In recent years, several studies have reported monocyte lymphocyte ratio (MLR) to predict prognosis in various tumors. Our study was performed to evaluate the association between preoperative MLR between prognostic variables in urothelial carcinoma patients. Systematic literature search was conducted in PubMed, Embase, Web of science. The correlation between preoperative MLR and overall survival (OS), cancer specific survival (CSS), disease free survival (DFS)/relapse free survival (RFS), progression free survival(PFS) was evaluated in urothelial carcinoma patients. Meanwhile, the association between MLR and clinicopathological characteristics was assessed. Finally, 12 comparative studies comprising a total of 6209 patients were included for pooled analysis. The hazard ratios (HRs), odds ratios (ORs)and 95% confidence intervals (CIs) were further analyzed as effect measures. The pooled results demonstrated that elevated preoperative MLR indicated unfavorable OS (HR = 1.29, 95%CI = 1.18-1.39, I2 = 33.6%), DFS/RFS (HR = 1.42, 95%CI = 1.30-1.55, I2 = 0.0%) and CSS (HR = 1.41, 95%CI = 1.29-1.52, I2 = 0.0%). Moreover, the pooled results also suggested that elevated preoperative MLR was correlated with high tumor stage (OR = 1.22, 95%CI = 1.07-1.37, I2 = 0.0%) in urothelial carcinoma patients. No significant association was found between preoperative MLR and PFS in upper urinary tract urothelial carcinoma (UUTUC) patients. Collectively, elevated preoperative MLR predicted poor prognosis in urothelial carcinoma and have the potential to be a feasible and cost-effective prognostic predictor for management of urothelial carcinoma.

The prognosis of colorectal cancer (CRC) is largely dependent on the early detection of hepatic metastases. With the advantages of nonradioactivity and the availability of multiple scanning sequences, the efficacy of magnetic resonance imaging (MRI) in the detection of colorectal liver metastases (CRLM) is not yet clear. We performed this meta-analysis to address this issue. PubMed, Embase, and the Cochrane Library were searched for studies reporting diagnostic performance of MRI for CRLM. Descriptive and quantitative data were extracted. The study quality was evaluated for the identified studies and a random effects model was used to determine the integrated diagnosis estimation. Meta-regression and subgroup analyses were implemented to investigate the potential contributors to heterogeneity. As a result, seventeen studies were included for analysis (from the year 1996 to 2018), comprising 1121 patients with a total of 3279 liver lesions. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.90 (95% confidence intervals (CI): 0.81-0.95), 0.88 (0.80-0.92), and 62.19 (23.71-163.13), respectively. The overall weighted area under the curve was 0.94 (0.92-0.96). Using two or more imaging planes and a quantitative/semiquantitative interpretation method showed higher diagnostic performance, although only the latter demonstrated statistical significance (P < 0.05). Advanced scanning sequences with DWI and liver-specific contrast media tended to increase the sensitivity for CRLM detection. We therefore concluded that contemporary MRI has high sensitivity and specificity for screening CRLM, especially for those with advanced scanning sequences. Using two or more imaging planes and adopting a quantitative/semiquantitative imaging interpretation may further improve diagnosis. However, the MRI results should be interpreted with caution because of substantial heterogeneity among studies.

The effect of pre-operative renal insufficiency on urothelial carcinoma (UC) prognosis has been investigated by numerous studies. While the majority report worse UC outcomes in patients with renal insufficiency, the results between the studies differed wildly. To enable us to better estimate the prognostic value of renal insufficiency on UC, we performed a systematic review and meta-analysis based on the published literature. A total of 16 studies which involved 5,232 patients with UC, investigated the relationship between pre-operative renal insufficiency and disease prognosis. Estimates of combined hazard ratio (HR) for bladder urothelial carcinoma recurrence, cancer-specific survival (CSS) and overall survival (OS) were 1.65 (95% CI, 1.11-2.19), 1.59 (95% CI, 1.14-2.05) and 1.45 (95% CI, 1.19-1.71), respectively; and for upper urinary tract urothelial carcinoma recurrence, CSS and OS were 2.27 (95% CI, 1.42-3.12), 1.02 (95% CI, 0.47-1.57) and 1.52 (95% CI, 1.05-1.99), respectively. Our results indicate that UC patients with pre-operative renal insufficiency tend to have higher recurrence rates and poorer survival compared to those with clinically normal renal function, thus renal function should be closely monitored in these patients. The impact of intervention for renal insufficiency on the prognosis of UC needs to be further studied.

Inconsistent findings have reported on the inflammatory potential of diet and cardiovascular disease (CVD) and mortality risk. The aim of this meta-analysis was to investigate the association between the inflammatory potential of diet as estimated by the dietary inflammatory index (DII) score and CVD or mortality risk in the general population. A comprehensive literature search was conducted in PubMed and Embase databases through February 2017. All prospective observational studies assessing the association of inflammatory potential of diet as estimated by the DII score with CVD and all-cause, cancer-related, cardiovascular mortality risk were included. Nine prospective studies enrolling 134,067 subjects were identified. Meta-analyses showed that individuals with the highest category of DII (maximal pro-inflammatory) was associated with increased risk of all-cause mortality (hazard risk [HR] 1.22; 95% confidence interval [CI] 1.06-1.41), cardiovascular mortality (RR 1.24; 95% CI 1.01-1.51), cancer-related mortality (RR 1.28; 95% CI 1.04-1.58), and CVD (RR 1.32; 95% CI 1.09-1.60) than the lowest DII score. More pro-inflammatory diets, as estimated by the higher DII score are independently associated with an increased risk of all-cause, cardiovascular, cancer-related mortality, and CVD in the general population, highlighting low inflammatory potential diet may reduce mortality and CVD risk.

Circular RNAs (circRNAs), a new class of regulatory noncoding RNAs, play important roles in human diseases. While a growing number of circRNAs have been characterized with biological functions, it is necessary to integrate all the information to facilitate studies on circRNA functions and regulatory networks in human diseases. Circ2Disease database contains 273 manually curated associations between 237 circRNAs and 54 human diseases with strong experimental evidence from 120 studies. Each association includes circRNA name, disease name, expression pattern, experimental method, a brief functional description of the circRNA-disease relationship, and other detailed information. The experimentally validated miRNAs that may be 'sponged up' by these circRNAs and their validated targets were also integrated to form a comprehensive regulatory network. Circ2Disease provides a user-friendly interface to browse, search, analyze regulatory network and download data. With the rapidly increasing interest in circRNAs, Circ2Disease will significantly improve our understanding of circRNA deregulation in diseases and is a useful resource for studying posttranscriptional regulatory roles of circRNAs in human diseases.

Periodontal disease is a common oral health problem in the elderly population. The prevalence varied substantially due to absence of a universal diagnostic criteria. We conducted a systematic review to identify the epidemiological characteristics of periodontal diseases among Chinese elderly people. A total of 19 articles were included. The pooled detection rates for three indicators, including bleeding on probing (BOP), pocket depth (PD) and clinical attachment loss (CAL), were 53.9% (95% CI: 43.8-63.9%), 57.0% (50.8-63.2%), and 70.1% (65.4-74.8%), respectively. No significant differences in these indicators between urban and rural population. When stratified by gender, BOP (+) detection rates did not show any differences, but the detection rates of PD ≥ 4 mm and CAL ≥ 4 mm were significantly higher in males than in females (59.3% [53.4-65.2%] versus 50.8% [43.5-58.0%], RRPD = 1.13 [1.01-1.26]; 73.8% [70.0-77.7%] versus 65.2% [60.2-70.2%], RRCAL = 1.21 [1.11-1.32]). No statistically significant differences were observed between CAL ≥ 4 mm and PD ≥ 4 mm (RR = 1.12, [0.83-1.50]). A geographical map based on available data during 1987-2015 showed wide variations of periodontal disease across the mainland China. Some factors such as heterogeneity of case definitions, no specific diagnosis of periodontitis, and variable quality of the included studies could affect the final results. Hence, further high-quality epidemiological studies with standardized diagnostic criteria are needed.

Early childhood caries (ECC) is the most common chronic disease in young children. A reliable predictive model for ECC prevalence is needed in China as a decision supportive tool for planning health resources. In this study, we first established the autoregressive integrated moving average (ARIMA) model and grey predictive model (GM) based on the estimated national prevalence of ECC with meta-analysis from the published articles. The pooled data from 1988 to 2010 were used to establish the model, while the data from 2011 to 2013 were used to validate the models. The fitting and prediction accuracy of the two models were evaluated by mean absolute error (MAE) and mean absolute percentage error (MAPE). Then, we forecasted the annual prevalence from 2014 to 2018, which was 55.8%, 53.5%, 54.0%, 52.9%, 51.2% by ARIMA model and 52.8%, 52.0%, 51.2%, 50.4%, 49.6% by GM. The declining trend in ECC prevalence may be attributed to the socioeconomic developments and improved public health service in China. In conclusion, both ARIMA and GM models can be well applied to forecast and analyze the trend of ECC; the fitting and testing errors generated by the ARIMA model were lower than those obtained from GM.

Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by enteroviruses. We analyzed the pathogenic characteristics of HFMD in Shaanxi province, China, during 2010-2016. Clinical samples were collected from HFMD cases. Real-time PCR and RT-PCR were used to identify the enterovirus(EVs) serotypes. Viral RNA sequences were amplified using RT-PCR and compared by phylogenetic analysis. Descriptive epidemiological methods were used to analyze. A total of 16,832 HFMD positive cases were confirmed in the laboratory. EV-A71 and CV-A16 were the main pathogens in 2010. EV-A71 was the dominant pathogen in the periods of 2011 to 2012 and 2014, 2016. In 2013 and 2015, other EVs increased greatly, in which CV-A6 was the predominant pathogen. EV-A71 was more frequently detected in deaths and severe cases. Phylogenetic analysis revealed that EV-A71 belonged to the C4a evolution branch of C4 sub-genotype and CV-A16 belonged to the B1a or B1b evolution branch of B1 sub-genotype, whereas CV-A6 strains were assigned to D2 or D3 sub-genotype. The pathogen spectrum of HFMD has changed in 7 years, and the major serotypes EV-A71, CV- A16 and CV- A6 alternated or co-circulated. Long-term surveillance and research of EVs should be strengthened for the prevention and control of HFMD.

Under hypoxic conditions, the expression of Vitreoscilla hemoglobin (VHb) in plants is proposed to increase the productivity of certain oxygen-requiring metabolic pathways by promoting the delivery of oxygen. Tropane alkaloids (TAs) are a class of important plant secondary metabolites with significant medicinal value; the final step in their biosynthesis requires oxygen. Whether heterologous expression of VHb, especially in different subcellular compartments, can accelerate the accumulation of TAs is not known. Herein, the effect of heterologous expression of VHb in different subcellular locations on the TA profile of H. niger hairy roots was investigated. The targeted expression of VHb in the plastids (using pVHb-RecA construct), led to the accumulation of 197.68 μg/g hyoscyamine in the transgenic H. niger hairy roots, which was 1.25-fold of the content present in the lines in which VHb expression was not targeted, and 3.66-fold of that present in the wild type (WT) lines. The content of scopolamine was increased by 2.20- and 4.70-fold in the pVHb-RecA transgenic lines compared to that in the VHb transgenic and WT lines. Our results demonstrate that VHb could stimulate the accumulation of TAs in the transgenic H. niger hairy roots. Quantitative RT-PCR analysis revealed that the expression of key genes involved in TA biosynthesis increased significantly in the VHb transgenic lines. We present the first description of a highly efficient strategy to increase TA content in H. niger. Moreover, our results also shed light on how the production of desired metabolites can be efficiently enhanced by using more accurate and appropriate genetic engineering strategies.

The discovery of fall armyworm, a native of the Western Hemisphere, in western Africa in 2016 was rapidly followed by detections throughout sub-Saharan Africa, India, and most recently southeastern Asia. This moth pest has a broad host range that threatens such important crops as corn, rice, millet, and sorghum, creating concern for its potential impact on agriculture in the Eastern Hemisphere. Although genetic data suggest populations sampled in Africa and India originate from a recent common source, it is not known whether this is the case for populations in southeastern Asia, nor whether the subgroup with a preference for rice and millet is present in the region. This study found through comparisons of genetic markers that the fall armyworm from Myanmar and southern China are closely related to those from Africa and India, suggesting a common origin for these geographically distant populations. The results are consistent with a single recent introduction into the Eastern Hemisphere followed by rapid dispersion. The molecular similarities include discrepancies between the genetic markers that brings into question whether the subpopulation most likely to be a threat to rice and millet is present in significant numbers in Asia.

A novel strain LTYR-11ZT that exhibited multiple plant growth promoting (PGP) traits was isolated from the surface-sterilized leaves of Alhagi sparsifolia Shap. (Leguminosae), which reprsents one of the top drought tolerant plants in north-west China. Phylogenetic analysis of 16S rRNA gene sequences and multilocus sequence analysis based on partial sequences of atpD, gyrB, infB and rpoB genes revealed that strain LTYR-11ZT was a member of the genus Pantoea, with Pantoea theicola NBRC 110557T and Pantoea intestinalis DSM 28113T as the closest phylogenetic relatives. The results of DNA-DNA hybridization, phenotypic tests and fatty acid analysis confirmed that strain LTYR-11ZT represents a novel species of the genus Pantoea, for which we propose the name Pantoea alhagi sp. nov. Confocal microscopy observation revealed that strain LTYR-11ZT effectively colonizes the rhizoplane of both Arabidopsis and wheat. Strain LTYR-11ZT was able to promote the growth of wheat enhancing its resistance to drought stress. Strain LTYR-11ZT led to increased accumulation of soluble sugars, decreased accumulation of proline and malondialdehyde (MDA), and decreased degradation of chlorophyll in leaves of drought-stressed wheat. Our findings will contribute to the development of a novel biotechnological agent to improve the adaptation of crop plants to drought in arid ecosystems.

Understanding the population structure and movements of the invasive fall armyworm (FAW, Spodoptera frugiperda) is important as it can help mitigate crop damage, and highlight areas at risk of outbreaks or evolving insecticide resistance. Determining population structure in invasive FAW has been a challenge due to genetic mutations affecting the markers traditionally used for strain and haplotype identification; mitochondrial cytochrome oxidase I (COIB) and the Z-chromosome-linked Triosephosphate isomerase (Tpi). Here, we compare the results from COIB and Tpi markers with highly variable repeat regions (microsatellites) to improve our understanding of FAW population structure in Africa. There was very limited genetic diversity using the COIB marker, whereas using the TpiI4 marker there was greater diversity that showed very little evidence of genetic structuring between FAW populations across Africa. There was greater genetic diversity identified using microsatellites, and this revealed a largely panmictic population of FAW alongside some evidence of genetic structuring between countries. It is hypothesised here that FAW are using long-distance flight and prevailing winds to frequently move throughout Africa leading to population mixing. These approaches combined provide important evidence that genetic mixing between invasive FAW populations may be more common than previously reported.

Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine inhibits expressions of CAR and its target genes CYP2B6 and CYP3A4. Furthermore, berberine enhances DNA methylation level in whole genome but reduces that in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condition. These results indicated that the antiproliferation of berberine might be mediated by the unique epigenetic modifying mechanism of CAR metabolic pathway, suggesting that berberine is a promising candidate in anticancer adjuvant chemotherapy, due to its distinct pharmacological properties in clinic.

Salvia miltiorrhiza Bunge, which contains tanshinones and phenolic acids as major classes of bioactive components, is one of the most widely used herbs in traditional Chinese medicine. Production of tanshinones and phenolic acids is enhanced by methyl jasmonate (MeJA). Transcription factor MYC2 is the switch of jasmontes signaling in plants. Here, we focused on two novel JA-inducible genes in S. miltiorrhiza, designated as SmMYC2a and SmMYC2b, which were localized in the nucleus. SmMYC2a and SmMYC2b were also discovered to interact with SmJAZ1 and SmJAZ2, implying that the two MYC2s might function as direct targets of JAZ proteins. Ectopic RNA interference (RNAi)-mediated knockdown experiments suggested that SmMYC2a/b affected multiple genes in tanshinone and phenolic acid biosynthetic pathway. Besides, the accumulation of tanshinones and phenolic acids was impaired by the loss of function in SmMYC2a/b. Meanwhile, SmMYC2a could bind with an E-box motif within SmHCT6 and SmCYP98A14 promoters, while SmMYC2b bound with an E-box motif within SmCYP98A14 promoter, through which the regulation of phenolic acid biosynthetic pathway might achieve. Together, these results suggest that SmMYC2a and SmMYC2b are JAZ-interacting transcription factors that positively regulate the biosynthesis of tanshinones and Sal B with similar but irreplaceable effects.

Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis, a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines.

Photosensitizer protoporphyrin IX (PpIX) fluorescence, intracellular localization and cell response to photodynamic therapy (PDT) were analyzed in MCF10A normal breast epithelial cells and a panel of human breast cancer cells including estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) positive and triple negative breast cancer (TNBC) cells after treatment with PpIX precursor aminolevulinic acid (ALA). Although PpIX fluorescence was heterogeneous in different cells, TNBC cells showed significantly lower PpIX level than MCF10A and ER- or HER2-positive cells. PpIX fluorescence in TNBC cells also had much less mitochondrial localization than other cells. There was an inverse correlation between PpIX fluorescence and cell viability after PDT. Breast cancer cells with the highest PpIX fluorescence were the most sensitive to ALA-PDT and TNBC cells with the lowest PpIX level were resistant to PDT. Treatment of TNBC cells with ABCG2 transporter inhibitor Ko143 significantly increased ALA-PpIX fluorescence, enhanced PpIX mitochondrial accumulation and sensitized cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. These results demonstrate that enhanced ABCG2 activity renders TNBC cell resistance to ALA-PDT and inhibiting ABCG2 transporter is a promising approach for targeting TNBC with ALA-based modality.

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with impact on axial skeleton, peripheral joints and enthuses, and it may result in severe disabilities of those parts. Tumor necrosis factor-α (TNF-α) inhibitors are considered as an effective treatment for patients with active AS. In this study, we conducted a network meta-analysis to compare the clinical outcomes of active AS patients treated with TNF-α inhibitors. Randomized controlled trials (RCTs) evaluating the efficacy and safety of TNF-α inhibitors were retrieved in literature search and selected for meta-analysis. Changes in ASAS20 response, ASAS40 response and BASDAI 50% response were regarded as efficacy outcomes; serious adverse events (SAE) and all cause withdrawals were regarded as safety outcomes. Both traditional pairwise meta-analysis and network meta-analysis were performed. The results showed that adalimumab and infliximab had better clinical outcomes. Infliximab consistently appeared to be the most effective TNF-α inhibitors with a high risk of adverse events for patients with active AS; meanwhile, adalimumab ranked highest with respect to adverse effects with efficacy secondary to infliximab. As a result, we were unable to conclude the optimal TNF-α inhibitor and this issue should be solved by future researchers.

The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens.

Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice. Diabetic Mst1 transgenic mice exhibited impaired cardiac microvessel integrity and decreased cardiac function. Mst1 overexpression deceased CMECs autophagy as evidenced by decreased LC3 expression and enhanced protein aggregation when subjected to high glucose culture. Mst1 knockout improved cardiac microvessel integrity and enhanced cardiac functions in diabetic mice. Mst1 knockdown up-regulated autophagy as indicated by more typical autophagosomes and increased LC3 expression in CMECs subjected to high glucose cultures. Mst1 knockdown also promoted autophagic flux in the presence of bafilomycin A1. Mst1 overexpression increased CMECs apoptosis, whereas Mst1 knockout decreased CMECs apoptosis. Sirt1 knockout abolished the effects of Mst1 overexpression in cardiac microvascular injury and cardiac dysfunction. In conclusion, Mst1 knockout preserved cardiac microvessel integrity and improved cardiac functions in diabetic mice. Mst1 decreased sirt1 activity, inhibited autophagy and enhanced apoptosis in CMECs, thus participating in the pathogenesis of diabetic coronary microvascular dysfunction.

Calcium disequilibrium is extensively involved in oxidative stress-induced neuronal injury. Although Homer1a is known to regulate several neuronal calcium pathways, its effects on, or its exact relationship with, oxidative stress-induced neuronal injury has not yet been fully elucidated. We found that Homer1a protected HT-22 cells from glutamate-induced oxidative stress injury by inhibiting final-phase intracellular calcium overload and mitochondrial oxidative stress. In these cells, stromal interactive molecule 1 (STIM1) puncta, but not the protein level, was significantly increased after glutamate treatment. Store-operated calcium entry (SOCE) inhibitors and cells in which a key component of SOCE (STIM1) was knocked out were used as glutamate-induced oxidative stress injury models. Both models demonstrated significant improvement of HT-22 cell survival after glutamate treatment. Additionally, increased Homer1a protein levels significantly inhibited SOCE and decreased the association of STIM1-Orai1 triggered by glutamate. These results suggest that up-regulation of Homer1a can protect HT-22 cells from glutamate-induced oxidative injury by disrupting the STIM1-Oria1 association, and then by inhibiting the SOCE-mediated final-phrase calcium overload. Thus, regulation of Homer1a, either alone or in conjunction with SOCE inhibition, may serve as key therapeutic interventional targets for neurological diseases in which oxidative stress is involved in the etiology or progression of the disease.