RESUMO
OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: ⢠This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. ⢠Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Antineoplásicos/uso terapêutico , Quimioembolização Terapêutica/efeitos adversos , Pontuação de Propensão , Estudos RetrospectivosRESUMO
The identification of additional Echinococcus granulosus sensu lato (s.l.) complex species/genotypes in recent years raises the possibility that there might be more variation among this species in China than is currently understood. The aim of this study was to explore intra- and inter-species variation and population structure of Echinococcus species isolated from sheep in three areas of Western China. Of the isolates, 317, 322, and 326 were successfully amplified and sequenced for cox1, nad1, and nad5 genes, respectively. BLAST analysis revealed that the majority of the isolates were E. granulosus s.s., and using the cox1, nad1, and nad5 genes, respectively, 17, 14, and 11 isolates corresponded to Elodea canadensis (genotype G6/G7). In the three study areas, G1 genotypes were the most prevalent. There were 233 mutation sites along with 129 parsimony informative sites. A transition/transversion ratio of 7.5, 8, and 3.25, respectively, for cox1, nad1, and nad5 genes was obtained. Every mitochondrial gene had intraspecific variations, which were represented in a star-like network with a major haplotype with observable mutations from other distant and minor haplotypes. The Tajima's D value was significantly negative in all populations, indicating a substantial divergence from neutrality and supporting the demographic expansion of E. granulosus s.s. in the study areas. The phylogeny inferred by the maximum likelihood (ML) method using nucleotide sequences of cox1-nad1-nad5 further confirmed their identity. The nodes assigned to the G1, G3, and G6 clades as well as the reference sequences utilized had maximal posterior probability values (1.00). In conclusion, our study confirms the existence of a significant major haplotype of E. granulosus s.s. where G1 is the predominant genotype causing of CE in both livestock and humans in China.
Assuntos
Equinococose , Echinococcus granulosus , Animais , Humanos , Ovinos , Echinococcus granulosus/genética , Tibet , Equinococose/epidemiologia , Equinococose/veterinária , China , Genótipo , Haplótipos , Mutação , Filogenia , Variação GenéticaRESUMO
This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.
Assuntos
Neuropatias Diabéticas , Medicamentos de Ervas Chinesas , Doenças do Sistema Nervoso Periférico , Humanos , Glicemia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Hemoglobinas Glicadas , Hipestesia/tratamento farmacológico , Estudos Multicêntricos como Assunto , Dor/tratamento farmacológico , Dor/etiologia , Resultado do Tratamento , Doenças do Sistema Nervoso Periférico/sangue , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/etiologiaRESUMO
The (co)variance components and corresponding phenotypic and genetic parameters for growth traits and wool traits of economic importance were estimated in the Alpine Merino sheep population maintained at Gansu Provincial Sheep Breeding Technology Extension Station in northwestern China. Data from a maximum of 49,474 animals sired by 526 rams and born from 22,531 ewes over 20 years from 2000 to 2019 were used in this study. Birth type, age of dam, birth year, sex and/or management group, and age at measurement were initially fitted as fixed effects in an animal model with various random effects. Genetic groups were defined for all animals by the sire breed and breed genotype interacted with dam-strain flocks and were fitted as one of the random effects. Analyses were conducted using a residual maximum likelihood procedure (ASReml). Seven different animal models were fitted for all traits, and the most appropriate model with relevant random effects was selected through log-likelihood ratio testing. After identifying the appropriate model through single-trait analysis, bivariate analyses were used to obtain the phenotypic and genetic correlations among the traits. The estimates of additive direct heritability for birth weight (BWT), weaning weight (WWT), preweaning growth rate (prwADG), postweaning growth rate (powADG), yearling body weight (YWT), average fibre diameter (AFD), greasy fleece weight (GFW), clean fleece weight (CFW), yield (YLD), yearling wool staple length (YSL), coefficient of variation of average fibre diameter (FDcv) and wool visual fineness counts (VFC) were 0.30, 0.18, 0.18, 0.20, 0.29, 0.20, 0.19, 0.20, 0.35, 0.19, 0.16 and 0.13, respectively, with standard errors ranging from 0.02 to 0.05. The corresponding ratios of genetic group variance to additive genetic variance were significant and, respectively, 0.35, 0.80, 0.62, 0.26, 0.13, 1.06, 0.38, 0.64, 0.09, 0.12, 0.06 and 0.58. These results suggest for these traits that there is potential to exploit both the additive genetic variation and between genetic group variation although for most traits the between group variation was smaller than the variation within groups. Favourable genetic correlations were found among the growth traits, and between growth traits and fleece production traits, and among wool traits GFW, CFW, YSL and YLD. This study provides the required estimates of genetic parameters of both growth and wool traits of the new breed for the design of more effective breeding programmes.
Assuntos
Carneiro Doméstico , Lã , Animais , Peso Corporal/genética , Feminino , Genótipo , Masculino , Fenótipo , Ovinos/genética , Carneiro Doméstico/genética , DesmameRESUMO
BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.
Assuntos
Antibacterianos , Infecções Pneumocócicas , Antibacterianos/uso terapêutico , Criança , China/epidemiologia , Humanos , Lactente , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/epidemiologia , Prescrições , Estudos RetrospectivosRESUMO
Cysticercosis caused by the metacestode larval stage of Taenia hydatigena formerly referred to as Cysticercus tenuicollis is a disease of veterinary importance that constitutes a significant threat to livestock production worldwide, especially in endemic regions due to condemnation of visceral organs and mortality rate of infected young animals. While the genetic diversity among parasites is found to be potentially useful in many areas of research including molecular diagnostics, epidemiology and control, that of T. hydatigena across the globe remains poorly understood. In this study, analysis of the mitochondrial DNA (mtDNA) of adult worms and larval stages of T. hydatigena isolated from dogs, sheep and a wild boar in China showed that the population structure consists of two major haplogroups with very high nucleotide substitutions involving synonymous and non-synonymous changes. Compared with other cestodes such as Echinococcus spp., the genetic variation observed between the haplogroups is sufficient for the assignment of major haplotype or genotype division as both groups showed a total of 166 point-mutation differences between the 12 mitochondrial protein-coding gene sequences. Preliminary analysis of a nuclear protein-coding gene (pepck) did not reveal any peculiar changes between both groups which suggests that these variants may only differ in their mitochondrial makeup.
Assuntos
DNA de Helmintos/genética , DNA Mitocondrial/genética , Taenia/genética , Teníase/veterinária , Sequência de Aminoácidos , Animais , China , DNA de Helmintos/química , DNA de Helmintos/metabolismo , DNA Mitocondrial/química , DNA Mitocondrial/metabolismo , Doenças do Cão/parasitologia , Cães , Haplótipos , Larva/genética , Larva/crescimento & desenvolvimento , Filogenia , Alinhamento de Sequência , Ovinos , Doenças dos Ovinos/parasitologia , Carneiro Doméstico , Sus scrofa , Suínos , Doenças dos Suínos/parasitologia , Taenia/crescimento & desenvolvimento , Taenia/metabolismo , Teníase/parasitologiaRESUMO
BACKGROUND & AIMS: The presence of multifocal tumors, developed either from intrahepatic metastasis (IM) or multicentric occurrence (MO), is a distinct feature of hepatocellular carcinoma (HCC). Immunogenomic characterization of multifocal HCC is important for understanding immune escape in different lesions and developing immunotherapy. METHODS: We combined whole-exome/transcriptome sequencing, multiplex immunostaining, immunopeptidomes, T cell receptor (TCR) sequencing and bioinformatic analyses of 47 tumors from 15 patients with HCC and multifocal lesions. RESULTS: IM and MO demonstrated distinct clonal architecture, mutational spectrum and genetic susceptibility. The immune microenvironment also displayed spatiotemporal heterogeneity, such as less T cell and more M2 macrophage infiltration in IM and higher expression of inhibitory immune checkpoints in MO. Similar to mutational profiles, shared neoantigens and TCR repertoires among tumors from the same patients were abundant in IM but scarce in MO. Combining neoantigen prediction and immunopeptidomes identified T cell-specific neoepitopes and achieved a high verification rate in vitro. Immunoediting mainly occurred in MO but not IM, due to the relatively low immune infiltration. Loss of heterozygosity of human leukocyte antigen (HLA) alleles, identified in 17% of multifocal HCC, hampered the ability of major histocompatibility complex to present neoantigens, especially in IM. An integrated analysis of Immunoscore, immunoediting, TCR clonality and HLA loss of heterozygosity in each tumor could stratify patients into 2 groups based on whether they have a high or low risk of recurrence (p = 0.038). CONCLUSION: Our study comprehensively characterized the genetic structure, neoepitope landscape, T cell profile and immunoediting status that collectively shape tumor evolution and could be used to optimize personalized immunotherapies for multifocal HCC. LAY SUMMARY: Immunogenomic features of multifocal hepatocellular carcinoma (HCC) are important for understanding immune-escape mechanisms and developing more effective immunotherapy. Herein, comprehensive immunogenomic characterization showed that diverse genomic structures within multifocal HCC would leave footprints on the immune landscape. Only a few tumors were under the control of immunosurveillance, while others evaded the immune system through multiple mechanisms that led to poor prognosis. Our study revealed heterogeneous immunogenomic landscapes and immune-constrained tumor evolution, the understanding of which could be used to optimize personalized immunotherapies for multifocal HCC.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/imunologia , Evasão Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/imunologia , Feminino , Predisposição Genética para Doença , Antígenos HLA/genética , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Receptores de Antígenos de Linfócitos T/genética , Transcriptoma , Sequenciamento do ExomaRESUMO
BACKGROUND: Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). METHODS: The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. RESULTS: ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. CONCLUSIONS: ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.
RESUMO
Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to personalized precision therapy, due to the individual differences of unique neoantigens. With the discovery of many common oncogenic mutations, and such mutation-associated neoantigens could cover more patients, and hence are valuable in clinical field. However, whether the common neoantigens can be identified in CRC is unknown. Combining the somatic mutations data from 321 CRC patients with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*1101-restricted common neoantigens with a high binding affinity (IC50<50 nmol/L) and presentation score (>0.90). Besides the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens specifically induced in vitro pre- stimulated cytotoxic lymphocyte (CTL) to secrete interferon gamma (IFN-γ). Moreover, combining cell-sorting technology and single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were analyzed and validated. Their related T-cell receptor engineered T cell (TCR-T) cells could also recognize the neoantigens and secrete IFN-γ. Hence, we have established a method to screen for common neoantigens with immunogenicity in CRC based on the public somatic mutation library. It can provide essential peptide and TCR information for immunotherapies, such as peptides, dendritic cells (DC) vaccines, TCR-like antibodies, TCR-T, etc., for the CRC and other cancers, which has practical application value in the clinics.
Assuntos
Antígenos de Neoplasias , Neoplasias Colorretais , Antígenos de Neoplasias/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Detecção Precoce de Câncer , Humanos , Mutação , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
BACKGROUND: Taenia hydatigena, T. multiceps, T. pisiformis, and Dipylidium caninum are four common large and medium-sized tapeworms parasitizing the small intestine of dogs and other canids. These parasites cause serious impact on the health and development of livestock. However, there are, so far, no commercially available molecular diagnostic kits capable of simultaneously detecting all four parasites in dogs. The aim of the study was therefore to develop a multiplex PCR assay that will accurately detect all four cestode infections in one reaction. METHODS: Specific primers for a multiplex PCR were designed based on corresponding mitochondrial genome sequences, and its detection limit was assessed by serial dilutions of the genomic DNAs of tapeworms examined. Furthermore, field samples of dog feces were tested using the developed assay. RESULTS: A multiplex polymerase chain reaction (PCR) assay was developed based on mitochondrial DNA (mtDNA) that accurately and simultaneously identify four cestode species in one reaction using specific fragment sizes of 592, 385, 283, and 190 bp for T. hydatigena, T. multiceps, T. pisiformis, and D. caninum, respectively. The lowest DNA concentration detected was 1 ng for T. hydatigena, T. multiceps and T. pisiformis, and 0.1 ng for D. caninum in a 25 µl reaction system. This assay offers high potential for the rapid detection of these four tapeworms in host feces simultaneously. CONCLUSIONS: This study provides an efficient tool for the simultaneous detection of T. hydatigena, T. multiceps, T. pisiformis, and D. caninum. The assay will be potentially useful in epidemiological studies, diagnosis, and treatment of these four cestodes infections during prevention and control program.
Assuntos
Cestoides , Infecções por Cestoides , Técnicas Microbiológicas/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Animais , Cestoides/genética , Cestoides/isolamento & purificação , Infecções por Cestoides/diagnóstico , Infecções por Cestoides/parasitologia , CãesRESUMO
Insulin resistance and insulin deficiency have long been believed to be the two main causes of type 2 diabetes mellitus (T2DM). However,recent studies have shown that paradoxical hypersecretion of glucagon may also contribute the pathogenesis of T2DM. This article reviews the role of paradoxical hypersecretion of glucagon in the pathogenesis of T2DM and the recent advances in relevant treatment options.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Glucagon/metabolismo , Humanos , Insulina , Resistência à InsulinaRESUMO
Although gankyrin is involved in the tumorigenicity and metastasis of some malignancies, the role of gankyrin in gastric cancer is not clear. In this study, we evaluated the function and mechanism of gankyrin in gastric cancer. The effects of gankyrin on gastric cancer growth, proliferation, and chemosensitivity were determined. Gankyrin expression was significantly increased in gastric cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo. Suppression of gankyrin downregulated cyclin D1, cyclin E, proliferating cell nuclear antigen, phosphoinositide 3-kinase, AKT, p-PI3K, and p-AKT but upregulated Rb, p53, and p27. However, gankyrin overexpression led to opposite results. Downregulation of gankyrin expression enhanced chemosensitivity to 5-fluorouracil and cisplatin by inducing cell apoptosis. However, upregulation of gankyrin expression led to the opposite outcomes. Gankyrin enhanced gastric cancer cell proliferation by regulating cell cycle-related proteins and by activating PI3K/AKT signaling pathway. Gankyrin played an important role in gastric carcinogenesis and could be a potential effective therapeutic target for enhancing chemosensitivity to 5-fluorouracil and cisplatin.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Complexo de Endopeptidases do Proteassoma/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Complexo de Endopeptidases do Proteassoma/genética , Proteínas Proto-Oncogênicas/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/patologiaRESUMO
The study illustrate the inner correlation between global DNA methylation variation and different birth weights. Infant birth weight was used to identify cases and controls. Cord blood and placentas were collected. We performed DNA methylation profiling of bisulphite-converted DNA. We have identified many differentially methylated CpG sites in experimental groups; these sites involved in hundreds of signalings. Among these, more than ten pathways were referred to the glucose and lipid metabolism. Methylation changes in the insulin-signaling pathway (ISP), adipocytokine signaling pathway (ASP) and MAPK signaling pathway are involved in the fetal programming of diabetes..
Assuntos
Peso ao Nascer , Metilação de DNA , Estudo de Associação Genômica Ampla , Feminino , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Humanos , Recém-Nascido , Masculino , Tamanho do Órgão , Placenta/anatomia & histologia , Gravidez , Transdução de SinaisRESUMO
OBJECTIVE: The aim of this study was to evaluate the 6-month efficacy of a Ketogenic diet (KD) in children with drug-resistant epilepsy and to analyze the associated factors that affect the efficacy of a KD. METHODS: Eighty-seven pediatric patients with drug-resistant epilepsy who followed a KD for at least 6 months were included in this study. The efficacy of a KD was assessed based upon the seizure frequency, as recorded by parents and caregivers. The number of cases and the degree of efficacy in different age ranges were also considered. The effects of gender, age, seizure type, etiology, blood glucose and ketone levels, seizure frequency before the diet, and cognition on the length of time on a KD were analyzed. RESULTS: (1) There was no significant correlation between the length of time on a KD and efficacy (χ(2)=2.31, P=0.51). The 3-month efficacy of a KD was 51%, which did not further increase when the course was extended to 6 months. (2) There was a positive correlation between increased cognition and the efficacy of a KD after 3 months (γ=0.31, P=0.003). (3) The efficacy analysis of 3-month treatment with a KD revealed, with respect to seizure types, that there were 37 patients with multiple seizure phenotypes and 50 patients with a single seizure phenotype. The overall efficacy of a KD in the group with multiple seizure phenotypes was 61%. The efficacy of a KD was not statistically associated with a coexisting syndrome or a type of syndrome; however, the efficacy of a KD had a tendency to be increased in certain types of syndromes. The overall efficacy in the group with a single seizure phenotype was 87%, and the efficacy was not associated with seizure type. (4) The 3-month efficacy of a KD was not correlated with age, gender, etiology, blood glucose or ketone levels, or the seizure frequency before treatment. CONCLUSION: An observation time of 3 months is appropriate for assessing the efficacy of a KD in treating children with drug-resistant epilepsy. The factors that likely influence the efficacy of a KD are unclear, but our study suggests that incorporating more patient samples will help determine whether patients with certain syndromes can benefit from a KD.
Assuntos
Dieta Cetogênica/métodos , Epilepsia Resistente a Medicamentos/dietoterapia , Convulsões/dietoterapia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Valor Preditivo dos Testes , Fatores Sexuais , Resultado do TratamentoAssuntos
Procedimentos Endovasculares/instrumentação , Extremidade Inferior/irrigação sanguínea , Trombectomia/instrumentação , Terapia Trombolítica/instrumentação , Dispositivos de Acesso Vascular , Trombose Venosa/terapia , Doença Aguda , Adulto , Idoso , Estudos de Casos e Controles , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos , Resultado do Tratamento , Grau de Desobstrução Vascular , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/fisiopatologiaRESUMO
Gold nanoparticles (GNPs) have been widely applied in industrial catalysis and electrocatalysis. Owing to their wide variety of shapes, sizes, and compositions, a range of different catalytic properties is possible. Thus, it is important to monitor catalytic processes and their mechanisms on single GNP surfaces to avoid averaging effects in bulk systems. Therefore, a novel method based on dark-field scattering spectroscopy was developed to monitor, in real-time, the electrocatalytic oxidation of hydrogen peroxide on a single gold nanoparticle surface. The catalytic mechanism was revealed via the plasmon resonance scattering spectral shift of single gold nanorod with the elimination of bulk effect. Moreover, we found that the presence of chloride ions could block the catalytic activity of nanorods for the oxidation of H2O2. Most importantly, it was discovered that individual nanoparticles have variable properties with different spectra shifts during the catalytic process. The obtained optical signals from individual nanorods not only offer versatile information regarding the reaction but also improve the understanding of electrochemistry and the catalysis mechanism of single nanoparticles.
Assuntos
Eletroquímica/métodos , Ouro/química , Nanotubos/química , Ressonância de Plasmônio de Superfície/métodos , Catálise , Eletrodos , Peróxido de Hidrogênio/química , Luz , Nitratos/química , Oxirredução , Cloreto de Potássio/química , Compostos de Potássio/química , Espalhamento de RadiaçãoRESUMO
The applications of organic-amine desulfurization have steadily increased owing to its high efficiency, low cost, and low energy consumption. Different proportions of organic amines exert different effects on sulfur dioxide removal. Therefore, the accurate determination of different organic amines in the desulfurization solution is of great importance. The ion-chromatographic method for the detection of organic amines does not require a derivatization step, has simple pretreatment procedures, and allows for the simultaneous determination of many types of organic amines. In this study, a method based on ion chromatography was developed for the simultaneous determination of ethanolamine (MEA), diethylethanolamine (DEEA), n-methyldiethanolamine (MDEA), 2-amino-2-methyl-1-propanol (AMP), hydroxyethylethylenediamine (AEEA), piperazine (PZ), n-hydroxyethylpiperazine (HEPZ), and diethylenetriamine (DETA). The separation efficiency of the eight organic amines in different types of columns, leaching solutions, and column temperatures were compared. The determination was performed using an IonPac CS17 column with column temperature of 35 â and gradient leaching with methyl sulfonic acid (MSA) solution via the inhibition conductance method. Samples of the desulfurization solution were analyzed using ultrapure water filtered through a 0.22 µm nylon microporous filter membrane and an OnGuard â ¡ RP column; thus, the pretreatment steps are simple. The eight organic amines showed a good linear relationship within a certain concentration range, and the coefficient of determinations (R2) were greater than 0.998. The limits of detection (LODs) and quantification (LOQs) were determined from the mass concentrations of the organic amines corresponding to signal-to-noise ratios (S/N) of 3 and 10, respectively. LODs of 0.02-0.08 mg/L and LOQs of 0.07-0.27 mg/L were determined from a 1.0 µL sample injection. The actual recoveries ranged from 93.0% to 111%, and the relative standard deviations (RSDs, n=5) ranged from 0.31% to 1.2%. The results indicated that the proposed method has good accuracy and precision; thus, it is suitable for the determination of various organic amines in desulfurization solution.
RESUMO
Our objective was to investigate the status and influence of myopia among primary school students in Fushun, Liaoning Province, China. We aimed to provide a theoretical and epistemological basis for implementing myopia prevention initiatives. We employed cluster sampling and surveyed 5216 primary school students from grades 1-6 across eight primary schools in Fushun City. Our participants included 2606 males and 2610 females whose average age was 9.25 (SD = 1.76) years. The rate of myopia among these primary school students was 29.54%, with statistically significant differences among students of different genders and grades. Logistic regression analysis further identified several possible protective factors, including appropriate reading distance, adequate home lighting, regular breaks between classes, conscientious eye exercises, and daily outdoor physical activity. Conversely, the associated risk factors were being female, being in a higher grade level, spending more than 4 hours on homework, occasionally reading while lying down, and having one or both parents with myopia. Overall, our results indicated a high incidence of myopia, highlighting the need for scientifically controlled interventions to manage and mitigate the occurrence and progression of myopia in this population.
Assuntos
Miopia , Humanos , Masculino , Feminino , Criança , Miopia/epidemiologia , Miopia/prevenção & controle , Inquéritos e Questionários , Estudantes , Instituições Acadêmicas , China/epidemiologia , PrevalênciaRESUMO
Background: In many clinical situations, it is critical to exclude or identify abnormally lymph nodes (LNs). The nature of superficial abnormally LNs is closely related to the stage, treatment, and prognosis of the disease. Ultrasound (US) is an important method for examining superficial LNs due to its cheap and safe characteristics. However, it is still difficult to determine the nature of some LNs with overlapping benign and malignant features in images. Contrast-enhanced ultrasound (CEUS) can be used to evaluate the microperfusion status of tissues in real time, and it can improve diagnostic accuracy to a certain extent. Therefore, in this study, we will analyze the correlation between CEUS quantitative parameters and benign and malignant superficial abnormally LNs, to evaluate the efficacy and value of CEUS in distinguishing benign and malignant superficial LNs. Methods: This study retrospectively analyzed 120 patients of abnormal LNs who underwent US and CEUS at the China-Japan Union Hospital of Jilin University from December 2020 to August 2023. All 120 cases of abnormal LNs underwent US-guided coarse needle biopsy, and accurate pathological results were obtained, along with complete US and CEUS images. According to the pathological results, LNs were divided into benign and malignant groups, and the qualitative and quantitative parameters of US and CEUS between the two groups were analyzed. The cutoff value is determined by the receiver operating characteristic (ROC) curve of the subjects, and sensitivity, specificity, and accuracy are applied to evaluate the ability of the cutoff value to distinguish between the two groups. Results: There were a total of 120 LNs, including 36 in the benign group and 84 in the malignant group. The results showed that malignant LNs were usually characterized by the disappearance of lymphatic hilum, round ness index (L/T) <2, irregular morphology, and the manifestation of uneven perfusion (P<0.05). The differences in the quantitative parameters peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in rate (WIR), and wash-out rate (WOR) were statistically significant (P<0.05). The result showed that RT and TTP in the malignant LNs were higher than those in the benign LNs, while the PE, WIR, and WOR were lower. A comparison of the ∆ values showed that the differences in ∆PE, ∆WIR, and ∆fall time (FT) were statistically significant (P<0.05), Among them, the ∆PE and ∆WIR of malignant LNs were higher than those of benign LNs, while the ∆FT was lower than that of benign LNs. Conclusions: Quantitative analysis of CEUS features is valuable in the diagnosis of benign and malignant LNs, and US combined with CEUS helps to improve the accuracy of identifying the nature of LNs.
RESUMO
BACKGROUND: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. METHODS: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan-Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. RESULTS: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. CONCLUSIONS: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.