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Hepatocellular carcinoma (HCC) is a serious threat to human health. miR-340 participates in HCC pathogenesis, but its specific mechanism is not completely clear. Therefore, our study assessed the mechanism by how miR-340 involves in HCC. The cancer tissues and paracancerous tissues of HCC patients were collected. miR-340 mimics/NC and Akt siRNA were transfected into HepG2 cells followed by analysis of miR-304 and EMT-related molecules expression by Real-time PCR, cell invasion and migration by Transwell assay, cell proliferation ability by CCK8 assay as well as p-Akt and p-mTOR level by Western blot. miR-340 in HCC tissues was significantly downregulated compared to adjacent tissues (P P

Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan Rabdosia rubescens with anti-tumor activity, unclear anti-tumor mechanisms and limited water solubility hamper its clinical application. Here, we showed a2, a new JDA derivative, inhibited the growth of gastric cancer cells. Subsequently, we discovered for the first time that a2 induced ferroptosis. Importantly, compound a2 decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity of a2. Furthermore, we demonstrated that a2 caused ferrous iron accumulation through the autophagy pathway, prevention of which rescued a2 induced ferrous iron elevation and cell growth inhibition. Moreover, a2 exhibited more potent anti-cancer activity than 5-fluorouracil in gastric cancer cell line-derived xenograft mice models. Patient-derived tumor xenograft models from different patients displayed varied sensitivity to a2, and GPX4 downregulation indicated the sensitivity of tumors to a2. Finally, a2 exhibited well pharmacokinetic characteristics. Overall, our data suggest that inducing ferroptosis is the major mechanism mediating anti-tumor activity of a2, and a2 will hopefully serve as a promising compound for gastric cancer treatment., Graphical abstract Natural product derivative, a2, exhibited anti-tumor activity by inducing ferroptosis through decreasing GPX4 and causing ferrous iron accumulation in gastric cancer cells.Image 1

The ubiquitin-like protein NEDD8 is a critical signaling molecule implicated in the functional maintenance and homeostasis of cells. Dysregulation of this process is involved in a variety of human diseases, including cancer. Therefore, NEDD8-activating enzyme E1 (NAE), the only activation enzyme of the neddylation pathway, has been an emergent anticancer target. In view of the single-agent modest response of the clinical NAE inhibitor, pevonedistat (compound 1, MLN4924), efforts on development of new inhibitors with both high potency and better safety profiles are urgently needed. Here, we report a structural hopping strategy by optimizing the central deazapurine framework and the solvent interaction region of compound 1, leading to compound 26 bearing a pyrimidotriazole scaffold. Compound 26 not only has compatible potency in the biochemical and cell assays but also possesses improved pharmacokinetic (PK) properties than compound 1. In vivo, compound 26 showed significant antitumor efficacy and good safety in xenograft models.

The relative efficacy of different sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in reducing cardiorenal events in type 2 diabetic adults is unclear. We searched PubMed and Embase. Three primary endpoints were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), and kidney function progression (KFP). Bayesian network meta-analysis was conducted to synthesize hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) to rank drug treatments. Subcutaneous semaglutide (HR 0.73, 95% CI 0.55-0.96) and albiglutide (HR 0.76, 95% CI 0.63-0.93) significantly reduced MACE versus lixisenatide. Canagliflozin (HRs: 0.69, 0.68, 0.67 and 0.58) and empagliflozin (HRs: 0.70, 0.69, 0.68 and 0.59) significantly reduced HHF versus dulaglutide, exenatide, lixisenatide and subcutaneous semaglutide. Dapagliflozin (HRs: 0.62, 0.60, 0.68 and 0.63) and empagliflozin (HRs: 0.64, 0.61, 0.69 and 0.64) significantly reduced KFP versus dulaglutide, exenatide, liraglutide and lixisenatide. Different drug treatments had the maximum SUCRA values as for preventing different cardiorenal endpoints. Different GLP-1 RAs and SGLT2 inhibitors have different efficacy in preventing cardiorenal endpoints in type 2 diabetes, and the most efficacious drugs are different as for preventing different cardiorenal endpoints.

Objectives. The association between platelet distribution width (PDW) and mortality in hemodialysis (HD) patients has received little attention. Methods. We retrospectively enrolled HD patients in a single center from January 1, 2008, to December 30, 2011. The primary and secondary endpoints were all-cause and cardiovascular mortality, respectively. The association between PDW and mortality was estimated by Cox regression model. Results. Of 496 patients, the mean age was 52.5 ± 16.6 years, and the Charlson comorbidity index was 4.39 ± 1.71. During the follow-up period of 48.8 ± 6.7 months, 145 patients (29.2%) died, including 74 (14.9%) cardiovascular deaths. 258 (52.0%) with PDW

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP), in which exon open reading frame 15 (ORF15) of RPGR has been implicated to play a substantial role. We identified a novel hemizygous missense mutation E585K of RPGR from whole-exome sequencing of RP. RNA-Seq analysis and functional study were conducted to investigate the underlying pathogenic mechanism of the mutation. Our results showed that the mutation actually affected RPGR ORF15 splicing. RNA-Seq analysis of the human retina followed by validation in cells revealed a complex splicing pattern near the 3′ boundary of RPGR exon 14 in the ORF15 region, resulting from a variety of alternative splicing events (ASEs). The wildtype RPGR mini-gene expressed in human 293T cells confirmed these ASEs in vitro. In contrast, without new RNA species detected, the mutant mini-gene disrupted the splicing pattern of the ORF15 region, and caused loss of RPGR transcript heterogeneity. The RNA species derived from the mutant mini-gene were predominated by a minor out-of-frame transcript that was also observed in wildtype RPGR, resulting from an upstream alternative 5′ splice site in exon 14. Our findings therefore provide insights into the influence of RPGR exonic mutations on alternative splicing of the ORF15 region, and the underlying molecular mechanism of RP.

Supplemental material, sj-docx-1-cll-10.1177_09636897221122997 for METTL3-Mediated m6A Modification of lncRNA MALAT1 Facilitates Prostate Cancer Growth by Activation of PI3K/AKT Signaling by Yuanshen Mao, Wenfeng Li, YiMing Weng, Bao Hua, Xin Gu, Chao Lu, Bin Xu, Huan Xu and Zhong Wang in Cell Transplantation

Background Acute respiratory infections (ARIs) remain a significant public threat with high morbidity and mortality worldwide; viruses are significant pathogens that cause ARIs. This study was conducted to better understand the epidemiological characteristics of respiratory viruses circulating in southern China. Methods We collected 22,680 respiratory samples from ARI patients in 18 hospitals in southern China during 2009–2018; seven common respiratory viruses including Flu, RSV, PIV, hMPV, ADV, HCoV, and HBoV were screened using in-house real-time PCR. Results Of all samples, 9760 ARI cases (9760/22680, 43.03%) tested positive for the seven common respiratory viruses. The most detected virus was Flu (14.15%), followed by RSV (10.33%) and PIV (5.43%); Flu-A, PIV3, and HCoV-OC43 were the predominant subtypes. Although most of the viruses were detected in male inpatients, Flu was more likely detected in female outpatients. Flu infection was more likely to cause URTI (upper respiratory tract infection), whereas RSV infection was more likely to cause pneumonia and bronchitis. The prevalence of Flu was particularly high in 2009. The epidemic level was found notably high in 2014–2018 for RSV, in 2016–2018 for PIV, in the summer of 2018 for ADV, in the summer of 2016 and winter of 2018 for HCoV, and in the summer of 2011 and autumn of 2018 for HBoV. The co-detection rate of the seven viruses was 4.70%; RSV, PIV, and Flu were the most commonly co-detected viruses. Conclusions This work demonstrates the epidemiological characteristics of seven common respiratory viruses in ARI patients in southern China.

Introduction The impact of reduction of systolic blood pressure or body weight on reduction of cardiovascular events during the treatment with glucagon-like peptide 1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2is) for type 2 diabetes is unclear. Methods We searched Embase and PubMed. We performed meta-analysis using hazard ratio (HR) and 95% confidence interval (CI) as effect size stratified by drug class on six endpoints of interest, which were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), cardiovascular death (CVD), myocardial infarction (MI), stroke, and all-cause death (ACD). We performed meta-regression to assess the difference between GLP-1RAs and SGLT2is, and the impact of reduction of systolic blood pressure or body weight on reduction of cardiovascular events. Results We included 11 randomized trials. Compared with placebo, SGLT2is reduced HHF by 32% (HR 0.68, 95% CI 0.60–0.76) whereas GLP-1RAs reduced HHF by only 9% (HR 0.91, 95% CI 0.83–0.99). The benefit from SGLT2is on HHF was significantly greater than that from GLP-1RAs (Psubgroup = 0.004). GLP-1RAs reduced stroke by 16% (HR 0.84, 95% CI 0.76–0.93) whereas SGLT2is did not reduce stroke (HR 0.96, 95% CI 0.82–1.12). GLP-1RAs and SGLT2is similarly reduced MACE by 12%, CVD by 15%, MI by 9%, and ACD by 13%. The effects of systolic blood pressure reduction and body weight reduction on the logarithms of HRs of GLP-1RAs or SGLT2is vs. placebo as for reducing six endpoints of interest were not statistically significant (β ranged from − 0.145 to 0.269, and P ranged from 0.211 to 0.941). Conclusions GLP-1RAs and SGLT2is lead to similar benefits on MACE, CVD, MI, and ACD in adults with type 2 diabetes. The benefit from SGLT2is on HHF is greater than that from GLP-1RAs, while GLP-1RAs vs. placebo significantly reduce stroke whereas SGLT2is do not. The two drug classes reduce cardiovascular events independent of reductions of systolic blood pressure and body weight. Electronic supplementary material The online version of this article (10.1007/s13300-020-00912-z) contains supplementary material, which is available to authorized users.

The present study aimed to analyse the relationship between tumour-infiltrating immune cells (TIICs) and the prognosis of bladder cancer (BC). In the present study, an established computational method (CIBERSORT) was used to analyse the gene expression profile of BC from 409 patients to infer the number of infiltrating immune cells among 22 immune cell subsets. The relationship between each cell type and overall survival (OS) was further analysed. Single-sample GSEA and ESTIMATE algorithms were performed to evaluate the composition of immune microenvironment in each immune cluster. A significant difference in immune cell infiltration between BC and bladder tissue was observed. Increased natural killer and CD8+ T cell infiltration was associated with longer OS, whereas a higher percentage of M0 macrophages among the total immune cells was associated with shorter OS. The number of M0 macrophages increased with increasing BC stage, whereas the percentage of activated memory CD4+ and CD8+ T cells decreased. Patients with BC were divided into three subgroups by hierarchical cluster analysis of immune cells, and each cluster was associated with distinct survival and immune characteristics. The data indicated differences in the cellular composition of TIICs in patients with BC. Moreover, these TIICs were shown to be potential drug targets and reliable prognostic indicators.

The objective of present study was to investigate the effects of alpha-lipoic acid (ALA) dietary supplementation on the behavior, physiological and oxidant stress indicators, and bone quality in broilers under high stocking density (HSD) stress. A total of one thousand eight hundred 22-day-old Arbor Acres male broiler chicks were randomly allocated to 18 pens (2.97 × 2.03 m) in 3 groups: 14 birds/m2 (NSD, normal stocking density) or 18 birds/m2 (HSD) or 18 birds/m2 plus 300 mg/kg ALA dietary supplement (HSD + ALA, high stocking density + alpha-lipoic acid). Each treatment had 6 replicates, and the experiment lasted 3 wk. The HSD group was significantly lower than the NSD group (P 0.05) in the standing and preening behavior, alkaline phosphatase activity, PTH concentration, H/L ratio, CAT, T-AOC, MDA, SOD, and GSH-Px. These results indicate that the increase of stocking density lowered the bone quality, increased the physiological and oxidative stress indicators, and modified the behavior of broilers, whereas ALA dietary supplementation could counteract the reduction in the performance and physiological responses of broilers under high-density environmental stress.

Highlights • For respiratory syncytial virus (RSV), an annual distribution pattern of 2-year RSV-A dominance followed by a 1-year RSV-B dominance was found in Guangzhou. • In 2011–2016 in south China, prevalent RSV-A genotypes were NA1 and ON1 and the prevalent RSV-B genotype was BA9. • The prevalent RSV-A genotype changed from Chongqing NA1 in 2011 to Hong Kong ON1 in 2014. • The highest RSV epidemic peak occurred in 2015, indicating a possible biennial peak. • The ongoing evolution of RSV-A ON1 and NA1 genotypes indicated high selection pressure., Background Human respiratory syncytial virus (RSV) is one of the most important pathogens that cause acute respiratory infections in children and immunocompromised adults. This work was conducted to understand the epidemiological and phylogenetic features of RSV in southern China during 2011–2016. Methods A total of 16 024 nasopharyngeal swabs were collected from patients with respiratory infections in 14 hospitals, and screened for RSV and seven other respiratory viruses using real-time PCR. Six hundred and twenty-three RSV-positive samples from 13 hospitals were further analyzed for subtypes. G gene sequencing and phylogenetic analysis were performed based on 46 RSV-A and 15 RSV-B strains. Results RSV was detected in 9.5% of the 16 024 specimens, the highest among the eight respiratory viruses screened. Most of these specimens came from inpatients and children under 3 years of age. The incidence of RSV-A (9.4%) was higher than that of RSV-B (4.4%) in children (

Objective The study was conducted to evaluate the effect of stocking density and alpha-lipoic acid (ALA) on the growth performance, feed utilization, carcass traits, antioxidative ability and immune response of broilers. Methods A total of 1530 22-day-old male broilers (Arbor Acres) with comparable body weights (731.92 ± 5.26) were placed into 18 cages (2.46 × 2.02 m) in groups of 75 birds (15 birds/m2, 37.5 kg/m2; LD, low stocking density), 90 birds (18 birds/m2, 45.0 kg/m2; HD, high stocking density) and 90 birds with 300 mg/kg ALA added to the basal diet (18 birds/m2, 45.0 kg/m2; HD+ALA, high stocking density + -lipoic acid); each treatment was represented by 6 replicates. The experimental period was 3 weeks. Results The results showed that the high stocking density regimen resulted in a decreased growth, feed conversion ratio, carcass weight, thigh yield and bursa weight relative to body weight (P < 0.05) on d 42. The abdominal fat yield in the HD+ALA group was lower (P = 0.031) than that of the LD group at 42 d. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum were increased, and malondialdehyde (MDA) content decreased after adding ALA product (P < 0.05) on d 42. Additionally, the serum concentrations of IgA and IgG were decreased (P < 0.05) and the level of diamine oxidase (DAO) was higher (P < 0.01) in the HD group on d 42. Conclusion The high stocking density significantly decreased broiler growth performance, feed utilization and carcass traits, increased physiological and oxidative stress and induced intestinal mucosal injury. The supplementation of ALA product in broiler diet at 300 mg/kg may reduce the adverse effects of high stocking density-mediated stress by maintaining the antioxidant system and humoral immune system.

Background A hepatitis E (HepE) vaccine was developed and released in China in 2011. Uptake is currently very limited. The aims of this study were to characterize what public health professionals thought about promoting the HepE vaccine in Shanghai, China, and to develop realistic goals for the HepE vaccine based on this information. Methods Public health professionals from Shanghai and other jurisdictions of China were contacted to participate in in-depth qualitative interviews between October 2017 and August 2018. Participants were asked about their perception of the HepE vaccine roll-out. Codes were initially based on the structure of the questionnaire. Subsequently, similar ideas were further developed into themes based on what was present in the transcript data. Results Thirty-five individuals participated. Major topics of discussion included (1) clarifying the roles and responsibilities of private and public institutions in promoting and marketing the HepE vaccine, (2) identifying what methods of promotion were most efficient, and, (3) endeavoring to formulate a reasonable and realistic goal, if any, for HepE prevention and control in China. Participants emphasized that public sector sources can be trusted sources of information (although the private vaccination company can also be useful in disseminating information) and social media such as WeChat can be good ways to disseminate articles (although netizens may be worried about the spread of fake news). Vaccine promotion is restrained given limited levels of knowledge in the government, hospitals, and public health vaccination centers. Conclusion Successful promotion and use of this vaccine in China, even in limited settings (for instance, certain workplaces, or certain groups) could provide additional information on long-term safety and could promote its adoption in other regions of the world where HepE has high morbidity among pregnant women and other populations.

Gastric cancer (GC) is the fourth largest cancer in the world, with a 5-year survival rate of

Background Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective. Aims The current study was aimed to investigate whether miR-494 influences epithelial-mesenchymal transition (EMT), tumor growth and metastasis of CCA. Methods The regulatory miRNAs of WDHD1 in CCA expression chip were predicted, followed by determination of the miR-494 and WDHD1 expression in normal cholangiocyte tissues and CCA tissues. The related protein levels were determined. CCA cell migration, invasion, viability, and cell cycle distribution and the dosage-dependent effect of miR-494 on CCA cell growth were subsequently detected. Finally, tumorigenicity and lymph node metastasis (LNM) were measured. Results Initially, miR-194 affected the CCA development via negatively regulating WDHD1 and miR-494 which were downregulated while WDHD1 was upregulated in CCA. In addition, miR-494 overexpression elevated E-cadherin expression while decreased expressions of WDHD1, N-cadherin, Vimentin, Snail, Twist and MMP-9. Finally, overexpressed miR-494 was observed to suppress EMT, cell viability, migration, invasion, arrest cell cycle progression, tumor formation, and LNM while accelerating cell apoptosis in vivo. Conclusion This study indicated that miR-494 overexpression suppresses EMT, tumor formation and LNM while promoting CCA cell apoptosis through inhibiting WDHD1 in CCA.

Surface modification of medical implants is considered as an effective method to improve cellular behaviors and the integration of tissues with materials. Titanium (Ti)-based materials with four different micro/nano-structures and compositions were prepared by acid etching, electrochemical anodization and alkali-heat treatment. The surface morphologies and compositions of the different surface-modified Ti materials were characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD). The effects of the micro/nano structured and compositions of the surfaces on cellular responses were investigated in vitro by observing the morphology, adhesion, proliferation and osteogenic differentiation of osteoblasts. To further investigate the underlying mechanisms, an RT-PCR assay was performed to analyze the expression levels of cell adhesion-related genes. Our results indicated that the nanosized structure and anatase composition could promote the adhesion and proliferation of MC3T3-E1 pre-osteoblast, as well as alkaline phosphatase activity and extracellular matrix mineralization via the integrin-FAK signaling pathway. Taken together, our innovation presented in this work demonstrated that the surface nano-structure design and composition of biomedical implants can be modified of for future orthopaedic applications.

Although the hard template method is often employed to prepare N-doped mesoporous carbon(N-MC), the removal of the silica template commonly involves the use of highly toxic HF or repeated treatment with NaOH solution. Herein, we report a polyvinylidene fluoride-assisted one-step method for synthesis of N-MC, namely the silica-free N-MC can be prepared via temperature-programmed thermal treatment of a slurry obtained by dispersing nano-silica into a solution containing sucrose, urea, oxalic acid, polyvinylidene fluoride and dimethylacetamide. The resulting N-MC, which owns 3.47%(mass fraction) nitrogen and a surface area of 929 m2/g, is a highly suitable support of Pd catalyst used in hydrodechlorination of 2,4-dichlorophenol, with its performance being much better than those of MC and activated carbon. The excellent catalytic hydrodechlorination activity of the Pd/N-MC catalyst can be attributed to its strong metal-support interaction which results in a good Pd dispersion and high resistance to the growth of nanosized Pd under reaction conditions.

The age, growth, and mortality of Gymnocypris firmispinatus were studied by 582 individuals that collected between July 2015 and June 2016 from the tributaries of the Anning River, China. The total length (TL) ranged from 27 mm to 242 mm, total weight (W) ranged from 0.2 g to 148.2 g. The relationship of total length and weight was expressed as W =7.754×10-6 TL3.304 for the total samples. The age classes of males were 1–9 a, and that of females were 1–13 a. The von Bertalanffy functions based on otolith readings and observed length data were Lt♂ =198.6(1–e-0.094 ( t +3.497) ), and Lt♀ =289.3(1–e-0.089 ( t +1.109) ). The total mortality ( Z ) of male and female G. firmispinatus was estimated as 0.73/a and 0.40/a, respectively. The natural mortality ( M ) was evaluated as 0.25/a for males and 0.20/a for females, fishing mortality ( F ) was 0.35/a for males and 0.16/a for females. The exploitation ratio of the population was 0.66/a for males and 0.50/a for females. It was concluded that the growth of the fish is relatively slower than other congeneric fishes. The population of G. firmispinatus in the tributaries of the Anning River might be in over-exploitation under the current fishing intensity.

Some progresses have been made in research of long non-coding RNA (hereunder referred to as LncRNA) related to breast cancer. Lots of data about LncRNA transcription concerning breast cancer have been obtained from large-scale omics research (e.g. transcriptomes and chips). Some LncRNAs would become indices for detecting breast cancer and judging its development and prognosis. LncRNAs may affect genesis and development of breast cancer in multiple ways. Perhaps they could develop into potential targets for treating breast cancer if they are carcinogenic. Like those from other studies of breast cancer, many data gained from omics research remain to be validated by much experimental work. For instance, it is still necessary to demonstrate reliability of LncRNAs as indices for diagnosing breast cancer and judging its prognosis (particularly for various subtypes of breast cancer), effectiveness and feasibility of these genes for treating breast cancer as targets. In this paper, recent years’ literatures about LncRNAs which are related to breast cancer are summarized and sorted out to review the research progresses in relationships between LncRNAs and breast cancer.

Monotherapy with poly ADP-ribose polymerase (PARP) inhibitors results in a limited objective response rate (≤60% in most cases) in patients with homologous recombination repair (HRR)-deficient cancer, which suggests a high rate of resistance in this subset of patients to PARP inhibitors (PARPi). To overcome resistance to PARPi and to broaden their clinical use, we performed high-throughput screening of 99 anticancer drugs in combination with PARPi to identify potential therapeutic combinations. Here, we found that GSK3 inhibitors (GSK3i) exhibited a strong synergistic effect with PARPi in a panel of colorectal cancer (CRC) cell lines with diverse genetic backgrounds. The combination of GSK3β and PARP inhibition causes replication stress and DNA double-strand breaks, resulting in increased anaphase bridges and abnormal spindles. Mechanistically, inhibition or genetic depletion of GSK3β was found to impair the HRR of DNA and reduce the mRNA and protein level of BRCA1. Finally, we demonstrated that inhibition or depletion of GSK3β could enhance the in vivo sensitivity to simmiparib without toxicity. Our results provide a mechanistic understanding of the combination of PARP and GSK3 inhibition, and support the clinical development of this combination therapy for CRC patients.

Background/AimsThe role of DHRS3 in human cancer remains unclear. Our study explored the role of DHRS3 in gastric cancer (GC) and its clinicopathological significance and associated mechanisms.MaterialsBisulfite-assisted genomic sequencing PCR and a Mass-Array system were used to evaluate and quantify the methylation levels of the promoter. The expression levels and biological function of DHRS3 was examined by both in vitro and in vivo assays. A two-way hierarchical cluster analysis was used to classify the methylation profiles, and the correlation between the methylation status of the DHRS3 promoter and the clinicopathological characteristics of GC were then assessed.ResultsThe DHRS3 promoter was hypermethylated in GC samples, while the mRNA and protein levels of DHRS3 were significantly downregulated. Ectopic expression of DHRS3 in GC cells inhibited cell proliferation and migration in vitro, decreased tumor growth in vivo. DHRS3 methylation was correlated with histological type and poor differentiation of tumors. GC patients with high degrees of CpG 9.10 methylation had shorter survival times than those with lower methylation.ConclusionDHRS3 was hypermethylated and downregulated in GC patients. Reduced expression of DHRS3 is implicated in gastric carcinogenesis, which suggests DHRS3 is a tumor suppressor.

The oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephrtitidae), and the Chinese citrus fly, Bactrocera minax (Enderlein) (Diptera: Tephritidae), are 2 destructive citrus fruit pests in China. A field study was conducted during Sep to Oct of 2018 in Dongkou County of Hunan Province to assess (1) fruit infestations at the time of harvest under 2 management levels, and (2) the efficacy of culling at harvest (i.e., visual inspection and removal of the infested fruits) on reducing the number of infested fruits. A total of 26,400 fruits of Satsuma mandarins, Citrus unshiu (Swingle) Marcov (Rutaceae), were harvested from 2 groves with 1 representing highly managed groves, and the other representing commonly managed groves (low management). Fruit culling was conducted immediately to separate fruits into 5 groups: (1) B. minax infested fruits, (2) B. dorsalis infested fruits, (3) B. minax + B. dorsalis infested fruits, (4) suspected fruit fly infested fruits, and (5) fruit fly free fruits. Fruit dissection was conducted 4 wk later to determine the actual number of the infested fruits, and also to act as a check on the accuracy of visual inspection on the reduction of the number of infested fruits. The highly managed grove had 0.02% infested fruits vs. 2.19% in the low managed grove, a 99.09% reduction in infestation rate. Culling reduced the infested rate to 0.0077% in the highly managed grove and 1.14% in the low managed grove, a reduction of 62% and 48%, respectively, compared to that before culling. About 99% and 73% of fruits which were identified as infested actually were pest free in the 2 groves, respectively. The result of this study suggests that field management is highly effective and critical in reducing fruit fly infestation. The efficacy of culling at harvest on reducing the number of infested fruits was moderate. The accuracy of using culling for identifying the infested fruits was unreliable. Resumo La mosca oriental de la fruta, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), y la mosca china de los citricos, Bactrocera minax (Enderlein) (Diptera: Tephritidae), son dos plagas destructivas de los citricos en China. Se realizo un estudio de campo durante septiembre a octubre del 2018 en el condado de Dongkou de la provincia de Hunan para evaluar (1) las infestaciones de frutas en el momento de la cosecha bajo 2 niveles de manejo, y (2) la eficacia de la eliminacion selectiva en la cosecha (inspeccion visual y eliminacion de los frutos infestados) sobre la reduccion del numero de frutos infestados. Un total de 26,400 frutos de mandarinas Satsuma, Citrus unshiu (Swingle) Marcov (Rutaceae), fueron recolectados de 2 huertos, con 1 representando huertos sumamente manejados y el otro representando huertos comunmente manejados (bajo manejo). Se separaron las frutas inmediatamente en 5 grupos: (1) frutas infestadas con B. minax, (2) frutas infestadas con B. dorsalis, (3) frutas infestadas con B. minax + B. dorsalis, (4) frutas sospechadas de ser infestadas con moscas de la fruta, y (5) frutas libres de moscas de la fruta. La diseccion de frutos se realizo 4 semanas despues para determinar el numero real de frutos infestados y tambien para actuar como una verificacion de la precision de la inspeccion visual sobre la reduccion del numero de frutos infestados. El huerto sumamente manejado tenia un 0.02% de frutos infestados versus un 2.19% en el huerto comunmente manejado, una reduccion del 99.09% en la tasa de infestacion. El descarte de frutas daňadas redujo la tasa de infestacion al 0,0077% en el huerto sumamente manejado y al 1,14% en el huerto comunmente manejado, una reduccion del 62% y 48%, respectivamente, en comparacion con los niveles antes del descarte de las frutas daňadas. Aproximadamente el 99% y el 73% de las frutas que se identificaron como infestadas en realidad estaban libres de plagas en los 2 huertos, respectivamente. El resultado de este estudio sugiere que el manejo de campo es altamente efectivo y critico para reducir la infestacion de moscas de la fruta. La eficacia del descarte de las frutas daňadas para reducir el numero de frutos infestados fue moderada. La precision de utilizar la seleccion para identificar las frutas infestadas no fue confiable. Key Words: systems approach; Bactrocera minax; Bactrocera dorsalis; fruit dissection; phytosanitary measures View this article in BioOne

Background: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists on major adverse cardiovascular events (MACE) in type 2 diabetic subgroups defined by race, ethnicity, and region are unestablished. Methods: We searched PubMed and Embase for related randomized controlled trials. We conducted random-effects meta-analysis, stratified by drug class, on MACE in various subgroups defined by 3 factors of interest (ie, race, ethnicity, and region) to estimate pooled hazard ratio (HR) and 95% confidence interval. Random-effects meta-regression was conducted to evaluate the differences between 2 drug classes. Results: We included 11 randomized controlled trials for pooled analysis. Compared with placebo, SGLT2is and GLP-1 RAs significantly reduced the risk of MACE (HR ranged from 0.76 to 0.93) in most diabetic subgroups defined by 3 factors of interest. The 2 drug classes did not significantly reduced this risk in the Black race group (HR 0.92, 95% confidence interval 0.70–1.20). The effect of the 2 drug classes on MACE was not significantly different in all diabetic subgroups of interest (P-value for subgroup differences ranged from .101 to .971). Conclusions: SGLT2is and glucagon-like peptide 1 receptor agonists can significantly reduce the risk of MACE in most type 2 diabetic subgroups defined by race, ethnicity, and region, whereas they fail to do it in Black individuals.

The study aimed to investigate the application of core needle biopsy through the trocar hole during surgery on endoscopically unresectable giant colon polyps. The clinical data of 51 patients with endoscopically unresectable giant colon polyps from May 2016 to May 2020 were retrospectively analyzed. The primary observational outcomes were two comparative analyses of pathologic results, using the kappa index: comparison of the pathologic results from the preoperative colonoscopy and the postoperative pathologic results and comparison of the intraoperative pathologic results from core needle biopsy of the intestinal wall and the postoperative pathologic results. The secondary observational outcomes were duration of needle biopsy, operation duration, volume of intraoperative hemorrhage, rate of postoperative wound infection, rate of abdominal cavity infection, length of stay, and number and positivity of lymph node dissections after laparoscopic radical resection of colon cancer. Poor consistency was found between the preoperative (colonoscopy) and postoperative pathologic results, with kappa = 0.222 (i.e., kappa

The comparative efficacy of different glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular events (MACE) in type 2 diabetes with or without cardiorenal disease is undefined. PubMed and Embase were searched for relevant randomized trials. We conducted network meta-analysis within the Bayesian framework. Effect sizes were measured using hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) values to rank drug interventions for different type 2 diabetic subgroups. Albiglutide (HR 0.76, 95% CI 0.63-0.93) and subcutaneous semaglutide (HR 0.71, 95% CI 0.52-0.95), with the maximum SUCRA values, significantly reduced MACE versus lixisenatide in people with diabetes with cardiovascular disease; albiglutide (HRs: 0.69 and 0.72), with the maximum SUCRA value, significantly reduced MACE versus dapagliflozin and exenatide in people with diabetes with heart failure; and canagliflozin (HRs: 0.72 and 0.72) and liraglutide (HRs: 0.68 and 0.68), with the maximum SUCRA values, significantly reduced MACE versus exenatide and lixisenatide in people with diabetes with chronic kidney disease. In preventing MACE in type 2 diabetes, subcutaneous semaglutide and albiglutide are most effective for diabetes with cardiovascular disease, albiglutide is most effective for diabetes with heart failure, and canagliflozin and liraglutide are most effective for diabetes with chronic kidney disease.

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP). Herein we used whole-exome sequencing to screen possible novel RPGR mutations in RP patients, and identified a novel missense mutation E585K in a patient with early onset but slow disease progression, and a frameshift deletion E998Gfs*78 in a patient with RP sine pigmento and high myopia. Intriguingly, bioinformatic analysis indicated that E585K probably affected RPGR RNA splicing instead of the protein sequence directly. Mini-gene assays in 293T cells revealed that splicing events of the E585K mutant were found to be also exist in wildtype, but with a shifted pattern. In the E585K mini-gene usage of an upstream alternative 5′ splice site (5′ ss) of exon 14 was enhanced, and other splicing events were suppressed, including the canonical 5′ ss of exon 14, skipping of exon 14/15 and retention of intron 14. As a result, RPGR splicing products of the E585K mini-gene were predominated by transcripts containing a 4-bp deletion, with a small fraction of in-frame transcripts containing a retended intron 14, which might explain the slow disease progression in the patient carrying the mutation. RNA-Seq analysis further confirmed existence of these splicing events in endogenous RPGR RNA in human retina, pointing to compromised splicing diversity in the E585K mutant. Our findings thus added to the understanding of genotype-phenotype correlation in RP, and suggested that compromised RPGR splicing diversity might play a role in molecular mechanism of the disease.

To investigate whether sodium glucose cotransporter 2 inhibitors (SGLT2is) can reduce important cardiorenal endpoints in type 2 diabetic adults without established cardiovascular disease (ECD), in those without heart failure (HF), and in those without chronic kidney disease (CKD). We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov. Event-driven randomized controlled trials (RCTs) and cohort studies were included. We conducted random-effects meta-analysis, respectively based on RCTs and cohort studies, on eight cardiorenal endpoints in three type 2 diabetic subgroups. Thirteen large studies were included. Meta-analysis of RCTs showed the high quality evidences: compared with placebo, SGLT2is significantly reduced the risk of major adverse cardiovascular events, cardiovascular death or hospitalization for HF, and progression of CKD in type 2 diabetic adults without ECD [HRs (95 % CIs): 0.88 (0.82, 0.94), 0.76 (0.70, 0.82), and 0.59 (0.52, 0.66), respectively; risk differences (95 % CIs): -1.6 (-2.4, -0.8), -2.6 (-3.3, -2.0), and -2.4 (-2.8, -2.0) per 1000 patient-years, respectively], in those without HF [HRs (95 % CIs): 0.89 (0.82, 0.95), 0.74 (0.67, 0.81), and 0.61 (0.55, 0.67), respectively; risk differences (95 % CIs): -1.7 (-2.9, -0.8), -5.8 (-7.3, -4.2), and -2.3 (-2.6, -1.9) per 1000 patient-years, respectively], and in those without CKD [HRs (95 % CIs): 0.88 (0.82, 0.94), 0.77 (0.71, 0.83), and 0.63 (0.57, 0.70), respectively; risk differences (95 % CIs): -2.4 (-3.6, -1.2), -6.1 (-7.6, -4.5), and -2.2 (-2.6, -1.8) per 1000 patient-years, respectively]. Meta-analysis of cohort studies also showed the benefits of SGLT2is on the three composite outcomes in the three diabetic subgroups. SGLT2is also significantly reduced some other cardiorenal endpoints in these diabetic subgroups. SGLT2is can significantly reduce important cardiorenal events in type 2 diabetic adults without ECD, in those without HF, and in those without CKD; which supports SGLT2is used in these diabetic subpopulations to prevent cardiorenal events.

Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or underlying mechanism of RASSF1A on the malignant phenotype. In the present study, we observed that RASSF1A expression inhibited the malignant phenotypes of NPC cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro. Mechanistically, RASSF1A inactivated Yes-associated Protein 1 (YAP1), a transcriptional coactivator, through actin remodeling, which further contributed to Platelet Derived Growth Factor Subunit B (PDGFB) transcription inhibition. Treatment with ectopic PDGFB partially increased the malignancy of NPC cells with transient knockdown of YAP1. Collectively, these findings suggest that RASSF1A inhibits malignant phenotypes by repressing PDGFB expression in a YAP1-dependent manner. PDGFB may serve as a potential interest of therapeutic regulators in patients with metastatic NPC.

Background: Diagnostic performance of PET/CT using 18F-fluciclovine (18F-FACBC) in patients with prostate cancer (PCa) has been evaluated in only a few studies. There is no consensus on the diagnostic value of 18F-FACBC PET/CT in PCa recurrence or metastasis (except for bone metastasis), the primary diagnosis of the lesion. Hence, a meta-analysis was conducted to evaluate the performance of 18F-FACBC PET/CT. Methods: The literature published from June 2015 to June 2019 on using 18F-FACBC PET/CT for the diagnosis of PCa was retrieved from PubMed and EMBASE. Pooled sensitivity (Sen), specificity (Spe), positive and negative likelihood ratios (LR+ and LR–), area under the curve (AUC), and diagnostic odds ratio (DOR) of 18F-FACBC PET/CT in patients with PCa were calculated. An SROC map was made, and a meta-regression analysis was carried out. A Fagan plot and likelihood ratio dot plot were drawn. Sensitivity and funnel plot analysis were made. Meta-disc, Review Manager 5.3, and STATA 13 were used for the meta-analysis. Results: A total of nine articles met the strict criteria for diagnostic meta-analysis, which included 363 patients and 345 lesions. Pooled Sen, Spe, LR+, LR–, DOR were 0.88, 0.73, 3.3, 0.17, and 20, respectively. Lesions detected on the PET/CT image included primary lesions and metastases. For the lesion, the doctors considered the abnormal part as a lesion on the PET/CT image by their own experience and expertise, including primary lesions and metastases. For the patient, patients who participated in the trial can be diagnosed as PCa through 18F-FACBC. Conclusion: This study comprehensively evaluated the diagnostic value of 18F-FACBC PET/CT on PCa. Our analysis suggests that 18F-FACBC PET/CT is a valuable agent in diagnosing PCa. More studies are needed for further validation.

Homeotransplantation of bones for replacement therapy have been demonstrated reliably in clinical data. However, human donor bones applicable for homeotransplantation are in short supply, which facilitates the search for suitable alternatives, such as xenografts grafts. The α-Gal antigen-related immune risk of xenografts directly affects the safety and effectiveness of the biomaterials and limits their applications in the clinic. The immune risk can be prevented by depletion or breaking anti-Gal antibody prior to transplant. Therefore, how to assess the immune risk of the bone substitutes and select the reliable animal research model become extremely important. In this study, we prepared lyophilized bone substitutes (T1) and Guanghao Biotech bone substitutes (T2, animal-derived biomaterials with α-Gal antigen decreased), aimed to assess the immune risk of xenografts bone substitutes on GGTA1 knockout mice. The α-Gal antigen contents of T1 and T2 were firstly detected by ELISA method in vitro. The bone substitutes were then implanted subcutaneously into GGTA1 knockout mice for 2, 4 and 12 weeks, respectively. The total serum antibody levels, anti-α-Gal antibody levels, inflammatory cytokine and splenic lymphocyte surface molecules were detected and histology analysis of skin and thymus were performed to systematically evaluate the immune response caused by the T1 and T2 bone substitutes in mice. In vitro results showed that the amount of α-Gal epitopes in T1 bone substitutes was significantly higher than T2 bone substitutes, and the clearance rate of α-Gal antigen in T2 bone substitutes achieved about 55.6%. Results of antibody level in vivo showed that the T1 bone substitutes group possessed significantly higher total IgG, IgM, IgA and anti-α-Gal IgG levels than T2 and control group, while T2 group showed no significant changes of these indexes compared with control. In terms of inflammatory cytokines, T1 bone substitutes showed evidently higher levels of IL-4, IL-12P70 and IL-10 than T2 and control, while T2 group was comparable to control. No changes in the levels of splenic lymphocyte surface molecules were found in the three groups (T1, T2 and control group) during the experimental periods. The pathological results demonstrated that the inflammatory response in T2 group was lighter than the T1 group, which was in accordance with the inflammatory cytokines levels. The above results indicated that the process of antigen removal effectively reduced the α-Gal antigens content in T2 bone substitutes, which caused little immune response in vivo and could be used as bone healing materials. This study also demonstrated that GGTA1 knockout mice can be used as a routine tool to assess the immune risk of animal-derived biomaterials.

Background The anatomical relationship between the root apices of maxillary molars and the maxillary sinus floor (MSF) is important for the treatment of dental implantations and endodontic procedures. In this study, the detailed anatomical relationships between the root apices of maxillary molars and the MSF were studied in a Chinese population using CBCT. Methods We collected the CBCT data files of patients who visited the stomatology outpatient clinic in Shanghai Fifth People’s Hospital, Fudan University from January 1, 2017 to January 1, 2019 and measured the following items: the distance between the molar root apices and the MSF, the thickness of the mucosa and cortical bone of the MSF closest to the root apices, and the angle between the buccal and palatal roots. Results The shortest distances between the root apices and the MSF were 1.57 ± 3.33 mm (the mesiobuccal root of the left second molar) and 1.61 ± 3.37 mm (the mesiobuccal root of the right second molar). Apical protrusion over the inferior wall of the sinus most often occurred in the mesiobuccal root of left second molar (frequency, 20.5%). The mucosa of the MSF was thinnest at the distobuccal root of the right second molar (1.52 ± 0.85 mm), the cortical bone of the MSF was thinnest at the mesiobuccal root of the right second molar (0.46 ± 0.28 mm), and the angle between the buccal and palatal roots ranged from 12.01° to 124.2° (42.36 ± 24.33 °). Conclusions Among the root apices of the maxillary molars, the mesiobuccal root apex of the left second molar was closest to the MSF, and it had the highest incidence of protrusion into the sinus. The unique anatomical relationship between the maxillary molars and the MSF in this Chinese population is critical for treatment planning for dental implantation or endodontic procedures.

Low- and middle-income countries receive limited guidance from external entities about how to introduce vaccines. This is especially true for the Hepatitis E (HepE) vaccine, which is currently only commercially available in China. The aims of this qualitative study are to identify which attributes of the HepE disease and vaccine are considered important, and to compare desired promotion methods between different stakeholders. Stakeholders included experts (Centers for Disease Control and Prevention staff, health care providers, and researchers), and nonexperts included members of high-risk populations, HepE cases, and vaccinees. Participants’ thoughts were coded and broadly summarized. We contacted 63 persons—35 experts and 28 nonexperts. Safety and effectiveness (but not price) of the vaccine, along with severity of disease and transmission route of infection, were all listed as important attributes. Emphasizing the importance of sharing stories from cases, relying on personal experiences, staying away from statistical explanations, and using the government as a source of promotion were other points repeatedly raised by the participants. Qualitative interviews with experts and nonexperts has revealed that focusing on attributes of disease severity and susceptibility to infection, as well as vaccine safety and effectiveness within stories of cases, are preferred ways to promote the vaccine.

Background. Gymnocypris firmispinatus Wu et Wu, 1988 is a small fish with the maximum total length of 242 mm, which occurs only in the Jinsha River and its tributaries (China), at altitudes above 2000 m. Nowadays, G. firmispinatus had been placed in a dangerous situation, due to hydropower station and excessive fishing. However, attempts to develop an effective population management strategy have been obstructed by lack of basic biological information, especially for age estimation. As we known, sectioned otoliths provide the most precise age estimates of many Schizothoracinae fishes, vertebrae and opercular bones were also used for age determination of some fish species. This work aimed to assess the suitability of three calcified structures (otolith, vertebra, and opercular bone) for age estimation of G. firmispinatus. Materials and methods. The annulus characteristics of otolith, vertebra, and opercular bone were described. Annual periodicity was verified by marginal increment ratio (MIR) analysis in otoliths and edge analysis in vertebrae and opercular bones. Otoliths, vertebrae, and opercular bones were examined to determine which structure produced the most precise and accurate age estimates in G. firmispinatus, mainly by scoring for readability on a five-point scale and calculating the index of the mean percentage error (IMPE). Results. Microscopically, otoliths and vertebrae showed a typical pattern of opaque-and translucent-zones, attributed to slow and fast growth periods. Annuli formed between March and May once a year in otoliths and vertebrae. Forty-four percent of the opercular bones were scored as unreadable. The value of IMPE between the two counts was lowest for otoliths (4.25%), followed by vertebrae (6.21%) and opercular bones (11.58%). The IMPE value of vertebra vs. otolith was 11.05%, while that of opercular bone vs. otolith was 23.03%. Vertebrae and otoliths matched closely only for the first 4 years of life, while opercular bones appeared to underestimate the age of G. firmispinatus. Conclusion. Annuli in the otoliths and vertebrae both formed once a year up to age 8, and otoliths would be the most precise structure for age determination in G. firmispinatus. Vertebrae and otoliths matched closely up to age 4, while opercular bones could not be used for age estimation for the species.

The present study aimed to identify potential genes associated with prostate cancer (PCa) recurrence following radical prostatectomy (RP) in order to improve the prediction of the prognosis of patients with PCa. The {"type":"entrez-geo","attrs":{"text":"GSE25136","term_id":"25136"}}GSE25136 microarray dataset, including 39 recurrent and 40 non-recurrent PCa samples, was downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) were identified using limma packages, and the pheatmap package was used to present the DEGs screened using a hierarchical cluster analysis. Furthermore, gene ontology functional enrichment analysis was used to predict the potential functions of the DEGs. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to analyze pathway enrichment of DEGs in the regulatory network. Lastly, a protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape software to understand the interactions between these DEGs. A total of 708 DEGs were identified in the recurrent and non-recurrent PCa samples. Functional annotation revealed that these DEGs were primarily involved in cell adhesion, negative regulation of growth, and the cyclic adenosine monophosphate and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, five key genes, including cluster of differentiation 22, insulin-like growth factor-1, inhibin β A subunit, MAPK kinase 5 and receptor tyrosine kinase like orphan receptor 1, were identified through PPI network analysis. The results of the present study have provided novel ideas for predicting the prognosis of patients with PCa following RP.

BACKGROUND: This study aimed to establish machine learning models for preoperative prediction of the pathological types of acute appendicitis. METHODS: Based on histopathology, 136 patients with acute appendicitis were included and divided into three types: acute simple appendicitis (SA, n=8), acute purulent appendicitis (PA, n=104), and acute gangrenous or perforated appendicitis (GPA, n=24). Patients with SA/PA and PA/GPA were divided into training (70%) and testing (30%) sets. Statistically significant features (P

Background: Besides effect of general anesthesia, sevoflurane also induces hyperactivity during induction and recovery, especially in young children. Lack of satisfied animal model impedes the investigation of causes of the hyperactivity as well as its prevention. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker might produce sedative effect. This study developed a novel mice model of hyperactive behaviors and further explored effects of HCN channel blocker on sevoflurane-induced hyperactivity. Methods: C57BL/6 mice were used in the present study. Maximal speed, mean speed, total movement distance and resting percentage of mice were quantitatively measured by behavioral tracking software. Age-dependence of this model was also analyzed. HCN channel blocker ZD7288 at doses of 6.25 and 12.5 μg/kg were intraperitoneal injected to prevent sevoflurane-induced hyperactivity. Results: In the behavioral model, sevoflurane could induce significant hyperactivity in mice under 1% sevoflurane inhalation and in recovery period, characterized as increased movement speed and total distance. The sevoflurane-induced hyperactivity was more significant in young mice than adult (P