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1.
Zhonghua Fu Chan Ke Za Zhi ; 58(10): 742-754, 2023 Oct 25.
Artigo em Zh | MEDLINE | ID: mdl-37849255

RESUMO

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Lesões Pré-Cancerosas , Gravidez , Feminino , Humanos , Adulto , Hiperplasia , Progestinas , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/cirurgia , Resultado do Tratamento , Fertilidade , Classe I de Fosfatidilinositol 3-Quinases , Estudos Retrospectivos
2.
Zhonghua Fu Chan Ke Za Zhi ; 58(7): 526-535, 2023 Jul 25.
Artigo em Zh | MEDLINE | ID: mdl-37474326

RESUMO

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.


Assuntos
Hiperplasia Endometrial , Acetato de Medroxiprogesterona , Feminino , Humanos , Adulto , Acetato de Medroxiprogesterona/efeitos adversos , Hiperplasia Endometrial/patologia , Didrogesterona/efeitos adversos , Hiperplasia , Estudos Prospectivos
3.
Lett Appl Microbiol ; 73(6): 694-707, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34418130

RESUMO

Low isobutanol tolerance of Saccharomyces cerevisiae limits its application in isobutanol fermentation. Here, we used global transcription machinery engineering to screen mutants with higher isobutanol tolerance and elevated isobutanol titres. TATA-binding protein Spt15 was used as the target of global transcription machinery engineering for improvement of such complex phenotypes. A random mutagenesis library of S. cerevisiae TATA-binding protein Spt15 was constructed and subjected to screening under isobutanol stress. A mutant strain (denoted as spt15-3) with improved isobutanol tolerance was identified. There were three mutations of Spt15 in strain spt15-3, including deletion of A at position -132 nt upstream of initiation codon, insertion of G at position -65 nt upstream of initiation codon and a synonymous mutation at position 315 nt (T → C) downstream of initiation codon. We then metabolically engineered isobutanol synthesis in strains harbouring plasmids YCplac22 containing these Spt15 mutations. Delta integration was used to overexpress ILV3 gene, and 2µ plasmids carrying PGK1p-ILV2 and PGK1p-ARO10 were used to overexpress ILV2 and ARO10 genes. After 24-h micro-aerobic fermentation, Engi-3 produced 0·556 g l-1 isobutanol, which was 404% and 25·3% greater than isobutanol produced by control Engi-1 and engineered Engi-2, respectively. After 28 h, Engi-4 produced 0·459 g l-1 isobutanol, which was 315% and 3·2% greater than isobutanol produced Engi-1 and Engi-2, respectively. RNA-Seq-based transcriptome analysis shows that mutations of Spt15 in strain spt15-3 increased the expression of SPT15. Meanwhile, compared with strain Engi-3, the spt15-3 mutation downregulated the expression of genes involved in the TCA cycle and glyoxylic acid cycle, but increased the expression of genes related to cell stability. This work demonstrates that isobutanol tolerance and production of S. cerevisiae can be improved by engineering its TATA-binding protein Spt15. This study clarified the molecular mechanisms regulating isobutanol production and tolerance in S. cerevisiae.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Butanóis , Fermentação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteína de Ligação a TATA-Box/genética , Proteína de Ligação a TATA-Box/metabolismo
4.
J Obstet Gynaecol Res ; 47(5): 1694-1703, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33634542

RESUMO

AIM: To evaluate the theme trends and knowledge structure of multifetal pregnancy reduction (MPR)-related literature by using bibliometric analysis. METHODS: Published scientific papers regarding MPR were retrieved from the PubMed database. Data extraction and statistics were conducted using Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). Furthermore, gCLUTO software was used in the study for bi-clustering analysis and strategic diagram analysis. RESULTS: According to the search strategy, 906 total papers were included. Among all the extracted MeSH terms, 41 high frequency ones were identified and hotspots were clustered into four categories. In the strategic diagram, research on intrauterine treatment of MPR was most well developed. In contrast, statistical data on the sequelae of fetal reduction surgery and applications of MPR in assisted reproductive technologies were relatively immature. CONCLUSION: The analysis of common terms among the high-frequency network terms in multiparous pregnancy reduction can help researchers and clinicians understand the hotspots, key topics, and issues to be discovered on MPR. Research on intrauterine treatment of MPR was most well developed.


Assuntos
Bibliometria , Redução de Gravidez Multifetal , Análise por Conglomerados , Bases de Dados Factuais , Feminino , Humanos , Gravidez
5.
Zhonghua Yi Xue Za Zhi ; 101(27): 2170-2172, 2021 Jul 20.
Artigo em Zh | MEDLINE | ID: mdl-34275254

RESUMO

This study reviewed the clinical data of patients who were hospitalized in the Department of Neurology of Henan Provincial People's Hospital from January 2017 to October 2020. A total of 46 patients with positive serum anti-CV2 antibody were included. The average age of the patients was (54±15) years old, with a male to female ratio of 1.88∶1. Twenty-six patients were diagnosed with paraneoplastic neurological syndrome (PNS). The most malignant tumors were thymoma, small cell lung cancer, and prostate cancer. The most common PNS included myasthenia gravis, subacute cerebellar degeneration, and subacute/chronic sensorimotor neuropathies. Twenty non-PNS patients exhibited subacute/old cerebral infarction, Parkinson's disease, Alzheimer's disease, and so on. Among them, brain magnetic resonance imaging (MRI) of 10 cases showed different degrees of white matter demyelination, some of which were accompanied by brain atrophy. The current study found that the positive predictive value of anti-CV2 antibody for the diagnosis of PNS was 56.5%, which was relatively weak. As an accompanying antibody, it may be a coincidence, and it may also be related to the involvement of family members in the pathological process of the diseases.


Assuntos
Neoplasias Pulmonares , Doenças do Sistema Nervoso , Síndromes Paraneoplásicas , Timoma , Neoplasias do Timo , Adulto , Idoso , Autoanticorpos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Zhonghua Wai Ke Za Zhi ; 59(1): 6-17, 2021 Jan 01.
Artigo em Zh | MEDLINE | ID: mdl-33412628

RESUMO

Objective: To summarize the experience of surgical treatment of primary liver cancer. Methods: The clinical data of 10 966 surgically managed cases with primary liver cancer, from January 1986 to December 2019 at Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The life table method was used to calculate the survival rate and postoperative recurrence rate. Log-rank test was used to compare the survival process of different groups, and the Cox regression model was used for multivariate analysis. In addition, 2 884 cases of hepatocellular carcinoma(HCC) with more detailed follow-up data from 2009 to 2019 were selected for survival analysis. Among 2 549 patients treated with hepatectomy, there were 2 107 males and 442 females, with an age of (56.6±11.1) years (range: 20 to 86 years). Among 335 patients treated with liver transplantation, there were 292 males and 43 females, with an age of (51.0±9.7) years (range: 21 to 73 years). The outcomes of hepatectomy versus liver transplantation, anatomic versus non-anatomic hepatectomy were compared, respectively. Results: Of the 10 966 patients with primary liver cancer, 10 331 patients underwent hepatectomy and 635 patients underwent liver transplantation. Patients with liver resection were categorized into three groups: 1986-1995(712 cases), 1996-2008(3 988 cases), 2009‒2019(5 631 cases). The 5-year overall survival rate was 32.9% in the first group(1986-1995). The 5-year overall survival rate of resected primary liver cancer was 51.7% in the third group(2009-2019), among which the 5-year overal survival rates of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%, 26.6% and 50.6%, respectively. Further analysis was performed on 2 549 HCC patients with primary hepatectomy. The 1-, 3-, 5-, and 10-year overall survival rates were 88.1%, 71.9%, 60.0%, and 41.0%, respectively, and the perioperative mortality rate was 1.0%. Two hundred and forty-seven HCC patients underwent primary liver transplantation, with 1-, 3-, 5-, and 10-year overall survival rates of 84.0%, 64.8%, 61.9%, and 57.6%, respectively. Eighty-eight HCC patients underwent salvage liver transplantation, with the 1-, 3-, 5-, and 10-year overall survival rates of 86.8%, 65.2%, 52.5%, and 52.5%, respectively. There was no significant difference in survival rates between the two groups with liver transplantation (P>0.05). Comparing the overall survival rates and recurrence rates of primary hepatectomy (2 549 cases) with primary liver transplantation (247 cases), the 1-, 3-, 5-, and 10-year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%, 87.1%, 76.9%, 54.7%, and 95.4%, 79.4%, 77.4%, 71.7%, respectively (P=0.754). The 1-, 3-, 5-year recurrence rates were 16.3%, 35.9%, 47.6% and 8.1%, 11.7%, 13.9%, respectively(P<0.01). The 1-, 3-, 5-, 10-year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%, 65.9%, 53.0%, 33.0% and 87.6%, 71.8%, 71.8%, 69.3%, respectively(P=0.003); the 1-, 3-, 5-year recurrence rate were 39.2%, 57.8%, 69.7% and 29.7%, 36.7%, 36.7%, respectively (P<0.01). The 1-, 3-, 5-, and 10-year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%, 36.1%, 22.2%, 15.0% and 62.9%, 31.8%,19.9%, 0, respectively (P=0.387); the 1-, 3-, 5-year recurrence rates were 61.5%, 74.7%, 80.8% and 59.7%, 82.9%, 87.2%, respectively(P=0.909). Independent prognostic factors for both overall survival and recurrence-free survival rates of HCC patients treated with liver resection included gender, neoadjuvant therapy, symptoms, AST, intraoperative or postoperative blood transfusion, tumor number, tumor size, cirrhosis, macrovascular invasion, microvascular invasion, and pathological differentiation. Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non-anatomical liver resection(P=0.895), but the recurrence rate of non-anatomical liver resection was higher than that of anatomical liver resection(P=0.035). Conclusions: In the past decade, the overall survival rate of HCC undergoing surgical treatment is significantly higher than before. For HCC patients with good liver function reservation, surgical resection can be performed first, and salvage liver transplantation can be performed after recurrence. The effect of salvage liver transplantation is comparable to that of primary liver transplantation. As for the choice of liver resection approaches, non-anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , China/epidemiologia , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
7.
Neoplasma ; 67(2): 371-378, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31986891

RESUMO

Glutamine addiction is a major feature of glioma cells and plays an important role in its growth and proliferation. GLUL (glutamate-ammonia ligase), which catalyzes glutamate and ammonia to synthesize glutamine, plays a crucial role in tumor growth and proliferation. We attempt to determine a pathway that limits the growth of glioma by targeting GLUL and explore effective strategies blocking glutamine metabolism. We note that miRNAs mediate regulation of genes participating directly or indirectly in cancer cell metabolism. The regulatory roles of miRNAs on metabolic enzymes are widely discussed, however miRNAs regulation of glutamine metabolism by targeting GLUL in glioma has not yet been reported. Here, we examined both the expression and functions of GLUL in glioma cells. Findings indicated that the expression of GLUL was upregulated in high-grade compared to low-grade glioma cells. Knockdown of GLUL effectively inhibited proliferation, migration and invasion of glioma cells in vitro. Bioinformatics analyses, as well as dual-luciferase reporter assays, revealed that miR-140-5p bound to GLUL mRNA at the 3'-UTR location. Furthermore, the proliferation, migration and invasion of glioma cells were also repressed by miR-140-5p. Overall, these results showed that miR-140-5p exerted its inhibitory effects on proliferation, migration and invasion in glioma cells through downregulating GLUL. Thus, the miR-140-5p/GLUL axis may function as a potential target for glioma treatment.


Assuntos
Glioma/patologia , Glutamato-Amônia Ligase/genética , MicroRNAs/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/enzimologia , Humanos , Invasividade Neoplásica
8.
Zhonghua Yi Xue Za Zhi ; 100(27): 2138-2143, 2020 Jul 21.
Artigo em Zh | MEDLINE | ID: mdl-32689756

RESUMO

Objective: To investigate the effect of 6% hydroxyethyl starch 130/0.4(HES) on protein in severe trauma orthopedic patients after acute hemodilution. Methods: Fourty-eight severe trauma patients who met the inclusion criteria were selected from June 2018 to December 2018 in Yantaishan Hospital, and were randomly divided into two groups (n=24): group A and group B. Group A was ringer's sodium lactate control group, and group B was HES treatment group. After the tracheal intubation, the patients of group A were infused with 10% blood volume of sodium lactate ringer at 0.5 ml·kg(-1)·min(-1), and the patients in group B were infused with 10% blood volume of HES at 0.5 ml·kg(-1)·min(-1). Total protein (TP), human serum albumin (HSA), numbers of circulating endothelium cells (CEC), C-reactive protein (CRP), and serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10 and IL-6 were measured immediately after acute hemodilution (T(0)), 24 hours (T(1)) and 48 hours (T(2)) after acute hemodilution. After infusion into human body, HES bond to HSA, and fluorescence spectroscopy was used to analyze the binding relationship between HES and HSA in order to further study the effects of HES on HSA. Results: The HSA, TP, CEC, TNF-α, IL-6, IL-10, CRP at T(0) of group A were (38±5) g/L, (66±5) g/L, (5.5±0.4)/0.9 µl, (24±5) µg/L, (8.9±0.8) µg/L, (44±6) µg/L, (13.6±1.4) mg/L; While at T(1) were (33±5) g/L, (60±6) g/L, (10.2±0.7)/0.9 µl, (87±9) µg/L, (38.8±2.3) µg/L, (57±7) µg/L, (23.4±2.4) mg/L. The HSA, TP, CEC, TNF-α, IL-6, IL-10, CRP at T(0) of group B were(38±4)g/L, (66±5) g/L, (5.4±0.6)/0.9 µl, (24±6) µg/L, (9.1±0.9) µg/L, (45±6) µg/L, (13.4±1.8) mg/L; While at T(1) were (35±5)g/L, (62±5)g/L, (7.4±0.6)/0.9 µl, (70±8) µg/L, (29.5±3.1) µg/L, (72±6) µg/L, (19.7±2.2) mg/L. HSA and TP decreased at T(1) in group A as compared with T(0) (P<0.05), contrarily CEC increased significantly at T(1), TNF-ɑ, IL-6, IL-10 and CRP augmented at T(1) and T(2) in two groups (P<0.05). In comparison with the patients of group A, CEC decreased significantly at T(1) (P<0.05). TNF-ɑ, IL-6, CRP reduced significantly at T(1) and T(2) (P<0.05), but IL-10 increased at T(1) and T(2) in group B (P<0.05). The secondary structure of HSA changed after HES was added in the HES solution. The fluorescence intensity of HSA decreased with the increase of HES concentration,which suggested that HES induced HSA fluorescence quenching. HES could bind to Trp-214 residue in HSA at a molecular ration of 1∶1. Conclusions: 6% HES reduces the occurrence of low protein level in severe trauma patients after operation. HES could bind to Trp-214 amino acid residue in HSA and form the complex at a molecular ratio of 1∶1. The formation of HES-HSA complex increases the volume of HES, avoids the vascular leakage, protects the vascular endothelial cells, and induces anti-inflammatory immunity in the patients with capillary syndrome.


Assuntos
Células Endoteliais , Derivados de Hidroxietil Amido/farmacologia , Albumina Sérica , Hemodiluição , Humanos , Lactato de Ringer , Albumina Sérica/efeitos dos fármacos
9.
Eur J Neurol ; 26(5): 800-807, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30584694

RESUMO

BACKGROUND AND PURPOSE: Subjective memory impairment (SMI) and amnestic mild cognitive impairment (aMCI) are thought to represent the pre-dementia stages of Alzheimer's disease (AD). SMI is considered a more advanced pre-clinical status prior to aMCI. Understanding the neuromechanism of SMI will have great benefits for monitoring the disease progression of AD. The study aims to explore whether SMI shows alterations of white matter (WM) integrity similar to the patterns of aMCI. METHODS: The atlas-based analyses were performed to investigate the diffusion changes in the major WM tracts amongst 22 individuals with normal cognition (NC), 22 SMI patients and 25 aMCI patients. The correlations between the altered diffusion metrics and cognitive performance in the SMI and aMCI groups were assessed. RESULTS: The diffusion tensor metrics of SMI were intermediate between the NC and aMCI groups. The aMCI group presented disrupted integrity in multiple WM tracts, including the left anterior thalamic radiation, right corticospinal tract and left cingulum of the hippocampus (CgH), compared to the NC group. The left CgH showed diffusion alterations in the SMI group. In the aMCI group, the mean diffusivity of the left CgH was negatively correlated with episodic memory, whilst the radial diffusivity of the right corticospinal tract was negatively correlated with executive function. No significant relationship was found in the SMI group. CONCLUSION: The study suggested that SMI patients might present detectable WM integrity changes in the left CgH before exhibiting objective cognitive dysfunction, which may provide novel insights into the pathological mechanisms of AD.


Assuntos
Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Transtornos da Memória/patologia , Substância Branca/patologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Atlas como Assunto , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Imagem de Tensor de Difusão , Função Executiva , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/psicologia , Memória Episódica , Pessoa de Meia-Idade , Testes Neuropsicológicos , Sintomas Prodrômicos , Desempenho Psicomotor , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Substância Branca/diagnóstico por imagem
10.
Indoor Air ; 28(2): 276-286, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29227564

RESUMO

In this study, we evaluated the long-term antifungal effectiveness of 3 types of interior building materials (gypsum board [GB], cement board [CB], and softwood plywood [S-PW]) impregnated with thermally reduced silver nanoparticles supported by titanium dioxide (AgNPs/TiO2 ) under 95% relative humidity for 4 weeks. AgNPs/TiO2 was synthesized at 2 thermal reduction temperatures (TRTs, 120 and 200°C) with 2 different AgNP weight percentages (2 and 5 wt%). Four different silver-loading levels (SLLs, 0.025, 0.05, and 0.5 µg/cm2 and the critical concentration required to inhibit fungal growth on agar plates) and 3 fungal species (Aspergillus niger, Penicillium spinulosum, and Stachybotrys chartarum) were used in the experiments. Higher temperature reduced more ionic Ag+ to metallic Ag0 and increased the dispersion of Ag on TiO2 surface. The 200°C thermally reduced AgNPs/TiO2 demonstrated excellent antifungal efficiency: Mold growth was almost completely inhibited for 28 days at the low SLL of 0.5 µg/cm2 . Additionally, AgNPs/TiO2 exhibited higher antifungal activity on GB and CB than on S-PW. The stepwise regression results indicated that the TRT of AgNPs/TiO2 (ß = -0.739 to -0.51), the SLL (ß = -0.477 to -0.269), and the Ag0 level in the AgNPs (ß = -0.379 to -0.136) were the major factors influencing antifungal activity and TRT might be the most significant one.


Assuntos
Antifúngicos , Materiais de Construção/microbiologia , Fungos/crescimento & desenvolvimento , Nanopartículas Metálicas , Prata , Temperatura Alta
11.
Cryo Letters ; 38(1): 37-42, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28376138

RESUMO

BACKGROUND: Oocyte vitrification is a practical tool in assisted reproductive technology and fertility preservation. However, vitrification requires high concentration of cryoprotectants (CPAs), which may cause osmotic injury and is toxic to oocytes during the addition and removal process of CPAs. OBJECTIVE: To minimize osmotic and toxic injuries, a microfluidic device was designed to provide continuous concentration changes of CPAs to oocytes. METHODS: Numerical simulations were first used to investigate the effects of geometric parameters of microchannel on water- Me2SO mixing performance. A microfluidic device was then fabricated via soft lithography. Distilled water and 30 percent Me2SO containing 1mM fluorescence dye FITC were mixed using the microfluidic device to verify the CPA diffusion behavior. RESULTS: The mixing performance in the microfluidic device strongly depends on the channel geometry and the flow rates of the fluids. Linear CPA loading profiles with diverse slopes were obtained by controlling the flow rate and the loading time of CPA and the buffer solution in the microfluidic device. CONCUSION: The designed microfluidic device can yield linear CPA loading profiles with different slopes.


Assuntos
Criopreservação/instrumentação , Crioprotetores/farmacologia , Dispositivos Lab-On-A-Chip , Modelos Teóricos , Oócitos/efeitos dos fármacos , Crioprotetores/química , Osmose , Soluções , Ésteres do Ácido Sulfúrico/química , Vitrificação , Água/química
12.
Z Rheumatol ; 76(4): 351-356, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27444626

RESUMO

OBJECTIVE: The aim of this study was to explore the value of laboratory indexes in the differential diagnosis of Henoch-Schoenlein purpura (HSP). METHODS: Patients with HSP hospitalized at the Children's Hospital of Zhejiang University School of Medicine between January 2010 and December 2014 were enrolled in this prospective study. In addition, septic patients with rash and patients with urticaria, simple hematuria, and acute appendicitis hospitalized during the same period were selected at random as differential diagnosis subjects, and healthy children were selected as normal controls. The levels of IgA, D­dimer, fibrinogen (FIB), and platelet (PLT) and the platelet distribution width (PDW) of these individuals were tested and analyzed, and the ROC curve was used to determine the applicability of these indexes to differentiate between patients with HSP and other diseases easily confused with HSP, as well as to determine the efficacy of combined diagnosis. RESULTS: There were remarkable differences in the levels of FIB, D­dimer, IgA, PLT, and PDW among patients with HSP, sepsis patients with rash, patients with urticaria, simple hematuria, or acute appendicitis and healthy children (P < 0.01). CONCLUSION: The levels of IgA, D­dimer, and PLT can be applied separately for the differential diagnosis of HSP, and these indexes and FIB can be combined appropriately to improve the diagnostic efficacy.


Assuntos
Técnicas de Laboratório Clínico/métodos , Vasculite por IgA/sangue , Vasculite por IgA/diagnóstico , Mediadores da Inflamação/sangue , Índice de Gravidade de Doença , Biomarcadores/sangue , Feminino , Humanos , Masculino , Fosfoproteínas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Beijing Da Xue Xue Bao Yi Xue Ban ; 49(5): 824-828, 2017 10 18.
Artigo em Zh | MEDLINE | ID: mdl-29045963

RESUMO

OBJECTIVE: To explore the function of tumor derived IgG (tIgG) and whether the tIgG can inhibit T cells activity. METHODS: The tIgG was purified from ovarian cancer tissue. The cord blood monocyte cells (CBMC) and cord blood lymphocyte (CBL) were isolate from human umbilical cord blood. The CBMC and CBL were stimulated with phytohaemagg lutinin (PHA) in order to let the CBMC and CBL in the state of proliferation. Carboxyfluorescein succinimidyl amino ester (CFSE) was cultured with CBMC and CBL. CFSE had no cell toxicity, which could penetrate through the cell membrane and combine the intracellular protein. The fluorescence intensity decreased with the proliferation of cells step by step, so the proliferation of these cells could be detected in flow ctytometry. The tIgG which was purified from ovarian cancer tissue was divided into three groups, 1 mg/L group, 10 mg/L group, and 100 mg/L group, and the intravenous immunoglobulin (IVIG) was also divided into three groups too. The CBMC and CBL were treated by tIgG with 1 mg/L, 10 mg/L, and 100 mg/L in order to observe the proliferation of T cells. The cells were treated with IVIG as a positive control group, and the cells were treated with phosphate buffer saline (PBS) as a negative control. The proliferation of CD4+ or CD8+ T cells were detected in CBMC and CBL. The proliferation of the T cells in CBMC and CBL after 64 h and 86 h were detected. RESULTS: In the system of CBMC, the tIgG could suppress the proliferation of CD4+ or CD8+ T cells. The results could also be found in the system of CBL. The CD4+ or CD8+ T cells in the group which were treated with PBS were more active than those in the group which were treated with tIgG and IVIG. The suppression in the group which were treated with tIgG, was stronger than that in the group treated with IVIG. In addition, the suppression of T cells in the group which were stimulated with tIgG as 100 mg/L was more effective than that in the group which were stimulated with tIgG as 10 mg/L. This could prove that tIgG had the function of immunomodulation. CONCLUSION: The tIgG can be involved in immune escape of cancer.


Assuntos
Proliferação de Células , Sangue Fetal , Linfócitos T , Células Cultivadas , Sangue Fetal/metabolismo , Humanos , Imunoglobulina G/fisiologia , Neoplasias , Linfócitos T/fisiologia , Evasão Tumoral
14.
Spinal Cord ; 54(4): 259-65, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26481704

RESUMO

STUDY DESIGN: This is an experimental study. OBJECTIVES: The objective of this study was to evaluate the neuroprotective effects of Ginkgo biloba extract 761 (EGb761) on histological features of injured sites and on functional performance of rats subjected to standardized spinal cord injury (SCI). SETTING: This study was conducted in Xian, Shaanxi, China. METHODS: Thirty female Sprague-Dawley rats were randomly divided into three groups: sham-operated, saline-treated control and EGb761-treated. The Basso, Beattie, Bresnahan Locomotor Rating Score (BBB score) was calculated and footprint analysis was performed to evaluate the functional performance of the rats in each group. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 staining were performed to evaluate the necrosis area and apoptotic cells at the injured site in each group. RESULTS: At 14, but not 1, 3 and 7, days post injury (DPI), rats in the EGb761-treated group exhibited significantly better BBB scores compared with the saline-treated control group (P<0.05). The EGb761-treated group also showed increased stride length, decreased stride width and reduced toe dragging at 14 DPI (P<0.05). Analysis of HE staining revealed that the EGb761-treated group had reduced necrosis at the injury site compared with the saline-treated control group (P<0.05). Analysis of TUNEL and caspase-3 staining demonstrated that cell apoptosis was increased at 1-14 DPI, peaking at 24-h post injury in the gray matter, and 7 DPI in the white matter. At 7 DPI, the quantity of apoptotic cells was significantly decreased in the EGb761-treated group. CONCLUSION: EGb761 administration during the acute phase after SCI significantly reduced secondary injury-induced tissue necrosis and cell apoptosis and improved functional performance in rats.


Assuntos
Extratos Vegetais/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Animais , Caspase 3/metabolismo , Contagem de Células , Modelos Animais de Doenças , Feminino , Ginkgo biloba , Marcação In Situ das Extremidades Cortadas , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Coluna Vertebral/efeitos dos fármacos , Coluna Vertebral/metabolismo , Coluna Vertebral/patologia , Fatores de Tempo
15.
Genet Mol Res ; 15(2)2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-27420986

RESUMO

Our study aimed to investigate the co-localization and protein-protein interactions between ezrin and p65 in human breast cancer cells. Liquid chromatography-mass spectrometry (LCMS) was used to uncover novel protein interactions with ezrin in MDA-MB-231 cells. Endogenous co-immunoprecipitation was used to validate protein-protein interactions between ezrin and p65 in MDA-MB-231. Exogenous interactions between ezrin and p65 were validated in MDA-MB-231 cells via Flag-ezrin and HA-p65 co-transfection and followed by co-immunoprecipitation. Immunofluorescence staining was used to visualize ezrin and p65 co-localization in MDA-MB-231. LCMS results showed that there were 1000 proteins interacting with ezrin in MDA-MB-231 cells. Ezrin and p65 interactions were confirmed with both endogenous and exogenous methods. We were also able to visualize ezrin and p65 co-localization in MDA-MB-231. In summary, we found protein-protein interactions between Ezrin and p65 in human breast cancer cells.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas do Citoesqueleto/metabolismo , Fator de Transcrição RelA/metabolismo , Linhagem Celular Tumoral , Humanos , Ligação Proteica
16.
Genet Mol Res ; 15(3)2016 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-27706768

RESUMO

Sacral nerve stimulation (SNS) is an alternative surgical approach to alleviate fecal incontinence and constipation. This study aimed to explore the effects and underlying mechanisms of SNS with acupuncture on gut transit time and colon c-kit protein expression in rats with slow transit constipation (STC). Fifty Sprague-Dawley rats were randomly divided into five groups: blank control, SNS, Mosapride, sham SNS, and STC model control group. The STC model was established by subcutaneous injection of morphine. Each group was treated over a 15-day period. Gut transit time was measured 1 day before the treatment started and after 5, 10, and 15 days of treatment. After the 15-day treatment, animals were sacrificed and colonic tissues were collected for analysis of c-kit protein expression, using western blot analysis. We found significant differences in gut transit time in the SNS group compared with the Mosapride group after 5 (P = 0.001) and 10 (P = 0.004) days of treatment. After 15 days of treatment, there were no differences in gut transit time among the SNS, Mosapride, and blank control groups. However, significant differences were observed when comparing the SNS and Mosapride groups with the STC model and sham SNS groups. A decreased c-kit protein expression was observed in the STC model control, sham SNS, and Mosapride groups, compared with the SNS group (P = 0.001). Our data indicate that SNS can decrease gut transit time and increase the expression of c-kit protein in rats with STC to improve colon transit function.


Assuntos
Terapia por Acupuntura , Colo/metabolismo , Colo/fisiopatologia , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Trânsito Gastrointestinal/fisiologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Sacro/inervação , Animais , Estimulação Elétrica , Feminino , Masculino , Ratos Sprague-Dawley , Fatores de Tempo
17.
Zhonghua Fu Chan Ke Za Zhi ; 51(6): 420-3, 2016 Jun 25.
Artigo em Zh | MEDLINE | ID: mdl-27356476

RESUMO

OBJECTIVE: To explore the the expression of Klotho mRNA and protein in placenta of macrosomia and its relationship with the birth weight of neonates. METHODS: The cases were from November 2014 to March 2015 in Shengjing Hospital of China Medical University, divided into 4 groups: the gestational diabetes with macrosomia group (GM), the gestational diabetes with normal birth weight group (GN), the normal pregnancy with macrosomia group (NM) and the normal pregnancy with normal birth weight group (NN). Klotho mRNA and protein expression in the placenta were detected by immunohistochemistry SP method, real-time fluorescent quantitative PCR and western blot, respectively, and were compared among the 4 groups. RESULTS: (1) Immunohistochemical detection showed the positive rate of Klotho protein was significantly higher in the placenta of GM (93%,28/30) than in the GN (73%,22/30; P<0.05). The positive rate was significantly higher in the placenta of NM (97%,29/30) than in the NN (80%,24/30; P<0.05). (2) Real-time fluorescent quantitative PCR showed the Klotho mRNA expression was significantly higher in the placenta of GM (4.3 ± 3.1) than in the GN (2.1 ± 2.4; P<0.05). The Klotho mRNA expression was also significantly higher in the placenta of NM (4.8± 3.4) than in the NN (2.6± 3.3; P<0.05). (3) Western blot showed the Klotho protein expression was significantly higher in the placenta of GM (1.27±0.90) than in the GN (0.64±0.24; P<0.05). It was also significantly higher in the placenta of NM (2.51±3.52) than in the NN (0.77±0.37; P<0.05). (4) There were no significant differences in the expression of Klotho mRNA and protein between GM and NM, GN and NN (P>0.05). CONCLUSIONS: The up-regulation of Klotho gene may be associated with macrosomia. The relationship is not affected by the complication of gestational diabetes.


Assuntos
Peso ao Nascer , Diabetes Gestacional/genética , Macrossomia Fetal/metabolismo , Glucuronidase/genética , Placenta/metabolismo , RNA Mensageiro/genética , Western Blotting , China , Feminino , Humanos , Imuno-Histoquímica , Recém-Nascido , Proteínas Klotho , Gravidez , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 50(11): 1011-1016, 2016 Nov 06.
Artigo em Zh | MEDLINE | ID: mdl-27903366

RESUMO

Dyslipidemias is one important risk factor associated with chronic diseases. Persistent organic pollutants are resistant to degradation and can be bio-accumulated and magnified through the food chain. Recently, the relation between dyslipidemias and organochlorine pesticides has attracted more attentions. In this review, we explored the distribution of organochloride pesticides in the environment and human body, as well as the possible underlying mechanisms of the association between dyslipidemias and organochloride pesticides, including accumulation and release of organochloride, simulation of estrogen, impact on PPARs, the metabolic fingerprint, and the inflammatory reaction.


Assuntos
Dislipidemias/induzido quimicamente , Dislipidemias/fisiopatologia , Poluentes Ambientais/intoxicação , Praguicidas/intoxicação , Dislipidemias/epidemiologia , Poluentes Ambientais/efeitos adversos , Humanos , Hidrocarbonetos Clorados/intoxicação , Compostos Orgânicos , Praguicidas/efeitos adversos , Fatores de Risco
19.
Genet Mol Res ; 14(4): 14119-22, 2015 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-26535727

RESUMO

Twelve polymorphic microsatellite loci were isolated in the Japanese gecko, Gekko japonicus. We genotyped one population from Wenzhou, Zhejiang Province, China (N = 36). The mean number of observed alleles per locus was 7.3 (range 4 to 13). Observed and expected heterozygosity values ranged from 0.200 to 0.944 and from 0.395 to 0.797, respectively. One locus (GJ20) showed significant departure from Hardy-Weinberg equilibrium; no linkage disequilibrium was found between any two loci. These informative microsatellite markers will be useful for population genetic analyses of G. japonicus and other species in the genus Gekko.


Assuntos
Lagartos/genética , Repetições de Microssatélites , Alelos , Animais , China , Marcadores Genéticos/genética , Variação Genética , Genética Populacional , Desequilíbrio de Ligação , Polimorfismo Genético , Mapeamento por Restrição/métodos , Mapeamento por Restrição/veterinária
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