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1.  Effect of Abnormal Fasting Plasma Glucose Level on All-Cause Mortality in Older Patients With Acute Myocardial Infarction: Results From the Beijing Elderly Acute Myocardial Infarction Study (BEAMIS) 
Mayo Clinic Proceedings  2011;86(2):94-104.
OBJECTIVE: To assess whether the relationship between abnormal fasting plasma glucose (FPG) levels and patient outcomes holds for both older men and older women with acute myocardial infarction (AMI).
PATIENTS AND METHODS: From April 1, 2004, to October 31, 2006, a total of 2016 consecutive older patients (age ≥65 years) presenting with AMI were screened. Of these patients, 1854 were consecutively enrolled in the study. Patients were categorized into 4 groups: the hypoglycemic group (FPG, ≤90.0 mg/dL [to convert to mmol/L, multiply by 0.0555]; n=443, 23.9%), the euglycemic group (FPG, 90.1-126.0 mg/dL; n=812, 43.8%), the mildly hyperglycemic group (FPG, 126.1-162.0 mg/dL; n=308, 16.6%), and the severely hyperglycemic group (FPG, ≥162.1 mg/dL; n=291, 15.7%). The primary outcomes were rates of in-hospital and 3-year mortality.
RESULTS: Female patients were older and had a higher incidence of diabetes mellitus but lower rates of smoking and use of invasive therapy. Men tended to have a higher frequency of hypoglycemia, whereas women tended to have a higher frequency of hyperglycemia. No significant difference was found in in-hospital (10.9% vs 9.1%; P=.36) or 3-year (24.5% vs 24.5%; P=.99) mortality between male and female patients, and FPG-associated mortality did not vary significantly by sex.
CONCLUSION: An increased FPG level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased FPG levels at admission could predict higher mortality rates regardless of sex. There was a striking U-shaped relationship between FPG levels and in-hospital and 3-year mortality. The effect of abnormal FPG level on outcomes among older patients with AMI did not vary significantly by sex.
An increased fasting plasma glucose level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased fasting plasma glucose levels at admission could predict higher mortality rates regardless of sex.
PMCID: PMC3031433  PMID: 21282483
2.  Salivirus in Children and Its Association with Childhood Acute Gastroenteritis: A Paired Case-Control Study 
PLoS ONE  2015;10(7):e0130977.
Salivirus was recently discovered in children with gastroenteritis and in sewage. Though a causative role for salivirus in childhood gastroenteritis was suggested in the previous study, the relationship between salivirus and acute gastroenteritis has not yet been clearly clarified. The sewage strain reported by Ng, although represented by incomplete genome sequencing data, was distinct from previously reported saliviruses, and had not previously been detected in humans. A case-control study examining 461 paired stool samples from children with diarrhea and healthy controls (1:1) was conducted in this study. Also, common diarrheal viruses were detected and complete genome of a salivirus was determined. Results showed that salivirus was detected in 16 (3.5%) and 13 (2.8%) of the case and control samples, respectively; no differences in detection rates (p=0.571) or mean values of viral loads (p=0.400) were observed between the groups. Multivariate Cox regression revealed no association between salivirus and gastroenteritis (p=0.774). The data also demonstrated that salivirus infection did not exacerbate clinical symptoms of gastroenteritis in children. Furthermore, complete genome sequence of a salivirus recovered from the feces of a child with diarrhea (i.e., SaliV-FHB) shared a 99% nucleotide identity with the sewage strain. In conclusion, a paired case-control study did not support a causative role for salivirus strains detected in this study with pediatric gastroenteritis. This study also demonstrated that all known saliviruses can be detected in the feces of children with or without gastroenteritis.
PMCID: PMC4507861  PMID: 26193371
3.  Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients 
PLoS ONE  2015;10(7):e0131736.
Symptomatic radiation pneumonitis (SRP), which decreases quality of life (QoL), is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4–12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT) to find the risk factors, which may have important effects on the risk of radiation-induced complications.
In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO) technique.
Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20), energy, age, body mass index (BMI) and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation.
We suggest to define a dose-volume percentage constraint of IV20< 37% (or AIV20< 310cc) for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung volume that received more than 20 Gy (cc).
PMCID: PMC4492617  PMID: 26147496
4.  Purple Sweet Potato Leaf Extract Induces Apoptosis and Reduces Inflammatory Adipokine Expression in 3T3-L1 Differentiated Adipocytes 
Background. Purple sweet potato leaves (PSPL) are widely grown and are considered a healthy vegetable in Taiwan. PSPL contain a high content of flavonoids, and the boiling water-extracted PSPL (PSPLE) is believed to prevent metabolic syndrome. However, its efficacy has not yet been verified. Therefore, we investigated the effect of PSPLE on adipocytes. Methods. The differentiated 3T3-L1 cells used in this study were derived from preadipocytes that were differentiated into adipocytes using an adipogenic agent (insulin, dexamethasone, and 3-isobutyl-1-methylxanthine); approximately 90% of the cells were differentiated using this method. Results. Treating the differentiated 3T3-L1 cells with PSPLE caused a dose-dependent decrease in the number of adipocytes rather than preadipocytes. In addition, treatment with PSPLE resulted in apoptosis of the differentiated 3T3-L1 cells as determined by DAPI analysis and flow cytometry. PSPLE also increased the expression of cleaved caspase-3 and poly ADP-ribose polymerase (PARP). Furthermore, PSPLE induced downregulation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) gene expression in the differentiated 3T3-L1 cells. Conclusions. These results suggest that PSPLE not only induced apoptosis but also downregulated inflammation-associated genes in the differentiated 3T3-L1 cells.
PMCID: PMC4480248  PMID: 26170870
5.  Effects of Benzoic Acid and Thymol on Growth Performance and Gut Characteristics of Weaned Piglets 
A total of 144 weaned crossed pigs were used in a 42-d trial to explore the effects of different concentrations/combinations of benzoic acid and thymol on growth performance and gut characteristics in weaned pigs. Pigs were randomly allotted to 4 dietary treatments: i) control (C), basal diet, ii) C+1,000 mg/kg benzoic acid+100 mg/kg thymol (BT1), iii) C+1,000 mg/kg benzoic acid+200 mg/kg thymol (BT2) and, iv) C+2,000 mg/kg benzoic acid+100 mg/kg thymol (BT3). Relative to the control, pigs fed diet BT3 had lower diarrhoea score during the overall period (p<0.10) and improved feed to gain ratio between days 1 to 14 (p<0.05), which was accompanied by improved apparent total tract digestibility of ether extract, Ca and crude ash (p<0.05), and larger lipase, lactase and sucrose activities in the jejunum (p<0.05) at d 14 and d 42. Similarly, relative to the control, pigs fed diet BT3 had higher counts for Lactobacillus spp in digesta of ileum at d 14 (p<0.05), and pigs fed diets BT1, BT2, or BT3 also had higher counts of Bacillus spp in digesta of caecum at d 14 (p<0.05), and lower concentration of ammonia nitrogen in digesta of caecum at d 14 and d 42 (p<0.05). Finally, pigs fed diet BT3 had higher concentration of butyric acid in digesta of caecum at d 42 (p<0.05), and a larger villus height:crypt depth ratio in jejunum and ileum at d 14 (p<0.05) than pigs fed the control diet. In conclusion, piglets fed diet supplementation with different concentrations/combinations of benzoic acid and thymol could improve feed efficiency and diarrhoea, and improve gut microfloral composition. The combination of 2,000 mg/kg benzoic acid+100 mg/kg thymol produced better effects than other treatments in most measurements.
PMCID: PMC4412979  PMID: 25925060
Benzoic Acid; Thymol; Growth Performance; Microflora; Gut Histo-morphology; Piglets
6.  Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults 
Nutrients  2015;7(6):4778-4791.
Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45–60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day−1 in men and 10 g day−1 in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: “Traditional Chinese”, “Animal food”, “Grains-vegetables” and “High-salt” dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the “Animal food” pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063–1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the “Grains-vegetables” pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618–0.977, p < 0.05). However, the “traditional Chinese” and “high-salt” dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the “Animal food” dietary pattern was associated with an increased risk of NAFLD.
PMCID: PMC4488813  PMID: 26083112
dietary patterns; factor analysis; non-alcoholic fatty liver disease; China
7.  Surgical Versus Non-Surgical Treatment for Vertebral Compression Fracture with Osteopenia: A Systematic Review and Meta-Analysis 
PLoS ONE  2015;10(5):e0127145.
Surgical and non-surgical interventions are the two categories for treatment of vertebral compression fractures (VCFs). However, there is clinical uncertainty over optimal management. This study aimed to examine the safety and effectiveness of surgical management for treatment of VCFs with osteopenia compared with non-surgical treatment.
We conducted a systematic search through electronic databases from inception to June 2014, with no limits on study data or language. Randomized controlled trials (RCTs) evaluating surgical versus non-surgical interventions for treatment of patients with VCFs due to osteopenia were considered. Primary outcomes were pain and adverse effects. A random-effects model was used to calculate the pooled mean difference (MD) or risk ratios with 95% confidence interval (CI).
Sixteen reports (11 studies) met the inclusion criteria, and provided data for the meta-analysis with a total of 1,401 participants. Compared with conservative treatment, surgical treatment was more effective in reducing pain (short-term: MD -2.05, 95% CI -3.55 to -0.56, P=0.007; mid-term: MD -1.70, 95% CI -2.78 to -0.62, P=0.002; long-term: MD -1.24, 95% CI -2.20 to -0.29, P=0.01) and disability on the Roland–Morris Disability score (short-term: MD -4.97, 95% CI -8.71 to -1.23, P=0.009), as well as improving quality of life on the Short-Form 36 Physical Component Summary score (short-term: MD 5.53, 95% CI 1.45 to 9.61, P=0.008) and the Quality of Life Questionnaire of the European Foundation for Osteoporosis score (short-term: MD -5.01, 95% CI -8.11 to -1.91, P=0.002). Indirect comparisons between vertebroplasty and kyphoplasty found no evidence that the treatment effect differed across the two interventions for any outcomes assessed. Compared with the sham procedure, surgical treatment showed no evidence of improvement in pain relief and physical function. Based on these two comparisons, no significant difference between groups was noted in the pooled results for adverse events.
Compared to conservative treatment, surgical treatment was more effective in decreasing pain in the short,mid and long terms. However, no significant mid- and long-term differences in physical function and quality of life was observed. Little good evidence is available for surgical treatment compared with that for sham procedure. PV and BK are currently used to treat VCFs with osteopenia, with little difference in treatment effects. Evidence of better quality and from a larger sample size is required before a recommendation can be made.
Systematic Review Registration PROSPERO registration number: CRD42013005142.
PMCID: PMC4447413  PMID: 26020950
8.  Novel immunological and nutritional-based prognostic index for gastric cancer 
AIM: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer.
METHODS: We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias.
RESULTS: Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively.
CONCLUSION: PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.
PMCID: PMC4438031  PMID: 26019461
Gastric cancer; Prognostic nutritional index; Canton score; Prognosis; Neutrophil-lymphocyte ratio; Platelet-lymphocyte ratio
9.  Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis 
Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn’s disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX.
PMCID: PMC4438047  PMID: 26019477
Henoch-Schönlein purpura; Infliximab; Vasculitis; Subcutaneous ecchymosis; Ulcerative colitis
10.  Cordyceps sinensis preserves intestinal mucosal barrier and may be an adjunct therapy in endotoxin-induced sepsis rat model: a pilot study 
Background: Cordyceps sinensis (C. sinensis), a traditional Chinese medicine, exhibits various pharmacological activities such as reparative, antioxidant, and apoptosis inhibitory effects. Intestinal barrier dysfunction plays a vital role in the progression of sepsis. We aimed to explore the effect of C. sinensis on the gut barrier and evaluate its efficacy in sepsis. Methods: A murine model of gut barrier dysfunction was created by intraperitoneal injection of endotoxin. C. sinensis or saline was administered orally after the induction of sepsis. Alterations of intestinal barrier were evaluated and compared in terms of epithelial cell apoptosis, proliferation index (PI), intercellular tight junction (TJ) and proliferating cell nuclear antigen (PCNA). Results: C. sinensis significantly decreased the percentage of apoptotic cells and promoted mucosal cells proliferation indicated by enhanced PI and PCNA expression in the intestinal mucosa compared to control group. The TJs between epithelial cells which were disrupted in septic rats were also restored by treatment of C. sinensis. In survival studies, C. sinensis was demonstrated to confer a protection against the lethal effect of sepsis. Conclusion: These results suggest that C. sinensis has gut barrier-protection effect in endotoxin-induced sepsis by promoting the proliferation and inhibiting the apoptosis of intestinal mucosal cells, as well as restoring the TJs of intestinal mucosa. C. sinensis may have the potential to be a useful adjunct therapy for sepsis.
PMCID: PMC4509218  PMID: 26221273
Cordyceps sinensis; intestinal barrier; gut barrier; sepsis
11.  Hemodynamic characteristics of high-altitude headache following acute high altitude exposure at 3700 m in young Chinese men 
This study aimed to identify the systemic and cerebral hemodynamic characteristics and their roles in high-altitude headache (HAH) among young Chinese men following acute exposure.
The subjects (n = 385) were recruited in June and July of 2012. They completed case report form questionnaires, as well as heart rate (HR), blood pressure, echocardiogram and transcranial Doppler examinations at 3700 m following a two-hour plane flight. A subgroup of 129 participants was examined at two altitudes (500 and 3700 m).
HAH was characterized by increased HR and cardiac output (CO) and lower saturation pulse oxygen (SpO2) (all p < 0.05). The change in tricuspid regurgitation was also different between the HAH positive (HAH+) and HAH negative (HAH-) subjects. Furthermore, the HAH+ subjects exhibited faster mean (Vm), systolic (Vs) and diastolic (Vd) velocities in the basilar artery (BA; all p < 0.05) and a faster Vd ( 25.96 ± 4.97 cm/s vs. 24.76 ± 4.76 cm/s, p = 0.045) in the left vertebral artery (VA). The bilateral VA asymmetry was also significantly different between the two groups. The pulsatility index (PI) and resistance index (RI) of left VA were lower in the HAH subjects (p < 0.05) and were negatively correlated with HAH (p < 0.05). Baseline CO and Vm in left VA (or right MCA in different regressions) were independent predictors for HAH, whereas CO/HR and ΔVd (Vd difference between bilateral VAs) were independent risk factors for HAH at 3700 m.
HAH was characterized, in part, by increased systemic hemodynamics and posterior cerebral circulation, which was reflected by the BA and left VA velocities, and lower arterial resistance and compliance. Furthermore, baseline CO and Vm in left VA or right MCA at sea level were independent predictors for HAH, whilst bilateral VA asymmetry may contribute to the development of HAH at high altitude.
Electronic supplementary material
The online version of this article (doi:10.1186/s10194-015-0527-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4431987  PMID: 25968101
Systemic circulation; Cerebral circulation; Hemodynamic characteristics; High-altitude headache; Acute exposure
12.  Jingtong Granule: A Chinese Patent Medicine for Cervical Radiculopathy 
Objective. This paper systematically assessed the efficacy and safety of Jingtong granule (JG) for cervical radiculopathy (CR). Methods. Randomized controlled trials comparing JG with no intervention, placebo, or conventional therapies were retrieved. The trials testing JG combined with conventional therapies versus conventional therapies were also enrolled. Study selection, methodological assessment, data extraction, and analysis were conducted in accordance with the Cochrane standards. The strength of evidence was evaluated according to GRADE approach. Results. Three trials with 400 participants were included. Methodological quality was evaluated as generally low. One study found that JG showed significant difference on decreasing pain scores compared with placebo. Meta-analysis indicated that JG plus conventional analgesic exhibited a significant immediate effect on the pain scores (WMD = 1.63; 95% CI: 1.29 to 1.98; P < 0.00001). Additionally, JG combined with analgesic presented beneficial immediate effect on neck disability index. However, the treatment effects of JG demonstrated in the trials were not large, and the safety of JG was unproven. Finally the evidence level was evaluated to be low. Conclusions. Our results indicated that JG showed some potential benefits for CR. Nevertheless, treatment effects are uncertain due to both the methodological concerns and the very modest reported improvements.
PMCID: PMC4443761  PMID: 26064154
13.  Epigenetic silencing of BCL6B inactivates p53 signaling and causes human hepatocellular carcinoma cell resist to 5-FU 
Oncotarget  2015;6(13):11547-11560.
BCL6B is a potential tumor suppressor in human gastric cancer, but the regulation and mechanism of BCL6B in human hepatocellular carcinogenesis remain unclear. This study is to explore the epigenetic change and mechanism of BCL6B in human hepatocellular carcinoma (HCC). Nineteen hepatic cancer cell lines, 50 cases of adjacent tissue and 149 cases of HCC samples were employed. BCL6B is methylated in 100% (19/19) of human HCC cell lines, 40.0% (20/50) of adjacent tissue samples and 86.6% (129/149) of primary cancer samples. Methylation of BCL6B is associated with HBV positive (p < 0.05). But no association was found with age, sex, tumor size, differentiation, TNM stage, recurrence and survival. Loss of BCL6B expression was found in 19 of completely methylated HCC cell lines. BCL6B was re-expressed after 5-aza-2′-deoxycytidine treatment. Restoration of BCL6B expression suppressed cell proliferation, induced apoptosis and G1/S arrest in HCC cells. The expression of EGR1, a key component of p53 signaling, was increased after re-expression BCL6B in HCC cells. Re-expression of BCL6B activated p53 signaling and sensitized HCC cells to 5-fluorouracil. BCL6B is frequently methylated in human HCC and the expression of BCL6B is regulated by promoter region hypermethylation. BCL6B activates p53 signaling by increasing EGR1 expression in HCC.
PMCID: PMC4484475  PMID: 25909168
BCL6B; DNA methylation; hepatocellular carcinoma; p53 signaling; 5-fluorouracil
14.  Association analysis of polymorphisms of the CRHR1 gene with infantile spasms 
Molecular Medicine Reports  2015;12(2):2539-2546.
While >200 types of etiologies have been shown to be involved in the pathogenesis of infantile spasms, the pathophysiology of infantile spasms remains largely elusive. Pre-natal stress and hypothalamic-pituitary-adrenal axis dysfunction were shown to be involved in the development of infantile spasms. To test the genetic association between the CRHR1 gene, which encodes the corticotrophin-releasing hormone (CRH) receptor, and infantile spasms, five single nucleotide polymorphisms (SNPs) in the CRHR1 gene were genotyped in a sample set of 128 cases with infantile spasms and 131 healthy controls. Correlation analysis was performed on the genotyped data. Under the assumption of the dominant model, the selected five SNPs, rs4458044, rs171440, rs17689966, rs28364026 and rs242948, showed no association with the risk of infantile spasms and the effectiveness of adrenocorticotropic hormone treatment. In addition, subsequent haplotype analysis suggested none of them was associated with infantile spasms. In conclusion, the experimental results of the present study suggested no association between the CRHR1 gene and infantile spasms in a Chinese population.
PMCID: PMC4464474  PMID: 25954915
infantile spasms; CRHR1 gene; single nucleotide polymorphism; haplotype
15.  Diastereoselective Three-Component Synthesis of β-Amino Carbonyl Compounds Using Diazo Compounds, Boranes, and Acyl Imines under Catalyst-Free Conditions 
The Journal of Organic Chemistry  2014;79(10):4694-4698.
Diazo compounds, boranes, and acyl imines undergo a three-component Mannich condensation reaction under catalyst-free conditions to give the anti β-amino carbonyl compounds in high diastereoselectivity. The reaction tolerates a variety of functional groups, and an asymmetric variant was achieved using the (−)-phenylmenthol as chiral auxiliary in good yield and selectivity. These β-amino carbonyl compounds are valuable intermediates, which can be transformed to many potential bioactive molecules.
PMCID: PMC4033649  PMID: 24787904
16.  Generating Personalized Web Search Using Semantic Context 
The Scientific World Journal  2015;2015:462782.
The “one size fits the all” criticism of search engines is that when queries are submitted, the same results are returned to different users. In order to solve this problem, personalized search is proposed, since it can provide different search results based upon the preferences of users. However, existing methods concentrate more on the long-term and independent user profile, and thus reduce the effectiveness of personalized search. In this paper, the method captures the user context to provide accurate preferences of users for effectively personalized search. First, the short-term query context is generated to identify related concepts of the query. Second, the user context is generated based on the click through data of users. Finally, a forgetting factor is introduced to merge the independent user context in a user session, which maintains the evolution of user preferences. Experimental results fully confirm that our approach can successfully represent user context according to individual user information needs.
PMCID: PMC4427129  PMID: 26000335
17.  Bilateral coronary artery fistula as a cause of angina pectoris 
BMJ Case Reports  2013;2013:bcr2013008971.
PMCID: PMC3645775  PMID: 23592818
18.  A Survey of the Practice and Perspectives of Chinese Acupuncturists on Deqi 
Deqi refers to the special sensation and reaction sensed mainly by both acupuncturist and patient when a needle was inserted into the acupoints and is considered to be vital to achieve acupuncture effect. For acupuncturist, it is important to judge and control Deqi in clinical practice. However, enough attention is paid to patients' feelings rather than acupuncturists' nowadays. We thus conducted this survey to determine acupuncturists' perspectives about Deqi and to further find the proper way to induce Deqi. A total of 250 questionnaires were sent out to acupuncturists and 202 (80.8%) were returned. According to the results, most acupuncturists believe that Deqi is vital to obtain preferable clinical effects. The reliability of acupuncturists' Deqi sensation ranks as sinking> tightening> astringent. The reliability of patients' Deqi sensations ranks as sourness> numbness> distention> heaviness> pain. The reliability of influential factors ranks as manipulation> specificity of acupoint> TCM constitution> disease status> patient's psychological condition> acupuncturists' psychological guidance> clinical environment. This study is believed to provide additional evidence to the qualitative and quantitative research of Deqi in the future.
PMCID: PMC4413523  PMID: 25960755
19.  Solid state fermentation of rapeseed cake with Aspergillus niger for degrading glucosinolates and upgrading nutritional value 
Rapeseed cake is a good source of protein for animal feed but its utilization is limited due to the presence of anti-nutritional substances, such as glucosinolates (Gls), phytic acid, tannins etc. In the present study, a solid state fermentation (SSF) using Aspergillus niger was carried out with the purpose of degrading glucosinolates and improving the nutritional quality of rapeseed cake (RSC). The effects of medium composition and incubation conditions on the Gls content in fermented rapeseed cake (FRSC) were investigated, and chemical composition and amino acid in vitro digestibility of RSC substrate fermented under optimal conditions were determined.
After 72 h of incubation at 34°C, a 76.89% decrease in Gls of RSC was obtained in solid medium containing 70% RSC, 30% wheat bran at optimal moisture content 60% (w/w). Compared to unfermented RSC, trichloroacetic acid soluble protein (TCA-SP), crude protein and ether extract contents of the FRSC were increased (P < 0.05) 103.71, 23.02 and 23.54%, respectively. As expected, the contents of NDF and phytic acid declined (P < 0.05) by 9.12 and 44.60%, respectively. Total amino acids (TAA) and essential amino acids (EAA) contents as well as AA in vitro digestibility of FRSC were improved significantly (P < 0.05). Moreover, the enzyme activity of endoglucanase, xylanase, acid protease and phytase were increased (P < 0.05) during SSF.
Our results indicate that the solid state fermentation offers an effective approach to improving the quality of proteins sources such as rapeseed cake.
PMCID: PMC4399751  PMID: 25883784
Aspergillus niger; Glucosinolates; Nutritional value; Rapeseed cake; Solid state fermentation
20.  Impacts of Gut Bacteria on Human Health and Diseases 
Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases.
PMCID: PMC4425030  PMID: 25849657
gut bacteria; human health; cancer; obesity
21.  Establishment of Hairy Root Cultures by Agrobacterium Rhizogenes Mediated Transformation of Isatis Tinctoria L. for the Efficient Production of Flavonoids and Evaluation of Antioxidant Activities 
PLoS ONE  2015;10(3):e0119022.
In this work, Isatis tinctoria hairy root cultures (ITHRCs) were established as an alternative source for flavonoids (FL) production. I. tinctoria hairy root line V was found to be the most efficient line and was further confirmed by the PCR amplification of rolB, rolC and aux1 genes. Culture parameters of ITHRCs were optimized by Box-Behnken design (BBD), and eight bioactive FL constituents (rutin, neohesperidin, buddleoside, liquiritigenin, quercetin, isorhamnetin, kaempferol and isoliquiritigenin) were quali-quantitatively determined by LC-MS/MS. Under optimal conditions, the total FL accumulation of ITHRCs (24 day-old) achieved was 438.10 μg/g dry weight (DW), which exhibited significant superiority as against that of 2 year-old field grown roots (341.73 μg/g DW). Additionally, in vitro antioxidant assays demonstrated that ITHRCs extracts exhibited better antioxidant activities with lower IC50 values (0.41 and 0.39, mg/mL) as compared to those of field grown roots (0.56 and 0.48, mg/mL). To the best of our knowledge, this is the first report describing FL production and antioxidant activities from ITHRCs.
PMCID: PMC4364778  PMID: 25785699
22.  Genome-wide analysis of cancer cell-derived Foxp3 target genes in human tongue squamous cell carcinoma cells 
International Journal of Oncology  2015;46(5):1935-1943.
The forkhead transcription factor Foxp3 is essential for differentiation and activation of regulatory T cells (Tregs), and used to be regarded as specific transcription factor of Tregs. In recent years, Foxp3 expression in tumor cells (cancer cell-derived Foxp3) has gained great interest, but its function and molecular mechanisms remain incompletely understood. In the present study, we detected dynamic nuclear translocation of Foxp3 in TSCC cells using immunofluorescent staining. Then we performed a genome-wide analysis of Foxp3 in TSCC cells using a combination of ChIP-on-chip and whole-genome microarray assays. We also compared Foxp3 biding sites in TSCC cells with the known binding sites in human Tregs to show the differences in transcriptional regulation profile. Results indicate that Foxp3 in TSCC cells has distinct biological functions compared with that in Tregs. Cancer cell-derived Foxp3 directly regulates the transcription of genes that affect certain internal biological processes of TSCC cells, and indirectly influences the extracellular microenvironment. This study reveals the relationship between direct and indirect targets genes of Foxp3 in TSCC cells and provide molecular basis of cancer cell-derived Foxp3 function.
PMCID: PMC4383015  PMID: 25779374
Foxp3; tongue squamous cell carcinoma; regulatory T cells; chromatin immunoprecipitation with DNA microarray; genome
23.  Accumulation of p53 is prognostic for aromatase inhibitor resistance in early-stage postmenopausal patients with ER-positive breast cancer 
OncoTargets and therapy  2015;8:549-555.
Studies have indicated that p53 protein accumulation exerts an adverse effect on the survival of breast cancer patients; however, the prognostic value of p53 protein accumulation for aromatase inhibitor (AI) resistance in ER-positive breast cancer is uncertain.
The expression level of p53 protein was detected by immunohistochemistry in primary early-stage ER-positive breast tumor specimens from 293 postmenopausal breast cancer patients who received first-line AI treatment (letrozole, anastrozole, or exemestane) until relapse, and analysis was performed to determine whether expression of p53 protein affected the response to endocrine therapy.
Of the 293 invasive ductal carcinomas, 65.4% were positive for p53 protein expression. All patients received AI therapy as first-line treatment until relapse. The 5-year disease-free survival rates in p53-positive and p53-negative patients were 78% and 89%, respectively. Patients with primary breast tumors that had p53 protein accumulation showed significantly more resistance to AI treatment (hazard ratio=1.729, 95% confidence interval=1.038–2.880, P=0.035).
This study demonstrated that p53 protein accumulation was helpful in choosing patients who may benefit from AI treatment and is a prognostic marker in ER-positive early-stage breast cancer.
PMCID: PMC4354449  PMID: 25767399
p53; breast cancer; prognosis; endocrine resistance
24.  Anti-inflammatory effect of 1,25-dihydroxyvitamin D3 is associated with crosstalk between signal transducer and activator of transcription 5 and the vitamin D receptor in human monocytes 
1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has an anti-inflammatory effect on human monocytes incubated with sera from patients with type 2 diabetes/diabetic nephropathy; however, the detailed mechanism behind the effect remains to be explored. The current study further validated the effects of 1,25-(OH)2D3 and lipopolysaccharide (LPS) + human recombinant interleukin (IL)-15 on the expression of the vitamin D receptor (VDR) and phosphorylated signal transducer and activator of transcription 5 (p-STAT5) in human monocytes and explored the possible interaction between VDR and p-STAT5. Synchronized THP-1 cells were divided into pre-intervened groups, namely the control, LPS + IL-15 and 1,25-(OH)2D3, groups, according to their differing treatments. The expression of STAT5 and p-STAT5 was evaluated by western blot analysis; the concentration of IL-6 in the supernatant was determined using an enzyme-linked immunosorbent assay; the expression of cytoskeletal proteins was observed using immunofluorescence and laser confocal microscopy; and the possible intranuclear interaction between VDR and p-STAT5 was investigated using immunofluorescence, immuno-coprecipitation and western blot analysis. LPS + IL-15 upregulated p-STAT5 expression and the IL-6 level (P<0.05), with cytoskeletal rearrangement. These effects were partially prevented through pretreatment with 1,25-(OH)2D3. The LPS + IL-15 group and the 1,25-(OH)2D3 group exhibited an interaction between p-STAT5 and VDR in the nucleus, with the latter group showing a significant increase compared with the former (P<0.05). The immuno-coprecipitation results provided evidence of the interaction between VDR and p-STAT5, which suggests the existence of STAT5-VDR crosstalk in THP-1 monocytes. Cytoskeletal rearrangement, VDR and p-STAT5 potentially have interactions in THP-1 monocytes. The anti-inflammatory effect of 1,25-(OH)2D3 may be associated with crosstalk between STAT5 and VDR, which further induces cytoskeletal rearrangement.
PMCID: PMC4471802  PMID: 26136886
1,25-dihydroxyvitamin D3; monocyte; lipopolysaccharide; interleukin-15; vitamin D receptor; signal transducer and transcription activator
25.  Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis 
Molecular Human Reproduction  2013;20(3):260-270.
Accumulating evidence indicates that reduced fecundity associated with endometriosis reflects a failure of embryonic receptivity. Microdomains composed of endometrial gap junctions, which facilitate cell–cell communication, may be implicated. Pharmacological or genetic inhibition of connexin (Cx) 43 block human endometrial cell differentiation in vitro and conditional uterine deletion of Cx43 alleles cause implantation failure in mice. The aim of this study was to determine whether women with endometriosis have reduced eutopic endometrial Cx43. Cx26 acted as a control. Endometrial biopsies were collected from age, race and cycle phase-matched women without (15 controls) or with histologically confirmed endometriosis (15 cases). Immunohistochemistry confirmed a predominant localization of Cx43 in the endometrial stroma, whereas Cx26 was confined to the epithelium. Cx43 immunostaining was reduced in eutopic biopsies of endometriosis subjects and western blotting of tissue lysates confirmed lower Cx43 levels in endometriosis cases, with Cx43/β-actin ratios =3.4 ± 1.5 in control and =1.2 ± 0.3 in endometriosis biopsies (P < 0.01). When endometrial stromal cells (ESC) were isolated from endometriosis cases, Cx43 levels and scrape loading-dye transfer were reduced by ∼45% compared with ESC from controls. In vitro decidualization of ESC derived from endometriosis versus control subjects resulted in lesser epithelioid transformation and a significantly reduced up-regulation of Cx43 protein (1.2 ± 0.2- versus 1.7 ± 0.4-fold, P < 0.01). No changes in Cx26 were observed. While basal steady-state levels of Cx43 mRNA did not differ with respect to controls, ESC from endometriosis cases failed to manifest a response to hormone treatment in vitro. In summary, eutopic endometrial Cx43 concentrations in endometriosis cases were <50% those of controls in vivo and in vitro, functional gap junctions were reduced and hormone-induced Cx43 mRNA levels were blunted.
PMCID: PMC3925331  PMID: 24270393
endometriosis; gap junctions; immunohistochemistry; western blot; gene expression

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