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1.  Biofunctional Understanding and Judgment of Size 
Research has shown that the meaningfulness of the material increases judged size, whereas symmetry decreases size judgments. These findings have been interpreted in terms of information processing, with a greater quantity of information leading to a judgment of larger size. An alternative view based on biofunctional understanding theory emphasizes the quality of affordance-triggered biological activity as reported and observed in attitudes toward playing sports, effortless understanding, knowledge-in-action, meditative wisdom, and body–mind cycle of adaptation. This alternative implies that affordance biofunctional activity is naturally size-diminishinging as it moves toward coherence and size-expanding as it moves away from coherence influencing judgments of size accordingly. Here we tested this hypothesis in the realm of sensorimotor integration. Our first experiment showed that phonologically unpronounced or symmetric symbols elicit smaller size judgments than phonologically pronounced and asymmetric symbols. Next, we manipulated the quantity of meaning with the affordance (possibilities for biofunctional activity) orthogonally in a second experiment; results indicated that meaning affects size judgments only in the absence of phonological information. We conclude that the biofunctional activity affordance may be responsible for observed differences in size judgment.
PMCID: PMC4805645  PMID: 27047438
embodied cognition; biofunctional understanding; action; affordances; size judgments
2.  Spatiotemporal distribution of caudal-type homeobox proteins during development of the hindgut and anorectum in human embryos 
PeerJ  2016;4:e1771.
Background. The objectives of this study were to determine the spatiotemporal distribution of human caudal-type homeobox proteins CDX1, CDX2 and CDX4 during development of the hindgut and anorectum in the embryo and to explore the possible roles of CDX genes during morphogenesis of the hindgut and anorectum.
Methods. Embryos (89) were cut into sections serially and sagittally. From gestation weeks 4–9, CDX1, CDX2 and CDX4 proteins were detected on the caudal midline by immunohistochemical staining.
Results. During week 4, extensive immunoreactivity of CDX1, CDX2 and CDX4 was detected in the dorsal urorectal septum, urogenital sinus and hindgut. From weeks 5–7, CDX1-, CDX2- and CDX4- positive cells were detected mainly in the mesenchyme of the urorectal septum and hindgut. The levels of CDX2 and CDX4 immunoreactivity were lower compared to CDX1. During weeks 8 and 9, the anorectal epithelium stained positive for CDX1 and CDX4, and the anal epithelium was positive for CDX2.
Conclusions. The CDX proteins are constantly distributed during development of the hindgut and anorectum and exhibit overlapping distribution patterns in the cloaca/hindgut, suggesting they are important in the morphogenesis of the human hindgut and anorectum. CDX genes might be involved in development of the anorectal epithelium after the rectum has separated from the urorectal septum.
PMCID: PMC4811170  PMID: 27042391
Human; Embryo; CDX; Hindgut; Anorectum
3.  Lipid-poor renal angiomyolipoma: Differentiation from clear cell renal cell carcinoma using wash-in and washout characteristics on contrast-enhanced computed tomography 
Oncology Letters  2016;11(3):2327-2331.
In the present study, a total of 82 patients (42 men and 40 women; age range, 24–84 years), including 34 patients with lipid-poor renal angiomyolipoma (AML) and 49 with clear cell renal cell carcinoma (RCC), who had undergone multiphase contrast-enhanced computed tomography (CT) (i.e., CT with unenhanced, corticomedullary, nephrographic and 5-min delay phase scanning) were evaluated. The peak enhancement attenuation value, net enhancement attenuation value, enhancement ratio, washout value and washout ratio were calculated to compare the enhancement characteristics between the two diseases. The results revealed that the lipid-poor AMLs had a significantly higher mean attenuation value compared with that of CCRCCs on unenhanced CT scans (37.8 vs. 30.9 HU; Mann-Whitney U test, P=0.003). In addition, significant differences were found between lipid-poor AMLs and CCRCCs with regard to wash-in (Mann-Whitney U test, P=0.001) and enhancement ratios (Mann-Whitney U test, P=0.010) on contrast-enhanced CT scans. A receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.722 using wash-in for differentiation between CCRCCs and lipid-poor AMLs. Lipid-poor AMLs exhibited a reduced washout of contrast enhancement (35.8±32.7 HU washout value; 29.4±0.187% washout ratio) compared with that of CCRCCs (48.3±28.4 HU washout value; 35.7±0.148% washout ratio; Mann-Whitney U test, P=0.037 and P=0.204, respectively). The ROC analysis result yielded an AUC of 0.639 for the use of washout to differentiate CCRCCs from lipid-poor AMLs. In summary, a larger wash-in and washout of contrast enhancement is a predictor that a lesion is CCRCC.
PMCID: PMC4774615  PMID: 26998171
renal angiomyolipoma; clear cell renal cell carcinoma; lipid-poor; washout; computed tomography; X-ray
4.  MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc 
Gene  2014;555(2):80-87.
Because miR-146a expression in articular chondrocytes is associated with osteoarthritis (OA), we assessed whether miR-146a is linked to cartilage degeneration in the spine. Monolayer cultures of nucleus pulposus (NP) cells from the intervertebral discs (IVD) of bovine tails were transfected with a miR-146a mimic. To provoke inflammatory responses and catabolic extracellular matrix (ECM) degradation, cells were co-treated with interleukin-1 (IL-1). Transfection of miR-146a decreases IL-1 induced mRNA levels of inflammatory genes and catabolic proteases in NP cells based on quantitative real-time reverse transcriptase PCR (qRT-PCR) analysis. Similarly, miR146a suppresses IL-1 induced protein levels of matrix metalloproteinases and aggrecanases as revealed by immunoblotting. Disc segments from wild type (WT) and miR-146a knockout (KO) mice were cultured ex vivo in the presence or absence of IL-1 for 3 days. Histological and immunohistochemical (IHC) analyses of disc organ cultures revealed that IL-1 mediates changes in proteoglycan (PG) content and in-situ levels of catabolic proteins (MMP-13 and ADAMTS-5) in the nucleus pulposus of the disc. However, these IL-1 effects are more pronounced in miR-146a KO discs compared to WT discs. For example, absence of miR-146a increases the percentage of MMP-13 and ADAMTS-5 positive cells after treatment with IL-1. Thus, miR-146a appears to protect against IL-1 induced IVD degeneration and inflammation. Stimulation of endogenous miR-146a expression or exogenous delivery of miRNA-146a are viable therapeutic strategies that may decelerate disc degeneration and regain a normal homeostatic balance in extracellular matrix production and turn-over.
PMCID: PMC4495656  PMID: 25311550
Intervertebral disc degeneration; miR-146a; IL-1; MMP-13; ADAMTS-5; Nucleus pulposus
5.  Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding 
PLoS ONE  2016;11(1):e0147187.
Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF:, for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection.
PMCID: PMC4723255  PMID: 26799713
6.  Small Bowel Stromal Tumors: Different Clinicopathologic and Computed Tomography Features in Various Anatomic Sites 
PLoS ONE  2015;10(12):e0144277.
Gastrointestinal stromal tumors (GISTs) can present with different clinical and immunohistochemical characteristics according to different anatomic sites. The aim of this study was to compare clinicopathologic and computed tomography (CT) features of small bowel stromal tumors located in the duodenum, jejunum, and ileum. In total, 197 patients (109 male, 88 female) with small bowel GISTs were retrospectively reviewed. All tumors had definite anatomic sites in the small bowel tract with surgical confirmation. The clinicopathologic variables included age, sex, onset of symptoms, and tumor risk category. CT variables included tumor size, degree enhancement, enhancement pattern (region of necrosis), adjacent tissue involvement, lymphadenopathy, and distant metastasis. We assessed any possible differences according to different GIST site of origin. Based on tumor size and mitotic count, the risk categories in different anatomic sites did not differ significantly between duodenal and jejunal GISTs. However, high risk ileum GISTs accounted for 66.0% of ileal cases, which was higher than duodenum cases (36.8%, P = 0.002) and jejunum cases (43.9%, P = 0.004). The mean size of GISTs in the ileum was 9.77 cm, which was significantly larger than in the duodenum (7.41 cm, P = 0.043), and in the jejunum (8.14 cm, P = 0.027). On CT images, enhancement degree appeared to gradually increase from the duodenum to the ileum in the portal phase, and the enhancement pattern presented a tendency for heterogeneity. In Conclusions, the clinicopathologic and CT features of small bowel GISTs can differ according to different primary anatomic sites.
PMCID: PMC4672882  PMID: 26646242
7.  Diagnostic value of SHOX2 DNA methylation in lung cancer: a meta-analysis 
OncoTargets and therapy  2015;8:3433-3439.
The diagnostic value of SHOX2 DNA methylation in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess diagnostic accuracy of SHOX2 DNA methylation in the lymph node, bronchial aspirates, pleural effusion, plasma, and tumor tissue for lung cancer. We conducted a comprehensive literature search in PubMed, Ovid, the Cochrane library, and Web of Science databases in May 2015. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve were pooled using STATA 12.0 software. A total of 2,296 subjects included 1,129 lung cancer patients in eight studies were recruited in this meta-analysis. The summary estimates for SHOX2 DNA methylation in the diagnosis of lung cancer in these studies were pooled SEN =0.70 (95% confidence interval [CI]: 0.46–0.87), SPE =0.96 (95% CI: 0.91–0.99), PLR 20.01 (95% CI: 6.96–57.52), NLR 0.31 (95% CI: 0.15–0.64), and DOR 65.11 (95% CI: 13.10–323.61), and the area under the curve (AUC) was 0.96 (95% CI: 0.94–0.97). SHOX2 DNA methylation has greater diagnostic value in detecting lung cancer. In addition, considering the potential publication bias and high heterogeneity, further research studies with more well-designed and large sample sizes are needed in the future.
PMCID: PMC4657794  PMID: 26640383
lung cancer; SHOX2; meta-analysis; diagnostic test
8.  Temporal and spatial expression of caudal-type homeobox proteins in the midgut of human embryos 
Background: This study aimed to determine the spatiotemporal expression of caudal-type homeobox genes (CDX1, CDX2 and CDX4) during development of the midgut in human embryos and to explore the possible roles of CDX genes during the morphogenesis of human midgut. Human embryos (n=28) were sectioned serially and sagittally and CDX1, CDX2 and CDX4 proteins were detected on the midline from the 5th to 9th weeks of gestation by immunohistochemical staining. Results: CDX1, CDX2 and CDX4 proteins were weakly expressed in epithelium and mesenchyme of the midgut in the 6th and 7th weeks of gestation and reached estimated optimal level on the 8th and 9th weeks of gestation. In the 9th week of gestation, immunoreactivities specific to CDX1, CDX2 and CDX4 were restricted in epithelium of the midgut. Conclusions: CDX1, CDX2 and CDX4 proteins began to express in human midgut in the 6th week of gestation. From the 6th to 9th week of gastation, the expression of CDX1, CDX2 and CDX4 proteins gradually increase and exhibited overlapping expression patterns, suggesting that CDX genes may be involved in early development of the epithelium of human midgut. Cross-regulatory interactions may exist among CDX genes with respect to human midgut development.
PMCID: PMC4723747  PMID: 26884902
Human; embryo; CDX; midgut; development
9.  Prognostic role of neutrophil to lymphocyte ratio in lung cancers: a meta-analysis including 7,054 patients 
OncoTargets and therapy  2015;8:2731-2738.
Neutrophil to lymphocyte ratio (NLR) has recently been reported to be a poor prognostic indicator in lung cancer. However, the prognostic value of the NLR in patients with lung cancer still remains controversial. We performed a meta-analysis to evaluate the prognostic value of NLR in patients with lung cancer.
We performed a comprehensive literature search in PubMed, Ovid, the Cochrane Library, and Web of Science databases in May 2015. Studies were assessed for quality using the Newcastle–Ottawa Scale.
Twenty-two studies with a total of 7,054 patients were included in this meta-analysis. The meta-analysis was performed to generate combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). Our analysis results indicated that high NLR predicted poorer OS (HR, 1.51; 95% confidence interval [CI], 1.33–1.71; P<0.001) and PFS (HR, 1.33; 95% CI, 1.07–1.67; P=0.012) in patients with lung cancer. High NLR was also associated with poor OS in lung cancer treated by surgical resection (HR, 1.59; 95% CI, 1.26–1.99; P<0.001) and chemotherapy (HR, 1.15; 95% CI, 1.08–1.22; P<0.001). In addition, NLR cut-off value =5 (HR, 1.57; 95% CI, 1.16–2.12; P=0.003) and NLR cut-off value <5 (HR, 1.47; 95% CI, 1.28–1.69; P<0.001).
This meta-analysis result suggested that NLR should have significant predictive ability for estimating OS and PFS in patients with lung cancer and may be as a significant biomarker in the prognosis of lung cancer.
PMCID: PMC4599071  PMID: 26491346
NLR; lung cancer; prognosis; meta-analysis
10.  Comorbid chronic diseases and their associations with quality of life among gynecological cancer survivors 
BMC Public Health  2015;15:965.
Many gynecological cancer survivors (GCS) have comorbid chronic diseases (CCD). This study was to estimate the impacts of CCD on quality of life (QOL) in GCS.
We collected cross-sectional self-reported survey data from 598 GCS between April and July 2013, in Shanghai, China. All the subjects were asked to complete a questionnaire containing the European Organization for Research and Treatment quality of life version 3 questionnaire (EORTC QLQ-C30) and questions on socio-demographic characteristics and CCD. In order to mitigate the bias caused by confounding factors, multiple linear models were employed to calculate adjusted means of QOL scores.
Approximately three-quarters of subjects reported at least one CCD. The highest overall prevalence of all CCD was found in endometrial cancer survivors. Subjects with CCD generally reported lower scores for most EORTC QLQ-C30 scales when compared to subjects without CCD, indicating poorer QOL, particularly for cardiovascular diseases, respiratory diseases, digestive diseases, and musculoskeletal disease.
The CCD are common health problems among GCS. CCD have significantly negative influence on QOL, and GCS with CCD generally reported lower QOL scores. These findings suggested comprehensive cares for GCS.
PMCID: PMC4582736  PMID: 26408314
Gynecological cancer survivors; Quality of life; Comorbid chronic diseases; Cancer care
11.  Progesterone is neuroprotective by inhibiting cerebral edema after ischemia 
Neural Regeneration Research  2015;10(7):1076-1081.
Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, progesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-regulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema.
PMCID: PMC4541237  PMID: 26330829
nerve regeneration; brain injury; gonadal hormone; cerebral ischemia; permeability; occludin; zonula occludens-1; Evans blue dye; penumbra; ischemic core; rats; neural regeneration
12.  Drug resistant tuberculosis in Shanghai, China, 2000–2006: Prevalence, trends, and risk factors 
During 2000–2006, a regional anti-tuberculosis drug resistance surveillance study was conducted in Shanghai, China.
To determine the prevalence, trends and risk factors for drug resistant tuberculosis (TB) in Shanghai, China.
A retrospective study of all pulmonary TB patients reported in Shanghai during 2000–2006 was performed.
Of 8419 pulmonary TB patients, 16.6% had resistance to any first-line anti-tuberculosis drug and 4.0% had multi-drug resistance (MDR). The percentage of TB patients with resistance to any first-line anti-tuberculosis drug and MDR significantly increased during 2000–2003 (P = 0.01 and P<0.01, respectively). After improvements in the TB control programme in 2004, the increasing trend in drug resistance was contained. Age 30–59 years old, being an urban migrant and residence in an urban area of Shanghai were independently associated with resistance to any first-line drug and MDR in new cases, while age 30–59 years and being an urban migrant were independently associated with resistance to any first-line drug and MDR in previously treated cases.
Drug-resistant TB and MDR-TB pose a challenge for TB control in Shanghai. Improved case management, including DOTS and appropriate treatment regimens, should be sustained to prevent further transmission and development of drug-resistant TB in this setting.
PMCID: PMC4486066  PMID: 19146756
tuberculosis; drug resistance; MDR-TB; epidemiology
13.  Facial and Cochlear Nerve Complications following Microsurgical Resection of Vestibular Schwannomas in a Series of 221 Cases 
Despite improvements in microsurgical technique and the use of intraoperative electrophysiological monitoring, the potential for facial and cochlear nerve injury remains a possibility in the resection of vestibular schwannomas (VS). We reviewed a series of 221 cases of VS resected via a retrosigmoid approach at our institution from October 2008 to April 2014 and determined the incidence of postoperative facial and cochlear deficits.
A total of 221 patients – 105 (47.5%) male and 116 (52.5%) female – with a mean age of 46.1 years (range 29–73 years), with VS ≥3 cm (n=183, 82.8%) and <3 cm (n=38, 17.2%) underwent surgical resection via a retrosigmoid approach and were evaluated for postoperative facial and cochlear nerve deficits.
Near-total resection (>95% removal) was achieved in 199 cases (90%) and subtotal resection (>90% removal) in 22 cases (10%). At 6 month follow-up, House-Brackmann grades I–III were observed in 183 cases (82.8%), grade IV in 16 cases (7.2%), and grade V in 22 cases (10%). Of the 10 patients that had preoperative functional hearing, 3 (33%) retained hearing postoperatively. Cerebrospinal fluid leakage occurred in 6 patients (2.7%), lower cranial nerve palsies in 9 patients (4.1%), and intracranial hematomas 3 cases (1.4%).
The observed incidence of persistent postoperative nerve deficits is very low. Meticulous microsurgical dissection of and around the facial and cochlear nerves with the aid of intraoperative electrophysiological nerve monitoring in the retrosigmoid approach allows for near-total resection of medium and large VS with the possibility of preservation of facial and cochlear nerve function.
PMCID: PMC4473800  PMID: 26056168
Cochlear Nerve; Facial Nerve; Neuroma, Acoustic; Vestibular Nuclei
14.  Acute thrombocytopenia: An uncommon complication occurring following transarterial chemoembolization in a patient with neuroendocrine hepatic metastases 
Oncology Letters  2015;10(1):247-249.
Neuroendocrine tumors are a group of carcinomas that secrete various polypeptides with hormonal activity. A significant percentage of patients already have hepatic metastases at the time of initial diagnosis, and 80–90% of these tumors are inoperable at the time of presentation. Transarterial chemoembolization (TACE) is the preferred approach for the management of neuroendocrine hepatic metastases. Although the technique is relatively safe, it is associated with several complications. The present study reported the case of a patient with neuroendocrine hepatic metastases who developed acute thrombocytopenia following TACE. To the best of our knowledge, acute thrombocytopenia occurring after TACE in a patient with neuroendocrine hepatic metastases has not been previously reported. In the present study, the hypothetical etiopathogenetic mechanisms were also discussed.
PMCID: PMC4487171  PMID: 26171007
neuroendocrine; liver; metastases; transarterial chemoembolization
15.  Preparation, characterization, and in vivo study of rhein-loaded poly(lactic-co-glycolic acid) nanoparticles for oral delivery 
A novel rhein formulation based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) suitable for oral administration was developed in this study. The designed nanosystems were obtained by a modified spontaneous emulsification solvent diffusion method. The morphology of rhein-loaded PLGA NPs showed a spherical shape with a smooth surface, without any particle aggregation. Mean size of the NPs was 140.5±4.3 nm, and the zeta potential was −16.9±3.1 mV. The average drug loading was 3.9%±0.7%, and encapsulation efficiency was 84.5%±6.2%. Meanwhile, NPs are characterized by the slower release (only about 70% of rhein is released within 5 hours), and the model that fitted best for rhein released from the NPs was Higuchi kinetic model with correlation coefficient r=0.9993, revealing that rhein could be controlled released from the NPs. In vivo, NPs altered the distribution of rhein, and the half-life after oral administration was prolonged remarkably more than those of suspensions (22.6 hours vs 4.3 hours). The pharmacokinetic results indicated that the NPs had sustained-release efficacy. The area under the curve0–∞ of the NPs formulation was 3.07-fold higher than that of suspensions, suggesting that the encapsulated rhein had almost been absorbed in rats over the period of 12 hours. Although rhein-loaded PLGA NP formulations are hopefully used as a chemotherapeutic or adjuvant agent for human gastric cancer (SGC-7901), their in vivo antitumor effect and mechanisms at the molecular level still need further study.
PMCID: PMC4410823  PMID: 25960633
rhein; PLGA; nanoparticles; release; pharmacokinetics; SGC-7901
16.  Epidemiology of norovirus infections among diarrhea outpatients in a diarrhea surveillance system in Shanghai, China: a cross-sectional study 
BMC Infectious Diseases  2015;15:183.
Norovirus is an important cause of gastroenteritis both in children and adults. In China, few studies have been conducted on adult populations. This study aimed to determine the contribution of norovirus to gastroenteritis, characterize the features of norovirus infections, compare them with other pathogens, and test the effectiveness of the surveillance system.
A citywide surveillance network on diarrhea patients was established. Samples were collected with intervals from both children and adults among diarrhea outpatients in hospitals and tested for viruses using rRT-PCR and for bacteria in CDCs. Patient information was acquired through interviews and recorded into a dedicated online system. The Pearsonχ2 test, multivariate logistic regression models and discriminant models were fitted into its comparisons with the non-norovirus group and other pathogens.
Norovirus was detected in 22.91% of sampled diarrhea patients. The seasonal distribution of norovirus infections was different from non-norovirus patients (p < 0.001), with a half-year peak. Higher proportions of males (p = 0.001, OR = 1.303, 95% CI = 1.110-1.529), local citizens (p < 0.001) and officials/clerks (p = 0.001, OR = 1.348, 95% CI = 1.124-1.618) were affected with norovirus when compared with non-norovirus patients. Diarrhea patients affected with norovirus featured nausea (p < 0.001, OR = 1.418, 95% CI = 1.176-1.709) and vomiting (p < 0.001, OR = 1.969, 95% CI = 1.618-2.398), while fewer manifested fever (p = 0.046, OR = 0.758, 95% CI = 0.577-0.996) and abdominal pain (p = 0.018, OR = 0.815, 95% CI = 0.689-0.965). Children were more vulnerable to rotavirus (p = 0.008, OR = 1.637, 95% CI = 1.136-2.358) and bacteria (p = 0.027, OR = 1.511, 95% CI = 1.053-2.169) than norovirus. There was a seasonal difference between the GI and GII genotypes (p < 0.001). Officials or clerks were more easily affected with GI than GII (p = 0.006, OR = 1.888, 95% CI = 1.205-2.958).
This study was based on a citywide hospital-sentinel surveillance system with multiple enteric pathogens included. Norovirus was recognized as the most prevalent enteric pathogen in Shanghai. The seasonal peak was from October to April. Males had a higher prevalence than females. Local citizens and officials/clerks were more vulnerable to norovirus than other pathogens. Compared with rotavirus and bacteria, children were less frequently affected by norovirus. Nausea and vomiting were typical of norovirus, whereas fever and abdominal pain were uncommon symptoms of this pathogen. GI and GII infections were centered in different seasons. Officials and clerks were more easily affected by GI than GII.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-015-0922-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4438334  PMID: 25884557
Human norovirus; Diarrhea; Surveillance; Epidemiology; Sporadic; All age groups; rRT-PCR
17.  Spatiotemporal expression of BMP7 in the development of anorectal malformations in fetal rats 
The aim of this study was to determine the expression patterns of bone morphogenetic protein 7 (BMP7) during anorectal development in normal rat embryos and in embryos with anorectal malformations (ARM), and to investigate the possible role of BMP7 in the pathogenesis of ARM. ARM was induced by treating rat embryos with ethylenethiourea on the 10th gestational day (GD10). Embryos were harvested by Cesarean delivery and the spatiotemporal expression of BMP7 was evaluated in normal (n=168) and ARM embryos (n=171) from GD13 to GD16 using immunohistochemistry staining and western blot analysis. Immunohistochemical staining in normal embryos revealed that BMP7 was abundantly expressed on the epithelium of the urorectal septum (URS) and the hindgut on GD13, and BMP7-immunopositive cells were extensively detected in the URS, hindgut, and cloacal membrane by GD14. Increased positive tissue staining was noted on the fused tissue of the URS and the thin anal membrane on GD15. In ARM embryos, the epithelium of the cloaca, URS, and anorectum were negatively or only faintly immunostained for BMP7. BMP7 protein expression showed time-dependent changes in the developing hindgut according to western blotting, and reached a peak on GD15 during anus formation. BMP7 expression levels from GD14 to GD15 were significantly lower in the ARM group compared with the normal group (P<0.05). Spatiotemporal expression of BMP7 was disrupted in ARM embryos during anorectal morphogenesis from GD13 to GD16. These results suggest that downregulation of BMP7 at the time of cloacal separation into the primitive rectum and UGS might be related to the development of ARM.
PMCID: PMC4466941  PMID: 26097554
Anorectal malformation; BMP7; embryogenesis; development; rat
18.  Cancer survivors’ perspectives and experience on western medicine and traditional Chinese medicine treatment and rehabilitation: a qualitative study 
In the People’s Republic of China, both western medicine (WM) and traditional Chinese medicine (TCM) are the main treatment and rehabilitation options for cancer patients. This study aimed to explore cancer survivors’ perspectives and experience of treatment and rehabilitation, in order to promote patient-centered activities of treatment and rehabilitation.
Using a qualitative research approach, 68 cancer survivors were recruited from eight community cancer rehabilitation organizations in Shanghai, People’s Republic of China. Eight focus group interviews were conducted. All these interviews were transcribed verbatim, and the data were analyzed by theme analysis.
WM was the main choice in treatment phase though study participants noted more side effects. TCM was primarily used in the recovery phase. The lack of communication between doctors and cancer patients appears to affect treatment adherence and impair the doctor–patient relationship. WM was expensive for diagnostic procedures and treatment, while the cumulative costs of frequent use of TCM in the long rehabilitation period were also high. Both treatment options created significant perceived economic burden on patients. Conflicting information about dietary supplements tended to make cancer survivors confused.
Improving the communication between doctors and cancer patients helps to ameliorate cancer patient adherence and the effect of treatments. It is essential to educate cancer patients about the effect and cost of both WM and traditional TCM. Meanwhile, marketing management and guidance to consumers regarding use of dietary supplements in the cancer rehabilitation field are also necessary.
PMCID: PMC4274133  PMID: 25565779
preference; adherence; cancer survivor education; focus group interview
19.  Utility of diffusion-weighted imaging to assess hepatocellular carcinoma viability following transarterial chemoembolization 
Oncology Letters  2014;8(2):831-836.
The purpose of the present study was to evaluate whether diffusion-weighted imaging (DWI) can be used to assess hepatocellular carcinoma (HCC) viability following transarterial chemoembolization (TACE). A total of 41 consecutive patients were treated according to chemoembolization protocols. The follow-up was performed between six and eight weeks post-chemoembolization by multidetector computed tomography [or enhanced magnetic resonance imaging (MRI)] and DW-MRI on the same day. The presence of any residual tumor and the extent of tumor necrosis were evaluated according to the European Association for the Study of the Liver. The apparent diffusion coefficient (ADC) values of the entire area of the treated mass and the vital and necrotic tumor tissues were recorded. Correlation coefficients were also calculated to compare the percentage of necrosis with ADC values. The mean ADC values of the necrotic and vital tumor tissues were 2.22±0.31×10−3 mm2/sec and 1.42±0.25×10−3 mm2/sec, respectively (Mann-Whitney U test, P<0.001). The results from the receiver operating characteristic analysis showed that the threshold ADC value was 1.84×10−3 mm2/sec with 92.3% sensitivity and 100% specificity for identifying the necrotic tumor tissues. A significant linear regression correlation was identified between the ADC value of the entire area of the treated mass and the extent of tumor necrosis (r=0.58; P<0.001). In conclusion, DWI can be used to assess HCC viability following TACE.
PMCID: PMC4081130  PMID: 25013505
hepatocellular carcinoma; chemoembolization; diffusion-weighted imaging; magnetic resonance imaging
20.  Synergistic effect of lidocaine with pingyangmycin for treatment of venous malformation using a mouse spleen model 
Aims: To explore whether lidocaine has the synergistic effect with pingyangmycin (PYM) in the venous malformations (VMs) treatment. Methods: The mouse spleen was chosen as a VM model and injected with different concentration of lidocaine or PYM or jointly treated with lidocaine and PYM. After 2, 5, 8 or 14 days, the mouse spleen tissues were acquired for hematoxylin-eosin (HE) staining, transmission electron microscopy (TEM) analysis, TUNEL assay and quantitative RT-PCR analysis to examine the toxicological effects of lidocaine and PYM on splenic vascular endothelial cells. Results: 0.4% of lidocaine mildly promoted the apoptosis of endothelial cells, while 2 mg/ml PYM significantly elevated the apoptotic ratios. However, the combination of 0.2% lidocaine and 0.5 mg/ml PYM notably elevated the apoptotic ratios of splenic cells and severely destroyed the configuration of spleen, compared to those of treatment with 0.5 mg/ml PYM alone. Conclusion: Lidocaine exerts synergistic effects with PYM in promoting the apoptosis of mouse splenic endothelial cells, indicating that lidocaine possibly promotes the therapeutic effects of PYM in VMs treatment via synergistically enhancing the apoptosis of endothelial cells of malformed venous lesions.
PMCID: PMC4069942  PMID: 24966943
Venous malformation; lidocaine; pingyangmycin; splenic endothelial cells; apoptosis
21.  The Molecular Detection and Clinical Significance of ALK Rearrangement in Selected Advanced Non-Small Cell Lung Cancer: ALK Expression Provides Insights into ALK Targeted Therapy 
PLoS ONE  2014;9(1):e84501.
This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients.
ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation.
The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival.
Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR.
PMCID: PMC3880316  PMID: 24404167
22.  Up-regulated FHL1 Expression Maybe Involved in the Prognosis of Hirschsprung's Disease 
Background: In a subset of patients with Hirschsprung's disease (HSCR), gastrointestinal motor dysfunction persisted long after surgical correction. Gastrointestinal motility is achieved through the coordinated activity of the enteric nervous system, interstitial cells of Cajal, and smooth muscle (SMC) cells. Inhibition of four-and-a-half LIM protein-1 (Fhl1) expression by siRNA significantly decreases pulmonary artery SMCs migration and proliferation. Furthermore when up-expressing FHL1 in atrial myocytes, K (+) current density markedly increases, therefore changing myocytes' response to an electrical stimulus. However whether FHL1 in colon SMCs (the final effector organ) influences intestinal motility in HSCR patients has not been clarified. Methods: FHL1 mRNA and protein expressions were analyzed in 32 HSCR colons and 4 normal colons. Results: Smooth muscle layers were thicken and disorganized in HSCR. FHL1 was expressed in the ganglion cells of the myenteric plexus, submucosa, as well as in the longitudinal and circular muscle layer of the ganglionic colon. FHL1 mRNA relative expression level in aganglionic colons was 1.06±0.49 (ganglionic colon relative expression level was 1) (P=0.44). FHL1 protein gray level relative to GAPDH in normal colons was 0.83±0.09. FHL1 expression level in ganglionic colon (1.66±0.30) or aganglionic colon (1.81±0.35) was significantly higher than that in normal colons (P=0.045 and P=0.041, respectively). Meanwhile, we found FHL1 expression in aganglionic colon was slightly stronger than that in ganglionic colon (P=0.036). Conclusion: These data suggested that up-regulated FHL1 in smooth muscle in HSCR might be associated with intestinal wall remodeling in HSCR and might be one of the risk factors for gastrointestinal motor dysfunction.
PMCID: PMC3917115  PMID: 24516350
FHL1; Hirschsprung's disease; expression; smooth muscle; prognosis
23.  Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B 
Background & aim
Due to known limitations of liver biopsy, reliable non-invasive serum biomarkers for chronic liver diseases are needed. We performed serum peptidomics for such investigation in compensated chronic hepatitis B (CHB) patients.
Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40 CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification from differentially expressed peptides in a validation set of sera from 86 CHB patients was done with multiple reaction monitoring (MRM).
21 differentially represented peptide peaks were found through LC-MS/MS. Ion pairs generated from eleven of these peptides (m/z < 800) were quantified by MRM. Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7, 459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase (DAK) fragment, decreased from mild to advanced stages of fibrosis or inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0-2). The diagnostic power of these models provides improved sensitivity and specificity for predicting disease progression as compared to aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Forn’s index and serum DAK protein.
The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated CHB patients.
PMCID: PMC3851457  PMID: 24289155
Peptidome; Dihydroxyacetone kinase; Chronic hepatitis B; Multiple reaction monitoring; Liquid chromatography combined with tandem mass spectrometry
24.  The development of a combined mathematical model to forecast the incidence of hepatitis E in Shanghai, China 
BMC Infectious Diseases  2013;13:421.
Sporadic hepatitis E has become an important public health concern in China. Accurate forecasting of the incidence of hepatitis E is needed to better plan future medical needs. Few mathematical models can be used because hepatitis E morbidity data has both linear and nonlinear patterns. We developed a combined mathematical model using an autoregressive integrated moving average model (ARIMA) and a back propagation neural network (BPNN) to forecast the incidence of hepatitis E.
The morbidity data of hepatitis E in Shanghai from 2000 to 2012 were retrieved from the China Information System for Disease Control and Prevention. The ARIMA-BPNN combined model was trained with 144 months of morbidity data from January 2000 to December 2011, validated with 12 months of data January 2012 to December 2012, and then employed to forecast hepatitis E incidence January 2013 to December 2013 in Shanghai. Residual analysis, Root Mean Square Error (RMSE), normalized Bayesian Information Criterion (BIC), and stationary R square methods were used to compare the goodness-of-fit among ARIMA models. The Bayesian regularization back-propagation algorithm was used to train the network. The mean error rate (MER) was used to assess the validity of the combined model.
A total of 7,489 hepatitis E cases was reported in Shanghai from 2000 to 2012. Goodness-of-fit (stationary R2=0.531, BIC= −4.768, Ljung-Box Q statistics=15.59, P=0.482) and parameter estimates were used to determine the best-fitting model as ARIMA (0,1,1)×(0,1,1)12. Predicted morbidity values in 2012 from best-fitting ARIMA model and actual morbidity data from 2000 to 2011 were used to further construct the combined model. The MER of the ARIMA model and the ARIMA-BPNN combined model were 0.250 and 0.176, respectively. The forecasted incidence of hepatitis E in 2013 was 0.095 to 0.372 per 100,000 population. There was a seasonal variation with a peak during January-March and a nadir during August-October.
Time series analysis suggested a seasonal pattern of hepatitis E morbidity in Shanghai, China. An ARIMA-BPNN combined model was used to fit the linear and nonlinear patterns of time series data, and accurately forecast hepatitis E infections.
PMCID: PMC3847129  PMID: 24010871
Hepatitis E; Combined mathematical model; Forecast
25.  Altered Expression of 14-3-3ζ Protein in Spinal Cords of Rat Fetuses with Spina Bifida Aperta 
PLoS ONE  2013;8(8):e70457.
A large number of studies have confirmed that excessive apoptosis is one of the reasons for deficient neuronal function in neural tube defects (NTDs). A previous study from our laboratory used 2-D gel electrophoresis to demonstrate that 14-3-3ζ expression was low in the spinal cords of rat fetuses with spina bifida aperta at embryonic day (E) 17. As a member of the 14-3-3 protein family, 14-3-3ζ plays a crucial role in the determination of cell fate and anti-apoptotic activity. However, neither the expression of 14-3-3ζ in defective spinal cords, nor the correlation between 14-3-3ζ and excessive apoptosis in NTDs has been fully confirmed.
Methodology/Principal Findings
We used immunoblotting and quantitative real-time PCR (qRT-PCR) to quantify the expression of 14-3-3ζ and double immunofluorescence to visualize 14-3-3ζ and apoptosis. We found that, compared with controls, 14-3-3ζ was down-regulated in spina bifida between E12 and E15. Excessive apoptotic cells and low expression of 14-3-3ζ were observed in the dorsal region of spinal cords with spina bifida during the same time period. To initially explore the molecular mechanisms of apoptosis in NTDs, we investigated the expression of microRNA-7 (miR-7), microRNA-375 (miR-375) and microRNA-451 (miR-451), which are known to down-regulate 14-3-3ζ in several different cell types. We also investigated the expression of p53, a molecule that is downstream of 14-3-3ζ and can be down-regulated by it. We discovered that, in contrast to the reduction of 14-3-3ζ expression, the expression of miR-451, miR-375 and p53 increased in spina bifida rat fetuses.
These data suggest that the reduced expression of 14-3-3ζ plays a role in the excessive apoptosis that occurs in spina bifida and may be partly regulated by the over-expression of miR-451 and miR-375, and the consequent up-regulation of p53 might further promote apoptosis in spina bifida.
PMCID: PMC3735597  PMID: 23936434

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