Pancreatic cancer is one of the most troublesome malignancies with dismal prognosis. H. pylori has been recognized as a type I carcinogen. Several studies have evaluated the association between H. ...pylori infection and pancreatic cancer development, however, the conclusions are inconsistent.
Literature search was carried out in PubMed, EMBASE, Cochrane Library and CNKI databases to identify eligible researches. We performed overall meta-analysis of all studies included and subgroup analysis based on regional distribution. Quality of the studies (assessed by Newcastle-Ottawa quality assessment scale for case-control studies) and CagA+ strains of H. pylori were taken into consideration, and we conducted additional analyses including high-quality researches and those concerning CagA+ H. pylori respectively.
9 studies involving 3033 subjects (1083 pancreatic cancer cases, 1950 controls) were included. Summary OR and 95%CI of the overall meta-analysis of all included studies were 1.47 and 1.22-1.77, pooled data of the 4 high-quality studies were OR 1.28, 95%CI 1.01-1.63. OR of the 5 studies examined CagA+ strains was 1.42, corresponding 95%CI was 0.79 to 2.57. Summary estimates of subgroup analysis based on regional distribution are as follows, Europe group: OR 1.56, 95%CI 1.15-2.10; East Asia group: OR 2.01, 95%CI 1.33-3.02; North America group: OR 1.17, 95%CI 0.87-1.58. There was not obvious heterogeneity across the 9 studies. No publication bias was detected.
H. pylori infection is significantly, albeit weakly, associated with pancreatic cancer development. The association is prominent in Europe and East Asia, but not in North America. CagA+ H. pylori strains appear not to be associated with pancreatic cancer. However, more studies, especially prospective studies, are needed to validate our results.
Background
Telomere length (TL) has been regarded as a biomarker of aging, and TL shortening is associated with numerous chronic illnesses. The mounting evidence has shown that inflammatory cytokines ...are involved in maintaining or shortening TL, the causality of cytokines with TL remains unknown. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to estimate the underlying correlations of circulating inflammatory cytokines with TL.
Methods
Genetic instrumental variables for inflammatory cytokines were identified through a genome-wide association study (GWAS) involving 8,293 European individuals. Summary statistics of TL were derived from a UK Bio-bank cohort comprising 472,174 samples of individuals with European descent. We employed the inverse-variance weighted (IVW) approach as our main analysis, and to ensure the reliability of our findings, we also conducted additional analyses including the weighted median, MR-Egger, MR pleiotropy residual sum and outlier test, and weighted model. Lastly, the reverse MR analyses were performed to estimate the likelihood of inverse causality between TL and the cytokines identified in the forward MR analysis. Cochran’s Q test were employed to quantify the degree of heterogeneity.
Results
After applying Bonferroni correction, a higher circulating level of Interleukin-7 (IL-7) was suggestively associated with TL maintaining (OR:1.01, 95%CI:1.00-1.02, P=0.032 by IVW method). The study also revealed suggestive evidence indicating the involvement of Interleukin-2 receptor, alpha subunit (IL-2Rα) level was negatively associated with TL maintaining (OR:0.98, 95%CI:0.96-1.00, P=0.045 by IVW method), and the weighted median approach was consistent (OR:0.99, 95%CI:0.97-1.00, P=0.035). According to the findings of reverse MR analysis, no significant causal relationship between TL and cytokines was explored. Our analysis did not reveal any substantial heterogeneity in the Single nucleotide polymorphisms or horizontal pleiotropy.
Conclusions
Our MR analysis yielded suggestive evidence supporting the causality between circulating IL-7 and IL-2Rα and telomere length, necessitating further investigations to elucidate the mechanisms by which these inflammatory cytokines may impact the progression of telomeres.
We carried out a systematic review and meta-analysis to evaluate the impact of prophylactic dexamethasone on post-operative nausea and vomiting (PONV), post-operative pain, and complications in ...patients undergoing thyroidectomy.
We searched Pubmed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the prophylactic effect of dexamethasone versus placebo with or without other antiemetics for PONV in patients undergoing thyroidectomy. Meta-analyses were performed using RevMan 5.0 software.
Thirteen RCTs that considered high quality evidence including 2,180 patients were analyzed. The meta-analysis demonstrated a significant decrease in the incidence of PONV (RR 0.52, 95% CI 0.43 to 0.63, P < 0.00001), the need for rescue anti-emetics (RR 0.42, 95% CI 0.30 to 0.57, P<0.00001), post-operative pain scores (WMD -1.17, 95% CI -1.91 to -0.44, P = 0.002), and the need for rescue analgesics (RR 0.65, 95% CI 0.50-0.83, P = 0.0008) in patients receiving dexamethasone compared to placebo, with or without concomitant antiemetics. Dexamethasone 8-10mg had a significantly greater effect for reducing the incidence of PONV than dexamethasone 1.25-5mg. Dexamethasone was as effective as other anti-emetics for reducing PONV (RR 1.25, 95% CI 0.86-1.81, P = 0.24). A significantly higher level of blood glucose during the immediate post-operative period in patients receiving dexamethasone compared to controls was the only adverse event.
Prophylactic dexamethasone 8-10mg administered intravenously before induction of anesthesia should be recommended as a safe and effective strategy for reducing the incidence of PONV, the need for rescue anti-emetics, post-operative pain, and the need for rescue analgesia in thyroidectomy patients, except those that are pregnant, have diabetes mellitus, hyperglycemia, or contraindications for dexamethasone. More high quality trials are warranted to define the benefits and risks of prophylactic dexamethasone in potential patients with a high risk for PONV.
Background and objectives Trastuzumab is an important targeted drug for HER2-positive gastric cancer. The treatment efficacy of a more cost-effective and accessible trastuzumab biosimilar, HLX02, was ...not well investigated, especially when combined with antiangiogenic treatment. In addition, the tumour microenvironment detected by functional MRI was still unclear during treatment. This study attempts to evaluate the therapeutic effect of antiangiogenic agents combined with HLX02 in a HER2-positive gastric cancer xenograft model and to detect microenvironmental changes using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). Materials and methods We subcutaneously injected MKN-45 human gastric cancer cells into BALB/C nude mice to establish a tumour model. Twenty-eight mice were divided into four groups and treated with saline (Group 1), Endostar (Group 2), trastuzumab biosimilar HLX02 (Group 3), or the combination of Endostar and HLX02 (Group 4). We then performed IVIM-DWI before and at different time points after treatment. HE, HER2, TUNEL, E-cadherin staining, and alpha-SMA and CD31 double-staining were used to confirm the pathological changes. Results Group 4 demonstrated the smallest tumour volume at the end of treatment. The D value in Group 4 increased more dramatically, with the highest value on Day 20, compared with the other groups. Perfusion-related parameters (D* and f values) in Groups 2 and 4 increased initially and reversed after Day 10. Group 4 showed the lowest CD31 and HER2 and the highest TUNEL- and E-cadherin-positive staining rates. The D value was positively correlated with TUNEL but negatively correlated with HER2 staining. The D* and f values had positive correlations with CD31 and E-cadherin expression and the vessel maturity index. Conclusions The trastuzumab biosimilar drug HLX02 exhibited good treatment efficacy in HER2-positive gastric cancer, especially when combined with Endostar. IVIM-DWI can noninvasively monitor the process of vascular normalization and reflect the treatment effect early at the molecular level. Keywords: HLX02, IVIM-DWI, Gastric cancer, HER2, Endostar, Vascular normalization
Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have garnered attention as a potential ...alternative source. Nonetheless, traditional primary porcine hepatocytes exhibit certain limitations in function maintenance and in vitro proliferation. This study has discovered that by using histone deacetylase inhibitors (HDACi), primary porcine hepatocytes can be successfully reprogrammed into liver progenitor cells with high proliferative potential. This method enables porcine hepatocytes to proliferate over an extended period in vitro and exhibit increased susceptibility in lentivirus-mediated gene modification. These liver progenitor cells can readily differentiate into mature hepatocytes and, upon microencapsulation transplantation into mice with acute liver failure, significantly improve the survival rate. This research provides new possibilities for the application of porcine hepatocytes in the treatment of end-stage liver disease.
Display omitted
•VPA can promote the long-term in vitro expansion of porcine hepatocytes by reprogramming PPHs into HPCs.•VPA-iHPCs showed high susceptibility to lentivirus-mediated gene modification.•VPA-iMHs showed mature liver function.•Microencapsulated VPA-iMHs can rescute acute liver failure mice.
Pancreatic cancer (PACA), which is characterized by an immunosuppressive nature, remains one of the deadliest malignancies worldwide. Aberrant DNA methylation (DNAm) reportedly influences tumor ...immune microenvironment. Here, we evaluated the role of DNA methylation driven genes (MDGs) in PACA through integrative analyses of epigenomic, transcriptomic, genomic and clinicopathological data obtained from TCGA, ICGC, ArrayExpress and GEO databases. Thereafter, we established a four-MDG signature, comprising GPRC5A, SOWAHC, S100A14, and ARNTL2. High signature risk-scores were associated with poor histologic grades and late TNM stages. Survival analyses showed the signature had a significant predictive effect on OS. WGCNA revealed that the signature may be associated with immune system, while high risk-scores might reflect immune dysregulation. Furthermore, GSEA and GSVA revealed significant enrichment of p53 pathway and mismatch repair pathways in high risk-score subgroups. Immune infiltration analysis showed that CD8+ T cells were more abundant in low score subgroups, while M0 macrophages exhibited an opposite trend. Moreover, negative regulatory genes of cancer-immunity cycle (CIC) illustrated that immunosuppressors TGFB1, VEGFA, and CD274 (PDL1) were all positively correlated with risk-scores. Furthermore, the four signature genes were negatively correlated with CD8+ lymphocytes, but positively associated with myeloid derived suppressor cells (MDSC). Conversely, specimens with high risk-scores exhibited heavier tumor mutation burdens (TMB) and might show better responses to some chemotherapy and targeted drugs, which would benefit stratification of PACA patients. On the other hand, we investigated the corresponding proteins of the four MDGs using paraffin-embedded PACA samples collected from patients who underwent radical surgery in our center and found that all these four proteins were elevated in cancerous tissues and might serve as prognostic markers for PACA patients, high expression levels indicated poor prognosis. In conclusion, we successfully established a four-MDG-based prognostic signature for PACA patients. We envisage that this signature will help in evaluation of intratumoral immune texture and enable identification of novel stratification biomarkers for precision therapies.
Several mitogen-activated protein kinases (MAPKs) are activated during thermal injury, and the p38 MAPK is specifically involved in endothelial cell (EC) actin and myosin rearrangement (stress-fiber ...formation) with ensuing cellular contraction and enhanced vessel permeability. Inhibition of p38 MAPK and extracellular signal-related kinase MAPK by their inhibitors SB203580 and PD98059, respectively, significantly reduces burn serum-induced EC stress-fiber formation, whereas SB203580 also inhibits burn serum-induced EC tight-junction damage and thereby general blood vessel hyperpermeability. The JNK MAPK inhibitor, SP600125, on the contrary, influences neither stress-fiber formation nor EC tight-junction damage. Extracellular signal-related kinase MAPK inhibition significantly decreases burn serum-induced Monocyte chemotactic protein-1 (MCP-1) release, whereas SB203580 and SP600125 have only limited such effects. Western blotting, real-time reverse transcriptase-polymerase chain reaction, and confocal laser scanning microscopy proved that SP600125 significantly inhibits burn serum-induced intercellular adhesion molecule 1 expression, whereas SB203580 depresses the expression of P selectin. In vivo studies, using the dominant negative adenoviral approach of MAPK kinase 3b and MAPK kinase 6b to block p38 MAPKs, and MKK4 and MKK7 to block JNK MAPKs, show that the latter MAPKs are involved in the regulation of P selectin and intercellular adhesion molecule 1 expression, respectively, following thermal injury. Taken together, the results suggest that several MAPKs play important, although different, roles in general EC alterations following burn injuries.
The rational design of the third component to enhance the efficiency and stability of organic solar cell (OSC) is a critical and challenge. Herein, a thieno3,2-bthiophene (TT) substituted ...wide-bandgap small molecule donor BTTC, was designed, synthesized and incorporated into the state-of-the-art PM6:L8-BO binary to construct ternary OSC. The rigid side chain and planar molecule skeleton enables strong crystallinity and complementary absorption with binary system. The introduction of BTTC enhanced the molecular packing, fibril-like film and preferred vertical phase separation, yielding balanced and higher charge transport, more efficient exciton dissociation and suppressed charge recombination. Besides, lower energy loss was attained and thus leading to higher open-circuit voltage (VOC). Consequently, the introduction of BTTC achieved the highest efficiency of 18.8% along with extended operational stability. Furthermore, replacing L8-BO to BTP-eC9 further boosted the ternary PCE to 19.18%, standing one of the best charge management in ternary OSC. This work presents efficient rigid side chain substitution strategy to construct the third component of small molecule donor for high performance ternary OSCs with comprehensively improved photovoltaic parameters. This strategy broadens the selection of guest materials toward realizing the actual commercial application of OSCs.
Display omitted
•The rigid side chain and planar molecule skeleton of BTTC enables strong crystallinity.•The PM6:BTTC:L8-BO blend film achieved 18.8% efficiency along with superior operational stability.•Replacing L8-BO to BTP-eC9 further boosted the PCE to 19.18%, standing one of the best charge management in ternary OSC.
The strategic and logical development of the third component (guest materials) plays a pivotal and intricate role in improving the efficiency and stability of ternary organic solar cells (OSCs). In ...this study, a novel guest material with a wide bandgap, named IDTR, is designed, synthesized, and incorporated as the third component. IDTR exhibits complementary absorption characteristics and cascade band alignment with the PM6:Y6 binary system. Morphological analysis reveals that the introduction of IDTR results in strong crystallinity, good miscibility, and proper vertical phase distribution, thereby realizing heightened and balanced charge transport behavior. Remarkably, the novel ternary OSCs have exhibited a significant enhancement in photovoltaic performance. Consequently, open‐circuit voltage (VOC), short‐circuit current (JSC), and fill factor (FF) have all witnessed substantial improvements with a remarkable power conversion efficiency (PCE) of 18.94% when L8‐BO replaced Y6. Beyond the pronounced improvement in photovoltaic performance, superior device stability with a T80 approaching 400 h is successfully achieved. This achievement is attributed to the synergistic interplay of IDTR, providing robust support for the overall enhancement of performance. These findings offer crucial guidance and reference for the design and development of efficient and stable OSCs.
In this study, IDTR and binary systems have complementary absorption characteristics and cascade alignment. The morphology analysis shows that the introduction of IDTR makes it have strong crystallinity, good miscibility, and reasonable vertical phase distribution, thus achieving higher and more balanced charge transport behavior. The PCE is significantly improved, and the continuously illuminated T80 successfully achieved excellent device stability of nearly 400 h.
Complement factor H-related protein 1 (CFHL1) was recently reported to be a potential biomarker in several types of cancer. CFHL1, however, has not been found to be of prognostic value in ...hepatocellular carcinoma (HCC) to date. In the present study, the expression levels of CFHL1 were evaluated in 8 pairs fresh frozen tissue samples using western blotting. Furthermore, the expression level of CFHL1 was evaluated in 76 pairs of formalin-fixed, paraffin-embedded (FFPE) HCC and peritumoral tissues (expression pattern cohort), and 278 FFPE HCC tissues (prognostic cohort) using tissue microarray-based immunohistochemistry. The Kaplan-Meier method, Cox regression proportional hazard model and receiver operating characteristic curve analysis were used to evaluate prognostic factors. The expression level of CFHL1 was reduced in HCC tissues in 67.1% (51/76) of the cases compared with the corresponding peritumoral tissues. Survival analyses indicated that patients with HCC with low CFHL1 expression had a worse time-to-recurrence (TTR) and overall survival (OS) compared with those with high CFHL1 expression in the prognostic cohort (P=0.002 for OS and P=0.017 for TTR). Both univariate and multivariate analyses indicated that CHFL1 was an independent prognostic factor for TTR and OS (P=0.017 and P=0.002, respectively). In addition, The Cancer Genome Atlas (TCGA) and Human Protein Atlas were used for further validation. Furthermore, a prognostic model included tumor size, tumor number, liver cirrhosis and CFHL1 expression was evaluated. The results of the present study demonstrated that CFHL1 was downregulated in HCC and its level was associated with patient prognosis; therefore, CFHL1 is a potential prognostic marker for HCC.
PDF
