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1.
Artigo em Inglês | MEDLINE | ID: mdl-34791345

RESUMO

CONTEXT: Metabolic disorders and cardiovascular disease threaten human health. Many studies have assessed the phenomenon of metabolic disorders and cardiovascular disease in patients with diabetes. However, in euglycemic individuals, the relationships between glucose regulation, metabolism and cardiovascular disease remain unclear. OBJECTIVE: To explore the associations between postprandial glucose dips, metabolic disorders and cardiovascular disease risk. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from the Thyroid disorders, Iodine status and Diabetes Epidemiological survey (TIDE study), which included 38878 euglycemic individuals from all 31 provinces of mainland China. MAIN OUTCOMES AND MEASURES: The prevalence of metabolic disorders and their related components and cardiovascular disease risk were calculated according to postprandial glucose dips. Logistic regression models of quartiles of postprandial glucose dips were used to further explore whether the prevalence of these disorders was associated with postprandial glucose dips. RESULTS: Odds ratios for the fourth versus the first quartile of glucose dips were 0.59 (95% confidence interval (CI) 0.55, 0.63) (P<0.001) for metabolic disorders, 0.48 (95% CI 0.44, 0.53) (P<0.001) for metabolic syndrome and 0.54 (95% CI 0.50, 0.59) (P<0.001) for hyperuricemia. The odds ratio of 10-year cardiovascular disease risk >20% for the fourth versus the first glucose dip quartile was 0.67 (95% CI 0.52, 0.85) (P<0.001). Models adjusted for BMI yielded similar results. CONCLUSIONS: Postprandial glucose dips are associated with metabolic disorders, metabolic syndrome and its related component diseases, and the cardiovascular disease risk. Glucose dips may be a marker of underlying metabolic abnormalities.

2.
Thyroid ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806437

RESUMO

BACKGROUND: Despite the implementation of the universal salt iodization (USI) program for correction of iodine deficiency in China for about 20 years, the actual iodine nutrition status of Chinese residents and the prevalence of iodine deficiency and iodine excess are issues that need to be addressed. This nationally representative cross-sectional study was conducted across all 31 provinces of mainland China to gather extensive data on iodine nutrition status and the influential factors. METHODS: This study included 78,470 participants, aged 18 years or older, who were interviewed and asked to answer a questionnaire. Urine iodine concentration (UIC) was measured by the inductively coupled plasma mass spectrometry method, and goiter was examined by thyroid ultrasonography. In addition, sixty 9 -11 years old school-children in each province were randomly selected to evaluate the UIC and thyroid ultrasonography. The iodine nutrition status was determined according to the WHO guidelines. RESULTS: The iodized salt coverage was 95.37%. The median urine iodine (MUI) was 177.89 µg/L (interquartile range [IQR], 117.89-263.90 µg/L) and goiter prevalence was 1.17% (95% CI, 0.95-1.43%) in the adult population. The MUI was 199.75 µg/L (IQR, 128.41-303.37 µg/L) in school-age children, and goiter prevalence was 3.50% (95% CI, 2.93-4.13%). The percentage of individuals with UIC < 50 µg/L was 3.43%, less than 20%. Analysis indicated that sex, age, geographic factors, BMI, smoking habits influence the iodine nutrition level. CONCLUSION: The mandatory USI program has successfully eliminated iodine deficiency disorders, and the findings indicate that the iodine nutrition level in the general population is within the safe range.

3.
ACS Appl Mater Interfaces ; 13(42): 49737-49753, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34648269

RESUMO

Peptide vaccines exhibit great potential in cancer therapy via eliciting antigen-specific host immune response and long-term immune memory to defend cancer cells. However, the low induced immune response of many developing vaccines implies the imperatives for understanding the favorable structural features of efficient cancer vaccines. Herein, we report on the two groups of self-adjuvanting peptide vaccines with distinct morphology and investigate the relationship between the morphology of peptide vaccines and the induced immune response. Two nanofibril peptide vaccines were created via co-assembly of a pentapeptide with a central 4-aminoproline residue, with its derivative functionalized with antigen epitopes derived from human papillomavirus E7 proteins, whereas utilization of a pentapeptide with a natural proline residue led to the formation of two nanoparticle peptide vaccines. The immunological results of dendritic cell (DCs) maturation and antigen presentation induced by the peptide assemblies implied the self-adjuvanting property of the resulting peptide vaccines. In particular, cellular uptake studies revealed the enhanced internalization and elongated retention of the nanofibril peptide vaccines in DCs, leading to their advanced performance in DC maturation, accumulation at lymph nodes, infiltration of cytotoxic T lymphocytes into tumor tissues, and eventually lysis of in vivo tumor cells, compared to the nanoparticle counterparts. The antitumor immune response caused by the nanofibril peptide vaccines was further augmented when simultaneously administrated with anti-PD-1 checkpoint blockades, suggesting the opportunity of the combinatorial immunotherapy by utilizing the nanofibril peptide vaccines. Our findings strongly demonstrate a robust relationship between the immune response of peptide vaccines and their morphology, thereby elucidating the critical role of morphological control in the design of efficient peptide vaccines and providing the guidance for the design of efficient peptide vaccines in the future.

4.
Lancet Reg Health West Pac ; 15: 100227, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34528008

RESUMO

Background: Previous studies have shown increases in the prevalence of obesity and hypertension, but nationally representative data on recent changes in prevalence adjusted for population structure changes are lacking. Two nationwide surveys were conducted in 2007 and 2017 to assess the prevalence changes of these conditions in China. Methods: A multistage stratified random sampling method was used to obtain a nationally representative sample of adults aged 20 years and older in mainland China in 2007 and 2017. Temporal changes in the prevalence of hypertension and obesity were investigated. Changes in blood pressure, body mass index (BMI) and waist circumference were also assessed. Logistic regression models were constructed to assess the changes in prevalence over time. Findings: The weighted prevalence of hypertension (25.7% vs. 31.5%, P=0.04), high-normal blood pressure (11.7% vs. 14.3%, P<0.0001), general obesity (31.9% vs. 37.2%, P=0.008), and central obesity (25.9% vs. 35.4%, P=0.0002) was significantly higher in 2017 (n=72824) than in 2007 (n=45956) in the overall population. No significant changes in the prevalence of overweight and grade 1 or grade 2 hypertension were observed in the overall population, but a significantly higher prevalence was observed among participants aged 20-29 years for grade 1 hypertension (P=0.002) and among participants aged 70 years and older for grade 2 hypertension (P=0.046) in 2017. Interpretation: Compared with 2007, the prevalence of hypertension and obesity was significantly higher among adults in mainland China after adjusting for demographic confounding factors in 2017. More targeted interventions and prevention strategies are needed to offset the increasing risk of cardiovascular disease due to increases in the prevalence of hypertension and obesity. Funding: The Clinical Research Fund of the Chinese Medical Association (Grant No. 15010010589), the National Natural Science Foundation of China (Grant No. 82000753), and the Chinese Medical Association Foundation and Chinese Diabetes Society (Grant No. 07020470055).

5.
J Inflamm Res ; 14: 2641-2646, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188514

RESUMO

Objective: This study aims to summarize the treatment of granulomatous lobular mastitis with a low recurrence rate and high satisfaction rate. Methods: In this study, the epidemiology and treatment effect was analyzed based on the general data and treatment effects. Patients treated for granulomatous lobular mastitis at the Dongzhimen Hospital, Beijing University of Chinese Medicine, and Beijing Contemporary Hospital from October 24, 2016, to May 8, 2019, were selected as subjects for the study. Results: The results revealed that the common features of granulomatous lobular mastitis were nipple retraction, history of induced abortion, nipple discharge, history of thyroid disease, history of lactation mastitis, and mental illness. The cure rate of the disease was 100%, the recurrence rate was 0.38%, and the patient satisfaction rate was 97.71%. Conclusion: The combination of mammary duct exploration and focal resection has a positive effect on the treatment of this disease and is worthy of clinical popularization.

6.
Front Endocrinol (Lausanne) ; 12: 651534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122333

RESUMO

Background: Universal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination. Methods: Data were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015-2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured. Results: After two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves' disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% vs. 0.64%, P<0.001; GD: 0.65% vs. 0.37%, P<0.001).Prevalence was significantly decreased after 60 years-of-age compared with 30-39 years-of-age (OH:0.61% vs. 0.81%, P<0.001; GD: 0.38% vs. 0.57%, P<0.001).Excessive iodine(EI) and deficient iodine(DI) were both related to increased prevalence of OH (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.68-2.59; OR1.35, 95%CI 1.07-1.72, respectively); however, only deficient iodine was associated with increased prevalence of GD (OR1.67, 95%CI 1.30-2.15). Increased thyroid peroxidase antibody and thyroglobulin antibody levels were significantly associated with prevalence of OH and GD, but not severe SCH and mild SCH. Although hyperthyroidism was more prevalent in women, the association disappeared after adjusting for other factors such as antibody levels. Conclusion: OH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.

7.
Biomaterials ; 275: 120921, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34139508

RESUMO

Nanovaccine can elicit antigen-specific immune responses against tumor cells expressing homologous antigens and has attracted enormous attention in cancer immunotherapy. However, tumor heterogeneity remarkably hinders the development of nanovaccines. Here we demonstrate that PTT-induced in situ vaccination cancer therapy can elicit potent antitumor immunity against disseminated and metastatic tumors. Gold nanorods (AuNRs) covalently coupled with amphiphilic polyTLR7/8a and MMP-2-sensitive R9-PEG conjugate (AuNRs-IMQD-R9-PEG) were developed as a new biocompatible PTT agent with favorable photothermal efficiency and stability. Importantly, AuNRs-IMQD-R9-PEG can effectively absorb tumor-derived protein antigens, forming nanovaccines directly in vivo and enhance the activation of host dendritic cells (DCs), thereby amplifying adaptive antitumor T-cell responses, triggering effector memory immune responses, and activating innate antitumor immunity. Remarkably, peri-tumoral administration of low-dose multifunctional AuNRs followed by non-invasive near-infrared (NIR) laser irradiation enables efficient tandem PTT-vaccination treatment modality that can inhibit local as well as untreated distant and metastatic tumors in mice inoculated with poorly immunogenic, highly metastatic 4T1 tumors. Our findings indicate that AuNRs-IMQD-R9-PEG-mediated in situ cancer vaccination provides a powerful immunotherapy characterized by markedly increased infiltration of effector CD8+ T, natural killer T (NKT) cells in tumors and long-term animal survival, thus, offering a promising therapeutic strategy for advanced, disseminated cancers.


Assuntos
Nanotubos , Neoplasias , Animais , Linhagem Celular Tumoral , Ouro , Camundongos , Neoplasias/terapia , Fototerapia , Terapia Fototérmica , Vacinação
8.
Front Endocrinol (Lausanne) ; 12: 659738, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149615

RESUMO

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease that features activation of thyroid antigen-specific helper T cells. HT patients have increased Th1 and Th17 T cell subsets. Glycolysis supports chronic activation of Th1 and Th17 T cells, but how this contributes to HT remains unknown. Methods: The metabolism of CD4+ T cells from 30 HT patients and 30 healthy controls was evaluated by determining the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). Mice in a subacute thyroiditis (SAT) model were treated with 2DG, metformin, or combination. Metrics of mTOR/HIF-1α/HK2/glycolysis were measured by western blot and Seahorse assay methods. The severity of SAT was measured by flow cytometry and HE staining. Results: CD4+ T cells from HT patients had enhanced ECAR and OCR. Levels of Glut1, HK2, PKM2, and LDHA in cultured HT CD4+ T cells were elevated. The expression of HK2 and PKM2 in cultured SAT CD4+ T cells was elevated compared with the control group. Activation of the mTOR and HIF-1α pathways was significant in SAT mice, and expression of HIF-1α in the 2DG treated group was reduced. Treatment with 2DG and/or metformin significantly decreased the ratio of Th17 and Th1 T cells. Conclusions: Thyroiditis results in elevation of the mTOR/HIF-1α/HK2/glycolysis pathway in CD4+ T cells. The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.

9.
Sci Rep ; 11(1): 12178, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108502

RESUMO

Purine rich element binding protein A (Purα), encoded by the Purα gene, is an important transcriptional regulator that binds to DNA and RNA and is involved in processes such as DNA replication and RNA translation. Purα also plays an important role in the nervous system. To identify the function of Pura, we performed RNA sequence (RNA-seq) analysis of Purɑ-KO mouse hippocampal neuron cell line (HT22) to analyze the effect of Purα deletion on neuronal expression profiles. And combined with ChIP-seq analysis to explore the mechanism of Purα on gene regulation. In the end, totaly 656 differentially expressed genes between HT22 and Purα-KO HT22 cells have been found, which include 7 Alzheimer's disease (AD)-related genes and 5 Aß clearance related genes. 47 genes were regulated by Purα directly, the evidence based on CHIP-seq, which include Insr, Mapt, Vldlr, Jag1, etc. Our study provides the important informations of Purα in neuro-development. The possible regulative effects of Purα on AD-related genes consist inthe direct and indirect pathways of Purα in the pathogenesis of AD.


Assuntos
Doença de Alzheimer/patologia , Sequenciamento de Cromatina por Imunoprecipitação/métodos , Proteínas de Ligação a DNA/metabolismo , Hipocampo/patologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia , RNA-Seq/métodos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo
10.
Ann Ital Chir ; 92: 135-141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34031280

RESUMO

OBJECTIVE: This study aims to investigate the clinical efficacy and safety of integrative Chinese and Western medicine in the treatment of granulomatous lobular mastitis. METHODS: In the present study, the clinical data of patients with granulomatous lobular mastitis in our hospital were retrospectively analyzed. According to the treatment regimens, these patients were divided into two groups: observation group (n=92) and control group (n=129). Patients in the observation group were treated with traditional Chinese medicine in combination with the surgical treatment of Western medicine, while the patents in the control group received surgical treatment alone. The main observation indexes included clinical cure rate, mass size, prolactin level and aesthetic evaluation results of the breasts. RESULTS: The results revealed that there was no significant correlation between the observation group and control group, in terms of age, prolactin level, and marriage and childbearing history (P>0.05). Furthermore, the recurrence rate was lower in the observation group, when compared to the control group, and the difference was statistically significant (P<0.05). The aesthetic evaluation was higher in the observation group than in the control group, and the difference was statistically significant (P<0.05). However, the difference in the transverse diameter and long diameter of the tumor and clinical cure rate was not statistically significant (P>0.05) between the observation group and control group. CONCLUSION: Compared with the simple surgical treatment of Western medicine, the combination of traditional Chinese medicine and Western medicine in the treatment of granulomatous lobular mastitis can significantly reduce the recurrence rate, and improve the symmetry and beauty of bilateral breasts, which is worthy of clinical application. KEY WORDS: Granulomatous lobular mastitis, Integrated Chinese and western medicine treatment, Unclog lacteal, Prolactin, Aesthetic evaluation of milk preservation.


Assuntos
Mastite Granulomatosa , Medicina Tradicional Chinesa , Administração Oral , Adulto , Mama/cirurgia , Desbridamento , Feminino , Mastite Granulomatosa/tratamento farmacológico , Mastite Granulomatosa/cirurgia , Humanos , Medicina Integrativa/métodos , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Thyroid ; 31(4): 563-571, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33138723

RESUMO

Background: Malnutrition in early life may permanently change the structure and function of the body, which lead to a number of diseases in adulthood. The effect of famine exposure during the early life on thyroid function and disorders remains unclear. This study investigated the association between exposure to the Great Chinese Famine (1959-1961) in early life and thyroid function and disorders in adulthood. Methods: Nine thousand eight hundred eighty-one subjects with appropriate birth dates derived from the Thyroid disorders, Iodine status, and Diabetes Epidemiological survey were included. Thyroid function and disorders were defined by the test results of blood sample and ultrasonography of all participants. Associations between famine exposure in early life and thyroid function and disorders in adulthood were assessed with binary logistic regression and linear regression. Results: Participants exposed to the Great Chinese Famine during the fetal stage was associated with a higher thyrotropin (TSH) level in adulthood (ß = 0.024; p = 0.038), compared with the nonexposed participants. The association was significant among rural participants (ß = 0.039; p = 0.02) but not in urban participants (ß = 0.005; p = 0.77). Fetal-exposed group did not show a higher risk of thyroid disorders than the age-matched balanced control group, including overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and thyroid nodules (p > 0.05). Conclusions: Famine exposure during the fetal stage was associated with a higher TSH level in adulthood. The fetal stage could be the critical period for programming the pituitary-thyroid axis.

13.
Biomaterials ; 268: 120579, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278683

RESUMO

Immunotherapy has revolutionized cancer treatment; however, only a limited portion of patients show responses to currently available immunotherapy regimens. Here, we demonstrate that RNA interference (RNAi) combined with immunogenic chemotherapy can elicit potent antitumor immunity against melanoma. Specially, we developed cationic polymer-lipid hybrid nanovesicles (P/LNVs) as a new delivery system for doxorubicin and small interfering RNA (siRNA) with extensive cytotoxicity and gene silencing efficiency towards B16 cells. The deployment of doxorubicin-loaded P/LNVs augmented the expression and presentation of endogenous tumor antigens directly in situ by inducing the immunogenic cell death of B16 cells through poly(ADP-ribose) polymerase 1-dependent (PARP1) apoptosis pathway; thereby, eliciting remarkable antitumor immune responses in mice. Leveraging dying B16 cells as a vaccination strategy in combination with RNAi-based programmed cell death ligand 1 (PD-L1) knockdown showed efficacy in both prophylactic and metastasis melanoma settings. Strikingly, PD-L1 blockade synergized with a sub-therapeutic dose of doxorubicin triggered robust therapeutic antitumor T-cell responses and eradicated pre-established tumors in 30% of mice bearing B16 melanoma. Our findings indicated that this combination treatment provided a new powerful immunotherapy modality, characterized by markedly increased infiltration of effector CD8+ T cells and effective alleviation of the immunosuppressive microenvironment in tumors. P/LNVs is a versatile and highly scalable carrier that can enable a broad combination of nanomedicine and RNAi, providing new therapeutic strategies for advanced cancers.


Assuntos
Antígeno B7-H1 , Melanoma Experimental , Animais , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Humanos , Imunoterapia , Lipídeos , Melanoma Experimental/terapia , Camundongos , Polímeros , Interferência de RNA , Microambiente Tumoral
14.
Ann Transl Med ; 8(19): 1232, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33178764

RESUMO

Background: Accelerated glycolysis is a characteristic of carcinoma. The herb-derived compound, beta (ß)-elemene, has shown promising anticancer effects against various tumors by inhibiting aerobic glycolysis. However, its activity against thyroid carcinoma and the mechanism is still unknown. Methods: Differentiated thyroid carcinoma (DTC) cell lines, including papillary thyroid carcinoma (PTC) cell lines (IHH-4, TPC-1, K1), and follicular thyroid carcinoma (FTC) cell line (FTC133) were treated with different concentration of ß-elemene. The viability of DTC cells was analyzed using the CCK8 method. Cell cycle and apoptosis analysis were performed by flow cytometry and western blotting. The cell invasion ability was evaluated in Transwell assays. Energy metabolism in living cells was measured using a Seahorse XF analyzer. The antitumor effects of ß-elemene were analyzed in vivo in a nude mouse xenograft tumors model. Results: CCK8 assays showed ß-elemene significantly inhibited DTC cell proliferation in a dose- and time-dependent manner. ß-elemene promoted cell apoptosis, with increased expression of cleaved caspase-9 and decreased BCL-2 expression. Transwell assays showed that ß-elemene significantly inhibited the invasion ability of DTC cells. ß-elemene also reduced angiogenesis by decreasing VEGF expression in DTC cells. ß-elemene reduces the basal oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and maximal glycolytic capacity as well as maximal respiration and ATP production. Moreover, ß-elemene inhibited tumor growth in a mouse xenograft model in vivo. Conclusions: In this study, we have provided the first evidence of the antitumor effects of ß-elemene, which was shown to inhibit cell proliferation, promote apoptosis, induce cell cycle arrest, inhibit cell invasion ability and reduce angiogenesis. Furthermore, we showed that ß-elemene significantly inhibits the respiratory and glycolytic ability of human DTC cells. Thus, our findings show the potential of ß-elemene as a novel treatment for DTC.

15.
Int J Mol Med ; 46(5): 1683-1694, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000179

RESUMO

The loss of function mutation of AT­rich interactive domain 1A (ARID1A) often occurs in patients with breast cancer. It has been found that ARID1A knockout can enhance both the migratory activity of renal carcinoma cells and their sensitivity to therapeutic drugs by promoting epithelial-mesenchymal transition (EMT); however, its mechanisms of action in breast cancer remain unclear. In the present study, immunohistochemistry and reverse transcription­quantitative polymerase chain reaction (RT­qPCR) revealed that the expression of ARID1A in breast cancer tissues was significantly lower than that in paracancerous tissues, and patients with a low ARID1A expression had a lower survival rate. ARID1A was expressed at low levels in breast cancer cells. In addition, siRNA targeting ARID1A (siARID1A) and ARID1A overexpression vector were transfected into MCF7 and MDA­MB­231 cells, respectively. Proliferation assay revealed that ARID1A silencing increased cell viability and partially reversed the inhibitory effects of 5­fluorouracil (5­FU) on the MCF7 cells, while ARID1A overexpression exerted an opposite effect on the MDA­MB­231 cells. ARID1A silencing promoted proliferation, migration, invasion and angiogenesis, and partly reversed the inhibitory effects of 5­FU on cell biological behaviors, while the overexpression of ARID1A further enhanced the inhibitory effect of 5­FU on the cells. Furthermore, ARID1A regulated the migration and invasion of breast cancer cells through EMT. On the whole, the findings of the present study demonstrate that ARID1A exerts an antitumor effect on breast cancer, and its overexpression can enhance the sensitivity of breast cancer cells to 5­FU.


Assuntos
Neoplasias da Mama/patologia , Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal , Fluoruracila/farmacologia , Fatores de Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Proteínas de Ligação a DNA/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neovascularização Patológica/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética
16.
Ann Palliat Med ; 9(5): 2631-2641, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921065

RESUMO

BACKGROUND: The objective of this study was to evaluate the clinical efficacy of the external application of internal expulsion pus-expelling decoction (IEPED) combined with surgery in the treatment of granulomatous lobular mastitis (GLM). METHODS: A total of 110 patients in our hospital with sepsis GLM were randomly divided into two groups: treatment group (n=60, the wound was treated with IEPED) and control group (n=50, the wound was not treated with IEPED). We assessed the recurrence, contra lateral breast form, and aesthetic evaluation of the patients in the two groups. RESULTS: The total effective rates in the patients in the treatment group and the control group were 90% and 68%, respectively, after the preoperative pretreatment and before radical surgery (P<0.05). After 10 days of receiving the debridement treatment, the two groups were compared in term of physical signs scores and the difference was statistically significant (P<0.05). Within one year of the regular follow-up after treatment, 0 case recurred in the treatment group and 1 case recurred in the control group (P>0.05). In the treatment group, 30 cases showed excellent results in the aesthetic evaluation of breast appearance, 18 cases were good, and the overall excellent and good rate was up to 80%. In the control group, 12 cases showed excellent results and 16 cases showed good results, with the overall excellent and good rate reaching 56% (P<0.05). CONCLUSIONS: In patients with abscess debridement of GLM, the external application of IEPED can significantly reduce the primary lesion of patients with abscess GLM, reduce the surgical resection area, and maximize the preservation of the patients' breast appearance.


Assuntos
Mastite Granulomatosa , Feminino , Mastite Granulomatosa/tratamento farmacológico , Humanos , Recidiva , Estudos Retrospectivos , Supuração , Resultado do Tratamento
17.
Thyroid ; 30(12): 1810-1819, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32762331

RESUMO

Background: Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Methods: Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. Results: The geometric mean serum TSH (2.5th-97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74-7.04 mIU/L) and 2.34 mIU/L (0.61-8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, p-value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27-4.2 mIU/L) and NACB standard interval in the TIDE study (0.74-7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%, p < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27-4.2 and 4.2-7.04 mIU/L TSH groups. Conclusions: Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32849304

RESUMO

Background: Antithyroperoxidase (TPOAb) and antithyroglobulin (TgAb) antibodies are associated with abnormal thyrotropin (TSH) levels. However, the effect of dynamic changes in TPOAb and TgAb on incident abnormal TSH is unknown. Methods: A total of 2,387 euthyroid participants aged 18 years or older from three rural areas in northern China were enrolled in this cohort study. Questionnaire interviews and laboratory measurements were performed at baseline in 1999 and at follow-up in 2004. Multinomial logistic regression was used to examine the relationship between changes in thyroid antibodies and incident abnormal TSH levels. Results: In this 5 year follow-up study, TPOAb tier gain was significantly associated with an increased risk of subnormal TSH levels (adjusted RR, 1.535; 95% CI: 1.357-1.736) and supranormal TSH levels (adjusted RR, 1.378; 95% CI: 1.196-1.587), and TgAb tier gain was significantly associated with an increased risk of supranormal (adjusted RR, 1.090; 95% CI: 1.007-1.179) TSH levels. Both thyroid antibody-positive seroconversion and persistent positivity were significantly associated with an increased risk of incident abnormal TSH levels. Thyroid antibody positive seroconversion was associated with a higher risk of incident subnormal TSH than incident supranormal TSH, whereas persistent positive thyroid antibody was associated with a higher risk of incident supranormal TSH than incident subnormal TSH. Conclusions: Dynamic thyroid antibody changes may be related to incident abnormal TSH levels. Those with persistent positive thyroid antibody were more likely to have supranormal TSH than subnormal TSH, and those with positive seroconversion were more likely to have subnormal TSH than supranormal TSH. Further studies are needed to confirm this conclusion and to explore this association mediated by TSH receptor antibodies.


Assuntos
Autoanticorpos/sangue , Biomarcadores/sangue , Iodeto Peroxidase/imunologia , Doenças da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/imunologia , Adulto Jovem
19.
Sci Rep ; 10(1): 11273, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647287

RESUMO

Progression of hepatocellular carcinoma involves multiple genetic and epigenetic alterations that promote cancer invasion and metastasis. Our recent study revealed that hyperphosphorylation of ezrin promotes intrahepatic metastasis in vivo and cell migration in vitro. Celastrol is a natural product from traditional Chinese medicine which has been used in treating liver cancer. However, the mechanism of action underlying celastrol treatment was less clear. Here we show that ROCK2 is a novel target of celastrol and inhibition of ROCK2 suppresses elicited ezrin activation and liver cancer cell migration. Using cell monolayer wound healing, we carried out a phenotype-based screen of natural products and discovered the efficacy of celastrol in inhibiting cell migration. The molecular target of celastrol was identified as ROCK2 using celastrol affinity pull-down assay. Our molecular docking analyses indicated celastrol binds to the active site of ROCK2 kinase. Mechanistically, celastrol inhibits the ROCK2-mediated phosphorylation of ezrin at Thr567 which harnesses liver cancer cell migration. Our findings suggest that targeting ROCK2-ezrin signaling is a potential therapeutic niche for celastrol-based intervention of cancer progression in hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/metabolismo , Proteínas do Citoesqueleto/química , Neoplasias Hepáticas/metabolismo , Triterpenos/farmacologia , Biotina/química , Domínio Catalítico , Movimento Celular , Progressão da Doença , Células HEK293 , Células Hep G2 , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Invasividade Neoplásica , Metástase Neoplásica , Fosforilação , Cicatrização , Quinases Associadas a rho/metabolismo
20.
Thyroid ; 30(11): 1656-1665, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32586221

RESUMO

Background: Iodine intake is associated with thyroid autoimmunity. In this study, we evaluated the changes in thyroid autoimmunity after 20 years of universal salt iodization (USI) in China. Methods: A total of 78,470 subjects (18 years or older) from 31 provincial regions of mainland China participated in the study. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), TSH receptor antibody, thyrotropin (TSH), and urinary iodine concentration (UIC) were measured. Results: Positive TPOAb and TgAb were detected in 10.19% [CI 9.80-10.59] and 9.70% [CI 9.28-10.13] of the subjects, respectively. The prevalence of positive isolated TPOAb (i-TPOAb), positive isolated TgAb (i-TgAb), and double positive TPOAb and TgAb (d-Ab) was 4.52%, 4.16%, and 5.94%, respectively. The prevalence of thyroid antibody positivity was the highest in the iodine-deficient (UIC <100 µg/L) groups. The prevalence of i-TPOAb was inversely associated with more than adequate iodine intake (MAI) and excessive iodine intake (EI); the odds ratio (OR) was 0.89 [CI 0.81-0.98] for MAI and 0.90 [CI 0.81-0.99] for EI. We observed that i-TgAb, like i-TPOAb, was a high-risk factor for subnormal TSH levels (OR = 3.64 [CI 2.62-5.05]) and elevated TSH levels (OR = 1.62 [CI 1.49-1.77]). The prevalence of thyroid antibody positivity varied among five ethnic groups. Conclusions: After two decades of USI, the prevalence of thyroid antibody positivity has remained low. MAI and EI had an inverse relationship with TPOAb positivity, which reveals that UIC between 100 and 299 µg/L is optimal and safe for thyroid autoimmunity. These conclusions need to be confirmed in a follow-up study because this study was a cross-sectional study.

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