A number of pancreatic anastomosis methods for pancreaticoduodenectomy including pancreaticogastrostomy(PG), duct-to-mucosa pancreaticojejunostomy(duct-to-mucosa PJ), invagination ...pancreaticojejunostomy(invagination PJ) and binding pancreaticojejunostomy(BPJ), but the optimal choice remains unclear. We performed a network meta-analysis to synthesize direct and indirect evidence to identify the optimal choice for pancreatic anastomosis after pancreaticoduodenectomy
We searched the Embase, PubMed and Cochrane library databases for randomized control trials. The relative risk (RR) and its 95% confidence interval (CI) were calculated. The primary outcome is postoperative pancreatic fistula (POPF).
In total, 16 RCT studies, including a total of 2396 patients, met our criteria. The results showed that PG is not superior to invagination PJ (RR 0.70 95%CI: 0.35–1.39) and duct-to-mucosa PJ (RR 0.58 95%CI: 0.30–1.10) according to the ISGPS definition. Furthermore PG cannot reduce the POPF rates than invagination PJ (RR 0.51 95%CI: 0.2–1.21) and duct-to-mucosa PJ (RR 0.46 95%CI: 0.16–1.14) according to the soft pancreatic texture. BPJ might reduce the incidence of POPF than duct-to-mucosa PJ (RR 0.00 95%CI: 0.00–0.04), invagination PJ (RR 0.00 95%CI: 0.00–0.03), PG (RR 0.00 95%CI: 0.00–0.03), but the results have major limitations with only one RCT reported BPJ and different definition of POPF.
There are no significant differences among BPJ, duct-to-mucosa PJ, invagination PJ and PG in the prevention of POPF, overall morbidity, mortality and DGE. However, further randomized controlled trials should be undertaken to ascertain these findings, especially for BPJ.
•A network meta-analysis is performed to synthesize direct and indirect evidence to identify the optimal choice for pancreatic anastomosis after pancreaticoduodenectomy.•PG is not superior to duct-to-mucosa PJ and invagination PJ in the prevention of POPF according to the ISGPS definition and pancreatic texture.•No significant differences among BPJ, duct-to-mucosa PJ, invagination PJ and PG in the prevention of POPF, overall morbidity, mortality and DGE.•However, further randomized controlled trials should be undertaken to ascertain these findings, especially for BPJ.
Accumulated evidences have demonstrated that long non-coding RNAs (lncRNAs) are correlated with prognosis of patients with hepatocellular carcinoma. The current study aimed to develop and validate a ...prognostic lncRNA signature to improve the prediction of overall survival in hepatocellular carcinoma patients.
The study cohort involved 348 hepatocellular carcinoma patients with lncRNA expression information and overall survival information. Through gene mining approach, the current study established a prognostic lncRNA signature (named LncRNA risk prediction score) for predicting the overall survival of hepatocellular carcinoma patients.
The current study built a predictive nomogram based on ten prognostic lncRNA predictors through Cox regression analysis. In model group, the Harrell's concordance indexes of LncRNA risk prediction score were 0.811 (95% CI 0.769-0.853) for 1-year overall survival, 0.814 (95% CI 0.772-0.856) for 3-year overall survival and 0.796 (95% CI 0.754-0.838) for 5-year overall survival respectively. In validation cohort, the Harrell's concordance indexes of LncRNA risk prediction score were 0.779 (95% CI 0.737-0.821), 0.828 (95% CI 0.786-0.870) and 0.796 (95%CI 0.754-0.838) for 1-year survival, 3-year survival and 5-year survival respectively. LncRNA risk prediction score could stratify hepatocellular carcinoma patients into low risk group and high risk group. Further survival curve analysis demonstrated that the overall survival rate of high risk patients was significantly poorer than that of low risk patients (
< 0.001).
In conclusion, the current study developed and validated a prognostic signature to predict the individual mortality risk for hepatocellular carcinoma patients. LncRNA risk prediction score is helpful to identify the patients with high mortality risk and optimize the individualized treatment decision. The web calculator can be used by click the following URL: https://zhangzhiqiao2.shinyapps.io/Smart_cancer_predictive_system_HCC_3/.
Doxorubicin (DOX) has received attention due to dose-dependent cardiotoxicity through abnormal redox cycling. Native fibroblast growth factor 1 (FGF1) is known for its anti-oxidative benefits in ...cardiovascular diseases, but possesses a potential tumorigenic risk. Coincidentally, the anti-proliferative properties of resveratrol (RES) have attracted attention as alternatives or auxiliary therapy when combined with other chemotherapeutic drugs. Therefore, the purpose of this study is to explore the therapeutic potential and underlying mechanisms of co-treatment of RES and FGF1 in a DOX-treated model. Here, various cancer cells were applied to determine whether RES could antagonize the oncogenesis effect of FGF1. In addition, C57BL/6J mice and H9c2 cells were used to testify the therapeutic potential of a co-treatment of RES and FGF1 against DOX-induced cardiotoxicity. We found RES could reduce the growth-promoting activity of FGF1. Additionally, the co-treatment of RES and FGF1 exhibits a more powerful cardio-antioxidative capacity in a DOX-treated model. The inhibition of SIRT1/NRF2 abolished RES in combination with FGF1 on cardioprotective action. Further mechanism analysis demonstrated that SIRT1 and NRF2 might form a positive feedback loop to perform the protective effect on DOX-induced cardiotoxicity. These favorable anti-oxidative activities and reduced proliferative properties of the co-treatment of RES and FGF1 provided a promising therapy for anthracycline cardiotoxicity during chemotherapy.
Enzymes involved in collagen biosynthesis, including lysyl oxidase （LOX）, have been proposed as potential therapeutic targets for idio- pathic pulmonary fibrosis. LOX expression is significantly ...upregulated in bleomycin （BLM）-induced lung fibrosis, and knockdown of LOX expression or inhibition of LOX activity alleviates the lung fibrosis. Unexpectedly, treatment of the mice with LOX inhibitor at the inflammatory stage, but not the fibrogenic stage, efficiently reduces collagen deposition and normalizes lung architecture. Inhibition of LOX impairs inflammatory ceU infiltration, TGF-β signaling, and myofibroblast accumulation. Furthermore, ectopic expres- sion of LOX sensitizes the fibrosis-resistant Balb/c mice to BLM-induced inflammation and lung fibrosis. These results suggest that LOX is indispensable for the progression of BLM-induced experimental lung fibrosis by aggravating the inflammatory response and subse- quent fibrosis process after lung injury.
Nearly one-quarter of all avian species is either threatened or nearly threatened. Of these, 73 species are currently being rescued from going extinct in wildlife sanctuaries. One of the previously ...most critically-endangered is the crested ibis, Nipponia nippon. Once widespread across North-East Asia, by 1981 only seven individuals from two breeding pairs remained in the wild. The recovering crested ibis populations thus provide an excellent example for conservation genomics since every individual bird has been recruited for genomic and demographic studies.
Using high-quality genome sequences of multiple crested ibis individuals, its thriving co-habitant, the little egret, Egretta garzetta, and the recently sequenced genomes of 41 other avian species that are under various degrees of survival threats, including the bald eagle, we carry out comparative analyses for genomic signatures of near extinction events in association with environmental and behavioral attributes of species. We confirm that both loss of genetic diversity and enrichment of deleterious mutations of protein-coding genes contribute to the major genetic defects of the endangered species. We further identify that genetic inbreeding and loss-of-function genes in the crested ibis may all constitute genetic susceptibility to other factors including long-term climate change, over-hunting, and agrochemical overuse. We also establish a genome-wide DNA identification platform for molecular breeding and conservation practices, to facilitate sustainable recovery of endangered species.
These findings demonstrate common genomic signatures of population decline across avian species and pave a way for further effort in saving endangered species and enhancing conservation genomic efforts.
Current guidelines recommend angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) as a first-line therapy in diabetic hypertensive patients and for secondary prevention ...in patients with obstructive coronary artery disease (OCAD). However, the effects of using ACEI/ARB before the initial diagnosis of OCAD on major adverse cardiac and cerebral event (MACCE) in diabetic hypertensive patients remain unclear. This study investigated whether using ACEI/ARB before the initial diagnosis of OCAD could be associated with improved clinical outcomes in diabetic hypertensive patients.
A total of 2501 patients with hypertension and diabetes, who were first diagnosed with OCAD by coronary angiography, were included in the analysis. Of the 2501 patients, 1300 did not used ACEI/ARB before the initial diagnosis of OCAD the ACEI/ARB(-) group; 1201 did the ACEI/ARB(+) group. Propensity score matching at 1:1 was performed to select 1050 patients from each group. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, heart function, and subsequent MACCE during a median of 25.4-month follow-up were determined and compared between the 2 groups.
Compared with the ACEI/ARB(-) group, the ACEI/ARB(+) group had significantly lower incidence of AMI (22.5% vs. 28.4%, p < 0.05), smaller infarct size in patients with AMI (pTNI: 5.7 vs. 6.8 ng/ml, p < 0.05; pCKMB: 21.7 vs. 28.7 ng/ml, p < 0.05), better heart function (LVEF: 60.0 vs. 58.5%, p < 0.05), and lower incidences of non-fatal stroke (2.4% vs. 4.6%, p < 0.05) and composite MACCE (23.1% vs. 29.7%, p < 0.05). No prior ACEI/ARB therapy was significantly and independently associated with non-fatal stroke and composite MACCE.
In diabetic hypertensive patients, treatment with ACEI/ARB before the initial diagnosis with OCAD was associated with decreased incidence of AMI, smaller infarct size, improved heart function, and lower incidences of non-fatal stroke and composite MACCE. Trial registration Retrospectively registered.
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•Most GTF hybrids exhibited strong inhibitory effect on Aβ aggregation and potent butyrylcholinesterase inhibitory potencies.•GTF cinnamate derivative A15 exhibited best inhibition of ...Aβ aggregation and potent AChE inhibitory activity.•GTF triazole derivative C4 showed the best inhibitory activity to BuChE.•A15 and C4 showed potent neuroprotective activities and nearly no toxicity on SH-SY5Y cells.
7-O-galloyltricetiflavan (GTF), a natural flavonoid, is known to exert anti-oxidation and neuroprotective activity, which are related to the prevention of Alzheimer’s disease (AD). In this study, three series of GTF hybrids have been designed, synthesized and evaluated as multifunctional agents for treatment AD. The biological assays indicated that most of them showed strong inhibitory effect on self-induced β-amyloid (Aβ) aggregation, and a significant ability to inhibit ChEs. Among them, compound A15 exhibited best inhibition of Aβ aggregation (78.81% at 20 μM), potent AChE inhibitory potencies (IC50, 0.56 μM), and compound C4 presented the highest ability to inhibit BuChE (IC50, 5.77 μM). Furthermore, kinetic, molecular modeling and molecular dynamics studies revealed that A15 and C4 could interact with the catalytic active site of AChE and BuChE, respectively. In addition, compounds A15 and C4 could cross the blood–brain barrier in vitro. More importantly, A15 and C4 also showed excellent neuroprotective activities against H2O2-induced human neuroblastoma SH-SY5Y cells damage and nearly no toxicity on SH-SY5Y cells. All of these outstanding in vitro results indicated A15 and C4 as the leading structure worthy of further investigation.
Taking loess as the research object, the influence of cement content on mechanical properties of loess was studied. Firstly, the basic physical parameters of loess were obtained through laboratory ...physical index test, and improved by using Portland cement. Secondly, under different incorporation ratios (3%, 5%, 7%, 9%), heavy compaction test and liquid-plastic limit test were carried out respectively to obtain mechanical parameters of cement-improved loess. Finally, the shear strength parameters and compressive strength of the improved soil samples are obtained by unconsolidation undrained triaxial shear test and unconfined compressive strength test. The results show that the liquid limit, plastic limit and plastic index of loess improved by adding cement increase compared with the original soil sample, indicating that the binding force between soil particles is improved and the plasticity is enhanced. The variation range of dry density and water content has no obvious relationship with the content of cement. At the same time, the compressibility of soil is reduced and the collapsibility of soil is eliminated. With the increase of age, the strength of cement-modified soil also increases. Through unconsolidated and undrained triaxial shear tests and unconfined compressive strength tests, the strength of loess improved significantly after adding cement, and the strength of soil-cement increased with the increase of cement content, and water stability was obviously improved.
The stability of loess subgrade is affected by many factors. Freeze-thaw cycles are a common factor that causes the strength of loess subgrades to be damaged. In order to study the influence of ...freezethaw cycles on the stability of loess subgrades, reveal the mechanism of freeze-thaw cycles on the strength of loess subgrades. It is necessary to sample the loess soil samples in this area, and perform compaction test, freeze-thaw cycle test, unconfined compression test and electron microscope scanning test on the soil sample to analyze the influence of freeze-thaw cycle on the strength and microstructure of loess soil. . In this way, the potential relationship between the microstructure and the strength of the soil can be obtained. The results found that the freeze-thaw cycle of loess led to a trend of first increase and then decrease in soil strength. The microstructure showed a trend of smaller soil particles and increased soil voids. The potential relationship between the microstructure and the strength of the soil was analyzed. It explains the conclusion that the strength of the soil first increases and then decreases.
•Kv channel-mediated vasodilation of coronary artery was impaired in ZDF rats.•AGEs reduced Kv expression and currents in CSMCs via activating NF-κB pathway.•Blocking AGEs or NF-κB pathway improved ...coronary artery dilation in ZDF rats.
Excessive formation of advanced glycation end products (AGEs) impairs voltage-gated potassium (Kv) channels in rat coronary artery smooth muscle cells (CSMCs), resulting in weakened Kv-mediated coronary vasodilation. We hypothesized that induction of the nuclear factor-κB (NF-κB) signaling pathway by AGEs plays a significant role in the regulation of Kv channel-mediated vasodilation in Zucker diabetic fatty (ZDF) rats. Assays of mRNA transcripts, protein expression, and intracellular localization as well as patch-clamp experiments in cultured CSMCs revealed that AGEs significantly induced activation of the NF-κB signaling pathway, reduced Kv1.2/1.5 expression, and inhibited Kv currents. In addition, silencing of the receptor for AGEs (RAGE) or p65 with siRNA and treatment with alagrebrium (ALA) or pyrrolidine dithiocarbamate (PDTC) alleviated the AGE-induced impairment of Kv channels in CSMCs. Compared with Zucker lean (ZL) rats, the amount of AGEs, RAGE protein expression, and NF-κB activity in coronary arteries were higher in ZDF rats; whereas Kv1.2/1.5 expression was significantly lower in ZDF rats. Reduced Kv1.2/1.5 expression in coronary arteries and impaired Kv-mediated coronary relaxation tested by wire myography in ZDF rats were markedly improved by treatment with aminoguanidine (AG), ALA, or PDTC. These effects were accompanied by diminished NF-κB activity, inflammation, and oxidative stress. Taken together, these results indicate that an increased interaction between AGEs and RAGE in diabetic rats leads to impaired Kv channel-mediated coronary vasodilation. Moreover, activation of the NF-κB signaling pathway and a subsequent increase of inflammation and oxidative stress may play an important role in AGE-induced impairment of coronary vasodilation in diabetes.
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