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1.
BMC Infect Dis ; 24(1): 479, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730338

RESUMO

BACKGROUND & AIMS: Pyogenic liver abscess (PLA) is a common hepatobiliary infection that has been shown to have an increasing incidence, with biliary surgery being identified as a trigger. Our aim was to investigate the clinical characteristics and treatments of PLA patients with and without a history of biliary surgery (BS). METHODS: The study included a total of 353 patients with PLA who received treatment at our hospital between January 2014 and February 2023. These patients were categorized into two groups: the BS group (n = 91) and the non-BS group (n = 262). In the BS group, according to the anastomosis method, they were further divided into bilioenteric anastomoses group (BEA, n = 22) and non-bilioenteric anastomoses group (non-BEA, n = 69). Clinical characteristics were recorded and analyzed. RESULTS: The percentage of PLA patients with BS history was 25.78%. The BS group exhibited elevated levels of TBIL and activated APTT abnormalities (P = 0.009 and P = 0.041, respectively). Within the BS group, the BEA subgroup had a higher prevalence of diabetes mellitus (P < 0.001) and solitary abscesses (P = 0.008) compared to the non-BEA subgroup. Escherichia coli was more frequently detected in the BS group, as evidenced by positive pus cultures (P = 0.021). The BS group exhibited reduced treatment efficacy compared to those non-BS history (P = 0.020). Intriguingly, the BS group received a higher proportion of conservative treatment (45.05% vs. 21.76%), along with reduced utilization of surgical drainage (6.59% vs. 16.41%). CONCLUSIONS: Patients with BS history, especially those who have undergone BEA, have an increased susceptibility to PLA formation without affecting prognosis.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Abscesso Hepático Piogênico , Humanos , Abscesso Hepático Piogênico/microbiologia , Abscesso Hepático Piogênico/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Antibacterianos/uso terapêutico , Escherichia coli/isolamento & purificação , Drenagem
2.
Cancer Immunol Immunother ; 72(7): 2137-2149, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36840762

RESUMO

There is a lack of effective programmed cell death protein 1 (PD-1)-targeted immunotherapy with good tolerability in patients with advanced hepatocellular carcinoma (HCC) and severely compromised liver function. We assessed patient outcomes after combined camrelizumab and molecular targeted therapy in a multicenter cohort study in China. The study included 99 patients with advanced HCC (58 Child-Pugh A and 41 Child-Pugh B), 84 of them received camrelizumab combined with molecular targeted therapy from January 10, 2019, to March 31, 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed. The median follow-up was 12.1 months. For patients with Child-Pugh B, the OS probability at 12-months, ORR and DCR were 49.7%, 31.7% and 65.9%, respectively, and the median PFS was 5.1 months [95% confidence interval (CI) 3.0-7.1], which were comparable with Child-Pugh A patients, although median OS was shorter in Child-Pugh B patients (20.5 vs.13.4 months, P = 0.12). In multivariate analysis, macrovascular infiltration (MVI), but not sex, age, hepatitis B virus etiology, extrahepatic metastasis, Child-Pugh B, or AFP > 400 ng/ml, was associated with 12-months OS [hazard ratio (HR) 2.970, 95% CI 1.276-6.917, P = 0.012] and ORR (HR 2.906, 95% CI 1.18-7.16, P = 0.020). Grade 3/4 immune-related AEs occurred in 26.8% of Child-Pugh B patients, including one potentially treatment-related death. In both groups, the most common AEs were immune thrombocytopenia and hepatotoxicity. Camrelizumab combined with targeted therapy showed favorable effectiveness and tolerability with manageable toxicities in Chinese HCC patients, regardless of Child-Pugh A/B liver function. MVI was associated with suboptimal immunotherapy response and poor prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Terapia de Alvo Molecular , Estudos de Coortes
3.
J Cell Physiol ; 236(2): 931-945, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32583428

RESUMO

Ischemia reperfusion (I/R)-induced acute kidney injury (AKI) is a common and serious condition. Irisin, an exercise-induced hormone, improves mitochondrial function and reduces reactive oxygen species (ROS) production. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis and its inactivation aggravates renal I/R injury by inducing ROS production. However, the effect of irisin on GPX4 and I/R-induced AKI is still unknown. To study this, male adult mice were subjected to renal I/R by occluding bilateral renal hilum for 30 min, which was followed by 24 hr reperfusion. Our results showed serum irisin levels were decreased in renal I/R mice. Irisin (250 µg/kg) treatment alleviated renal injury, downregulated inflammatory response, improved mitochondrial function, and reduced ER stress and oxidative stress after renal I/R, which were associated with upregulation of GPX4. Treated with RSL3 (a GPX4 inhibitor) abolished irisin's protective effect. Thus, irisin attenuates I/R-induced AKI through upregulating GPX4.


Assuntos
Injúria Renal Aguda/metabolismo , Fibronectinas/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Ferroptose/fisiologia , Inflamação/metabolismo , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Reperfusão/métodos , Regulação para Cima/fisiologia
4.
J Cell Mol Med ; 24(1): 996-1009, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31701659

RESUMO

Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco-2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK-UCP 2 pathway via binding to the integrin αVß5 receptor. Inhibition of integrin αVß5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin αVß5-AMPK-UCP 2 pathway.


Assuntos
Epitélio/metabolismo , Fibronectinas/administração & dosagem , Enteropatias/prevenção & controle , Mucosa Intestinal/metabolismo , Receptores de Vitronectina/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Estresse do Retículo Endoplasmático , Epitélio/patologia , Fibronectinas/metabolismo , Enteropatias/etiologia , Enteropatias/patologia , Mucosa Intestinal/lesões , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais
5.
BMC Infect Dis ; 20(1): 145, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066406

RESUMO

BACKGROUND: Pyogenic liver abscess (PLA) is an inflammatory disease with increasing incidence. When it occurs with diabetes mellitus (DM), the risk of recurrence and mortality may increase. However, the effect of DM on the short-term prognosis of PLA patients after hospitalization remained unknown. METHODS: Two hundred twenty-seven PLA patients who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to January 2018 were retrospectively enrolled. They were divided into two groups as the DM group (n = 61) and the Non-DM group (n = 166). In the DM group, HbA1C level < 7% was considered to be good-control of glycaemia (n = 23). The clinical characteristics and overall short-term survival were analyzed. RESULTS: The proportion of PLA patients with DM was 26.87%. In the DM group, there was a higher incidence of hypertension and Candida spp. infection. Conservative administration and percutaneous drainage were mainly used in patients with good- (60.87%) and poor-control (60.53%) of glycaemia, respectively. During follow-up, 24 (10.57%) died due to uncontrolled systemic infections and other serious complications. Compared with PLA patients without DM, patients in the DM group had significantly increased 6-month mortality rate after discharge (Log-Rank test, P = 0.021). Poor-control of glycaemia did not reduce the six-month survival, while the recurrence rate of PLA within 3 months showed an almost 3-fold increase (13.16% vs. 4.35%). Further multivariate analyses found that DM was the only independent risk factor for the PLA six-month survival (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.138-8.010, P = 0.026). However, the blood glucose level had no significant effect on the short-term survival of PLA patients with DM (Log-Rank test, P = 0.218). CONCLUSIONS: In PLA patients, DM aggravated short-term mortality and blood glucose levels should be well controlled.


Assuntos
Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Abscesso Hepático Piogênico/complicações , Abscesso Hepático Piogênico/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Criança , Complicações do Diabetes/mortalidade , Feminino , Hospitalização , Humanos , Abscesso Hepático Piogênico/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
6.
BMC Infect Dis ; 19(1): 233, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845927

RESUMO

BACKGROUND: Pyogenic liver abscess (PLA) in the elderly is insufficiently elucidated. A few studies attempted to investigate the role of age in PLA have yielded controversial results. The purpose of this study was to explore the possible differences in the comorbidity, microbiological characteristics and clinical course between elderly and young PLA patients. METHODS: The clinical data of 332 adult PLA patients who received treatment at our hospital from January 2010 to December 2016 were collected. The demographic data, etiologies, comorbidities, clinical features, laboratory results, imaging findings, microbiological characteristics, choices of treatment and clinical outcomes were analyzed. RESULTS: Eighty-two (24.7%) patients were older than 65 years. Comorbidities including hypertension, diabetes mellitus, and cholelithiasis were more frequently found in older patients. Elderly PLA patients were more likely to present with atypical symptoms and signs on admission. The laboratory abnormalities and imaging findings were similar between the two groups. Klebsiella pneumonia was the most common pathogen on pus culture in both groups. There were no statistically significant differences in choices of treatment, PLA-related complications and length of in-hospital stay between the two groups. And there was no in-hospital mortality. CONCLUSIONS: The clinical characteristics were similar in young and elderly PLA patients. However, elderly PLA patients were more likely to have underlying diseases and tended to have atypical presentations. Physicians need to be vigilant when encounter possible elderly patients with PLA. However, older PLA patients had comparable outcomes as their younger counterparts. With effective treatment, both elderly and young PLA patients can be cured.


Assuntos
Abscesso Hepático Piogênico/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Comorbidade , Feminino , Humanos , Klebsiella pneumoniae/isolamento & purificação , Tempo de Internação , Abscesso Hepático Piogênico/complicações , Abscesso Hepático Piogênico/tratamento farmacológico , Abscesso Hepático Piogênico/microbiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/etiologia , Resultado do Tratamento , Adulto Jovem
7.
Cytokine ; 111: 237-245, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30195979

RESUMO

BACKGROUND & AIMS: Gut ischemia reperfusion (I/R) injury is a life-threatening condition. The immune response plays an important role in I/R-induced organ injury. Alpha-galactosylceramide (α-GalCer) is a potent natural killer T (NKT) cell stimulator. Activation of NKT cells by α-GalCer has been shown to reduce I/R-induced injury in the liver and heart. However, whether α-GalCer has any protective effects on gut I/R-induced organ injury remained unknown. The aim of this study was to test the hypothesis that α-GalCer attenuates gut I/R-induced local and remote organ injury through modulating immune responses. METHODS: Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery for 30 min in male adult mice. After removing the clip, α-GalCer (2 µg/mouse) or normal saline containing 0.5% Tween 20 (Vehicle) was administered intraperitoneally. Blood, gut, lung and mesenteric lymph node (MLN) samples were collected 4 h after reperfusion to detect bacterial translocation, tight junction protein, tissue damage, edema, apoptosis, IL-4, IL-10, IFN-γ and TNF-α levels. RESULTS: α-GalCer significantly reduced bacterial translocation to the MLN, restored tight junction protein and attenuated gut and lung injury after gut I/R. α-GalCer markedly stimulated the production of IL-4, IL-10 and IFN-γ, but had no obvious effects on TNF-α production in gut I/R mice. Pretreatment with anti-CD1d, IL-4 or IL-10, but not IFN-γ blocking antibodies abolished the protective effects of α-GalCer in gut I/R. CONCLUSIONS: α-GalCer treatment improved gut barrier function and attenuated gut and lung injury after gut I/R. The beneficial effects of α-GalCer in gut I/R were NKT cell dependent and mediated through upregulation of IL-4 and IL-10. Thus, activation of NKT cells by α-GalCer may serve as a novel option in the treatment of gut I/R injury.


Assuntos
Galactosilceramidas/farmacologia , Células T Matadoras Naturais/metabolismo , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Citotoxicidade Imunológica/efeitos dos fármacos , Edema/tratamento farmacológico , Edema/metabolismo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Ligantes , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Pancreatology ; 2018 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-29325893

RESUMO

This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

9.
J Surg Res ; 222: 69-74, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29273377

RESUMO

BACKGROUND: Postoperative complications after splenectomy are not rare and can be serious in cirrhotic patients. The purpose of this study was to assess postoperative complications using the comprehensive complication index (CCI) after splenectomy in cirrhotic patients and identify risk factors for those who developed a high postoperative CCI score. MATERIALS AND METHODS: This retrospective study included 208 adult patients with viral hepatitis-related cirrhosis, who underwent elective splenectomy at our hospital from January 2002 to June 2012. The primary outcome was the CCI score. A CCI score >30 was considered to be a high CCI score. RESULTS: The median CCI score in this cohort was 25.6 (range: 8.7-62.9), and 66 patients (31.7%) had a CCI score >30. Univariable and multivariable analyses showed that the risk factors independently associated with a high CCI score were a history of hypertension and a model for end-stage liver disease (MELD) score ≥10 prior to splenectomy. CONCLUSIONS: A high CCI score is common in cirrhotic patients undergoing splenectomy. The CCI is a useful grading system to assess postoperative morbidity in cirrhotic patients undergoing splenectomy. Preoperative blood pressure control is recommended and cirrhotic patients with an elevated MELD score should consider other treatment options for hypersplenism.


Assuntos
Cirrose Hepática/complicações , Complicações Pós-Operatórias/epidemiologia , Esplenectomia , Adulto , Idoso , China/epidemiologia , Feminino , Hepatite Viral Humana/complicações , Humanos , Hiperesplenismo/cirurgia , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
10.
World J Surg ; 41(4): 1100-1109, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27878349

RESUMO

BACKGROUND: Surgeons are likely to get progressively fatigued and work less effectively during the course of a normal workday. We sought to examine the effects of surgery start times (morning vs. afternoon) and workload of the surgeons on morbidity of patients after partial liver resection (LR). METHODS: A total of 155 pairs of the patients from 383 patients undergoing LR were generated by propensity score analysis (PSM) according to the start times of surgery: group M (morning surgery, 8 a.m.-1 p.m.) and group A (afternoon surgery, 1 p.m.-6 p.m.). Patients in group A were further divided depending on whether or not the surgeons had performed other surgeries earlier in the day and the exact duration of the other surgeries before the afternoon surgery (≤180 and >180 min). The incidence and severity of postoperative complications were compared between different groups. RESULTS: By using PSM analysis, the patients in group M and group A were well matched in basic characteristics. The incidence and severity of the postoperative complications were similar between the two groups (all p > 0.05). Whether the surgeons had performed other surgeries prior to the afternoon surgery seemed not affecting the postoperative outcome (all p > 0.05). Moreover, the duration of other surgeries the surgeons had performed did not have significant influence on the outcome of patients undergoing afternoon surgery (all p > 0.05). CONCLUSIONS: Surgery start times and workload of surgeons during working time did not measurably affect short-term outcomes of the patients. The negative findings might be a manifestation of professional judgment and self-regulation of the experienced physicians.


Assuntos
Hepatectomia/efeitos adversos , Duração da Cirurgia , Fadiga , Feminino , Hepatectomia/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Morbidade , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Fatores de Tempo , Resultado do Tratamento , Carga de Trabalho
11.
World J Surg ; 40(9): 2237-44, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27393054

RESUMO

BACKGROUND: Abdominal incision closure technique seriously influences patient prognosis. Most studies have focused on the different suture techniques and materials on midline incision, while little data are available in wide transverse or oblique incisions after liver resection (LR). The aim of the present study is to compare the two major incision suture methods after LR in our institute: Mass continuous suture (group P) and layered interrupted suture (group S). STUDY DESIGN: 258 patients undergoing LR with abdominal transverse or oblique incisions were prospectively enrolled. They were divided into two groups according to different abdominal incision suture methods and compared with the preoperative, intraoperative parameters, and postoperative wound complications. RESULTS: There were 118 patients in group P and 140 patients in group S, which was similar in general condition, primary disease, liver, and renal function. Incision length, total operation time, intraoperative blood loss, or perioperative antibiotics use were not different between the two groups. However, abdominal incision closure time and interval time for stitches removing after operation was significantly shorter in group P than group S (both p < 0.001). After a median follow-up of 16 months, the incidence of wound infection and fat liquefaction was more than two times higher in group S than group P, which, however, was not statistically different. Moreover, there was no difference in wound disruption or incisional hernia between the two groups. CONCLUSIONS: Although similar in occurrence of postoperative wound complications, mass continuous suture with polydioxanone seemed to be more timesaving in incision closure and motivated in wound healing.


Assuntos
Técnicas de Fechamento de Ferimentos Abdominais , Hepatectomia , Técnicas de Fechamento de Ferimentos Abdominais/efeitos adversos , Perda Sanguínea Cirúrgica , Feminino , Seguimentos , Humanos , Hérnia Incisional/etiologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Polidioxanona , Complicações Pós-Operatórias/etiologia , Infecção da Ferida Cirúrgica/etiologia , Suturas , Cicatrização
12.
Front Oncol ; 13: 1195065, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397360

RESUMO

Background: China has experienced one of the fastest increases in the incidence of acute lymphoid leukemia (ALL). The aim of this study was to assess the long-term trends of the incidence and mortality of ALL in mainland China between 1990 and 2019 and to project these trends through 2028. Methods: Data on ALL were extracted from the Global Burden of Disease Study 2019; population data were extracted from World Population Prospects 2019. An age-period-cohort framework was used in the analysis. Results: The net drift for the incidence of ALL was 7.5% (95% confidence interval [CI]: 7.1%, 7.8%) per year in women and 7.1% (95% CI: 6.7%, 7.6%) in men, and local drift was found to be higher than 0 in every studied age group (p<0.05). The net drift for mortality was 1.2% (95% CI: 1.0%, 1.5%) in women and 2.0% (95% CI: 1.7%, 2.3%) in men. Local drift was lower than 0 in boys aged 0-4 years and girls aged 0-9 years and higher than 0 in men aged 10-84 years and women aged 15-84 years. The estimated period relative risks (RRs) for both incidence and mortality showed increasing trends in the recent period. The cohort RRs for incidence showed increasing trends in both sexes; however, the cohort RR for mortality was decreased in the recent birth cohort (women born after 1988-1992 and men born after 2003-2007). Compared with that in 2019, the incidence of ALL in 2028 is projected to increase by 64.1% in men and 75.0% in women, and the mortality is predicted to decrease by 11.1% in men and 14.3% in women. The proportion of older adult/adults individuals with incident ALL and ALL-related death was projected to increase. Conclusions: Over the last three decades, the incidence and mortality rates of ALL have generally increased. It is projected that the incidence rate of ALL in mainland China will continue to increase in the future, but the associated mortality rate will decline. The proportion of older adult/adults individuals with incident ALL and ALL-related death was projected to increase gradually among both sexes. More efforts are needed, especially for older adult/adults individuals.

13.
Cell Biosci ; 13(1): 64, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36964632

RESUMO

BACKGROUND: Endoplasmic reticulum (ER) stress plays an important role in the occurrence and development of various liver diseases. However, there are no effective prevention and treatment strategies. We aimed to determine the role of heat shock factor 2 binding protein (HSF2BP) in ER stress. METHODS: HSF2BP expression in mice and cultured hepatocytes was measured during ER stress induced by tunicamycin, and its importance in ER stress was evaluated in hepatocyte-specific HSF2BP transgenic (TG) and knockout (KO) mice. The effects and mechanisms of HSF2BP on ER stress were further probed in hepatic ischemia-reperfusion (I/R) injury. RESULTS: HSF2BP expression was significantly upregulated during tunicamycin-induced ER stress in mice and cultured hepatocytes. Liver injury and ER stress were reduced in HSF2BP overexpressing mice after treating with tunicamycin, but were aggravated in HSF2BP knockout mice compared to the controls. In hepatic I/R injury, HSF2BP expression was significantly upregulated, and HSF2BP overexpressing mice had reduced liver injury and inflammation. These improvements were associated with ER stress inhibition. However, these results were reversed in hepatocyte-specific HSF2BP knockout mice. HSF2BP overexpression increased cytoplasmic CDC73 levels and inhibited the JNK signaling pathway. CDC73 knockdown using siRNA eliminated the protection exerted by HSF2BP overexpression in hypoxia/reoxygenation (H/R)-induced ER stress in hepatocytes. CONCLUSION: HSF2BP is a previously uncharacterized regulatory factor in ER stress-likely acts by regulating CDC73 subcellular localization. The feasibility of HSF2BP-targeted treatment in ER stress-related liver disease deserves future research.

14.
Front Public Health ; 10: 1021646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353279

RESUMO

Background: High body mass index (BMI) is an important risk factor for stroke. The aim of this study was to assess the long-term trend of high BMI-attributed stroke mortality and make projections through 2030. Methods: Data were extracted from the Global Burden of Disease Study 2019 and World Population Prospects 2019. An age-period-cohort framework was used in the analysis. Results: From 1990 to 2019, the age-standardized mortality rate (ASMR) of high BMI-attributed stroke among females decreased by 15.2%, while among males, it increased by 31.1%. All of the age groups studied showed an increasing pattern over the last 30 years in males, and in female, the age groups encompassing participants who were 25-69 years old showed a decreasing pattern. In the same birth cohort, high BMI-attributable stroke mortality rates increased exponentially with age in both sexes. For females, the period rate ratios (RR) showed a downward trend after 2000-2004, and the cohort RR also showed a downward trend after the birth cohort 1930-1934. For males, the period RR showed an upward trend, but this increase was halted in the most recent period, and the cohort RRs showed a monotonic increasing pattern. It was projected that the ASMR of high BMI-attributed stroke would decrease among females and increase among males in the near future and that the proportion of elderly individuals with death due to high BMI-attributed stroke was projected to increase. Conclusions: Over the last three decades, the high BMI-attributed stroke mortality rate decreased among females and increased among males, and these trends are projected to continue in the future. In addition, the proportion of elderly individuals with high BMI-attributed stroke mortality was projected to increase gradually in both men and women. More health-promoting efforts are needed, especially for elderly individuals and males.


Assuntos
Acidente Vascular Cerebral , Masculino , Feminino , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Índice de Massa Corporal , Acidente Vascular Cerebral/epidemiologia , China/epidemiologia , Fatores de Risco , Previsões
15.
Cell Death Dis ; 13(9): 830, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36167792

RESUMO

Heat shock proteins (HSPs) depletion and protein misfolding are important causes of hepatocyte death and liver regeneration disorder in liver injury. HSF2BP, as its name implies, is a binding protein of HSF2, but the specific role of HSF2BP in heat shock response (HSR) remains unknown. The aim of this study is to identify the role of HSF2BP in HSR and acute liver injury. In this study, we found that HSF2BP expression increased significantly within 24 h after APAP administration, and the trend was highly consistent with that of HSP70. hsf2bp-KO and hsf2bp-TG mouse models demonstrated HSF2BP reduced hepatocyte death, ameliorated inflammation, and improved liver function in APAP- or D-GalN/LPS- induced liver injury. Meanwhile, a significant increase of the survival rate was observed in hsf2bp-TG mice after APAP administration. Further studies showed that HSF2BP upregulated the expression of HSF2 and HSP70 and inhibited the activation of Jnk1/2 and P38 MAPK. Additionally, HSP70 siRNA pretreatment abolished the effect of HSF2BP on the MAPK pathway in APAP-treated hepatocytes. The results reveal that HSF2BP is a protective factor in acute liver injury, and the HSF2BP/HSP70/MAPK regulatory axis is crucial for the pathogenesis of liver injury. HSF2BP is a potential therapeutic target for liver injury.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen/farmacologia , Animais , Proteínas de Transporte/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Hepatócitos/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Shock ; 55(2): 268-273, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32694396

RESUMO

ABSTRACT: Neonatal sepsis is a life-threatening inflammatory condition. Extracellular cold-inducible RNA-binding protein (CIRP), a proinflammatory mediator, plays a critical role in the pathogenesis of sepsis-induced lung injury in neonates. Luteolin, a polyphenolic flavonoid, has potent anti-inflammatory properties. However, the effects of luteolin on CIRP production and neonatal sepsis-induced lung injury remained unknown. We therefore hypothesize that treatment with luteolin suppresses CIRP production and attenuates lung injury in neonatal sepsis. To study this, sepsis was induced in C57BL/6J mouse pups (5-7 days) by intraperitoneal cecal slurry injection (CSI). One hour after CSI, luteolin (10 mg/kg body weight) or vehicle (normal saline) was administered through intraperitoneal injection. CIRP mRNA and protein were determined and lung injury was assessed at 10 h after CSI. Our results showed that administration of luteolin decreased CIRP mRNA and protein, improved lung architecture, reduced lung edema, and apoptosis after CSI. To examine the direct effect of luteolin on CIRP production, peritoneal macrophages were isolated from neonatal mice and stimulated with 100 ng/mL LPS with or without the presence of luteolin. The result indicates that luteolin directly inhibited LPS-induced CIRP production in neonatal macrophages. In addition, luteolin also downregulated hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor 3 (NLRP3) expression in septic neonates and in LPS-stimulated neonatal macrophages. In conclusion, administration of luteolin suppresses CIRP production and attenuates lung injury in neonatal sepsis. The beneficial effect of luteolin may be related to downregulation of HIF-1α and NLRP3 expression in neonatal macrophages. Luteolin may be developed as an adjunctive therapy for neonatal sepsis.


Assuntos
Lesão Pulmonar/prevenção & controle , Luteolina/farmacologia , Luteolina/uso terapêutico , Proteínas de Ligação a RNA/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Feminino , Lesão Pulmonar/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Ligação a RNA/biossíntese , Sepse/complicações , Sepse/metabolismo
17.
Surg Infect (Larchmt) ; 22(4): 427-433, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32857017

RESUMO

Background: Gas-forming pyogenic liver abscess (GFPLA) accounts for up to 30% of all pyogenic liver abscess (PLA) cases. However, little is known of the differences in clinical features and prognosis between GFPLA and non-GFPLA. Aim: This retrospective study compared the clinical features and prognosis of GFPLA and non-GFPLA. Patients and Methods: Data for 392 patients with PLA treated from January 1, 2007 to December 31, 2016 were reviewed. Gas-forming pyogenic liver abscess was defined as gas in the abscess. Liver abscesses were considered non-GFPLA (n = 326) or GFPLA (n = 66). The clinical features and outcomes of patients with GFPLA were compared with that of patients without GFPLA. Results: The groups were similar in gender ratio, age, smoking, drinking, and comorbidities. Klebsiella pneumoniae was the most common pathogenic bacteria, but the negative rate of bacterial culture of the non-GFPLA group was higher than that of the GFPLA. In etiologies, the GFPLA group had more biliary source infection and less cryptogenic infection. In addition, the GFPLA group had a higher rate of previous hepatobiliary surgery, especially biliary enteric anastomosis. Compared with the non-GFPLA group, the percentage of the GFPLA group with antibiotic agents combined with percutaneous drainage was higher, whereas the percentages given antibiotic agents alone and antibiotic agents combined with surgical drainage were lower. Patients with GFPLA had higher rates of sepsis and pleural effusion, and longer hospital stays than did non-GFPLA patients. No patient died during hospitalization. Conclusions: The GFPLA group had more biliary source infection and less cryptogenic infection in etiologies. Gas-forming pyogenic liver abscess is associated with past hepatobiliary surgery, especially biliary enteric anastomosis and has high rates of sepsis and long hospitalization. Thus, the patients with PLA with a history of hepatobiliary surgery should be monitored more closely in the early stage of the PLA. It needs to be recognized as a distinct clinical entity.


Assuntos
Abscesso Hepático Piogênico , Antibacterianos/uso terapêutico , Humanos , Klebsiella pneumoniae , Abscesso Hepático Piogênico/tratamento farmacológico , Abscesso Hepático Piogênico/epidemiologia , Prognóstico , Estudos Retrospectivos
18.
Risk Manag Healthc Policy ; 14: 1555-1562, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889038

RESUMO

PURPOSE: Advances in surgical techniques and intensive care over the past decades have significantly reduced the mortality rates of critically ill surgical patients. However, evaluations of risk factors associated with mortality in surgical intensive care units (ICUs) are limited. The aim of this study was to analyze the independent risk factors for 28-day mortality of surgical ICU patients. PATIENTS AND METHODS: The clinical data of adult patients who were admitted to the surgical ICU in the First Affiliated Hospital of Xi'an Jiaotong University from June 2013 to June 2017 were collected. Univariate and multivariable logistic regression analyses were performed to examine risk factors associated with 28-day mortality. RESULTS: A total of 347 patients were included in this analysis. The overall 28-day mortality rate was 32.6%. The major causes of surgical ICU admission were gastrointestinal diseases (46.7%), infection (20.5%), trauma (8.9%), respiratory diseases (8.9%) and cardiovascular diseases (6.6%). The univariate analysis showed age, total bilirubin, prothrombin time, international normalized ratio, arterial lactate level, APACHE II and SOFA score at ICU admission were significantly associated with 28-day mortality. In the multivariate analysis, however, age [Odds Ratio (OR): 2.899, 95% CI: 1.427-5.890, P=0.003], hypertension [OR: 3.630, 95% CI: 1.545-8.531, P=0.003], platelet count [OR: 1.004, 95% CI: 1.001-1.007, P=0.015], arterial lactate level [OR: 1.186, 95% CI: 1.088-1.293, P<0.001] and SOFA score [OR: 1.289, 95% CI: 1.131-1.469, P<0.001] were identified as the independent risk factors for 28-day mortality of patients in the surgical ICU. CONCLUSION: In patients admitted to the surgical ICU, age 65 and older, a high arterial lactate level and SOFA score at ICU admission were associated with increased 28-day mortality.

19.
World J Gastroenterol ; 27(14): 1507-1523, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33911471

RESUMO

BACKGROUND: Whether to use a T-tube for biliary anastomosis during orthotopic liver transplantation (OLT) remains a debatable question. Some surgeons chose to use a T-tube because they believed that it reduces the incidence of biliary strictures. Advances in surgical techniques during the last decades have significantly decreased the overall incidence of postoperative biliary complications. Whether using a T-tube during OLT is still associated with the reduced incidence of biliary strictures needs to be re-evaluated. AIM: To provide an updated systematic review and meta-analysis on using a T-tube during adult OLT. METHODS: In the electronic databases MEDLINE, PubMed, Scopus, ClinicalTrials.gov, the Cochrane Library, the Cochrane Hepato-Biliary Group Controlled Trails Register, and the Cochrane Central Register of Controlled Trials, we identified 17 studies (eight randomized controlled trials and nine comparative studies) from January 1995 to October 2020. The data of the studies before and after 2010 were separately extracted. We chose the overall biliary complications, bile leaks or fistulas, biliary strictures (anastomotic or non-anastomotic), and cholangitis as outcomes. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to describe the results of the outcomes. Furthermore, the test for overall effect (Z) was used to test the difference between OR and 1, where P ≤ 0.05 indicated a significant difference between OR value and 1. RESULTS: A total of 1053 subjects before 2010 and 1346 subjects after 2010 were included in this meta-analysis. The pooled results showed that using a T-tube reduced the incidence of postoperative biliary strictures in studies before 2010 (P = 0.012, OR = 0.62, 95%CI: 0.42-0.90), while the same benefit was not seen in studies after 2010 (P = 0.60, OR = 0.76, 95%CI: 0.27-2.12). No significant difference in the incidence of overall biliary complications (P = 0.37, OR = 1.41, 95%CI: 0.66-2.98), bile leaks (P = 0.89, OR = 1.04, 95%CI: 0.63-1.70), and cholangitis (P = 0.27, OR = 2.00, 95%CI: 0.59-6.84) was observed between using and not using a T-tube before 2010. However, using a T-tube appeared to increase the incidence of overall biliary complications (P = 0.049, OR = 1.49, 95%CI: 1.00-2.22), bile leaks (P = 0.048, OR = 1.91, 95%CI: 1.01-3.64), and cholangitis (P = 0.02, OR = 7.21, 95%CI: 1.37-38.00) after 2010. A random-effects model was used in biliary strictures (after 2010), overall biliary complications (before 2010), and cholangitis (before 2010) due to their heterogeneity (I 2 = 62.3%, 85.4%, and 53.6%, respectively). In the sensitivity analysis (only RCTs included), bile leak (P = 0.66) lost the significance after 2010 and a random-effects model was used in overall biliary complications (before 2010), cholangitis (before 2010), bile leaks (after 2010), and biliary strictures (after 2010) because of their heterogeneity (I 2 = 92.2%, 65.6%, 50.9%, and 80.3%, respectively). CONCLUSION: In conclusion, the evidence gathered in our updated meta-analysis showed that the studies published in the last decade did not provide enough evidence to support the routine use of T-tube in adults during OLT.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Sistema Biliar , Transplante de Fígado , Procedimentos de Cirurgia Plástica , Adulto , Anastomose Cirúrgica , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Humanos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
20.
Clin Transl Med ; 11(2): e295, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33634976

RESUMO

Acute pancreatitis (AP) remains a significant clinical challenge. Mitochondrial dysfunction contributes significantly to the pathogenesis of AP. Milk fat globule EGF factor 8 (MFG-E8) is an opsonizing protein, which has many biological functions via binding to αvß3/5 integrins. Ligand-dependent integrin-FAK activation of STAT3 was reported to be of great importance for maintaining a normal mitochondrial function. However, MFG-E8's role in AP has not been evaluated. METHODS: Blood samples were acquired from 69 healthy controls and 134 AP patients. Serum MFG-E8 levels were measured by ELISA. The relationship between serum concentrations of MFG-E8 and disease severity were analyzed. The role of MFG-E8 was evaluated in experimental models of AP. RESULTS: Serum concentrations of MFG-E8 were lower in AP patients than healthy controls. And serum MFG-E8 concentrations were negatively correlated with disease severity in AP patients. In mice, MFG-E8 administration decreased L-arginine-induced pancreatic injury and mortality. MFG-E8's protective effects in experimental AP were associated with improvement in mitochondrial function and reduction in oxidative stress. MFG-E8 knockout mice suffered more severe pancreatic injury and greater mitochondrial damage after l-arginine administration. Mechanistically, MFG-E8 activated the FAK-STAT3 pathway in AP mice. Cilengitide, a specific αvß3/5 integrin inhibitor, abolished MFG-E8's beneficial effects in AP. PF00562271, a specific FAK inhibitor, blocked MFG-E8-induced STAT3 phosphorylation. APTSTAT3-9R, a specific STAT3 antagonist, also eliminated MFG-E8's beneficial effects under such a condition. CONCLUSIONS: MFG-E8 acts as an endogenous protective mediator in the pathogenesis of AP. MFG-E8 administration protects against AP possibly by restoring mitochondrial function via activation of the integrin-FAK-STAT3 signaling pathway. Targeting the action of MFG-E8 may present a potential therapeutic option for AP.


Assuntos
Antígenos de Superfície/sangue , Integrinas/sangue , Proteínas do Leite/sangue , Mitocôndrias/genética , Pancreatite/sangue , Pancreatite/genética , Fator de Transcrição STAT3/sangue , Animais , Antígenos de Superfície/genética , Modelos Animais de Doenças , Feminino , Quinase 1 de Adesão Focal/sangue , Quinase 1 de Adesão Focal/genética , Humanos , Integrinas/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas do Leite/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética
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