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1.  Survival and prognostic factors of non-small cell lung cancer patients with postoperative locoregional recurrence treated with radical radiotherapy 
Locoregional recurrence remains the challenge for long-term survival of non-small cell lung cancer (NSCLC) patients after radical surgery, and curative-intent radiotherapy could be a treatment choice. This study aimed to assess the survival and prognostic factors of patients with postoperative locoregionally recurrent NSCLC treated with radical radiotherapy.
We reviewed medical records of 74 NSCLC patients with postoperative locoregional recurrence who received radical radiotherapy between April 2012 and February 2016 at Sun Yat-sen University Cancer Center (Guangzhou, China). The efficacy and safety of radical radiotherapy were analyzed. The probability of survival was estimated using the Kaplan–Meier method and compared using the log-rank test. The Cox proportional hazards model was used to identify prognostic factors.
Grade 3/4 adverse events included neutropenia (8 cases, 10.8%), esophagitis (7 cases, 9.5%), pneumonitis (1 case, 1.4%), and vomiting (1 case, 1.4%). The 2-year overall survival, progression-free survival, local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of all patients were 84.2, 42.5, 70.0, and 50.9%, respectively. Univariate and multivariate analyses showed that a higher biological effective dose (BED) of radiation was associated with longer LRFS [hazard ratios (HR) = 0.317, 95% confidence interval (CI) = 0.112–0.899, P = 0.016] and that wild-type epidermal growth factor receptor (EGFR) was associated with longer DMFS compared with EGFR mutation (HR = 0.383, 95% CI = 0.171–0.855, P = 0.019).
Radical radiotherapy is effective and well-tolerated in NSCLC patients with postoperative locoregional recurrence. High BED is a predictor for long LRFS, and the presence of wild-type EGFR is a predictor for long DMFS.
PMCID: PMC5725840  PMID: 29228994
Non-small cell lung cancer; Locoregional recurrence; Radical radiotherapy; Biological effective dose; Epidermal growth factor receptor
2.  The Borrelia burgdorferi CheY3 Response Regulator is Essential for Chemotaxis and Completion of its Natural Infection Cycle 
Cellular microbiology  2016;18(12):1782-1799.
Borrelia burgdorferi possesses a sophisticated and complex chemotaxis system but how the organism utilizes this system in its natural enzootic life cycle is poorly understood. Of the three CheY chemotaxis response regulators in B. burgdorferi, we found that only deletion of cheY3 resulted in an altered motility and significantly reduced chemotaxis phenotype. Though ΔcheY3 maintained normal densities in unfed ticks, their numbers were significantly reduced in fed ticks compared to the parental or cheY3-complemented spirochetes. Importantly, mice fed upon by the ΔcheY3-infected ticks did not develop a persistent infection. Intravital confocal microscopy analyses discovered that the ΔcheY3 spirochetes were motile, but appeared unable to reverse direction and perform the characteristic backward-forward motility displayed by the parental strain. Subsequently, the ΔcheY3 became “trapped” in the skin matrix within days of inoculation, were cleared from the skin needle-inoculation site within 96 hours post-injection, and did not disseminate to distant tissues. Interestingly, although ΔcheY3 cells were cleared within 96 hours post-injection, this attenuated infection elicited significant levels of B. burgdorferi-specific IgM and IgG. Taken together, these data demonstrate that cheY3-mediated chemotaxis is crucial for motility, dissemination, and viability of the spirochete both within and between mice and ticks.
PMCID: PMC5116424  PMID: 27206578
3.  Reductions in the mitochondrial enzyme α-ketoglutarate dehydrogenase complex in neurodegenerative disease - beneficial or detrimental? 
Journal of neurochemistry  2016;139(5):823-838.
Reductions in metabolism and excess oxidative stress are prevalent in multiple neurodegenerative diseases. The activity of the mitochondrial enzyme α-ketoglutarate dehydrogenase complex (KGDHC) appears central to these abnormalities. KGDHC is diminished in multiple neurodegenerative diseases. KGDHC can be rate limiting for NADH production and for substrate level phosphorylation, but is also a source of reactive oxygen species (ROS). The goal of these studies was to determine how changes in KGDHC modify: baseline ROS, the ability to buffer ROS, baseline glutathionylation, calcium modulation and cell death in response to external oxidants. In vivo, reducing KGDHC with adeno virus diminished neurogenesis and increased oxidative stress. In vitro, treatments of short duration increased ROS and glutathionylation and enhanced the ability of the cells to diminish the ROS from added oxidants. However, long term reductions lessened the ability to diminish ROS, diminished glutathionylation and exaggerated oxidant induced changes in calcium and cell death. Increasing KGDHC enhanced the ability of the cells to diminish externally added ROS and protected against oxidant induced changes in calcium and cell death. The results suggest that brief periods of diminished KGDHC are protective, while prolonged reductions are harmful. Furthermore, elevated KGDHC activities are protective. Thus, mitogenic therapies that increase KGDHC may be beneficial in neurodegenerative diseases.
Graphical Abstract
Reductions in the activity of the mitochondrial enzyme α-ketoglutarate dehydrogenase complex (KGDHC) occur in multiple neurodegenerative diseases. KGDHC is important in energy production, but is also a source of reactive oxygen species. The goal of the studies was to determine whether the reduction was good or bad. Short term reduction of KGDHC activity leads to enhanced buffering of ROS and increased glutathionylation-both of which are protective. However, prolonged reduction in activity diminishes buffering and glutathionylation. Increasing KGDHC activity was always protective.
PMCID: PMC5123932  PMID: 27580471
Mitochondria; α-ketoglutarate dehydrogenase complex; cell death; oxidative stress
4.  Malignant acanthosis nigricans: an early diagnostic clue for gastric adenocarcinoma 
Malignant acanthosis nigricans (MAN), characterized by the presence of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous sign of internal malignancy. Few MAN has been reported in the Asian race ever before.
Case presentation
Here, we report a rare case of MAN with severe mucosa and soles and extraordinary facial involvement in the Asian race. A 74-year-old man presented with hyperkeratotic eruption for 7 months. Physical examination revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels, and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia tubular adenocarcinoma. The patient was diagnosed with MAN associated with gastric adenocarcinoma, immediately following tumor resection and lymphadenectomy. A slight improvement was seen in the skin condition but died of cancer cachexia 3 months later.
We report our typical patient to highlight the importance of MAN, which was an early clue to the discovery of gastric adenocarcinoma.
PMCID: PMC5702104  PMID: 29178944
Malignant acanthosis nigricans; Hyperkeratosis; Papillomatosis; Gastric adenocarcinoma
5.  Trial to Incentivise Adherence for Diabetes (TRIAD): study protocol for a randomised controlled trial 
Trials  2017;18:551.
Many people with diabetes have suboptimal glycaemic control due to not being adherent to their treatment regimen. Behavioural economic theory suggests that the lack of adherence results from the disconnect between the timing of when costs and benefits accrue. One strategy to address this discontinuity is to offer patients a near-term benefit, such as a financial reward. Whereas there is evidence that rewards can improve treatment adherence and sometimes health outcomes, further research is needed to determine whether rewards are more effective when targeting processes or intermediary health outcomes. In the Trial to Incentivise Adherence for Diabetes (TRIAD) we test whether adding financial incentives to usual care can improve HbA1c levels among people with diabetes and whether the financial incentives work better when targeting processes (adherence to blood glucose testing, medication, and daily physical activity) or the primary intermediary health outcome of self-monitored blood glucose within an acceptable range.
TRIAD is a randomised, controlled, open-label, single-centre superiority trial with three parallel arms. A total of 240 patients with suboptimally controlled diabetes (HbA1c ≥ 8%) from a polyclinic in Singapore are block-randomised (blocking factor: current vs. new glucometer users) into three arms, namely (1) usual care (UC) only, (2) UC with process incentive and (3) UC with outcome incentive, in a 2:3:3 ratio. Masking the arm allocation will be precluded by the behavioural nature of the intervention but blocking size will not be disclosed to protect concealment. The primary outcome (change in HbA1c level at month 6) will be measured by a laboratory that is independent from the study team. Secondary outcomes (at month 6) include the number of blood glucose testing days, glucose readings within the normal range (between 4 to 7 mmol/L), medication-adherent days, physically active days, and average incentives earned and time spent administrating the incentives.
This study will provide evidence on whether financial incentives can cost-effectively improve glycaemic control. It will also provide evidence on the benefit incidence of interventions involving financial incentives. By comparing process to outcome incentives, this study will inform the design of future incentive strategies in chronic disease management and beyond.
Trial registration registry, ID: NCT02224417. Registered on 22 August 2014.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-017-2288-6) contains supplementary material, which is available to authorized users.
PMCID: PMC5693491  PMID: 29149912
Diabetes; Medication adherence; Blood glucose monitoring; Physical activity; Financial incentive; Behaviour change
6.  Yes-Associated Protein (YAP) Promotes Tumorigenesis in Melanoma Cells Through Stimulation of Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) 
Scientific Reports  2017;7:15528.
YAP is a critical protein in cancer development and can induce transformative phenotypes in mammary epithelial cells. Previous studies have provided evidence that YAP can contribute to the metastatic behavior of melanoma, since specific knockdown of YAP leads to reduced metastatic and invasive capacity in vitro. However, the mechanism by which YAP regulates the function of melanoma is unknown. Here, we identified that YAP has a positive impact on the expression of LRP1, which also plays critical roles in cancer. Mechanically, knockdown of YAP resulted in a significant down-regulation of LRP1 at both the protein and mRNA levels. Tissue microarray analysis (TMA) also showed a positive correlation between YAP and LRP1 expression. In addition, reduction of YAP-impaired pro-carcinogenic phenotypes could be partially reversed by simultaneous overexpression of LRP1, suggesting that LRP1 is functionally important in YAP-induced melanoma tumorigenesis. Furthermore, we found that LRP1 was regulated by YAP through a transcription- and promoter-dependent mechanism. Taken together, our results suggest that YAP regulates LRP1 through stimulation of the LRP1 promoter and that LRP1 may be an important target for influencing YAP in melanoma.
PMCID: PMC5686191  PMID: 29138479
7.  Garcin syndrome caused by parotid gland adenoid cystic carcinoma 
Medicine  2017;96(45):e8508.
Garcin syndrome is characterized by the gradual involvement, and ultimately, unilateral paralysis of at least 7 and sometimes all cranial nerves, without intracranial hypertension or any long tract signs.
Patient concerns:
We report the case of a 59-year-old woman who presented with Garcin syndrome, which gradually progressed over a period of 2 years.
A left parotid gland biopsy revealed parotid gland adenoid cystic carcinoma (PGACC) with perineural invasion of a peripheral nerve bundle and lymph node metastasis.
The patient was treated 3 times with local-field palliative radiotherapy.
She died after several months.
To the best of our knowledge, this is the first report of PGACC presenting as Garcin syndrome. PGACC is a rare tumor with a high propensity for perineural spread, and it should be considered as a possible cause of Garcin syndrome.
PMCID: PMC5690742  PMID: 29137049
adenoid cystic carcinoma; cranial nerves palsy; Garcin syndrome; parotid gland; PGACC
8.  Identification of the First Riboflavin Catabolic Gene Cluster Isolated from Microbacterium maritypicum G10* 
The Journal of Biological Chemistry  2016;291(45):23506-23515.
Riboflavin is a common cofactor, and its biosynthetic pathway is well characterized. However, its catabolic pathway, despite intriguing hints in a few distinct organisms, has never been established. This article describes the isolation of a Microbacterium maritypicum riboflavin catabolic strain, and the cloning of the riboflavin catabolic genes. RcaA, RcaB, RcaD, and RcaE were overexpressed and biochemically characterized as riboflavin kinase, riboflavin reductase, ribokinase, and riboflavin hydrolase, respectively. Based on these activities, a pathway for riboflavin catabolism is proposed.
PMCID: PMC5095406  PMID: 27590337
cloning; enzyme mechanism; flavoprotein; quorum sensing; riboflavin; Vitamin B2; catabolism; lyase; reconstitution
9.  Fusion imaging of contrast-enhanced ultrasound and contrast-enhanced CT or MRI before radiofrequency ablation for liver cancers 
The British Journal of Radiology  null;89(1067):20160379.
To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers.
45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded.
On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous lesions to 49 (70.0%) (70.0% vs 35.7%; p < 0.001 in comparison with conventional ultrasound). With the use of CEUS and CECT/CEMRI fusion imaging, the number of the conspicuous lesions further increased to 67 (95.7%, 67/70) (95.7% vs 70.0%, 95.7% vs 35.7%; both p < 0.001 in comparison with ultrasound and ultrasound-CECT/CEMRI fusion imaging, respectively). With the assistance of CEUS and CECT/CEMRI fusion imaging, the confidence level of the operator for performing RFA improved significantly with regard to visualization of the target lesions (p = 0.001). The CR rate for RFA was 97.0% (64/66) in accordance to the CECT/CEMRI results 1 month later. No procedure-related deaths and major complications occurred during and after RFA.
Fusion of CEUS and CECT/CEMRI improves the visualization of those inconspicuous lesions on conventional ultrasound. It also facilitates improvement in the RFA operators' confidence and CR of RFA.
Advances in knowledge:
CEUS and CECT/CEMRI fusion imaging is better than both conventional ultrasound and ultrasound-CECT/CEMRI fusion imaging for lesion visualization and improves the operator confidence, thus it should be recommended to be used as a routine in ultrasound-guided percutaneous RFA procedures for liver cancer.
PMCID: PMC5124839  PMID: 27626506
10.  A Simple Assay for Ultrasensitive Colorimetric Detection of Ag+ at Picomolar Levels Using Platinum Nanoparticles 
Sensors (Basel, Switzerland)  2017;17(11):2521.
In this work, uniformly-dispersed platinum nanoparticles (PtNPs) were synthesized by a simple chemical reduction method, in which citric acid and sodium borohydride acted as a stabilizer and reducer, respectively. An ultrasensitive colorimetric sensor for the facile and rapid detection of Ag+ ions was constructed based on the peroxidase mimetic activities of the obtained PtNPs, which can catalyze the oxidation of 3,3’,5,5’-tetramethylbenzidine (TMB) by H2O2 to produce colored products. The introduced Ag+ would be reduced to Ag0 by the capped citric acid, and the deposition of Ag0 on the PtNPs surface, can effectively inhibit the peroxidase-mimetic activity of PtNPs. Through measuring the maximum absorption signal of oxidized TMB at 652 nm, ultra-low detection limits (7.8 pM) of Ag+ can be reached. In addition to such high sensitivity, the colorimetric assay also displays excellent selectivity for other ions of interest and shows great potential for the detection of Ag+ in real water samples.
PMCID: PMC5713046  PMID: 29099050
platinum nanoparticles; peroxidase-mimic activity; colorimetric sensor; silver ions detection
11.  Mycobacterium tuberculosis found at both skin lesions and Mantoux testing site in a patient with erythema induratum of Bazin 
The Journal of Dermatology  2017;44(10):1145-1147.
Mycobacterium tuberculosis is very rarely found in erythema induratum of Bazin; recently, we found an unusual case with positive acid‐fast bacilli and polymerase chain reaction for detecting M. tuberculosis in both skin lesions of the extremities and the site of Mantoux test.
PMCID: PMC5655927  PMID: 28470727
erythema induratum of Bazin; erythematous macules; Mantoux testing; tuberculosis; Ziehl–Neelsen staining
12.  An analysis of the gene interaction networks identifying the role of PARP1 in metastasis of non-small cell lung cancer 
Oncotarget  2017;8(50):87263-87275.
Background and Objective
Though there were many researches about the effects of cancer cells on non-small cell lung cancer (NSCLC) currently, it has been rarely reported completed oncogene and its mechanism in tumors by far. Here, we used biological methods with known oncogene of NSCLC to find new oncogene and explore its functionary mechanism in NSCLC.
The study firstly built NSCLC genetic interaction network based on bioinformatics methods and then combined shortest path algorithm with significance test to confirmed core genes that were closely involved with given genes; real-time qPCR was conducted to detect expression levels between patients with NSCLC and normal people; additionally, detection of PARP1's role in migration and invasion was performed by trans-well assays and wound-healing.
Through gene interaction network, it was found that, core genes like PARP1, EGFR and ALK had a direct interaction. TCGA database showed that PARP1 presented strong expression in NSCLC and the expression level of metastatic NSCLC was significantly higher than that of non-metastatic NSCLC. Cell migration of NSCLC in accordance to the scratch test was suppressed by PARP1 silence but stimulated noticeably by PARP1 overexpression. According to Kaplan-meier survival curve, the higher PARP1 expression, the poorer patient survival rate and prognosis. Thus, PARP1 expression had a negative correction with patient survival rate and prognosis.
New oncogene PARP1 was found from known NSCLC oncogene in terms of gene interaction network, demonstrating PARP1's impact on NSCLC cell migration.
PMCID: PMC5675631
NSCLC; gene interaction network; shortest path; PARP1; migration and invasion
13.  The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells 
Oncotarget  2017;8(49):85276-85289.
Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells. Overexpression of miR-200b-3p and miR-429-5p significantly inhibited the proliferation, migration, and invasion of TNBC cells; suppressed the expression of markers for proliferation and metastasis in TNBC cells. We next demonstrated that LIM domain kinase 1 (LIMK1) is a direct target gene of miR-200b-3p and miR-429-5p. Inhibition of LIMK1 reduced the expression and phosphorylation of cofilin 1 (CFL1), which polymerizes and depolymerizes F-actin and G-actin to reorganize cellular actin cytoskeleton. In addition, transfection with mimics for miR-200b-3p and miR-429-5p arrested G2/M and G0/G1 cell cycles respectively, suppressed the expression of the cell cycle–related complexes, cyclin D1/CDK4/CDK6 and cyclin E1/CDK2, in TNBC cells. In conclusion, miR-200b-3p and miR-429-5p suppress proliferation, migration, and invasion in TNBC cells, via the LIMK1/CFL1 pathway. These results provide insight into how specific miRNAs regulate TNBC progression and suggest that the LIMK1/CFL1 pathway is a therapeutic target for treating TNBC.
PMCID: PMC5689609
miR-200b-3p; miR-429-5p; triple-negative breast cancer; proliferation; cell motility
14.  The β-glucan from Lentinus edodes suppresses cell proliferation and promotes apoptosis in estrogen receptor positive breast cancers 
Oncotarget  2017;8(49):86693-86709.
Breast cancer is now the most common cancer in worldwide women, and novel interventions are needed to overcome the resistance occurring in the estrogen-targeted endocrine therapy. Herein, we demonstrate that the β-glucan from Lentinus edodes (LNT) exhibited a profound inhibition ratio of ∼53% against estrogen receptor positive (ER+) MCF-7 tumor growth in nude mice similar to the positive control of cisplatin. Immunohistochemistry images showed that LNT evidently suppressed cell proliferation and promoted apoptosis in MCF-7 tumor tissues. The Western blotting analysis indicated that LNT up-regulated the tumor suppressor p53, phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2), cleaved-Caspase 3 and poly [ADP (ribose)] polymerase 1 (PARP 1) protein levels, and reduced the expression of mouse double minute 2 (MDM2), telomerase reverse transcriptase (TERT), nuclear factor-kappa B (NF-κB) p65, B-cell lymphoma-2 (Bcl-2), estrogen receptor α (ERα), etc. in tumor tissues. Moreover, LNT significantly suppressed phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt) and mammalian target of rapamycin (mTOR) protein levels. It was thus proposed that LNT inhibited MCF-7 tumor growth through suppressing cell proliferation and enhancing apoptosis possibly via multiple pathways such as PI3K/Akt/mTOR, NF-κB-, ERK-, ERα-, caspase- and p53-dependent pathways. Interestingly, the cell viability assay, siRNA transfection, Western blotting and flow cytometric analysis suggested that LNT targeted p53/ERα to only suppress cell proliferation via cell cycle arrest at G2/M phase without apoptosis in vitro. The big difference between in vivo and in vitro data suggested that the immune responses triggered by the polysaccharide should mainly contribute to the apoptotic effect in vivo. Overall, this work provides a novel strategy to treat ER+ breast cancers by using a naturally occurring β-glucan from mushrooms.
PMCID: PMC5689718
β-glucan; breast cancer; estrogen receptor positive; proliferation; apoptosis
15.  Clinical features and CKD-related quality of life in patients with CKD G3a and CKD G3b in China: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) 
BMC Nephrology  2017;18:311.
This study aimed to compare clinical features and health-related quality of life (HRQoL) in the Chinese chronic kidney disease (CKD) 3 population and determined the necessity of the subdivision of CKD3 in Chinese patients with CKD.
Participants with stage 3 CKD (18–74 years of age) were recruited at 39 clinical centers located at 28 cities in 22 provinces of China. The sociodemographic status, medical history, anthropometric measurements, and lifestyle behaviors were documented at entry, and blood and urine samples were collected. The estimated glomerular filtration rate was calculated using the CKD-EPI creatinine equation. The HRQoL was evaluated using the kidney disease quality-of-life instrument. A linear regression model was used to estimate the association between HRQoL and CKD stages (G3b vs G3a).
The levels of intact parathyroid hormone, systolic blood pressure, uric acid, and high-density lipoprotein cholesterol were statistically significantly higher, whereas the levels of serum bicarbonate and hemoglobin were statistically significantly lower in the G3b group compared with the G3a group. Compared with CKD G3a group, the proportions of subjects with hyperuricemia and anemia were significantly higher in CKD G3b group (61.4% vs. 52.0% and 26.4% vs. 17.9%, respectively, P< 0.01). The HRQoL scores in “physical functioning (PCS)”, “symptoms and problems”, “effects of the kidney disease” and “burden of the kidney disease” were statistically significantly lower in the CKD G3b group compared with the CKD G3a group (90.88 ± 11.05 vs. 89.30 ± 11.52, 88.29 ± 11.94 vs. 86.49 ± 13.45, 55.86 ± 26.40 vs. 52.10 ± 27.64, 46.56 ± 8.16 vs. 44.51 ± 9.22, respectively, P< 0.01). Further, CKD G3b was associated with a lower score of physical functioning compared with G3a (regression coefficient =−1.12 [95%CI: −2.23, −0.16]).
The preliminary results of this study suggested that modest differences existed in many important clinical features and KDQoL between patients with G3a and G3b CKD in a Chinese population. Also, a significant association between CKD3 subdivision of the disease and PCS was detected. Although further work is needed, we can speculate based on these results the CKD3 subdivision may be clinically meaningful for Chinese patients with CKD.
Electronic supplementary material
The online version of this article (doi: 10.1186/s12882-017-0725-0) contains supplementary material, which is available to authorized users.
PMCID: PMC5640906  PMID: 29029600
Chronic kidney disease stage 3; Clinical features; Health-related quality of life; Subdivision
16.  Association between alcohol consumption and the risk of gastric cancer: a meta-analysis of prospective cohort studies 
Oncotarget  2017;8(48):84459-84472.
Alcohol consumption is inconsistently associated with the risk of gastric cancer morbidity and mortality. The aim of this study was to systematically evaluate the association between alcohol consumption on gastric cancer risk. The PubMed, Embase, and Cochrane Library databases were searched from inception through April 2017. Prospective cohort studies evaluating the association between alcohol consumption and risk of gastric cancer which report its effect estimates with 95% confidence intervals (CIs) were included. The results summary was performed using the random-effect model. Twenty-two cohort studies involving 22,545 cases of gastric cancer and 5,820,431 participants were identified and included in our data analysis. Overall, drinking had little or no effect on gastric cancer as compared with non-drinkers. Furthermore, light and moderate alcohol consumption had no significant effect on gastric cancer risk when compared with non-drinkers. However, heavy alcohol consumption was associated with a greater risk of gastric cancer when compared with non-drinkers. The findings of the subgroup analyses indicated that light alcohol consumption was associated with a lower risk of gastric cancer in women, while heavy alcohol consumption was associated with an increased risk of gastric cancer regardless of country, gender, whether the study reported gastric cancer incidence, or whether the study adjusted for body mass index, educational attainment, or physical activity. The findings of this study suggest that light alcohol consumption might play a protective effect on gastric cancer in women, while heavy alcohol consumption is associated with a significantly increased risk of gastric cancer in all subgroups.
PMCID: PMC5663611
gastric cancer; alcohol consumption; meta-analysis; heavy alcohol consumption; cancer risk
17.  Complete genome sequence of Thermotoga sp. strain RQ7 
Thermotoga sp. strain RQ7 is a member of the family Thermotogaceae in the order Thermotogales. It is a Gram negative, hyperthermophilic, and strictly anaerobic bacterium. It grows on diverse simple and complex carbohydrates and can use protons as the final electron acceptor. Its complete genome is composed of a chromosome of 1,851,618 bp and a plasmid of 846 bp. The chromosome contains 1906 putative genes, including 1853 protein coding genes and 53 RNA genes. The genetic features pertaining to various lateral gene transfer mechanisms are analyzed. The genome carries a complete set of putative competence genes, 8 loci of CRISPRs, and a deletion of a well-conserved Type II R-M system.
PMCID: PMC5637354
Thermotoga; T. sp. strain RQ7; Natural competence; CRISPR; Restriction-modification system; TneDI; CP007633
18.  Efficacy and safety of intraperitoneal chemotherapy in patients with advanced gastric cancer: a cumulative meta-analysis of randomized controlled trials 
Oncotarget  2017;8(46):81125-81136.
Even when a curative gastrectomy is conducted, the majority of advanced gastric cancer patients with invasion die due to peritoneal recurrence. We performed electronic searches to identify randomized controlled trials published through April 2017 evaluating the effect of intraperitoneal chemotherapy (IPC) on survival rates. We included 23 trials reporting data on 2,767 patients with advanced gastric cancer. Overall, we noted that patients who received IPC had a significantly increased 1-year survival rate, and the treatment effect of IPC on 1-year survival was most prominent in studies conducted in Japan or those with a mean age of less than 60 years. IPC was also associated with an increased incidence of 2-year survival rate, but it was not seen to have this effect in studies conducted in China or Australia or with a mean age greater than 60 years. Similarly, IPC associated with a significantly increased 3-year survival rate, but this difference was not detected in studies conducted in Austria or with a mean age greater than 60 years. IPC has no significant effect on the 5-year survival rate. Finally, IPC was associated with a lower risk of recurrence in patients with advanced gastric cancer. The findings of this study suggest that gastric cancer patients who receive IPC associate with increased 1-year, 2-year, and 3-year survival rates, but this does not extend out to a 5-year survival rate. IPC is also shown to play a protective role against the risk of recurrence in patients with advanced gastric cancer.
PMCID: PMC5655267
gastric cancer; intraperitoneal chemotherapy; prognosis; meta-analysis
19.  Ligustilide Relieves Complete Freund's Adjuvant-induced Mechanical Hyperalgesia through Inhibiting the Activation of Spinal c-Jun N-terminal Kinase/c-Jun Pathway in Rats 
Pharmacognosy Magazine  2017;13(52):634-638.
Ligustilide, an active ingredient in a traditional Chinese medicine, has anti-inflammatory and analgesic effects. The underlying mechanisms of the anti-inflammatory pain effects of ligustilide are not completely understood.
The aim of this study to investigate whether ligustilide conducts its analgesic effects on the complete Freund's adjuvant (CFA)-induced inflammatory pain through regulating the c-Jun N-terminal kinase (JNK)/c-Jun pathway in the spinal cord.
Materials and Methods:
Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) were tested to examine the analgesic effect of ligustilide on CFA-induced inflammatory pain in rats. The change of spinal JNK/c-Jun activation was detected by western blotting after CFA injection with or without consecutive intrathecal ligustilide administration. After SP600125 (JNK inhibitor) was intrathecally injected in CFA rats, PWTs and PWLs were tested to investigate the change of ligustilide's analgesic effect.
Repeated intravenous injection of ligustilide could attenuate the pain hypersensitivity induced by CFA. CFA caused increased activation of spinal JNK/c-Jun, which could be inhibited by ligustilide administration. Intrathecal injection of JNK inhibitor inhibited the CFA-induced mechanical hyperalgesia.
Ligustilide could inhibit the upregulation of spinal p-JNK/p-c-Jun caused by CFA, and the inhibition of JNK/c-Jun activation is closely related to its anti-mechanical hyperalgesia effect in inflammatory pain.
Ligustilide, an active ingredient in a popular traditional Chinese medicine, has effective anti-inflammatory and analgesic effects. Ligustilide inhibits the complete Freund's adjuvant-induced activation of spinal c-Jun N-terminal kinase-(JNK)/c-Jun pathway in rats. The inhibition of JNK/c-Jun activation is closely related to the anti-mechanical hyperalgesia effect of ligustilide.
Abbreviations used: CFA: Complete Freund's adjuvant, JNK: c-Jun N-terminal kinase, MAPK: Mitogen-activated protein kinase, PWT: Paw withdrawal threshold, PWL: Paw withdrawal latency.
PMCID: PMC5701403
c-Jun; c-Jun N-terminal kinase; complete Freund's adjuvant; ligustilide; mechanical hyperalgesia; pain
20.  Expression, regulation and mechanism of action of the miR-17-92 cluster in tumor cells (Review) 
MicroRNAs (miRNAs), a class of short, single-stranded non-coding RNAs, regulate and control gene expression in eukaryotes by degrading mRNA at the post-transcriptional level. Regulation by miRNAs involves a plethora of biological processes, such as cell differentiation, proliferation, metastasis, metabolism, apoptosis, tumorigenesis and others. miRNAs also represent a powerful tool in disease diagnosis and prognosis. The miR-17-92 cluster, one of the most extensively investigated microRNA clusters, comprises six mature miRNA members, including miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a. Originally identified as being involved in tumorigenesis, it is currently evident that the expression of the miR-17-92 cluster is upregulated in a wide range of tumor cells and cancer types; thus, this cluster has been identified as a potential oncogene. Considering the growing interest in the field of miR-17-92 research, we herein review recent advances in the expression and regulation of this cluster in various cancer cells, discuss the proposed mechanism of action for tumorigenesis and tumor development, and propose clinical and therapeutic applications for miR-17-92 cluster members, such as potential cancer biomarkers.
PMCID: PMC5716450  PMID: 29039606
miR-17-92 cluster; cancer cell; oncogene and tumor suppressor gene; mechanism; post-transcriptional regulation
21.  In situ solid-state fabrication of hybrid AgCl/AgI/AgIO3 with improved UV-to-visible photocatalytic performance 
Scientific Reports  2017;7:12365.
The AgCl/AgI/AgIO3 composites were synthesized through a one-pot room-temperature in situ solid-state approach with the feature of convenient and eco-friendly. The as-prepared composites exhibit superior photocatalytic performance than pure AgIO3 for the degradation of methyl orange (MO) under both UV and visible light irradiation. The photodegradation rate toward MO of the AgCl/AgI/AgIO3 photocatalyst can reach 100% after 12 min irradiation under UV light, or 85.4% after 50 min irradiation under visible light, being significantly higher than AgCl, AgI, AgIO3 and AgI/AgIO3. In addition, the AgCl/AgI/AgIO3 photocatalyst possesses strong photooxidation ability for the degradation of rhodamine B (RhB), methylene blue (MB), phenol, bisphenol A (BPA) and tetracycline hydrochloride under visible light irradiation. The reactive species capture experiments confirmed that the h+ and •O2− play an essential role during the photocatalytic process under UV light or visible light irradiation. The enhanced effect may be beneficial from the enhanced light adsorption in full spectrum and increased separation efficiency of photogenerated hole-electron pairs, which can be ascribed to the synergistic effect among AgCl, AgI and AgIO3 nanoplates in AgCl/AgI/AgIO3 composites.
PMCID: PMC5620062  PMID: 28959028
22.  Chemical Profile and Antioxidant Activity of the Oil from Peony Seeds (Paeonia suffruticosa Andr.) 
Peony seed oil (PSO) is a novel vegetable oil developed from the seeds of Paeonia suffruticosa Andr. The present study aimed to make an overall investigation on the chemical profile and antioxidant activities of PSO for reasonable development and utilization of this new resource food. Chemical analysis revealed that PSO was characterized by an uncommon high portion of α-linolenic acid (>38%), fairly low ratio of n-6 to n-3 polyunsaturated fatty acids (0.69), and much higher content of γ-tocopherol than various conventional seed oils. In vitro assay indicated that PSO is a more potent scavenger of free radicals than extra virgin olive oil. Moderate intake of PSO exhibited obvious protection against various oxidative damages such as tetrachloromethane-induced acute liver injury in mice and diet-induced hyperlipidemia in rats. The changes in the key indicators of oxidative injury and fatty acid composition in the liver caused by PSO administration were measured, and the results demonstrated that antioxidant properties of PSO are closely related to their characteristic chemical composition. Consequently, the present study provided new evidence for the health implications of PSO, which deserves further development for medical and nutritional use against oxidative damages that are associated with various diseases.
PMCID: PMC5634581
23.  Allochroic thermally activated delayed fluorescence diodes through field-induced solvatochromic effect 
Science Advances  2017;3(9):e1700904.
A novel thermally activated delayed fluorescence (TADF) allochroic diode can change emission color through adjusting voltage.
Allochroic organic light-emitting devices (AOLEDs) characterized by field-dependent emissive color variation are promising as visible signal response units for intelligent applications. Most of the AOLEDs were realized by changing their recombination zones or inter- and intramolecular energy transfer, rendering the limited repeatability, stability, and electroluminescence (EL) performance. We report a novel thermally activated delayed fluorescence (TADF) diode that featured a successive and irreversible emission color change from bluish green to deep blue during voltage increase, which uses the significant influence of host polarity on the emission color of TADF dyes, namely, solvatochromic effect. Its host 3,6-di-tert-butyl-1,8-bis(diphenylphosphoryl)-9H-carbazole (tBCzHDPO) was designed with remarkable field-dependent polarity reduction from 7.9 to 3.3 D by virtue of hydrogen bond–induced conformational isomerization. This TADF device achieves the best EL performance among AOLEDs, to date, with, for example, an external quantum efficiency beyond 15%, as well as the unique irreversible allochroic characteristic for visible data storage and information security.
PMCID: PMC5600533  PMID: 28929136
24.  Polyene Phosphatidylcholine inhibited the inflammatory response in LPS-stimulated macrophages and ameliorated the adjuvant-induced rat arthritis 
This study sought to investigate the anti-inflammatory effect of Polyene Phosphatidylcholine (PPC), a clinical drug that is used to treat hepatopathy, on lipopolysaccharide (LPS)-stimulated macrophages and on bovine collagen II-induced arthritis (CIA) rats. In stimulated primary and Raw264.7 macrophages by LPS, PPC significantly down-regulated the relative expression of mRNA such as IL-6, TNF-α, TLR-2, TLR-4, MyD88, and NF-κB while up-regulated IL-10 and TGF-β expression. Moreover, the concentration of IL-6, TNF-α, IL-10, and TGF-β in the cultured supernatants showed the similar tendency with their mRNA alterations. In addition, PPC could significantly inhibit the LPS-induced expression of MyD88 and NF-κB p65 in both mRNA and protein levels. These results suggest that PPC could down-regulate the LPS-stimulated inflammation in macrophages through TLR-2/TLR-4/MyD88/NF-κB pathway in vitro. Furthermore, to explore its effects in vivo, PPC was administrated to CIA rats. In comparison to CIA group, PPC-treated rats showed decreased arthritis score and osteopenia. Besides, PPC exhibited its ability to alleviate the degree of synovial hyperplasia, inflammatory cell infiltration, and destruction of cartilage and bone, thus remarkably improving the condition of CIA rats. In short, this study demonstrated that PPC had the potential to be an anti-inflammatory drug to treat inflammatory disorders such as rheumatoid arthritis.
PMCID: PMC5622263
Polyene Phosphatidylcholine; collagen-induced arthritis; macrophages; toll-like receptor
25.  Malignancy risk stratification of thyroid nodules: comparisons of four ultrasound Thyroid Imaging Reporting and Data Systems in surgically resected nodules 
Scientific Reports  2017;7:11560.
To compare the efficiency of four different ultrasound (US) Thyroid Imaging Reporting and Data Systems (TI-RADS) in malignancy risk stratification in surgically resected thyroid nodules (TNs). The study included 547 benign TNs and 464 malignant TNs. US images of the TNs were retrospectively reviewed and categorized according to the TI-RADSs published by Horvath E et al. (TI-RADS H), Park et al. (TI-RADS P), Kwak et al. (TI-RADS K) and Russ et al. (TI-RADS R). The diagnostic performances for the four TI-RADSs were then compared. At multivariate analysis, among the suspicious US features, marked hypoechogenicity was the most significant independent predictor for malignancy (OR: 15.344, 95% CI: 5.313-44.313) (P < 0.05). Higher sensitivity was seen in TI-RADS H, TI-RADS K, TI-RADS R comparing with TI-RADS P (P < 0.05 for all), whereas the specificity, accuracy and area under the ROC curve (Az) of TI-RADS P were the highest (all P < 0.05). Higher specificity, accuracy and Az were seen in TI-RADS K compared with TI-RADS R (P = 0.003). With its higher sensitivity, TI-RADS K, a simple predictive model, is practical and convenient for the management of TNs in clinical practice. The study indicates that there is a good concordance between TI-RADS categories and histopathology.
PMCID: PMC5599531  PMID: 28912438

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