Compromised browning in white adipose tissue of ageing people.

BACKGROUND: Adipose tissue plays a pivotal role in the pathology of metabolic disorders. In the past decade, brown and brown-like adipose tissues were detected in adult humans and show therapeutic potential in ageing-related metabolic diseases. OBJECTIVE: This study investigated expressions of major brown adipose markers in white adipose tissue (WAT) of different ages. Their associations with metabolic parameters and key adipokines were interrogated. DESIGN: Cross-sectional study, 2019-2021. METHODS: We recruited 21 young, 67 middle-aged, and 34 older patients. Omental adipose tissues were collected, and expressions of key brown markers and adipokines and the adipocyte size were evaluated. The fat depot distribution was evaluated by computed tomography. RESULTS: UCP1 and PRDM16 mRNA expressions declined with ageing in WAT and were more associated with age, than with the body mass index (BMI). The increased visceral adipose tissue (VAT) amount, as well as the VAT to subcutaneous adipose tissue (SAT) ratio, was decreased in the highest tertile of UCP1 expression, while individuals in different PRDM16 mRNA tertiles exhibited similar fat distribution. UCP1 mRNA was positively correlated with ADIPOQ and the strength of the correlation declined with ageing. In contrast, the association between UCP1 and LEP was insignificant in young and middle-aged groups but became significantly correlated in the older-people group. We also found a positive correlation between UCP1 and PRDM16. CONCLUSIONS: PRDM16 and UCP1, despite their key functions in adipose browning, exhibit differential clinical correlations with metabolic features in human WAT in an age-dependent manner. These two genes may participate in the pathogenesis of ageing-related metabolic diseases, but with distinct mechanisms.

The value of a risk model combining specific risk factors for predicting postoperative severe morbidity in biliary tract cancer.

Purpose: Several surgical risk models are widely utilized in general surgery to predict postoperative morbidity. However, no studies have been undertaken to examine the predictive efficacy of these models in biliary tract cancer patients, and other perioperative variables can also influence morbidity. As a result, the study's goal was to examine these models alone, as well as risk models combined with disease-specific factors, in predicting severe complications. Methods: A retrospective study of 129 patients was carried out. Data on demographics, surgery, and outcomes were gathered. These model equations were used to determine the morbidity risks. Severe morbidity was defined as the complication comprehensive index ≥ 40. Results: Severe morbidity was observed in 25% (32/129) patients. Multivariate analysis demonstrated that four parameters [comprehensive risk score ≥1, T stage, albumin decrease value, and international normalized ratio (INR)] had a significant influence on the probability of major complications. The area under the curve (AUC) of combining the four parameters was assessed as having strong predictive value and was superior to the Estimation of Physiologic Ability and Surgical Stress System (E-PASS) alone (the AUC value was 0.858 vs. 0.724, p = 0.0375). The AUC for the modified E-PASS (mE-PASS) and Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) in patients over the age of 70 was classified as no predictive value (p = 0.217 and p = 0.063, respectively). Conclusion: The mE-PASS and POSSUM models are ineffective in predicting postoperative morbidity in patients above the age of 70. In biliary tract cancer (BTC) patients undergoing radical operation, a combination of E-PASS and perioperative parameters generates a reasonable prediction value for severe complications.

Chyme reinfusion improved outcomes after definitive surgery for small-intestinal enteroatmospheric fistula in patients with enteral nutrition.

PURPOSE: In patients suffering from small-intestinal enteroatmospheric fistula who are receiving enteral nutrition (EN), although the function of the small intestine is sufficient, without chyme reinfusion (CR), disuse of the distal intestine of enteroatmospheric fistula may occur. However, CR reverses such pathological changes and have an influence on improving outcomes following definitive surgery (DS) for small-intestinal enteroatmospheric fistula. This study attempted to investigate the effect of preoperative CR in patients with EN on the outcomes after DS for small-intestinal enteroatmospheric fistula. METHODS: According to whether CR was performed between January 2012 and December 2019, patients receiving DS for small intestinal enteroatmospheric fistula were divided into the CR group and non-CR group. The effect of preoperative CR was then investigated. RESULTS: A total of 159 patients were finally enrolled, of which 72 patients were in the CR group and 87 patients were in the non-CR group. A total of 47 (29.56%) patients were found to have recurrent fistula after DS, the recurrent fistula rate in the CR group (multivariate odds ratio = 0.557; 95% CI, 0.351-0.842; P = 0.019) was lower. CR was also shown to promote postoperative recovery of bowel function (hazard ratio [HR] = 1.982; 95% CI, 1.199-3.275; P = 0.008), and shorten postoperative length of stay (LOS) (HR = 1.739; 95% CI, 1.233-2.453; P = 0.002). CONCLUSION: Preoperative CR may reduce the incidence of recurrent fistula, time to return of bowel function and postoperative LOS following DS for small-intestinal enteroatmospheric fistula.

Effect of long non-coding RNA H19 on oxidative stress and chemotherapy resistance of CD133+ cancer stem cells via the MAPK/ERK signaling pathway in hepatocellular carcinoma.

We explored the ability of a long non-coding RNA H19, to influence oxidative stress (OS) and chemotherapy resistance of CD133 + cancer stem cells via the MAPK/ERK signaling pathway in HCC. HCC tissues with corresponding adjacent normal tissues were collected. CD133 + HuH7 cells were sorted and assigned into five groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to determine expression levels mRNAs and proteins. Levels of reactive oxygen species (ROS) and malonaldehyde (MDA), and activity of superoxide dismutase (SOD) were measured. Cell viability was analyzed by MTT assay and cell apoptosis by flow cytometry. Compared with adjacent normal tissues, the H19 expression level was higher and MAPK and ERK protein levels were lower in HCC tissues. Compared with the blank group, in the pcDNA-H19 group, H19 expression level, MAPK and ERK protein levels, MDR1 and GST-π expression levels were increased, ROS and MDA levels were decreased, SOD activity was weakened, cell viability was promoted, and cell apoptosis was inhibited; in the siH19 group, H19 expression level, MAPK and ERK protein levels, MDR1 and GST-π expression levels were reduced, ROS and MDA levels were elevated, SOD activity was enhanced, cell viability was inhibited, and cell apoptosis was promoted. There was no significant difference among blank, NC and pcDNA-H19 + PD98059 groups. The study provides evidence that downregulation of H19 may induce OS and reverse chemotherapy resistance of CD133 + cancer stem cells by blocking the MAPK/ERK signaling pathway in HCC.

The impact of RAGE inhibition in animal models of bacterial sepsis: a systematic review and meta-analysis.

Objective To evaluate the impact of inhibition of the receptor for advanced glycation end products (RAGE) on the outcome of bacterial sepsis in animal models. Methods Relevant publications were identified by systematic searches of PubMed, ISI Web of Science and Elsevier-Scopus databases. Results A total of Eleven studies with moderate quality were selected for analysis. A meta-analysis of survival rates revealed a significant advantage of RAGE inhibition in comparison with controls (HR 0.67, 95% CI 0.52-0.86). This effect was most pronounced in polymicrobial infection (HR 0.28, 95% CI 0.14-0.55), followed by Gram positive (G+) bacterial infection (HR 0.70, 95% CI 0.50-0.97) and Gram negative (G-) bacterial infection (HR 0.89, 95% CI 0.58-1.38). For G+ bacterial infection, RAGE inhibition decreased bacterial outgrowth and dissemination, inflammatory cell influx, plasma cytokine levels, and pulmonary injury. Conclusions RAGE inhibition appears to have a beneficial impact on the outcome of sepsis in animal models, although there are discrepancies between different types of infection.

Nonstrict and individual enhanced recovery after surgery (ERAS) in partial hepatectomy.

BACKGROUND: We aimed to evaluate postoperative recovery and short-term outcomes of patients undergoing partial hepatectomy managed with a nonstrict and individual enhanced recovery after surgery (ERAS) program. METHODS: A retrospective analysis of 168 partial hepatectomy patients in our institution was included. The discharged day and the respective impact of element application throughout the duration were analyzed. RESULTS: When all the required elements of ERAS were fully implemented, the median discharge day was 6. The more deviation occurred, the more delayed the patient discharged (P < 0.01). Preoperative ASA score, basic conditions of patients and ages were revealed closely associated with discharge day (P < 0.001). Without or an early removal of tubes and early oral feeding reduced hospital stay statistically (P < 0.01). Early discharge of patients (<3 days) did not show an increased complication incidence or readmission (P > 0.05). CONCLUSION: Nonstrict and individual use of ERAS in partial hepatectomy reduced postoperative length of stay without increasing complication rate. Our study proposes a modulation of ERAS according to the needs and acceptance of patients. In a word, better optionally required rather than mandatorily meet.

Fast-track surgery and exclusive enteral nutrition applied to a rat model of heterotopic intestinal transplantation.

The present study applied fast-track surgery (FTS) concepts and exclusive enteral nutrition (EEN) to a rat model of heterotopic intestinal transplantation (HIT). A total of 96 pairs of Sprague-Dawley rats were randomly distributed into three groups, as follows: i) The conventional group (group 1); ii) the FTS group (group 2); and iii) the FTS with EEN group (EEN group). FTS alterations to the HIT protocol were as follows: i) The use of sevoflurane as an anesthetic; ii) alterations to the order of the procedure and iii) a modified suturing technique. In addition, the EEN group rats underwent an early EEN gavage. The operation time, success rate, recovery state and morphological characteristics of the grafts were compared among the groups. The average operative time was significantly decreased in the group 2 and EEN group rats (137.44±16.03 and 139.67±15.25 min, respectively), as compared with the group 1 rats (169.36±13.72 min; P<0.05). In addition, the percentage of rats surviving >14 days was significantly increased in the group 2 (87.5%) and EEN group (90.6%) rats, as compared with the group 1 rats (68.7%; P<0.05). Furthermore, the villi of graft in EEN group appeared longer, and exhibited narrower interspaces. The ischemia-reperfusion injury and mononuclear cell infiltration were attenuated at postoperative day 7. The results of the present study suggested that the application of FTS concepts and EEN gavage to HIT may accelerate recovery and ameliorate graft damage following surgery.

PU.1-Silenced Dendritic Cells Induce Mixed Chimerism and Alleviate Intestinal Transplant Rejection in Rats via a Th1 to Th2 Shift.

BACKGROUND/AIMS: Intestinal transplantation is an effective treatment for end-stage bowel failure; however, graft rejection and the toxicity associated with non-specific immunosuppression are major limitations of this procedure. Studies have shown that mixed chimerism can produce post-transplantation immune tolerance. Here, we demonstrate that in rat intestinal transplantation, PU.1-silenced dendritic cells (DCs) plus bone marrow (BM) cell transfusion results in mixed chimerism, and we investigate the mechanisms responsible for the effects of mixed chimerism rejection. METHODS: In a model of intestinal transplantation, male Brown Norway rats were the donors, and female Lewis rats were the recipients that were randomly divided into 4 groups: control, BM, BM-imDCs and BM-PU.1. The dynamic changes in graft morphology, rejection scoring and serum concentrations of Th1/Th2-related cytokines were investigated on postoperative days 0, 7, 14, 21, and 30. RESULTS: The BM-PU.1 group had better graft health, milder pathologic injuries, and lower rejection grades compared with the other groups. The rates of mixed chimerism were significantly highest in the BM-PU.1 group and correlated with decreases in serum IL-2 and increases in serum IL-10. CONCLUSION: Transfusion of PU.1-silenced DCs and BM cells induces stable mixed chimerism and has the potential to reduce pathologic injuries via a pro-Th2 shift in the Th1/Th2 balance.