Background and Objective
Despite great progress in treatment, the prognosis for patients with esophageal squamous cell carcinoma (ESCC) remains poor, highlighting the importance of early detection. Although upper endoscopy can be used for the screening of esophagus, it has limited sensitivity for early stage disease. Thus, development of new diagnosis approach to improve diagnostic capabilities for early detection of ESCC is an important need. The aim of this study was to assess the feasibility of using cathepsin B (CB) as a novel imaging target for the detection of human ESCC by near-infrared optical imaging in nude mice.
Initially, we examined specimens from normal human esophageal tissue, intraepithelial neoplasia lesions, tumor in situ, ESCC and two cell lines including one human ESCC cell line (Eca-109) and one normal human esophageal epithelial cell line (HET-1A) for CB expression by immunohistochemistry and western blot, respectively. Next, the ability of a novel CB activatable near-infrared fluorescence (NIRF) probe detecting CB activity presented in Eca-109 cells was confirmed by immunocytochemistry. We also performed in vivo imaging of tumor bearing mice injected with the CB probe and ex vivo imaging of resected tumor xenografts and visceral organs using a living imaging system. Finally, the sources of fluorescence signals in tumor tissue and CB expression in visceral organs were identified by histology.
CB was absent in normal human esophageal mucosa, but it was overexpressed in ESCC and its precursor lesions. The novel probe for CB activity specifically detected ESCC xenografts in vivo and in vitro.
CB was highly upregulated in human ESCC and its precursor lesions. The elevated CB expression in ESCC allowed in vivo and in vitro detection of ESCC xenografts in nude mice. Our results support the usefulness of CB activity as a potential imaging target for the detection of human ESCC.
Lumbar posterior ring apophysis fracture (PRAF) is an uncommon disorder frequently accompanied by lumbar disc herniation (LDH). Over the years, there have constantly been published studies concerning this disorder. Due to its rarity, there is lack of an agreed treatment strategy, and lots of different opinions exist, including the choice of decompressive modalities, whether removal of apophyseal fragments or/and disc material, and the necessity of additional spinal fusion. The purpose of this review is to provide a collective opinion on the treatment of PRAF with LDH.
A MEDLINE search in the English language literature was performed from 1980 to 2012. To be included in the study, it was strictly necessary for each clinical article to provide information about the description of apophyseal fracture such as location, treatment methods and clinical outcome. The studies were mainly analyzed for general features, the related classifications and treatments.
The literature searching yielded 19 articles reporting 366 patients experiencing 380 sites of fractures. All of them were case reports or case series. The classification systems of PRAF were various based on the morphology, mobilization, size or localization, and relationship between disc and fragment. The most used surgical options were posterior discectomy simultaneous excision of apophyseal fragments without spine fusion. Surgical treatment for PRAF with LDH had equally excellent clinical outcome compared with LDH alone.
The diverse features of apophyseal fracture lead to various modalities of classifications and operation options. Prior to operation, the surgeons should carefully make a plan to consider decompressive scope, removal of apophyseal fragment or/and disc and fusion or not. Because of methodological shortcomings in publications, it is not possible to definitively conclude what treatment modality is the best for the treatment of PRAF. More high-quality clinical studies are needed to draw more confirmable conclusions.
Ring apophysis fracture; Lumbar disc herniation; Low back pain; Adolescent; Systematic review
Although diagnostic methods, surgical techniques, and perioperative care have undergone significant advancement over the past decades, the prognosis of primary hepatocellular carcinoma (HCC) remains discouraged because of the high postoperative recurrence rate and high cancer mortality. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is a recently developed means for the treatment of HCC. In this study, we analyzed the efficacy of RFA plus TACE in 487 cases of HCC in our institution. We observed that the 1-, 2-, 3-, 4- and 5-year rates of overall survival rates after RFA and TACE treatment were 97.5% (475/487), 89.4% (277/310), 84.2% (181/215), 80.4% (150/186) and 78.7% (141/177), respectively. We did not find that age or tumor location (the caudate group or non-caudate group) plays a role in this cohort. However, we have identified that tumor recurrent status, the number of tumors, albumin (ALB), prothrombin time (PT) and platelet count (PLT) were significantly associated with poor overall survival in HCC patients receiving RFA combined with TACE. Interestingly, tumor size did not significantly impact overall survival, indicating that RFA combined with TACE for HCC treatment has the same efficiency for different sizes of tumors. Our results provide evidence for the rationale for using combined RFA and TACE in the treatment of primary HCC.
Purpose. Human papillomavirus (HPV) as a risk factor for esophageal squamous cell carcinoma (ESCC) has previously been studied, but importance of HPV status in ESCC for prognosis is less clear. Methods. A total of 105 specimens with ESCC were tested by in situ hybridization for HPV 16/18 and immunohistochemistry for p16 expression. The 5-year overall survival (OS) and progression-free survival were calculated in relation to these markers and the Cox proportional hazards model was used to determine the hazard ratio (HR) of variables in univariate and multivariate analysis. Results. HPV was detected in 27.6% (29) of the 105 patients with ESCC, and all positive cases were HPV-16. Twenty-five (86.2%) of the 29 HPV-positive tumors were stained positive for p16. HPV infected patients had better 5-year rates of OS (65.9% versus 43.4% among patients with HPV-negative tumors; P = 0.002 by the log-rank test) and had a 63% reduction in the risk of death (adjusted HR = 0.37, 95% CI = 0.16 to 0.82, and P = 0.01). Conclusions. HPV infection may be one of many factors contributing to the development of ESCC and tumor HPV status is an independent prognostic factor for survival among patients with ESCC.
Emerging evidence suggests that the tumor microenvironment plays a critical role in regulating cancer stem cells (CSCs) and tumor progression through both autocrine and paracrine signaling. Elevated production of bone morphogenetic proteins (BMPs) from human ovarian cancer cells and stroma has been shown to increase CSC proliferation and tumor growth. Here, we report that Lin28, a stem cell factor, binds to BMP4 mRNA in epithelial ovarian carcinoma cells, thereby promoting BMP4 expression at the post-transcriptional level. As co-expression of Lin28 and Oct4 (another stem cell factor) has been implicated in ovarian cancer CSCs, we also determined that high levels of Lin28 are associated with an unfavorable prognosis when co-expressed with high levels of Oct4. Together, these findings uncover a new level of regulation of BMP4 expression and imply a novel Lin28/Oct4/BMP4-mediated mechanism of regulating ovarian tumor cell growth, thus holding potential for the development of new strategies for the diagnosis and treatment of ovarian cancer.
BMP4; Lin28/Oct4; ovarian cancer; posttranscriptional; tumor microenvironment
Simple and sensitive detection of infectious disease at an affordable cost is urgently needed in developing nations. In this regard, the dot blot immunoassay has been used as a common protein detection method for detection of disease markers. However, the traditional signal reporting systems, such as those using enzymes or gold nanoparticles lack sensitivity and thus restrict the application of these methods for disease detection. In this study, we report a simple and sensitive detection method for the detection of infectious disease markers that couples the dot-blot immunoassay with quantum dots nanobeads (QDNBs) as a reporter. First, the QDNBs were prepared by an oil-in-water emulsion-evaporation technique. Because of the encapsulation of several QDs in one particle, the fluorescent signal of reporter can be amplified with QDNBs in a one-step test and be read using a UV lamp obviating the need for complicated instruments. Detection of disease-associated markers in complex mixture is possible, which demonstrates the potential of developing QDNBs into a sensitive diagnostic kit.
dot-blot immunoassay; HBsAg; quantum dots; nanobeads.
The availability of oral fluid HIV rapid testing provides an approach that may have the potential to expand HIV testing in China, especially among most-a-risk populations. There are few investigations about the acceptability of oral fluid HIV testing among most-at-risk populations in China.
A cross-sectional study with men who have sex with men (MSM), female sex workers (FSW) and voluntary counseling and testing (VCT) clients was conducted in three cities of Shandong province, China from 2011 to 2012. Data were collected by face-to-face questionnaire.
About 71% of participants were willing to accept the oral fluid HIV rapid testing, and home HIV testing was independently associated with acceptability of the new testing method among MSM, FSW and VCT clients (AOR of 4.46, 3.19 and 5.74, respectively). Independent predictors of oral fluid HIV rapid testing acceptability among MSM were having ever taken an oral fluid HIV rapid test (AOR= 15.25), having ever taken an HIV test (AOR= 2.07), and education level (AOR= 1.74). Engagement in HIV-related risk behaviors (AOR= 1.68) was an independent predictor of acceptability for FSW. Having taken an HIV test (AOR= 2.85) was an independent predictor of acceptability for VCT clients. The primary concern about the oral fluid HIV testing was accuracy. The median price they would pay for the testing ranged from 4.8 to 8.1 U.S. dollars.
High acceptability of oral fluid HIV rapid testing was shown among most-at-risk populations. Findings provide support for oral rapid HIV testing as another HIV prevention tool, and provide a backdrop for the implementation of HIV home testing in the near future. Appropriate pricing and increased public education through awareness campaigns that address concerns about the accuracy and safety of the oral fluid HIV rapid testing may help increase acceptability and use among most-at-risk populations in China.
Nanoscale plasmonic assemblies display exceptionally strong chiral optical activity. So far, their structural design was primarily driven by challenges related to metamaterials whose practical applications are remote. Here we demonstrate that gold nanorods assembled by the polymerase chain reaction into DNA-bridged chiral systems have promising analytical applications. The chiroplasmonic activity of side-by-side assembled patterns is attributed to a 7–9 degree twist between the nanorod axes. This results in a strong polarization rotation that matches theoretical expectations. The amplitude of the bisignate ‘wave’ in the circular dichroism spectra of side-by-side assemblies demonstrates excellent linearity with the amount of target DNA. The limit of detection for DNA using side-by-side assemblies is as low as 3.7 aM. This chiroplasmonic method may be particularly useful for biological analytes larger than 2–5 nm which are difficult to detect by methods based on plasmon coupling and ‘hot spots’. Circular polarization increases for inter-nanorod gaps between 2 and 20 nm when plasmonic coupling rapidly decreases. Reaching the attomolar limit of detection for simple and reliable bioanalysis of oligonucleotides may have a crucial role in DNA biomarker detection for early diagnostics of different diseases, forensics and environmental monitoring.
Nanoscale plasmonic assemblies are known to display exceptionally strong chiral optical activity. Here, the authors assemble gold nanorods into DNA-bridged chiral systems, and demonstrate their high efficiency for DNA detection at very low concentrations.
During speech perception, humans integrate auditory information from the voice with visual information from the face. This multisensory integration increases perceptual precision, but only if the two cues come from the same talker; this requirement has been largely ignored by current models of speech perception. We describe a generative model of multisensory speech perception that includes this critical step of determining the likelihood that the voice and face information have a common cause. A key feature of the model is that it is based on a principled analysis of how an observer should solve this causal inference problem using the asynchrony between two cues and the reliability of the cues. This allows the model to make predictions about the behavior of subjects performing a synchrony judgment task, predictive power that does not exist in other approaches, such as post-hoc fitting of Gaussian curves to behavioral data. We tested the model predictions against the performance of 37 subjects performing a synchrony judgment task viewing audiovisual speech under a variety of manipulations, including varying asynchronies, intelligibility, and visual cue reliability. The causal inference model outperformed the Gaussian model across two experiments, providing a better fit to the behavioral data with fewer parameters. Because the causal inference model is derived from a principled understanding of the task, model parameters are directly interpretable in terms of stimulus and subject properties.
causal inference; synchrony judgments; speech perception; multisensory integration; Bayesian observer
Lin28 plays important roles in development, stem cell maintenance, oncogenesis and metabolism. As an RNA-binding protein, it blocks the biogenesis primarily of let-7 family miRNAs and also promotes translation of a cohort of mRNAs involved in cell growth, metabolism and pluripotency, likely through recognition of distinct sequence and structural motifs within mRNAs. Here, we show that one such motif, shared by multiple Lin28-responsive elements (LREs) present in Lin28 mRNA targets also participates in a Drosha-dependent regulation and may contribute to destabilization of its cognate mRNAs. We further show that the same mutations in the LREs known to abolish Lin28 binding and stimulation of translation also abrogate Drosha-dependent mRNA destabilization, and that this effect is independent of miRNAs, uncovering a previously unsuspected coupling between Drosha-dependent destabilization and Lin28-mediated regulation. Thus, Lin28-dependent stimulation of translation of target mRNAs may, in part, serve to compensate for their intrinsic instability, thereby ensuring optimal levels of expression of genes critical for cell viability, metabolism and pluripotency.
Lin28; Drosha; stem cell; oncogene; RNA stability; metabolism
The Sun’s procedure is a surgical technique proposed by Dr. Li-Zhong Sun in 2002 that integrates total aortic arch replacement using a tetrafurcated graft with implantation of a specially designed frozen elephant trunk (Cronus®) in the descending aorta. It is used as a treatment option for extensive aortic dissections or aneurysms involving the ascending aorta, aortic arch and the descending aorta. The technical essentials of Sun’s procedure include implantation of the special open stented graft into the descending aorta, total arch replacement with a 4-branched vascular graft, right axillary artery cannulation, selective antegrade cerebral perfusion for brain protection, moderate hypothermic circulatory arrest at 25 °C, a special anastomotic sequence for aortic reconstruction (i.e., proximal descending aorta → left carotid artery → ascending aorta → left subclavian artery → innominate artery), and early rewarming and reperfusion after distal anastomosis to minimize cerebral and cardiac ischemia. The core advantage of Sun’s procedure lies in the use of a unique stented graft, which has superior technical simplicity, flexibility, inherent mechanical durability and an extra centimeter of attached regular vascular graft at both ends. Since its introduction in 2003, the Sun’s procedure has produced satisfactory early and long-term results in over 8,000 patients in China and more than 200 patients in South American countries. In a series of 1,092 patients, the authors have achieved an in-hospital mortality rate of 6.27% (7.98% in emergent or urgent vs. 3.98% in elective cases). Given the accumulating clinical experience and the consequent, continual evolution of surgical indications, the Sun’s procedure is becoming increasingly applied/used worldwide as an innovative and imaginative enhancement of surgical options for the dissected (or aneurysmal) ascending aorta, aortic arch and proximal descending aorta, and may become the next standard treatment for type A aortic dissections requiring repair of the aortic arch.
Sun’s procedure; frozen elephant trunk; aortic arch surgery; aortic dissection; aortic aneurysm
Acute type A aortic dissection (AAAD) remains one of the most lethal conditions requiring surgical repair, and is associated with a high rate of postoperative mortality and morbidity. Despite the satisfactory clinical outcomes achieved with the frozen elephant trunk technique so far, controversies still exist regarding the use of this aggressive approach in patients with AAAD. In this study, we seek to analyze the early outcomes of the Sun’s procedure, which is an approach integrating total arch replacement using a 4-branched graft with implantation of a special stented graft in the descending aorta, and identify the risk factors for postoperative mortality and morbidity of the Sun’s procedure in patients with AAAD.
Clinical data of 398 consecutive AAAD patients undergoing the Sun’s procedure were analyzed. The associations between 20 preoperative and intraoperative variables and early mortality were assessed by univariate and multivariate analysis.
Early mortality occurred in 31 patients (7.8%, 31/398), with leading causes including multi-organ failure in 16 patients (51.6%), permanent neurologic deficit in 6 (19.4%), and low cardiac output syndrome in 4 (12.9%). Permanent neurologic deficit and spinal cord injury occurred, each in 10 patients (2.5%, 10/398). Five significant risk factors for early mortality were identified with multivariate analysis: preexisting cerebrovascular disease [relative risk (RR) 14.76; P<0.001], acute heart failure (RR 18.18; P=0.001), spinal cord malperfusion (RR 60.13; P<0.002), visceral malperfusion (RR 30.25; P<0.001) and cardiopulmonary bypass time >190 minutes (RR 3.62; P=0.007).
The Sun’s procedure has generated a relatively lower mortality rate in 398 patients with AAAD. Patients with preexisting cerebrovascular disease, acute heart failure, spinal cord malperfusion, visceral malperfusion and long cardiopulmonary bypass time are at a higher risk of early mortality.
Aortic dissection; stented graft; surgery; outcome; mortality; complication
WRINKLED1 (AtWRI1) is a key transcription factor in the regulation of plant oil synthesis in seed and non-seed tissues. The structural features of WRI1 important for its function are not well understood. Comparison of WRI1 orthologs across many diverse plant species revealed a conserved 9 bp exon encoding the amino acids “VYL”. Site-directed mutagenesis of amino acids within the ‘VYL’ exon of AtWRI1 failed to restore the full oil content of wri1-1 seeds, providing direct evidence for an essential role of this small exon in AtWRI1 function. Arabidopsis WRI1 is predicted to have three alternative splice forms. To understand expression of these splice forms we performed RNASeq of Arabidopsis developing seeds and queried other EST and RNASeq databases from several tissues and plant species. In all cases, only one splice form was detected and VYL was observed in transcripts of all WRI1 orthologs investigated. We also characterized a phylogenetically distant WRI1 ortholog (EgWRI1) as an example of a non-seed isoform that is highly expressed in the mesocarp tissue of oil palm. The C-terminal region of EgWRI1 is over 90 amino acids shorter than AtWRI1 and has surprisingly low sequence conservation. Nevertheless, the EgWRI1 protein can restore multiple phenotypes of the Arabidopsis wri1-1 loss-of-function mutant, including reduced seed oil, the “wrinkled” seed coat, reduced seed germination, and impaired seedling establishment. Taken together, this study provides an example of combining phylogenetic analysis with mutagenesis, deep-sequencing technology and computational analysis to examine key elements of the structure and function of the WRI1 plant transcription factor.
Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment, of which osteogenic cells play a crucial role. While evidence is accumulating for an important role of intrinsic miR-17 in regulating HSCs and HPCs, whether miR-17 signaling pathways are also necessary in the cell-extrinsic control of hematopoiesis hereto remains poorly understood.
Using the immortalized clone with the characteristics of osteoblasts, FBMOB-hTERT, in vitro expansion, long-term culture initiating cell (LTC-IC) and non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice repopulating cell (SRC) assay revealed that the ectopic expression of miR-17 partly promoted the ability of FBMOB-hTERT to support human cord blood (CB) CD34+ cell expansion and maintain their multipotency. It also seemed that osteoblastic miR-17 was prone to cause a specific expansion of the erythroid lineage. Conversely, deficient expression of miR-17 partly inhibited the hematopoietic supporting ability of FBMOB-hTERT. We further identified that HIF-1α is responsible for, at least in part, the promoted hematopoietic supporting ability of FBMOB-hTERT caused by miR-17. HIF-1α expression is markedly enhanced in miR-17 overexpressed FBMOB-hTERT upon interaction with CB CD34+ cells compared to other niche associated factors. More interestingly, the specific erythroid lineage expansion of CB CD34+ cells caused by osteoblastic miR-17 was abrogated by HIF-1α knock down.
Our data demonstrated that CB CD34+ cell expansion can be partly promoted by osteoblastic miR-17, and in particular, ectopic miR-17 can cause a specific expansion of the erythroid lineage through augmenting HIF-1α in osteoblasts.
The ability to search efficiently for a target in a cluttered environment is one of the most remarkable functions of the nervous system. This task is difficult under natural circumstances, as the reliability of sensory information can vary greatly across space and time and is typically a priori unknown to the observer. In contrast, visual-search experiments commonly use stimuli of equal and known reliability. In a target detection task, we randomly assigned high or low reliability to each item on a trial-by-trial basis. An optimal observer would weight the observations by their trial-to-trial reliability and combine them using a specific nonlinear integration rule. We found that humans were near-optimal, regardless of whether distractors were homogeneous or heterogeneous and whether reliability was manipulated through contrast or shape. We present a neural-network implementation of near-optimal visual search based on probabilistic population coding. The network matched human performance.
β-Lactamase residues in milk represent a public health risk. The cylinder plate detection method, which is based on bacterial growth, is laborious and time consuming. In this study, 15 monoclonal antibodies (mAbs) were selected against Temoneira (TEM) 1 β-lactamase. A sandwich enzyme-linked immunosorbent assay (ELISA) based on an optimum mAb pair was developed and validated for the detection of β-lactamase. The limit of detection and linear dynamic range of the method were 4.17 ng/mL and 5.5–100 ng/mL, respectively. β-Lactamase recovery in pure milk was 96.82–103.13%. The intra- and inter-assay coefficients of variation were 6.21–7.38% and 12.96–13.74%, respectively. Our developed sandwich ELISA can be used as a rapid detection method of β-lactamase in milk.
β-lactamase; monoclonal antibody; sandwich ELISA; milk; detection
We have established a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) based on two monoclonal antibodies (mAb) to measure the content of the major peanut allergen Ara h 1 in foods. Two mAbs were selected out of 12 murine hybridoma cells secreting Ara h 1-specific antibody. Using mAb 6 as the capture antibody and HRP-labelled mAb 4 as the detection antibody, the limit of detection (LOD) the assay was 0.34 ng/mL. Cross-reaction analysis showed that this method was strongly specific and had no cross-reactions with Ara h 2, pea protein or soy protein. Sample analysis showed that this ELISA was a useful tool to monitor peanut allergens in food products by measuring Ara h 1 content.
peanut allergen; Ara h 1; monoclonal antibody; sandwich ELISA
A monoclonal antibody specifically recognizing dibutyl phthalate (DBP) was prepared based on a hapten (di-n-butyl-4-aminophthalate). After optimizing various parameters such as concentrations of antibody, coating antigen and composition of the assay buffer, an inhibition curve was plotted with the 50% inhibition concentration value (IC50) 33.6 ± 2.5 ng/mL. A low level of cross-reactivity (<5%) was found for other phthalate esters. Recovery tests were conducted using liquor simulant (a mixture of water and ethanol) at two fortification levels (100 ng/mL and 300 ng/mL). The recovery rates ranged from 84.7% to 94.5% with a coefficient of variation between 7.1% and 12.8%. Nine liquor samples of different alcoholic strengths were detected using the proposed measure and confirmatory analysis was performed using liquid chromatography-mass spectroscopy (LC-MS). The detection results showed good consistency between the two measures and all the data above indicated that the proposed ELISA could be applied in DBP screening.
di-n-butyl phthalate; ELISA; liquor; monoclonal antibody
It has been reported that the prevalence of chronic diseases is high among old people and they have poor chronic diseases knowledge. This study was therefore designed to evaluate the awareness rate of chronic diseases knowledge among people aged over 60 years, to explore its related factors and to provide evidence for future health education.
A cross-sectional study was conducted from April to August in 2011. People aged 60 years and above from 3 communities in Jinan were selected by cluster sampling. Nine hundred and twenty five participants were interviewed face-to-face using a structured questionnaire.
The awareness rates of chronic diseases knowledge varied from 29.5% to 90.2%. Four healthy lifestyles including quitting smoking and less drinking, keeping broad-minded, maintaining balanced diet and moderate physical activity were best known (from 86.3% to 90.2%). The least known knowledge were 2 complications of hypertension: nephropathy (29.5%) and retinopathy (37.2%). Participants with the following characteristics or behaviors were more likely to have higher chronic diseases knowledge: younger age, female, Han Chinese, higher level of education, having health insurance, participating in societies, having family history of chronic diseases, frequently gathering with friends/relatives, usually going to provincial hospitals/hospitals affiliated with medical universities, usually going to municipal hospitals and usually going to community health center/station.
Old people in Jinan had incomplete chronic diseases knowledge and the overall awareness rate was not high. The older people’s chronic diseases knowledge should be improved and health education programs should target males, older people with lower educational level, having no health insurance, having no family history of chronic diseases, participating in no societies, and less frequently gathering with friends/relatives. Also, lower level medical facilities should improve their skills of health education.
Chiral nanoscale photonic systems typically follow either tetrahedral or helical geometries that require four or more different constituent nanoparticles. Smaller number of particles and different chiral geometries taking advantage of the self-organization capabilities of nanomaterials will advance understanding of chiral plasmonic effects, facilitate development of their theory, and stimulate practical applications of chiroplasmonics. Here we show that gold nanorods self-assemble into side-by-side orientated pairs and “ladders” in which chiral properties originate from the small dihedral angle between them. Spontaneous twisting of one nanorod versus the other one breaks the centrosymmetric nature of the parallel assemblies. Two possible enantiomeric conformations with positive and negative dihedral angles were obtained with different assembly triggers. The chiral nature of the angled nanorod pairs was confirmed by 4π full space simulations and the first example of single-particle CD spectroscopy. Self-assembled nanorod pairs and “ladders” enable the development of chiral metamaterials, (bio)sensors, and new catalytic processes.
Persistent and heavy rainfall in the upper and middle Huaihe River of China brought about severe floods during the end of June and July 2007. However, there has been no assessment on the association between the floods and infectious diarrhea. This study aimed to quantify the impact of the floods in 2007 on the burden of disease due to infectious diarrhea in northwest of Anhui Province.
A time-stratified case-crossover analysis was firstly conducted to examine the relationship between daily cases of infectious diarrhea and the 2007 floods in Fuyang and Bozhou of Anhui Province. Odds ratios (ORs) of the flood risk were quantified by conditional logistic regression. The years lived with disability (YLDs) of infectious diarrhea attributable to floods were then estimated based on the WHO framework of the calculating potential impact fraction in the Burden of Disease study.
A total of 197 infectious diarrheas were notified during the exposure and control periods in the two study areas. The strongest effect was shown with a 2-day lag in Fuyang and a 5-day lag in Bozhou. Multivariable analysis showed that floods were significantly associated with an increased risk of the number cases of infectious diarrhea (OR = 3.175, 95%CI: 1.126–8.954 in Fuyang; OR = 6.754, 95%CI: 1.954–23.344 in Bozhou). Attributable YLD per 1000 of infectious diarrhea resulting from the floods was 0.0081 in Fuyang and 0.0209 in Bozhou.
Our findings confirm that floods have significantly increased the risks of infectious diarrhea in the study areas. In addition, prolonged moderate flood may cause more burdens of infectious diarrheas than severe flood with a shorter duration. More attention should be paid to particular vulnerable groups, including younger children and elderly, in developing public health preparation and intervention programs. Findings have significant implications for developing strategies to prevent and reduce health impact of floods.
Growing evidence has demonstrated a neuroprotective role of autophagy in Alzheimer’s disease (AD). Thus, autophagy has been regarded as a potential therapeutic target, attracting increasing interest in pharmaceutical autophagy modulation by small molecules. We designed a two-cycle screening strategy on the basis of imaging high-throughout screening (HTS) and cellular toxicity assay, and have identified a novel autophagy inducer known as GTM-1. We further showed that GTM-1 exhibits dual activities, such as autophagy induction and antagonism against Aβ-oligomer toxicity. GTM-1 modulates autophagy in an Akt-independent and mTOR-independent manner. In addition, we demonstrated that GTM-1 enhances autophagy clearance and reverses the downregulation of autophagy flux by thapsigargin and asparagine. Furthermore, administration of GTM-1 attenuated Aβ pathology and ameliorated cognitive deficits in AD mice.
This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC).
Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed.
The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis (P<0.001). The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Although univariate regression analysis showed significant difference between the two groups (P=0.014), multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and residual tumor (P=0.026) were the independent prognostic factors.
LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.
Esophageal squamous cell carcinoma; lymphatic vessel invasion; D2-40; lymph node metastasis; prognosis
To identify the compounds absorbed in rat serum after the oral administration of Wu-Jia Sheng-Hua (WJSH) capsule, a traditional Chinese medicine (TCM) compound prescription, an ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC/ESI-MS) method, was established. The chromatographic separation of the absorbed compounds and metabolites was achieved with an ACQUITY UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) under a gradient elution. The mobile phase was composed of acetonitrile and water buffered with ammonium acetate (10 mM) and formic acid (0.1%, V/V). Twelve absorbed compounds and four metabolites were found. Seven of the absorbed compounds were identified by ESI-MS. The identification of absorbed compounds might be helpful for the better understanding of the mechanisms underlying the pharmacological effects of WJSH capsule.