Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 87
Filtrar
1.
Hum Reprod ; 39(1): 43-52, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37994690

RESUMO

STUDY QUESTION: What is the impact of male hepatitis B virus (HBV) infection on sperm quality, embryonic development, and assisted reproductive outcomes? SUMMARY ANSWER: Male HBV infection did not affect assisted reproductive outcomes, but HBV is capable of impairing human sperm and embryo formation in the early stages following fertilization. WHAT IS KNOWN ALREADY: HBV is found in germ cells and early embryos of patients with HBV. HBV may impair human sperm function via increasing reactive oxygen species. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study of 1581 infertile couples, including 496 male patients clinically confirmed to have hepatitis B infection, and a laboratory study of effects of HBV proteins on early embryos, using human embryonic stem cells (hESCs), human sperm, and golden hamster oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 1581 infertile couples (24-40 years of age) who were admitted to a reproductive medicine center to undergo ART for the first time from January 2019 to November 2021 were selected as the study subjects. The case group was composed of 469 couples with hepatitis B surface antigen (HBsAg)-seropositive men and seronegative women (368 for IVF and 101 for ICSI treatment). The negative control group was composed of 1112 couples where both men and women were seronegative for hepatitis B antigen. We divided these couples into three comparison groups (IVF/ICSI, IVF, and ICSI). IVF of human sperm and hamster oocytes was used to evaluate the influence of the HBV HBs protein on formation of 2-cell embryos. Mitochondrial membrane potential (MMP) of hESCs was assayed via a fluorescence intensity system. Immunofluorescence staining of the phosphorylated histone H2A.X was applied to identify DNA damage to hESCs caused by the HBV X (HBx) protein. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm concentration, total sperm number, and sperm with normal morphology were decreased in the couples with HBV-infected males in couples who were undergoing IVF/ICSI (male HBV(+) vs control: 469 vs 1112 individuals; sperm number, P < 0.01; normal sperm morphology, P < 0.01), IVF (368 vs 792; sperm number, P < 0.01; normal sperm morphology, P ≤ 0.05), and ICSI (101 vs 306; sperm number, P < 0.01; normal sperm morphology, P < 0.001). There was no significant difference in the number of embryo cleavages, blastocyst formation, biochemical pregnancy rate, clinical pregnancy rate, and live-birth rate between case and control groups. The 2PN fertilization rate in IVF/ICSI (P < 0.01) and ICSI (P < 0.05) couples, and the number of 2PN-fertilized oocytes in IVF (P < 0.001) couples were lower in couples with male HBV infection compared to control couples. HBV HBs protein reduced the MMP of human sperm and decreased 2-cell embryo formation in IVF of human sperm and zona-free-hamster oocyte. A reduction in fluorescence intensity and immunofluorescence staining of phosphorylated histone H2A.X indicated that HBx caused MMP impairment and DNA damage in human early embryonic cells, respectively. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: HBV can be examined in samples of sperm or discarded IVF early embryos from HBsAg-seropositive men and seronegative women. The hESC model in vitro may not fully mimic the natural embryos in vivo. WIDER IMPLICATIONS OF THE FINDINGS: This study furthers our understanding of the influence of male HBV infection on embryonic development. Our results suggest that a semen-washing process may be necessary for male patients with HBV undergoing ART to minimize the potential negative effects of HBV infection on the early embryo. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by grants from the National Natural Science Foundation of China, grant numbers 81870432 and 81570567 to X.Z., 81571994 to P.S., and 81950410640, the Natural Science Foundation of Guangdong Province, China (No. 2023A1515010660 to X.Z.), and the Li Ka Shing Shantou University Foundation (Grant No. L11112008). The authors have no conflicts of interest.


Assuntos
Vírus da Hepatite B , Hepatite B , Gravidez , Humanos , Masculino , Feminino , Fertilização in vitro , Injeções de Esperma Intracitoplásmicas , Estudos Retrospectivos , Sêmen , Antígenos de Superfície da Hepatite B , Histonas , Taxa de Gravidez , Desenvolvimento Embrionário , Espermatozoides
2.
Neoplasma ; 71(3): 243-254, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38958714

RESUMO

Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.


Assuntos
Proliferação de Células , Dissulfetos , Ferroptose , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Espécies Reativas de Oxigênio , Ácidos Sulfínicos , Humanos , Ferroptose/efeitos dos fármacos , Dissulfetos/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Proliferação de Células/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Movimento Celular/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Glutationa/metabolismo , Sobrevivência Celular/efeitos dos fármacos
3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 293-297, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36949688

RESUMO

Objective: To analyze the electroencephalogram (EEG) features of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) and to study the clinical assessment value of the degree of EEG background slowing and the presence of δ brush. Methods: We enrolled 52 patients with anti-NMDARE and collected their clinical data, including age, sex, form of disease onset, status of tumor comorbidity, auxiliary examination findings (cerebrospinal fluid [CSF] anti-methyl-D-aspartate receptor antibody titers, magnetic resonance imaging [MRI] reports, and EEG results), treatment status, and follow-up after discharge. The degree of EEG background abnormality and the presence of δ brush in the EEG of patients with different clinical features were analyzed. Results: Among the 52 patients, 7 (14%) had normal EEG, and 45 (87%), abnormal EEG, including 25 (48%) with mild abnormalities, 11 (21%) with moderate abnormalities, and 9 (17%) with severe abnormalities. δ brush was seen in 6 (12%) patients. At the time of EEG, 32 (62%) patients were in the mild condition group and 20 (38%) patients were in the severe condition group. After 1 year of follow-up, there were 45 (86%) patients in the good prognosis group and 7 (14%) patients in the poor prognosis group. The exacerbation of EEG background abnormalities and the presence of δ brush were indications for an increase in the proportion of patients who were in severe condition, who needed ICU admission, and who had poor prognosis ( P<0.01). The worse the EEG background abnormalities, the higher the proportion of CSF antibody titers>1∶10 ( P=0.035), and the higher the proportion of patients initiating second-line immunotherapy ( P=0.008). The δ brush was seen a higher proportion in patients with comorbid tumors ( P=0.012). The probability of δ brush presence was higher in the first-time diagnosis cases than that in recurrent cases ( P=0.023). Conclusions: The degree of EEG slowing and the presence of δ brush have shown consistent performance in assessing patients' condition and predicting prognosis. The slower the EEG, the more severe the disease, and the worse the prognosis. The presence of δ brush indicates severe disease and poor prognosis. EEG slowing is correlated with the immune status of patients with anti-NMDARE. The slower the EEG, the more severe the immune abnormalities. In clinical practice, patient EEG should be under dynamic monitoring in order to evaluate the effect of immunotherapy. If EEG slowing is not improved, enhanced immunotherapy should be considered as early as possible. The δ brush is seen at a higher proportion in patients with comorbid tumors. Therefore, active efforts should be made to screen for tumors when δ brush is present.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Eletroencefalografia/métodos , Hospitalização
4.
Gut ; 71(2): 322-332, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33632712

RESUMO

OBJECTIVE: The systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing. DESIGN: Whole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells. RESULTS: Based on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations in ZFP36L2, which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout of ZFP36L2 enhances the metastatic potential of CRC cells. CONCLUSION: Our results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Mutação/genética , Fatores de Transcrição/genética , China , Estudos de Coortes , Evolução Molecular , Humanos , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Modelos Genéticos , Sequenciamento do Exoma
5.
J Nutr ; 152(6): 1549-1559, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35278080

RESUMO

BACKGROUND: Telomere length (TL) serves as a marker of cellular senescence and appears to plateau between the age of 4 y and young adulthood, after which the gut microbiota are supposed to be established. However, scarce data are available regarding the correlation between gut microbiota composition and TL in the pediatric population. OBJECTIVES: We aimed to investigate whether the gut microbiota and the concentrations of SCFAs in feces are associated with leukocyte TL in children. METHODS: In total, 401 children aged 6-9 y from Guangzhou were enrolled in this cross-sectional study. qPCR was used to determine relative TL in peripheral blood leukocytes. The gut microbiota was characterized by 16S ribosomal RNA amplicon sequencing and the fecal concentrations of total SCFAs and SCFA subtypes were determined using HPLC. The multivariate methods with an unbiased variable selection (MUVR) algorithm and partial least square models were used to select predictable operational taxonomic units (OTUs). Further correlation analyses were performed based on multiple linear regression models with adjustment for covariates and false discovery rate. RESULTS: With the use of MUVR, 35 relevant and minimal optimal OTUs were finally selected. Multiple linear regression analysis showed that the abundance of several OTUs, including OTU334 (belonging to the genus Family XIII AD3011 group), OTU726 (belonging to the species Lachnoclostridium phocaeense), OTU1441 (belonging to the genus Ruminococcus torques group), OTU2553 (belonging to the genus Lachnospiraceae UCG-010), and OTU3375 (belonging to the family Lachnospiraceae), was negatively associated with leukocyte TL (ß: -0.187 to -0.142; false discovery rate (FDR)-corrected P value (PFDR) = 0.009-0.035]. However, neither SCFA subtype nor total SCFA content in feces exhibited significant associations with TL (ß: -0.032 to 0.048; PFDR = 0.915-0.969). CONCLUSIONS: The gut microbiota, but not fecal SCFA concentration, was significantly associated with TL in this pediatric population.


Assuntos
Microbioma Gastrointestinal , Adulto , Criança , Estudos Transversais , Ácidos Graxos Voláteis/análise , Fezes/química , Microbioma Gastrointestinal/genética , Humanos , Leucócitos/química , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Telômero , Adulto Jovem
6.
J Cell Mol Med ; 24(10): 5555-5564, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32270599

RESUMO

The role of long non-coding RNAs (lncRNAs) in kidney diseases has been gradually discovered in recent years. LINC00963, as an lncRNA, was found to be involved in chronic renal failure. However, the role and molecular mechanisms of LINC00963 engaged in acute kidney injury (AKI) were still unclear. In this study, we established rat AKI models by ischaemia and reperfusion (I/R) treatment. Urea and creatinine levels were determined, and histological features of kidney tissues were examined following HE staining. CCK8 assay was chosen to assess the viability of hypoxia-induced HK-2 cells. Dual-luciferase reporter gene assays were performed to verify the target relationship between LINC00963 and microRNA. The mRNA and protein levels were assayed by RT-qPCR and Western blot, respectively. Annexin V-FITC/PI and TUNEL staining were used to evaluate apoptosis. LINC00963 was highly expressed in the cell and rat models, and miR-128-3p was predicted and then verified as a target gene of LINC00963. Knockdown of LINC00963 reduced acute renal injury both in vitro and in vivo. LINC00963 activated the JAK2/STAT1 pathway to aggravate renal I/R injury. LINC00963 could target miR-128-3p to reduce G1 arrest and apoptosis through JAK2/STAT1 pathway to promote the progression of AKI.


Assuntos
Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Janus Quinase 2/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT1/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose/genética , Linhagem Celular , Técnicas de Inativação de Genes , Masculino , Ratos
7.
Anal Chem ; 92(7): 5509-5516, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32188244

RESUMO

In this work, asymmetric nanochannel-ionchannel of porous anodic alumina (PAA) coupled with electrochemical detector was used for sensitive and label-free detection of cell surface glycan. The amplified ionic current caused by array nanochannels as well as the ionic current rectification (ICR) caused by asymmetric geometry endows PAA with sensitive ionic current response. Functionalized with the special molecular probe, the constructed nanofluidic device can be used for selective recognition and detection of glycan in a real-time and label-free format. In addition, due to the subnanosize of ionchannels, the probe immobilization and glycan recognition is carried out on the outer surface of PAA, avoiding the blockage of PAA nanochannel by samples, which promises the reproducibility and accuracy of the present method toward bioanalysis. Results show that the glycan concentration ranging from 10 fM to 10 nM can be successfully detected with a detection limit of ∼10 aM, which is substantially lower than most previous works. The designed strategy provides a valuable platform for sensitive and label-free detection of cell surface glycan, which acts as a promising candidate in pathological research and cancer diagnosis.


Assuntos
Limite de Detecção , Nanotecnologia/instrumentação , Polissacarídeos/análise , Eletroquímica , Propriedades de Superfície
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(3): 416-421, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32543153

RESUMO

OBJECTIVE: To study the association of glucose variability and ICU delirium of patients after liver transplantation. METHODS: This was a retrospective, single-center cohort study. Patients who admitted to ICU after liver transplantation during Aug. 2016 to Dec. 2018 were enrolled. They were divided into two groups accoding to whether they had delirium in ICU. Multivariate logistic regression analysis model was used to analyze the relationship between glucose variability and ICU delirium, and Cochran-Armitage trend test was used to analyze the linear relationship between blood glucose variability levels and the incidence of delirium. RESULTS: A total of 242 patients were enrolled, among them, 36 patients had delirium. The occurrence rate of delirium was 14.9% (36/242). Results indicated that glucose variability was an independently risk factor of ICU delirium for liver transplant patients ( P=0.045), and delirium was more common in patients with higher glucose variability (fourth quartile vs. first quartile, odds ratio =5.283, 95% confidence interval: 1.092~25.550, P=0.038). Results of Cochran-Armitage trend test indicated that there was a linear relationship between blood glucose variability level and ICU delirium rate, with the increase of glucose variability level, the risk of ICU delirium was increased too ( P<0.001). CONCLUSION: Glucose variability was an independently risk factor of ICU delirium in liver transplantation patients.


Assuntos
Glicemia , Delírio , Transplante de Fígado , Estudos de Coortes , Delírio/epidemiologia , Delírio/etiologia , Humanos , Unidades de Terapia Intensiva , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(2): 145-151, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31106530

RESUMO

OBJECTIVE: To test the killing effect of type Ⅰ receptor tyrosine kinase-like orphan receptor (ROR1) chimeric antigen receptor T cell (CAR-T) on several ROR1-expressing tumor cells in vitro. METHODS: The CAR gene was designed and synthesized by constructing the lentiviral vector plasmid, and BamHⅠ/EcoRⅠ was used to identify the plasmid. The expression levels of ROR1 among a variety of tumor cell lines were compared using flow cytometry (FCM). The killing effect of CAR-T on positive cells was detected by FCM, the LDH assay and ELISA. RESULTS: The double enzyme digestion identified CAR gene was successfully constructed to the lentivirus vector plasmid. FCM detection showed that the efficiency of CAR-T infection was about 47.23%. Multiple tumor cells expressed ROR1 in varying degrees. The FCM and the LDH assay indicated that CAR-T specifically killed ROR1-positive tumor cells. On positive target cells, more interferonI-γ (FN-γ) could be released during the CAR-T killing process than control T (P<0.05). CONCLUSION: We successfully constructed ROR1 CAR-T. CAR-T can specifically kill ROR1-positive tumor cells and cause the release of large amounts of IFN-γ, providing an experimental basis for clinical application.


Assuntos
Imunoterapia Adotiva , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/imunologia , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos , Linfócitos T/citologia , Linhagem Celular Tumoral , Humanos , Lentivirus
10.
Langmuir ; 34(26): 7859-7868, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29863877

RESUMO

Polymer/inorganic nanocomposites exhibit special properties due to highly intimate interactions between organic and inorganic phases and thus have been deployed for various applications. Among them, nanocomposites with monolayer polymer coverage on the inorganic surface demonstrate the highest efficiency for applications. However, the controllable synthesis of the polymer monolayer in mesopores of inorganic substrates remains a challenge. In this study, poly(acrylic acid)/γ-alumina nanocomposites (PAA/alumina) were synthesized via the in situ polymerization of acrylic acid impregnated in mesopores of alumina. By applying the preneutralization of monomers, the polymerization was found to be highly controllable in generating monolayer PAA coverage. The formation of monolayers was verified by thermogravimetry, semiquantitative Fourier transform infrared spectroscopy, N2 adsorption-desorption, and Pb(II) adsorption. Alternatively, the organic loadings of PAA/alumina composite samples could be controlled in the range of 0.2 to 1.0 equiv of monolayer, together with the linearly correlated metal ion adsorption capacity. As calculated by the complexation model, one Pb(II) is combined with two carboxylate groups of PAA. The formation of the monolayer polymer inside mesoporous oxide channels represents a method for the development of highly promising functional nanocomposites.

11.
BMC Gastroenterol ; 18(1): 119, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053840

RESUMO

BACKGROUND: Stress is a common contributing factor for irritable bowel syndrome (IBS). This study was to evaluate the efficacy of the centralized health education program in improving the quality of life (QOL) of middle school students with IBS who experienced the Wenchuan earthquake on May 12, 2008. METHODS: A multi-center, randomized and open evaluation study design was adopted. A total of 584 students who met the Rome III criteria for IBS in four middle schools were identified. Of these students, 29 were excluded for various reasons, and the remaining 555 students were randomly assigned to either the health education group (n = 277) or the control group (n = 278, received no health education). De-identified data were collected via the IBS quality of life (IBS-QOL) questionnaire and abdominal pain was assessed during the 5-year follow-up survey. RESULTS: The IBS-QOL mean total score was comparable at baseline between no-education group and education group no matter in quake-unaffected areas or quake-affected areas (52.27 vs 51.43, t = 1.15, P > 0.05; 51.02 vs 50.64, t = 1.98, P > 0.05). During the 5-year study period, 84 students opted out during follow-up. After 5 years, a significant difference of the IBS-QOL mean total score was observed between the no-education group and education group in quake-unaffected areas (80.53 vs 93.67, t = - 55.45, P < 0.01), which was also observed in quake-affected areas (64.23 vs 93.80, t = - 188.10, P < 0.01). In addition, there was a reciprocal action between factor 1(health education or not) and factor 2(affected by the earthquake or not) regarding IBS-QOL for dysphoria(Q1), interference with activity(Q2), food avoidance(Q5) and relationships(Q8)(P < 0.001) at year 1, 3 and 5. In all students, abdominal pain scores gradually reduced from baseline in each subgroup over 5 years (P < 0.001).The improvement was greater in the education group than in the control group no matter in quake-unaffected area and in quake-affected areas(P < 0.001). There was a reciprocal action between factor 1(health education or not) and factor 2(duration of follow-up) regarding the mean abdominal pain symptom score irrespective of quake-unaffected or quake-affected areas (P = 0.029 and P < 0.001). CONCLUSION: The health education program improved quality of life and abdominal pain in middle school IBS students in Wenchuan quake-affected areas.


Assuntos
Terremotos , Educação em Saúde , Síndrome do Intestino Irritável/psicologia , Qualidade de Vida , Estresse Psicológico , Dor Abdominal/psicologia , Adolescente , China , Feminino , Seguimentos , Humanos , Masculino
12.
Chin J Traumatol ; 21(6): 323-328, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30591258

RESUMO

PURPOSE: Early application of protease inhibitors through the intestinal lumen could increase survival following experimental shock by blocking the pancreatic digestive enzymes. Hence, it was hypothesized that two-route injection (intraintestinal + intravenous) of ulinastatin (UTI), a broad-spectrum protease inhibitor, could better alleviate intestinal injury than single-route injection (either intravenous or intraintestinal). METHODS: A sepsis model induced by lipopolysaccharide on rats was established. The rats were randomly divided into five groups: sham, sepsis, UTI intravenous injection (Uiv), UTI intraintestinal injection (Uii), and UTI intraintestinal + intravenous injection (Uii + Uiv) groups. The mucosal barrier function, enzyme-blocking effect, levels of systemic inflammatory cytokines, and 5-day survival rate were compared among groups. The small intestinal villus height (VH), crypt depth (CD), and two components of mucosal barrier (E-cadherin and mucin-2) were measured to evaluate the mucosal barrier function. The levels of trypsin and neutrophil elastase (NE) in the intestine, serum, and vital organs were measured to determine the enzyme-blocking effect. RESULTS: Compared with the single-route injection group (Uiv or Uii), the two-route injection (Uii + Uiv) group displayed: (1) significantly higher levels of VH, VH/CD, E-cadherin, and mucin-2; (2) decreased trypsin and NE levels in intestine, plasma, and vital organs; (3) reduced systemic inflammatory cytokine levels; and (4) improved survival of septic rats. CONCLUSION: Two-route UTI injection was superior to single-route injection in terms of alleviating intestinal injury, which might be explained by extensive blockade of proteases through different ways.


Assuntos
Glicoproteínas/administração & dosagem , Enteropatias/tratamento farmacológico , Enteropatias/etiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Sepse/complicações , Inibidores da Tripsina/administração & dosagem , Inibidores da Tripsina/farmacologia , Animais , Caderinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Glicoproteínas/farmacologia , Mediadores da Inflamação/metabolismo , Injeções Intralesionais , Injeções Intravenosas , Enteropatias/metabolismo , Intestinos , Elastase de Leucócito/metabolismo , Masculino , Mucina-2/metabolismo , Ratos Wistar , Tripsina/metabolismo
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(1): 140-144, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29737106

RESUMO

OBJECTIVE: To explore the predictors of long-term mortality and healthy related quality of life (HR-QoL) for elderly patients with sepsis. METHODS: Two hundred and thirty-eight septic patients older than 60 years old admitted to intensive care unit (ICU) were enrolled in the study,and were followed up by telephone interview one year after ICU discharge. The hospital mortality and cumulative one-year mortality were analyzed,single and multiple factors analysis were used to for the risk factors of 1-year mortality. Quality of life (QoL) was evaluated by the Euro QoL-5 Dimensions (EQ5D) questionnaire,and the influential factors of long-term QoL were also analyzed. RESULTS: A total of 238 patients were enrolled,58 patients of them(24.4%) died during hospitalization and one-year accumulative mortality was 59.7% (142 cases). Single factor analysis showed that acute physiology and chronic health evaluation (APACHE Ⅱ),continuous renal replacement therapy (CRRT),fungal infection,sepsis,tracheal extubation and use of vasopressor within 24 h,the length of mechanical ventilation were correlated with one-year mortality. Multivariate regression analysis showed that APACHE Ⅱscore,CRRT and fungal infection were independent risk factors for one-year mortality,while tracheal extubation within 24 h and shorter length of ICU stay were related to better quality of life. CONCLUSION: One-year mortality of elderly patients with sepsis was high. Tracheal extubation in 24 h and length of hospital stay were predictor of long-term QoL.


Assuntos
Qualidade de Vida , Sepse/mortalidade , APACHE , Idoso , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Pessoa de Meia-Idade , Fatores de Risco
14.
Acta Pharmacol Sin ; 38(7): 1038-1047, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28414200

RESUMO

Over half of patients with BRCA1-deficient cancers do not respond to treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. In this study, we report that a combination of 53BP1 and BRCA1 may serve as a biomarker of PARP inhibitor sensitivity. Based on the mRNA levels of four homologous recombination repair (HR) genes and PARP inhibitor sensitivity, we selected BRCA1-deficient MDA-MB-436 cells to conduct RNA interference. Reducing expression of 53BP1, but not the other three HR genes, was found to lower simmiparib sensitivity. Additionally, we generated 53BP1-/-/BRCA1-/- clonal variants by the transcription activator-like effector nuclease (TALEN) technique and found that depleting 53BP1 impaired PARP inhibitor sensitivity with a 36.7-fold increase in their IC50 values. Consistent with its effect on PARP inhibitor sensitivity, 53BP1 loss alleviated cell cycle arrest and apoptosis and partially restored HR function. Importantly, 53BP1 depletion dramatically reduced the ability of PARP inhibitors to suppress tumor growth in vivo. The inhibition rate of simmiparib was 74.16% for BRCA1-deficient MDA-MB-436 xenografts, but only 7.79% for 53BP1/BRCA1-deficient xenografts. Re-expressing 53BP1 in the dual-deficient cells restored PARP inhibitor sensitivity and the levels of HR regulators. Considering that at least 10% of BRCA1-deficient breast and ovarian cancers have reduced expression of 53BP1, using a combination of 53BP1 with BRCA1 as a biomarker for patient selection should reduce the number of patients undergoing futile treatment with PARP inhibitors.


Assuntos
Antineoplásicos/farmacologia , Proteína BRCA1/antagonistas & inibidores , Biomarcadores Tumorais/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/antagonistas & inibidores , Animais , Antineoplásicos/química , Proteína BRCA1/deficiência , Proteína BRCA1/metabolismo , Biomarcadores Tumorais/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/química , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Relação Estrutura-Atividade , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/deficiência , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
15.
J Med Virol ; 88(5): 871-6, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26455510

RESUMO

In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis.


Assuntos
Herpesvirus Humano 4/genética , Mononucleose Infecciosa/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adolescente , Adulto , Criança , Pré-Escolar , DNA Viral/análise , DNA Viral/genética , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Lactente , Masculino , Sensibilidade e Especificidade , Carga Viral/métodos , Adulto Jovem
16.
Prep Biochem Biotechnol ; 46(4): 399-405, 2016 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-26176886

RESUMO

Strains of Leuconostoc mesenteroides, Pediococcus pentosaceus, and Lactobacillus brevis were identified from mango fruits by partial 16S rDNA gene sequence. Based on the ability of producing mannitol and diacetyl, Leuconostoc mesenteroides MPL18 and MPL39 were selected within the lactic acid bacteria isolates, and used as mixed starters to ferment mango juice (MJ). Both the autochthonous strains grew well in fermented mango juice (FMJ) and remained viable at 9.81 log cfu mL(-1) during 30 days of storage at 4°C. The content of total sugar of FMJ was lower than that of MJ, while the concentration of mannitol was higher than that of MJ, and the concentration of diacetyl was 3.29 ± 0.12 mg L(-1). Among detected organic acids including citric acid, gallic acid, lactic acid, and acetic acid, only citric acid and gallic acid were found in MJ, while all detected organic acids were found in FMJ. The concentration of lactic acid of FMJ was the highest (78.62 ± 13.66 mM) among all detected organic acids. The DPPH radical scavenging capacity of FMJ was higher than that of MJ. Total phenolic compounds were better preserved in FMJ. The acidity and sweetness had a noticeable impact on the overall acceptance of the treated sample.


Assuntos
Fermentação , Lactobacillaceae/metabolismo , Mangifera/metabolismo , Probióticos , Genótipo , Lactobacillaceae/genética , Filogenia
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(4): 570-573, 2016 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28591964

RESUMO

Sepsis is a critical clinical syndrome which keep puzzling the medical profession for many years. Recently, the results from several large-scale trials challenged the necessity of early goal directed therapy (EGDT) in surviving sepsis bundle, These trials were not opposed to EGDT but bring new concept that it is essential to utilize therapy with multiple monitoring measures in order to minimize injury while guarantee the safety . Deeper understanding in the pathogenesis of sepsis gives rise to the update of its definition based on vital organ dysfunction. The importance of dynamic monitoring in defining sepsis also need to be emphasized. Developing more effective monitoring measures could provide better treatments, thus improve the prognosis of septic patients.


Assuntos
Sepse/mortalidade , Terapia Precoce Guiada por Metas , Humanos , Prognóstico , Análise de Sobrevida
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(4): 589-593, 2016 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28591968

RESUMO

OBJECTIVES: To determine risk factors associated with mortality of patients with sepsis complicated with active tuberculosis (TB) in intensive care units (ICU). METHODS: We reviewed medical records of 61 TB patients whom were admitted to the ICU in West China Hospital of Sichuan University, among whom 19 were dead. Logistic regression models were established to determine predictors of mortality. RESULTS: The acute physiology and chronic health evaluation (APACHE Ⅱ) score, smear-positive sputum, delayed treatment of active TB and acute kidney dysfunction were independent predictors of mortality. CONCLUSIONS: Mortality of patients with sepsis complicated with active tuberculosis is high. APACHE Ⅱ score, smear-positive sputum, delayed treatment of active TB and acute kidney dysfunction are independent predictors of mortality.


Assuntos
Sepse/mortalidade , Tuberculose/mortalidade , China , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sepse/complicações , Tuberculose/complicações
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(4): 594-598, 2016 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28591969

RESUMO

OBJECTIVES: To explore the characteristics and prognostic factors associated with the death of systemic lupus erythematosus (SLE) with sepsis in intensive care unit(ICU). METHODS: Clinical and laboratory documents of SLE patients with sepsis from Jan 2010 to Dec 2014 were retrospectively analyzed, including active organ involvement, systemic lupus erythematosus disease activity index (SLEDAI) score, acute physiology and chronic health evaluation (APACHE) Ⅱ score, sites of infection and organisms cultured. Prognostic factors were analyzed by multivariate logistic regression analysis. RESULTS: Included patients were mainly females (86%, 43/50). For all patients, SLEDAI was 15.8±6.3; APACHE Ⅱ was 25.8±6.5; the mortality rate during ICU hospitalization was 46%. The most common causes of death and admission were multiple organ dysfunction syndrome and respiratory failure, respectively. The most common pathogen was Gram-negative bacteria.Multivariate logistic regression analysis suggested that gastrointestinal bleeding, septic shock and high APACHE Ⅱ score were independent risks for mortality. CONCLUSIONS: Gastrointestinal bleeding, septic shock and high APACHE Ⅱ score were risk factors in SLE patients with sepsis in ICU.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Sepse/complicações , APACHE , Antracenos , Feminino , Hemorragia Gastrointestinal/complicações , Humanos , Unidades de Terapia Intensiva , Lúpus Eritematoso Sistêmico/complicações , Masculino , Prognóstico , Estudos Retrospectivos , Choque Séptico/complicações
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(4): 574-579, 2016 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28591965

RESUMO

OBJECTIVES: To determine the predictive value of early changes in sublingual microcirculation on organ failure of patients with septic shock. METHODS: Side-streamdark field imaging (SDF) videomicroscopy was performed to assess sublingual microcirculation of 34 adult patients at 0 h, 6 h and 24 h after they were diagnosed with septic shock.The patients were subject to sequential organ failure assessment (SOFA24 h-0 h). The patients with ΔSOFA24 h-0 h≥1 (deteriorated conditions) were compared with those with ΔSOFA24 h-0 h<1 in regard to sublingual microcirculation and the traditional hemodynamic indicators such as heart rate, mean arterial pressure, central venous pressure, urine output and lactate. RESULTS: No significant baseline differences were found between the two groups of patients in age, sex and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ), nor any differences in the traditional hemodynamic indicators, as well as dose of vasopressor, infusion of crystalloids, and colloids after septic shock was diagnosed. The patients with deteriorated conditions had lower proportion of perfused small vessels (PPVs) compared with the non-deteriorated patients at 0 h [(75.96±10.55)% vs.(84.03±10.16)%, P=0.032] and 24 h [(79.43±9.23)% vs.(86.32±9.02)%, P=0.037]. The ROC analysis showed a greater area under the curve (AUC) for PPVs at 0 h [0.750 (95%CI, 0.586-0.914)] compared with the AUC for Lac at 0 h [0.588 (95%CI, 0.370-0.805) ], albeit a lack of statistical significance ( P>0.05). The incidence of organ failure in the patients with a lower than optimal cut-off point (81.5%) of PPVs was significantly higher than that of those above the cut-off point (71.4% vs. 20.0%). CONCLUSIONS: Changes in sublingual microcirculation (e.g. PPVs) can predict the development of organ failure earlier than systemic hemodynamic indicators in patients with septic shock.


Assuntos
Microcirculação , Soalho Bucal/irrigação sanguínea , Insuficiência de Múltiplos Órgãos/diagnóstico , Choque Séptico/diagnóstico , Adulto , Frequência Cardíaca , Hemodinâmica , Humanos , Valor Preditivo dos Testes
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa