N. Dislocation of superior and inferior fracture site was analysed with a multidirectional ultrasonic measuring system. Results: No statistically significant difference was found at each of the superior and inferior fracture sites between the three types of fixation. In each group, the vector dislocation at superior fracture site was significantly larger than inferior one.
All those three described fixation constructs can provide sufficient stability for posterior acetabular fractures and allow early mobilization under experimental conditions. Higher posterior acetabular fracture line, transecting the weight-bearing surface, may indicate a substantial increase in instability, and need more stable pattern of fixation.
PMCID: PMC3876999  PMID: 24391733
10.  Application of Ni-Ti Alloy connector for the treatment of comminuted coronal plane supracondylar-condylar femoral fractures: a retrospective review of 21 patients 
Our preliminary retrospective study assessed outcomes after the use of Ni-Ti arched shape-memory connector (ASC) combined with partially threaded cancellous screws (PTCS) to repair coronal plane supracondylar-condylar femoral fractures.
Twenty-one patients (16 men and 5 women) with a mean age of 34.1 years (range, 28 to 44 years) with coronal plane supracondylar and condylar fractures of the distal femur were included in this study. Each patient underwent open reduction and internal fixation using the ASC and PTCS. Active functional exercises with restricted weight bearing were initiated the first postoperative day. A gradual increase in weight bearing status and range of motion was permitted and subjects progressed to full weight bearing by 8 weeks. Surgical time, blood loss, postoperative knee range of motion, American Knee Society Scores (KSS), and postoperative complications were assessed.
The mean surgical time was 75 mins (range, 45 to 100 mins) and average blood loss was 105 ml (range, 35 to 130 ml). Mean follow-up was 65 months (range, 22 to 90 months). No subjects demonstrated evidence of osteonecrosis or arthritis at the final follow-up. The mean KSS was excellent (≥85) in 8 subjects, good (70-84) in 11 subjects, and fair (60-69) in 2 subjects. The mean active range of motion of knee flexion at final follow-up was 100 degrees (range, 85 to 110 degrees).
ASC combined with PTCS can serve as an effective means for managing comminuted femoral fractures that extend from the condyle to the supracondylar region. However, further prospective comparative studies and biomechanical analyses are needed to evaluate long-term outcomes using these materials.
PMCID: PMC3878495  PMID: 24341860
Shape memory alloy; Treatment; Comminuted; Coronal plane; Femoral fracture
11.  6,7-Dihydroxy-1-oxoisoindoline-4-sulfonamide-containing HIV-1 Integrase Inhibitors 
Although an extensive body of scientific and patent literature exists describing the development of HIV-1 integrase (IN) inhibitors, Merck’s raltegravir and Gilead’s elvitegravir remain the only IN inhibitors FDA-approved for the treatment of AIDS. The emergence of raltegravir-resistant strains of HIV-1 containing mutated forms of IN underlies the need for continued efforts to enhance the efficacy of IN inhibitors against resistant mutants. We have previously described bicyclic 6,7-dihydroxyoxoisoindolin-1-ones that show good IN inhibitory potency. This report describes the effects of introducing substituents into the 4- and 5- positions of the parent 6,7-dihydroxyoxoisoindolin-1-one platform. We have developed several sulfonamide-containing analogs that enhance potency in cell-based HIV assays by more than two orders-of-magnitude and we describe several compounds that are more potent than raltegravir against the clinically relevant Y143R IN mutant.
PMCID: PMC3523327  PMID: 23149229
HIV-1 integrase; Inhibit; Raltegravir; Sulfonamide
12.  Novel Recombinant Hepatitis B Virus Vectors Efficiently Deliver Protein and RNA Encoding Genes into Primary Hepatocytes 
Journal of Virology  2013;87(12):6615-6624.
Hepatitis B virus (HBV) has extremely restricted host and hepatocyte tropism. HBV-based vectors could form the basis of novel therapies for chronic hepatitis B and other liver diseases and would also be invaluable for the study of HBV infection. Previous attempts at developing HBV-based vectors encountered low yields of recombinant viruses and/or lack of sufficient infectivity/cargo gene expression in primary hepatocytes, which hampered follow-up applications. In this work, we constructed a novel vector based on a naturally occurring, highly replicative HBV mutant with a 207-bp deletion in the preS1/polymerase spacer region. By applying a novel insertion strategy that preserves the continuity of the polymerase open reading frame (ORF), recombinant HBV (rHBV) carrying protein or small interfering RNA (siRNA) genes were obtained that replicated and were packaged efficiently in cultured hepatocytes. We demonstrated that rHBV expressing a fluorescent reporter (DsRed) is highly infective in primary tree shrew hepatocytes, and rHBV expressing HBV-targeting siRNA successfully inhibited antigen expression from coinfected wild-type HBV. This novel HBV vector will be a powerful tool for hepatocyte-targeting gene delivery, as well as the study of HBV infection.
PMCID: PMC3676104  PMID: 23552416
13.  Interactive regulation of nitrogen and aluminum in rice 
Plant Signaling & Behavior  2013;8(6):e24355.
Despite many studies on the high aluminum (Al) tolerance of rice (Oryza sativa), its exact mechanisms remain largely unknown. It is also unclear why Al improves growth of some plants. Our research on interactions between nitrogen (N) and Al may help to understand these phenomena. Previously, we found that ammonium-supplemented rice was more Al tolerant than nitrate-supplemented rice. Furthermore, Al-tolerant rice varieties preferred ammonium, while Al-sensitive ones preferred nitrate; in fact, Al tolerance was significantly correlated with the ammonium/nitrate preference among rice varieties. Al even enhanced growth of ammonium-supplemented rice, while it inhibited growth of nitrate-supplemented rice. Based on our own and other reports on N-Al interactions, we propose that intermediate products of N metabolism may play a role in rice Al tolerance. Al-enhanced ammonium utilization may explain why Al promotes growth of some plants, since Al often coexists with higher levels of ammonium than nitrate in acid soils.
PMCID: PMC3907435  PMID: 23531694
rice; aluminum tolerance; nitrate; ammonium; preference; toxicity
14.  Tumor necrosis factor-α attenuates starvation-induced apoptosis through upregulation of ferritin heavy chain in hepatocellular carcinoma cells 
BMC Cancer  2013;13:438.
Tumor microenviroment is characteristic of inflammation, ischemia and starvation of nutrient. TNF-α, which is an extraordinarily pleiotropic cytokine, could be an endogenous tumor promoter in some tumor types. The basic objective of this study was to investigate the effects of TNF-α on the cell viability and apoptosis of hepatocellular carcinoma cells under serum starvation, and to identify the molecular mechanisms involved.
For this purpose, five different concentrations of TNF-α and two different serum settings (serum-cultured and serum-deprived) were used to investigate the effects of TNF-α on the cell viability and apoptosis of Hep3B and SMMC-7721 cells.
TNF-α (10 ng/ml) attenuated serum starvation-induced apoptosis of hepatocellular carcinoma cells, and autophagy conferred this process. BAY11-7082, a specific inhibitor of NF-κB, reversed the suppression of serum starvation-induced apoptosis by TNF-α. Moreover, TNF-α-induced NF-κB transactivation was suppressed by autophagy inhibitor 3-MA. In addition, TNF-α up-regulated Ferritin heavy chain (FHC) transiently by NF-κB activation and FHC levels were correlated with the TNF-α-induced protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells. Furthermore, FHC-mediated inhibition of apoptosis depended on suppressing ROS accumulation.
Our findings suggested that autophagy conferred the TNF-α protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells, the mechanism involved with the activation of the TNF-α/ NF-κB /FHC signaling pathway.
PMCID: PMC3849379  PMID: 24066693
TNF-α; Starvation; NF-κB; Ferritin heavy chain; Autophagy; Hepatocellular carcinoma
15.  Cell-Based Microscale Isolation of Glycoaminoglycans for Glycomics Study 
Journal of carbohydrate chemistry  2012;31(4-6):420-435.
Glycomics research requires the isolation of glycans from cells for structural characterization and functional studies of the glycans. A method for cell-based microscale isolation and quantification of highly sulfated, moderately sulfated, and nonsulfated glycosaminoglycans (GAGs) was developed using Chinese hamster ovary (CHO) cells. This microscale isolation relies on a mini-strong anion exchange spin column eluted stepwise with different concentrations of sodium chloride solution. Hyaluronic acid, chondroitin sulfate, and heparin were used to optimize the isolation of the endogenous glycosaminoglycans in CHO cells. This method can also be used to determine the presence of nonsulfated GAGs including heparosan, hyaluronic acid, and nonsulfated chondroitin.
PMCID: PMC3779912  PMID: 24068855
Chinese hamster ovary cells; Glycosaminoglycans; Anion exchange chromatography; Heparosan; Disaccharide analysis
16.  {9-Hexyl-2-[2-phenyl-6-(pyridin-2-yl)pyridin-4-yl]-9H-carbazole}di­iodido­zinc 
In the title compound, [ZnI2(C34H31N3)], the ZnII atom is four-coordinated by two I atoms and the pyridine N atoms from the bidentate 6′-phenyl-2,2′-bi­pyridine ligand in a distorted tetra­hedral geometry.
PMCID: PMC3790359  PMID: 24098181
17.  Small interfering RNA survivin and GRIM-19 co-expression salmonella plasmid inhibited the growth of laryngeal cancer cells in vitro and in vivo 
Objective: To investigate the inhibitory effect of plasmid-based survivin-specific short hairpin RNA and GRIM-19 on the growth of Hep-2 laryngeal cancer cells. Methods: The plasmid expressing survivin-specific short hairpin RNA (shRNA) and GRIM-19 (p-siRNA survivin/GRIM-19) was prepared and transfected into Hep-2 cells with Lipofectamine 2000. The mRNA and protein expression of surviving and GRIM-19 were measured with RT-PCR and western blot assay, respectively. MTT assay was employed to detect the proliferation of Hep-2 cells, and flow cytometry and AO/EB assay were done to determine the apoptosis of Hep-2 cells. Results: In the p-siRNA survivin/GRIM-19, the mRNA and protein expression of survivin was markedly reduced by 54.4% and 42.2%, and the reduction in protein expression of surviving was more obvious than that in the p-siRNA survivin group (37%) (P<0.05). The protein expression of GRIM-19 was markedly enhanced when compared with the control group (P<0.01). MTT assay revealed the proliferation of Hep-2 cells undergoing transfection with p-siRNA survivin/GRIM-19 was markedly inhibited, and the inhibition rate was as high as 79%, which was higher than that in the psi-survivin group (45%) and p-GRIM-19 group (35%). AO/EB assay and flow cytometry indicated that the apoptotic cells in the p-siRNA survivin/GRIM-19 group were dramatically increased as compared to the psi-survivin group and p-GRIM-19 group. Conclusion: The p-siRNA survivin/GRIM-19 has marked decrease in survivin expression and dramatic increase in GRIM-19 expression. Moreover, silencing of survivin and over-expression of GRIM-19 can significantly inhibit the growth and induce the apoptosis of Hep-2 in vitro and in vivo.
PMCID: PMC3796229  PMID: 24133585
Co-expression plasmid; gene silencing; survivin; laryngeal cancer
18.  High normal plasma triglycerides are associated with preserved cognitive function in Chinese oldest-old 
Age and Ageing  2012;41(5):600-606.
Objective: to explore the relationship between blood lipids/lipoproteins and cognitive function in the Chinese oldest-old.
Design: multivariate statistical analysis using cross-sectional data.
Setting: community-based setting in longevity areas in China.
Subjects: eight hundred and thirty-six subjects aged 80 and older were included in the sample.
Methods: plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, blood pressure and fasting plasma glucose were measured and information about demographics and lifestyle was collected. Cognitive status was assessed using the Mini-Mental State Examination (MMSE).
Results: cumulative logit model analysis showed that triglyceride was significantly negatively associated with cognitive impairment. By general linear modelling, there was a significant linear trend of MMSE scores with the level of triglyceride, but not with levels of cholesterol after adjustment. The odds ratio (OR) of cognitive impairment (MMSE score < 18) was significantly reduced for the highest quartile of plasma triglyceride concentration (OR: 0.52, 95% CI: 0.33–0.84), but not for the second or third quartile, compared with the lowest quartile (adjusted models). There were no significant associations between cognitive impairment and cholesterol.
Conclusion: we concluded that high normal plasma triglyceride was associated with preservation of cognitive function while lower concentrations were not in the Chinese oldest-old.
PMCID: PMC3500861  PMID: 22447910
triglycerides; cognitive function; lipids; oldest-old; elderly
19.  Factors associated with burnout among Chinese hospital doctors: a cross-sectional study 
BMC Public Health  2013;13:786.
Burnout has been a major concern in the field of occupational health. However, there is a paucity of research exploring the factors related to burnout among Chinese doctors. Investigation of these factors is important to improve the health of doctors and the quality of healthcare services in China.
The study population consisted of 1,618 registered hospital doctors from Liaoning province of China. Burnout was measured using the Chinese version of the Maslach Burnout Inventory-General Survey. Occupational stress was measured using the Chinese versions of the Job Content Questionnaire and the Effort-Reward Imbalance Questionnaire. Data were collected on the respondents’ demographic characteristics and work situations. Of the doctors solicited for enrollment, 1,202 returned the completed questionnaire (555 men, 647 women), giving a response rate of 74.3%. A general linear regression model was applied to analyze the factors associated with burnout.
The burnout mean scores were 11.46 (7.51) for emotional exhaustion, 6.93 (5.15) for cynicism, and 24.07 (9.50) for professional efficacy. In descending order of standardized estimates, variables that predicted a high level of emotional exhaustion included: high extrinsic effort, dissatisfaction with doctor-patient relationship, high overcommitment, working >40 h per week, low reward, and high psychological job demands. Variables that predicted a high level of cynicism included: high extrinsic effort, low reward, dissatisfaction with doctor-patient relationship, high overcommitment, low decision authority, low supervisor support, and low skill discretion. Variables that predicted a low perceived professional efficacy included: high psychological job demands, low coworker support, high extrinsic effort, low decision authority, low reward, and dissatisfaction with doctor-patient relationship.
These findings suggest that occupational stress is strongly related to burnout among hospital doctors in China. Strategies that aim to improve work situations and decrease occupational stress are necessary to reduce burnout, including health education, health promotion, and occupational training programs.
PMCID: PMC3765838  PMID: 23985038
Burnout; Doctors; Maslach Burnout Inventory-General Survey; Occupational stress
20.  Prevalence of hepatitis C infection among intravenous drug users in Shanghai 
AIM: To characterize the prevalence of hepatitis C virus (HCV) infection among Chinese intravenous drug users (IDUs).
METHODS: A total of 432 adult IDUs (95 women and 337 men) in Shanghai were included in the study. The third-generation Elecsys Anti-HCV assay (Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305, Mannheim, Germany) was used to screen for antibodies against HCV. The RIBA strip, a supplemental anti-HCV test with high specificity, was performed on all of the samples that tested positive during the initial screening. All of the anti-HCV positive samples were analyzed with a Cobas TaqMan 48 Analyzer (Roche Diagnostics) for direct detection of HCV RNA. All of the HCV RNA-positive samples were sequenced for genotype determination.
RESULTS: The preliminary screening identified 262 (60.6%) subjects who were seropositive for HCV. Of the 62 females and 200 males seropositive subjects, 16 (16.7%) and 65 (19.3%), respectively, were confirmed by RIBA, yielding an overall HCV seropositive rate of 18.8%. Four female (6.5%) and 14 male (7.0%) subjects tested positive for HCV RNA, indicating an active infection rate of 4.2% for the entire study population. The 18 HCV RNA-positive serum samples were genotyped. Seven individuals were genotype 1b, and four were genotype 1a. One individual each was infected with genotypes 2a, 2b and 3a. Four subjects were co-infected with multiple strains: two with genotypes 1a and 2a, and two with genotypes 1b and 2a. The active infection rate among HCV-seropositive individuals was 22.2%, which was significantly lower than most estimates.
CONCLUSION: The prevalence of HCV is relatively low among IDUs in Shanghai, with a spontaneous recovery rate much higher than previous estimates.
PMCID: PMC3752567  PMID: 23983436
Hepatitis C; Anti-hepatitis C virus antibodies; Prevalence of hepatitis C virus; Active infection rate; Intravenous drug users
21.  Analysis of glycosaminoglycan-derived disaccharides by capillary electrophoresis using laser-induced fluorescence detection 
Analytical biochemistry  2012;427(1):91-98.
A quantitative and highly sensitive method for the analysis of glycosaminoglycan (GAG)-derived disaccharides is presented that relies on capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection. This method enables complete separation of seventeen GAG-derived disaccharides in a single run. Unsaturated disaccharides were derivatized with 2-aminoacridone (AMAC) to improve sensitivity. The limit of detection was at the attomole level and about 100-fold more sensitive than traditional CE-ultraviolet detection. A CE separation timetable was developed to achieve complete resolution and shorten analysis time. The RSD of migration time and peak areas at both low and high concentrations of unsaturated disaccharides are all less than 2.7% and 3.2%, respectively, demonstrating that this is a reproducible method. This analysis was successfully applied to cultured Chinese hamster ovary cell samples for determination of GAG disaccharides. The current method simplifies GAG extraction steps, and reduces inaccuracy in calculating ratios of heparin/heparan sulfate to chondroitin sulfate/dermatan sulfate, resulting from the separate analyses of a single sample.
PMCID: PMC3409464  PMID: 22609076
2-aminoacridone; capillary electrophoresis; chondroitin /dermatan sulfate; heparan sulfate /heparin; hyaluronan; glycosaminoglycan
22.  Stress and Temperature Sensitivity of Photonic Crystals Resonant Cavity 
The Scientific World Journal  2013;2013:805470.
The temperature and stress characteristic of photonic band gap structure resonant cavities with square and graphite lattice have been studied by finite-difference time-domain method. The results show that the resonant cavities, both square and graphite lattice, have more and more resonant frequency with the cavity enlarging. And the curves between the resonant frequency and stress have better linearity. When the cavity enlarges enough, the curve between resonant frequency and temperature will become sectionalized line from nonlinear curve. Especially, the temperature sensitivity will be descending as the cavity is enlarging. Nevertheless, once some structures are put in the center of the cavity, the temperature sensitivity will be rising fast for this kind of cavity. Obviously, this character is convenient for us to achieve the specification measurement for temperature and stress.
PMCID: PMC3725802  PMID: 23935434
23.  Clinical implications of cancer stem cell-like side population cells in human laryngeal cancer 
Tumour Biology  2013;34(6):3603-3610.
In this study, we try to detect and isolate the cancer stem cell-like side population cells (SP) from the laryngeal carcinoma cell line and primary laryngeal carcinoma and explore the clinical implications of SP cells in laryngeal carcinoma. The SP cells and non-side population cells (NSP) cells were sorted by Hoechst 33342 through FACS. The proliferation capacity, invasion ability, migration ability, and tumorigenic activity of the SP cells were evaluated. In addition, the association between the SP cells ratio and the prognostic factors of laryngeal cancer was analyzed. As a result, the percentage of the SP cells in Hep-2 cells was 5.1 %. The SP cells depicted float colonies, but the NSP cells failed to generate the typical cell spheres. The clone formation ratios were 47.47 ± 10.20 % vs. 4.98 ± 1.41 % in the flat plates and 46.82 ± 5.67 % vs. 12.53 ± 3.51 % in the soft agar for SP and NSP cells (P = 0.01 and 0.01). The SP cells depicted a higher migrating potency than the NSP cells in both the transwell assay and scarification test (all P < 0.05). The matrigel invasion assay showed that the artificial basement membrane penetration rate of SP cells was 39.04 ± 4.78 %, which was higher than 25.16 ± 4.63 % of the NSP cells (P < 0.05). Only 103 SP cells were able to form tumors in mice, whereas 104 NSP cells failed to form tumors. The SP cells were correlated with the differentiation, lymph node metastasis, and clinical stage of the laryngeal cancers. In conclusion, SP cells may be a potential prognostic factor of laryngeal cancer.
PMCID: PMC3879800  PMID: 23807678
Tumor stem cell; Side population; ABCG2; Laryngeal carcinoma
24.  TRIF and IRF-3 Binding to the TNF Promoter Results in Macrophage TNF Dysregulation and Steatosis Induced by Chronic Ethanol1 
Chronic ethanol (EtOH) abuse results in the development of steatosis, alcoholic hepatitis, and cirrhosis. Augmented TNF-α production by macrophages and Kupffer cells and signaling via the p55 TNF receptor have been shown to be critical for these effects of chronic EtOH; however, the molecular mechanisms leading to augmented TNF-α production remain unclear. Using cell culture models and in vivo studies we demonstrate that chronic EtOH results in increased TNF-α transcription, which is independent of NF-κB. Using reporter assays and chromatin immunoprecipitation we found that this increased transcription is due to increased IRF-3 binding to and transactivation of the TNF promoter. As IRF-3 is downstream from the TLR4 adaptor TIR-domain-containing adapter-inducing IFN-β (Trif), we demonstrate that macrophages from Trif−/− mice are resistant to this dysregulation of TNF-α transcription by EtOH in vitro as well as EtOH-induced steatosis and TNF dysregulation in vivo. These data demonstrate that the Trif/IRF-3 pathway is a target to ameliorate liver dysfunction associated with chronic EtOH.
PMCID: PMC3690475  PMID: 18713975
25.  Autophagy lessens ischemic liver injury by reducing oxidative damage 
Cell & Bioscience  2013;3:26.
Hepatic ischemia/reperfusion is a multi-factorial process which causes liver injury. It is reported that ischemia alone is sufficient to induce liver injury. Nutrient deprivation is a crucial factor impacting ischemic injury of the liver. Therefore, we explored the role of autophagy in ischemia through using hepatic ischemia rat model in vivo and nutrient-free model in vitro.
We found that both ischemia in vivo and nutrient deprivation in vitro activated autophagy, inhibition of which aggravated ischemia- or nutrient deficiency-induced injury. In the nutrient-free condition, autophagy inhibition enhanced liver cell necrosis but not apoptosis by promoting reactive oxygen species (ROS) accumulation, and antioxidant NAC could reverse this trend. Inhibition of autophagy also resulted in the increase of the percentage of necrotic cell but not apoptotic cell in the ischemia-treated rat livers. Further studies showed that under nutrient deprivation, autophagy inhibition promoted mitochondrial ROS generation, which further aggravated mitochondria damage. These changes formed a “vicious cycle” that accelerated the process of cell necrosis. Autophagy inhibition also increased mitochondrial oxidative stress during hepatic ischemia, and antioxidant could suppress the aggravation of ischemia-induced liver damage in the co-treatment of autophagy inhibitor.
Taken together, our results suggested that autophagy suppressed ischemic liver injury by reducing ROS-induced necrosis. This finding will contribute to the development of the therapeutic strategy about the pre-treatment of liver surgery.
PMCID: PMC3693965  PMID: 23758862
Liver ischemia; Nutrient deprivation; Autophagy; Reactive oxygen species; Necrosis

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