RESUMO
BACKGROUND AND AIM: Healthcare-associated infections (HAIs) after pancreaticoduodenectomy (PD) are one of the common postoperative complications. This study aims to investigate the epidemiology of postoperative HAIs in patients with open pancreaticoduodenectomy (OPD) and robotic pancreaticoduodenectomy (RPD). METHODS: This retrospective cohort study described the trend of HAIs in patients undergoing PD from January 2013 to December 2022 at a tertiary hospital. Patients were divided into OPD and RPD, and the HAIs and outcomes were compared. RESULTS: Among 2632 patients who underwent PD, 230 (8.7%, 95% confidence interval [CI] 7.7-9.9%) were diagnosed with HAIs, with a decreasing trend from 2013 to 2022 (P < 0.001 for trend). The incidence of postoperative HAIs was significantly higher in patients with OPD than RPD (9.6% vs 5.8%; P = 0.003). The incidence of HAIs for patients with OPD showed a decreasing trend (P = 0.001 for trend), and the trend for RPD was not significant (P = 0.554 for trend). Logistic regression showed that RPD was significantly associated with postoperative HAIs after adjusting for covariates (adjusted odds ratio = 0.654; 95% CI 0.443-0.965; P = 0.032), especially in the subgroup of patients without preoperative biliary drainage (adjusted odds ratio = 0.486; 95% CI 0.292-0.809; P = 0.006). Regarding clinical outcomes, RPD has a shorter length of stay and a more expensive charge than OPD (all P < 0.05). CONCLUSION: Postoperative HAIs in patients with PD showed a decreasing trend in recent years, especially in OPD. RPD was significantly associated with reduced postoperative HAIs and length of stay, although the charge is more expensive. Attention should be paid to postoperative HAIs in OPD, and it is imperative to continue reducing the costs of RPD.
Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Estudos Retrospectivos , Pancreaticoduodenectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Tempo de Internação , Complicações Pós-Operatórias/etiologia , Atenção à SaúdeRESUMO
BACKGROUND: Ferritin is one of the key proteins that regulate iron homeostasis and is widely available clinical biomarker of iron status. This study aimed to discuss the influence of serum ferritin (SF) on cardiovascular risk factors in the first-degree relatives with family history of type 2 diabetes (FHD). METHODS: This cross-sectional study included 232 men. Anthropometric measurements and blood samples were analyzed. The people were divided into four groups according to median SF (102.8 ng/ml) and people with or without FHD. Group A (FHD-and low SF), group B (FHD-and high SF), group C (FHD+ and low SF), and group D (FHD+ and high SF). RESULTS: The subjects in different categories of SF concentrations showed significant differences in BMI (SF main effect: P = 0.010), WC (P = 0.030), SBP (P < 0.001), FPG (P < 0.001), PPG-2 h (P < 0.001), FINS (P < 0.001), and HOMA-IR (P = 0.015; all: 2-way ANOVA). There was a significant difference in SBP (FHD main effect: P = 0.003), DBP (P = 0.006), and FINS (P = 0.013, all: 2-way ANOVA) between the groups with or without FHD. The interaction term between SF and FHD was significant for SBP (P = 0.011), DBP (P = 0.012), and PPG-2 h (P = 0.022). Logistic analysis showed that accumulation of CVD risk factors, which were ≥ 2 items and ≥ 3 items in group D were 7.546 and 3.343 times higher compared with group A (P < 0.05). CONCLUSIONS: The increased SF levels increased the risk of cardiovascular risk factors and the occurrence of insulin resistance in first-degree relatives with FHD.
Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Família , Ferritinas/sangue , Resistência à Insulina , Síndrome Metabólica/sangue , Adulto , Povo Asiático/genética , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/genética , China/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Família/etnologia , Predisposição Genética para Doença , Hereditariedade , Humanos , Resistência à Insulina/etnologia , Resistência à Insulina/genética , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etnologia , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Linhagem , Prognóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais , Regulação para CimaRESUMO
BACKGROUND: The aim of this study was to evaluate serum irisin levels and analyze its related factors in Han adults with metabolically healthy obesity. METHODS: This cross-sectional study included 75 metabolically healthy, non-obese adults and 51 metabolically healthy, obese adults. Anthropometric measurements, including height, weight, waist circumference (WC), and blood pressure, were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 hours of fasting, and the levels of glucose, insulin, lipids, and serum irisin were measured. RESULTS: The levels of serum irisin (5.40 ± 1.69 vs. 6.46 ± 1.37 µg/mL) were significantly lower in the metabolically healthy obese group (p < 0.05). Irisin correlated positively with high density lipoprotein cholesterol (HDL-C) (r = 0.303) and correlated negatively with body mass index (BMI) (r = -0.389), WC (r = -0.324), fasting plasma glucose (FPG) (r = -0.441), HOMA-IR (r = -0.429), triglycerides (TG) (r = -0.185), total cholesterol (TC) (r = -0.209), low density lipoprotein cholesterol (LDL-C) (r = -0.157) (p < 0.05). Multiple regression analysis revealed that FPG (ß = -1.720, p = 0.001) and HOMA-IR (ß = -0.399, p = 0.006) were still significantly associated with irisin. Serum irisin (ß = -0.246, p = 0.005) and BMI (ß = 0.078, p = 0.043) were significant independent predictors for HOMAIR. CONCLUSIONS: Serum irisin levels were reduced in metabolically healthy, obese Han adults. Irisin reduction appears to be associated with elevated FPG and insulin resistance but not obesity. In additional, falling irisin may increase the occurrence of insulin resistance in metabolically healthy Han adults and should be examined in future studies.
Assuntos
Fibronectinas/sangue , Resistência à Insulina , Obesidade Metabolicamente Benigna , Adulto , Glicemia , Índice de Massa Corporal , Estudos Transversais , Humanos , Insulina , ObesidadeRESUMO
Background: Apolipoprotein (Apo) may be associated with sarcopenia in elderly inpatients with type 2 diabetes mellitus (T2DM), but fewer studies are available. In this study, we explored the association of ApoA1, ApoB, and ApoB/ApoA1 with sarcopenia and compared the predictive role of Apo indicators for sarcopenia in an elderly T2DM. Objective: To investigate the relationships between the Apo and sarcopenia in elderly inpatients with T2DM. Methods: This study included 253 inpatients with T2DM (mean age of 70.11±5.44 years, 32.8% male). The inpatients were divided into the sarcopenic group (n = 100) and non-sarcopenic group (n = 153). The associations among the Apo and sarcopenia were assessed using multivariate analyses. Results: Inpatients in the sarcopenia group showed lower ApoA1 levels than those in the non-sarcopenia group (1.25±0.21 vs 1.36±0.20 g/L, P < 0.05) and showed higher ApoB/ApoA1 and ApoB levels than those in the non-sarcopenia group (0.82±0.27 vs 0.69±0.19 g/L, P < 0.05;1.00±0.32 vs 0.93±0.24 g/L, P < 0.05, respectively). After adjusting for age and BMI, the logistic regression model indicated that ApoA1 was a protective factor for elderly inpatients with T2DM sarcopenia.(OR =0.079,95% CI: 0.021~0.306, P < 0.05);ApoB and AopB/AopA1 were risk factors for elderly inpatients with T2DM sarcopenia.(OR =3.578,95% CI:1.318~9.715, P < 0.05;OR =16.440,95% CI:4.437~60.427, P < 0.05, respectively). AopB/AopA1 provided an AUC value of 0.765 in elderly men.(95% CI: 0.665~0.866, P<0.05). Conclusion: ApoA1, AopB, and AopB/AopA1 are associated with sarcopenia in elderly inpatients with T2DM, and AopB/AopA1 may be a potential predictor of sarcopenia in elderly men with T2DM.
RESUMO
Background: There is increasing evidence that immunotherapy (programmed cell death-1 (PD-1) inhibitor) combined with chemotherapy is superior to chemotherapy alone in neoadjuvant therapy for patients with previously untreated, unresectable advanced, or metastatic esophageal adenocarcinoma (EAC)/gastric/gastroesophageal junction adenocarcinoma (GEA). However, the results of recent studies have been contradictory. Therefore, the aim of this article is to evaluate the efficacy and safety of PD-1 inhibitors combined with chemotherapy in neoadjuvant therapy through meta-analysis. Method: We comprehensively reviewed the literature and clinical randomized controlled trials (RCTs) by February 2022 by searching Medical Subject Headings (MeSH) and keywords such as "esophageal adenocarcinoma" or "immunotherapy" in several databases, including the Embase, Cochrane, PubMed, and ClinicalTrials.gov websites. Two authors independently selected studies, extracted data, and assessed the risk of bias and quality of evidence by using standardized Cochrane Methods procedures. The primary outcomes were 1-year overall survival (OS) and 1-year progression-free survival (PFS), estimated by calculating the 95% confidence interval (CI) for the combined odds ratio (OR) and hazard ratio (HR). Secondary outcomes estimated using OR were disease objective response rate (DORR) and incidence of adverse events. Results: Four RCTs with a total of 3,013 patients researching the efficacy of immunotherapy plus chemotherapy versus chemotherapy alone on gastrointestinal cancer were included in this meta-analysis. The results showed that immune checkpoint inhibitor plus chemotherapy treatment was associated with an increased risk of PFS (HR = 0.76 [95% CI: 0.70-0.83]; p < 0.001), OS (HR = 0.81 [95% CI: 0.74-0.89]; p < 0.001), and DORR (relative ratio (RR) = 1.31 [95% CI: 1.19-1.44]; p < 0.0001) when compared with chemotherapy alone in advanced, unresectable, and metastatic EAC/GEA. However, immunotherapy combined with chemotherapy increased the incidence of adverse reactions such as alanine aminotransferase elevation (OR = 1.55 [95% CI: 1.17-2.07]; p = 0.003) and palmar-plantar erythrodysesthesia (PPE) syndrome (OR = 1.30 [95% CI: 1.05-1.63]; p = 0.02). Nausea (OR = 1.24 [95% CI: 1.07-1.44]; p = 0.005) and white blood cell count decreased (OR = 1.40 [95% CI: 1.13-1.73]; p = 0.002), and so on. Fortunately, toxicities were within acceptable limits. Meanwhile, for patients with a combined positive score (CPS) ≥1, compared with chemotherapy alone, immunotherapy combined with chemotherapy had a better overall survival rate (HR = 0.81 [95% CI: 0.73-0.90]; p = 0.0001). Conclusion: Our study shows that immunotherapy plus chemotherapy has an obvious benefit for patients with previously untreated, unresectable advanced, or metastatic EAC/GEA when compared with chemotherapy alone. However, a high risk of adverse reactions may occur during immunotherapy plus chemotherapy, and more studies focusing on the treatment strategies of untreated, unresectable advanced, or metastatic EAC/GEA are warranted. Systematic review registration: www.crd.york.ac.uk, identifier CRD42022319434.
RESUMO
BACKGROUND: Obesity is associated with a better prognosis in patients with community-acquired pneumonia (the so-called obesity survival paradox), but conflicting results have been found. AIM: To investigate the relationship between all-cause mortality and body mass index in patients with community-acquired pneumonia. METHODS: This retrospective study included patients with community-acquired pneumonia hospitalized in the First Hospital of Qinhuangdao from June 2013 to November 2018. The patients were grouped as underweight (< 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), and overweight/obesity (≥ 24 kg/m2). The primary outcome was all-cause hospital mortality. RESULTS: Among 2327 patients, 297 (12.8%) were underweight, 1013 (43.5%) normal weight, and 1017 (43.7%) overweight/obesity. The all-cause hospital mortality was 4.6% (106/2327). Mortality was lowest in the overweight/obesity group and highest in the underweight group (2.8%, vs 5.0%, vs 9.1%, P < 0.001). All-cause mortality of overweight/obesity patients was lower than normal-weight patients [odds ratio (OR) = 0.535, 95% confidence interval (CI) = 0.334-0.855, P = 0.009], while the all-cause mortality of underweight patients was higher than that of normal-weight patients (OR = 1.886, 95%CI: 1.161-3.066, P = 0.010). Multivariable analysis showed that abnormal neutrophil counts (OR = 2.38, 95%CI: 1.55-3.65, P < 0.001), abnormal albumin levels (OR = 0.20, 95%CI: 0.06-0.72, P = 0.014), high-risk Confusion-Urea-Respiration-Blood pressure-65 score (OR = 2.89, 95%CI: 1.48-5.64, P = 0.002), and intensive care unit admission (OR = 3.11, 95%CI: 1.77-5.49, P < 0.001) were independently associated with mortality. CONCLUSION: All-cause mortality of normal-weight patients was higher than overweight/ obesity patients, lower than that of underweight patients. Neutrophil counts, albumin levels, Confusion-Urea-Respiration-Blood pressure-65 score, and intensive care unit admission were independently associated with mortality in patients with community-acquired pneumonia.
RESUMO
Background: The effect of chronic psychological stress on hepatitis and liver fibrosis is concerned. However, its mechanism remains unclear. We investigated the effect and mechanism of chronic psychological stress in promoting liver injury and fibrosis through gut. Methods: Sixty male SD rats were randomly assigned to 6 groups. Rat models of chronic psychological stress (4 weeks) and liver fibrosis (8 weeks) were established. The diversity of gut microbiota in intestinal feces, permeability of intestinal mucosa, pathologies of intestinal and liver tissues, collagen fibers, protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa ß (NF-κß), tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) in liver tissue, liver function and coagulation function in blood and lipopolysaccharide (LPS) in portal vein blood were detected and analyzed. Results: The diversities and abundances of gut microbiota were significant differences in rats among each group. The pathological lesions of intestinal and liver tissues, decreased expression of occludin protein in intestinal mucosa, deposition of collagen fibers and increased protein expression of TLR4, MyD88, NF-κß, TNF-α and IL-1 in liver tissue, increased LPS level in portal vein blood, and abnormalities of liver function and coagulation function, were observed in rats exposed to chronic psychological stress or liver fibrosis. There were significant differences with normal rats. When the dual intervention factors of chronic psychological stress and liver fibrosis were superimposed, the above indicators were further aggravated. Conclusion: Chronic psychological stress promotes liver injury and fibrosis, depending on changes in the diversity of gut microbiota and increased intestinal permeability caused by psychological stress, LPS that enters liver and acts on TLR4, and active LPS-TLR4 pathway depend on MyD88. It demonstrates the possibility of existence of brain-gut-liver axis.
Assuntos
Lipopolissacarídeos , Receptor 4 Toll-Like , Ratos , Masculino , Animais , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , Fator 88 de Diferenciação Mieloide/metabolismo , Ratos Sprague-Dawley , NF-kappa B/metabolismo , Cirrose Hepática , Interleucina-1/metabolismo , Interleucina-1/farmacologia , Colágeno/metabolismo , Encéfalo/metabolismoRESUMO
AIMS: Scientific evidence imply the strong correlation between diabetes and breast cancer. Glucagon-like peptide-1 (GLP-1) and its analogue liraglutide, have been widely used for diabetes treatment. However, the role of GLP-1 receptor (GLP-1R) in breast cancer requires further elucidation. This study aimed to investigate the risk and the molecular mechanisms of liraglutide using in breast cancer. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction, western blot or immunohistochemistry were used to detect the expressions of GLP-1R, NADPH oxidase 4 (NOX4) and vascular endothelial growth factor (VEGF) in human triple negative breast cancer (TNBC) cells (MDA-MB-231 and MDA-MB-468) and tissues derived from BALB/cfC3H mouse bearing 4T1 cells inoculation. Cell proliferation and migration was detected using the Cell Counting Kit-8, adenosine triphosphate assay, and transwell assay, respectively. Flow cytometry was used to measure the level of reactive oxygen species (ROS). KEY FINDINGS: We found that the expression of GLP-1R increased after liraglutide treatment in breast cancer cells and the transplanted tumors. Liraglutide, at a slightly higher concentration, accelerated breast cancer progress in vitro (100 nM) and in vivo (400µg/kg) through the NOX4/ROS/VEGF signal pathway after activating GLP-1R. The GLP-1R inhibitor, Exendin (9-39), significantly inhibited the effect of liraglutide, inducing a reversed function of GLP-1R activation. SIGNIFICANCE: Our study illustrated that in an approximately toxicology context, liraglutide may promote the malignant progression of TNBC. The dosage and the phenotype of the breast cancer should be considered as important factors for the rational administration of antidiabetic drugs, especially that of liraglutide in breast cancer patients.
Assuntos
Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Liraglutida/toxicidade , NADPH Oxidase 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/metabolismo , Proliferação de Células , Feminino , Humanos , Hipoglicemiantes/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Nus , NADPH Oxidase 4/genética , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: The published evidence from several randomized controlled clinical trials of immunotherapy for advanced esophageal squamous cell carcinoma has shown promising results. This study aimed to investigate the efficacy and safety of immune checkpoint inhibitor treatment in esophageal squamous cell carcinoma. METHODS: PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published before December 30, 2020. The data for efficacy and safety of immune checkpoint inhibitor treatment were subjected to meta-analysis. RESULTS: Seven clinical trials comprising 1733 patients were included. The results showed that immune checkpoint inhibitor treatment as second- or later-line treatment was associated with an increased risk of the objective response rate (relative risk: 1.82, 95% confidence interval: 0.82-4.04; P=0.002) and median overall survival (hazard ratio: 0.75, 95% confidence interval: 0.67-0.85; P<0.001) compared with chemotherapy in locally advanced or metastatic esophageal squamous cell carcinoma. Moreover, immune checkpoint inhibitor treatment was associated with significant improvement in median overall survival (hazard ratio: 0.61, 95% confidence interval: 0.48-0.77, P<0.001) compared with chemotherapy in the programmed death-ligand 1 (PD-L1)-positive population. However, immune checkpoint inhibitor treatment was also effective in all patients independent of PD-L1 expression. The most common grade ≥3 treatment-related adverse events with immune checkpoint inhibitor therapy were anemia, asthenia, rash, fatigue, decreased appetite, diarrhea, pneumonia, decreased neutrophil count, and vomiting. Patients undergoing immune checkpoint inhibitor therapy was associated with a decreased risk of treatment-related adverse events (relative risk: 0.82, 95% confidence interval: 0.62-1.08; P<0.001) and grade ≥3 treatment-related adverse events (relative risk: 0.50, 95% confidence interval: 0.42-0.60; P<0.001) compared with those undergoing chemotherapy. CONCLUSIONS: Immune checkpoint inhibitors as second- or later-line therapy may improve overall response rate and overall survival but not all oncological outcomes for patients with locally advanced or metastatic esophageal squamous cell carcinoma. Patients treated with immune checkpoint inhibitors might experience fewer treatment-related adverse events of any grade, but specifically grade ≥3, compared with those treated with chemotherapy.
RESUMO
BACKGROUND & AIMS: N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous tetrapeptide which has antifibrogenic effects at physiological concentrations in various tissues. AcSDKP is produced locally in the liver, however, little is known about its biological effect in this organ. We hypothesize that basal levels of endogenous AcSDKP decrease during the development of liver fibrosis and preservation of basal AcSDKP attenuates liver fibrosis. METHODS: Endogenous levels of AcSDKP in the liver were measured by enzyme immunoassay after 2, 6, and 10 weeks of carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. Subcutaneous osmotic pump infusion of vehicle or AcSDKP (800 microg/kg/day) was administered to CCl(4)-treated rats for 8 weeks to study the effect of exogenous AcSDKP on liver fibrosis. The effect of AcSDKP on profibrogenic properties of hepatic stellate cells was studied in vitro. RESULTS: Endogenous AcSDKP was significantly decreased in the liver of CCl(4)-treated rats. Chronic AcSDKP infusion preserved basal levels of AcSDKP and reduced liver injury, inflammation, fibrosis, and profibrogenic transforming growth factor-beta signaling. This was demonstrated by decreased aminotransferase serum levels, CD45 positive cells, collagen accumulation, alpha-smooth muscle actin positivity, transforming growth factor-beta1, phosphorylated Smad2/3 protein, increased bone morphogenetic protein-7, and phosphorylated Smad1/5/8. Further, AcSDKP exerts antifibrogenic effects on hepatic stellate cells (HSCs) by downregulation of HSC activation in vitro. CONCLUSIONS: Maintaining physiological levels of AcSDKP is critical in negatively regulating the development of fibrosis in chronic liver injury. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.
Assuntos
Intoxicação por Tetracloreto de Carbono/metabolismo , Cirrose Hepática Experimental/metabolismo , Oligopeptídeos/metabolismo , Actinas/metabolismo , Animais , Intoxicação por Tetracloreto de Carbono/patologia , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Colágeno/genética , Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Técnicas In Vitro , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , Cirrose Hepática Experimental/prevenção & controle , Masculino , Oligopeptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND/AIMS: To reveal the microRNA (miRNA) expression profile and related roles in rat HSCs during activation. METHODS: miRNA expression profiling was analyzed in quiescent and in culture-activated HSCs by microarray. The differentially expressed miRNAs, as verified by RT-PCR, were subjected to gene ontology (GO) analysis. Furthermore, the effects of miR-16 and miR-15b on the apoptosis of activated HSCs were investigated by Hoechst 33258, TUNEL staining and annexin-V/PI labeling flow cytometry. The underlying mechanism related to Bcl-2 and caspases was assessed. RESULTS: The upregulated and downregulated miRNAs in activated HSCs were 12 miRNAs and 9 miRNAs, respectively. The differential expression of miR-16, -15b, -122, -138, -143, and -140 was validated. High-enrichment GOs containing apoptosis-related targeted genes and miRNA-gene networks characterized by Bcl-2, which was targeted by the miR-15/16 family, uncovered the critical role of miR-16 and miR-15b in apoptosis. Restoring the intracellular miRNAs by miR-16 and miR-15b administration greatly reduced Bcl-2, and increased the expression of caspases 3, 8, and 9. Significantly elevated rates of apoptosis were then induced in activated HSCs. CONCLUSIONS: The activation of HSCs relate to 21 miRNAs. Among these, mir-15b and miR-16 may be essential for apoptosis by targeting Bcl-2 and the caspase signaling pathway.
Assuntos
Apoptose/fisiologia , Células Estreladas do Fígado/fisiologia , MicroRNAs/genética , Actinas/genética , Animais , Primers do DNA , Desmina/genética , Regulação para Baixo , Citometria de Fluxo , Células Estreladas do Fígado/citologia , Marcação In Situ das Extremidades Cortadas , Masculino , Análise em Microsséries , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para CimaRESUMO
OBJECTIVE: To explore effect of interleukin 10 (IL-10) gene-modified bone marrow-derived liver stem cells (BDLSCs) transplantation on hepatic inflammatory response and liver regeneration in rats with liver fibrosis. METHODS: 50 female Wistar rats were randomly divided into 4 groups: (1) control group: 10 rats were subcutaneously injected with olive oil for 8 weeks; (2) fibrosis groups: 16 rats were subcutaneously injected with carbon tetrachloride (CCl4) for 8 weeks to induce liver fibrosis; (3) BDLSC group: 12 rats were subcutaneously injected with CCl4 for 8 weeks, and were transplanted with 2 x 10(5) BDLSC at week 4; (4) BDLSC/IL-10 group: 12 rats were subcutaneously injected with CCl4 for 8 weeks, and were transplanted with 2 x 10(5) IL-10 gene-modified BDLSC at week 4. IL-10 and tumor necrosis factor alpha (TNFa) in liver tissues were detected by ELISA. HE stained liver tissues were observed under light microscope. The expression of hepatocyte growth factor (HGF) was quantified by real-time RT-PCR, and the expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry. RESULTS: The ratio of IL-10/TNFa in fibrosis group (0.05+/-0.01) was lower than that in control group (0.26+/-0.04) (P < 0.01). Transplantation of untreated BDLSCs did not improve the ratio (P > 0.05), however, transplantation of IL-10 modified BDLSCs improved the ratio significantly (P < 0.01). Severe inflammatory response and fibrosis were observed in fibrosis group. Inflammatory response was alleviated to some extent in the BDLSC group, and the histopathology of BDLSC/IL-10 group was not significantly different from that of the control group. Compared to the control group, the expression of HGF mRNA and PCNA protein was increased in the fibrosis group (P < 0.01). The expression of HGF and PCNA was further increased by BDLSCs or IL-10 modified BDLSCs transplantation. Compared to BDLSCs, IL-10 gene-modified BDLSCs were more potent to induce the expression of HGF and PCNA. CONCLUSION: Transplantation of IL-10 gene-modified BDLSCs can alleviate hepatic inflammatory response and promote liver regeneration in hepatic fibrosis rats.
Assuntos
Células da Medula Óssea/citologia , Interleucina-10/genética , Cirrose Hepática/terapia , Regeneração Hepática , Fígado/metabolismo , Transplante de Células-Tronco , Adenoviridae/genética , Animais , Proliferação de Células , Modelos Animais de Doenças , Feminino , Terapia Genética/métodos , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Imuno-Histoquímica , Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante de Células-Tronco/métodos , Transdução Genética , Fator de Necrose Tumoral alfa/metabolismoAssuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Excisão de Linfonodo , Prognóstico , Linfonodos/cirurgia , Linfonodos/patologia , Esofagectomia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
OBJECTIVE: To explore the best waist circumference (WC) cut-point for identifying cardiovascular risk factors among adolescents. METHODS: Human basic parameters were measured among 3986 adolescents aged 14 - 18 in Qinhuangdao. Receiver operator characteristic curve (ROC) analysis was employed to determine the optimal WC cut-point for detecting cardiovascular risk factors. RESULTS: The prevalence of the clustering of cardiovascular risk factors significantly increased after the WC was >or= 80th percentiles (77.0 - 79.0 cm for the boys and 70.0 - 72.5 cm for the girls). The age standardization detection rate was 24.9% in boys and 9.9% in girls. ROC analysis showed that the optimal WC cut-point was 80th percentiles, with the sensitivity of 84.3% and specificity of 85.9% in boys, and with sensitivity of 90.7% and specificity of 83.2% in girls. CONCLUSION: There is a significant correlation between WC and cardiovascular risk factors. The optimal WC cut-point for predicting the clustering of cardiovascular risk factors is the 80th percentile.
Assuntos
Doenças Cardiovasculares/epidemiologia , Relação Cintura-Quadril , Gordura Abdominal , Adolescente , Glicemia , Índice de Massa Corporal , Peso Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Curva ROC , Fatores de Risco , Circunferência da CinturaRESUMO
AIM: To explore the effectiveness for treating liver fibrosis by combined transplantation of bone marrow-derived endothelial progenitor cells (BM-EPCs) and bone marrow-derived hepatocyte stem cells (BDHSCs) from the liver fibrosis environment. METHODS: The liver fibrosis rat models were induced with carbon tetrachloride injections for 6 wk. BM-EPCs from rats with liver fibrosis were obtained by different rates of adherence and culture induction. BDHSCs from rats with liver fibrosis were isolated by magnetic bead cell sorting. Tracing analysis was conducted by labeling EPCs with PKH26 in vitro to show EPC location in the liver. Finally, BM-EPCs and/or BDHSCs transplantation into rats with liver fibrosis were performed to evaluate the effectiveness of BM-EPCs and/or BDHSCs on liver fibrosis. RESULTS: Normal functional BM-EPCs from liver fibrosis rats were successfully obtained. The co-expression level of CD133 and VEGFR2 was 63.9% ± 2.15%. Transplanted BM-EPCs were located primarily in/near hepatic sinusoids. The combined transplantation of BM-EPCs and BDHSCs promoted hepatic neovascularization, liver regeneration and liver function, and decreased collagen formation and liver fibrosis degree. The VEGF levels were increased in the BM-EPCs (707.10 ± 54.32) and BM-EPCs/BDHSCs group (615.42 ± 42.96), compared with those in the model group and BDHSCs group (P < 0.05). Combination of BM-EPCs/BDHSCs transplantation induced maximal up-regulation of PCNA protein and HGF mRNA levels. The levels of alanine aminotransferase (AST), aspartate aminotransferase, total bilirubin (TBIL), prothrombin time (PT) and activated partial thromboplastin time in the BM-EPCs/BDHSCs group were significantly improved, to be equivalent to normal levels (P > 0.05) compared with those in the BDHSC (AST, TBIL and PT, P < 0.05) and BM-EPCs (TBIL and PT, P < 0.05) groups. Transplantation of BM-EPCs/BDHSCs combination significantly reduced the degree of liver fibrosis (staging score of 1.75 ± 0.25 vs BDHSCs 2.88 ± 0.23 or BM-EPCs 2.75 ± 0.16, P < 0.05). CONCLUSION: The combined transplantation exhibited maximal therapeutic effect compared to that of transplantation of BM-EPCs or BDHSCs alone. Combined transplantation of autogenous BM-EPCs and BDHSCs may represent a promising strategy for the treatment of liver fibrosis, which would eventually prevent cirrhosis and liver cancer.
Assuntos
Transplante de Medula Óssea , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Células Progenitoras Endoteliais/transplante , Hepatócitos/transplante , Cirrose Hepática Experimental/prevenção & controle , Fígado/patologia , Transplante de Células-Tronco , Antígeno AC133/metabolismo , Animais , Tetracloreto de Carbono , Proliferação de Células , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colágeno/metabolismo , Células Progenitoras Endoteliais/metabolismo , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Regeneração Hepática , Masculino , Neovascularização Patológica , Fagocitose , Fenótipo , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Wistar , Fatores de Tempo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
This study aimed to observe the change in nonhigh-density lipoprotein cholesterol (non-HDL-C) levels and analyzed its related factors in adults with prediabetes (impaired fasting glucose and/or impaired glucose tolerance).This case-controlled study included 56 adults with normal glucose tolerance (NGT) and 74 adults with prediabetes. The cases and controls were age and gender-matched. Anthropometric measurements including height, weight, waist circumference, and blood pressure were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 hours of fasting, and the levels of glucose, insulin, lipids, and uric acid were measured.The levels of non-HDL-C (3.63â±â0.92 vs 3.27â±â1.00âmmol/L) were significantly higher in prediabetic subjects than in NGT subjects (Pâ<â.05). Non-HDL-C positively correlated with HOMA-IR (râ=â0.253, Pâ=â.004), triglyceride (râ=â0.204, Pâ=â.020), and uric acid (râ=â0.487, Pâ=â.000). After multivariate analysis, uric acid continued to be significantly associated with non-HDL-C (ßâ=â0.006, Pâ=â.000).Non-HDL-C is elevated in adults with prediabetes. A relationship between non-HDL-C and uric acid was observed.
Assuntos
Glicemia/análise , Colesterol/sangue , Intolerância à Glucose/sangue , Lipoproteínas/sangue , Estado Pré-Diabético/sangue , Adulto , Antropometria , Pressão Sanguínea , Estatura , Peso Corporal , Estudos de Casos e Controles , Jejum/sangue , Feminino , Intolerância à Glucose/etiologia , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estado Pré-Diabético/complicações , Ácido Úrico/sangue , Circunferência da CinturaRESUMO
Personal exposure to PM2.5 associated with heavy metals were investigated at and around the same road by cycling, walking, taxi and bus in Tianjin, China. One trip on each mode was undertaken during 4 h of both morning and evening peak hours. Results of one-way analysis of variance (ANOVA) to compare mean concentrations of PM2.5 and each metal measured by four modes, the enrichment level of heavy metals in four modes and the carcinogenic, non-carcinogenic risk and probabilistic estimation of health risks of metals (Cr, Ni, Cu, Zn and Pb). Arithmetic means of PM2.5 personal exposure were 323.66, 313.37, 214.84 and 160.71 µg/m3 for cycling, walking, bus and taxi, which resulted from the difference of source (vehicle exhaust and road dust) of exposure to PM2.5. Na has the highest concentration, followed by Al, Ca, K, Fe, Mg, Zn, Ni, Pb, Cu and Cr. The higher Na concentrations were observed in Tianjin in light of its major sea salt influence. The concentrations of Ca, Mg, Fe and Zn in four modes followed different orders, while other metals have no significant difference between four modes. Enrichment factors of metals in PM2.5 showed that some metals are enriched, ranging from contaminated to extremely contaminated, for example, Ni, Cu, Zn, Pb, Na and Cr. Others are barely enriched such as Ca, K, Mg and Fe. It illustrated the former is mainly effected by anthropogenic activates and the source of latter comes from crust. From the results of non-carcinogenic and carcinogenic risks of metals, the intake of metals with inhalation for 4 h by four modes did not pose a significant potential chronic-toxic risk and was an acceptable or tolerable risk at present. But uncertainty analysis of health risks showed there were 4.05 and 6.87% probability that make carcinogenic risk values to exceed 10-4 when male choose walking/cycling to work. Commuters' rush hour exposures were significantly influenced by mode of transport. We suggest that future work should focus on further research between heavy metals in PM2.5 exposure and its specific epidemiology effects.
Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Exposição por Inalação/análise , Metais Pesados/análise , Material Particulado/análise , Emissões de Veículos/análise , China , Poeira/análise , Tamanho da Partícula , Medição de Risco , Estações do Ano , Meios de TransporteRESUMO
The exact mechanism through which elevated serum ferritin promotes the development of type 2 diabetes is unknown. This study showed that ferritin concentration in impaired glucose regulation and newly diagnosed diabetes mellitus subjects of nonobesity already significantly increased when compared with normal glucose tolerant subjects of nonobesity. Elevated serum ferritin levels are associated with insulin resistance and may be not associated with the decline of insulin beta cells in different status of glucose tolerance in nonobese Han adults.
RESUMO
Scrub typhus is one of the most common infectious diseases of rural south and southeastern Asia and the western Pacific. It emerged in Shandong Province in northern China from autumn to winter of 1986. Since then, the "autumn-winter type scrub typhus" has been found in many areas of northern China. However, the principle genotypes of Orientia tsutsugamushi still remain unknown. This study was undertaken to identify the genotypes of O. tsutsugamushi obtained from scrub typhus patients, chigger mites and rodents from the focal point of the problem in Shandong Province. Forty-four isolates from patients, rodents, and chiggers, 47 blood clots from patients during the acute phase, 10 eschars from patients during the convalescence phase and 16 pools of larval chiggers were tested for the scrub typhus antigen 56-kD protein (Sta56) gene by nested PCR methodology and additional sequence analysis including DNA sequence alignment and phylogenetic analysis. Based on nested PCR, ninety-five initial PCR-positive samples produced amplicons using Kawasaki strain-specific primers, while the other two (the FXS4 and LHGM2 strains) produced amplicons using Karp strain-specific primers. The partial Sta56 gene sequence analysis indicated that the sequence homologies of 3 selected isolates (the B16, FXS2, and XDM2 strains) and 7 eschars out of the 95 samples, which were nested PCR-positive using Kawasaki strain-specific primers, were 94-98% to that of Kawasaki strain. The sequence homology of the FXS4 and LHGM2 strains to that of the Karp strain was respectively 83 and 96%. These findings implied that the key genotypes of O. tsutsugamushi in patients, rodents, and chiggers in Shandong Province were identical and similar to Kawasaki strains.
Assuntos
Orientia tsutsugamushi/genética , Tifo por Ácaros/epidemiologia , Animais , Antígenos de Bactérias/química , Antígenos de Bactérias/classificação , Antígenos de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , Sequência de Bases , China/epidemiologia , Genótipo , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/classificação , Proteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Orientia tsutsugamushi/isolamento & purificação , Filogenia , Tifo por Ácaros/genética , Tifo por Ácaros/microbiologia , Alinhamento de Sequência , TrombiculidaeRESUMO
The aim of the present study was to evaluate the clinical usefulness of applying RT-nested PCR along with RFLP as a method for diagnosis and genotypic differentiation of Hantavirus in the acute-stage sera of HFRS patients as compared to the ELISA technique. A prospective study of patients with suspected HFRS patients was carried out. Sera were collected for serological evaluation by ELISA and RT-nested PCR testing. Primers were selected from the published sequence of the S segment of HTNV strain 76-118 and SEOV strain SR-11, which made it possible to obtain an amplicon of 403 bp by RT-nested PCR. The genotypic differentiations of the RT-nested PCR amplicons were carried out by RFLP. Sequence analyses of the amplicons were used to confirm the accuracy of the results obtained by RFLP. Of the 48 acute-stage sera from suspected HFRS patients, 35 were ELISA-positive while 41 were positive by RT-nested PCR. With Hind III and Hinf I, RFLP profiles of the RT-nested PCR amplicons of the 41 positive sera exhibited two patterns. 33 had RFLP profiles similar to the reference strain R22, and thus belonged to the SEOV type. The other 8 samples which were collected during October-December had RFLP profiles similar to the reference strain 76-118, and thus belonged to the HTNV type. Sequence phylogenetic analysis of RT-nested PCR amplicons revealed sdp1, sdp2 YXL-2008, and sdp3 as close relatives of HTNV strain 76-118, while sdp22 and sdp37 as close relatives of SEOV strain Z37 and strain R22 located in two separate clusters in the phylogenetic tree. These results were identical to those acquired by RFLP. RT-nested PCR integrated with RFLP was a rapid, simple, accurate method for detecting and differentiating the genotypes of Hantavirus in the acute-stage sera of suspected HFRS patients. In Shandong province, the main genotypes of Hantavirus belonged to the SEOV types, while the HTNV types were observed during the autumn-winter season.