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Background: Multiple liver metastases is considered a risk factor for overall survival of colorectal liver metastases patients (CRLM) after curative resection. However, whether the prognostic factors were constant in patients with various liver metastases (LM) numbers has not been adequately investigated. This retrospective study aimed to evaluate the changing of prognostic factors on overall survival (OS) in CRLM patients with various LM after curative resection. Methods: Patients who underwent liver resection for CRLM between January 2000 and November 2020 were retrospectively studied. They were divided into three subgroups according to LM numbers by X-tile analysis. Multivariable analysis identified prognostic factors in each subgroup. Nomograms were built using different prognostic factors in three subgroups, respectively. Performance of the nomograms was assessed according to the concordance index (C-index) and calibration plots. The abilities of different scoring systems predicting OS were compared by calculating the area under the time-dependent receiver operating characteristic (ROC) curve (AUC). Results: A total of 1095 patients were included. Multivariable analysis showed tumor number increasing was an independent risk factor. Patients were subsequently divided into 3 subgroups according to the number of LM by X-tile analysis, namely solitary (n = 375), 2–4 (n = 424), and ≥ 5 (n = 296). The 3-year and 5-year OS rates were 64.1% and 54.0% in solitary LM group, 58.1% and 41.7% in 2–4 LM group, and 50.9% and 32.0% in ≥ 5 LM group, respectively (p < 0.001). In multivariable analysis, RAS mutation was the only constant independent risk factor in all subgroups. The nomograms were built to predict survival based on independent factors in three subgroups. The C-index for OS prediction was 0.707 (95% CI 0.686–0.728) in the solitary LM group, 0.695 (95% CI 0.675–0.715) in the 2–4 LM group, and 0.687 (95% CI 0.664–0.710) in the ≥ 5 LM group. The time-dependent AUC values of nomograms developed using different risk factors after stratifying patients by tumor number were higher than the traditional scoring systems without patient stratification. Conclusions: The prognostic factors varied among CRLM patients with different LM numbers. RAS mutation was the only constant risk factor. Building prediction models based on different prognostic factors improve patient stratification. [ABSTRACT FROM AUTHOR]

It is assumed that the impact of primary tumor stage (PTS) on prognosis gradually weakens with increasing disease-free interval (DFI) from colorectal cancer resection to liver metastases. Data from 733 patients undergoing hepatectomy in the Hepato-pancreato-biliary Surgery Department I of Peking University Cancer Hospital were retrospectively analyzed. Early and late metastases were defined as DFI ≤ and >12 months, respectively. In early metastases group, patients with T 4 stage had a significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with T 1-3 stage (P = 0.002 and P < 0.001, respectively). Patients with N 1-2 stage disease also demonstrated a worse RFS and OS than those with N 0 stage (P = 0.006 and P = 0.007, respectively). In late metastases group, patients with T 4 and T 1-3 stages as well as patients with N 1-2 and N 0 stages, had comparable RFS (P = 0.395 and P = 0.996, respectively) and OS (P = 0.387 and P = 0.684, respectively). T and N stages were independent prognostic predictors only in patients with early metastases. The impact of PTS on prognosis is diminished with increasing DFI and limited only to patients with early metastases. [ABSTRACT FROM AUTHOR]

Acute alcoholism (AAI) is a common emergency. Currently, there is a lack of preventive and therapeutic drugs with superior safety and efficacy. Curcuma longa, Panax ginseng, Pueraria lobata, Pueraria flower, and Hovenia dulcis Thunb., which are the components of compound turmeric recipe (CTR), are, respectively, used in China as adjuvant therapeutic agents for AAI and alcoholic liver injury, respectively. The purpose of this research was to investigate the effect of traditional compound turmeric recipe in anti-inebriation treatment and to identify its underlying mechanisms. The mice were administered with CTR mixture, and ethanol was subsequently given to mice by gavage. The effects of CTR on the righting reflex, 24-hour survival, drunken behavior, blood ethanol concentration, and pathological changes of liver are depicted. The activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were detected. Besides, the activities of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 (P450), superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver and the levels of β-endorphin (β-EP) and leucine enkephalin (LENK) in the brain were also measured. Our results demonstrated that CTR can increase the activities of ADH, ALDH, P450, and SOD and decrease the contents of TNF-α, IL-8, and MDA in the liver. In addition, it can decrease the activities of ALT, AST, and ALP in serum and β-EP and LENK activities in the brain. CTR showed effects on prevention of acute alcoholism, promoting wakefulness, and alleviating alcoholic liver injury, which were likely mediated by the above mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: To characterize profile of cytokines in aqueous humour of common macular diseases during intravitreal anti‐VEGF therapy. Methods: Aqueous humour from eyes with central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), diabetic macular oedema (DME), neovascular age‐related macular degeneration (nAMD) or pathologic myopia associated choroidal neovascularization (pmCNV) was sampled prior to 1st (n = 144) and 2nd (n = 48) intravitreal anti‐VEGF therapy. Cytokines including vascular endothelium growth factor (VEGF), intercellular adhesion molecule 1 (ICAM‐1) and interleukin 6 (IL‐6) were quantitated and analysed along with retinal thickness data by optical coherence tomography (OCT) across two intravitreal injections and five macular disease types. Results: ICAM‐1, IL‐6 and VEGF are positively associated in the aqueous humour of naive eyes (r = 0.39–0.77, p = 0.018 to <0.0001). ICAM‐1, VEGF and IL‐6 were significantly higher in CRVO and DME while lowest in pmCNV (p < 0.0001). Reduction of central retinal thickness (CRT) as a favourable response to anti‐VEGF therapy was in the order of CRVO, BRVO, DME and nAMD/pmCNV (p < 0.0001). The strongest predictor for favourable CRT reduction was baseline CRT (p < 0.0001) followed by baseline ICAM‐1 (p = 0.04). After the 1st intravitreal anti‐VEGF therapy, VEGF in aqueous humour lowered significantly but ICAM‐1 and IL‐6 levels remained unchanged. ICAM‐1 was not predictive for CRT reduction following 2nd anti‐VEGF therapy. Conclusion: Rate of cytokine production is disease‐dependent and higher in CRVO and DME. Anatomical response to intravitreal anti‐VEGF therapy is disease‐specific and best in RVO patients. A combination therapy using both anti‐VEGF and anti‐inflammatory therapeutics may be superior to single anti‐VEGF therapy, at least for RVO and DME. [ABSTRACT FROM AUTHOR]

Abstract Background Microvascular invasion (MVI) is a powerful predictor of recurrence in patients who undergo liver resection for hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in HCC patients with MVI, and further select potential patients benefitting from PA-TACE. Methods Patients who had HCC with MVI and underwent liver resection between September 2004 and December 2015 were identified for further analysis. Overall survival (OS) and disease-free survival (DFS) were compared between patients treated with and without PA-TACE. Propensity score matching analysis was used to minimize inter-group differences. Results A total of 176 patients with HCC and MVI were included. In both the entire and propensity-matched cohorts, OS and DFS were higher in PA-TACE group than non-TACE group (all P < 0.05). In subgroup analyses, PA-TACE showed efficacy in improving OS and DFS in HCC patients at early stage beyond Milan criteria and intermediate stage, but not in patients within Milan criteria. Multivariable analysis identified PA-TACE as a significantly favorable factor of OS and DFS for patients beyond Milan criteria, but not for those within Milan criteria. Conclusion PA-TACE could be beneficial for patients who have HCC with MVI beyond Milan criteria, but not for those within Milan criteria. [ABSTRACT FROM AUTHOR]

Summary: Background: The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used staging system for hepatocellular carcinoma (HCC). However, the classifications of early (BCLC‐A) and intermediate (BCLC‐B) stage HCC remain controversial. Aim: To refine the staging of BCLC‐A and ‐B. Methods: A total of 986 patients with HCC undergoing liver resection from two institutions formed the training cohort, and 694 from another institution were the validation cohort. Time‐dependent receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of tumour size in predicting overall survival (OS), and determined the optimised cut‐off. Discriminatory performance was evaluated using Harrell's concordance index (C‐index). Results: Patients with multiple tumours exceeding Milan criteria but within up‐to‐seven criteria had similar OS and disease‐free survival (DFS) to those with multiple tumours meeting Milan criteria, and were assigned to the modified BCLC‐A stage. The area under the ROC curve of tumour size for predicting OS was 0.778, and the diameter of 7 cm was the optimal cut‐off to identify patients with single tumours who had higher OS than BCLC‐B stage patients. Due to the similar OS, patients with single HCCs >7 cm were assigned to the modified BCLC‐B stage. The C‐indexes of the modified BCLC classification for OS and DFS were higher compared to the original version. The findings were supported by the validation cohort. Conclusions: The modified staging of BCLC‐A and ‐B, based on single tumour >7 cm and multiple tumours beyond up‐to‐seven criteria, could be more accurate to predict the prognosis of HCC patients. Liver resection could benefit patients with resectable multifocal HCCs beyond the Milan criteria. [ABSTRACT FROM AUTHOR]

Background and objectives: The research work in the past years showed that detection of phospholipase A2 receptor (PLA2R) antigen and its dominant IgG4 autoantibody in glomerular deposits of patients with membranous nephropathy (MN) was useful for the differentiation between primary MN (PMN) and secondary MN (SMN), but so far such research data from large Chinese patient series is little. Here, we are going to report a research work in a Chinese cohort. Design, setting, participants, & measurements: This study enrolled 179 patients with PMN, 40 patients with membranous lupus nephritis (LN-MN), 26 patients with hepatitis B virus-associated MN (HBV-MN), 2 patients with malignancy-associated MN (M-MN) and one patient with IgG4-related MN (IgG4-MN). PLA2R and IgG subclasses in glomerular deposits of these patients were examined by and/or staining, and the potential value of the above examinations for differential diagnosis of PMN and SMN was evaluated. Results: Glomerular PLA2R deposition was present in 92.2% patients with PMN and 7.7% patients with HBV-MN, but none of the patients with LN-MN. Predominant/codominant IgG4 deposition was found in 93.3% patients with PMN and 11.5% patients with HBV-MN, but none of the patients with LN-MN. The two M-MN patients both had glomerular PLA2R and predominant/codominant IgG4 deposition. The one IgG4-MN patient had deeply staining IgG4 but no PLA2R in glomeruli. Conclusions: The glomerular PLA2R and predominant/codominant IgG4 deposition is frequently observed in Chinese patients with PMN. and staining of renal biopsy tissue for detection of glomerular PLA2R and IgG subclasses deposition can help to distinguish PMN from LN-MN and most of HBV-MN. [ABSTRACT FROM AUTHOR]

: Background: The influence of diabetes mellitus (DM) on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. Here we investigated the impact of DM on the prognosis of such patients after curative hepatectomy. Methods: A consecutive cohort of 505 patients with HCC (134 with DM, 371 without) underwent curative hepatectomy were retrospectively evaluated. Postoperative morbidity and mortality, overall survival (OS) and disease-free survival (DFS) were compared between patients with or without DM. Independent prognostic predictors were identified using the Cox proportional hazards model. Results: Patients with or without DM showed similar morbidity and 30- and 90- day mortality after curative hepatectomy (all P>0.05), as well as similar DFS at 1, 3, 5 years (P = 0.781). However, the group of patients with DM showed significantly lower OS at 1, 3, 5 years than the group without DM (P = 0.038). Similar results were obtained in the propensity-matched cohort. Cox multivariate analysis identified DM as an independent predictor of poor OS, but not of poor DFS. We repeat compared OS and DFS for DM and non-DM subgroups defined according to the presence or absence of hepatitis B virus infection and cirrhosis. Similar results were obtained in all subgroups except the non-cirrhotic subgroup which showed patients with and without DM had similar OS. Conclusions: DM does not significantly affect the postoperative morbidity or mortality or the DFS of patients with HCC after curative hepatectomy. It is, however, associated with significantly lower OS, especially in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Dendritic cells are able to present Ag-derived peptides on MHC class I and II molecules and induce T cells priming. Lipopolysaccharides (LPS), an activator of Toll-like 4 receptor (TLR4) signaling, has been demonstrated to facilitate Ag-presentation, up-regulate surface molecules expression but impair T cells priming. In this study, we investigated the effect of LPS on nicotine-enhanced DCs-dependent T cells priming and the mechanisms of LPS orchestrating the immunosuppressive program. We could demonstrate that the treatment with LPS resulted in increased surface molecules expression, enhanced Ag-presentation, up-regulated release of TGF-beta, TNF-alpha, IL-6, and IFN-beta. Concomititantly, the upregulation of IFN-beta in DCs induces the up-regulation of coinhibitory molecules B7H1 and GITRL, which cause an impaired activation of naïve Ag-specific T cells and the induction of T cell tolerance by enhancing B7H1-PD-1 interactions and promoting GITRL-GITL facilitated Treg generation, respectively. These data provide a mechanistic basis for the immunomodulatory action of IFN-beta which might open new possibilities in the development of therapeutic approaches aimed at the control of excessive immune response and persistent infection. [ABSTRACT FROM AUTHOR]

The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β secretion. Inflammasome activation is mediated by NLR proteins that respond to stimuli. Among NLRs, NLRP3 senses the widest array of stimuli. NLRP3 inflammasome plays an important role in the development of many cancer types. However, Whether NLRP3 inflammasome plays an important role in the process of hepatocellular carcinoma (HCC) is still unknown. Here, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, against HCC cells and the underlying mechanisms were investigated. Luteoloside significantly inhibited the proliferation of HCC cells in vitro and in vivo. Live-cell imaging and transwell assays showed that the migration and invasive capacities of HCC cells, which were treated with luteoloside, were significantly inhibited compared with the control cells. The inhibitory effect of luteoloside on metastasis was also observed in vivo in male BALB/c-nu/nu mouse lung metastasis model. Further studies showed that luteoloside could significantly reduce the intracellular reactive oxygen species (ROS) accumulation. The decreased levels of ROS induced by luteoloside was accompanied by decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by luteoloside resulted in inhibition of IL-1β. Thus, luteoloside exerts its inhibitory effect on proliferation, invasion and metastasis of HCC cells through inhibition of NLRP3 inflammasome. Our results indicate that luteoloside can be a potential therapeutic agent not only as an adjuvant therapy for HCC, but also, in the control and prevention of metastatic HCC. [ABSTRACT FROM AUTHOR]

Objective To understand the detection of four prohibited veterinary drugs of fresh and live freshwater fish sold in Guangzhou by analyzing the test data from risk monitoring and supervision sampling, so as to provide reference basis for food safety supervision. Methods Through the Guangzhou Food Safety Risk Monitoring system and the Food Safety Supervision and Inspection Public Information report of Guangzhou Market Administration, the test results of fresh water fish samples col-lected from supermarkets, markets, and online e-commerce in Guangzhou from 2017 to 2021 were obtained. The detection of nitrofuran drugs, chloramphenicol, sodium pentachloro phenate, and malachite green drugs were analyzed. Results The total detection rate of banned veterinary drugs in risk monitoring samples was 35.3% (84/238), and that in supervised sampling samples was 3.10% (118/3 806). The banned veterinary drugs with high detection rates of the two data sources were different. The risk monitoring rates of chloramphenicol and sodium pentachloro phenate were 17.23% (41/238) and 17.23% (41/238), respectively, and that of malachite green was 2.18% (83/3 806). The drug detection rate of the samples collected by risk monitoring in the network e-commerce link was Al.50% (19/40), which was the highest among all sampling links. The results of the two data sources showed that the detection rate of banned veterinary drugs in the wholesale market was high: 47.37% (18/38) and 4.13% (5/121), respectively. Conclusion The results of data analysis from the two sources complement each other and jointly reveal the problem of banned veterinary drug residues in fresh freshwater fish sold in Guangzhou from 2017 to 2021. It is suggested that the relevant departments pay more attention to the illegal use of chloramphenicol, sodium pentachloro phenate, and malachite green drugs. [ABSTRACT FROM AUTHOR]

COL4A4 mutation in thin basement membrane disease previously described in Alport syndrome. Background. Carriers of autosomal-recessive and X-linked Alport syndrome often have a thinned glomerular basement membrane (GBM) and have mutations in the COL4A3/COL4A4 and COL4A5 genes respectively. Recently, we have shown that many individuals with thin basement membrane disease (TBMD) are also from families where hematuria segregates with the COL4A3/COL4A4 locus. This study describes the first COL4A4 mutation in an individual with biopsy-proven TBMD who did not have a family member with autosomal-recessive or X-linked Alport syndrome, inherited renal failure, or deafness. Methods. The index case and all available family members were examined for dysmorphic hematuria> 50,000/mL using phase contrast microscopy and for segregation of hematuria with the COL4A3/COL4A4 and COL4A5 loci using DNA satellite markers. COL4A4 exons from the index case were then studied using the enzyme mismatch cleavage method, and exons that demonstrated abnormal cleavage products were sequenced. Results. Hematuria in this family segregated with a haplotype at the COL4A3/COL4A4 locus (P = 0.031) but not with haplotypes at the COL4A5 locus. A mutation in COL4A4 that changed C to T resulting in an arginine residue being replaced by a stop codon (R1377X) was demonstrated in exon 44, which encodes part of the α4(IV) collagen sequence close to the junction with the noncollagenous domain. This mutation was present in all five family members with hematuria, but not in the four unaffected family members, 33 unrelated individuals with TBMD, or 22 nonhematuric normals. Conclusions. R1377X has been described previously in a compound heterozygous form of autosomal-recessive Alport syndrome. Our observation is evidence that TBMD can represent a carrier state for autosomal-recessive Alport syndrome in at least some individuals. [ABSTRACT FROM AUTHOR]

In the chiral unitary approach, we have studied the single Cabibbo-suppressed decays Λ c → p K + K - and Λ c → p π + π - by taking into account the s-wave meson–meson interaction as well as the contributions from the intermediate vectors ϕ and ρ 0 . Our theoretical results for the ratios of the branching fractions of Λ c → p K ¯ ∗ 0 and Λ c → p ω with respect to the one of Λ c → p ϕ are in agreement with the experimental data. Within the picture that the scalar resonances f 0 (500) , f 0 (980) , and a 0 (980) are dynamically generated from the pseudoscalar-pseudoscalar interactions in s-wave, we have calculated the K + K - and π + π - invariant mass distributions respectively for the decays Λ c → p K + K - and Λ c → p π + π - . One can find a broad bump structure for the f 0 (500) and a narrow peak for the f 0 (980) in the π + π - invariant mass distribution of the decay Λ c → p π + π - . For the K + K - invariant mass distribution, in addition to the narrow peak for the ϕ meson, there is an enhancement structure near the K + K - threshold mainly due to the contribution from the f 0 (980) . Both the π + π - and K + K - invariant mass distributions are compatible with the BESIII measurement. We encourage our experimental colleagues to measure these two decays, which would be helpful to understand the nature of the f 0 (500) , f 0 (980) , and a 0 (980) . [ABSTRACT FROM AUTHOR]

The resource utilization of non-metallic components (NMC) in waste printed circuit boards (WPCBs) was concerned in this study. Pyrolysis oil, calorific value and building materials in NMC were recovered and utilized. Organic matter in NMC was recycled in the form of pyrolysis oil by pyrolysis treatment. The pyrolysis temperature was determined by thermogravimetric analysis. The composition of pyrolysis oil was analyzed by GC-MS. Thermogravimetric analysis shows that 300–400 °C is the main temperature range for the formation of pyrolysis oil, and the weight loss reaches 20.58%. Further, weight loss only achieves 6.38% within 400–800 °C. The GC-MS results show that the main components are phenols, which can be used for the synthesis of oil-based resins. In addition, the calorific value of pyrolysis residues was measured. The results show that the calorific value of pyrolysis residues obtained at 400 °C and 800 °C reaches 4.62 MJ/kg and 3.76 MJ/kg respectively in aerobic conditions. Finally, the residue without calorific value was prepared into building material with cement, and the compressive strength is proven to reach 9.43 MPa. This study provides a practical approach to the reutilization of NMC in WPCBs. Image 10502 • Non-metallic components in the separation tailings of WPCBs are fully utilized. • Organic matter in WPCBs is converted into pyrolysis oil. • The calorific value in the pyrolysis products is deeply utilized. • Fiberglass residues can be used as building materials. • The economic value of WPCBs is fully demonstrated. [ABSTRACT FROM AUTHOR]

Background. There are few studies comparing recurrences between endoscopic retrograde cholangiopancreatography (ERCP) and open choledochotomy (OCT). Aims. To compare the effect of different surgical methods on single and multiple recurrences of choledocholithiasis. Methods. A total of 1255 patients with choledocholithiasis who underwent ERCP or OCT were retrospectively studied. The recurrence of choledocholithiasis was calculated by the Kaplan–Meier method with the log-rank test. Multivariate analyses of recurrent choledocholithiasis were performed by introducing variables with P < 0.20 in univariate analysis into the logistic regression model. Results. A total of 204 (16.7%, 204/1225) patients relapsed. Among the 204 patients, 74.5% relapsed within three years after surgery, of whom 39.7% (81/204) had multiple relapses (≥ 2). The recurrence rate of ERCP (17.2%, 119/692) was higher than that of OCT (15.1%, 85/563), but the difference was not statistically significant. The independent risk factors for a single recurrence of choledocholithiasis were diabetes, stone number ≥ 2 , maximum stone diameter ≥ 15 mm , sedentary occupation, the approach of ERCP (EST or EPBD), periampullary diverticulum, primary suture, high-fat diet (postoperative), frequency of weekly vegetable intake (< 4, postoperative), and drinking (postoperative). However, the ERCP approach (EST or EPBD), OCT approach (LCBDE), primary suture, high-fat diet (postoperative), and frequency of weekly vegetable intake (< 4, postoperative) were independent risk factors for multiple recurrences of choledocholithiasis. Conclusion. Patients with choledocholithiasis should be followed up regularly for one to three years after treatment. Stone number ≥ 2, diabetes mellitus, periampullary diverticulum, surgical methods, and lifestyle are all risk factors for the recurrence of choledocholithiasis. ERCP is still the preferred surgical method based on the advantages of low risk of cholangitis recurrence, less hospital stay, minimally invasive surgery, fewer postoperative complications, and easier acceptance by elderly patients. In addition to optimizing the treatment plans, postoperative lifestyle management is also vital. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to explore the relationship between family communication, family violence, problematic internet use, anxiety, and depression and validate their potential mediating role. Methods: The study population consisted of Chinese adolescents aged 12 to 18 years, and a cross-sectional survey was conducted in 2022. Structural equation models were constructed using AMOS 25.0 software to examine the factors that influence adolescent anxiety and depression and the mediating effects of problematic internet use and family violence. Results: The results indicate that family communication was significantly and negatively related to family violence (β = -.494, p < 0.001), problematic internet use (β = -.056, p <.05), depression (β = -.076, p <.01), and anxiety (β = -.071, p <.05). And the finds also indicate that family violence mediated the relationships between family communication and depression (β = -.143, CI: -.198 -.080), and between family communication and anxiety (β = -.141; CI: -.198 -.074). Chain indirect effects between family communication and depression (β = -.051; CI: -.081 -.030) or anxiety (β = -.046; CI: -.080 -.043) via family violence and then through problematic internet use were also found in the present study. Conclusions: In conclusion, positive family communication is crucial in reducing anxiety and depression in adolescents. Moreover, problematic internet use and family violence mediate the effects of positive family communication on anxiety and depression. Therefore, improving family communication and promoting interventions aimed at reducing family violence and problematic internet use can help reduce anxiety and depression in adolescents, thus promoting their healthy development. [ABSTRACT FROM AUTHOR]

Plant R2R3-MYB transcription factors (TFs) have been suggested to play crucial roles in the response to diverse abiotic and biotic stress factors but there is little molecular evidence of this role in soybean plants. In this work, we identified and functionally characterized an R2R3-MYB TF, namely, GsMYB15, from the wild soybean ED059. Protein and promoter sequence analysis indicated that GsMYB15 is a typical R2R3-MYB TF and contains multiple stress-related cis-elements in the promoter region. GsMYB15 is located in the nucleus and exhibits transcriptional activation activity. QPCR assays suggested that the expression of GsMYB15 could be induced by NaCl, insect attacks and defense-related hormones (MeJA and SA). Furthermore, GsMYB15 exhibited highest expression in pods compared to other tissues. Functional analysis of GsMYB15 demonstrated that overexpression of GsMYB15 could increase salt tolerance and enhance the resistance to H. armigera larvae in transgenic Arabidopsis plants. Moreover, overexpression of GsMYB15 also affected the expression levels of salt stress- and defense-related genes in the transgenic plants. Feeding with transgenic Arabidopsis plant leaves could significantly suppress the expression levels of immunity-related genes in H. armigera larvae. Overexpression of GsMYB15 also increased mesophyll cell levels in transgenic plants. Taken together, these results provide evidence that GsMYB15 is a positive regulator of salt stress tolerance and insect resistance in transformed Arabidopsis plants. [ABSTRACT FROM AUTHOR]

Background: Twin growth discordance was demonstrated to be a risk factor for adverse perinatal outcomes, and prenatal ultrasonographic methods were utilized to predict twin growth discordance to improve outcomes. The results currently reported are not consistent due to the poor unified parameters and gestational durations.Methods: A total of 71 dichorionic twins with growth discordance and 346 dichorionic twins with normal growth were respectively included in the retrospective cohort study. The weight discordance of more than 25% was defined as a "growth discordant twin". The clinical baseline information, maternal outcomes, twin birth weights and fetal growth parameters (which were measured by ultrasound) were compared between the two groups from early gestation to late gestation. Multiple logistic regression and receiver operating characteristic curves were adopted to evaluate the predictive value of the growth parameters.Results: Compared with normal dichorionic twins, the clinical baseline conditions were similar in the twins those finally developed growth discordance. The fetal growth parameters and the deepest volume pocket of amniotic fluid in early and mid-pregnancy showed no obvious predictive values. The fetal growth parameters in late pregnancy showed predictive values, especially the discordance of estimated fetal weight (EFW) in the early third-trimester (P < 0.001, area under the curve, 0.822; the cut-off value, 20%; sensitivity, 66.67%; specificity, 91.30%; positive predictive value, 88.46%).Conclusion: Two assessment approaches were suggested and adopted to predict twin growth discordance in the current study. Twin growth should be assessed longitudinally and dynamically. Normal twins may show growth imbalance in the early stage. The discordance of EFW in late pregnancy may be a useful indicator for a growth discordance of more than 25%, which is required further confirmation. [ABSTRACT FROM AUTHOR]

To clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues. Similar results was confirmed at the protein level using immunohistochemistry and Western blotting. High AKR1B10 expression was negatively correlated with serum alpha-fetoprotein level and positively correlated with HBV-DNA level. Patients with high AKR1B10 expression had significantly higher disease-free survival than those with low expression within 2 years after liver resection. Multivariate analysis also confirmed high AKR1B10 expression to be a predictor of low risk of early HCC recurrence. In addition, high AKR1B10 expression was found to be a favorable factor of overall survival. These results suggest that AKR1B10 is involved in HBV-related hepatocarcinogenesis, but its high expression could predict low risk of early tumor recurrence in patients with HBV-related HCC after liver resection. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that human circulating microRNAs (miRNAs) could serve as diagnostic and prognostic biomarkers in various cancers. We aimed to explore novel miRNA biomarkers in the blood of breast cancer patients based on miRNA profiling. A miRCURY™ LNA Array was used to identify differentially altered miRNAs in the whole blood of breast cancer patients (n = 6) and healthy controls (n = 6). Levels of candidate miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in whole blood specimens of 15 breast cancer patients and 13 age-matched healthy control individuals. The miRWalk database was used to predict miRNA targets and the DAVID tool was used to identify significant enrichment pathways. A total of 171 differentially expressed miRNAs were identified by microarray, including 169 upregulated and 2 downregulated miRNAs in breast cancer. Five upregulated miRNAs (miR-30b-5p, miR-96-5p, miR-182-5p, miR-374b-5p, and miR-942-5p) were confirmed by qRT-PCR. The areas under the receiver operating characteristic curve of miR-30b-5p, miR-96-5p, miR-182-5p, miR-374b-5p, and miR-942-5p were 0.9333, 0.7692, 0.7590, 0.8256, and 0.8128, respectively. Importantly, upregulation of these five miRNAs was observed even in patients with very early-stage breast cancer. A total of 855 genes were predicted to be targeted by the five miRNAs, and the one cut domain family member 2 gene ( ONECUT2 ) was a shared target of the five miRNAs. Analysis of publicly available data revealed that these dysregulated miRNAs and the target genes were associated with the survival of breast cancer patients. Furthermore, the five miRNAs were significantly enriched in numerous cancer-related pathways, including “MicroRNAs in cancer”, “Pathways in cancer”, “FoxO signaling pathway”, “Ras signaling pathway”, “Rap1 signaling pathway”, “MAPK signaling pathway”, and “PI3K-Akt signaling pathway”. Our data support the potential of the five identified miRNAs as novel biomarkers for the detection of breast cancer, and indicate that they may be involved in breast cancer development and progression. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17263 and https://doi.org/10.1111/apt.17423 [ABSTRACT FROM AUTHOR]

Epidemiological studies have indicated that natural disasters have important impacts on ischemic stroke. This study determined the associations between natural disasters and the incidence and prevalence of ischemic stroke at the global level. A 28-year ecological trend study was performed to estimate worldwide changes in the incidence and prevalence of ischemic stroke and their associations with natural disasters by analyzing data from 193 countries. Quantum geographic information system-based visualization and multivariable linear regression were used. Changes in the incidence and prevalence of ischemic stroke, as well as disaster occurrence, varied among the different regions over the past 28 years (p < 0.001). Multiple linear regression revealed an independent and positive association between disaster occurrence and the incidence of ischemic stroke in males, females and both sexes combined (standardized coefficients = 0.515, 0.470 and 0.483, p < 0.001); similar associations were found for the prevalence of ischemic stroke (standardized coefficients = 0.471, 0.417 and 0.438, p < 0.001). The incidence and prevalence of ischemic stroke changed significantly at the global level and were independently associated with natural disasters. Both males and females show common but different vulnerabilities to natural disasters. This evidence supports policy making and resource allocation for disaster response and disease burden reduction. [ABSTRACT FROM AUTHOR]

Intravitreal anti-VEGF (anti-vascular endothelial growth factor) biologics have revolutionized the pharmacological management of chorioretinal diseases. However, the systemic adverse events such as stroke or bleeding are the concerns for many patients and physicians. The mechanism to develop these side effects are poorly understood. Consecutive 95 patients with retinal diseases were studied for their blood activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), and concentration of fibrinogen before and after intravitreal conbercept. Additionally, plasma nitric oxide (NO) and endothelin-1 (ET-1) were investigated on 38 of the 95 patients. Compared with the pre-injection, 4-week post-injection values of APTT and PT were increased by 0.582 s (p = 0.038, paired t test) and by 0.086 s (p = 0.080, paired t test; p = 0.0475, Sign test), respectively. At the same time, fibrinogen decreased by 0.048 g/L. Plasma levels of NO or ET-1 or VEGF did not significantly change from pre-injection levels. Our findings advanced the understanding of mechanism for systemic side effects associated with intravitreal anti-VEGF and emphasized paying more attention to higher risk of possible bleedings for patients following intravitreal conbercept. [ABSTRACT FROM AUTHOR]

Mutations in the COL4A4 gene in thin basement membrane disease. Background. Patients with thin basement membrane disease (TBMD) are often from families where hematuria segregates with the COL4A3 and COL4A4 genes. These genes also are affected in autosomal recessive Alport syndrome. The aim of this study was to demonstrate COL4A4 mutations in TBMD. Methods. Forty-eight unrelated individuals with TBMD who had no family members with autosomal recessive Alport syndrome were examined for COL4A4 mutations. The diagnosis of TBMD had been confirmed by renal biopsy (43/48, 90%) or by a family history of hematuria but without a renal biopsy (5/48, 10%). The 47 coding exons of COL4A4 were screened for mutations with the methods of enzyme mismatch cleavage or single stranded conformational polymorphism (SSCP) analysis, and exons that demonstrated electrophoretic abnormalities were sequenced. Results. Nine variants that altered the coding sequences were identified. These were nonsense and frameshift mutations that resulted in stop codons (N = 3), and glycine (N = 3) and non-glycine missense variants (N = 3). Four intronic variants and three neutral polymorphisms were also detected. In total, four variants were considered ‘pathogenic’ principally because they resulted in stop codons or were not present in non-hematuric normal subjects. Three variants were considered ‘possibly pathogenic’ but two of these were each present in one of 46 non-hematuric normal subjects. Conclusions. Pathogenic COL4A4 mutations were demonstrated in three of the nine (33%) families in whom hematuria segregated with the COL4A3/COL4A4 locus. Two stop codons (R1377X and 2788/91delG) and a glycine substitution (G960R) resulted in hematuria in all 16 members who were tested from these three families. The S969X mutation described here in TBMD for the first time, as well as the R1377X mutation, also occur in autosomal recessive Alport syndrome. [ABSTRACT FROM AUTHOR]

MDMB-CHMINACA is a newly synthetic cannabinoid, which scoped in NMS Lab, USA. Since there are currently no published data on MDMB-CHMINACA metabolism, we aimed to identify its biotransformation pathways and major metabolites. Liquid chromatography Q-exactive HF hybrid quadrupole-orbitrap mass spectrometry (LC–QE-HF-MS) using full scan positive ion mode and targeted MS-MS (ddms2) techniques with accurate mass measurement were employed to analyze the metabolic sites and pathways. An in vivo metabolic animal model of zebrafish was established to verify the metabolic pathways of MDMB-CHMINACA obtained from human liver microsomal experiment in vitro. The results showed that 29 metabolites were generated in the zebrafish animal model and human liver microsomes model. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, minor reactions also occurred at the tert-butyl chain and no reaction was analyzed at the indazole ring. We recommend M1 group (MDMB-CHMINACA ester hydroxylation) and M2 group (MDMB-CHMINACA monohydroxylation) as the potential poisoning markers to document MDMB-CHMINACA intake in clinical and forensic cases. Additionally, this study provides preliminary information regarding the metabolism of MDMB-CHMINACA that will guide analytical standard manufacturers to better provide suitable references for further studies on newly encountered designer drugs. [ABSTRACT FROM AUTHOR]

Yueju, a famous classic Chinese prescription, has been extensively used in treating depression syndromes for hundreds of years. Recent studies have reported that Yueju showed good effects in treating metabolic diseases, such as obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH), which leads to cirrhosis and severe cardiovascular diseases, is closely linked to obesity and abnormal lipid metabolism. In this study, Yueju could decrease the levels of alanine aminotransferase, aspartate transaminase, triglyceride, cholesterol, and low-density lipoprotein-C but increase the high-density lipoprotein-C in the serum of the NASH rat model induced by high-fat and high-cholesterol diet. Yueju could alleviate hepatosteatosis by increasing the phosphorylation of acetyl-CoA carboxylase and inhibiting the expression of fatty acid synthase and stearoyl-CoA desaturase 1. Yueju downregulated the expression of α-smooth muscle actin and collagen type 1A1, ameliorating the liver fibrilization. Yueju could also protect the hepatocytes from apoptosis by upregulating antiapoptosis protein Bcl-2 and X-linked inhibitor of apoptosis protein and downregulating apoptotic proteins Bax and cleaved poly ADP-ribose polymerase. Thus, Yueju could improve liver function, regulate lipid metabolism, alleviate hepatosteatosis and fibrosis, and protect hepatocytes from apoptosis against NASH. Yueju may be used as an alternative effective medicine for NASH treatment. [ABSTRACT FROM AUTHOR]

We reported a large Chinese family diagnosed with autosomal dominant tubulointerstitial kidney disease caused by MUC1 mutation (ADTKD-MUC1). Cytosine duplication within a string of 7 cytosines in the variable-number tandem repeats (VNTR) region of the MUC1 gene was detected by long-read single-molecule real-time (SMRT) sequencing. MUC1 frameshift protein (MUC1fs) was found to be expressed in renal tubules and urinary exfoliated cells by pathological examination. The family, which consisted of 5 generations including 137 individuals, was followed for 5 years. Genetic testing was performed in thirty-four individuals, 17 of whom carried MUC1 mutations. The ADTKD-MUC1-affected individuals had an elevated incidence of hyperuricaemia without gout attack. Within five years, higher baseline levels of urinary α1-microglobulin were detected in affected individuals with rapidly progressing renal failure than in affected individuals with stable renal function, and the increases manifested even before increases in serum creatinine. This study demonstrates that SMRT sequencing is an effective method for the identification of MUC1 mutations. The pathological examination of MUC1fs expression in renal tissue and urinary exfoliated cells can contribute to early screening of family members suspected to be affected. It is suggested that affected individuals with elevated urinary α1-microglobulin levels should be closely monitored for renal function. [ABSTRACT FROM AUTHOR]

Platelets (PLTs) are involved in tumor growth, metabolism and vascular activation. PLT-based models have been reported to have significant value on the recurrence of malignant hepatic tumors. The present study aimed to investigate the effect of PLT count and 18 PLT-based models on the prognosis of patients with malignant hepatic tumors. The clinical data from 189 patients with malignant hepatic tumors were retrospectively analyzed and used to calculate the scores of the 18 PLT-based models. Receiver operating characteristic curve was used to determine the suitable cut-off values of mortality and recurrence in patients with malignant hepatic tumors. The overall survival and cumulative recurrence rates of patients were calculated using Kaplan-Meier survival curves and the difference was analyzed using log-rank test. Multivariate analysis was performed to determine the independent risk factors of recurrence-free survival and overall survival. In the present study, 11 models were considered as predictors of mortality (P<0.05) and six models were considered as predictors of recurrence (P<0.05). The results from multivariate analysis demonstrated that vascular cancer embolus, uric acid >231 µmol/l, hemoglobin >144 g/l and the Lok index model >0.695 were considered as independent risk factors of mortality (P<0.05). Furthermore, vascular cancer embolus, PLT to lymphocyte ratio (PLR) >175 and fibrosis-4 (FIB-4) >4.82 were independent factors of recurrence (P<0.05). In addition, the results from this study indicated that the Lok-index could be considered as a predictor of the overall survival rate. In conclusion, the FIB-4 and PLR model may be valuable for predicting the recurrence-free rate of patients with malignant hepatic tumors. [ABSTRACT FROM AUTHOR]

Series of 1,2,4-triazole Schiff bases (2a-2d, 2f-2h and 3a-3h) have been designed and synthesized. The structure of title compounds was confirmed on the basis of their spectral data and elemental analysis. All the target compounds were screened for their in vitro antifungal activity and antibacterial activity. Two of the tested compounds (2a and 2b) exhibited significant antifungal activity against most fungi, especially compound 2a showed better antifungal activity than triadimefon. Meanwhile, the antibacterial activity assay also indicated compound 2a exhibited excellent antibacterial activities comparable to chloramphenicol. The SAR manifested no substitution at position 5 of the triazole ring caused an increase in activity, and 3-phenoxy phenyl group introduced in 1,2,4-triazole scaffold can enhance the antibacterial activity. The DFT calculation indicated triazole ring, S atom and benzene ring in both of the 2a and 3a make a major contribution to the activity. [ABSTRACT FROM AUTHOR]

We investigated the beneficial effects and underlying mechanisms of Zhuanggu Guanjie (ZGGJ) pill in osteoporosis in vitro and in vivo. Bone marrow macrophages from 4–6-week-old mice were cultured in the presence of macrophage colony-stimulating factor (15 ng/mL) and receptor activator of nuclear factor-κB ligand (30 ng/mL). Osteoclast differentiation was determined by quantification of tartrate-resistant acid phosphatase activity. Gelatin zymography was used to detect the activity of matrix metalloproteinases in osteoclasts. Ovariectomized rats were administered orally with estradiol valerate or ZGGJ for 8 weeks. Blood was collected to measure serum indices. Tibiae were harvested to carry out bone microcomputed tomography scanning, histomorphological analysis, and bone strength determination. ZGGJ inhibited tartrate-resistant acid phosphatase activity, matrix metalloproteinase 9 expression, and bone resorption in vitro. At doses of 0.55, 1.1, and 2.2 g/kg, ZGGJ exerted significant osteoprotective effects including inhibition of bone turnover markers and improved tibia bone strength in ovariectomized rats. Microcomputed tomographic analysis showed that ZGGJ improved the trabecular architecture with increased connectivity density and trabecular thickness and decreased trabecular spacing. These results revealed that ZGGJ prevents bone loss induced by ovariectomy in rats and that inhibition of bone resorption is involved in the bone-protective effects of ZGGJ. [ABSTRACT FROM AUTHOR]

This study aims to clarify the relationship and mechanism between expression of autophagy-related protein P62 and prognosis of patients with hepatocellular carcinoma ( HCC) involving chronic hepatitis B virus ( HBV) infection and aflatoxin B1 ( AFB1) exposure. HCC patients who underwent resection were divided into three groups: HBV(+)/ AFB1(+) ( n = 26), HBV(+)/ AFB1(−) ( n = 68), and HBV(−)/ AFB1(−) ( n = 14). The groups were compared in terms of mRNA and protein levels of P62, disease-free survival ( DFS), and overall survival ( OS) and the expression of NRF2, Nqo1, and AKR7A3 in P62 high-expression and low-expression group. HBV(+)/ AFB1(+) group has lower DFS and OS, and higher P62 expression than in the other two groups. P62 expression generally correlated with elevated NRF2 and Nqo1 expression, and reduced AKR7A3 expression. Patients expressing high levels of P62 showed significantly lower DFS and OS rates than patients expressing low levels. HCC involving HBV infection and AFB1 exposure is associated with relatively high risk of tumor recurrence, and this poor prognosis may relate to high P62 expression. High P62 expression activates the NRF2 pathway, promotes tumor recurrence. The downregulation of AKR7A3 also reduced liver detoxification of aflatoxin B1. [ABSTRACT FROM AUTHOR]

Objective: To investigate the inhibitory effect of Hirsutella sinensis (HS) on epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells induced by aristolochic acid (AA) and its possible mechanism. Methods: 18 male Sprague-Dawley rats were randomly and equally divided into the following 3 groups: AA group, AA+HS group and control group. Urinary protein excretion and creatinine clearance (CCr) were measured. All rats were sacrificed at the end of 12th week. The pathological examination of renal tissue was performed and the mRNA and protein expression of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), cytokeratin-18 and Snail in renal cortex were determined by real time quantitative PCR and immunohistochemical staining respectively. In addition, human renal proximal tubule epithelial cells line (HKC) was divided into the following 4 groups: AA group, AA+HS group, HS control group and control group. The above mRNA and protein expression in HKC was determined by real time quantitative PCR and Western blot respectively. Results: (1) CCr was significantly decreased, and the urinary protein excretion and relative area of renal interstitial fibrosis were significantly increased in the rats of AA and AA+HS group compared to those in control group (P<0.05 or P<0.01); all the above abnormalities significantly lightened in the rats of AA+HS group compared to those in AA group (P<0.05). (2) The mRNA and protein expression of TGF-β1, α-SMA and Snail was significantly up-regulated and the expression of cytokeratin-18 was significantly down-regulated in the rat renal cortex as well as in the cultured HKC cells in AA and AA+HS groups compared to those in control group (P<0.05 or P<0.01); all the above abnormalities significantly alleviated in AA+HS group compared to those in AA group (P<0.05 or P<0.01). (3) Knockdown endogenous Snail expression by siRNA could ameliorate AA-induced EMT of HKC cells, while overexpression of Snail by plasmid transfection diminished the antagonistic effect of HS on AA-induced EMT. These results suggest Snail might be a potential target of HS effect. Conclusion: HS is able to antagonize, to some extent, tubular EMT and renal interstitial fibrosis caused by AA, which might be related to its inhibitory effects on the TGF-β1 and Snail expression. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of curcumin, one of the most important active ingredients of turmeric, on podocyte injury in vitro and obesity-related glomerulopathy (ORG) in vivo. Cellular experiments in vitro showed that curcumin significantly antagonized leptin-induced downregulation of the mRNA and protein expression of podocyte-associated molecules including nephrin, podocin, podoplanin, and podocalyxin. Animal experiments in vivo showed that curcumin significantly reduced the body weight, Lee’s index, abdominal fat index, urinary protein excretion, and average glomerular diameter and significantly upregulated the mRNA and protein expressions of the above podocyte-associated molecules in ORG mice. Furthermore, the experiments in vitro and in vivo both displayed that curcumin could downregulate the mRNA and protein expressions of Wnt1, Wnt2b, Wnt6, and β-catenin and upregulate the phosphorylation level of β-catenin protein in podocytes and renal tissue. In conclusion, curcumin is able to alleviate the harmful reaction of leptin on podocytes and reduce the severity of ORG. The above protective effects are associated with the inhibition of Wnt/β-catenin signaling activation in podocytes. [ABSTRACT FROM AUTHOR]

Background: The perennial O. rufipogon (common wild rice), which is considered to be the ancestor of Asian cultivated rice species, contains many useful genetic resources, including drought resistance genes. However, few studies have identified the drought resistance and tissue-specific genes in common wild rice. Results: In this study, transcriptome sequencing libraries were constructed, including drought-treated roots (DR) and control leaves (CL) and roots (CR). Using Illumina sequencing technology, we generated 16.75 million bases of high-quality sequence data for common wild rice and conducted de novo assembly and annotation of genes without prior genome information. These reads were assembled into 119,332 unigenes with an average length of 715 bp. A total of 88,813 distinct sequences (74.42% of unigenes) significantly matched known genes in the NCBI NT database. Differentially expressed gene (DEG) analysis showed that 3617 genes were up-regulated and 4171 genes were down-regulated in the CR library compared with the CL library. Among the DEGs, 535 genes were expressed in roots but not in shoots. A similar comparison between the DR and CR libraries showed that 1393 genes were up-regulated and 315 genes were down-regulated in the DR library compared with the CR library. Finally, 37 genes that were specifically expressed in roots were screened after comparing the DEGs identified in the above-described analyses. Conclusion: This study provides a transcriptome sequence resource for common wild rice plants and establishes a digital gene expression profile of wild rice plants under drought conditions using the assembled transcriptome data as a reference. Several tissue-specific and drought-stress-related candidate genes were identified, representing a fully characterized transcriptome and providing a valuable resource for genetic and genomic studies in plants. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis has decreased significantly in prevalence and intensity of infection in China, thus more accurate and sensitive methods are desperately needed for the further control of schistosomiasis. The present work aimed to assess the utility of the loop-mediated isothermal amplification (LAMP) for detection of light intensity infection or false-negative patients and patients post-treatment, targeting the highly repetitive retrotransposon SjR2 of Schistosoma japonicum. Methodology/ Principal Findings: LAMP was first assessed in rabbits with low intensity infection (EPG<10). Then 110 patient sera from Hunan Province, China, and 47 sera after treatment by praziquantel were used to evaluate the diagnostic validity of LAMP. Meanwhile, 42 sera from healthy individuals in a non-endemic area, and 60 sera from "healthy" residents who were identified as being negative for feces examination and immuno-methods in an endemic area were also examined. The results showed that LAMP could detect S. japonicum DNA in sera from rabbits at 3rd day post-infection. Following administration of praziquantel, the S. japonicum DNA in rabbit sera became negative at 10 weeks post-treatment. Of 110 sera from patients, LAMP showed 95.5% sensitivity, and even for 41 patients with less than 10 EPG, the sensitivity of LAMP still reached to 95.1%. For 47 patients after treatment, the negative conversion rate of S. japonicum DNA in patient sera increased from 23.4%, 61.7% to 83.0% at 3 months, 6 months and 9 months post-treatment, respectively. No false-positive result was obtained for 42 human sera from non-endemic area, while for the 60 "healthy" individuals from endemic area, 10 (16.7%) individuals were positive by LAMP, which suggested that these individuals might be false-negative patients. Conclusions/ Significance: The present study demonstrated that the LAMP assay is sensitive, specific, and affordable, which would help reduce schistosomiasis transmission through targeted treatment of individuals, particularly for those with negative stool examinations who may yet remain infected. The LAMP assay may provide a potential tool to support schistosomiasis control and elimination strategies. Author Summary: Accurate diagnostic tests play a key role in patient management and control of schistosomiasis, especially in China where the prevalence and intensity of Schistosoma japonicum infection is low in recent years. The present study aimed to assess the utility of the loop-mediated isothermal amplification (LAMP) assay for detection of light intensity infection or false-negative patients and for the evaluation of chemotherapy effectiveness in patients, targeting the highly repetitive retrotransposon SjR2 of S. japonicum, using 110 serum samples of schistosomiasis patients. The results showed that the LAMP assay had high sensitivity of 95.1% for the diagnosis of S. japonicum infection with the lowest intensity (EPG<10). For the assessment of efficacy after treatment with praziquantel, the negative conversion rate increased from 23.4%, 61.7% to 83.0% at 3 months, 6 months and 9 months post-treatment by LAMP, whereas for ELISA and IHA, the negative conversion rate remains at a low level (25.5% by ELISA and 31.9% by IHA) even at 9 months after treatment. Our results demonstrated that the LAMP assay may provide a valuable tool for the diagnosis of Schistosoma infection, especially for cases of light infection which is coincident with the current endemic situation. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis has decreased significantly in prevalence and intensity of infection in China, thus more accurate and sensitive methods are desperately needed for the further control of schistosomiasis. The present work aimed to assess the utility of the loop-mediated isothermal amplification (LAMP) for detection of light intensity infection or false-negative patients and patients post-treatment, targeting the highly repetitive retrotransposon SjR2 of Schistosoma japonicum. Methodology/ Principal Findings: LAMP was first assessed in rabbits with low intensity infection (EPG<10). Then 110 patient sera from Hunan Province, China, and 47 sera after treatment by praziquantel were used to evaluate the diagnostic validity of LAMP. Meanwhile, 42 sera from healthy individuals in a non-endemic area, and 60 sera from "healthy” residents who were identified as being negative for feces examination and immuno-methods in an endemic area were also examined. The results showed that LAMP could detect S. japonicum DNA in sera from rabbits at 3rd day post-infection. Following administration of praziquantel, the S. japonicum DNA in rabbit sera became negative at 10 weeks post-treatment. Of 110 sera from patients, LAMP showed 95.5% sensitivity, and even for 41 patients with less than 10 EPG, the sensitivity of LAMP still reached to 95.1%. For 47 patients after treatment, the negative conversion rate of S. japonicum DNA in patient sera increased from 23.4%, 61.7% to 83.0% at 3 months, 6 months and 9 months post-treatment, respectively. No false-positive result was obtained for 42 human sera from non-endemic area, while for the 60 “healthy” individuals from endemic area, 10 (16.7%) individuals were positive by LAMP, which suggested that these individuals might be false-negative patients. Conclusions/ Significance: The present study demonstrated that the LAMP assay is sensitive, specific, and affordable, which would help reduce schistosomiasis transmission through targeted treatment of individuals, particularly for those with negative stool examinations who may yet remain infected. The LAMP assay may provide a potential tool to support schistosomiasis control and elimination strategies. [ABSTRACT FROM AUTHOR]

Background & Aims: Official guidelines do not recommend hepatic resection (HR) for patients with hepatocellular carcinoma (HCC) and portal hypertension (PHT). This study aims to investigate the safety and efficacy of HR for patients with HCC and PHT. Methods: Mortality and survival after HR were analyzed retrospectively in a consecutive sample of 1738 HCC patients with PHT (n = 386) or without it (n = 1352). To assess the robustness of findings, we repeated the analysis using propensity score-matched analysis. We also comprehensively searched the PubMed database for studies evaluating the efficacy and safety of HR for patients with HCC and PHT. Results: The 90-day mortality rate was 6.7% among those with PHT and 2.1% among those without it (P<.001). Patients without PHT had a survival benefit over those with PHT at 1, 3, and 5 years (96% vs 90%, 75% vs 67%, 54% vs 45%, respectively; P = .001). In contrast, PHT was not associated with worse short- or long-term survival when only propensity score-matched pairs of patients and those with early-stage HCC or those who underwent minor hepatectomy were included in the analysis (all P>.05). Moreover, the recurrence rates were similar between the two groups. Consistent with our findings, all 9 studies identified in our literature search reported HR to be safe and effective for patients with HCC and PHT. Conclusions: HR is safe and effective in HCC patients with PHT and preserved liver function. This is especially true for patients who have early-stage HCC or who undergo minor hepatectomy. [ABSTRACT FROM AUTHOR]

Urotensin II (UII) is implicated in immune inflammatory diseases through its specific high-affinity UT receptor (UTR). Enhanced expression of UII/UTR was recently demonstrated in the liver with acute liver failure (ALF). Here, we analysed the relationship between UII/UTR expression and ALF in lipopolysaccharide (LPS)/D-galactosamine (GalN)-challenged mice. Thereafter, we investigated the effects produced by the inhibition of UII/UTR system using urantide, a special antagonist of UTR, and the potential molecular mechanisms involved in ALF. Urantide was administered to mice treated with LPS/GalN. Expression of UII/UTR, releases of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interferon-γ (IFN-γ), and activation of nuclear factor κB (NF-κB) signaling pathway were assessed in the lethal ALF with or without urantide pretreatment. We found that LPS/GalN-challenged mice showed high mortality and marked hepatic inflammatory infiltration and cell apoptosis as well as a significant increase of UII/UTR expression. Urantide pretreatment protected against the injury in liver following downregulation of UII/UTR expression. A close relationship between the acutely flamed hepatic injury and UII/UTR expression was observed. In addition, urantide prevented the increases of proinflammatory cytokines such as TNF-α, IL-1β and IFN-γ, and activation of NF-κB signaling pathway induced by LPS/GalN in mice. Thus, we conclude that UII/UTR system plays a role in LPS/GalN-induced ALF. Urantide has a protective effect on the acutely inflamed injury of liver in part through preventing releases of proinflammatory cytokines and activation of NF-κB pathway. [ABSTRACT FROM AUTHOR]

Changhsingian (latest Permian) reefs are reported from the Wubaiti structure, northern Sichuan Basin of southwest China. Here, reefs grew along the platform margins and their tempo-spatial distribution and growth stages were determined based on the integration of detailed seismic profiles, well logs and core data. The Wubaiti reefs experienced two distinct development stages. The first episode of reef development was characterized by the growth of coral and sponge patch reefs during early-middle Changhsingian time. The second episode, the main growth phase of the Wubaiti reefs, occurred in late Changhsingian time when both sponges and algae acted as major reef-builders. These reef-building organisms disappeared in the Permian-Triassic mass extinction. Reef growth coincided with a local transgression event, but ceased due to a fall in local sea-level in the latest Changhsingian time. Dolostones of various parts of the Wubaiti reefs provide considerably high-quality reservoirs for natural gas in the Sichuan Basin. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBFα)-ETO, CBFβ-MYH11, PML-RARα, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients < 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance. [ABSTRACT FROM AUTHOR]

Abstract: Hydrophobins are a family of natural self-assembling proteins with high biocompability, which are apt to form strong and ordered assembly onto many kinds of surfaces. These physical-chemical and biological properties make hydrophobins suitable for surface modification and biomolecule immobilization purposes. A class II hydrophobin HFBI was used as enzyme immobilization matrix on platinum electrode to construct amperometric glucose biosensor. Permeability of HFBI self-assembling film was optimized by selecting the proper HFBI concentration for electrode modification, in order to allow H2O2 permeating while prevent interfering compounds accessing. HFBI self-assembly and glucose oxidase (GOx) immobilization was monitored by quartz crystal microbalance (QCM), and characterization of the modified electrode surface was obtained by scanning electron microscope (SEM). The resulting glucose biosensors showed rapid response time within 6s, limits of detection of 0.09mM glucose (signal-to-noise ratio=3), wide linear range from 0.5 to 20mM, high sensitivity of 4.214×10−3 AM−1 cm−2, also well selectivity, reproducibility and lifetime. The all-protein modified biosensor exhibited especially high efficiency of enzyme utilization, producing at most 712μA responsive current for per unit activity of GOx. This work provided a promising new immobilization matrix with high biocompatibility and adequate electroactivity for further research in biosensing and other surface functionalizing. [Copyright &y& Elsevier]

Abstract: A novel amperometric glucose biosensor based on the nine layers of multilayer films composed of multi-wall carbon nanotubes (MWCNTs), gold nanoparticles (GNp) and glucose oxidase (GOD) was developed for the specific detection of glucose. MWCNTs were chemically modified with the H2SO4–HNO3 pretreatment to introduce carboxyl groups which were used to interact with the amino groups of poly(allylamine) (PAA) and cysteamine via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide cross-linking reaction, respectively. A cleaned Pt electrode was immersed in PAA, MWCNTs, cysteamine and GNp, respectively, followed by the adsorption of GOD, assembling the one layer of multilayer films on the surface of Pt electrode (GOD/GNp/MWCNTs/Pt electrode). Repeating the above process could assemble different layers of multilayer films on the Pt electrode. PBS washing was applied at the end of each assembly deposition for dissociating the weak adsorption. Film assembling and characterization were studied by transmission electron microscopy and quartz crystal microbalance, and properties of the resulting glucose biosensors were measured by electrochemical measurements. The marked electrocatalytic activity of Pt electrode based on multilayer films toward H2O2 produced during GOD enzymatic reactions with glucose permitted effective low-potential amperometric measurement of glucose. Taking the sensitivity and selectivity into consideration, the applied potential of 0.35V versus Ag/AgCl was chosen for the oxidation detection of H2O2 in this work. Among the resulting glucose biosensors, the biosensor based on nine layers of multilayer films was best. It showed a wide linear range of 0.1–10mM glucose, with a remarkable sensitivity of 2.527μA/mM, a detection limit of 6.7μM estimated at a signal-to-noise ratio of 3 and fast response time (within 7s). Moreover, it exhibited good reproducibility, long-term stability and the negligible interferences of ascorbic acid, uric acid and acetaminophen. The study can provide a feasible approach on developing new kinds of oxidase-based amperometric biosensors, and can be used as an illustration for constructing various hybrid structures. [Copyright &y& Elsevier]

Background: To develop a nomogram for predicting the International Study Group of Liver Surgery (ISGLS) grade B/C posthepatectomy liver failure (PHLF) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients.Methods: Patients initially treated with hepatectomy were included. Univariate regression analysis and stochastic forest algorithm were applied to extract the core indicators and reduce redundancy bias. The nomogram was then constructed by using multivariate logistic regression, and validated in internal and external cohorts, and a prospective clinical application.Results: There were 900, 300 and 387 participants in training, internal and external validation cohorts, with the morbidity of grade B/C PHLF were 13.5, 11.0 and 20.2%, respectively. The nomogram was generated by integrating preoperative total bilirubin, platelet count, prealbumin, aspartate aminotransferase, prothrombin time and standard future liver remnant volume, then achieved good prediction performance in training (AUC = 0.868, 95%CI = 0.836-0.900), internal validation (AUC = 0.868, 95%CI = 0.811-0.926) and external validation cohorts (AUC = 0.820, 95%CI = 0.756-0.861), with well-fitted calibration curves. Negative predictive values were significantly higher than positive predictive values in training cohort (97.6% vs. 33.0%), internal validation cohort (97.4% vs. 25.9%) and external validation cohort (94.3% vs. 41.1%), respectively. Patients who had a nomogram score < 169 or ≧169 were considered to have low or high risk of grade B/C PHLF. Prospective application of the nomogram accurately predicted grade B/C PHLF in clinical practise.Conclusions: The nomogram has a good performance in predicting ISGLS grade B/C PHLF in HBV-related HCC patients and determining appropriate candidates for hepatectomy. [ABSTRACT FROM AUTHOR]

In vitro and in vivo metabolism of synthetic cannabinoid, N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluropentyl)-1H-indazole-3-carboxamide (PX-2), has been studied based on human liver microsomes and zebrafish using ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). The dd-MS2 spectra technique is used to analysis metabolic sites and pathway by accurate mass measurement in the research process. An animal model of zebrafish in vivo metabolism is established to verify the in vitro metabolism pathway of PX-2. The results indicated that 20 kinds of metabolites were generated in the zebrafish animal model and human liver microsome model. Biotransformations mainly occurred at the amino of the compound, and minor reaction occurred at the pentyl chain and benzyl. We recommend M1.1 (PX-2 amide hydrolysis metabolites), and M3.1 (PX-2 oxidative defluorination and hydroxylation) combined M1.4 (PX-2 Phenylalanine loss) to be the potential poisoning markers. Metabolism of the synthetic cannabinoid PX-2 in vitro human liver microsomes and in vivo zebrafish. Image 1 • Analysis of in vivo metabolites and metabolic pathways by new experimental animal zebrafish. • Mass spectrometry analysis of PX-2 original drugs and metabolites. • Analysis of in vivo and in vitro metabolites and biotransformations of PX-2. [ABSTRACT FROM AUTHOR]

Serum interleukin-17 is closely related to inflammatory liver injury after hepatitis B virus (HBV) infection. The objective is to study the expression of interleukin-17 (IL-17) in different immune phases in patients with chronic hepatitis B. Whole venous blood was obtained from normal controls (n = 20) and four patient groups (n = 213): immune tolerance phase (IT, n = 57), immune clearance phase (IC, n = 59), non (low)-replicating phase (LR, n = 44), and reactivation phase (RA, n = 53). We measured IL-17, IL-6, and tumor necrosis factor alpha (TNF-α) levels in serum samples and measured IL-17, IL-6, and TNF-α messenger RNA (mRNA) levels in peripheral blood mononuclear cell (PBMC). Compared to normal controls, IL-17, IL-6, and TNF-α protein levels in serum and mRNA levels in PBMC were significantly higher in the four groups. IL-17 protein levels in serum and mRNA levels in PBMC were positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-6, and TNF-α. Compared to patients in the IT phase and LR phase, patients in the IC phase exhibited the highest serum IL-17 and PBMC mRNA levels. The IL-17 mRNA levels of patients in RA phase were higher than those in patients in IT phase. IL-17 plays an important part in the various immune phases of chronic hepatitis B (CHB). [ABSTRACT FROM AUTHOR]