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Background: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. Methods: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. Results: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). Conclusions: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients. [ABSTRACT FROM AUTHOR]

Background: Necroptosis of macrophages is a necessary element in reinforcing intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that sparks macrophage necroptosis is still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor expressed broadly on monocytes/macrophages. The influence of TREM-1 on the destiny of macrophages in ALI requires further investigation. Methods: TREM-1 decoy receptor LR12 was used to evaluate whether the TREM-1 activation induced necroptosis of macrophages in lipopolysaccharide (LPS)-induced ALI in mice. Then we used an agonist anti-TREM-1 Ab (Mab1187) to activate TREM-1 in vitro. Macrophages were treated with GSK872 (a RIPK3 inhibitor), Mdivi-1 (a DRP1 inhibitor), or Rapamycin (an mTOR inhibitor) to investigate whether TREM-1 could induce necroptosis in macrophages, and the mechanism of this process. Results: We first observed that the blockade of TREM-1 attenuated alveolar macrophage (AlvMs) necroptosis in mice with LPS-induced ALI. In vitro, TREM-1 activation induced necroptosis of macrophages. mTOR has been previously linked to macrophage polarization and migration. We discovered that mTOR had a previously unrecognized function in modulating TREM-1-mediated mitochondrial fission, mitophagy, and necroptosis. Moreover, TREM-1 activation promoted DRP1Ser616 phosphorylation through mTOR signaling, which in turn caused surplus mitochondrial fission-mediated necroptosis of macrophages, consequently exacerbating ALI. Conclusion: In this study, we reported that TREM-1 acted as a necroptotic stimulus of AlvMs, fueling inflammation and aggravating ALI. We also provided compelling evidence suggesting that mTOR-dependent mitochondrial fission is the underpinning of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future. [ABSTRACT FROM AUTHOR]

Background: Ornamental trees with seasonally-dependent leaf color, such as Acer palmatum, have gained worldwide popularity. Leaf color is a main determinant of the ornamental and economic value of A. palmatum. However, the molecular mechanisms responsible for leaf color changes remain unclear. Results: We chose A. palmatum cultivars with yellow ('Jinling Huangfeng') and red ('Jinling Danfeng') leaves as the ideal material for studying the complex metabolic networks responsible for variations in leaf coloration. The 24 libraries obtained from four different time points in the growth of 'Jinling Huangfeng' and 'Jinling Danfeng' was subjected to Illumina high-throughput sequencing. We observed that the difference in cyanidin and delphinidin content is the primary reason behind the varying coloration of the leaves. Transcriptomic analyses revealed 225,684 unigenes, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes (DEGs) confirmed that they were involved in 'anthocyanin biosynthesis.' Eighteen structural genes involved in anthocyanin biosynthesis were thought to be related to anthocyanin accumulation, whereas 46 MYBs, 33 basic helix-loop-helixs (bHLHs), and 29 WD40s were presumed to be involved in regulating anthocyanin biosynthesis. Based on weighted gene co-expression network analysis (WGCNA), three candidate genes (ApRHOMBOID, ApMAPK, and ApUNE10) were screened in the significant association module with a correlation coefficient (r2) of 0.86. Conclusion: In this study, the leaf color changes of two A. palmatum genotypes were analyzed. These findings provide novel insights into variations in leaf coloration and suggest pathways for targeted genetic improvements in A. palmatum. [ABSTRACT FROM AUTHOR]

Research question: What influence does seven days of oestrogen administration versus fourteen days have on the reproductive outcomes of frozen-thawed embryo transfer (FET) in programmed endometrial preparation cycles? Design: In a retrospective study, conducted at a university-affiliated tertiary hospital, a total of 2628 infertile patients (4142 FET cycles) were divided into one of two groups between January 2014 and December 2020: group A (n = 1406, seven days of oestrogen before progesterone (P4) supplementation) and group B (n = 2716, fourteen days of oestrogen before P4 supplementation). The primary outcome was cumulative live birth rate (CLBR). Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Results: No significant difference in CLBR was observed when comparing seven versus fourteen days of oestrogen administration before starting P4 supplementation (47.6% vs. 48.8%, P = 0.537). Furthermore, multivariable logistic regression analysis revealed that oestrogen administration in programmed FET cycles (7 days vs. 14 days) was not significantly associated with CLBR (OR 1.04, 95% CI 0.89–1.23). The risks of maternal and neonatal complications were comparable between the two groups. Conclusions: Variation in the duration of oestradiol supplementation before P4 initiation does not impact FET reproductive outcomes. For infertile women who desire to conceive as soon as feasible, short (seven days) oestrogen administration in a programmed FET cycle may be a suitable alternative. [ABSTRACT FROM AUTHOR]

Background: Precocious puberty is frequently associated with obesity, which will lead to long-term effects, especially on growth and reproduction. However, the effect of precocious puberty on children's neurodevelopment is still unknown. Objectives: Here we evaluated the effect of High fat diet (HFD)-induced precocious puberty on neurodevelopment and behaviors of animals. Methods: Ovaries sections were stained with hematoxylin–eosin (H&E) using standard techniques. Behavioral tests included elevated plus maze (EPM), open field exploration, Y-Maze, marble burying test, and novelty- suppressed feeding. The expression of genes related to puberty and neural development was detected by immunohistochemistry and Western blot. Results: Our results showed HFD-induced precocious puberty increased the risk-taking behavior and decreased memory of mice. The content of Tyrosine hydroxylase (TH) and Arginine vasopressin (AVP) in hypothalamus were higher in HFD group than control group. Although the recovery of normal diet will gradually restore the body fat and other physiological index of mice, the anxiety increases in adult mice, and the memory is also damaged. Conclusions: These findings describe the sensitivity of mice brain to HFD-induced precocious puberty and the irrecoverability of neural damage caused by precocious puberty. Therefore, avoiding HFD in childhood is important to prevent precocious puberty and neurodevelopmental impairment in mice. [ABSTRACT FROM AUTHOR]

Background: Formin, a highly conserved multi-domain protein, interacts with microfilaments and microtubules. Although specifically expressed formin genes in anthers are potentially significant in research on male sterility and hybrid wheat breeding, similar reports in wheat, especially in thermo-sensitive genic male sterile (TGMS) wheat, remain elusive. Results: Herein, we systematically characterized the formin genes in TGMS wheat line BS366 named TaFormins (TaFHs) and predicted their functions in inducing stress response. In total, 25 TaFH genes were uncovered, majorly localized in 2A, 2B, and 2D chromosomes. According to the neighbor-joining (NJ) method, all TaFH proteins from wheat and other plants clustered in 6 sub-groups (A-F). The modeled 3D structures of TaFH1-A/B, TaFH2-A/B, TaFH3-A/B and TaFH3-B/D were validated. And different numbers of stress and hormone-responsive regulatory elements in their 1500 base pair promoter regions were contained in the TaFH genes copies. TaFHs had specific temporal and spatial expression characteristics, whereby TaFH1, TaFH4, and TaFH5 were expressed highly in the stamen of BS366. Besides, the accumulation of TaFHs was remarkably lower in a low-temperature sterile condition (Nanyang) than fertile condition (Beijing), particularly at the early stamen development stage. The pollen cytoskeleton of BS366 was abnormal in the three stages under sterile and fertile environments. Furthermore, under different stress levels, TaFHs expression could be induced by drought, salt, abscisic acid (ABA), salicylic acid (SA), methyl jasmonate (MeJA), indole-3-acetic acid (IAA), polyethylene glycol (PEG), and low temperature. Some miRNAs, including miR167, miR1120, and miR172, interacts with TaFH genes; thus, we constructed an interaction network between microRNAs, TaFHs, phytohormone responses, and distribution of cytoskeleton to reveal the regulatory association between upstream genes of TaFH family members and sterile. Conclusions: Collectively, this comprehensive analysis provides novel insights into TaFHs and miRNA resources for wheat breeding. These findings are, therefore, valuable in understanding the mechanism of TGMS fertility conversion in wheat. [ABSTRACT FROM AUTHOR]

Background: Postoperative infectious complications (ICs) after surgery for colorectal cancer (CRC) increase in-hospital deaths and decrease long-term survival. However, the methodology for IC preoperative and intraoperative risk assessment has not yet been established. We aimed to construct a risk model for IC after surgery for CRC. Methods: Between January 2016 and June 2020, a total of 593 patients who underwent curative surgery for CRC in Chengdu Second People's Hospital were enrolled. Preoperative and intraoperative factors were obtained retrospectively. The least absolute shrinkage and selection operator (LASSO) method was used to screen out risk factors for IC. Then, based on the results of LASSO regression analysis, multivariable logistic regression analysis was performed to establish the prediction model. Bootstraps with 300 resamples were performed for internal validation. The performance of the model was evaluated with its calibration and discrimination. The clinical usefulness was assessed by decision curve analysis (DCA). Results: A total of 95 (16.0%) patients developed ICs after surgery for CRC. Chronic pulmonary diseases, diabetes mellitus, preoperative and/or intraoperative blood transfusion, and longer operation time were independent risk factors for IC. A prediction model was constructed based on these factors. The concordance index (C-index) of the model was 0.761. The calibration curve of the model suggested great agreement. DCA showed that the model was clinically useful. Conclusion: Several risk factors for IC after surgery for CRC were identified. A prediction model generated by these risk factors may help in identifying patients who may benefit from perioperative optimization. [ABSTRACT FROM AUTHOR]

Background: A better comprehension of the redox status during the periparturient period may facilitate the development of management and nutritional solutions to prevent subclinical hyperketonemia (SCHK) and subclinical hypocalcemia (SCHC) in dairy goats. We aimed to evaluate the variation in the redox status of dairy goats with SCHK and SCHC during their periparturient periods. Guanzhong dairy goats (n = 30) were assigned to SCHK (n = 10), SCHC (n = 10), and healthy (HEAL, n = 10) groups based on their blood β-hydroxybutyrate (BHBA) and calcium (Ca) concentrations. Blood were withdrawn from goats every week from 3 weeks before the expected parturition date to 3 weeks post-kidding. On the same day, the body condition scores (BCS) were evaluated, and the milk yield was recorded for each goat. The metabolic profile parameters and the indicators of oxidative status were determined by using the standard biochemical techniques. Results: In comparison with the HEAL goats, SCHK and SCHC goats presented with a more dramatic decline of BCS post-kidding and a significant decrease in the milk yield at 2- and 3-weeks postpartum, ignoring the obvious increase at 1-week postpartum. The levels of non-esterified fatty acids (NEFA) peaked at parturition, exhibiting significantly higher levels from 1-week prepartum to the parturition day in the SCHK and SCHC groups. The malondialdehyde (MDA) concentration was increased in the SCHK goats from 1-week antepartum until 3-weeks postpartum, with its concentration being significantly higher in the SCHC goats at parturition. The hydrogen peroxide (H2O2) concentration was significantly lower in the SCHK and SCHC goats from 2-weeks antepartum to 1-week post-kidding. The total antioxidant capacity (T-AOC) and the superoxide dismutase (SOD) level were decreased at 1-week antepartum in the SCHK and SCHC goats, respectively. The glutathione peroxidase (GSH-Px) level was increased in the SCHK and SCHC goats during the early lactation period. Conclusions: The SCHK and SCHC goats exerted more efforts to maintain their redox homeostasis and to ensure the production performance than the HEAL goats during their periparturient period, probably owing to more intense fat mobilization and lipid peroxidation in the former. [ABSTRACT FROM AUTHOR]

Background: Glutathione S-transferase mu 3 (GSTM3) plays a crucial role in tumor progression in various cancers. However, the relationship between GSTM3 expression and the clinical prognosis of esophageal squamous cell carcinoma (ESCC) has not been studied to date. We aimed to characterize the role of GSTM3 in predicting postoperative prognosis of ESCC patients. Methods: In the retrospective study, GSTM3 mRNA levels in 184 ESCC tissues and matched 43 adjacent nontumorous tissues were measured by quantitative real-time PCR. GSTM3 protein levels in 247 ESCC tissues were measured by immunohistochemistry. Results: Downregulation of GSTM3 occurred in 62.8 % of primary ESCC tissues compared with their nontumor counterparts. Patients with low GSTM3 expression tended to exhibit an increased rate of poor differentiation in both the mRNA cohort (p = 0.024) and protein cohort (p = 0.004). In the mRNA cohort, low GSTM3 expression was associated with unfavorable 3-year disease-free survival (DFS) (39.2 % vs. 57.4 %) and 5-year DFS (26.8 % vs. 45.1 %) (p = 0.023). The result was confirmed in the protein cohort. Patients with low GSTM3 expression had unfavorable 3-year disease-free survival (DFS) (18.7 % vs. 33.5 %) and 5-year DFS (5.3 % vs. 30.5 %) (p = 0.006). Cox multivariate analysis revealed that GSTM3 expression was an independent prognostic factor. Conclusions: The findings of the present study provide evidence that GSTM3 may function as a tumor suppressor in ESCC and represents a potential novel prognostic biomarker for disease-free survival for resected ESCC patients. [ABSTRACT FROM AUTHOR]

Background: NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER (NRT1/PTR) family (NPF) members are essential transporters for many substrates in plants, including nitrate, hormones, peptides, and secondary metabolites. Here, we report the global characterization of NPF in the important oil crop Brassica napus, including that for phylogeny, gene/protein structures, duplications, and expression patterns. Results: A total of 199 B. napus (BnaNPFs) NPF-coding genes were identified. Phylogenetic analyses categorized these genes into 11 subfamilies, including three new ones. Sequence feature analysis revealed that members of each subfamily contain conserved gene and protein structures. Many hormone−/abiotic stress-responsive cis-acting elements and transcription factor binding sites were identified in BnaNPF promoter regions. Chromosome distribution analysis indicated that BnaNPFs within a subfamily tend to cluster on one chromosome. Syntenic relationship analysis showed that allotetraploid creation by its ancestors (Brassica rapa and Brassica oleracea) (57.89%) and small-scale duplication events (39.85%) contributed to rapid BnaNPF expansion in B. napus. A genome-wide spatiotemporal expression survey showed that NPF genes of each Arabidopsis and B. napus subfamily have preferential expression patterns across developmental stages, most of them are expressed in a few organs. RNA-seq analysis showed that many BnaNPFs (32.66%) have wide exogenous hormone-inductive profiles, suggesting important hormone-mediated patterns in diverse bioprocesses. Homologs in a clade or branch within a given subfamily have conserved organ/spatiotemporal and hormone-inductive profiles, indicating functional conservation during evolution. qRT-PCR-based comparative expression analysis of the 12 BnaNPFs in the NPF2–1 subfamily between high- and low-glucosinolate (GLS) content B. napus varieties revealed that homologs of AtNPF2.9 (BnaNPF2.12, BnaNPF2.13, and BnaNPF2.14), AtNPF2.10 (BnaNPF2.19 and BnaNPF2.20), and AtNPF2.11 (BnaNPF2.26 and BnaNPF2.28) might be involved in GLS transport. qRT-PCR further confirmed the hormone-responsive expression profiles of these putative GLS transporter genes. Conclusion: We identified 199 B. napus BnaNPFs; these were divided into 11 subfamilies. Allopolyploidy and small-scale duplication events contributed to the immense expansion of BnaNPFs in B. napus. The BnaNPFs had preferential expression patterns in different tissues/organs and wide hormone-induced expression profiles. Four BnaNPFs in the NPF2–1 subfamily may be involved in GLS transport. Our results provide an abundant gene resource for further functional analysis of BnaNPFs. [ABSTRACT FROM AUTHOR]

Background: The disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein (FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological functions of alternatively spliced isoforms remain elusive. In a previous study, we identified a new 140bp exon from the intron 9 of human FMR1 gene. In this study, we further examined the biological functions of this new exon and its underlying signaling pathways. Results: qRT-PCR results showed that this novel exon is commonly expressed in the peripheral blood of normal individuals. Comparative genomics showed that sequences paralogous to the 140 bp sequence only exist in the genomes of primates. To explore the biological functions of the new transcript, we constructed recombinant eukaryotic expression vectors and lentiviral overexpression vectors. Results showed that the spliced transcript encoded a truncated protein which was expressed mainly in the cell nucleus. Additionally, several genes, including the BEX1 gene involved in mGluR-LTP or mGluR-LTD signaling pathways were significantly influenced when the truncated FMRP was overexpressed. Conclusions: our work identified a new exon from amid intron 9 of human FMR1 gene with wide expression in normal healthy individuals, which emphasizes the notion that the AS of FMR1 gene is complex and may in a large part account for the multiple functions of FMRP. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease and has become a heavy economic and social burden due to its high prevalence and morbidity. The most effective strategy is that patients with DKD should be diagnosed and treated early. Preliminary studies showed that the Chinese herbal Tangshen Formula (TSF) may delay the progression of DKD, reducing microalbuminuria and macroalbuminuria and improving renal function. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of TSF in patients with DKD.Methods/design: This trial is a 13-center, randomized, double-blind, placebo-controlled study. A total of 632 participants will be randomized in a 1:1 ratio to an experiment group (TSF plus losartan) and a control group (placebo plus losartan). The trial cycle will last 24 weeks. The primary outcome will be the change in the urine microalbumin-creatinine ratio from baseline to week 24. The secondary outcome will be the change in the rate of progression to the clinical proteinuria period after intervention, the rate of urine microalbumin negative conversion, the rate of normal urinary microalbumin, the doubling rate of the baseline creatinine value and the glomerular filtration rate between the two groups. Safety in medication will also be evaluated.Discussion: We hypothesize that patients with type 2 diabetes in the early stage of DKD will benefit from TSF. If successful, this study will provide evidence-based recommendations for clinicians.Trial Registration: ClinicalTrials.gov, NCT03009864. Registered January 2017. [ABSTRACT FROM AUTHOR]

Background: Diabetic distal symmetric polyneuropathy (DSPN) is one of the most common microvascular complications of diabetes mellitus, and it has become a major public health problem worldwide because of its high and increasing prevalence, morbidity, and disability rate. The current medications for DSPN are not entirely satisfactory. Preliminary studies indicated that the Chinese herbal TangBi Formula may alleviate signs and symptoms and improve the velocity of nerve conduction in patients with DSPN. This study was designed to determine if Chinese herbal medicine used in combination with conventional treatment is more effective than conventional treatment alone.Methods/design: We are conducting a multicenter, placebo-controlled, double-blind, randomized, controlled clinical trial as a means of assessing the therapeutic effects of traditional Chinese medicine (TCM) treatment. A total of 188 patients will be randomized in a 1:1 ratio to a treatment group (TangBi Formula plus mecobalamin) and a control group (placebo plus mecobalamin). The test period lasts 6 months, during which all of the patients will be given standard medical care as recommended by established guidelines. The primary outcome will be development of differences in changes in clinical symptoms and signs in patients and changes in Michigan Diabetic Neuropathy Score (MDNS) between the two groups before and after treatment. The secondary outcome will be changes in nerve conduction velocity and in single clinical signs and symptoms. Safety assessments and adverse events will also be evaluated.Discussion: We postulate that patients with DSPN will benefit from therapy that includes TCM. If successful, this work will provide an evidence-based complementary therapeutic approach for treatment of DSPN.Trial Registration: ClinicalTrials.gov, NCT03010241 . Registered on 2 January 2017. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to present an accessible C-shaped partial stapled hemorrhoidopexy (C-PSH) in the treatment of grade IV hemorrhoids and to assess long-term outcomes of this technique compared with circular stapled hemorrhoidopexy (CSH). Methods: Conventional CSH kits combined with an intestinal spatula were used for performing C-PSH. A total of 256 patients with grade IV hemorrhoids referred to Hangzhou Third People's Hospital between January 2016 and June 2017 were obtained: 122 (47.7%) with C-PSH, and 134 (52.3%) with CSH. After propensity score matching, 222 patients (111 in C-PSH group and 111 in CSH group) were ultimately analyzed. The primary outcome was the five-year recurrence rate of hemorrhoids. Secondary outcomes included intraoperative outcomes, postoperative outcomes and complications. Results: The operative time in the C-PSH group was slightly longer than that in the CSH group (p < 0.01). The vertical length of rectal mucosa specimen in the C-PSH group was shorter than that in the CSH group (p < 0.01). Compared with the CSH group, fecal urgency incidence and numeric rating scale (NRS) score at first defecation were lower in the C-PSH group (p < 0.05). Major complication rate in the CSH group was higher than that in the C-PSH group (p = 0.03). Five-year recurrence rate between the C-PSH group and CSH group was comparable (p > 0.05). Multivariate Cox regression analysis revealed that constipation was an independent prognostic factor for hemorrhoidal recurrence. Conclusions: The accessible C-PSH seems to be a safe and effective technique in managing grade IV hemorrhoids. It has advantages in alleviating postoperative pain at first defecation, fecal urgency and major complications compared with CSH. It could be an alternative technique in the treatment of grade IV hemorrhoids. [ABSTRACT FROM AUTHOR]

Background: Gaining and maintaining spinal balance after surgery is of great importance for early onset scoliosis (EOS). However, tendency of balance on the coronal plane after growing rod surgery has not been studied before. This study evaluated the effect of growing rod treatment on coronal balance (CB) during serial lengthening surgeries in EOS. Methods: All EOS patients treated with growing rod technique in our hospital from August 2002 to June 2014 were retrospectively reviewed. Radiographic data before the sixth lengthening surgery were measured on the posteroanterior X-ray images, including global CB (C7 plumbline-central sacral vertical line, C7PL-CSVL), regional CB (apical vertebrae-CSVL), Cobb angle of the main curve and pelvic inlet width (PIW). Global CB index and regional CB index were calculated as dividing global CB and regional CB by PIW, respectively. The changes of these parameters during repeated lengthening surgeries were analyzed. Results: Five hundred seventy Radiographs of 67 patients, including 134 images before and after growing rod insertion surgeries and 436 images pre- and post-lengthening surgeries were measured. Global CB and global CB index did not show significant differences between every two set points during lengthening procedures (P > 0.05). The percentage of patients with C7PL-CSVL distance more than 20 mm roughly ranged from 30 to 45 % during the lengthening process. With regards to regional CB and main curve Cobb angles, there were significant differences between every two adjacent set points during the first five lengthening surgeries (P < 0.05). Conclusions: Global CB did not significantly change during serial lengthening surgeries and C7PL-CSVL distances of greater than 20 mm comprised of over one third of patients during growing rod treatment. However, worsening regional CB and Cobb angles of the main curve during lengthening intervals were corrected by lengthening manipulation and maintained at a stable level. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has become a severe burden on global health due to its high morbidity and mortality rates. However, effective treatments for HCC are limited. The lack of suitable preclinical models may contribute to a major failure of drug development for HCC. Here, we overview several well-established mouse models of HCC, including genetically engineered mice, chemically-induced models, implantation models, and humanized mice. Immunotherapy studies of HCC have been a hot topic. Therefore, we will introduce the application of mouse models of HCC in immunotherapy. This is followed by a discussion of some other models of HCC-related liver diseases, including non-alcoholic fatty liver disease (NAFLD), hepatitis B and C virus infection, and liver fibrosis and cirrhosis. Together these provide researchers with a current overview of the mouse models of HCC and assist in the application of appropriate models for their research. [ABSTRACT FROM AUTHOR]

Background: 3-Hydroxypropionic acid (3-HP) is an important platform chemical, serving as a precursor for a wide range of industrial applications such as the production of acrylic acid and 1,3-propanediol. Although Escherichia coli or Saccharomyces cerevisiae are the primary industrial microbes for the production of 3-HP, alternative engineered hosts have the potential to generate 3-HP from other carbon feedstocks. Methylobacterium extorquens AM1, a facultative methylotrophic α-proteobacterium, is a model system for assessing the possibility of generating 3-HP from onecarbon feedstock methanol. Results: Here we constructed a malonyl-CoA pathway by heterologously overexpressing the mcr gene to convert methanol into 3-HP in M. extorquens AM1. The engineered strains demonstrated 3-HP production with initial titer of 6.8 mg/l in shake flask cultivation, which was further improved to 69.8 mg/l by increasing the strength of promoter and mcr gene copy number. In vivo metabolic analysis showed a significant decrease of the acetyl-CoA pool size in the strain with the highest 3-HP titer, suggesting the supply of acetyl-CoA is a potential bottleneck for further improvement. Notably, 3-HP was rapidly degraded after the transition from exponential phase to stationary phase. Metabolomics analysis showed the accumulation of intracellular 3-hydroxypropionyl-CoA at stationary phase with the addition of 3-HP into the cultured medium, indicating 3-HP was first converted to its CoA derivatives. In vitro enzymatic assay and β-alanine pathway dependent 13C-labeling further demonstrated that a reductive route sequentially converted 3-HP-CoA to acrylyl-CoA and propionyl-CoA, with the latter being reassimilated into the ethylmalonyl-CoA pathway. The deletion of the gene META1_4251 encoding a putative acrylyl-CoA reductase led to reduced degradation rate of 3-HP in late stationary phase. Conclusions: We demonstrated the feasibility of constructing the malonyl-CoA pathway in M. extorquens AM1 to generate 3-HP. Furthermore, we showed that a reductive route coupled with the ethylmalonyl-CoA pathway was the major channel responsible for degradation of the 3-HP during the growth transition. Engineered M. extorquens AM1 represents a good platform for 3-HP production from methanol. [ABSTRACT FROM AUTHOR]

Background: Phytohormones play crucial roles in almost all stages of plant growth and development. Accurate and simultaneous determination of multiple phytohormones enabled us to better understand the physiological functions and the regulatory networks of phytohormones. However, simultaneous determination of multiple phytohormones in plant is still a challenge due to their low concentrations, structural and chemical diversity, and complex matrix of plant tissues. Therefore, development of a simple and selective method for the simultaneous determination of multiple phytohormones is highly needed. Results: We developed a clean-up strategy for profiling of multiple phytohormones, which can overcome the challenge of structural and chemical diversity. By using a one-step dispersive solid-phase extraction (DSPE) combined with UPLC-MS/MS, 54 phytohormones including auxins, ABA, SA, JA, GAs and CKs were simultaneously analyzed from a single rice sample extract. Using the developed method, we investigated the spatiotemporal distribution of phytohormones in rice. The profiling of various tissues of rice at different growth stages revealed the complexity of metabolic regulation and allocations of phytohormone species. Conclusion: A rapid one-step method was developed for the simultaneous analysis of six groups of phytohormones, including cytokinins, auxins, salicylic acid, jasmonates, abscisic acid and gibberellins in a single run, using UPLC-ESI-MS/MS. The proposed method was successfully applied to investigate spatiotemporal distribution of multiple phytohormones in rice. The spatiotemporal information obtained may be helpful for better understanding of phytohormones functions throughout life cycle of rice when integrated into transcriptome and other omics data. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have been widely proven effective for therapeutic angiogenesis in ischemia animal models as well as clinical vascular diseases. Because of the invasive method, limited resources, and aging problems of adult tissue-derived MSCs, more perinatal tissue-derived MSCs have been isolated and studied as promising substitutable MSCs for cell transplantation. However, fewer studies have comparatively studied the angiogenic efficacy of MSCs derived from different tissues sources. Here, we evaluated whether the in-situ environment would affect the angiogenic potential of MSCs. Methods: We harvested MSCs from adult bone marrow (BMSCs), adipose tissue (AMSCs), perinatal umbilical cord (UMSCs), and placental chorionic villi (PMSCs), and studied their "MSC identity" by flow cytometry and in-vitro trilineage differentiation assay. Then we comparatively studied their endothelial differentiation capabilities and paracrine actions side by side in vitro. Results: Our data showed that UMSCs and PMSCs fitted well with the minimum standard of MSCs as well as BMSCs and AMSCs. Interestingly, we found that MSCs regardless of their tissue origins could develop similar endothelial-relevant functions in vitro, including producing eNOS and uptaking ac-LDL during endothelial differentiation in spite of their feeble expression of endothelial-related genes and proteins. Additionally, we surprisingly found that BMSCs and PMSCs could directly form tubular structures in vitro on Matrigel and their conditioned medium showed significant proangiogenic bioactivities on endothelial cells in vitro compared with those of AMSCs and UMSCs. Besides, several angiogenic genes were upregulated in BMSCs and PMSCs in comparison with AMSCs and UMSCs. Moreover, enzyme-linked immunosorbent assay further confirmed that BMSCs secreted much more VEGF, and PMSCs secreted much more HGF and PGE2. Conclusions: Our study demonstrated the heterogeneous proangiogenic properties of MSCs derived from different tissue origins, and the in vivo isolated environment might contribute to these differences. Our study suggested that MSCs derived from bone marrow and placental chorionic villi might be preferred in clinical application for therapeutic angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Illegal drug use has long been a global concern. Taiwan and Korea are geographically adjacent and both countries have experienced the illegal use problems of methamphetamine, a predominant prototype of New Psychoactive Substances (NPS). NPS, a term coined by the United Nations Office on Drugs and Crime (UNODC) in recent years, have not been scrutinized for their safety and may become a new threat to public health and security worldwide. To conduct evidence-based drug policy, it is imperative to estimate the trend and pattern of illegal drug use. Therefore, this study aims to analyze and compare the current status of drug-related seizures, arrests and illegal drug use, with a focus on methamphetamine and NPS, between Taiwan and Korea. Methods: Data of illegal drug (including NPS)-related seizures and arrests were collected via anti-drug related agencies of both countries from 2006 through 2014.Since listing of NPS as controlled substances was a result of NPS abuse liability through official evaluation, the items of controlled NPS were used as an indicator of emerging use. These data obtained from Taiwan and Korea was then compared. Results: The results showed that while methamphetamine remained as a predominant drug in both Taiwan and Korea for decades, different illegal drug use patterns have been observed in these two countries. In Taiwan, the major illegal drugs were methamphetamine, heroin, and ketamine, whereas in Korea those were methamphetamine and cannabis. By comparison of per capita illicit drug seizures, the illegal drug use situation in Taiwan was at a higher stake than that in Korea. In terms of NPS use, ketamine has been a major drug in Taiwan, but it was seldom found in Korea. Besides ketamine, the major type of NPS was synthetic cathinones in Taiwan whereas it was synthetic cannabinoids and phenethylamines in Korea. The difference in the numbers of controlled NPS items between Taiwan (23) and Korea (93) may be due to the implementation of temporary control on NPS in Korea since 2011. Conclusion: While the problem of methamphetamine still lingers, NPS have emerged as a new issue in both countries. However, the NPS pattern was different between Taiwan and Korea. Although the controlled NPS items in Taiwan were far less than those in Korea, the quantity of total NPS seizures, especially with ketamine, was much larger in Taiwan than in Korea. Different NPS pattern may also imply they were from different sources. Factors other than geographical proximity, such as drug policy and availability and accessibility to drugs, should be taken into account for the current status of illegal drug use in Korea and Taiwan. [ABSTRACT FROM AUTHOR]

Tumor microenvironment and metabolic reprogramming are critical for tumor metastasis. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely involved in the formation of tumor microenvironment and present oncogenic phenotypes to facilitate lymph node metastasis (LNM) in response to small extracellular vesicles (sEV) released by gastric cancer (GC) cells. However, whether metabolic reprograming mediates transformation of BM-MSCs remains elusive. Herein, we revealed that the capacity of LNM-GC-sEV educating BM-MSCs was positively correlated with the LNM capacity of GC cells themselves. Fatty acid oxidation (FAO) metabolic reprogramming was indispensable for this process. Mechanistically, CD44 was identified as a critical cargo for LNM-GC-sEV enhancing FAO via ERK/PPARγ/CPT1A signaling. ATP was shown to activate STAT3 and NF-κB signaling to induce IL-8 and STC1 secretion by BM-MSCs, thereby in turn facilitating GC cells metastasis and increasing CD44 levels in GC cells and sEV to form a persistent positive feedback loop between GC cells and BM-MSCs. The critical molecules were abnormally expressed in GC tissues, sera and stroma, and correlated with the prognosis and LNM of GC patients. Together, our findings uncover the role of metabolic reprogramming mediated BM-MSCs education by LNM-GC-sEV, which presents a novel insight into the mechanism underlying LNM and provides candidate targets for GC detection and therapy. [ABSTRACT FROM AUTHOR]

Tumor microenvironment and metabolic reprogramming are critical for tumor metastasis. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely involved in the formation of tumor microenvironment and present oncogenic phenotypes to facilitate lymph node metastasis (LNM) in response to small extracellular vesicles (sEV) released by gastric cancer (GC) cells. However, whether metabolic reprograming mediates transformation of BM-MSCs remains elusive. Herein, we revealed that the capacity of LNM-GC-sEV educating BM-MSCs was positively correlated with the LNM capacity of GC cells themselves. Fatty acid oxidation (FAO) metabolic reprogramming was indispensable for this process. Mechanistically, CD44 was identified as a critical cargo for LNM-GC-sEV enhancing FAO via ERK/PPARγ/CPT1A signaling. ATP was shown to activate STAT3 and NF-κB signaling to induce IL-8 and STC1 secretion by BM-MSCs, thereby in turn facilitating GC cells metastasis and increasing CD44 levels in GC cells and sEV to form a persistent positive feedback loop between GC cells and BM-MSCs. The critical molecules were abnormally expressed in GC tissues, sera and stroma, and correlated with the prognosis and LNM of GC patients. Together, our findings uncover the role of metabolic reprogramming mediated BM-MSCs education by LNM-GC-sEV, which presents a novel insight into the mechanism underlying LNM and provides candidate targets for GC detection and therapy. [ABSTRACT FROM AUTHOR]

Background: Thoracic ossification of ligamentum flavum (TOLF) is a progressively disabling disease. Isolated or continuous TOLF has been frequently reported in literature, however there are very few reports of multilevel or non-continuous TOLF. The purpose of the study was to discuss the surgical strategy of multilevel TOLF and evaluate safety and efficacy of a two-stage operation regimen. Methods: From October 2007 to May 2014, eleven patients (4 males, 7 females) that underwent two-stage surgery for multilevel spinal stenosis were retrospectively reviewed. The follow-up period lasted at least 12 months. Demographic data, radiological findings as well as operative data were collected. Postoperative functional outcomes evaluated by the modified Japanese Orthopedic Association score (mJOA) and complications were analyzed. Results: The patients ranged in age from 30 to 65 years (average, 50.2 ± 11.8 years), and comprised 4 men and 7 women. All patients exhibited significant improvements in neurological deficits. The mJOA score improved from a mean of 3.5 ± 2.2 preoperatively to 4.6 ± 2.3 before second-stage surgery and to 7.5 ± 2.2 at final follow-up. The improvement was statistically significant in the average mJOA improvement rate at final follow-up. No staging-related complications were noted in this study. Conclusions: Staged surgery can effectively achieve neurological functional recovery in patients with multi-segment spinal stenosis in thoracic and lumbar regions, with favorable efficacy and safety. Yet, slight neurological deterioration was observed during the intervals of these two index surgeries. [ABSTRACT FROM AUTHOR]

Background: Difficulties in emotion regulation (DER) are widely considered to underlie anxiety and depression. Given the prevalence of anxiety and depression in adolescents and the fact that adolescence is a key period for the development of emotion regulation ability, it is important to examine how DER is related to anxiety and depression in adolescents in clinical settings. Methods: In the present study, we assessed 209 adolescents in clinical settings using the Difficulties in Emotion Regulation Scale (DERS) and the Hospital Anxiety and Depression Scale (HADS) and examined the associations between six components of DER and 14 symptoms of anxiety and depression. We used network analysis, constructed circular and multidimensional scaling (MDS) networks, and calculated network centrality, bridge centrality, and stability of centrality indices. Results: The results showed that: (1) The global centrality index shows that the Strategy component (i.e., lack of access to strategies) is the center in the whole network, ranking highest in strength, closeness, betweenness, and expected influence. (2) The MDS network showed a closeness of anxiety and depression symptoms, while Awareness component (i.e., lack of emotional awareness) stayed away from other DER components, but Awareness is close to some depression symptoms. (3) The bridge nodes of three groups, Strategy from DERS, Worry and Relax from anxiety symptoms, and Cheerful and Slow from depression symptoms, had the strongest relationships with the other groups. Conclusion: Lack of access to strategies remains in the center not only in DER but also in the DER-anxiety-depression network, while lack of awareness is close to depression but not to anxiety. Worrying thoughts and inability to relax are the bridging symptoms for anxiety, while lack of cheerful emotions and slowing down are the bridging symptoms for depression. These findings suggest that making emotion regulation strategies more accessible to patients and reducing these bridging symptoms may yield the greatest rewards for anxiety and depression therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and third leading cause of cancer-related death worldwide in 2020. Exosomes derived from cancer-associated fibroblasts (CAFs-exo) can promote tumor progression in various human cancers. However, the underlying regulatory mechanism controlling how CAFs-exo can promote HCC progression remains poorly understood. Methods: CAFs and para-cancer fibroblasts (PAFs) were isolated from HCC tissues and corresponding para-cancer tissues, then were cultured in vitro. CAFs and PAFs were characterized by immunofluorescence and western blot (WB) assays. Exosomes were isolated by ultracentrifugation, and characterized by transmission electron microscopy, nanoflow cytometry, and WB assay. The internalization of exosomes by HCC cells was observed under a fluorescence microscope. Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell proliferation. Wound healing and transwell assays were used for migration and invasion experiments. RT-PCR assay was used to examine differentially expressed microRNAs (miRNAs) in exosomes and HCC cells. The TargetScan database was used to predict miRNA target genes. Hedgehog interacting protein (HHIP) expression analysis, prognostic analysis, and enrichment analysis of HHIP-related co-expressed genes were performed using the TIMER, UALCAN, Kaplan–Meier plotter, and LinkedOmics databases. Results: CAFs-exo were internalized by HCC cells. CAFs-exo contributed to the aggressive phenotype of HCC cells, while inhibiting exosome secretion reversed these effects. Mechanistically, miRNAs in the DLK1-DIO3 imprinted region (miR-329-3p, miR-380-3p, miR-410-5p, miR-431-5p) were increased in HCC cells co-cultured with CAFs-exo compared with PAFs-exo. Expression of HHIP, a possible miR-431-5p target gene, was significantly downregulated in HCC cells. Low HHIP expression level in tumor tissues could predict poor prognosis in HCC patients. HHIP-related co-expressed genes were mainly associated with cell adhesion molecules. Conclusions: CAFs-exo can promote HCC progression by delivering miRNAs in the DLK1-DIO3 imprinted region to HCC cells, subsequently inhibiting HHIP expression. HHIP is a potential prognostic biomarker in HCC. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled inflammation is an important factor in the occurrence and development of acute lung injury (ALI). Fibroblast growth factor-inducible 14 (Fn14), a plasma membrane-anchored receptor, takes part in the pathological process of a variety of acute and chronic inflammatory diseases. However, the role of Fn14 in ALI has not yet been elucidated. This study aimed to investigate whether the activation of Fn14 exacerbated lipopolysaccharide (LPS)-induced ALI in mice. Methods: In vivo, ALI was induced by intratracheal LPS-challenge combined with/without Fn14 receptor blocker aurintricarboxylic acid (ATA) treatment in C57BL/6J mice. Following LPS administration, the survival rate, lung tissue injury, inflammatory cell infiltration, inflammatory factor secretion, oxidative stress, and NLRP3 inflammasome activation were assessed. In vitro, primary murine macrophages were used to evaluate the underlying mechanism by which Fn14 activated the NLRP3 inflammasome. Lentivirus was used to silence Fn14 to observe its effect on the activation of NLRP3 inflammasome in macrophages. Results: In this study, we found that Fn14 expression was significantly increased in the lungs of LPS-induced ALI mice. The inhibition of Fn14 with ATA downregulated the protein expression of Fn14 in the lungs and improved the survival rate of mice receiving a lethal dose of LPS. ATA also attenuated lung tissue damage by decreasing the infiltration of macrophages and neutrophils, reducing inflammation, and suppressing oxidative stress. Importantly, we found that ATA strongly inhibited the activation of NLRP3 inflammasome in the lungs of ALI mice. Furthermore, in vitro, TWEAK, a natural ligand of Fn14, amplified the activation of NLRP3 inflammasome in the primary murine macrophage. By contrast, inhibition of Fn14 with shRNA decreased the expression of Fn14, NLRP3, Caspase-1 p10, and Caspase-1 p20, and the production of IL-1β and IL-18. Furthermore, the activation of Fn14 promoted the production of reactive oxygen species and inhibited the activation of Nrf2-HO-1 in activated macrophages. Conclusions: Our study first reports that the activation of Fn14 aggravates ALI by amplifying the activation of NLRP3 inflammasome. Therefore, blocking Fn14 may be a potential way to treat ALI. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. Methods: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8–11), moderate (4–7), and low (0–3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). Results: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. Conclusions: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk. [ABSTRACT FROM AUTHOR]

Background: The cell division cycle 20 homolog (CDC20) is an essential cofactor of the anaphase-promoting complex (APC/C). CDC20 overexpression has been detected in many types of human cancers; however, its clinical role in colorectal cancer remains unknown. Methods: Western blotting and immunohistochemistry were used to compare CDC20 expression in adjacent non-cancerous, cancerous and liver metastatic tissues as well as in colon cancer cell lines and normal colon epithelial cell lines. Additionally, the correlation of CDC20 expression with patient clinical parameters and its diagnostic value were statistically analyzed. Results: CDC20 was overexpressed in colon cancer cell lines/primary cancer tissues compared with normal colon epithelial cell lines/adjacent noncancerous tissue samples. Interestingly, CDC20 expression was further increased in metastatic liver tissues. CDC20 protein expression was significantly correlated with clinical stage (P = 0.008), N classification (P = 0.020), M classification (P = 0.013) and pathologic differentiation (P = 0.008). Patients with higher CDC20 expression had a shorter overall survival than those with lower CDC20 expression. Univariate and multivariate analyses indicated that CDC20 expression was an independent prognostic factor (P < 0.001). Conclusion: CDC20 may serve as a potential prognostic biomarker of human colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: This prospective study was conducted to evaluate inter- and intra-fraction errors in nasopharyngeal carcinoma (NPC) patients undergoing volumetric modulated arc therapy (VMAT) using cone-beam computed tomography (CBCT) and to thus obtain planning target volume (PTV) margins to effectively guide treatment in the future. Methods: Fifteen NPC patients scheduled to undergo VMAT were prospectively enrolled in the study. For each patient, three CBCT scans were obtained; one after daily conventional positioning, one after online correction with 2 mm tolerance and one after 1 week of VMAT delivery. The scans were registered to the planning CT to determine the inter- and intra-fraction errors. Patient positioning errors were analyzed for time trends over the course of radiotherapy. PTV margins were calculated from the systematic (∑) and random (σ) errors. Results: The average absolute values of the pre-correction, post-correction and intra-fraction errors (in order) were 1.1, 0.6 and 0.4 mm in the medial-lateral (ML) direction, 1.2, 0.7 and 0.5 mm in the superior-inferior (SI) direction and 1.1, 0.7 and 0.5 mm in the anterior-posterior (AP) direction. The corresponding ∑ were 1.0-1.4 mm, 0.4-0.5 mm and 0.2-0.4 mm, while the corresponding s were 0.7-0.8 mm, 0.6-0.7 mm and 0.5-0.6 mm. With time, gradual increases in both the inter- and intra-fraction three-dimensional displacements were observed (P = 0.019 and P = 0.044, respectively). The total PTV margins accounting for pre-correction and intra-fraction errors were 3.4-4.1 mm and those accounting for post-correction and intra-fraction errors were 1.7-2.2 mm. Conclusions: CBCT is an effective modality to evaluate and improve the accuracy of VMAT in NPC patients. Inter- and intra-fraction three-dimensional displacements increased as a function of time during the course of radiotherapy. In our institution, we recommend a PTV margin of 5 mm for NPC patients undergoing VMAT without CBCT and 3 mm for those treated with rigorous daily CBCT scans. [ABSTRACT FROM AUTHOR]

Background: Melanoma antigen D1 (MAGED1) is a member of the type II melanoma antigen (MAGE) family. The down-regulation of MAGED1 expression has been shown in breast carcinoma cell lines and in glioma stem cells and may play an important role in apoptosis and anti-tumorigenesis. However, there is no report on its clinical role in colorectal cancer (CRC). Methods: We examined the expression of MAGED1 by qPCR in colorectal cancer tissues and their adjacent nontumorous tissues taken from 6 cases and performed Western blotting and IHC analyses. In addition, we analyzed MAGED1 expression in 285 clinicopathologically characterized colorectal cancer patients. Results: MAGED1 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues and was associated with clinical stage (p < 0.001), T classification (p = 0.001), N classification (p < 0.001), M classification (p < 0.001) and pathologic differentiation (p = 0.002). Patients with lower MAGED1 expression had a shorter survival time than those with higher MAGED1 expression. Univariate and multivariate analyses indicated that MAGED1 expression was an independent prognostic factors (p < 0.001). Conclusions: MAGED1 may serve as a novel prognostic biomarker of human colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Bacteriophages have the destructive damage on the industrial bioprocess. 2-Keto-gluconic acid (2KGA) producing bacteria had also been attacked and lysed by bacteriophages which lowered the glucose consumption and 2KGA yield and even stopped the fermentation process. In this study, we presented the characteristics of a novel virulent bacteriophage specifically infecting Pseudomonas fluorescens K1005 and proposed an efficient remedial action for this phage infection to reduce the production loss. Results: The phage KSL-1 of Pseudomonas fluorescens K1005 was isolated from abnormal 2KGA fermentation broth. It belonged to the Siphoviridae family with a hexagonal head diameter of about 99 nm and a non-contractile tail of about 103 nm × 39 nm. The genome size of phage KSL-1 was estimated to be approximately 53 kbp. Its optimal MOI to infect P. fluorescens K1005 was about 0.001. One-step growth curve gave its latent and burst periods of 90 min and 75 min with a burst size of 52 phage particles per infected cell. This phage was stable with a pH range of 7.0-10.0, and sensitive to thermal treatment. Finally, a simple remedial action was proposed by feeding fresh seed culture. Compared with the infected 2KGA fermentation, the remedial experiments restored 2KGA fermentation performance by increasing the produced 2KGA concentration to 159.89 g/L and shortening the total fermentation time of 80 h with the productivity and yield of 2.0 g/L.h and 0.89 g/g. The obtained data proved that this method was effective to combat the phage infections problems during the 2KGA fermentation. Conclusion: The phage KSL-1 was a novel bacteriophage specifically infecting Pseudomonas fluorescens K1005. The remedial action of feeding fresh seed culture to the infected broth was an easily-operating and effective method to maintain a high 2KGA yield and avoid the draft of infected broth. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled inflammation is an important factor in the occurrence and development of acute lung injury (ALI). Fibroblast growth factor-inducible 14 (Fn14), a plasma membrane-anchored receptor, takes part in the pathological process of a variety of acute and chronic inflammatory diseases. However, the role of Fn14 in ALI has not yet been elucidated. This study aimed to investigate whether the activation of Fn14 exacerbated lipopolysaccharide (LPS)-induced ALI in mice. Methods: In vivo, ALI was induced by intratracheal LPS-challenge combined with/without Fn14 receptor blocker aurintricarboxylic acid (ATA) treatment in C57BL/6J mice. Following LPS administration, the survival rate, lung tissue injury, inflammatory cell infiltration, inflammatory factor secretion, oxidative stress, and NLRP3 inflammasome activation were assessed. In vitro, primary murine macrophages were used to evaluate the underlying mechanism by which Fn14 activated the NLRP3 inflammasome. Lentivirus was used to silence Fn14 to observe its effect on the activation of NLRP3 inflammasome in macrophages. Results: In this study, we found that Fn14 expression was significantly increased in the lungs of LPS-induced ALI mice. The inhibition of Fn14 with ATA downregulated the protein expression of Fn14 in the lungs and improved the survival rate of mice receiving a lethal dose of LPS. ATA also attenuated lung tissue damage by decreasing the infiltration of macrophages and neutrophils, reducing inflammation, and suppressing oxidative stress. Importantly, we found that ATA strongly inhibited the activation of NLRP3 inflammasome in the lungs of ALI mice. Furthermore, in vitro, TWEAK, a natural ligand of Fn14, amplified the activation of NLRP3 inflammasome in the primary murine macrophage. By contrast, inhibition of Fn14 with shRNA decreased the expression of Fn14, NLRP3, Caspase-1 p10, and Caspase-1 p20, and the production of IL-1β and IL-18. Furthermore, the activation of Fn14 promoted the production of reactive oxygen species and inhibited the activation of Nrf2-HO-1 in activated macrophages. Conclusions: Our study first reports that the activation of Fn14 aggravates ALI by amplifying the activation of NLRP3 inflammasome. Therefore, blocking Fn14 may be a potential way to treat ALI. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a life-threatening emergency and could also seriously affect the life quality of patients, continuous efforts have been made to create an effective strategy to prevent the occurrence of MI and reduce MI-related mortality. Numerous studies have confirmed that neutrophils play important roles in inflammation and innate immunity, which provide the first line of defense against microorganisms by producing inflammatory cytokines and chemokines, releasing reactive oxygen species, and degranulating components of neutrophil cytoplasmic granules to kill pathogens. Recently, researchers reported that neutrophils are closely related to the severity and prognosis of patients with MI, and neutrophil to lymphocyte ratio in post-MI patients had predictive value for major adverse cardiac events. Neutrophils have been increasingly recognized to exert important functions in MI. Especially, granule proteins released by neutrophil degranulation after neutrophil activation have been suggested to involve in the process of MI. This article reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. BFFxxmL5fSszn23-NqgRi8 Video abstract Neutrophils played a crucial role throughout the process of MI, and neutrophil degranulation was the crucial step for the regulative function of neutrophils. Both neutrophils infiltrating and neutrophil degranulation take part in the injury and repair process immediately after the onset of MI. Since different granule subsets (e g. MPO, NE, NGAL, MMP‐8, MMP‐9, cathelicidin, arginase and azurocidin) released from neutrophil degranulation show different effects through diverse mechanisms in MI. In this review, we reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Myeloperoxidase (MPO); Neutrophil elastase (NE); Neutrophil gelatinase-associated lipocalin (NGAL); Matrix metalloproteinase 8 (MMP‐8); Matrix metalloproteinase 9 (MMP‐9). [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome has become a major health threat throughout the world, but there are few studies that focus on the effects of housework on human metabolism. This study explores the association between housework and metabolic markers and examines whether there are gender differences in the relationship of housework intensity on these markers. Methods: We obtained data for 2,624 participants from the China Health and Nutrition Survey and used binary logistic regression to analyze the association between housework and metabolic markers (triglycerides, high- and low-density lipoprotein cholesterol, hemoglobin, blood glucose, cholesterol, and blood pressure). Results: We observed no association between housework and metabolic markers for men. However, we find that women who engaged in housework had a higher risk of triglycerides than those who did not (OR=1.16, 95% CI: 1.16, 4.25). Compared with low-intensity, we also find that women who performed moderate- and high-housework intensity had a higher risk of triglycerides (moderate-intensity: OR=1.78, 95% CI: 1.14, 2.78; high-intensity: OR=1.91, 95% CI: 1.22, 2.98), MetS (OR=1.54, 95% CI: 0.98, 2.43; OR=1.68, 95% CI: 1.07, 2.66), pre-hypertension (OR=1.68, 95% CI: 1.08, 2.62; OR=1.63, 95% CI: 1.04, 2.55), and obesity (OR=1.65, 95% CI: 1.01, 2.70; OR=1.66, 95% CI: 1.01, 2.72). Conclusion: In women, we find that housework is positively associated with the metabolic markers, triglycerides, MetS, and pre-hypertension. However, we did not find evidence that this relationship exists in men, f or any biomarkers we considered. One possible explanation is that people who engage in high-intensity housework are more stressed and sleep less, which could be a mechanism by which housework becomes associated with metabolic disease. [ABSTRACT FROM AUTHOR]

Background: In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat. Results: This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens. Conclusion: This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated. Methods: The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively. Results: Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients. Conclusions: A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV) represents an important pathogenic factor of lymphoma and is significantly associated with poor clinical outcome of diffuse large B-cell lymphoma (DLBCL). Circular RNAs (circRNAs) play an essential role in lymphoma progression. However, the underlying mechanism of circRNA on DLBCL progression related to EBV remains largely unknown. Methods: CircRNA was screened by high-throughput sequencing in tumor samples of 12 patients with DLBCL according to EBV infection status. Expression of circEAF2, as well as the relationship with clinical characteristics and prognosis, were further analyzed in tumor samples of 100 DLBCL patients using quantitative real-time PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of circEAF2 both in vitro and in vivo. The underlying mechanism of circRNA on DLBCL progression were further determined by RNA sequencing, RNA pull down assay, dual-luciferase reporter assay, rescue experiments and western blotting. Results: We identified a novel circRNA circEAF2, which was downregulated in EBV + DLBCL and negatively correlated with EBV infection and DLBCL progression. In EBV-positive B lymphoma cells, circEAF2 overexpression induced lymphoma cell apoptosis and sensitized lymphoma cells to epirubicin. As mechanism of action, circEAF2 specifically targeted EBV-encoded miR-BART19-3p, upregulated APC, and suppressed downstream β-catenin expression, resulting in inactivation of Wnt signaling pathway and inhibition of EBV + DLBCL cell proliferation. In EBV-positive B-lymphoma murine models, xenografted tumors with circEAF2 overexpression presented decreased Ki-67 positivity, increased cell apoptosis and retarded tumor growth. Conclusions: CircEAF2 counteracted EBV + DLBCL progression via miR-BART19-3p/APC/β-catenin axis, referring circEAF2 as a potential prognostic biomarker. Therapeutic targeting EBV-encoded miRNA may be a promising strategy in treating EBV-associated lymphoid malignancies. [ABSTRACT FROM AUTHOR]

Background: Prediabetes has become a pandemic. This study aimed to identify a better predictor for the incidence of prediabetes, which we hypothesize to be the triglyceride-glucose (TyG) index, a simplified insulin resistance index. We compared its predictive value with the other common risk factors of prediabetes. Methods: The participants of this analysis were derived from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 4543 participants without initial prediabetes or diabetes were followed up for 3.25 years. Using multivariate logistic regression model, the associations between baseline obesity, lipid profiles and non-insulin-based insulin resistance indices with the incidence of prediabetes were analyzed. To assess which is better predictor for the incidence of prediabetes, the area under curves (AUCs) calculated from the receiver operating characteristic curve analyses were used to evaluate and compare with the predictive value of the different indices. Results: During the 3.25 years, 1071 out of the 4543 participants developed prediabetes. Using the logistic regression analysis adjusted for some potential confounders, the risk of incidence of prediabetes increased 1.38 (1.28–1.48) fold for each 1–SD increment of TyG index. The predictive ability (assessed by AUCs) of TyG index for predicting prediabetes was 0.60 (0.58–0.62), which was superior to the indices of obesity, lipid profiles and other non-insulin-based insulin resistance indices. Although the predictive ability of the TyG index was overall similar to fasting plasma glucose (FPG) (P = 0.4340), TyG index trended higher than FPG in females (0.62 (0.59–0.64) vs. 0.59 (0.57–0.61), P = 0.0872) and obese subjects (0.59 (0.57–0.62) vs. 0.57 (0.54–0.59), P = 0.1313). TyG index had superior predictive ability for the prediabetic phenotype with isolated impaired glucose tolerance compared with FPG (P < 0.05) and other indices. Furthermore, TyG index significantly improved the C statistic (0.62 (0.60–0.64)), integrated discrimination improvement (1.89% (1.44–2.33%)) and net reclassification index (28.76% (21.84–35.67%)) of conventional model in predicting prediabetes than other indices. Conclusions: TyG could be a potential predictor to identify the high risk individuals of prediabetes. [ABSTRACT FROM AUTHOR]

Background: The incidence of thyroid carcinoma is increasing all over the world. Some studies have suggested that the change of adipokines expression can induce thyroid carcinoma. However, other studies have come to the opposite conclusion. Therefore, we studied the relationship between adipokines and thyroid carcinoma.Methods: Databases-PubMed, Cochrane Library, SinoMed, CNKI, Wanfang, and clinical trial registries were searched. A meta-analysis was then performed through a fixed or random-effects model to calculate I values for heterogeneity analysis.Results: Twenty-nine articles were finally included for analysis. The level of serum tumor necrosis factor-alpha (TNF-α) [standardized mean difference (SMD) =1.31, 95% confidence interval (95% CI): 0.35 to 2.28, I2 = 98%, P = 0.008] and the ratio of TNF-α immunoreactivity in tissues [odds ratios (OR) =6.36, 95% CI: 1.92 to 21.05, I2 = 66%, P = 0.002] in thyroid carcinoma are significantly higher than those in control. The serum interleukin-6 (IL-6) in patients with thyroid carcinoma is higher than that in control (SMD = 1.04, 95% CI: 0.40 to 1.67, I2 = 96%, P = 0.001). There is no significant difference of the ratio of IL-6 immunoreactivity in tissues between carcinoma and control (OR = 1.23, 95% CI: 0.62 to 2.43, I2 = 86%, P = 0.55). The ratio of leptin immunoreactivity in tissues is significantly associated with the risk of thyroid carcinoma (OR = 12.21, 95% CI: 3.36 to 44.40, I2 = 85%, P < 0.00001). However, after analyzing the expression level of serum adiponectin in three studies, no significant difference is found between thyroid carcinoma and the control (P = 0.81).Conclusions: Adipokines (TNF-α, IL-6 and leptin) show a strong relationship between elevated concentrations (in serum and/or tissue) and thyroid carcinoma. However, the association between adiponectin and thyroid carcinoma needs further research. [ABSTRACT FROM AUTHOR]

Background: Solobacterium moorei, the only species in the genus Solobacterium, is a Gram-positive, non-spore-forming, strict anaerobic, short to long bacillus. It has rarely been documented to cause blood stream infections. Here we report the first case of bacteremia caused by S.moorei in China.Case Presentation: A 61-year-old male presented to Peking Union Medical College Hospital (Beijing) with thrombotic thrombocytopenic purpura (TTP) and several other underlying diseases. He also had persistent coma accompanied by intermittent convulsions, halitosis, and intermittent fever. Blood cultures taken when the patient had a high fever were positive, with the anaerobic bottle yielding an organism identified as S.moorei by 16S rRNA gene sequencing, whilst the aerobic bottle grew Streptococcus mitis. After replacement of venous pipeline, and empirical use of vancomycin and meropenem, the patient's body temperature and white blood cell count returned to normal. Unfortunately, the patient died of severe TTP.Conclusion: This is the first case report of S. moorei isolation from blood stream in China. 16S rRNA gene sequencing is the only method that can identify S. moorei. Blood cultures must be taken before administration of antibiotics, and anaerobic culture should be considered for such rare pathogens in patients with oral diseases and immune deficiency. [ABSTRACT FROM AUTHOR]

Antibiotic exposure during pregnancy will adversely affect the growth of offspring; however, this remains controversial and the mechanism is poorly understood. To study this phenomenon, we added ceftriaxone sodium to the drinking water of pregnant rats and continuously monitored the body weight of their offspring. The results showed that compared with the control group, the offspring exposed to antibiotics during pregnancy had a higher body weight up to 3 weeks old but had a lower body weight at 6 weeks old. To determine the role of the gut microbiota and its metabolites in the growth of offspring, we collected feces for sequencing and further established that the experimental group has a different composition ratio of dominant bacteria at 6 week old, among which S24–7 correlated negatively with body weight and the metabolites that correlated with body weight-related unique flora were L-Valine, L-Leucine, Glutaric acid, N-Acetyl-L-glutamate, and 5-Methylcytosine. To further explore how they affect the growth of offspring, we submitted these data to Kyoto Encyclopedia of Genes and Genomes website for relevant pathway analysis. The results showed that compared with the control, the following metabolic pathways changed significantly: Valine, leucine, and isoleucine biosynthesis; Protein digestion and absorption; and Mineral absorption. Therefore, we believe that our findings support the conclusion that ceftriaxone sodium exposure in pregnancy has a long-lasting adverse effect on the growth of offspring because of an imbalance of gut microbiota, especially S24–7, via different metabolic pathways. [ABSTRACT FROM AUTHOR]

Background: School bullying victimization (SBV) occurs more frequently in students with autism spectrum disorder (ASD) in general education than in special classes, and there is a cumulative risk effect on SBV exposure among young people with ASD reported by their parents and teachers. However, SBV is a personal experience, the predictive patterns of cumulative risk on SBV reported by themselves and its psychological mechanism remain unclear. This study aims to explore the relationship between cumulative risk and SBV based on self-report, and to test whether internalizing problems mediates this relationship among adolescents with ASD placed in regular classes. Methods: This study used data from the Taiwan Special Needs Education Longitudinal Study (SNELS) in 2011. The analysis included 508 adolescents with ASD who were in regular classes across Taiwan. The primary variables under study were the quality of friendship interactions, teacher-student relationship, school connection, perceived stigma, the impact caused by the disabilities, internalizing problem, and whether the participants had experienced SBV over the past semester, while control variables were adaptability and social-emotional skills. Established risk factors were summed to form a cumulative risk score. Results: The cumulative risk was positively associated with SBV. The relationship was characterized by the nonlinear pattern of the quadratic function (negative acceleration model) between cumulative risk and SBV. Internalizing problem played a partial mediating role in the effect of cumulative risk on SBV. Conclusions: Intervention measures to reduce SBV should include the strategies to reduce the number of risks to which adolescents with ASD in regular classes are exposed, comprehensive prevention targeting each risk factor is needed specially when the number of risks is one or two, and more attention needs to be given to their internalizing problem in various ways. [ABSTRACT FROM AUTHOR]

Background: Many controversies still exist concerning the optimal extent of lymphadenectomy during esophagectomy in esophageal squamous cell carcinoma (ESCC). The objective of this study was to explore the characteristics of 4R metastasis and evaluate the clinical value of 4R node dissection in ESCC. Methods: A total of 736 ESCC patients who underwent radical esophagectomy between 2005 and 2013 were retrospectively collected, among which 393 ones underwent 4R dissection. Propensity score matching (PSM) method was applied to reduce the effects of confounding variables between the 4R dissection and non-dissection groups to analyze overall survival. Results: Patients showed a low 4R metastasis rate of 5.1% (20/393) (5.2%, 5.8%, and 1.8% for upper, middle, and lower tumors, respectively). Correlation analyses identified that 4R metastasis was significantly associated with station 2R metastasis (p < 0.001) and pathologic tumor-node-metastasis (pTNM) stage (p < 0.001). All 4R metastases were observed in stages IIIB and IVA. Moreover, patients with station 4R dissection failed to achieve significantly improved overall survival compared with those without 4R dissection, regardless of tumor stage (overall: p = 0.696; stage 0-IIIA: p = 0.317; stage IIIB-IVA: p = 0.619). Conclusion: 4R metastasis is likely to be associated with more aggressive disease, and routine 4R node dissection might not be necessary for ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinoma (EC) is the second most common gynecological malignancy, and the differences between different pathological types are not entirely clear. Here, we retrospectively collected eligible EC patients to explore their differences regarding clinical characteristics and prognosis. Methods: Five hundred seventy EC patients from the First Affiliated Hospital of Zhengzhou University were included. Prognostic factors were measured using the univariate/multivariate Cox models. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. Results: In total, 396 patients with uterine endometrioid carcinoma (UEC), 106 patients with uterine serous carcinoma (USC), 34 patients with uterine mixed carcinoma (UMC), and 34 patients with uterine clear cell carcinoma (UCCC) were included. Comparison of baseline characteristics revealed patients diagnosed with UEC were younger, had more early clinical stage, and had lower incidence of menopause and lymph node metastasis. Compared to UEC, other pathological EC obtained more unfavorable OS (UCCC: HR = 12.944, 95%CI = 4.231–39.599, P < 0.001; USC: HR = 5.958, 95%CI = 2.404–14.765, P < 0.001; UMC: HR = 1.777, 95%CI = 0.209–15.114, P = 0.599) and PFS (UCCC: HR = 8.696, 95%CI = 1.972–38.354, P = 0.004; USC: HR = 4.131, 95%CI = 1.243–13.729, P = 0.021; UMC: HR = 5.356, 95%CI = 0.935–30.692, P = 0.060). Compared with UEC patients, the OS of UCCC patients in stage I–II and USC patients in stage III–IV were significantly worse, while UMC patients in stage I–II favored poorer PFS. The OS of UCCC patients receiving no postoperative adjuvant therapy or chemotherapy alone were significantly worse. Conclusions: The baseline characteristics of UEC and other rare EC types varied greatly, and the prognostic significance of different pathological types on EC patients depended on clinical tumor stages and therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) and genetic determinants of resistance of N. gonorrhoeae isolates from Hefei, China, were characterized adding a breadth of information to the molecular epidemiology of gonococcal resistance in China.Methods: 126 N. gonorrhoeae isolates from a hospital clinic in Hefei, were collected between January, 2014, and November, 2015. The minimum inhibitory concentration (MIC) of N. gonorrhoeae isolates for seven antimicrobials were determined by the agar dilution method. Isolates were tested for mutations in penA and mtrR genes and 23S rRNA, and also genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST).Results: All N. gonorrhoeae isolates were resistant to ciprofloxacin; 81.7% (103/126) to tetracycline and 73.8% (93/126) to penicillin. 39.7% (50/126) of isolates were penicillinase producing N. gonorrhoeae (PPNG), 31.7% (40/126) were tetracycline resistant N. gonorrhoeae (TRNG) and 28.6% (36/126) were resistant to azithromycin. While not fully resistant to extended spectrum cephalosporins (ESCs), a total of 14 isolates (11.1%) displayed decreased susceptibility to ceftriaxone (MIC ≥ 0.125 mg/L, n = 10), cefixime (MIC ≥ 0. 25 mg/L, n = 1) or to both ESCs (n = 3). penA mosaic alleles XXXV were found in all isolates that harbored decreased susceptibility to cefixime, except for one. Four mutations were found in mtrR genes and mutations A2143G and C2599T were identified in 23S rRNA. No isolates were resistant to spectinomycin. Gonococcal isolates were distributed into diverse NG-MAST sequence types (STs); 86 separate STs were identified.Conclusions: N. gonorrhoeae isolates from Hefei during 2014-2015, displayed high levels of resistance to antimicrobials that had been recommended previously for treatment of gonorrhea, e.g., penicillin, tetracycline and ciprofloxacin. The prevalence of resistance to azithromycin was also high (28.6%). No isolates were found to be fully resistant to spectinomycin, ceftriaxone or cefixime; however, 11.1% isolates, overall, had decreased susceptibility to ESCs. [ABSTRACT FROM AUTHOR]

Background: Nowadays, few surgery analysis has been reported in cases of epilepsy after viral encephalitis(VE). Herein, this study was to evaluate the efficacy of surgery and capability of stereoelectroencephalography (SEEG) in the definition of the epileptogenic zone (EZ) after VE, and also to explore the relationship between the SEEG features and the surgical outcomes.Methods: We retrospectively analyzed 10 surgically treated patients that identified to suffer from epilepsy secondary to VE using SEEG, and investigated the SEEG features associated with surgical outcomes in these patients. Besides visual analysis, we used the epileptogenicity index (EI), a semi-quantitative and supplementary tool to evaluate the validity of SEEG in the context of VE.Results: Among the 10 operated patients, 3 of them became completely seizure-free. The patients who got totally seizure free or significant improvement, the seizure onset was located either in the antero-mesial temporal structures or focal gyrus; patients who got worthwhile improvement or no improvement, the seizure started from multiple brain lobes. The number of electrodes classified as epileptogenic visually involved were closely correlated with EI positive onses.Anatomic areas defined and shown as EZ on MRI by visual assessment were also defined as epileptogenic by the EI in these cases.Conclusion: Apart from exploring the surgical outcome related to epilepsy after VE, we also bring insight into the relationship between the SEEG features and surgical outcome with the application of the supplementary methods. [ABSTRACT FROM AUTHOR]

Background: Gliomas are the most common primary tumors in central nervous system. Despite advances in diagnosis and therapy, the prognosis of glioma remains gloomy. Autophagy is a cellular catabolic process that degrades proteins and damaged organelles, which is implicated in tumorigenesis and tumor progression. Autophagy related 4C cysteine peptidase (ATG4C) is an autophagy regulator responsible for cleaving of pro-LC3 and delipidation of LC3 II. This study was designed to investigate the role of ATG4C in glioma progression and temozolomide (TMZ) chemosensitivity. Methods: The association between ATG4C mRNA expression and prognosis of gliomas patients was analyzed using the TCGA datasets. The role of ATG4C in proliferation, apoptosis, autophagy, and TMZ chemosensitivity were investigated by silencing ATG4C in vivo. Ectopic xenograft nude mice model was established to investigate the effects of ATG4C on glioma growth in vivo. Results: The median overall survival (OS) time of patients with higher ATG4C expression was significantly reduced (HR: 1.48, p = 9.91 × 10− 7). ATG4C mRNA expression was evidently increased with the rising of glioma grade (p = 2.97 × 10− 8). Knockdown ATG4C suppressed glioma cells proliferation by inducing cell cycle arrest at G1 phase. ATG4C depletion suppressed autophagy and triggered apoptosis through ROS accumulation. Depletion of ATG4C suppressed TMZ-activated autophagy and promoted sensitivity of glioma cells to TMZ. Additionally, ATG4C knockdown suppressed the growth of glioma remarkably in nude mice. Conclusion: ATG4C is a potential prognostic predictor for glioma patient. Targeting ATG4C may provide promising therapy strategies for gliomas treatment. [ABSTRACT FROM AUTHOR]

Background: The Captopril challenge test (CCT) is an easy-conduct confirmatory test for diagnosing primary aldosteronism (PA). Guidelines show that plasma aldosterone is normally suppressed by captopril (> 30%) in primary hypertension (PH) and in healthy people. It is unclear whether this standard is applicable in Chinese subjects. The aim of the present study was to investigate the post-CCT efficacy of plasma aldosterone concentration (PAC) suppression and determine the post-CCT aldosterone renin activity ratio (ARR) and PAC for PA diagnosis. Methods: We recruited 110 consecutive patients with PA, 163 with primary hypertension (PH), and 40 healthy volunteers (NC). The CCT was conducted in all patients. Total sodium intake was estimated from 24-h urinary excretions. ROC curves were used to analyze the efficiency of different CCT diagnostic criteria for diagnosing PA. Results: In NC and PH patients, PRA was increased and PAC was decreased post-CCT (P < 0.05). The mean degree of PAC decline after CCT was approximately 9.3%, and only 11.7% of the patients with PH showed a greater than 30% suppression of PAC after CCT. In patients with PA, the post-CCT change in PRA and PRC was slight. The post-CCT degree of PAC decline was unrelated to dietary salt intake. The areas under the ROC for the post-CCT ARR, PAC and PAC suppression % were 0.994, 0.754 and 0.606, respectively. The optimal post-CCT cutoff value for ARR for diagnosing PA was 20, which yielded a sensitivity and specificity of 94.0 and 99.4%, respectively. Conclusions: The PAC suppression percentage after CCT recommended by current clinical guidelines is not applicable when diagnosing Chinese subjects with PA. Compared to post-CCT PAC, post-CCT ARR was a better approach, having an optimal cutoff of 20 when interpreting the results of the CCT in Chinese patients. We found no relationship between high salt intake and low responses of the renin-angiotensin system (RAS) to the CCT. [ABSTRACT FROM AUTHOR]

Background: The transcription factor PR domain containing 16 (PRDM16) is known to play a significant role in the determination and function of brown and beige fat. However, the role of PRDM16 in tumor biology has not been well addressed. Here we investigated the impact of PRDM16 on tumor growth and metastasis in lung cancer. Methods: UALCAN database, immunoblotting and immunohistochemistry analysis were used to assess PRDM16 expression in lung cancer patients. Kaplan-Meier plotter database was used to analyze the overall survival of patients with lung cancer stratified by PRDM16 expression. PRDM16 overexpression and knockdown experiments were conducted to assess the effects of PRDM16 on growth and metastasis in vitro and in vivo, and its molecular mechanism was investigated in lung adenocarcinoma cells by chromatin immunoprecipitation-sequencing (ChIP-Seq), real time-quantitative PCR (RT-qPCR), luciferase assay, xenograft models and rescue experiments. Results: PRDM16 was downregulated in lung adenocarcinomas, and its expression level correlated with key pathological characteristics and prognoses of lung adenocarcinoma patients. Overexpressing PRDM16 inhibited the epithelial-to-mesenchymal transition (EMT) of cancer cells both in vivo and in vitro by repressing the transcription of Mucin-4 (MUC4), one of the regulators of EMT in lung adenocarcinomas. Furthermore, deleting the PR domain from PRDM16 increased the transcriptional repression of MUC4 by exhibiting significant differences in histone modifications on its promoter. Conclusions: Our findings demonstrate a critical interplay between transcriptional and epigenetic modifications during lung adenocarcinoma progression involving EMT of cancer cells and suggest that PRDM16 is a metastasis suppressor and potential therapeutic target for lung adenocarcinomas. [ABSTRACT FROM AUTHOR]

Background: Although mounting non-hereditary colorectal cancer (NHCRC) associated single nucleotide polymorphisms (SNPs) have been observed, no field synopsis and meta-analysis has been conducted through systematically assessing cumulative evidence, during the past 5 years. Methods: We retrieved the database via the PubMed, Web of Science and Embase gateways to identify publications concerning the associations between SNPs and risk of NHCRC, up to May 1st, 2017. To assess the finding credibility, cumulative evidence was graded based on the Venice criteria. Meta-analysis was also performed for three subgroups including ethnicity (Asian vs Caucasian), primary cancer site (colon vs rectum) and TNM stage (I II vs III IV). Then, we arranged those high quality SNPs into different regions according to their locations on genes to evaluate their functional roles on CRC development. Results: 5114 publications were collected and 1001 of them met our inclusion criteria, which totally included 1788 SNPs in 793 genes or distinct chromosomal loci. Totally, we performed 359 primary and subgroup meta-analyses for 160 SNPs in 96 distinct genes. By utilizing the Venice criteria, we identified 15 high quality SNPs with 25 high credibility significant associations. Furthermore, we artificially divided the high quality SNPs into different groups, based on their SNP loci (exon region, intron region, promoter region, downstream region, non-coding region and intergenic region). Conclusion: We have identified 15 high quality SNPs which may act as promising genetic biomarkers for clinical NHCRC susceptibility screening and explored their functional roles on the NHCRC development based on their locations on genes. [ABSTRACT FROM AUTHOR]