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Pangolins are the most trafficked wild animal in the world according to the World Wildlife Fund. The discovery of SARS-CoV-2-related coronaviruses in Malayan pangolins has piqued interest in the viromes of these wild, scaly-skinned mammals. We sequenced the viromes of 161 pangolins that were smuggled into China and assembled 28 vertebrate-associated viruses, 21 of which have not been previously reported in vertebrates. We named 16 members ofHunnivirus,PestivirusandCopiparvoviruspangolin-associated viruses. We report that thel-protein has been lost from all hunniviruses identified in pangolins. Sequences of four human-associated viruses were detected in pangolin viromes, including respiratory syncytial virus,Orthopneumovirus,RotavirusAandMammalian orthoreovirus. The genomic sequences of five mammal-associated and three tick-associated viruses were also present. Notably, a coronavirus related to HKU4-CoV, which was originally found in bats, was identified. The presence of these viruses in smuggled pangolins identifies these mammals as a potential source of emergent pathogenic viruses.

ObjectiveStromal barriers, such as the abundant desmoplastic stroma that is characteristic of pancreatic ductal adenocarcinoma (PDAC), can block the delivery and decrease the tumour-penetrating ability of therapeutics such as tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), which can selectively induce cancer cell apoptosis. This study aimed to develop a TRAIL-based nanotherapy that not only eliminated the extracellular matrix barrier to increase TRAIL delivery into tumours but also blocked antiapoptotic mechanisms to overcome TRAIL resistance in PDAC.DesignNitric oxide (NO) plays a role in preventing tissue desmoplasia and could thus be delivered to disrupt the stromal barrier and improve TRAIL delivery in PDAC. We applied an in vitro–in vivo combinatorial phage display technique to identify novel peptide ligands to target the desmoplastic stroma in both murine and human orthotopic PDAC. We then constructed a stroma-targeted nanogel modified with phage display-identified tumour stroma-targeting peptides to co-deliver NO and TRAIL to PDAC and examined the anticancer effect in three-dimensional spheroid cultures in vitro and in orthotopic PDAC models in vivo.ResultsThe delivery of NO to the PDAC tumour stroma resulted in reprogramming of activated pancreatic stellate cells, alleviation of tumour desmoplasia and downregulation of antiapoptotic BCL-2 protein expression, thereby facilitating tumour penetration by TRAIL and substantially enhancing the antitumour efficacy of TRAIL therapy.ConclusionThe co-delivery of TRAIL and NO by a stroma-targeted nanogel that remodels the fibrotic tumour microenvironment and suppresses tumour growth has the potential to be translated into a safe and promising treatment for PDAC.

Previous studies have identified multiple viruses in dead or severely diseased pangolins, but descriptions of the virome in healthy pangolins are lacking. This poses a greater risk of cross-species transmission due to poor preventive awareness and frequent interactions with breeders. In this study, we investigated the viral composition of 34 pangolins with no signs of disease at the time of sampling and characterized a large number of arthropod-associated viruses belonging to 11 families and vertebrate viruses belonging to eight families, including those with pathogenic potential in humans and animals. Several important vertebrate viruses were identified in the pangolins, including parvovirus, pestivirus, and picobirnavirus. The picobirnavirus was clustered with human and grey teal picobirnaviruses. Viruses with cross-species transmission ability were also identified, including circovirus, rotavirus, and astrovirus. Our study revealed that pangolins are frequently exposed to arthropod-associated viruses in the wild and can carry many vertebrate viruses under natural conditions. This study provides important insights into the virome of pangolins, underscoring the importance of monitoring potential pathogens in healthy pangolins to prevent outbreaks of infectious diseases in domesticated animals and humans.先前的研究已经从死亡或严重患病的穿山甲中发现了大量病毒，但对健康穿山甲的病毒组的研究较少。而且由于缺乏健康动物携带病原体的防范意识，并且野生动物与饲养员频繁接触，正常野生动物携带的病毒存在更高的跨物种传播风险。在该研究中，我们调查了34只穿山甲的病毒组成，它们在被取样时没有疾病迹象，并对属于11个科的大量节肢动物相关病毒和属于8个科的各种脊椎动物病毒进行了鉴定，包括一些已知的对人类和动物有致病潜力的病毒。一些重要的脊椎动物病毒已在穿山甲中被发现，包括parvovirus（细小病毒），pestivirus（瘟疫病毒），和picobirnavirus（小双节RNA病毒）。其中我们发现的picobirnavirus与感染人类和灰鸭的picobirnavirus病毒聚集。我们还发现了许多具有跨物种传播潜力的病毒，包括circovirus（圆环病毒）、rotavirus（轮状病毒）和astrovirus（星状病毒）等。我们的研究表明，穿山甲在野外经常接触到节肢动物相关的病毒，并且在自然条件下可以携带许多感染脊椎动物的病毒。该研究提供了对穿山甲病毒组的重要见解，强调了监测健康穿山甲中潜在病原体的重要性，以防止在驯养动物和人类中爆发传染病。.

Respiratory syncytial virus (RSV) is an enveloped non-segmented negative sense RNA virus that belongs to Orthopneumovirus genus of the Pneumoviridae family in the order Mononegavirales. The virus is the leading cause of severe respiratory disease in children under two years of age and is responsible for substantial disease burden in infants and elder people in both developed and developing countries

Metastasis is one of the most threatening aspects of cervical cancer. We developed a method to intraoperatively map the primary tumor, metastasis and metastatic sentinel lymph nodes (SLNs), providing real-time intraoperative guidance in cervical cancer. Methods: TMTP1, a tumor metastasis targeting peptide, was employed to modify the indocyanine green (ICG)-loaded poly (ethylene glycol)- poly (lactic-co-glycolic acid) (PEG-PLGA) micelles. The cervical cancer subcutaneous tumor model and lung metastasis model were established to determine the active targeting of ICG-loaded TMTP1-PEG-PLGA micelles (ITM) for the primary tumor and occult metastasis of cervical cancer. Human cervical cancer HeLa cells engineered by firefly luciferase were injected into the right hocks of BALB/c nude mice to develop the SLN metastasis model. The ITM and control ICG-loaded PEG-PLGA micelles (IM) were injected into the right hind footpads in the SLN metastasis model, and the migration and retention of micelles were recorded under near-infrared fluorescence. K14-HPV16 transgenic mice were also used to detect the image capability of ITM to target cancerous lesions. Results: ITM could actively target imaging of the primary tumor and cervical cancer metastasis. ITM quickly diffused from the injection site to SLNs along lymphatic capillaries and remained in the SLNs for 12 h. Moreover, ITM specifically accumulated in the tumor metastatic SLNs (T-SLNs), which could be successfully distinguished from normal SLNs (N-SLNs). Conclusion: ITM could achieve active targeting of the primary tumor, metastasis and T-SLNs, providing precise and real-time intraoperative guidance for cervical cancer.

Food grains constitute a vital part of the daily diet of the population worldwide, and are generally considered as safe products with high storage stability due to their low moisture contents. However, post-harvest losses (PHL) caused by insects, fungi, food-borne pathogens, and undesirable enzymes remain a major concern for the grain industry. Thermal treatments are commonly used to reduce the PHL of grains and their products without any chemical residues. Among which, radio frequency (RF) technology has been regarded as a promising alternative to traditional heating methods for improving safety and quality of food grains due to its fast, volumetric, and deep penetration heating characteristics. This review provided comprehensive information about principles of RF technology and its main applications including disinfestation, pasteurization, enzyme inactivation, drying, and roasting for processing food grains and their products. The methods to improve the RF heating uniformity and effects of RF heating on product quality were also reviewed. Finally, the current problems and recommendations for future work related to RF processing of grains and their products were discussed. This review would improve the understanding of RF heating for food grains and their products and promote the application of RF technology in the food grain industry.

Background Long non-coding RNAs (lncRNAs) are novel regulatory molecules in breast cancer development. LncRNA LUCAT1 is a potential tumor promoter in human cancers. In this study, we aimed to explore the role of LUCAT1 in human breast cancer tissues and cells. Methods A total of 31 breast cancer patients who underwent tumor resection, but without chemo- or radiotherapy or acute lung/heart/kidney diseases, provided tumor and adjacent normal tissues. Bioinformatic analysis, qRT-PCR, and luciferase reporter assay were carried out during the study. Results qRT-PCR analysis indicated that, compared with the adjacent tissues and MCF-10A normal breast epithelial cells, LUCAT1 was markedly up-regulated in the breast cancer tissues and five BC cell lines, including MDA-MB-231, MDA-MB-468, MDA-MB-435, SKBR3, and MCF-7. The knockdown of LUCAT1, through the transfection of small interfering RNA (siRNA) specific to LUCAT1, resulted in inhibition of proliferation in breast cancer cells. The expression levels of miR-181a-5p were decreased in the breast cancer tissues and five BC cell lines. Bioinformatic analysis and luciferase reporter assay suggested the interaction between miR-181a-5p and LUCAT1. In addition, the effects of LUCAT1 on promoting cell proliferation were attenuated by overexpression of miR-181a-5p through the transfection of miR-181a-5p mimic. Moreover, bioinformatics and luciferase reporter assay confirmed that miR-181a-5p targeted the 3′-UTR region of KLF6 and KLF15 mRNA, which were two tumor suppressor genes. LUCAT1/miR-181a-5p axis regulated the expression of KLF6 and KLF15 both in vitro and in vivo. Conclusions Our data indicate that LUCAT1/miR-181a-5p axis can serve as a novel therapeutic target in breast cancer.

War and natural disaster have been spurs to the creation of rehabilitation services. The COVID-19 pandemic poses a different question for existing rehabilitation services: how best to respond to a disaster that is anticipated from afar, but whose shape has yet to take full form?Applying the 5-phase crisis management model ofContingency rehabilitation planning can be framed in a 5-phase crisis management model that includes (i) signal detection; (ii) prevention/preparedness; (iii) damage limitation; (iv) recovery; and (v) learning. We have reported the impact of COVID-19 on rehabilitation services within a Scottish context and shared some of our learning.COVID-19 has challenged healthcare worldwide and has served as an amplifier for the recognised ill effects of poverty and inequality. As rehabilitation clinicians, we are in a position to continue advocating for people facing disability, and also seeking and responding to signals of COVID-19's late effects in both COVID-19 and non-COVID-19 patients alike. IMPLICATIONS FOR REHABILITATION COVID-19 has resulted in unprecedented challenges in rehabilitation service planning. Contingency rehabilitation planning can be framed in a 5-phase crisis management model of

The application of prostate-specific antigen (PSA) in the screening and diagnosis of prostate cancer (PCa) has improved the clinical management of PCa patients. However, the PSA assay has been faced with criticism due to its potential association with over-diagnosis and subsequent overtreatment of indolent patients. Matrix metalloproteinase-26 (MMP26) is a member of matrix metalloproteinases (MMPs) and has been reported to be highly expressed in many cancers. This investigation evaluated the potential of serum MMP26 as a biomarker for PCa. The level of serum MMP26 was measured by enzyme-linked immunosorbent assay (ELISA) in 160 subjects including PCa group (n=80), benign prostatic hyperplasia (BPH) group (n=40) and control group (n=40). Furthermore, we evaluated the expression of MMP26 in tissues by immunohistochemistry. The results showed the serum MMP26 levels were significantly higher in PCa group than in BPH group and control group. Similarly, the MMP26 protein was positive in PCa tissues and negative in BPH tissues and control tissues. In conclusion, these results suggested MMP26 could be used as a potential serum biomarker in the diagnosis of PCa.

Low quality of life, depression and poor quality of sleep are associated with increased mortality in hemodialysis patients. It is not clear which factor has the highest predictive power and what the core element is to explain the predictability. We thus conducted a prospective cohort study that included 151 hemodialysis adults. Three traits of interest were assessed by World Health Organization Quality of Life questionnaire, an abbreviated version (WHOQOL-BREF), Taiwanese Depression Questionnaire, and Athens Insomnia Scale, respectively. They were followed for more than 3 years and the all-cause mortality was 30.5%. The prevalence of quality of life at the lowest tertile, depression and poor quality of sleep was 19.9%, 43.0% and 74.2%, respectively. Discriminant analysis showed the standardized coefficient of each factor as 0.813, −0.289 and 0.066, indicating the highest discriminating power by quality of life to predict mortality. Question 15 “how well are you able to get around?” in the physical health domain of WHOQOL-BREF independently associated a hazard ratio of mortality 0.623 (95% confidence interval 0.423-0.918). Subjective perception of overall quality of life was more related to psycho-social-environmental factors. In conclusion, mobility is an independent and powerful predictor to long term mortality in patients on chronic hemodialysis.

Objective To investigate the cytotoxicity of cytokine induced killer (CIK) and natural killer (NK) cells derived from human peripheral blood on MDA-MB-231 breast cancer in vitro. Methods The MDA-MB-231 human breast cancer cells were infected with lentivirus containing red fluorescent protein (RFP) and luciferase (Luc) genes. The expression of RFP and Luc genes were detected by florescence microscopy. Peripheral blood mononuclear cells (PBMCs) were isolated from the patients to induce the information of dendritic cells (DCs), CIK and NK cells. Then DCs and CIK cells were co-cultured to induce the formation of DC-CIK cells. The amplification effect and the immunophenotypes of immune cells were detected by flow cytometry. And then the cytotoxicity of immune cells DC-CIK, CIK and NK cells on MDA-MB-231 breast cancer cells were analyzed at different effector-target ratios. Results he effects of DC-CIK, NK and CIK cells on MDA-MB-231 tumor cells increased with the increase of effector-target ratio and the extension of action time. After co-culture of 72 hours, the killing rate of immune cells on target cells reached more than 90%. Conclusion CIK, DC-CIK and NK cells amplified in vitro have apoptosis effects on breast cancer cells.

While most patients with an acquired brain injury (ABI) receive appropriate post-acute care and rehabilitation via established pathways from critical care units and tertiary neurosciences centres, a small number of these patients do fall through the cracks and end up in the general medical ward.

Inpatient specialist neurorehabilitation in the United Kingdom is based on providing a service to "working-age" adults (65 years), with little evidence for outcomes for older adults involved with these services.The aim of this study is to determine any difference in outcome after inpatient neurorehabilitation between younger and older adults assessed as having rehabilitation potential.A two-centre retrospective review was performed comparing patients aged65 and≥65 years by diagnostic group in terms of length of stay, changes in UK Functional Independence Measure+Functional Assessment Measure (UK FIM+FAM) scores and discharge destination.Six hundred and sixteen patients (32%≥65 years) were included. The 2 age groups did not differ in length of stay (median difference 7 days, 95% confidence interval [CI] -2 to 15, P=0.112), but both UK FIM+FAM change and efficiency were higher for the older than younger group (median difference 7, 95% CI 2-13, P=0.006 and 0.10, 0.01-0.19, P=0.031 respectively). Older age was associated with discharge to long-term care (6%65 years; 11%≥65 years, xOlder adults considered to have rehabilitation potential may have greater functional gains from inpatient specialist inpatient rehabilitation than younger adults. Age alone should not exclude admission to inpatient specialist neurorehabilitation.

Depression is more common in many medical conditions than among the general population and is associated with an increased risk of mortality. We aimed to determine whether somatic symptoms of depression were more predictive of mortality than affective and cognitive symptoms in hemodialysis patients. We conducted a prospective cohort study in which the survival outcomes of 151 subjects were followed for more than 3 years. Depression was assessed with the Taiwanese Depression Questionnaire (TDQ). Subjects with TDQ scores 19–54 (correlated with clinically significant depressive symptoms) and those with scores 15–18 had higher 3-year mortality rates than the two groups with lower scores (40.0%, 46.7%, 16.0% and 19.6%, p = 0.021, ANOVA). Affective and cognitive symptoms, including sadness, tenseness, indecisiveness and low self-confidence, and one somatic item (bodily discomfort) were associated with mortality. Affective and cognitive symptoms affected quality of life more than somatic symptoms. The somatic subscale was associated with female gender, low income and education, dialysis vintage, and low serum creatinine and albumin levels, whereas the affective and cognitive subscale was associated with less education and a low serum albumin level. In conclusion, affective and cognitive symptoms of depression may better predict long-term mortality in patients undergoing chronic hemodialysis than somatic symptoms.

Growing evidences have shown that the IL-6/IL-6R signal pathway promotes the tumor growth, angiogenesis, invasion and migration in various cancers, especially for epithelial ovarian cancer. Hence, including anti-IL-6 antibody (Siltuximab) and anti-IL-6R antibody (Tocilizumab), more and more therapeutic drugs targeting IL-6/IL-6R pathway were developed to block their activity. The molecular imaging of IL-6R is a significant factor for predicting tumor response to IL-6/IL-6R targeted drugs. However, few probes targeting IL-6R were designed and used for the specific detection. The purpose of this study was to develop and evaluate a novel radiotracer, (99m)Tc-HYNIC-Aca-LSLITRL, for SPECT imaging of interleukin-6 receptor. The expression of IL-6R was determined by western blot, immunofluorescence and immunohistochemistry. HYNIC-Aca-LSLITRL and HYNIC-Aca-TLQASIL were synthesized, and then were labeled with 99mTc. The stability and the cell-binding assay were performed. Ovarian tumor xenografts were established and subjected to SPECT imaging after injection of these two radiopharmaceuticals with or without excess primary peptides. The biodistribution of these two radiotracers was performed in nude mice bearing C13K tumors. (99m)Tc-HYNIC-Aca-LSLITRL and (99m)Tc-HYNIC-Aca-TLQASIL were obtained in >95 % labeling yield with favorably stability. In vitro studies demonstrated that the interleukin-6 receptor was overexpressed in ovarian cancer C13K cells. The SPECT imaging of interleukin-6 receptor and biodistribution studies showed that (99m)Tc-HYNIC-Aca-LSLITRL had higher tumor uptake and significantly lower kidney accumulation compared to (99m)Tc-HYNIC-Aca-TLQASIL. (99m)Tc-HYNIC-Aca-LSLITRL could be a promising agent for SPECT imaging of interleukin-6 receptor of ovarian cancer especially for those anti-IL-6R drugs under clinical trials, such as tocilizumab.

Chronic liver diseases have recently garnered substantial attention as a leading cause of death around the world. During the progression of liver fibrosis/cirrhosis induced by chronic liver injury, hepatic stellate cells (HSCs) play key roles in the regulation of liver fibrogenesis and can even accelerate the progression of hepatocellular carcinoma (HCC). Thus, inhibition of HSC activation or suppression of inflammatory cytokine secretion by HSCs may be an efficient therapeutic strategy to ameliorate liver fibrosis/cirrhosis. In this study, we demonstrated that Cellax NPs (Carboxymethylcellulose - docetaxel-conjugated nanoparticles), which are nanoscale Pegylated carboxymethylcellulose - DTX conjugates, selectively target activated HSCs and abrogate their fibrogenic properties in vitro. Furthermore, Cellax NPs alleviated CCl

XPNPEP2 is a proline hydrolytic enzyme that hydrolyzes several biologically active peptides and causes a loss of substrate activity. However, its function in cancer is still unknown. Our study showed that XPNPEP2 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and cervical intraepithelial neoplasm tissues. Statistical analysis showed that XPNPEP2 expression was associated with the International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Overexpression of XPNPEP2 in SiHa and HeLa cells promoted cell invasion and migration without affecting cell proliferation and apoptosis. Mechanistically, we found that XPNPEP2 facilitated cervical cancer cell invasion and migration by inducing epithelial–mesenchymal transition. Furthermore, we demonstrated that XPNPEP2 had significant effects on the metastasis of xenografted tumors in vivo. Collectively, our findings identify the novel function of XPNPEP2 in the metastasis of cervical cancer and suggest that XPNPEP2 could be a novel potential therapeutic target for the treatment of cervical cancer.

Major depressive disorder (MDD) has become a leading contributor to the global burden of disease; however, there are currently no reliable biological markers or physiological measurements for efficiently and effectively dissecting the heterogeneity of MDD. Here we propose a novel method based on scalp electroencephalography (EEG) signals and a robust spectral-spatial EEG feature extractor called kernel eigen-filter-bank common spatial pattern (KEFB-CSP). The KEFB-CSP first filters the multi-channel raw EEG signals into a set of frequency sub-bands covering the range from theta to gamma bands, then spatially transforms the EEG signals of each sub-band from the original sensor space to a new space where the new signals (i.e., CSPs) are optimal for the classification between MDD and healthy controls, and finally applies the kernel principal component analysis (kernel PCA) to transform the vector containing the CSPs from all frequency sub-bands to a lower-dimensional feature vector called KEFB-CSP. Twelve patients with MDD and twelve healthy controls participated in this study, and from each participant we collected 54 resting-state EEGs of 6 s length (5 min and 24 s in total). Our results show that the proposed KEFB-CSP outperforms other EEG features including the powers of EEG frequency bands, and fractal dimension, which had been widely applied in previous EEG-based depression detection studies. The results also reveal that the 8 electrodes from the temporal areas gave higher accuracies than other scalp areas. The KEFB-CSP was able to achieve an average EEG classification accuracy of 81.23% in single-trial analysis when only the 8-electrode EEGs of the temporal area and a support vector machine (SVM) classifier were used. We also designed a voting-based leave-one-participant-out procedure to test the participant-independent individual classification accuracy. The voting-based results show that the mean classification accuracy of about 80% can be achieved by the KEFP-CSP feature and the SVM classifier with only several trials, and this level of accuracy seems to become stable as more trials (i.e.

Abdominal aortic calcification (AC) has been reported to be associated with cardiovascular disease (CVD) in hemodialysis patients but is rarely discussed in peritoneal dialysis (PD) patients. We examined the independent predictors and predictive power for survival of AC in prevalent PD patients.AC was detected by computed tomography (CT) and represented as the percentage of the total aortic cross-section area affected by AC (%AC). The predictors of %AC ≥ 15 were examined by multiple logistic regression analysis. Cox proportional hazard analysis was used to determine the hazard ratios associated with high %AC. A total of 183 PD patients were recruited to receive CT scans and divided into group 1 (%AC15, n = 97), group 2 (%AC ≥ 15, n = 41), and group 3 (diabetic patients, n = 45). Group 1 patients had lower osteoprotegerin (OPG) levels than group 2 patients (798 ± 378 vs. 1308 ± 1350 pg/mL, p0.05). The independent predictors for %AC ≥ 15 included the atherogenic index, OPG, and C-reactive protein (CRP). The age-adjusted hazard ratios associated with %AC ≥ 15 were 3.46 (p = 0.043) for mortality and 1.90 (p = 0.007) for hospitalization.%AC can predict mortality and morbidity in non-diabetic PD patients, and 15% is a good cut-off value for such predictions. There are complex associations among mineral metabolism, inflammation, and dyslipidemia in the pathogenesis of AC.

Background Cdc42 is a small guanosine-5′-triphosphatase of the Rho family and plays essential roles in the establishment of cellular polarity and tight junctions in epithelial cells. Adenomatous polyposis coli-associated exchange factor (Asef) is a canonical guanine nucleotide exchange factor of Cdc42 and renders Cdc42 to be guanosine-5′-triphosphate bound and activated. The expression patterns and their significance in human renal diseases are unknown. Methods We examined the expression of Cdc42 and Asef in kidney biopsy specimens of 15 patients and in normal kidney tissue using immunofluorescence and correlated the expression patterns with the clinical characteristics. We also analyzed the coexpression pattern of Ki-67, a marker indicating cell division, and Asef in selected patients. Results Expression of Asef and Cdc42 together was associated with tubular injury with 100% specificity. Expression of Asef, regardless of Cdc42, also showed a significant diagnostic odds ratio for the presence of the injury. Expression of Asef was associated with lower estimated glomerular filtration rate at the time of biopsy and larger area of interstitial fibrosis. All Ki-67–expressing tubular cells expressed Asef. Conclusions Induction of Asef and Cdc42 in the renal tubules is a cellular response to injury. Asef induction seems a necessary step for injured tubular cells to enter cell cycle.

We report on a 12-year-old female patient with lipoprotein glomerulopathy (LPG) who was proven to be heterozygous for ApoE2 Kyoto (Arg25Cys). Her family members have the same variant but do not have obvious signs of renal function impairment. Six months of treatment with a statin caused significant clinical improvement in the lipid profile, proteinuria, and renal function. Our case suggests that administration of a statin is a potential therapeutic strategy for improving nephrotic syndrome in patients with LPG.

Background: In the treatment of nail psoriasis, standardized therapeutic regimens are currently lacking. Objective: To evaluate the therapeutic efficacy of indigo naturalis oil extract in patients with nail psoriasis. Methods: Patients with nail psoriasis applied indigo naturalis oil extract on affected nails twice daily for 24 weeks. Efficacy was evaluated using the Nail Psoriasis Severity Index (NAPSI) and modified target NAPSI for the single most severely affected nail. Results: Twenty-eight out of 32 patients completed the study. The mean NAPSI was 36.1 ± 14.7 at baseline and decreased to 14.9 ± 11.1 at week 24 while the mean modified target NAPSI was 11.7 ± 3.9 at baseline and decreased to 3.6 ± 3.2 at week 24. Conclusions: Indigo naturalis oil extract appeared to improve nail psoriasis. Although preliminary, these results indicate that it could provide a novel therapeutic option for nail psoriasis, a disease notoriously difficult to treat.

Peritoneal fibrosis (PF), including simple sclerosis and encapsulating peritoneal sclerosis (EPS), is a serious complication in patients on long-term peritoneal dialysis. Tamoxifen has successfully been used in treating EPS; however, the mechanism of tamoxifen in treating EPS fibrosis disorders remains unclear. This study demonstrates a possible antifibrotic mechanism of tamoxifen. A bleach-induced PF rat model was applied as the in vivo treatment target. Tamoxifen was intraperitoneally injected daily to treat PF. The PF scores and thickness of the submesothelial zone over the liver surface were measured as indicators for the severity of PF. Human peritoneal mesothelial cells (HPMC) were used as an in vitro model to test the antifibrotic effect of tamoxifen. Gene expressions of transforming growth factors-β (TGF-β), connective tissue growth factor (CTGF) and collagen were investigated using quantitative polymerase chain reactions. In HPMC, tamoxifen showed paradoxical effects between collagen I and TGF-β. Tamoxifen also inhibited TGF-β-induced collagen and CTGF. The possible antifibrotic effect of tamoxifen is through inhibiting CTGF to block collagen synthesis, although it enhances TGF-β which increases fibrosis. These results provide a possible molecular mechanism for tamoxifen.

Patients with end-stage renal disease (ESRD) who are on hemodialysis have high risk of vascular diseases. Our study sought to examine whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin type 1 receptor blockers (ARBs) could reduce the frequencies of cardiovascular and cerebrovascular events in patients receiving hemodialysis using the medication possession ratio (MPR) method of analysis. This retrospective cohort study identified cases of ESRD with dialysis from the National Health Insurance Research Database between 1999 and 2006, and used Cox-regression methods to evaluate risk of poor outcomes. Primary outcomes, including death from any cause, and secondary outcomes, including admission for stroke, myocardial infarction, and heart failure, were examined. Compared to the nonuser group, the adjusted HRs for mortality of the nonadherence group and the adherence group were 0.81 (95% CI: 0.76–0.86) and 0.98 (95% CI: 0.86–1.13), respectively. Cardiovascular events were more frequent in patients with ESRD receiving ACEIs /ARBs than in nonusers. Compared with nonusers, the hazard of secondary outcome significantly increased in the nonadherence group or adherence group in 10 years follow-up. Compared with patients with diabetes or chronic kidney disease, patients on hemodialysis may not experience the same cardiovascular and cerebrovascular benefits from ACEIs/ARBs use.

Introduction TMTP1 (NVVRQ) is a novel tumor-homing peptide, which specifically targets tumor metastases, even at the early stage of occult metastasis foci. Fusing TMTP1 to therapeutic peptides or proteins can increase its anti-cancer efficacy both in vivo and in vitro. Here, we labeled TMTP1 with 99m Tc to evaluate its targeting properties in an ovarian cancer xenograft tumor mouse model and a gastric cancer xenograft mouse model. Methods The invasion ability of SKOV3 and highly metastatic SKOV3.ip cell lines were performed by the Transwell Invasion Assays, and then Rhodamine-TMTP1 was used to detect its affinity to these two cells. Using the co-ligand ethylenediamine- N , N ′-diacetic acid (EDDA) and the bifunctional chelator 6-hydrazinonicotinic acid (HYNIC), the TMTP1 peptide was labeled with 99m Tc. A cell-binding assay was performed by incubating cancer cells with 99m Tc-HYNIC-TMTP1 with or without an excess dose of cold HYNIC-TMTP1. To evaluate the probe in vivo, nude mice bearing SKOV3, SKOV3.ip and MNK-45 tumor cells were established and subjected to SPECT imaging after injection with 99m Tc-HYNIC-TMTP1. Ex vivo γ-counting of dissected tissues from the mice was used to evaluate its biodistribution. Results 99m Tc-HYNIC-TMTP1 was successfully synthesized. The radiotracer also exhibited high hydrophilicity and excellent stability in vitro and in vivo. It has strong affinity to highly metastatic cancer cell lines but not to poorly metastatic cell lines. After mice were injected with 99m Tc-HYNIC-TMTP1, non-invasive SPECT imaging detected SKOV3.ip and MNK-45 xenograft tumors but not SKOV3 xenograft tumors. This result can be inhibited by excess HYNIC-TMTP1. The uptake of 99m Tc-HYNIC-TMTP1 in SKOV3.ip xenograft tumors was 0.182±0.017% ID/g at 2h p.i. with high renal uptake (74.32±15.05% ID/g at 2h p.i.). Conclusion 99m Tc-HYNIC-TMTP1 biodistribution and SPECT imaging demonstrated its ability to target highly metastatic tumors. Therefore, metastasis can be non-invasively investigated by SPECT imaging using 99m Tc-HYNIC-TMTP1. Meanwhile, this radiotracer has some shortages in the low % ID/g of tumors and high accumulation in the kidney.

Electroencephalogram-based emotion recognition (EEG-ER) has received increasing attention in the fields of health care, affective computing, and brain-computer interface (BCI). However, satisfactory ER performance within a bi-dimensional and non-discrete emotional space using single-trial EEG data remains a challenging task. To address this issue, we propose a three-layer scheme for single-trial EEG-ER. In the first layer, a set of spectral powers of different EEG frequency bands are extracted from multi-channel single-trial EEG signals. In the second layer, the kernel Fisher’s discriminant analysis method is applied to further extract features with better discrimination ability from the EEG spectral powers. The feature vector produced by layer 2 is called a kernel Fisher’s emotion pattern (KFEP), and is sent into layer 3 for further classification where the proposed imbalanced quasiconformal kernel support vector machine (IQK-SVM) serves as the emotion classifier. The outputs of the three layer EEG-ER system include labels of emotional valence and arousal. Furthermore, to collect effective training and testing datasets for the current EEG-ER system, we also use an emotion-induction paradigm in which a set of pictures selected from the International Affective Picture System (IAPS) are employed as emotion induction stimuli. The performance of the proposed three-layer solution is compared with that of other EEG spectral power-based features and emotion classifiers. Results on 10 healthy participants indicate that the proposed KFEP feature performs better than other spectral power features, and IQK-SVM outperforms traditional SVM in terms of the EEG-ER accuracy. Our findings also show that the proposed EEG-ER scheme achieves the highest classification accuracies of valence (82.68%) and arousal (84.79%) among all testing methods.

BackgroundPeritoneal calcification (PC) is a specific finding in patients undergoing peritoneal dialysis (PD), but its prevalence, risk factors, and impacts in PD patients remain unclear. The present study investigated these issues and provided information useful for the management of PC.MethodsThe study included 183 PD patients. The severity of PC was determined using abdominal computed tomography (CT), and we summed up all scores from slices obtained from the diaphragm to the pelvic floor normalized to body surface area. We analyzed the associations between PC and demographic and clinical characteristics, and between PC and levels of biomarkers, including C-reactive protein (CRP), osteoprotegrin and fetuin-A. The determinants of PC were examined using multiple regression analysis.ResultsPatients were categorized into group 1 (without PC, n = 133) and group 2 (with PC, n = 50). Group 2 patients showed different degrees of PC with a mean of 160±769 mm(2)/m(2). Group 1 patients had higher fetuin-A levels than group 2 patients (861±309 vs. 760±210 µg/mL; p = 0.021). The independent risk factors for the presence of PC included male gender, previous peritonitis, and PD adequacy (KT/V). Further analysis performed in group 2 patients showed that the dosage of vitamin D, serum levels of CRP, and dialysate calcium load were the independent determinants of PC. However, the presence of PC did not affect patients' technique survival, peritonitis incidence, or mortality in the mean follow up period of 28±12 months.ConclusionsThe presence and severity of PC were associated with inflammation, peritoneal KT/V, and mineral metabolism. The impact of PC on the outcomes of PD patients requires further study with a longer follow-up.

Purpose Diabetes mellitus (DM) is the most common cause of end-stage renal disease and is an important risk factor for morbidity and mortality after dialysis. However, glycemic control among such patients is difficult to assess. The present study examined glycemic control parameters and observed glucose variation after refilling different kinds of fresh dialysate in peritoneal dialysis (PD) patients. Methods A total of 25 DM PD patients were recruited, and continuous glucose monitoring system (CGMS) was applied to measure interstitial fluid (ISF) glucose levels at 5-min intervals for 3 days. Patients filled out diet and PD fluid exchange diaries. The records measured with CGMS were analyzed and correlated with other glycemic control parameters such as fructosamine, albumin-corrected fructosamine (AlbF), glycosylated hemoglobin (HbA1c), and glycated albumin levels. Results There were significant correlations between mean ISF glucose and fructosamine (r = 0.45, P

BACKGROUND: Reduced lean body mass (LBM) is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD) patients' outcomes and the factors related to increasing LBM are seldom reported. METHODS: We enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan-Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. RESULTS: Using the median LBM value (70% for men and 64% for women), patients were divided into group 1 (n = 52; low LBM) and group 2 (n = 51; high LBM). Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p

Studies addressing the association of metabolic syndrome and insulin resistance with the risks of incident chronic kidney disease (CKD) and the progression of renal function were either lacking or inconclusive.The aim of this study was to define the effect of metabolic syndrome and insulin resistance on the development of new CKD and the decline in renal function.A prospective cohort study was conducted at a tertiary university-based hospital in Taiwan.We studied a total of 1456 Asians 65 or older who were followed for an average of 3.15 yr. Within the cohort, we measured insulin resistance using the homeostasis model assessment formula in 652 nondiabetic participants.There were no interventions.We measured the prevalence and incidence of CKD and the annual decline of the estimated glomerular filtration rate.We found that the adjusted odds ratio for prevalent CKD in association with metabolic syndrome was 1.778 (95% confidence interval, 1.188 to 2.465), the hazard ratio for rapid decline in renal function was 1.042 (0.802-1.355), and the hazard ratio for incident CKD was 1.931 (1.175-3.174). With each one-unit increment of insulin resistance, the odds ratio of prevalent CKD and proteinuria were raised 1.312-fold (1.114 to 1.545) and 1.278-fold (1.098 to 1.488), respectively. Insulin resistance was not associated with incident CKD. Increment of insulin resistance per unit was associated with 1.16-fold (1.06 to 1.26) elevation in the hazard ratios of the decline in renal function.Metabolic syndrome predicts the risks of prevalent and incident CKD, whereas insulin resistance is associated with prevalent CKD and rapid decline in renal function in elderly individuals.

We documented a hyponatremic patient who developed imminent cardiac tamponade upon oral salt supplement. A 72-year-old diabetic woman had hemorrhagic stroke; pericardial effusion; and chronic kidney disease, stage IV. She developed hyponatremia (serum sodium level, 125 mmol/L), compatible with the syndrome of inappropriate antidiuretic hormone, and received oral salt supplement 9 g/d for 4 days. Shortness of breathing and increasing heart rate ensued, and the echocardiography found accumulation of pericardial effusion with signs of impending cardiac tamponade. Pig-tail drainage through pericardiocentesis was done, and the vital signs were stabilized. We found the production of pericardial effusion increased from 100 to 220 mL/d after oral salt supplement at 3 g/d was reassumed. We discuss the relationship between serum sodium levels, the dose of salt supplement and the accumulation of pericardial effusion.

All four mammalian Notch proteins interact with a single DNA-binding protein (RBP-jkappa), yet they are not equivalent in activating target genes. Parallel assays of three Notch-responsive promoters in several cell lines revealed that relative activation strength is dependent on protein module and promoter context more than the cellular context. Each Notch protein reads binding site orientation and distribution on the promoter differently; Notch1 performs extremely well on paired sites, and Notch3 prefers single sites in conjunction with a proximal zinc finger transcription factor. Although head-head sites can elicit a Notch response on their own, use of CBS (CSL binding site) in tail-tail orientation is context-dependent. Bias for specific DNA elements is achieved by interplay between the N-terminal RAM (RBP-jkappa-associated molecule/ankyrin region), which interprets CBS proximity and orientation, and the C-terminal transactivation domain that interacts specifically with the transcription machinery or nearby factors. To confirm the prediction that modular design underscores the evolution of functional divergence between Notch proteins, we generated a synthetic Notch protein (Notch1 ankyrin with Notch3 transactivation domain) that displayed superior signaling strength on the hes5 promoter. Consistent with the prediction that "preferred" targets (Hes1) should respond faster and at lower Notch concentration than other targets, we showed that Hes5-GFP was extinguished fast and recovered slowly, whereas Hes1-GFP was inhibited late and recovered quickly after a pulse of DAPT in metanephroi cultures.

Background In the general population, metabolic syndrome (MetS) is correlated with visceral fat and a risk factor for cardiovascular disease (CVD); however, little is known about the significance of abdominal fat and its association with inflammation and medication use in peritoneal dialysis (PD) patients. We investigated the relationship of visceral fat area (VFA) with C-reactive protein (CRP) levels and medication use in PD patients and followed their clinical outcomes. Methods In a prospective study from February 2009 to February 2012, we assessed diabetes mellitus (DM) status, clinical and PD-associated characteristics, medication use, CRP levels, components of MetS, and VFA in 183 PD patients. These patients were categorized into 3 groups based on MetS and DM status: non-MetS (group 1, n = 73), MetS (group 2, n = 65), and DM (group 3, n = 45). VFA was evaluated by computed tomography (CT) and corrected for body mass index (BMI). Results Patients in group 1 had smaller VFAs than patients in groups 2 and 3 (3.2 ± 1.8, 4.6 ± 1.9, and 4.9 ± 2.0 cm2/[kg/m2], respectively, P P Conclusion This study showed that VFA and MetS are associated with CRP levels but cannot predict survival in PD patients without DM. The complex relationship of nutritional parameters to VFA and MetS may explain these results. The type of antihypertensive medication used was also associated with the VFA. The mechanisms behind these findings warrant further investigation.