RESUMEN
OBJECTIVES: The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. MATERIALS AND METHODS: In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. CONCLUSION: Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Cisplatino , Etopósido , Neoplasias Pulmonares , Puntaje de Propensión , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Carcinoma Pulmonar de Células Pequeñas/terapia , Carcinoma Pulmonar de Células Pequeñas/patología , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Anciano , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Quimioradioterapia/métodos , Estudios Retrospectivos , Estudios Prospectivos , Estadificación de Neoplasias , Adulto , Supervivencia sin Progresión , Esquema de MedicaciónRESUMEN
BACKGROUND: For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC. METHODS: This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325-0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236-0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280-0.858], P = 0.011; HR 0.454 [95%CI 0.246-0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis. CONCLUSIONS: Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/terapia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Estudios Retrospectivos , Estudios Prospectivos , Puntaje de Propensión , Quimioradioterapia/métodos , Inmunoterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Objectives: This study aimed to characterize the genomic epidemiology of human adenoviruses (HAdVs) in Hubei, China, using metagenomic next-generation sequencing (mNGS). Methods: In total, 25 HAdV-positive samples collected from 21 pediatric patients were sequenced and subjected to mNGS using the NextSeq 550 and GenoLab M sequencing platforms. The metagenomic data were assembled de novo for molecular typing, phylogenetic and recombination analyzes. Results: We assembled 50 HAdV genomes, 88% (22/25) genomes from GenoLab M, and 84% (21/25) genomes from NextSeq 550 have perfect alignments to reference genomes with greater than 90%. The most fully assembled 25 genomes were categorized into 7 HAdV genotypes, the most abundant of which were HAdV-B3 (9/25) and HAdV-C2 (6/25). Phylogenetic analyzes revealed that the newly isolated HAdV-B3 strains diverged into separate clusters according to their genotypes. Vigilance is needed that HAdV-B3 isolates have begun to form new distinct clusters. High nucleotide identity was observed in the whole genome level within the same HAdV genotypes, while marked differences of three capsid genes across HAdV genotypes were noted. The high nucleotide diversity regions were concordant with the reported hypervariable regions. Further, three recombinant strains were identified: S64 and S71 originated from the parental strains HAdV-B14 and HAdV-B11, and S28 originated from HAdV-C1, HAdV-C5, and HAdV-CBJ113. GenoLab M and NextSeq 550 showed comparable performance with respect to data yield, duplication rate, human ratio, and assembly completeness. Conclusion: The sequencing quality and assembly accuracy showed that mNGS assembled genomes can be used for subsequently HAdV genotyping and genomic characterization. The high nucleotide diversity of capsid genes and high frequency of recombination events has highlighted the necessity for HAdV epidemiological surveillance in China.
RESUMEN
Insulin resistance (IR) is one of the most common features of polycystic ovary syndrome (PCOS), which is related to obesity. Whether increased anti-Müllerian hormone (AMH) levels in PCOS are involved in the pathogenesis of insulin resistance remains unclear. We investigated serum levels of leptin and AMH along with basic clinical and metabolic parameters in 114 PCOS patients and 181 non-PCOS women. PCOS patients presented higher fasting blood glucose, insulin concentrations and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in addition to body mass index (BMI), lipids profiles and hormone levels. HOMA-IR showed a positive correlation with BMI, AMH, leptin, and low-density lipoprotein-cholesterol (LDL-c) levels. Interestingly, AMH is strongly positively correlated with HOMA-IR and insulin concentrations for 1st and 2nd hours of glucose treatment after fasting. Among PCOS women with BMI≥25 kg/m2, high AMH level group showed an increased HOMA-IR when compared to normal AMH level. However, among PCOS women with normal BMI, women with high AMH presented an elevated fasting insulin levels but not HOMA-IR when compared to normal AMH group. In vitro treatment of isolated islet cells with high concentration of leptin (200 ng/ml) or high leptin plus high concentration of AMH (1 ng/ml) significantly enhanced insulin secretion. Importantly, co-treatment of AMH plus leptin upregulates the expression of pro-apoptotic proteins, such as Bax, caspase-3, and caspase-8 after incubating with a high level of glucose. These results suggest that AMH may involve in the pathological process of pancreatic ß-cells in obese PCOS women.
Asunto(s)
Hormona Antimülleriana/fisiología , Resistencia a la Insulina , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Animales , Hormona Antimülleriana/sangre , Hormona Antimülleriana/farmacología , Femenino , Humanos , Hiperinsulinismo/etiología , Secreción de Insulina/efectos de los fármacos , Leptina/farmacología , Ratas , Adulto JovenRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with poor overall survival. BPDCN is derived from plasmacytoid dendritic cells (pDCs) and its pathogenesis is unclear. The tumor cells show aberrant expression of CD4, CD56, interleukin-3 receptor alpha chain (CD123), blood dendritic cell antigen 2 (BDCA 2/CD303), blood dendritic cell antigen 4 (BDCA4) and transcription factor (E protein) E2-2 (TCF4). The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma. Relapse with drug resistance generally occurs quickly. Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy. In this review, we summarize the differentiation of BPDCN from its cell origin, its connection with normal pDCs, clinical characteristics, genetic mutations and advances in treatment of BPDCN. This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.
Asunto(s)
Células Dendríticas/patología , Neoplasias Hematológicas/genética , Neoplasias Cutáneas/genética , Enfermedad Aguda/epidemiología , Antígenos de Superficie/genética , Antígenos CD4/genética , Antígeno CD56/genética , Diferenciación Celular/genética , Células Dendríticas/metabolismo , Progresión de la Enfermedad , Neoplasias Hematológicas/patología , Humanos , Subunidad alfa del Receptor de Interleucina-3/genética , Lectinas Tipo C/genética , Glicoproteínas de Membrana/genética , Receptores Inmunológicos/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Factor de Transcripción 4/genéticaRESUMEN
Some new information on a poorly studied lepidopterous family, Immidae Heppner, 1977, is reported from Guangdong Province, in the southern part of mainland China. A new species, viz. Moca austrasinensis Huang Wang sp. nov. is described from Mt. Wutong, Shenzhen. Imma lathidora Meyrick, 1914 is recorded in Mt. Nankun, Huizhou, representing the first record from mainland China. Adults and male genitalia of the species mentioned are illustrated.
Asunto(s)
Lepidópteros , Mariposas Nocturnas , Distribución Animal , Estructuras Animales , Animales , China , Masculino , Tamaño de los ÓrganosRESUMEN
OBJECTIVE: To explore the effect of concentrated growth factors (CGF) on postoperative pain and swelling in patients with complex dental implants. METHODS: A total of 28 patients with single maxillary anterior teeth loss and labial orbital bone defect were recruited randomly and divided into two groups. Each group included 14 patients. The experimental group was applied with CGF membrane to guide bone regeneration, whereas the control group was treated with collagen membrane to guide bone regeneration. The postoperative pain degree and swelling degree were compared, and data were analyzed with SPSS 23.0 software. Postoperative pain was measured by visual analogue scale (VAS), and the degree of swelling was divided into four grades according to swelling range. RESULTS: VAS scores of patients in experimental and control groups reached 35.1±22.5 and 47.0±20.3, respectively. The duration of postoperative pain in experimental and control groups totaled (2.1±1.5) and (2.8±1.0) days, respectively. No statistically significant difference was observed between the two groups (P>0.05). Percentages of non-swelling, mild swelling, moderate swelling, and severe swelling in experimental group reached 21.4%, 57.1%, 21.4%, and 0, respectively, and those in control group were 7.1%, 35.7%, 35.7%, and 21.4%. Swelling duration reached (2.4±1.4) and (4.2±2.2) days in the experimental and control groups, respectively. A statistically significant difference was observed in the swelling degree of experimental and control groups (P<0.05). CONCLUSIONS: The use of CGF can significantly reduce the degree of postoperative swelling and shorten swelling time but cause no significant effect on pain.
Asunto(s)
Regeneración Ósea , Implantes Dentales , Estética , Humanos , Péptidos y Proteínas de Señalización Intercelular , Maxilar , Dolor PostoperatorioRESUMEN
Myc and p53 proteins are closely associated with many physiological cellular functions, including immune response and lymphocyte survival, and are expressed in the lymphoid organs, which are sites for the development and activation of B-cell malignancies. Genetic alterations and other mechanisms resulting in constitutive activation, rearrangement, or mutation of MYC and TP53 contribute to the development of lymphomas, progression and therapy resistance by gene dysregulation, activation of downstream anti-apoptotic pathways, and unfavorable microenvironment interactions. The cross-talk between the Myc and p53 proteins contributes to the inferior prognosis in many types of B-cell lymphomas. In this review, we present the physiological roles of Myc and p53 proteins, and recent advances in understanding the pathological roles of Myc, p53, and their cross-talk in lymphoid neoplasms. In addition, we highlight clinical trials of novel agents that directly or indirectly inhibit Myc and/or p53 protein functions and their signaling pathways. Although, to date, these trials have failed to overcome drug resistance, the new results have highlighted the clinical efficiency of targeting diverse mechanisms of action with the goal of optimizing novel therapeutic opportunities to eradicate lymphoma cells.
RESUMEN
BACKGROUND: Studies have shown that bone marrow mesenchymal stem cells (BMSCs) can treat central nervous system diseases. BMSCs have the function of self-renewal and differentiation into a variety of neural cell types. BMSCs with self-renewal and multi-directional differentiation abilities can successfully differentiate into dopaminergic neurons after transplantation into an animal model. OBJECTIVE: To observe the effect of transplanted BMSCs on behavior and dopaminergic neurons in rats with manganese poisoning. METHODS: Rat models of manganese poisoning were constructed by intraperitoneal injection of MnCl2?4H2O into Sprague-Dawley rats. The model rats were then randomly divided into two groups, BMSCs and phosphate buffered solution (PBS) control group, and 5 μL of passage 3 human BMSCs suspension or equivalent PBS was transplanted into the right striatum of the manganese poisoning rats. One month after transplantation, the rats were subjected to behavioral assessment. The differentiation of BMSCs was observed by immunofluorescence. The contents of dopamine, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor in the right striatum of rats were detected by ELISA. RESULTS AND CONCLUSION: The behavioral score of the BMSCs treated group was significantly lower than that of the PBS control group after transplantation (P < 0.05). Double-labeled positive cells for human-specific nuclear antigen/tyrosine hydroxylase (hNUC/TH) and human-specific nuclear antigen/glial cell-derived acidic protein (hNUC/GFAP) were observed in the BMSCs treated group after transplantation. Meanwhile, hNUC/TH and hNUC/GFAP double-labeled positive cells were undetected in the PBS control group after transplantation. The expression levels of dopamine, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor in the BMSCs treated group were higher than those in the PBS control group. This suggests that BMSCs can improve the behavior of manganese poisoning rats and can differentiate into dopaminergic neurons and astrocytes.
RESUMEN
Obesity appears to be associated with female reproductive dysfunction and infertility. Women with obesity undergoing in vitro fertilization (IVF) had poor oocyte quality, decreased embryo development, and poor pregnancy outcome. However, the mechanism linking obesity to poor reproductive outcomes is still unclear. Obesity is frequently accompanied with elevated leptin levels. Here we aimed to evaluate the effect of high leptin level in follicular fluid (FF) on the proliferation and apoptosis in granule cells and correlate these findings with poor reproductive outcomes in infertile women with overweight or obesity who underwent IVF treatment. We investigated clinical and ongoing pregnancy rates in 189 infertile women who underwent IVF. Leptin levels were quantified in peripheral blood and FF as well. In vitro cell model was used to explore the potential effect of high leptin on the proliferation and apoptosis in granulosa cells. Results showed reduced clinical and ongoing pregnancy rates in overweight/obesity women who underwent IVF compared to control with normal BMI. On the other hand, leptin levels presented significant increase in peripheral blood and FF in overweight/obese women. Leptin level in FF was negatively correlated to good quality embryo rate. Importantly, in vitro study showed that leptin inhibited cells proliferation and promoted apoptosis by upregulation of caspase-3 and downregulation of Bcl-2 in granulosa cells in a dose dependent manner. These observations suggest that leptin may acts as a local mediator to attenuate embryo development and reduce fertility in obese patients.
Asunto(s)
Apoptosis , Proliferación Celular , Desarrollo Embrionario , Fertilización In Vitro , Células de la Granulosa/metabolismo , Infertilidad Femenina/sangre , Leptina/sangre , Obesidad/sangre , Adulto , Femenino , Humanos , Infertilidad Femenina/terapia , EmbarazoRESUMEN
BACKGROUND: Ovarian hyperstimulation syndrome (OHSS), a complication of ovarian stimulation, has various adverse effects on both pregnant women and their offspring. However, whether OHSS will affect intellectual ability in offspring is still unknown. METHODS: We recruited 86 Chinese children born to OHSS women and 172 children conceived with non-OHSS In Vitro Fertilization (IVF) in this cohort study. Their intellectual ability was assessed according to the Revised Chinese Version of the Wechsler Intelligence Scale for Children (C-WISC). Verbal Intelligence Quotient (VIQ), Performance Intelligence Quotient (PIQ), and Full Intelligence Quotient (FIQ) were calculated. The investigation was registered in Chinese Clinical Trial Registry (ChiCTR-SOC-16009555). FINDINGS: OHSS offspring scored less on C-WISC (mean (standard deviation [SD]): (VIQ=92.7 (14.7), PIQ=108.9 (13.1), FIQ=100.6 (13.4)) compared with non-OHSS IVF offspring (VIQ=100.1 (13.2), PIQ=113.7 (10.8), FIQ=107.4 (11.5)). The prevalence of low IQ (<80) children was 4.7 times higher in OHSS offspring compared with non-OHSS offspring. Maternal estradiol level on hCG administration day was negatively associated with FIQ in offspring. INTERPRETATION: OHSS offspring displayed reduced intellectual ability. Prenatal estradiol exposure might be involved in underlying mechanism.
Asunto(s)
Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/etiología , Exposición Materna/efectos adversos , Síndrome de Hiperestimulación Ovárica/complicaciones , Efectos Tardíos de la Exposición Prenatal , Preescolar , Estudios de Cohortes , Estradiol/efectos adversos , Femenino , Fertilización In Vitro/efectos adversos , Humanos , Discapacidad Intelectual/epidemiología , Pruebas de Inteligencia , Embarazo , Complicaciones del Embarazo , Resultado del EmbarazoRESUMEN
BACKGROUND: Excessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells. METHODS: Of 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010. Of 1198 women who delivered, 1116 eligible mothers (147 with hyperandrogenism and 969 normal) were recruited. 1216 children (156 children born to mothers with hyperandrogenism and 1060 born to normal mother) were followed up their glycometabolism in mean age of 5years. Imprinting genes of oocyte from mothers and lymphocytes from children were examined. A pregestational hyperandrogenism rat model was also established. FINDINGS: Children born to women with hyperandrogenism showed increased serum fasting glucose and insulin levels, and were more prone to prediabetes (adjusted RR: 3.98 (95%CI 1.16-13.58)). Oocytes from women with hyperandrogenism showed increased insulin-like growth factor 2 (IGF2) expression. Lymphocytes from their children also showed increased IGF2 expression and decreased IGF2 methylation. Treatment of human oocytes with dihydrotestosterone upregulated IGF2 and downregulated DNMT3a levels. In rat, pregestational hyperandrogenism induced diabetic phenotypes and impaired insulin secretion in offspring. In consistent with the findings in human, hyperandrogenism also increased Igf2 expression and decreased DNMT3a in rat oocytes. Importantly, the same altered methylation signatures of Igf2 were identified in the offspring pancreatic islets. INTERPRETATION: Pregestational hyperandrogenism may predispose offspring to glucose metabolism disorder via epigenetic oocyte inheritance. Clinical trial registry no.: ChiCTR-OCC-14004537; www.chictr.org.
Asunto(s)
Epigénesis Genética , Hiperandrogenismo/genética , Madres/estadística & datos numéricos , Estado Prediabético/genética , Adulto , Animales , Glucemia/metabolismo , Niño , Preescolar , China/epidemiología , Modelos Animales de Enfermedad , Femenino , Humanos , Hiperandrogenismo/complicaciones , Insulina/sangre , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Linfocitos/citología , Linfocitos/metabolismo , Masculino , Oocitos/citología , Oocitos/metabolismo , Estado Prediabético/epidemiología , Estado Prediabético/etiología , Embarazo , Prevalencia , Estudios Prospectivos , Ratas , Factores de RiesgoRESUMEN
Mechanisms underlying female gonadal dysgenesis remain unclarified and relatively unstudied. Whether X-chromosome inactivation (XCI)-escaping genes and microRNAs (miRNAs) contribute to this condition is currently unknown. We compared 45,X Turner Syndrome women with 46,XX normal women, and investigated differentially expressed miRNAs in Turner Syndrome through plasma miRNA sequencing. We found that miR-320a was consistently upregulated not only in 45,X plasma and peripheral blood mononuclear cells (PBMCs), but also in 45,X fetal gonadal tissues. The levels of miR-320a in PBMCs from 45,X, 46,XX, 46,XY, and 47,XXY human subjects were inversely related to the expression levels of XCI-escaping gene KDM5C in PBMCs. In vitro models indicated that KDM5C suppressed miR-320a transcription by directly binding to the promoter of miR-320a to prevent histone methylation. In addition, we demonstrated that KITLG, an essential gene for ovarian development and primordial germ cell survival, was a direct target of miR-320a and that it was downregulated in 45,X fetal gonadal tissues. In conclusion, we demonstrated that downregulation of miR-320a by the XCI-escaping gene KDM5C contributed to ovarian development by targeting KITLG.
Asunto(s)
Histona Demetilasas/genética , MicroARNs/genética , Ovario/crecimiento & desarrollo , Síndrome de Turner/genética , Inactivación del Cromosoma X/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Regulación hacia Abajo , Femenino , Regulación de la Expresión Génica , Ontología de Genes , Células HEK293 , Humanos , Leucocitos Mononucleares/metabolismo , MicroARNs/sangre , Regiones Promotoras Genéticas , Análisis de Secuencia de ARN , Regulación hacia Arriba , Adulto JovenRESUMEN
Based on a geo-weighted regression model, this study analyzes the relationship between the landscape patterns of sources and sinks in urban areas and atmospheric haze pollution. First, the classification result of the study area is divided into a number of square grids with side lengths of 2-9 km. Heterogeneity indices at different scales are calculated and compared to select an optimal scale for the following analysis. Then, the category level landscape indices, such as PLAND, PD, COHEDION, LPI, and FRAC_MN, are calculated in each grid. The aerosol optical thickness (AOD) of Wuhan is used to represent the degree of atmospheric haze pollution. Furthermore, the mean value of the pixels in each grid is regarded as the value of the grid's center. Next, the landscape sources and sinks of atmospheric haze pollution are selected based on the analysis of the correlation between landscape indices and AOD. To make the following analysis more efficient, the indices selected previously are determined using their correlation coefficients. Finally, the geo-weighted regression analysis model is used to analyze the relationship between the landscape indices of the category level and AOD. In addition, the influences of industrial, commercial, and residential areas on haze pollution are analyzed based on the result of the classification of urban functional areas. The results show that the heterogeneity of the whole landscape is most obvious at a 6 km scale, so 6 km is the optimal scale for the analysis. The landscape sources of atmospheric haze pollution are the buildings, and the landscape sinks are shrubs and woodland. Reducing the proportion of landscape source area and increasing the degree of fragmentation can cut down aerosol optical thickness. Distributing the landscape sources and sinks evenly and interspersedly could effectively reduce aerosol optical thickness, which represents atmospheric haze pollution. For Wuhan City, the main sources of haze pollution are commercial and residential areas in the city center, representing public sources. Since it is not easy to adjust existing facilities and infrastructure, adjusting built-up areas slightly and planning reasonably for those areas that are not yet built up can reduce atmospheric haze pollution.
RESUMEN
Our previous studies have shown that maternal high estradiol (E2) environment increased the risk of thyroid dysfunction in offspring. However, the mechanism involved remains unexplored. To evaluate the thyroid function of offspring after high E2 exposure and to explore the underlying mechanism, we established a high E2 mouse model of early pregnancy, and detected thyroid hormones of their offspring. In thyroids of offspring, the expressions of Tg, Nis, Tpo, Pax8, and Titf1 and CpG island methylation status of Pax8 and genes involved in methylation were analyzed. We found that thyroxine (T4) and FT4 levels of offspring were obviously increased in the high-E2 group, especially in females. In both 3- and 8-week-old offspring of the high-E2 group, Pax8 was significantly up-regulated in thyroid glands, accompanied by the abnormal CpG island methylation status in the promoter region. Furthermore, Dnmt3a and Mbd1 were obviously down-regulated in thyroids of the high E2 group. Besides, the disturbance of thyroid function in females was more severe than that in males, implying that the effects were related to gender. In summary, our study indicated that maternal high E2 exposure disturbed the thyroid function of offspring through the dysregulation and abnormal DNA methylation of Pax8.
Asunto(s)
Estradiol/efectos adversos , Exposición Materna/efectos adversos , Factor de Transcripción PAX8/genética , Efectos Tardíos de la Exposición Prenatal/genética , Tiroxina/metabolismo , Regulación hacia Arriba , Animales , Islas de CpG/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Marcadores Genéticos/efectos de los fármacos , Masculino , Ratones , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/metabolismoRESUMEN
Our previous study indicated that maternal high-estrogen environment in the first trimester is correlated with increased risks of low birth weight (LBW) and adult diseases. The present study aimed to establish an animal model to confirm such an effect in mice, and to further explore the mechanism involved. A mouse model with high estradiol (E2) exposure during early pregnancy was established, and the birth weight, growth after birth, and expression levels of insulin-like growth factor-binding protein 1 (IGFBP1) of pups were examined. Meanwhile, IGFBP1 expression after treatment of E2 was examined in a HepG2 hepatoma cell line. We found that after exposure to a high-E2 environment the weight of the pups decreased significantly, not only before but also after birth. Meanwhile, both mRNA and protein expressions of IGFBP1 were elevated in placenta and liver tissues. Furthermore, the level of IGFBP1 in the HepG2 cell line was elevated by the treatment of E2, whereas this effect was blocked by estrogen receptor antagonist ICI 182780. In summary, maternal high estrogen up-regulates expression of IGFBP1 in placenta and fetal livers, which contributes to LBW and decreases body weight in offspring.
Asunto(s)
Peso al Nacer/efectos de los fármacos , Estradiol/farmacología , Estrógenos/farmacología , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Animales , Peso al Nacer/fisiología , Estradiol/análogos & derivados , Antagonistas de Estrógenos/farmacología , Femenino , Fulvestrant , Células Hep G2 , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Hígado/metabolismo , Ratones , Placenta/metabolismo , EmbarazoRESUMEN
AIM: To establish a new animal model for the research of human rotavirus (HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines. METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and Bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PBS (control), respectively, and fecal samples of pigs from 0 to 7 d post infection (DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. The HRV was tested by real-time PCR (RT-PCR). The sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography. RESULTS: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an age-dependent manner and shed HRV antigen of the same inoculum, as demonstrated by RT-PCR. Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal mini-pigs. Guizhou mini-pigs were more sensitive to HRV than Bamma with respect to RV antigen shedding and clinical diarrhea. CONCLUSION: These results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.
Asunto(s)
Diarrea/etiología , Infecciones por Rotavirus/complicaciones , Animales , Antígenos Virales/análisis , Modelos Animales de Enfermedad , Humanos , Intestino Delgado/patología , Intestino Delgado/virología , Infecciones por Rotavirus/patología , Porcinos , Porcinos EnanosRESUMEN
Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 µg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Metilación de ADN/efectos de los fármacos , Metabolismo de los Lípidos , Hígado/efectos de los fármacos , Hígado/metabolismo , Fenoles/toxicidad , Tejido Adiposo/metabolismo , Animales , Glucemia/análisis , Línea Celular , Colesterol/metabolismo , Islas de CpG , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Femenino , Hepatocitos/citología , Masculino , Ratones , Obesidad/metabolismo , ARN Interferente Pequeño/metabolismo , Triglicéridos/metabolismoRESUMEN
The draft genomes of Thermus tengchongensis YIM 77401 and T. caliditerrae YIM 77777 are 2,562,314 and 2,218,114 bp and encode 2,726 and 2,305 predicted genes, respectively. Gene content and growth experiments demonstrate broad metabolic capacity, including starch hydrolysis, thiosulfate oxidation, arsenite oxidation, incomplete denitrification, and polysulfide reduction.