A novel four­gene biomarker for tobacco smoking -induced colorectal cancer progression.

INTRODUCTION: Cigarette smoking greatly promotes the progression and poor prognosis of colorectal cancer (CRC) patients, with the molecular mechanism still not fully clear. METHODS: In this study, CRC cells were exposed to tobacco specific nitrosamine 4­(methylnitrosamino)­1­(3­pyridyl) 1­butanone (NNK), and the differentially expressed smoking-related genes were identified based on both NNK-induced CRC cells and a total of 763 CRC tissues from TCGA cohort. Cox regression analysis, ROC curve and Kaplan-Meier plot were used to establish the risk score model for CRC prognosis. Moreover, qRT-PCR, western blotting, colony formation, migration and invasion assays were performed to verify the core differentially expressed smoking-related gene and its molecular function in NNK-induced CRC progression. RESULTS: Results indicated NNK significantly enhanced CRC cell proliferation, migration and invasion. Moreover, a four-gene signature containing AKR1B10, CALB2, PLAC1, GNA15 was established as CRC prognosis marker. Among these four genes, AKR1B10 was further validated as the core gene, and its expression was significantly inhibited after NNK exposure in CRC cells. Results of gene enrichment analysis and western blotting suggested AKR1B10 might reduce the malignant progression of NNK-induced CRC cells through inhibiting Wnt signaling pathway by promoting E-Cadherin expression and inhibiting the expression of N-Cadherin, ß-Catenin, Vimentin and Snail. CONCLUSION: In conclusion, a new four smoking-related genes can be jointly used as prognostic markers for CRC. AKR1B10 served as a tumor suppressor, can be used as a potential target to inhibit NNK-induced CRC malignant progression through regulating Wnt signaling pathway. IMPLICATIONS: This study demonstrates tobacco-derived NNK dependence would promote the malignant progression of colorectal cancer through regulating the expressions of AKR1B10/Wnt signaling pathway. And a novel four-gene signature is established for the prognosis prediction of smoking CRC patients. These findings have important translational implications given the continued use of tobacco and the difficulty in smoking cessation worldwide, which can be applied to alleviate the adverse effects induced by tobacco dependence on colorectal cancer patients.

Exploring global research status and trends in anti-obesity effects of traditional Chinese medicine through intestinal microbiota: a bibliometric study.

Background: The intestinal microbiota (IM) has been found to contribute to metabolic disorders that lead to excessive fat accumulation, systemic and chronic low-grade inflammation, and insulin resistance in the host. Current research highlights a pivotal interaction between IM and traditional Chinese medicine (TCM) in mitigating obesity-related diseases. Undeniably, IM stands as a central focus in TCM research aimed at preventing and treating obesity. Therefore, tracing the progress and trends in this field can offer valuable references and insights for future studies. Methods: On June 17, 2023, we conducted a literature search on the topic of "IM and obesity in TCM" spanning the period from 2009 to 2023. We extracted the primary information of the publications, which includes complete records and reference citations, from the Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection (WoSCC). To visualize and analyze the literature, we utilized CiteSpace and VOSviewer for bibliometric analysis. Results: During the past fifteen years, a rapid increase in the number of publications has been observed. The cooperative networks demonstrate China, Beijing University of Chinese Medicine, and Food & Function as the most active countries, organizations, and journals in this field, respectively. Liu Bin has contributed the most publications. A paper by Xu Jia, published in 2014, holds the highest Local Citation Score (LCS). Analyses of keyword co-occurrence and reference co-citation indicate that the research hotspots of IM and obesity in TCM are primarily focused on the metabolic benefits driven by endogenous functional metabolic molecules generated by TCM regulation of IM. Other focal points include the mechanism by which TCM regulates IM to restore the intestinal mucosal barrier This is a provisional file, not the final typeset article, and manages the gut-organ axis, the metabolic advantages of acupuncture's regulation of IM, and the process by which Chinese medicine small molecules transform IM. Conclusion: This research offers a comprehensive understanding of the current status, hotspots, and trends in global TCM research. Additionally, it provides a comprehensive summary and exploration of the latest advancements in this field, thereby emphasizing the essence of TCM more effectively.

Purple Yam Polyphenol Extracts Exert Anticolitis and Anticolitis-Associated Colorectal Cancer Effects through Inactivation of NF-κB/p65 and STAT3 Signaling Pathways.

Colorectal cancer is a malignancy with high incidence and mortality worldwide, and ulcerative colitis (UC) is strongly associated with colorectal cancer. Purple yam, also known as Dioscorea alata, has been reported to be rich in plant polyphenols that have possessed anti-inflammatory, antioxidant, and antitumor properties. However, it is not clear whether purple yam polyphenol extracts (PYPE) can improve colitis and inhibit colitis-related colorectal tumorigenesis. Therefore, we used dextran sulfate sodium (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated colorectal cancer (CAC) models in mice to evaluate the preventive value and possible mechanisms of PYPE. It was found that PYPE effectively alleviated DSS-induced colitis, inhibited macrophage infiltration, and reduced the production of the pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, IL-17A, CXCL1, and MCP-1, and the higher the concentration of PYPE, the better the inhibitory effect. In addition, PYPE dramatically prevented the development of CAC and tumor proliferation in mice. Furthermore, PYPE inactivated NF-κB and STAT3 signaling to exert anti-inflammatory and anticancer effects. Taken together, these findings indicate that PYPE may be used as a promising preventive strategy against UC and CAC.

Effectiveness of multiple eHealth-delivered lifestyle strategies for preventing or intervening overweight/obesity among children and adolescents: A systematic review and meta-analysis.

Objective: To investigate the effect of multiple eHealth-delivered lifestyle interventions on obesity-related anthropometric outcomes in children and adolescents. Methods: The Medline (via PubMed), Embase, Cochrane Library, Web of Science, CBM, VIP, CNKI, and Wanfang electronic databases were systematically searched from their inception to March 18, 2022, for randomized controlled trials (RCTs). Meta-analyses were performed to investigate the effect of multiple eHealth-delivered lifestyle interventions on obesity-related anthropometric outcomes (body mass index [BMI], BMI Z-score, waist circumference, body weight, and body fat%). Two independent investigators reviewed the studies for accuracy and completeness. All included studies were evaluated using the Cochrane Risk-of-Bias (ROB) Tool. Results: Forty trials comprising 6,403 patients were selected for the meta-analysis. The eligible trials were published from 2006 to 2022. Compared with the control group, the eHealth-intervention group was more effective in reducing BMI (weighted mean difference [WMD] = -0.32, 95% confidence interval [CI]: -0.50 to -0.13, I2 = 85.9%), BMI Z-score (WMD = -0.08, 95% CI: -0.14 to -0.03, I2 = 89.1%), waist circumference (WMD = -0.87, 95% CI: -1.70 to -0.04, I2 = 43.3%), body weight (WMD = -0.96, 95% CI: -1.55 to -0.37, I2 = 0.0%), and body fat% (WMD = -0.59, 95% CI: -1.08 to -0.10, I2 = 0.0%). The subgroup analysis showed that parental or school involvement (WMD = -0.66, 95% CI: -0.98 to -0.34), eHealth-intervention duration of >12 weeks (WMD = -0.67, 95% CI: -0.96 to -0.38), and mobile-based interventions (WMD = -0.78, 95% CI: -1.13 to -0.43) had a significantly greater intervention effect size on BMI. Conclusions: This review recommends that multiple eHealth-delivered lifestyle strategies may be useful for preventing or treating overweight and obesity among children and adolescents. However, our results should be cautiously interpreted due to certain limitations in our study.

Income, workload, and any other factors associated with anticipated retention of rural doctors?

OBJECTIVE: The turnover of rural doctors, including doctors who leave clinical practice in rural areas, may disrupt the continuity of care. Though strategies had been formulated to address the problems associated with low retention rates, they proved to be unrewarding. This study aimed to investigate how we could anticipate the loss of rural doctors to facilitate their retention in advance. DESIGN: We conducted a cross-sectional survey and collected data from rural doctors in Jiangsu Province. SETTING: Research on the employment status of target admission graduates in Jiangsu. PARTICIPANTS: Multi-stage stratified sampling methods were employed to select the respondents in this study. We selected 722 rural physicians, who represented all the rural physicians from Northern, Central, and Southern Jiangsu. MEASURES: Factors affecting anticipated rural retention (odds ratios (OR)). RESULTS: The anticipated rural retention rate was 72.8% for the 722 respondents from Jiangsu province. Economically developed work areas (ORCentral JS = 0.501, ORSouthern JS = 0.475), a higher monthly income (OR 3000∼ = 0.584, OR6000∼ = 0.255), and an advanced rank among counterparts (OR = 0.507) were protective factors for anticipated rural retention. Risk factors involved the monthly expenditure, mainly for socialization with others (OR = 1.856), working hours of more than 50 hours/week (OR = 2.076), assignment of outpatient work (OR = 1.991), and filing work (OR = 1.544) as the main tasks on a daily basis. CONCLUSION: A combination of strategies, including the strengthening of economic incentive as well as the ability to deal with a heavy workload, could increase the recruitment and retention rate in Jiangsu Province.

Identification and validation of a cigarette smoke-related five-gene signature as a prognostic biomarker in kidney renal clear cell carcinoma.

Cigarette smoking greatly promotes the progression of kidney renal clear cell carcinoma (KIRC), however, the underlying molecular events has not been fully established. In this study, RCC cells were exposed to the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine) for 120 days (40 passages), and then the soft agar colony formation, wound healing and transwell assays were used to explore characteristics of RCC cells. RNA-seq was used to explore differentially expressed genes. We found that NNK promoted RCC cell growth and migration in a dose-dependent manner, and RNA-seq explored 14 differentially expressed genes. In TCGA-KIRC cohort, Lasso regression and multivariate COX regression models screened and constructed a five-gene signature containing ANKRD1, CYB5A, ECHDC3, MT1E, and AKT1S1. This novel gene signature significantly associated with TNM stage, invasion depth, metastasis, and tumor grade. Moreover, when compared with individual genes, the gene signature contained a higher hazard ratio and therefore had a more powerful value for the prognosis of KIRC. A nomogram was also developed based on clinical features and the gene signature, which showed good application. Finally, AKT1S1, the most crucial component of the gene signature, was significantly induced after NNK exposure and its related AKT/mTOR signaling pathway was dramatically activated. Our findings supported that NNK exposure would promote the KIRC progression, and the novel cigarette smoke-related five-gene signature might serve as a highly efficient biomarker to identify progression of KIRC patients, AKT1S1 might play an important role in cigarette smoke exposure-induced KIRC progression.

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a pregnancy-specific multisystem disease as well as an important cause of maternal and perinatal death. This study aimed to analyze the placental transcriptional data and clinical information of PE patients available in the published database and predict the target genes for prevention of PE. METHODS: The clinical information and corresponding RNA data of PE patients were downloaded from the GEO database. Cluster analysis was performed to examine the correlation between different genotyping genes and clinical manifestations. Then, bioinformatic approaches including GO, KEGG, WGCNA, and GSEA were employed to functionally characterize candidate target genes involved in pathogenesis of PE. RESULTS: Two PE datasets GSE60438 and GSE75010 were obtained and combined, thereby providing the data of 205 samples in total (100 non-PE and 105 PE samples). After eliminating the batch effect, we grouped and analyzed the integrated data, and further performed GSEA analysis. It was found that the genes in group 1 and group 2 were different from those in normal samples. Moreover, WGCNA analysis revealed that genes in group 1 were up-regulated in turquoise module, including SASH1, PIK3CB and FLT-1, while genes in group 2 were up-regulated in the blue and brown modules. We further conducted GO and KEGG pathway enrichment analyses and found that the differential genes in turquoise module were mainly involved in biological processes such as small molecular catabolic process, while being highly enriched in pathways, including MAPK signaling pathway and Rap1 signaling pathway. CONCLUSION: FLT-1 was conventionally used to predict PE risk, and sFLT-1 could also be used as an indicator to evaluate PE treatment effect. As a candidate biomarker for predicting PE, SASH1 may participate in proliferation, migration, invasion and epithelial mesenchymal transformation of human trophoblast cells by regulating MAPK pathway and Rap1 signaling pathway, thus affecting the progression of PE. The mechanism allowing PIK3CB to regulate PE development was not clear, while the gene could be another candidate biomarker for PE risk prediction. This is an exploratory study and our findings were still required verification in further studies.

Nicotine-derived NNK induces the stemness enrichment of CRC cells through regulating the balance of DUSP4-ERK1/2 feedback loop.

Cigarette smoking has been considered as an independent risk factor for colorectal cancer (CRC) initiation and progression. In this study, we found that cigarette smoking was significantly associated with poor CRC differentiation (P = 0.040). Since studies have indicated that poorly differentiated tumors are more aggressive and metastasize earlier, leading to poorer prognosis; and cancer stem cells (CSCs) are largely responsible for tumor differentiation state, here we observed that the exposure of nicotine-derived 4-(methylnitrosamino)- 1-(3-pyridyl)- 1-butanone (NNK) promoted cell sphere formation and the expression of the stem cell markers, CD44, OCT4, C-MYC and NANOG in HCT8 and DLD-1 cells. Further colony formation assay, CCK-8 assay and tumor-bearing experiment showed that NNK exposure significantly increased the proliferative and growth ability of CRC cells. In mechanism, we found that NNK-activated ERK1/2 played an important role in enrichment of CRC stem cells and the up-regulation of DUSP4, a major negative regulator of ERK1/2. Moreover, DUSP4 up-regulation was essential for maintaining NNK-activated ERK1/2 in an appropriate level, which was an required event for NNK-induced stemness enrichment of CRC cells. Taken together, our findings provided a possible mechanistic insight into cigarette smoking-induced CRC progression.

miR­3133 inhibits proliferation and angiogenesis by targeting the JUNB/VEGF pathway in human umbilical vein endothelial cells.

Membranous obstruction of the inferior vena cava (MOVC) has the highest incidence rate among the different types of Budd­Chiari syndrome (BCS) in China. The inferior vena cava septum of patients with MOVC contains capillaries and the two surfaces of the membrane are composed of vascular endothelial tissue. Membrane formation occurs due to endothelial damage. MicroRNAs (miRNAs/miRs) have been verified to be involved in the pathogenesis and progression of various human diseases. A previous study by our group suggested that miR­3133 was downregulated in the serum of patients with MOVC. In the present study, the possible mechanistic implication of miR­3133 in MOVC­associated processes was further explored. It was observed that miR­3133 overexpression inhibited, whereas miR­3133 knockdown enhanced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the CCK­8 and tube formation assays. JUNB, a member of activator protein 1 and an important upstream transcriptional molecule of vascular endothelial growth factor (VEGF), was proven to be a direct target gene of miR­3133 using a bioinformatics prediction and luciferase reporter assay. Meanwhile, the mRNA and protein expression of JUNB and VEGF was determined by PCR, ELISA and western blot analyses. Of note, miR­3133 overexpression downregulated, while miR­3133 knockdown elevated the expression of JUNB and VEGF significantly. Furthermore, it was demonstrated that JUNB upregulated the expression and secretion of VEGF to promote HUVEC proliferation and angiogenesis. miR­3133 was able to inhibit the effect of JUNB overexpression to promote cell proliferation, angiogenesis and the expression of VEGF. In conclusion, the present study demonstrated that miR­3133 regulated endothelial cell proliferation and angiogenesis through the JUNB/VEGF pathway, which may provide an approach for inhibiting diaphragm formation of the inferior vena cava in MOVC.

Hemin impairs resolution of inflammation via microRNA-144-3p-dependent downregulation of ALX/FPR2.

BACKGROUND: The pathomechanisms of complications due to blood transfusion are not fully understood. Elevated levels of heme derived from stored RBCs are thought to be associated with transfusion reactions, especially inflammatory responses. Recently, the proinflammatory effect of heme has been widely studied. However, it is still unknown whether heme can influence the resolution of inflammation, a key step of inflammatory response. STUDY DESIGN AND METHODS: A murine model of self-limited peritonitis was used, and resolution was assessed by resolution indices. Western blot, quantitative reverse transcriptase polymerase chain reaction, chemotaxis assay, luciferase reporter assay, and lentivirus infections were used to investigate possible mediating mechanisms in neutrophils. RESULTS: The administration of hemin by intraperitoneal injection significantly increased the leukocyte infiltration and prolonged the resolution interval by approximately 7 hours in mouse peritonitis. In vitro, hemin significantly downregulated ALX/FPR2 protein levels (p < 0.05), a key resolution receptor, leading to the suppression of proresolution responses triggered by the proresolution ligand resolvin D1. Subsequently, miR-144-3p, selected by prediction databases, was found to be significantly upregulated by hemin (p < 0.05). The inhibition of miR-144-3p attenuated the inhibitory effect of hemin on lipoxin A4 receptor (ALX)/formyl peptide receptor 2 (FPR2) protein expression (p < 0.05). Luciferase reporter assay confirmed that miR-144-3p directly bound ALX/FPR2 3'-UTR. MiR-144-3p overexpression significantly downregulated ALX/FPR2 protein levels, whereas miR-144-3p inhibition led to a significant increase in ALX/FPR2 (p < 0.05). CONCLUSION: Our results suggest that hemin prolongs resolution in self-limited inflammation, and this action is associated with downregulation of ALX/FPR2 mediated by hemin-induced miR-144-3p. These findings demonstrate a novel mechanism of hemin derived from stored RBCs for inflammatory response.

N-methyl-N-nitro-N-nitrosoguanidine-mediated ING4 downregulation contributed to the angiogenesis of transformed human gastric epithelial cells.

AIMS: Angiogenesis is associated with the progression and mortality of gastric cancer. Epidemiological evidences indicate that long-term N-nitroso compounds (NOCs) exposure predominantly contributes to the mortality of gastric cancer. Therefore, further reduced mortality of gastric cancer demands to explore the exact mechanisms of NOCs induced angiogenesis. As a tumor suppressor gene, inhibitor of growth protein 4 (ING4) plays an important role in pathological angiogenesis. In this study, we will investigate ING4 expression level in human gastric epithelial cells after the long-term low dose exposure of N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and the pathological impact of MNNG-reduced ING4 on angiogenesis of transformed cells. MAIN METHODS: The soft agar colony formation assay, Western blotting, immunofluorescence and wound healing assay were used to evaluate the characteristics of transformed cells. HUVEC growth and tube formation assays were performed to test the angiogenic abilities. EMSA, luciferase reporter gene assay, real-time PCR and Western blotting were used to explore the exact mechanism. KEY FINDINGS: By establishing transformed human gastric epithelial cells via chronic low dose treatment, a gradually ING4 downregulation was observed in the later-stage of MNNG-induced cell transformation. Moreover, we demonstrated that MNNG exposure-reduced ING4 expression significantly resulted into aggravating angiogenesis through increasing the phosphorylation level of NF-κB p65 and subsequently DAN binding activity and regulating the expressions of NF-κB p65 downstream pro-angiogenic genes, MMP-2 and MMP-9. SIGNIFICANCE: Our findings provided a significant mechanistic insight into angiogenesis of MNNG-transformed human gastric epithelial cell and supported the concept that ING4 may be a relevant therapeutic target for gastric cancer.

Early Goal-Directed Therapy in Severe Sepsis and Septic Shock: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.

INTRODUCTION: The Surviving Sepsis Campaign guidelines recommend early goal-directed therapy (EGDT) for the resuscitation of patients with sepsis; however, the recent evidences quickly evolve and convey conflicting results. We performed a meta-analysis to evaluate the effect of EGDT on mortality in adults with severe sepsis and septic shock. METHODS: We searched electronic databases to identify randomized controlled trials that compared EGDT with usual care or lactate-guided therapy in adults with severe sepsis and septic shock. Predefined primary outcome was all-cause mortality at final follow-up. RESULTS: We included 13 trials enrolling 5268 patients. Compared with usual care, EGDT was associated with decreased mortality (risk ratio [RR]: 0.87, 95% CI: 0.77-0.98; 4664 patients, 8 trials; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] quality of evidence was moderate). Compared with lactate clearance-guided therapy, EGDT was associated with increased mortality (RR: 1.60, 95% CI: 1.24-2.06; 604 patients, 5 trials; GRADE quality of evidence was low). Patients assigned to EGDT received more intravenous fluid, red cell transfusion, vasopressor infusion, and dobutamine use within the first 6 hours than those assigned to usual care (all P values < .00001). CONCLUSION: Adults with severe sepsis and septic shock who received EGDT had a lower mortality than those given usual care, the benefit may mainly be attributed to treatments administered within the first 6 hours. However, the underlying mechanisms by which lactate clearance-guided therapy benefits these patients are yet to be investigated.

Experimental Evaluation of Tranexamic Acid-Loaded Porous Starch as a Hemostatic Powder.

We evaluated the effectiveness of a novel hemostatic powder called Tranexamic Acid-loaded Porous Starch (TAPS) developed recently on blood clotting activity and hemostasis. The effectiveness of TAPS was evaluated by comparing hemostatic properties with those of Quick-acting Styptic Powder (QSP) and Compound Microporous Polysaccharide Haemostatic powder (CMPHP). The blood clotting activities of human blood were analyzed by thromboela-stogram (TEG) assays in vitro. The hemostatic effectiveness in vivo was evaluated using a rat model with hepatic traumatic hemorrhage. The blood loss and standardized bleeding score, which reflects the degree of bleeding after treatment with styptic powder, were used to evaluate hemostatic efficacy. In vitro, the values of TEG parameters in TAPS group were significantly different, compared with untreated controls or CMPHP group (p < 0.05). In vivo, the application of QSP, CMPHP and TAPS led to significantly decreased post-treatment blood loss than in the control group (p < 0.01). The scores of the groups treated with QSP, CMPHP and TAPS (0, 0.2±0.422, 0.3±0.483, respectively) were significant lower than with gauze control (1.6±0.516) which success hemostatic was achieved at 5 minutes (p < 0.01). Hemostasis was achieved successfully within approximately 4 minutes after the application of TAPS. TAPS could help blood to form an artificial scab on a wound and to seal injuries for hemostasis to reduce blood loss in rats with hepatic trauma and hemorrhage. It was safe to use with no impact on blood clotting function or other apparent side effects.

The common promoter polymorphism rs11666254 downregulates FPR2/ALX expression and increases risk of sepsis in patients with severe trauma.

BACKGROUND: Formyl peptide receptor 2-lipoxin receptor (FPR2/ALX) modulates the anti-inflammatory response and therefore may be a target for treating sepsis. The purpose of this study was to investigate the association between genetic variants of the FPR2/ALX gene and sepsis after severe trauma as well as to further analyze the functions of sepsis-related genetic polymorphisms. METHODS: Three tag single-nucleotide polymorphisms (tag SNPs) that captured all common alleles across the FPR2/ALX genomic region were genotyped using pyrosequencing in an initial sample consisting of 275 patients with severe trauma. The rs11666254 polymorphism, which had statistical significance, was genotyped in an additional 371 patients, and logistic regression analysis was performed to determine associations between the FPR2/ALX gene polymorphism and sepsis susceptibility after severe trauma. The messenger RNA (mRNA) and protein levels of FPR2/ALX in the lipopolysaccharide-stimulated white blood cells of trauma patients were determined by performing quantitative polymerase chain reactions and Western blot analysis. Tumor necrosis factor (TNF)-α production was measured by enzyme-linked immunosorbent assay. The effects of the promoter polymorphism rs11666254 on the transcription activity of FPR2/ALX were analyzed using a luciferase reporter assay. RESULTS: Among the three tag SNPs, only the rs11666254 polymorphism was found to be significantly associated with sepsis in trauma patients, and this association persisted after a pooled analysis of all 646 trauma patients, which showed that patients who carried the A allele of rs11666254 had a significantly higher risk of developing sepsis than individuals who carried the G allele. This SNP was also significantly associated with lower FPR2/ALX mRNA and protein expression as well as higher TNF-α production from the peripheral blood leukocyte response to bacterial lipoprotein stimulation. In addition, the rs11666254 polymorphism could significantly decrease the promoter activity of the FPR2/ALX gene. CONCLUSIONS: The rs11666254 polymorphism in the FPR2/ALX gene is a functional SNP that increases sepsis susceptibility in patients after traumatic injury.

Comparison of Growth and the Cytokines Induced by Pathogenic Yersinia enterocolitica Bio-Serotypes 3/O: 3 and 2/O: 9.

Pathogenic Yersinia enterocolitica is widely distributed in China where the primary bio-serotypes are 3/O: 3 and 2/O: 9. Recently, the distribution of 2/O: 9 strains are being gradually replaced by 3/O: 3 strains where presently 3/O: 3 strains are the major pathogenic Y. enterocolitica in China. To identify the growth conditions and cytokines induced by Y. enterocolitica and providing some clues for this shift, we performed competitive growth in vitro and in vivo for these two bio-serotype strains; and we also compared the cytokines induced by them in infected BALB/C mice. We found 2/O: 9 strains grew more in vitro, while 3/O: 3 strains grew more in vivo regardless of using single cultures or mixed cultures. The cytokines induced by the two strains were similar: interleukin-6 (IL-6), IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), chemokines (KC), monocyte chemotactic protein 1 (MCP-1), macrophage inflammation protein-1α (MIP-1α), tumor necrosis factor-α (TNF-α), and RANTES were statistically up-regulated upon activation of normal T cells compared to the control. The cytokine values were higher in mixed infections than in single infections except for IL-6, G-CSF, and KC. The data illustrated the different growth of pathogenic Y. enterocolitica bio-serotype 3/O: 3 and 2/O: 9 in vitro and in vivo, and the cytokine changes induced by the two strains in infected BALB/C mice. The growth comparisons of two strains maybe reflect the higher pathogenic ability or resistance to host immune response for Y. enterocolitica bio-serotype 3/O: 3 and maybe it as one of the reason for bacteria shift.

Plasma Transfusion in Patients With Cirrhosis in China: A Retrospective Multicenter Cohort Study.

Patients with cirrhosis used to be associated with frequent use of blood components because of their complex disorder of hemostasis and bleeding complications. Recent findings have indicated that patients with cirrhosis have a state of "rebalanced" or even procoagulant hemostasis and have questioned the prophylactic use of plasma. To evaluate the current status of plasma use in patients with cirrhosis, we conducted a retrospective survey in 11 tertiary-care hospitals in China from September 1 to October 31, 2013. All patients admitted with cirrhosis during the study period were included in the study. The survey collected information including patients' diagnostic and demographic data, clinical course including bleeding complications and invasive procedures, laboratory results, and plasma transfusion data. Among 1595 patients with cirrhosis admitted to the 11 hospitals, 236 (14.8%) patients received 1 or more plasma transfusions during the study period. The number of plasma transfusions is defined as the number of transfusion orders. A total of 1037 plasma transfusions were administered to these patients, with a mean of 4.4 transfusions per transfused patient, ranging from 1 to 22 transfusions per transfused patient. Most plasma transfusions (760/1037; 73.3%) were given to patients without bleeding, for treatment of coagulopathy either without planned invasive procedures (70.4%) or before invasive procedures (2.9%). The median dose of plasma transfusion was 3.8 mL/kg. The rate of plasma transfusion of participating hospitals varied from 5.3% to 31.8%. It is encouraging to see that in one teaching hospital, 85.7% plasma transfusions were given to patients with bleeding indication, showing a promising sign in appropriate transfusion. Prophylaxis or empirical plasma transfusion is still a common problem in managing patients with liver cirrhosis. Wide variations are found in plasma transfusion practice among hospitals. Effective measures to control and reduce empirical correction of abnormal coagulation tests through transfusing plasma should be strengthened urgently.

ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer.

ING4, a potential tumor suppressor, is implicated in cell cycle arrest, apoptosis, cell migration and angiogenesis. Here, we investigated the clinical value of ING4 and its impact on angiogenesis in colorectal cancer (CRC). In this study, we found that ING4 expression was significantly reduced in CRC tissues versus paired normal colon tissues. Moreover, low ING4 expression was significantly associated with increased lymph node metastasis, advanced TNM stage and poor overall survival. Multivariate Cox regression analysis showed that ING4 expression was an independent favourable prognostic factor for CRC (hazard ratio = 0.45, P = 0.001). In addition, we found that ING4 strongly inhibited CRC angiogenesis by suppressing Sp1 expression and transcriptional activity through ubiquitin degradation and down-regulating the expressions of Sp1 downstream pro-angiogenic genes, MMP-2 and COX-2. Moreover, ING4 might inhibit phosphorylation activity of cyclin/CDK2 complexes to trigger Sp1 degradation by inducing p21 expression in despite of p53 status. Our findings imply that reduced ING4 expression in CRC resulted in increased angiogenesis and contributed to CRC metastasis and poor prognosis. Restoration of ING4 may be a novel strategy for the treatment of metastatic CRC.

A multicenter study of blood component transfusion in patients with liver cirrhosis in China: Patient characteristics, transfusion practice, and outcomes.

BACKGROUND: Cirrhosis is a complex acquired disorder of hemostasis and patients frequently receive blood transfusions. But there is very limited data on patterns of blood use at a patient level. AIMS: To characterize blood use in cirrhotic patients in China and compare with recommendations to help identify areas where quality improvement strategies can be targeted. We also compared findings to a similar study undertaken in UK. METHODS: A cross-sectional study was conducted in 11 hospitals over a 2-month period. Data were collected prospectively on each hospitalized cirrhotic patient to day 28. RESULTS: 1595 cirrhotic patients were included and 20.6% were transfused. 48.2% of transfused patients received transfusion for bleeding, most commonly gastrointestinal bleeding (65.8%). The remaining 51.8% were transfused for non-bleeding indications. 32.5% of patients transfused for gastrointestinal bleeding with red blood cells had a pre-transfusion haemoglobin >7g/dL. 89.1% of patients transfused frozen plasma for non-bleeding indications received them in the absence of a planned procedure. The patterns of blood transfusion in cirrhosis were different between China and UK. Of note, empirical prophylactic use of frozen plasma was more common in the Chinese study (89%) than in the UK (24%). CONCLUSION: Education and research should be implemented to improve patient blood management, especially in prophylactic frozen plasma use area.

Circulating microRNA profile in patients with membranous obstruction of the inferior vena cava.

Membranous obstruction of the inferior vena cava (MOVC) is a common type of Budd-Chiari syndrome. However, the pathogenesis of MOVC has not been fully elucidated. Recent studies demonstrated that microRNAs (miRNAs or miRs) are involved in multiple diseases. To the best of our knowledge, specific changes in the expression of miRNAs in MOVC patients have not been previously assessed. The present study used a microarray analysis, followed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation, with the aim to access the miRNA expression levels in the plasma of 34 MOVC patients, compared with those in healthy controls. The results revealed a total of 16 differentially expressed miRNAs in MOVC patients. Subsequently, RT-qPCR analysis verified the statistically consistent expression of 5 selected miRNAs (miR-125a-5p, miR-133b, miR-423-5p, miR-1228-5p and miR-1266), in line with the results of the microarray analysis. These 5 miRNAs, which were described as crucial regulators in numerous biological processes and vascular diseases, may play an important role in the pathogenesis of MOVC. Bioinformatics analysis of target genes of the differentially expressed miRNAs revealed that these predicted targets were significantly enriched and involved in several key signaling pathways important for MOVC, including the ErbB, Wnt, MAPK and VEGF signaling pathway. In conclusion, miRNAs may involve in multiple signaling pathways contributing to the pathological processes of MOVC. The present study offers an intriguing new perspective on the involvement of miRNAs in MOVC; however, the precise underlying mechanisms require further validation.

Association Between Interleukin-6 -572 C>G and -174 G>C Polymorphisms and Hypertension: A Meta-analysis of Case-control Studies.

Whether hypertension is associated with -572 C>G or -174 G>C polymorphism in interleukin (IL)-6 genes still remains hazy and ambiguous.We conducted a meta-analysis to offer a more reliable and clearer evaluation about the association.Electronic literature databases including PubMed, Web of Science, EMBASE, Google Scholar, Chinese National Knowledge Infrastructure and Wanfang database were searched.The study included the following: evaluating associations between -572 C>G or -174 G>C polymorphism in IL-6 gene and hypertension; case-control design; essential information must be offered; precise diagnostic criteria of hypertension; and no language restriction.Patients who met the diagnostic criteria and controls without a history of hypertension were included. Interventions were not available.A quality assessment was conducted using Newcastle-Ottawa scale. Combined odds ratios with 95% confidence intervals were calculated in 5 genetic models. Sources of heterogeneity were explored by subgroup analysis, meta-regression, and Galbraith plots. Finally, test for publication bias was performed to prove the stabilization.Fifteen studies were finally included. Eleven articles were judged high-quality reports. Overall, the -572 C>G polymorphism was proved to be significantly associated with hypertension in 4 genetic models. Subgroup analysis based on ethnicity revealed significant associations in Asian population in recessive model and homozygote comparison. The association in Europeans and Mid-East required further confirmation. No significant association was observed between the -174 G>C polymorphism and hypertension under all of the genetic models.The limitations of the study were the following: restrictive number of eligible studies limited the extrapolation range in subgroup analysis; gene-environment factors could not be described due to lack of data; some relevant studies could not be included because of various reasons.Current researches supported the association between the development of hypertension and the -572 C>G rather than -174 G>C polymorphism. Future well designed epidemiological studies may evaluate the possible gene-environment interactions.