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INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.
Subject(s)
Hepatitis B, Chronic , Humans , Adult , Tenofovir/adverse effects , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Retrospective Studies , Alanine/therapeutic use , Adenine/therapeutic use , Kidney/physiology , Antiviral Agents/adverse effects , Treatment OutcomeABSTRACT
ABSTRACT Introduction Soccer games are of long duration and more confrontational; in the second half of the game, many players have a decline in their physical level, leading to loss of matches. Objective To explore the effect of weight training on lower limb fitness in soccer players. Methods 60 athletes were included as subjects and randomly divided into control group, weight training group, and traditional physical fitness training group. All athletes trained for 45 minutes 3 times a week for 6 weeks. Before and after training, lower limb strength and proprioception were evaluated, and the strength of the knee flexor and extensor group was assessed by isokinetic muscle tester. Results Both weight training and traditional physical training were able to improve the vertical jump performance of young soccer players, the training effects of both groups were equivalent. Conclusion Weight training has the same enhancing effect as traditional physical training in terms of strength and explosive power, promoting athletic performance in youth soccer players. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução Os jogos de futebol são de longa duração e de maior confrontação; na segunda metade do jogo, muitos jogadores têm um declínio em seu nível físico, levando à perda das partidas. Objetivo Explorar o efeito do treinamento com peso na condição física nos membros inferiores dos jogadores de futebol. Métodos 60 atletas foram incluídos como sujeitos e divididos aleatoriamente em grupo de controle, grupo de musculação e grupo de musculação física tradicional. Todos os atletas treinaram por 45 minutos 3 vezes por semana durante 6 semanas. Antes e depois do treinamento, a força dos membros inferiores e a propriocepção foram avaliadas, e a força do grupo flexor e extensor do joelho foi avaliada pelo testador muscular isocinético. Resultados Tanto o treinamento físico com peso quanto o treinamento físico tradicional conseguiram melhorar o desempenho do salto vertical dos jovens jogadores de futebol, os efeitos do treinamento dos dois grupos foram equivalentes. Conclusão O treinamento com peso tem o mesmo efeito de aprimoramento que o treinamento físico tradicional em termos de força e poder explosivo, promovendo o desempenho atlético em jogadores de futebol juvenil. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción Los partidos de fútbol son de larga duración y de mayor confrontación; en la segunda mitad del partido, muchos jugadores tienen un descenso en su nivel físico, lo que lleva a la pérdida de partidos. Objetivo Explorar el efecto del entrenamiento con pesas sobre la aptitud de las extremidades inferiores en jugadores de fútbol. Métodos Se incluyeron 60 atletas como sujetos y se dividieron aleatoriamente en el grupo de control, el grupo de entrenamiento con pesas y el grupo de acondicionamiento físico tradicional. Todos los atletas entrenaron 45 minutos 3 veces por semana durante 6 semanas. Antes y después del entrenamiento, se evaluó la fuerza de las extremidades inferiores y la propiocepción, y la fuerza del grupo de flexores y extensores de la rodilla se evaluó mediante un probador muscular isocinético. Resultados Tanto el entrenamiento con pesas como el entrenamiento físico tradicional fueron capaces de mejorar el rendimiento del salto vertical de los jóvenes futbolistas, los efectos del entrenamiento de ambos grupos fueron equivalentes. Conclusión El entrenamiento con pesas tiene el mismo efecto potenciador que el entrenamiento físico tradicional en términos de fuerza y potencia explosiva, promoviendo el rendimiento atlético en los jugadores de fútbol juvenil. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
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ABSTRACT Introduction The explosive power of the lower limbs is an indispensable index in soccer. Having a good level of explosive power establishes a solid foundation for the performance and the competitive level of soccer players. Objective Promote the conditions to improve the explosive level of soccer players and improve their performance and competitive level. Methods This paper presents the influence of compound strength training on the explosive power of the lower limbs of soccer athletes. Based on 27 young 9-year-old soccer players from Zai Ming Football Club of a sports college as experimental material, the composite training was carried out. Results The growth rates of these rates in the experimental group were 3.3%, 2.3%, 5.0%, 3.6%, 9.2%, 12.1%, 20.5%, 5.7%, 11.9%, 16.9% and 19.5% respectively, while those in the control group were 1.2%, 0.7%, 4.2%, 3.1%, 6.8%, 7.8%, 5.1%, 4.2%, 4.8%, 12.5% and 19.2% respectively. The growth rate of the experimental group was higher than that of the control group and the blank control group. Conclusion Compared with the control group and the neutral control group, the experimental group with compound training has a better training effect on improving the lower limb explosiveness of youth soccer players. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução A potência explosiva dos membros inferiores é um índice indispensável no futebol. Ter um bom nível de potência explosiva estabelece uma base sólida para o desempenho e o nível competitivo dos futebolistas. Objetivo Promover as condições para melhorar o nível explosivo dos jogadores de futebol e aperfeiçoar seu desempenho e nível competitivo. Métodos Este documento apresenta a influência do treinamento de força composta no poder explosivo dos membros inferiores dos atletas de futebol. Com base em 27 jovens jogadores de futebol com 9 anos de idade do Zai Ming Football Club de uma faculdade esportiva como material experimental, foi realizado o treinamento composto. Resultados As taxas de crescimento destes índices no grupo experimental foram de 3,3%, 2,3%, 5,0%, 3,6%, 9,2%, 12,1%, 20,5%, 5,7%, 11,9%, 16,9% e 19,5% respectivamente, enquanto os do grupo de controle foram de 1,2%, 0,7%, 4,2%, 3,1%, 6,8%, 7,8%, 5,1%, 4,2%, 4,8%, 12,5% e 19,2% respectivamente. A taxa de crescimento do grupo experimental foi maior do que a do grupo de controle e do grupo de controle em branco. Conclusão Em comparação com o grupo de controle e o grupo de controle neutro, o grupo experimental com treinamento composto tem um melhor efeito de treinamento para melhorar a explosividade dos membros inferiores dos jogadores de futebol juvenil. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción La potencia explosiva de los miembros inferiores es un índice indispensable en el fútbol. Tener un buen nivel de potencia explosiva establece una base sólida para el rendimiento y el nivel competitivo de los futbolistas. Objetivo Promover las condiciones para mejorar el nivel explosivo de los futbolistas y mejorar su rendimiento y nivel competitivo. Métodos Este trabajo presenta la influencia del entrenamiento de fuerza compuesta en la potencia explosiva de los miembros inferiores de los atletas de fútbol. Se llevó a cabo el entrenamiento compuesto con 27 jóvenes jugadores de fútbol de 9 años del Club de Fútbol Zai Ming de una escuela deportiva como material experimental. Resultados Las tasas de crecimiento de estos índices en el grupo experimental fueron del 3,3%, 2,3%, 5,0%, 3,6%, 9,2%, 12,1%, 20,5%, 5,7%, 11,9%, 16,9% y 19,5% respectivamente, mientras que las del grupo de control fueron del 1,2%, 0,7%, 4,2%, 3,1%, 6,8%, 7,8%, 5,1%, 4,2%, 4,8%, 12,5% y 19,2% respectivamente. La tasa de crecimiento del grupo experimental fue mayor que la del grupo de control y del grupo de control en blanco. Conclusión En comparación con el grupo de control y el grupo de control neutro, el grupo experimental con entrenamiento compuesto tiene un mejor efecto de entrenamiento para mejorar la explosividad de las extremidades inferiores de los futbolistas juveniles. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
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Disturbance of commensal intestinal microbiota is related to chronic inflammatory dermatosis. We analyzed the diversity of the gut microbiota to characterize the biological variation of psoriasis (Ps). Significant differences of gut microbiome profiles were revealed in murine model with psoriasis by sequencing 16S rRNA V3-V4 variable region. Group comparisons included the imiquimod cream (IMQ group, n=8), the imiquimod cream and antibiotics (ATB) (PC+IMQ group, n=8) and the healthy control (CTRL group, n=8). The gut microbiota existed in Ps groups including IMQ group and PC+IMQ group encompassed less diversity than controls, which were attributed to decreased presence of several taxa. The two Ps groups were characterized by significant reduction in firmicutes. In this study, microbiota of psoriasis was defined by an increase presence of Bacteroides. After treated with ATB, we found substantial increase of Lactobacillales but significant decrease of Clostridiales and Coriobacteriales. Relative lower abundance of multiple intestinal bacteria was observed in Ps groups. Although part of genera were concomitantly reduced in both IMQ and PC+IMQ conditions, we discovered the specialty of PC+IMQ group samples was that contained lower abundance of beneficial taxa. Characteristics of gut microbiota profiles in Ps mice were comparable to profiles in patients with Ps, which were related to alteration of specific inflammatory proteins in disease groups but were significantly different from control group. Thus, this study emphasizes the role of intestinal microbiota in the pathogenesis of Ps and provides new insight for investigating association between intestinal microbes and immune inflammation.
A perturbação da microbiota intestinal comensal está relacionada à dermatose inflamatória crônica. Analisamos a diversidade da microbiota intestinal para caracterizar a variação biológica da psoríase (Ps). Diferenças significativas do perfil microbiológico intestinal foram reveladas no modelo murino com psoríase pelo sequenciamento da região variável 16S rRNA V3-V4. As comparações de grupo incluíram o creme imiquimod (grupo IMQ, n=8), o creme imiquimod e antibióticos (ATB) (grupo PC+IMQ, n=8) e o controle saudável (grupo CTRL, n=8). A microbiota intestinal existia nos grupos Ps, incluindo o grupo IMQ e o grupo PC+IMQ englobava menos diversidade do que os controles, que foram atribuídos à diminuição da presença de vários taxa. Os dois grupos de Ps caracterizavam-se por uma redução significativa nos firicutes. Neste estudo, a microbiota da psoríase foi definida por um aumento da presença de bacteroides. Após o tratamento com ATB, encontramos um aumento substancial de Lactobacillales mas uma diminuição significativa de Clostridiales e Coriobacteriales. Uma menor abundância relativa de bactérias intestinais múltiplas foi observada nos grupos de Ps. Embora parte dos gêneros tenha sido concomitantemente reduzida tanto em condições IMQ como PC+IMQ, descobrimos que a especialidade das amostras do grupo PC+IMQ era que continham menor abundância de taxas benéficas. As características dos perfis de microbiota intestinal em ratos de Ps eram comparáveis aos perfis em pacientes com Ps, que estavam relacionados à alteração de proteínas inflamatórias específicas em grupos de doenças, mas eram significativamente diferentes do grupo controle. Assim, este estudo enfatiza o papel da microbiota intestinal na patogênese do Ps e fornece novos conhecimentos para investigar a associação entre micróbios intestinais e inflamação imunológica.
Subject(s)
Animals , Psoriasis/complications , Dermatitis/veterinary , Gastrointestinal Microbiome , Muridae/microbiologyABSTRACT
ABSTRACT Background The purpose is to compare the efficacy and safety of mini percutaneous nephrolithotomy (mini-PCNL) versus standard percutaneous nephrolithotomy (standard-PCNL) in patients with renal stones >2cm. Materials and Methods A systematic literature search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library databases to identify relevant studies before March 8, 2021. Stone-free rate (SFR), operation time, fever rate, hemoglobin drop, blood transfusion rate, and hospitalization time were used as outcomes to compare mini-PCNL and standard-PCNL. The meta-analysis was performed using the Review Manager version 5.4. Results Seven randomized controlled trials were included in our meta-analysis, involving 1407 mini-PCNL cases and 1436 standard-PCNL cases. Our results reveal that, for renal stones >2cm, mini-PCNL has a similar SFR (risk ratio (RR)=1.01, 95% confidence interval (CI): 0.98 to 1.04, p=0.57) and fever rate (RR=1.22, 95% CI: 0.97-1.51, p=0.08). Standard-PCNL was associated with a significantly shorter operating time (weighted mean difference (WMD)=8.23, 95% CI: 3.44 to 13.01, p <0.01) and a longer hospitalization time (WMD=-20.05, 95% CI: -29.28 to -10.81, p <0.01) than mini-PCNL. Subgroup analysis showed hemoglobin drop and blood transfusion for 30F standard-PCNL were more common than mini-PCNL (WMD=-0.95, 95% CI: -1.40 to -0.50, p <0.01; RR=0.20, 95% CI: 0.07 to 0.58, p <0.01). Conclusion In the treatment of >2cm renal stones, mini-PCNL should be considered an effective and reliable alternative to standard-PCNL (30F). It achieves a comparable SFR to standard-PCNL, but with less blood loss, lower transfusion rate, and shorter hospitalization. However, the mini-PCNL does not show a significant advantage over the 24F standard-PCNL. On the contrary, this procedure takes a longer operation time. Trial registration This meta-analysis was reported consistent with the PRISMA statement and was registered on PROSPERO, with registration number 2021CRD42021234893.
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BACKGROUND: The purpose is to compare the efficacy and safety of mini percutaneous nephrolithotomy (mini-PCNL) versus standard percutaneous nephrolithotomy (standard-PCNL) in patients with renal stones >2cm. MATERIALS AND METHODS: A systematic literature search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library databases to identify relevant studies before March 8, 2021. Stone-free rate (SFR), operation time, fever rate, hemoglobin drop, blood transfusion rate, and hospitalization time were used as outcomes to compare mini-PCNL and standard-PCNL. The meta-analysis was performed using the Review Manager version 5.4. RESULTS: Seven randomized controlled trials were included in our meta-analysis, involving 1407 mini-PCNL cases and 1436 standard-PCNL cases. Our results reveal that, for renal stones >2cm, mini-PCNL has a similar SFR (risk ratio (RR)=1.01, 95% confidence interval (CI): 0.98 to 1.04, p=0.57) and fever rate (RR=1.22, 95% CI: 0.97-1.51, p=0.08). Standard-PCNL was associated with a significantly shorter operating time (weighted mean difference (WMD)=8.23, 95% CI: 3.44 to 13.01, p <0.01) and a longer hospitalization time (WMD=-20.05, 95% CI: -29.28 to -10.81, p <0.01) than mini-PCNL. Subgroup analysis showed hemoglobin drop and blood transfusion for 30F standard-PCNL were more common than mini-PCNL (WMD=-0.95, 95% CI: -1.40 to -0.50, p <0.01; RR=0.20, 95% CI: 0.07 to 0.58, p <0.01). CONCLUSION: In the treatment of >2cm renal stones, mini-PCNL should be considered an effective and reliable alternative to standard-PCNL (30F). It achieves a comparable SFR to standard-PCNL, but with less blood loss, lower transfusion rate, and shorter hospitalization. However, the mini-PCNL does not show a significant advantage over the 24F standard-PCNL. On the contrary, this procedure takes a longer operation time. TRIAL REGISTRATION: This meta-analysis was reported consistent with the PRISMA statement and was registered on PROSPERO, with registration number 2021CRD42021234893.
Subject(s)
Kidney Calculi , Nephrolithotomy, Percutaneous , Hemoglobins , Humans , Kidney Calculi/surgery , Nephrolithotomy, Percutaneous/methods , Operative Time , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: Epilepsy is one of the most common diseases of the nervous system. Approximately one-third of epilepsy cases are drug-resistant, among which generalized-onset seizures are very common. The present study aimed to analyze abnormalities of the thalamocortical fiber pathways in each hemisphere of the brains of patients with drug-resistant generalized epilepsy. MATERIALS AND METHODS: The thalamocortical structural pathways were identified by diffusion tensor imaging (DTI) in 15 patients with drug-resistant generalized epilepsy and 16 gender/age-matched controls. The thalami of both groups were parcellated into subregions according to the local thalamocortical connectivity pattern. DTI measures of thalamocortical connections were compared between the two groups. RESULTS: Probabilistic tractography analyses showed that fractional anisotropy of thalamocortical pathways in patients with epilepsy decreased significantly, and the radial diffusivity of the left thalamus pathways with homolateral motor and parietal-occipital cortical regions in the drug-resistant epilepsy group increased significantly. In addition to the right thalamus pathway and prefrontal cortical region, fractional anisotropy of all other pathways was inversely correlated with disease duration. CONCLUSION: The results provide evidence indicating widespread bilateral abnormalities in the thalamocortical pathways in epilepsy patients and imply that the degree of abnormality in the pathway increases with the disease duration.
Subject(s)
Cerebral Cortex/pathology , Drug Resistant Epilepsy/pathology , Epilepsy, Generalized/pathology , Thalamus/pathology , Adult , Anisotropy , Diffusion Tensor Imaging , Female , Humans , Male , Neural Pathways/pathologyABSTRACT
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive with poor prognosis. Long non-coding RNAs (lncRNAs), a group of non-coding RNAs, play important roles in the progression of PDAC. This study aimed to investigate the potential involvement of lncRNA CCAT2 in PDAC tumorigenesis. METHODS: Expression of CCAT2 was detected by quantitative real-time PCR (qRT-PCR) in 80 human PDAC tissues and three PDAC cell lines. The effects of CCAT2 silencing in PANC-1 cells on cell proliferation and invasion were studied using MTT assay and transwell assay, respectively. The effect of CCAT2 silencing on tumorigenesis was assessed by PANC-1 xenograft in vivo. Using si-KRAS, the role of KRAS to regulate CCAT2 was evaluated by qRT-PCR and luciferase reporter assay. The involvement of MEK/ERK and PI3K/AKT signaling in CCAT2 regulation was investigated by pathway inhibitors PD98059 and LY294002, respectively. RESULTS: CCAT2 was significantly elevated in high-grade PDAC tissues and higher CCAT2 expression was correlated with lower survival rate in PDAC patients. CCAT2 was up-regulated in PDAC cell lines, as compared with normal pancreatic cells. Silencing of CCAT2 inhibited cell proliferation and invasion in PANC-1 cells in vitro, and attenuated tumorigenesis of PANC-1 xenograft in vivo. Furthermore, CCAT2 was regulated by KRAS through MEK/ERK signaling pathway. CONCLUSIONS: CCAT2 is an oncogenic lncRNA in PDAC likely regulated by the KRAS-MEK/ERK pathway. It could be a potential diagnostic biomarker and therapeutic target for PDAC.
Subject(s)
Carcinoma, Pancreatic Ductal/genetics , Mutation/genetics , Proto-Oncogene Proteins p21(ras)/genetics , RNA, Long Noncoding/genetics , Carcinoma, Pancreatic Ductal/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Real-Time Polymerase Chain ReactionABSTRACT
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive with poor prognosis. Long non-coding RNAs (lncRNAs), a group of non-coding RNAs, play important roles in the progression of PDAC. This study aimed to investigate the potential involvement of lncRNA CCAT2 in PDAC tumorigenesis. Methods Expression of CCAT2 was detected by quantitative real-time PCR (qRT-PCR) in 80 human PDAC tissues and three PDAC cell lines. The effects of CCAT2 silencing in PANC-1 cells on cell proliferation and invasion were studied using MTT assay and transwell assay, respectively. The effect of CCAT2 silencing on tumorigenesis was assessed by PANC-1 xenograft in vivo. Using si-KRAS, the role of KRAS to regulate CCAT2 was evaluated by qRT-PCR and luciferase reporter assay. The involvement of MEK/ERK and PI3K/AKT signaling in CCAT2 regulation was investigated by pathway inhibitors PD98059 and LY294002, respectively. Results CCAT2 was significantly elevated in high-grade PDAC tissues and higher CCAT2 expression was correlated with lower survival rate in PDAC patients. CCAT2 was up-regulated in PDAC cell lines, as compared with normal pancreatic cells. Silencing of CCAT2 inhibited cell proliferation and invasion in PANC-1 cells in vitro, and attenuated tumorigenesis of PANC-1 xenograft in vivo. Furthermore, CCAT2 was regulated by KRAS through MEK/ERK signaling pathway. Conclusions CCAT2 is an oncogenic lncRNA in PDAC likely regulated by the KRAS-MEK/ERK pathway. It could be a potential diagnostic biomarker and therapeutic target for PDAC.
Subject(s)
Female , Humans , Male , Middle Aged , Proto-Oncogene Proteins p21(ras)/genetics , Carcinoma, Pancreatic Ductal/genetics , RNA, Long Noncoding/genetics , Mutation/genetics , Prognosis , Carcinoma, Pancreatic Ductal/pathology , Real-Time Polymerase Chain Reaction , Neoplasm StagingABSTRACT
Among the seven tetraploid cotton species, little is known about transmission genetics and genome organization in Gossypium mustelinum, the species most distant from the source of most cultivated cotton, G. hirsutum In this research, an F2 population was developed from an interspecific cross between G. hirsutum and G. mustelinum (HM). A genetic linkage map was constructed mainly using simple sequence repeat (SSRs) and restriction fragment length polymorphism (RFLP) DNA markers. The arrangements of most genetic loci along the HM chromosomes were identical to those of other tetraploid cotton species. However, both major and minor structural rearrangements were also observed, for which we propose a parsimony-based model for structural divergence of tetraploid cottons from common ancestors. Sequences of mapped markers were used for alignment with the 26 scaffolds of the G. hirsutum draft genome, and showed high consistency. Quantitative trait locus (QTL) mapping of fiber elongation in advanced backcross populations derived from the same parents demonstrated the value of the HM map. The HM map will serve as a valuable resource for QTL mapping and introgression of G. mustelinum alleles into G. hirsutum, and help clarify evolutionary relationships between the tetraploid cotton genomes.
Subject(s)
Chromosome Mapping , Genome, Plant , Genomics , Gossypium/genetics , Quantitative Trait Loci , Chromosomes, Plant , Crosses, Genetic , Genetic Association Studies , Genetic Linkage , Genomics/methods , Gossypium/classification , Phylogeny , Physical Chromosome Mapping , Quantitative Trait, Heritable , TetraploidyABSTRACT
Four new isocoumarins (1-4), along with three known ones (5-7), were isolated from the 70% ethanol extract of the whole body of the traditional Chinese insect medicine, American cockroach (Periplaneta americana). The structures with absolute configurations of new compounds were elucidated by extensive spectroscopic methods in combination with X-ray diffraction experiment and CD analyses. Compounds 3-5 showed significant cytotoxic activities in HepG2 and MCF-7 cells with IC50 values in the ranges 6.41-23.91 µM and 6.67-39.07 µM, respectively.
Subject(s)
Isocoumarins/pharmacology , Periplaneta/chemistry , Animals , Cell Line, Tumor , Cell Survival/drug effects , Crystallography, X-Ray , Humans , Inhibitory Concentration 50 , Isocoumarins/chemistry , Isocoumarins/isolation & purification , Medicine, Chinese Traditional , Molecular StructureABSTRACT
OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.
Subject(s)
Antiviral Agents/therapeutic use , Aspartic Acid/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Methionine/genetics , Mutation/genetics , Tyrosine/genetics , Adult , Amino Acid Motifs/drug effects , Amino Acid Motifs/genetics , DNA, Viral/analysis , Female , Genotype , Hepatitis B virus/drug effects , Hepatitis B, Chronic/virology , Humans , Male , Polymerase Chain ReactionABSTRACT
OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.