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1.
J Surg Res ; 270: 539-546, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34808473

RESUMO

BACKGROUND: The eighth edition of new staging systems for breast cancer incorporated four biological factors and the anatomic staging system. Validating analysis on Chinese patients has been limited. Our study performed analysis comparing the prognostic value of the staging system based on Chinese data. METHODS AND MATERIALS: All patients were classified according to the eighth edition and compared between anatomic and prognostic staging systems. The Kaplan-Meier test was used to calculate the overall survival (OS) and disease-free survival (DFS). We performed Harrell concordance index (C-index) analyses to quantify a models' predictive performance. Akaike information criterion (AIC) via Cox regression analysis was used to conduct bootstrap-based goodness-of-fit comparisons of the competing staging systems. RESULTS: A total of 1556 patients were enrolled in the cohort. The median follow-up time was 76 mo (range, 4-146 mo), the median age was 48 y old (range, 21-87 y). The ratio of movement between anatomic stage (AS) and prognostic stage (PS) was 50.9%. Of these, 691 (44.5%) AS patients were down staged and 100 (6.4%) patients were upstaged when reclassified based on PS. Significant differences between two stages were achieved for stage IIIC in 5-y OS rates and for IIIB in 5-y DFS rates (63.5% versus 50.0% and 58.0% versus44.0%). The value of the C-index for PS and AS were 0.711 and 0.687 (P = 0.04). The AIC reaches a value of 3452.9 for the PS and a value of 3476.4 for the AS. CONCLUSIONS: The PS might provide better accuracy than the AS in predicting the prognosis of Chinese female breast cancer patients. It also provides a strong basis for the utility of clinical biomarkers to evaluate the prognosis of patients.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Estados Unidos
2.
Chem Biodivers ; 19(12): e202200490, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36266258

RESUMO

2-(2-Phenylethyl)chromone derivatives are regarded as key components in agarwood. An oxygen-containing heterocycle with a benzoannelated γ-pyrone moiety form the bioactive core of 2-(2-phenylethyl)chromones. With different substituents and positions, 2-(2-phenylethyl)chromone derivatives exhibit diverse biological properties, such as antioxidant, antimicrobial, neuroprotective, anti-inflammatory, and acetylcholinesterase inhibitory activities. In this review, we summarized the studies (from January 1976 to September 2021) on phytochemistry, bioactivity and quality control of 2-(2-phenylethyl)chromones. These studies aimed to clarify the chemical specificity, diversity and structure-activity relationship of 2-(2-phenylethyl)chromones. In addition, we assumed that diverse factors such as tree species, induction methods and formation time contribute to the chemical diversity of 2-(2-phenylethyl)chromones. Furthermore, this review contends that different types of 2-(2-phenylethyl)chromones should be utilized in the quality control methods of agarwood.


Assuntos
Cromonas , Thymelaeaceae , Cromonas/química , Acetilcolinesterase , Thymelaeaceae/química , Flavonoides/farmacologia , Flavonoides/química , Estrutura Molecular
3.
Mol Hum Reprod ; 27(5)2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33848337

RESUMO

Acephalic spermatozoa syndrome (ASS) is a rare teratozoospermia that leads to male infertility. Previous work suggested a genetic origin. Variants of Sad1 and UNC84 domain containing 5 (SUN5) are the main genetic cause of ASS; however, its pathogenesis remains unclear. Here, we performed whole-exome sequencing in 10 unrelated ASS and identified 2 homozygous variants, c.381delA[p.V128Sfs7*] and c.675C>A[p.Y225X], and 1 compound variant, c.88 C > T[p.R30X] and c.381 delA [p.V128Sfs7*], in SUN5 in 4 patients. The c.381delA variant had been identified as pathogenic in previous reports, while c.675C>A and c.88 C > T were two novel variants which could lead to a premature termination codon (PTC) and resulted in loss of SUN5, and may also be pathogenic. SUN5 mRNA and protein were present at very low levels in ASS patients with SUN5 nonsense mutation. Furthermore, the distribution of outer dense fiber protein 1 (ODF1) and Nesprin3 was altered in sperm of ASS patients with SUN5 variants. The co-immunoprecipitation analysis indicated that SUN5 and ODF1, SUN5 and Nesprin3, and ODF1 and Nesprin3 interacted with each other in transfected HEK293T cells. Thus, we propose that SUN5, Nesprin3, and ODF1 may form a 'triplet' structure through interactions at neck of sperm. When gene variants resulted in a loss of SUN5, the 'triplet' structure disappears and then the head-tail junction becomes fragile, leading to the occurrence of ASS.


Assuntos
Proteínas de Membrana/genética , Espermatozoides/ultraestrutura , Teratozoospermia/genética , Análise Mutacional de DNA , Fertilidade , Proteínas de Choque Térmico/metabolismo , Homozigoto , Humanos , Masculino , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Análise do Sêmen , Cabeça do Espermatozoide/patologia , Sequenciamento do Exoma
4.
Neoplasma ; 68(4): 742-750, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33847134

RESUMO

Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades (ICBs) without the specific radiation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT. The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, p=0.043 and 5% vs. 45%, p=0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, p=0.011, 90% vs. 0%, p=0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than long-course RT (22.5% vs. 8.0%, p=0.0440 in ICs; 0% vs. 70%, p<0.001 in TCs). On the contrary, CD8 was higher after long-course RT (15% vs. 8%, p=0.0146). Interestingly, the level of ICs TIM-3 was low in > eight weeks after long-course RT (p=0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (p=0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95% CI 0.089-0.840; p=0.024) and ICs TIM-3 (HR 0.425; 95% CI 0.203-0.890; p=0.023) were independent prognostic factors of DFS in rectal cancer patients following NRT. In conclusion, we have identified that PD-1 and ICs LAG-3 presented a trend towards increased expression after NRT, supporting the ICBs and NRT combination as a potential treatment option for local advanced rectal cancer patients. The radiotherapeutic mode and timing of the treatment might significantly affect the expression of ICBs, which indicated that the sequencing and time window of ICBs immunotherapy utility might deserve a high value.


Assuntos
Antígenos CD , Receptor Celular 2 do Vírus da Hepatite A , Receptor de Morte Celular Programada 1 , Neoplasias Retais , Humanos , Terapia Neoadjuvante , Neoplasias Retais/radioterapia , Proteína do Gene 3 de Ativação de Linfócitos
5.
Ren Fail ; 43(1): 840-850, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34016023

RESUMO

BACKGROUND: The therapeutic effects of tacrolimus (TAC) versus cyclophosphamide (CTX) were not fully illustrated for patients with idiopathic membranous nephropathy (IMN). METHODS: The PubMed, EmBase, Cochrane library, and CNKI were systematically searched throughout March 2020 for randomized controlled trials evaluating the therapeutic effects of TAC versus CTX for IMN patients treated with steroids. The pooled relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Twelve trials recruited a total of 868 IMN patients were identified and contained in final meta-analysis. Patients in TAC group was associated with an increased incidence of overall remission (12 trials: 868 patients; RR: 1.21; 95% CI: 1.11-1.31; p < 0.001) and complete remission (12 trials: 868 patients; RR: 1.50; 95% CI: 1.25-1.80; p < 0.001). Moreover, we noted TAC therapy significantly reduced urinary protein excretion (9 trials: 567 patients; WMD: -1.06; 95%CI: -1.41 to -0.71; p < 0.001), and increased serum albumin (9 trials: 567 patients; WMD: 5.37; 95%CI: 2.97 to 7.77; p < 0.001) than CTX therapy. Furthermore, no significant difference between TAC and CTX for serum creatinine was detected (6 trials: 378 patients; WMD: 0.15; 95%CI: -3.46 to 3.75; p = 0.936). Finally, the risk of alopecia (p = 0.008), infection (p = 0.045), leukocytosis (p = 0.002), and elevated ALT/AST (p = 0.011) in TAC group was significantly lower than CTX group, whereas TAC was associated with an increased risk of tremor than CTX (p = 0.010). CONCLUSIONS: This study found IMN patients treated with TAC combined with steroids provides a better therapeutic effect and less adverse events than those treated with CTX combined with steroids, with moderate-certainty evidence.


Assuntos
Ciclofosfamida/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Esteroides/efeitos adversos , Tacrolimo/efeitos adversos
6.
Proc Biol Sci ; 287(1926): 20200470, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32370674

RESUMO

The cuticle of ecdysozoans (Panarthropoda, Scalidophora, Nematoida) is secreted by underlying epidermal cells and renewed via ecdysis. We explore here the relationship between epidermis and external cuticular ornament in stem-group scalidophorans from the early Cambrian of China (Kuanchuanpu Formation; ca 535 Ma) that had two types of microscopic polygonal cuticular networks with either straight or microfolded boundaries. Detailed comparisons with modern scalidophorans (priapulids) indicate that these networks faithfully replicate the cell boundaries of the epidermis. This suggests that the cuticle of early scalidophorans formed through the fusion between patches of extracellular material secreted by epidermal cells, as observed in various groups of present-day ecdysozoans, including arthropods. Key genetic, biochemical and mechanical processes associated with ecdysis and cuticle formation seem to have appeared very early (at least not later than 535 Ma) in the evolution of ecdysozoans. Microfolded reticulation is likely to be a mechanical response to absorbing contraction exerted by underlying muscles. The polygonal reticulation in early and extant ecdysozoans is clearly a by-product of the epidermal cell pavement and interacted with the sedimentary environment.


Assuntos
Artrópodes , Células Epidérmicas , Animais , Evolução Biológica , China , Epiderme , Fósseis , Muda , Filogenia
7.
J Med Virol ; 92(2): 191-200, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31513283

RESUMO

Emerging suggest that microRNAs (miRNAs) play vital roles in the occurrence and development of hepatitis B virus (HBV) infectious disease. However, miRNAs in occult hepatitis B virus infection (OBI), a special stage of HBV infection, remain largely unknown. Herein, we conducted this study to identify differentially expressed miRNAs and then to investigate the potential roles of these miRNAs in OBI. Plasma miRNA expression profiles of three OBI patients and three healthy controls were analyzed with high through-put miRNA sequencing technology. Altered expression of miRNAs was further confirmed with reverse transcription quantitative polymerase chain reaction (qRT-PCR). Finally, bioinformatics analysis was conducted to investigate the involved pathways and target genes for these differentially expressed miRNAs. Totally, 32 differentially expressed miRNAs were identified between OBI and healthy controls by miRNA sequencing (fold change ≥ 1.5, P < .1, and counts per million reads ≥ 1), including 16 downregulated and 16 upregulated miRNAs. Differential expression of hsa-miR-486-5p, -25-3p, and -92a-3p and -1-3p was further validated by qRT-PCR analysis, which was consistent with miRNA sequencing analysis. Moreover, these four miRNAs might distinguish OBI from HCs efficiently. Bioinformatics analyses indicated that the differentially expressed miRNAs were primarily involved in various biological processes related to gene expression and transcription, cell development and metabolism, protein modification and kinase activity regulation, as well as multiple signaling pathways such as PI3K/Akt signaling pathway. This study provided a global view of miRNA expression in plasma from OBI patients. These differentially expressed miRNAs might play important roles in the development of OBI, which provided intriguing insights into the screening and molecular mechanism of OBI.


Assuntos
MicroRNA Circulante/sangue , Perfilação da Expressão Gênica , Hepatite B/genética , Adulto , Biologia Computacional , Feminino , Regulação da Expressão Gênica , Vírus da Hepatite B , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Transdução de Sinais
8.
Hum Mol Genet ; 26(23): 4752-4763, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29036319

RESUMO

Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity of genetic factors in tuberculosis (TB) susceptibility. Despite having the third highest global TB burden, no TB-related GWAS has been performed in China. Here, we performed the first three-stage GWAS on TB in the Han Chinese population. In the stage 1 (discovery stage), after quality control, 691 388 SNPs present in 972 TB patients and 1537 controls were retained. After replication on an additional 3460 TB patients and 4862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1.41 × 10-11, odds ratio = 0.79). The aforementioned three SNPs were harbored by MFN2, RGS12 and human leukocyte antigen class II beta chain paralogue encoding genes, all of which are candidate immune genes associated with TB. Our findings provide new insight into the genetic background of TB in the Han Chinese population.


Assuntos
GTP Fosfo-Hidrolases/genética , Proteínas Mitocondriais/genética , Proteínas RGS/genética , Tuberculose/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Etnicidade/genética , Feminino , GTP Fosfo-Hidrolases/metabolismo , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Proteínas RGS/metabolismo
9.
Cell Physiol Biochem ; 52(6): 1446-1462, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31088038

RESUMO

BACKGROUND/AIMS: Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. Recent studies have shown that phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the surviva of fibroblast-like synoviocytes (FLSs) and the production of pro-inflammatory cytokines in RA. The purpose of this study was to explore the functions and underlying mechanisms of PTEN in the proliferation and migration of FLSs. METHODS: FLSs were obtained from adjuvant-induced arthritis (AIA) and normal rats. The expression levels of PTEN, c-Myc, cyclin D1, PCNA, and MMP-9 were detected by quantitative-real-time-PCR and western blot assay. A BrdU proliferation assay, cell cycle analysis, and a wound-healing assay were used to study the role of PTEN in FLSs treated with PTEN inhibitor bpv, specific small interfering RNA targeting PTEN (PTEN-RNAi) or a PTEN over-expression vector (PTEN-GV141). Chromatin immunoprecipitation and methylation-special PCR assays were used to study the expression of PTEN mRNA in the presence of DNA methylation. RESULTS: PTEN expression was downregulated in AIA FLSs in comparison to normal rats. Moreover, inhibition of PTEN expression by bpv or PTEN-RNAi could promote the proliferation and migration of FLSs, and increase the expression of c-Myc, cyclin D1, PCNA, and MMP-9 in AIA FLSs, but had no effect on TIMP-1 expression.In addition, transfection of AIA FLSs with PTEN-GV141 reduced their proliferation and migration. Further study indicated that DNA methylation could regulate PTEN expression in AIA. CONCLUSION: Our findings suggest that PTEN might play a pivotal role in the proliferation and migration of FLSs through the activation of the AKT signaling pathway. Additionally, PTEN expression may be regulated by DNA methylation in the pathogenesis of AIA.


Assuntos
Artrite Experimental/metabolismo , Movimento Celular , Proliferação de Células , Fibroblastos/metabolismo , Regulação da Expressão Gênica , PTEN Fosfo-Hidrolase/biossíntese , Sinoviócitos/metabolismo , Animais , Artrite Experimental/genética , Artrite Experimental/patologia , Feminino , Fibroblastos/patologia , PTEN Fosfo-Hidrolase/genética , Ratos , Ratos Sprague-Dawley , Sinoviócitos/patologia
10.
Pediatr Allergy Immunol ; 30(3): 378-386, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30716179

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disease in China, and very little large-scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients. METHODS: Pediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016. RESULTS: A total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X-linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P < 0.05). Approximately 64% (92/144) of the pediatric patients suffered from abnormal response to BCG vaccination. The most frequent pathogens were Aspergillus and Mycobacterium tuberculosis. Gene analysis indicated that 132 cases (89%, 132/147) harbored CYBB pathogenic variants, 7 (5%, 7/147) carried CYBA pathogenic variants, 4 (3%, 4/147) had NCF1 pathogenic variants, and 4 (3%, 4/147) had NCF2 pathogenic variants. The overall mortality rate in this study was 43%, particularly the patients were males, with CYBB mutant and did not receive HSCT treatment. CONCLUSIONS: Chronic granulomatous disease is a rare disease affecting Chinese children; however, it is often diagnosed at a later age, and thus, the mortality rate is relatively high. The prevalence and the severity of disease in XL-CGD are higher than AR-CGD.


Assuntos
Doença Granulomatosa Crônica/diagnóstico , NADPH Oxidases/genética , Adolescente , Anti-Infecciosos/uso terapêutico , Povo Asiático/genética , Criança , Pré-Escolar , China , Feminino , Testes Genéticos/métodos , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Estudos Retrospectivos
11.
Sheng Li Xue Bao ; 70(5): 539-547, 2018 Oct 25.
Artigo em Zh | MEDLINE | ID: mdl-30377693

RESUMO

Songbird has become an ideal model for studying motor learning due to its unique learned song behavior. It has been proved that song behavior is directly regulated by song control system in the forebrain of songbirds. There are lines of evidence to show that cholinergic transmitters and their receptors are distributed in song control system, and vocal control nuclei in song control system are innervated by cholinergic nerves from the central cholinergic system in basal forebrain, which can affect activities of vocal control nuclei through cholinergic transmitters, and then affect song behavior. Studies in mammals have confirmed that the central cholinergic system is involved in the regulation of motor behavior and neural process of motor learning. Elucidation of regulation of songbirds' song behavior by central cholinergic system would shed light on the neural mechanism of song motor control and song learning and memory in songbirds, and provide theoretical insights for researches on other animals' sensorimotor processes and human language learning. This review summarized recent progresses, including the research work of our laboratory, in the studies on the selectivity of cholinergic transmitters to their receptors and their effects on neuronal activities in vocal control nuclei of songbirds and provided valuable clues for revealing the regulation mechanism of central cholinergic system on songbirds' song behavior.


Assuntos
Neurônios Colinérgicos/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Aves Canoras/fisiologia , Vocalização Animal , Animais , Aprendizagem , Memória , Prosencéfalo/fisiologia
12.
Cell Physiol Biochem ; 41(5): 2067-2076, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28419994

RESUMO

BACKGROUND/AIMS: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. METHODS: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting. The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation assay. RESULTS: Cell growth was inhibited by bufalin in a time and dose-dependent manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA expression in H1975 cells, but strongly promoted Mcl-1 protein degradation. Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect NOXA protein levels, but downregulated the expression of p-GSK-3ß. GSK-3 inhibitor and GSK-3ß siRNA resulted in increased levels of Mcl-1 and reversed the bufalin-induced Mcl-1 degradation. CONCLUSION: Bufalin induced cell apoptosis in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of Mcl-1 via GSK-3ß activation was involved in bufalin-induced apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Bufanolídeos/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteólise/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética
13.
Antimicrob Agents Chemother ; 60(5): 2807-12, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26902762

RESUMO

Mycobacterium tuberculosis can acquire resistance to rifampin (RIF) through mutations in the rpoB gene. This is usually accompanied by a fitness cost, which, however, can be mitigated by secondary mutations in the rpoA or rpoC gene. This study aimed to identify rpoA and rpoC mutations in clinical M. tuberculosis isolates in northern China in order to clarify their role in the transmission of drug-resistant tuberculosis (TB). The study collection included 332 RIF-resistant and 178 RIF-susceptible isolates. The majority of isolates belonged to the Beijing genotype (95.3%, 486/510 isolates), and no mutation was found in rpoA or rpoC of the non-Beijing genotype strains. Among the Beijing genotype strains, 27.8% (89/320) of RIF-resistant isolates harbored nonsynonymous mutations in the rpoA (n = 6) or rpoC (n = 83) gene. The proportion of rpoC mutations was significantly higher in new cases (P = 0.023) and in strains with the rpoB S531L mutation (P < 0.001). In addition, multidrug-resistant (MDR) strains with rpoC mutations were significantly associated with 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat clustering (P = 0.016). In summary, we believe that these findings indirectly suggest an epistatic interaction of particular mutations related to RIF resistance and strain fitness and, consequently, the role of such mutations in the spread of MDR M. tuberculosis strains.


Assuntos
Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Proteínas de Bactérias/genética , China , Farmacorresistência Bacteriana Múltipla/genética , Genótipo , Testes de Sensibilidade Microbiana , Mutação/genética , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos/genética
14.
BMC Microbiol ; 16: 85, 2016 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-27176471

RESUMO

BACKGROUND: As the epidemic of MDR-TB and XDR-TB becomes increasingly severe, it is important to determine the clinical characteristics and molecular epidemiology of MDR-TB and XDR-TB. Recently, many studies have shown that clinical features and molecular characteristics of drug-resistant strains vary in different geographical areas, however, further information is needed to assess the dynamic evolution of drug-resistant TB. Comparative studies between different time periods are necessary to elucidate the development of drug-resistant TB. RESULTS: A total of 255 and 537 strains were collected from Beijing Chest Hospital in 2006 and in 2012, respectively. Drug-resistance rates and mutations associated with resistance to first-line anti-tuberculosis (TB) drugs were compared. The overall rate of drug resistance among strains of TB in 2012 was 54.4 %, significantly higher than that in 2006 (34.9 %, P < 0.001). Rates of resistance to each first-line drug (isoniazid, rifampicin, streptomycin and ethambutol) and to second-line drug ofloxacin increased significantly from 2006 to 2012. The overall MDR rate also increased significantly from 2006 (14.9 %) to 2012 (27.0 %). The rate of MDR increased significantly between these two time periods in previously treated cases (P = 0.023) but not in new cases (P = 0.073), and the rate of XDR was similar in new cases at the two time periods, but was marginally higher in 2012 in previously treated cases (P = 0.056). Previous treatment was found to be a risk factor for drug-resistant TB, especially for MDR-TB. In addition, the proportion of drug resistant isolates in which katG, the mabA-inhA promoter, oxyR-ahpC intergenic region, rpoB, rpsL, and embB were mutated was similar in 2006 and 2012, however patterns of mutation in these loci were more diverse in 2012 compared to 2006. CONCLUSIONS: Our data suggests that the prevalence of drug resistant TB remains high in Beijing, China, and that increasing rates of resistance in M. tuberculosis to all anti-TB drugs should be considered when choosing an optimal anti-TB regimen. Moreover, acquired multi-drug resistance may play a primary role in the MDR-TB epidemic in Beijing, China. Consequently, this highlights the importance of an earlier start to effective and supervised treatment in order to reduce the burden of retreatment.


Assuntos
Antituberculosos/farmacologia , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Mycobacterium tuberculosis/classificação , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Proteínas de Bactérias/genética , China , Farmacorresistência Bacteriana Múltipla , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Taxa de Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
15.
Biochem Biophys Res Commun ; 459(3): 398-404, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25735977

RESUMO

The echinoderm microtubule-associated protein-like 4(EML4)--anaplastic lymphoma kinase (ALK) fusion gene has been identified as a driver mutation in non-small-cell lung cancer (NSCLC). However, the role of EML4-ALK in malignant transformation is not entirely clear. Here, for the first time, we showed that H1299 NSCLC cells stably expressing EML4-ALK acquire EMT phenotype, associated with enhanced invasive migration and increased expression of EMT-inducing transcription factors. H1299-EML4-ALK cells also displayed cancer stem cell-like properties with a concomitant up-regulation of CD133 and enhanced ability of mammospheres formation. Moreover, we found that inhibition of ERK1/2 reversed EMT induced by EML4-ALK in H1299 cells. Taken together, these results suggested that EML4-ALK induced ERK activation is mechanistically associated with EMT phenotype. Thus, inhibition of ERK signaling pathway could be a potential strategy in treatment of NSCLC patients with EML4-ALK translocation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas de Fusão Oncogênica/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular , Transformação Celular Neoplásica , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias Pulmonares/genética , Sistema de Sinalização das MAP Quinases , Invasividade Neoplásica , Fusão Oncogênica , Proteínas de Fusão Oncogênica/genética , Fenótipo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia
16.
BMC Complement Altern Med ; 15: 66, 2015 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-25887432

RESUMO

BACKGROUND: Tang Bi Kang (TBK) is a traditional Chinese medicine granule. It has been shown to have effects on nerve conduction velocity deficits, blood-related factors and oxidative stress. This study was undertaken to evaluate proposed antioxidative and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy (DPN). METHODS: DPN was induced in male Wistar rats by intraperitoneal administration of streptozocin (STZ) (60 mg/kg.b.w) for 8 weeks. Fasting blood glucose (FBG) levels were measured in the blood obtained by clipping the tails of the rats. Tail-flick tests were conducted with a tail-flick analgesic meter. Motor and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured directly at two sites using a Functional Experiment System. Oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD) and glutathione peroxidase (GSH-Px), inflammatory cytokines such as interleukin (IL)-6, and tumour necrosis factor (TNF)-α were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis of variance (ANOVA), followed by least-significant difference post hoc with SPSS. RESULTS: The administration of TBK for 4 weeks in DPN rats resulted in a significant decrease in FBG levels compared to untreated DPN rats. There was a significant increase in MNCV and SNCV in the DPN rats compared to untreated DPN rats. Serum level of MDA was significantly reduced while the activities of SOD and GSH-pX were significantly increased in the TBK treated DPN rats. TBK prevented DPN-induced increase in the serum levels of IL-6 and TNF-α. CONCLUSION: The results of this study demonstrate that the therapeutic effect of TBK on DPN rats may be associated with the antioxidative and anti-inflammatory responses.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Nervo Isquiático/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glicemia/metabolismo , Citocinas/sangue , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/induzido quimicamente , Neuropatias Diabéticas/fisiopatologia , Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Malondialdeído/sangue , Condução Nervosa/efeitos dos fármacos , Ratos Wistar , Nervo Isquiático/fisiologia , Estreptozocina , Superóxido Dismutase/metabolismo
17.
Acta Crystallogr C ; 69(Pt 9): 1070-2, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24005524

RESUMO

The title compound, C25H22NO2P, was synthesized in high yield by a three-component Kabachnik-Fields reaction of diphenylphosphine oxide, salicylaldehyde and aniline in dry toluene at room temperature. It precipitates as racemic crystals, in which strong hydrogen bonds between the hydroxy group and the P=O group of a neighbouring molecule form one-dimensional heterochiral chains along the crystallographic a axis, with an O···O separation of 2.568 (2) Å. The pseudo-tetrahedral environment of the P atom is distorted, with O-P-C bond angles significantly larger than the C-P-C angles.


Assuntos
Compostos de Anilina/química , Compostos de Anilina/síntese química , Cristalografia por Raios X , Fenóis/química , Fenóis/síntese química , Aldeídos/química , Ligação de Hidrogênio , Estrutura Molecular , Fosfinas/química
18.
Medicine (Baltimore) ; 102(24): e33899, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37327297

RESUMO

The aim of this study was to evaluate the feasibility, safety, and optimal dose of oral intake of carbohydrate-rich drinks 2 hours before painless colonoscopy. All patients receiving painless colonoscopy were randomly divided into 3 groups: control group (no carbohydrate-rich drink, n = 33), low-dose group (5 mL/kg carbohydrate-rich drink, n = 30), and high-dose group (8 mL/kg carbohydrate-rich drink, n = 30). Use of vasoactive drugs, the visual analog scale including thirst and hunger, degree of satisfaction, the time required for Modified Post Anesthetic Discharge Scoring System scale, first urination time, electrolyte level (sodium, potassium, and calcium), and blood glucose level were also determined. A total of 93 patients were recruited in this study. No significant difference was observed in the cross-sectional area (CSA) of the gastric antrum area at T0 between low- and high-dose groups (P = .912). There was a significant difference in CSA of gastric antrum at 120 minutes after oral intake between the low- and high-dose groups (P = .015). No significant difference was observed in the CSA of gastric antrum at 0 minutes and 120 minutes in the low-dose group (P = .177). In the high-dose group, the CSA of gastric antrum significantly differed at 0 minutes and 120 minutes (P < .001). There was a significant difference in the visual analog scale scores of thirst and hunger at 4 and 5 hours after bowel preparation among 3 groups (P = .001, P = .029, P < .001, P = .001). The degree of satisfaction in low- and high-dose groups was significantly higher than that in the control group (both P < .001). In conclusion, it is feasible and safe to deliver an oral intake of 5 mL/kg carbohydrate-rich drink 2 hours before painless colonoscopy. The comfort level and degree of satisfaction of patients can be further improved.


Assuntos
Carboidratos , Sede , Humanos , Colonoscopia , Cuidados Pré-Operatórios
19.
World J Psychiatry ; 13(10): 793-802, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-38058683

RESUMO

BACKGROUND: Acute cerebral infarction (ACI) is characterized by a high incidence of morbidity, disability, recurrence, death and heavy economic burden, and has become a disease of concern in global researchers. As ACI has serious effects on patients' physical status, life and economy, often causing anxiety, depression and other psychological problems, these problems can lead to the aggravation of physical symptoms; thus, it is very important to understand the factors affecting the mental health of these patients. AIM: To understand the elements that affect the mental health of patients who have suffered an ACI. METHODS: A questionnaire survey was conducted among patients with ACI admitted to three tertiary hospitals (Quanzhou First Hospital, Fuqing City Hospital Affiliated to Fujian Medical University, and the 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China) in Fujian Province from January 2022 to December 2022 using the convenience sampling method. ACI inpatients who met the inclusion criteria were selected. Informed consent was obtained from the patients before the investigation, and a face-to-face questionnaire survey was conducted using a unified scale. The questionnaire included a general situation questionnaire, Zung's self-rating depression scale and Zung's self-rating anxiety scale. All questionnaires were checked by two researchers and then the data were input and sorted using Excel software. The general situation of patients with ACI was analyzed by descriptive statistics, the influence of variables on mental health by the independent sample t test and variance analysis, and the influencing factors on psychological distress were analyzed by multiple stepwise regression. RESULTS: The average age of the 220 patients with ACI was 68.64 ± 10.74 years, including 142 males and 78 females. Most of the patients were between 60 and 74 years old, the majority had high school or technical secondary school education, most lived with their spouse, and most lived in cities. The majority of patients had a personal income of 3001 to 5000 RMB yuan per month. The new rural cooperative medical insurance system had the largest number of participants. Most stroke patients were cared for by their spouses and of these patients, 52.3% had previously smoked. Univariate analysis showed that gender, age, residence, course of disease, number of previous chronic diseases and smoking history were the main factors affecting the anxiety scores of patients with ACI. Age, living conditions, monthly income, course of disease and knowledge of disease were the primary variables influencing the depression score in patients with ACI. The findings of multivariate analysis revealed that the course of disease and gender were the most important factors influencing patients' anxiety scores, and the course of disease was also the most important factor influencing patients' depression scores. CONCLUSION: Long disease course and female patients with ACI were more likely to have psychological problems such as a high incidence of emotional disorders. These groups require more attention and counseling.

20.
J Cancer Res Clin Oncol ; 149(13): 12469-12477, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37442865

RESUMO

BACKGROUND: Lymph node metastasis (LNM) is a critical prognostic factor in resectable pancreatic cancer (PC) patients, determining treatment strategies. This study aimed to develop a clinical model to adequately and accurately predict the risk of LNM in PC patients. METHODS: 13,200 resectable PC patients were enrolled from the SEER (Surveillance, Epidemiology, and End Results) database, and randomly divided into a training group and an internal validation group at a ratio of 7:3. An independent group (n = 62) obtained from The First Affiliated Hospital of Xinxiang Medical University was enrolled as the external validation group. The univariate and multivariate logistic regression analyses were used to screen independent risk factors for LNM. The minimum Akaike's information criterion (AIC) was performed to select the optimal model parameters and construct a nomogram for assessing the risk of LNM. The performance of the nomogram was assessed by the receiver operating characteristics (ROC) curve, calibration plot, and decision curve analysis (DCA). In addition, an online web calculator was designed to assess the risk of LNM. RESULT: A total of six risk predictors (including age at diagnosis, race, primary site, grade, histology, and T-stage) were identified and included in the nomogram. The areas under the curves (AUCs) [95% confidential interval (CI)] were 0.711 (95%CI: 0.700-0.722), 0.700 (95%CI: 0.683-0.717), and 0.845 (95%CI: 0.749-0.942) in the training, internal validation and external validation groups, respectively. The calibration curves showed satisfied consistency between nomogram-predicted LNM and actual observed LNM. The concordance indexes (C-indexes) in the training, internal, and external validation sets were 0.689, 0.686, and 0.752, respectively. The DCA curves of the nomogram demonstrated good clinical utility. CONCLUSION: We constructed a nomogram model for predicting LNM in pancreatic cancer patients, which may help oncologists and surgeons to choose more individualized clinical treatment strategies and make better clinical decisions.


Assuntos
Nomogramas , Neoplasias Pancreáticas , Humanos , Metástase Linfática , Área Sob a Curva , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas
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