The Toggle Switch Model for Gene Expression Change during the Prenatal-to-Postnatal Transition in Mammals.

The prenatal-to-postnatal transition is a pivotal process in the life cycle whereby an organism shifts from responding to intrauterine cues to undergoing extrauterine stresses with many physiological adaptations. However, the molecular basis underlying the evolutionarily conserved physiological adaptations remains elusive. Here, we analyze the transcriptomes of seven organs across developmental time points from five mammalian species by constructing computational coexpression networks and report a developmental shift of gene expression at the perinatal stage. The low-to-high and high-to-low expressed genes tightly coalesce in the functional categories and gene regulatory pathways that implicate the physiological adaptions during the prenatal-to-postnatal transition, including lipid metabolism, circadian rhythm, immune response, cell cycle, and cell division. The low-to-high and high-to-low expressed genes around the perinatal stage tend to form the mutually inhibitory toggle switch gene pairs linking the gene regulatory networks in response to the environmental changes. We thus propose the toggle switch model for the developmental shift of gene expression as a mechanic framework to investigate how the physiological adaptations occur during the prenatal-to-postnatal transition.

Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3.

Aberrant alternative splicing has been highlighted as a potential hallmark of cancer. Here, we identify TDP43 (TAR DNA-binding protein 43) as an important splicing regulator responsible for the unique splicing profile in triple-negative breast cancer (TNBC). Clinical data demonstrate that TDP43 is highly expressed in TNBC with poor prognosis. Knockdown of TDP43 inhibits tumor progression, including proliferation and metastasis, and overexpression of TDP43 promotes proliferation and malignancy of mammary epithelial cells. Deep sequencing analysis and functional experiments indicate that TDP43 alters most splicing events with splicing factor SRSF3 (serine/arginine-rich splicing factor 3), in the regulation of TNBC progression. The TDP43/SRSF3 complex controls specific splicing events, including downstream genes PAR3 and NUMB The effect of reduced metastasis and proliferation upon the knockdown of TDP43 or SRSF3 is mediated by the splicing regulation of PAR3 and NUMB exon 12, respectively. The TDP43/SRSF3 complex and downstream PAR3 isoform are potential therapeutic targets for TNBC.

The protective effects of L-carnitine on myocardial ischaemia-reperfusion injury in patients with rheumatic valvular heart disease undergoing CPB surgery are associated with the suppression of NF-κB pathway and the activation of Nrf2 pathway.

Myocardial ischaemia-reperfusion injury (MIRI) is a main pathophysiologic change following CPB surgery. L-carnitine, a natural amino acid, is able to transport fatty acids for generating energy and has a protective effect on MIRI. We aim to investigate the protective effect of L-carnitine on MIRI in patients with rheumatic valvular heart disease (RVHD) performed CPB surgical operation and the underlying mechanism. In this study, patients were randomized to three groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (6 g/L) and experimental group 2 (12 g/L), whereas no L-carnitine was used in the control group. Our results showed that L-carnitine significantly attenuated myocardial injury after surgery in these patients. L-carnitine decreased serum markers of myocardial injury including CK-MB, cTnI, hs-cTnT and IMA. L-carnitine increased left ventricular ejection fraction (LVEF) but reduced wall motion score index (WMSI) after operation. L-carnitine also inhibited myeloperoxidase (MPO) activity and inflammatory cytokines in the myocardium of patients after unclamping the aorta. Additionally, L-carnitine increased levels of superoxide dismutase (SOD) and catalase (CAT) while decreased levels of malondialdehyde (MDA) and protein carbonyl content in the myocardium of patients after unclamping the aorta. Moreover, L-carnitine suppressed the activation of nuclear factor kappa B (NF-κB) and activated nuclear factor erythroid 2-related factor 2 (Nrf2). There was also no significant difference in these indices between two experimental groups after unclamping the aorta. Taken together, L-carnitine had a protective effect against CPB-induced MIRI in patients with RVHD, which might be related to its modulation of NF-κB and Nrf2 activities.

Zinc mediates the SREBP-SCD axis to regulate lipid metabolism in Caenorhabditis elegans.

Maintenance of lipid homeostasis is crucial for cells in response to lipid requirements or surplus. The SREBP transcription factors play essential roles in regulating lipid metabolism and are associated with many metabolic diseases. However, SREBP regulation of lipid metabolism is still not completely understood. Here, we showed that reduction of SBP-1, the only homolog of SREBPs in Caenorhabditis elegans, surprisingly led to a high level of zinc. On the contrary, zinc reduction by mutation of sur-7, encoding a member of the cation diffusion facilitator (CDF) family, restored the fat accumulation and fatty acid profile of the sbp-1(ep79) mutant. Zinc reduction resulted in iron overload, which thereby directly activated the conversion activity of stearoyl-CoA desaturase (SCD), a main target of SREBP, to promote lipid biosynthesis and accumulation. However, zinc reduction reversely repressed SBP-1 nuclear translocation and further downregulated the transcription expression of SCD for compensation. Collectively, we revealed zinc-mediated regulation of the SREBP-SCD axis in lipid metabolism, distinct from the negative regulation of SREBP-1 or SREBP-2 by phosphatidylcholine or cholesterol, respectively, thereby providing novel insights into the regulation of lipid homeostasis.

Targeting PSG1 to enhance chemotherapeutic efficacy: new application for anti-coagulant the dicumarol.

Chemotherapeutic response is critical for the successful treatment and good prognosis in cancer patients. In this study, we analysed the gene expression profiles of preoperative samples from oestrogen receptor (ER)-negative breast cancer patients with different responses to taxane-anthracycline-based (TA-based) chemotherapy, and identified a group of genes that was predictive. Pregnancy specific beta-1-glycoprotein 1 (PSG1) played a central role within signalling pathways of these genes. Inhibiting PSG1 can effectively reduce chemoresistance via a transforming growth factor-ß (TGF-ß)-related pathway in ER-negative breast cancer cells. Drug screening then identified dicumarol (DCM) to target the PSG1 and inhibit chemoresistance to TA-based chemotherapy in vitro, in vivo, and in clinical samples. Taken together, this study highlights PSG1 as an important mediator of chemoresistance, whose effect could be diminished by DCM.

Transcriptome Profile Reveals that Pu-Erh Tea Represses the Expression of Vitellogenin Family to Reduce Fat Accumulation in Caenorhabditis elegans.

Due to misbalanced energy surplus and expenditure, obesity has become a common chronic disorder that is highly associated with many metabolic diseases. Pu-erh tea, a traditional Chinese beverage, has been believed to have numerous health benefits, such as anti-obesity. However, the underlying mechanisms of its anti-obesity effect are yet to be understood. Here, we take the advantages of transcriptional profile by RNA sequencing (RNA-Seq) to view the global gene expression of Pu-erh tea. The model organism Caenorhabditis elegans was treated with different concentrations of Pu-erh tea water extract (PTE, 0 g/mL, 0.025 g/mL, and 0.05 g/mL). Compared with the control, PTE indeed decreases lipid droplets size and fat accumulation. The high-throughput RNA-Sequence technique detected 18073 and 18105 genes expressed in 0.025 g/mL and 0.05 g/mL PTE treated groups, respectively. Interestingly, the expression of the vitellogenin family (vit-1, vit-2, vit-3, vit-4 and vit-5) was significantly decreased by PTE, which was validated by qPCR analysis. Furthermore, vit-1(ok2616), vit-3(ok2348) and vit-5(ok3239) mutants are insensitive to PTE triggered fat reduction. In conclusion, our transcriptional profile by RNA-Sequence suggests that Pu-erh tea lowers the fat accumulation primarily through repression of the expression of vit(vitellogenin) family, in addition to our previously reported (sterol regulatory element binding protein) SREBP-SCD (stearoyl-CoA desaturase) axis.

Chronic lead exposure and burden of cardiovascular disease during 1990-2019: a systematic analysis of the global burden of disease study.

Background: Cardiovascular diseases (CVD) are the leading causes of death and disability worldwide. Lead exposure is an important risk factor for CVD. In our study, we aimed to estimate spatial and temporal trends in the burden of cardiovascular disease associated with chronic lead exposure. Methods: The data collected for our study were obtained from Global Burden of Disease (GBD) study 2019 and analyzed by age, sex, cause, and location. To assess the temporal trends in burden of CVD attributable to chronic lead exposure over 30 years, we used Joinpoint regression analysis. Results: In 2019, the number of lead exposure-attributable CVD deaths and disability-adjusted life-years (DALYs) were 0.85 and 17.73 million, 1.7 and 1.4 times more than those observed in 1990, respectively. However, the corresponding age-standardized rates (ASR) of death and DALY gradually decreased from 1990 to 2019, especially from 2013 to 2019. Over the last 30 years, among 21 GBD regions and 204 countries and territories, the High-income Asia Pacific and the Republic of Korea experienced the largest reductions in age-standardized DALY and death rates, while Central Asia and Afghanistan experienced the largest increases. Males and the elderly population suffered higher death rates and DALY burdens than females and the young population. Furthermore, we observed that higher socio-demographic index (SDI) regions demonstrated lower ASR of death and DALY rates. In 2019, the low and low-middle SDI regions, especially South Asia, exhibited the highest burden of CVD attributable to lead exposure. Conclusion: Our study provides a thorough understanding of the burden of CVD attributable to chronic lead exposure. The findings confirm the significance of implementing lead mitigation strategies and increasing investment in CVD prevention and treatment. These measures are crucial in reducing the burden of CVD and promoting public health on a global scale.

Neferine Pretreatment Attenuates Isoproterenol-Induced Cardiac Injury Through Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats.

Heart attacks, also known as myocardial infarctions (MIs), are one of the main reasons people die from cardiovascular diseases (CVDs) worldwide. Neferine, an alkaloid derived from Nelumbo nucifera seeds, has garnered interest due to its purported medicinal effects. In the current research, we induced MI in rats using the ß-adrenergic agonist isoproterenol to investigate whether neferine can improve cardiac dysfunction. The rats were separated into four groups: control, isoproterenol (ISO), and two treatment groups received neferine at doses of 10 or 20 mg/kg once daily for 28 days. On days 27 and 28, the groups undergoing treatment were administered with an ISO injection. Results showed that pretreatment with neferine strongly protected against changes in lipid profiles and cardiac functional markers in ISO-administered rats. Neferine attenuated histopathologic changes, collagen deposition, and myocardial fibrosis in rats administered ISO. Neferine pretreatment significantly inhibited the oxidative stress, inflammatory, and apoptotic markers in the heart of ISO-injected rats. This was achieved through Nrf2/Keap1/ARE signaling stimulation, TLR4/NF-κB/MAPK-mediated signaling inhibition, and activation of the intrinsic apoptotic pathway. Using CB-Dock-2, researchers determined that neferine has a high binding affinity with protein receptors that are pivotal in several biological processes. In conclusion, the study provides strong evidence that pretreatment with neferine protects rats from ISO-induced heart damage.

Quercetin Prevents HSpertension in Dahl Salt-sensitive Rats Fed a High-salt Diet Through Balancing Endothelial Nitric Oxide Synthase and Sirtuin 1.

BACKGROUND: A high-salt diet is a leading dietary risk factor for elevated blood pressure and cardiovascular disease. Quercetin reportedly exhibits cardioprotective and antihypertensive therapeutic effects. OBJECTIVES: The objective of this study is to examine the effect of quercetin on high-salt dietinduced elevated blood pressure in Dahl salt-sensitive (SS) rats and determine the underlying molecular mechanism. MATERIALS AND METHODS: Rats of the Dahl SS and control SS-13 BN strains were separated into five groups, SS-13 BN rats fed a low-salt diet (BL group), SS-13 BN rats fed a high-salt diet (BH group), Dahl SS rats fed a low-salt diet (SL group), Dahl SS rats fed a high-salt diet (SH group), and SH rats treated with quercetin (SHQ group). Blood pressure was checked three weeks into the course of treatment, and biochemical markers in the urine and serum were examined. Additionally, western blot was done to evaluate the sirtuin 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) expression levels. Immunohistochemical analysis was performed to verify SIRT1 levels. RESULTS: We demonstrated that a high-salt diet elevated blood pressure in both SS-13 BN and Dahl SS rats, and quercetin supplementation alleviated the altered blood pressure. Compared with the SH group, quercetin significantly elevated the protein expression of SIRT1 and eNOS. Immunohistochemistry results further confirmed that quercetin could improve the protein expression of SIRT1. CONCLUSION: Quercetin reduced blood pressure by enhancing the expression of SIRT1 and eNOS in Dahl SS rats fed a high-salt diet.

Experimental evidence for cancer resistance in a bat species.

Mammals exhibit different rates of cancer, with long-lived species generally showing greater resistance. Although bats have been suggested to be resistant to cancer due to their longevity, this has yet to be systematically examined. Here, we investigate cancer resistance across seven bat species by activating oncogenic genes in their primary cells. Both in vitro and in vivo experiments suggest that Myotis pilosus (MPI) is particularly resistant to cancer. The transcriptomic and functional analyses reveal that the downregulation of three genes (HIF1A, COPS5, and RPS3) largely contributes to cancer resistance in MPI. Further, we identify the loss of a potential enhancer containing the HIF1A binding site upstream of COPS5 in MPI, resulting in the downregulation of COPS5. These findings not only provide direct experimental evidence for cancer resistance in a bat species but also offer insights into the natural mechanisms of cancer resistance in mammals.

A Convergent fabrication of silk fibroin nanoparticles on quercetin loaded metal-organic frameworks for promising nanocarrier of myocardial infraction.

The biomacromolecule silk fibroin (SF) may be constructed to promote biomimetic nucleation and nanostructures of inorganic nanomaterials, offering it a promising candidate for use in various biomimetic applications. We combined SF-NPs and ZIF-8-NPs to fabricate new drug vehicles that effectively release the drug. SF nanoparticles (SF-NPs) were assembled into quercetin (QCT), a myocardial drug added to fabricate QSF-NPs. By acting as a template for the ZIF-8 nucleation onto the surface, the QSF-NPs fabricated core-shell-structured nanocomposites (named QSF@Z-NCs) with ZIF-8 as the core-shell and the QSF-NPs. The biocompatibility analysis using the MTT assay revealed that the developed QCT, SF-NPs, and QSF@Z-NCs are not harmful to cardiac myoblast (H9C2) cells. The in vivo model demonstrated that H9C2 cells encouraged cardiomyocyte fibre regeneration in myocardial infarction rats. We fabricated a brand-new technique using H9C2 cells and QSF@Z-NCs that might encourage the healing processes in myocardial ischemia cells. This study's results demonstrate that it successfully treats myocardial injury.

Serum CIRP increases the risk of acute kidney injury after cardiac surgery.

Introduction: Acute kidney injury (AKI) is a frequent perioperative complication. The underlying mechanisms of cardiac surgery-associated AKI are still not completely elucidated. Cold-induced RNA-binding protein (CIRP) has been subsequently found to be regulated by various stress conditions. During cardiac surgery and cardiopulmonary bypass (CPB), the host is subjected to hypothermia and inadequate organ perfusion, resulting in an upregulation of CIRP secretion. The aim of this study is to evaluate the role of elevated extracellular CIRP level as a contributing factor in the development of AKI. Methods: A total of 292 patients who underwent cardiac surgery were retrospectively enrolled and their serum samples were collected preoperative and postoperative. Demographic data, intraoperative data, in-hospital outcomes, and the occurrence of AKI were also collected for the patients. The correlation between CIRP and intraoperative procedures, as well as its association with postoperative outcomes were analyzed. Results: In multivariable analysis, higher ΔCIRP (p = 0.036) and body mass index (p = 0.015) were independent risk factors for postoperative AKI. Meanwhile, patients with postoperative AKI exhibited lower survival rate in 2-year follow-up (p = 0.008). Compared to off-pump coronary artery bypass grafting surgery, patients who underwent on-pump coronary artery bypass grafting, valve surgery, aortic dissection and other surgery showed higher ΔCIRP, measuring 1,093, 666, 914 and 258 pg/mL, respectively (p < 0.001). The levels of ΔCIRP were significantly higher in patients who underwent CPB compared to those who did not (793.0 ± 648.7 vs. 149.5 ± 289.1 pg/mL, p < 0.001). Correlation analysis revealed a positive correlation between ΔCIRP levels and the duration of CPB (r = 0.502, p < 0.001). Patients with higher CIRP levels are at greater risk of postoperative AKI (OR: 1.67, p = 0.032), especially the stage 2-3 AKI (OR: 2.11, p = 0.037). Conclusion: CIRP secretion increases with prolonged CPB time after cardiac surgery, and CIRP secretion is positively correlated with the duration of CPB. Cardiac surgeries with CPB exhibited significantly higher levels of CIRP compared to non-CPB surgeries. Elevation of CIRP level is an independent risk factor for the incidence of AKI, especially the severe AKI, and were associated with adverse in-hospital outcomes.

High throughput-screening of native herbal compounds identifies taccaoside A as a cytotoxic compound that mediates RAS signaling in cancer stem cells.

BACKGROUND: Cancer stem cells (CSCs) are characterized by their ability to self-renew, to differentiate into multiple cell types and also drive tumor formation, altogether making them important cellular targets for therapeutic intervention. However, existing CSC-targeting drugs do not significantly improve clinical outcomes. More recently, preclinical studies of natural product-derived compounds have demonstrated their potential usefulness as a therapeutic cancer treatment through their cytotoxic actions on CSCs. PURPOSE: Here, we identify CSC-specific compounds derived from natural products and characterize their putative mechanisms of action in CSCs. METHODS: Glioblastoma stem cells (GSCs) were labeled with EGFP via homologous recombination and utilized for a high-throughput screen of 8,344 fractions from 386 herbal medicines. The fractions that extinguished EGFP fluorescence signal were then further characterized by LC-MS/MS. Next, several putative cytotoxic compounds were evaluated for their cytotoxic effects on GSCs, cancer cell lines and immortalized cells using a variety of methods to study cell proliferation (EdU incorporation assay), cell death (cleaved-Caspase-3 immunostaining), DNA damage (comet assay), mitochondrial membrane changes (JC-1 immunostaining), and tumor formation in vitro (soft agar colony forming assay). We also performed surface plasmon resonance analysis, western blotting, and immunohistochemistry to characterize the putative mechanisms underlying the cytotoxic effects of putative compounds on GSCs. Finally, we carried out xenograft tumor growth assays to study the cytotoxic potential of several candidates in vivo. RESULTS: Our high throughput screen led to the identification of the furostanol saponin taccaoside A and its two homologs from the rhizomatous geophyte Tacca. subflabellata that were cytotoxic to GSCs. Interestingly, the cytotoxic effect of taccaoside A on cell lines was significantly less compared to its homologs, owing to stereochemical differences of a carbon-carbon double bond between C-20 and C-22. Molecular studies revealed that taccaoside A binds to RAS to inhibit downstream effector signaling. Correspondingly, blockade of the interaction between taccaoside A and RAS abolished the inhibitory effect of this compound on CSCs. Furthermore, taccaoside A treatment was effective in limiting tumor cell growth in vivo. CONCLUSION: Our study yielded an effective approach to screen for CSC-specific agents. Through this approach, we identified taccaoside A from the rhizomatous geophyte Tacca. subflabellata are cytotoxic to CSCs through a molecular mechanism that involves RAS binding and suppression of its downstream signaling. Our findings indicate taccaoside A is a potential lead compound for anti-CSC drug discovery.

Risk factors, prediction model, and prognosis analysis of myocardial injury after acute upper gastrointestinal bleeding.

Background: Cardiovascular complications in patients with acute upper gastrointestinal bleeding (AUGIB) have been associated with a high-risk of subsequent adverse consequences. This study aimed to analyze the risk factors for myocardial injury in AUGIB patients, predict the risk of myocardial injury, and explore the clinical prognosis and influencing factors in AUGIB patients with myocardial injury. Materials and methods: A retrospective case-control study based on AUGIB patients in the First Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2020 was performed. We divided the enrolled patients into a myocardial injury group and a control group according to whether they developed myocardial injury. The variables significant in the univariate analysis were subjected to binary logistic regression for risk factor analysis and were used to establish a nomogram for predicting myocardial injury. In addition, logistic regression analysis was performed to better understand the risk factors for in-hospital mortality after myocardial injury. Result: Of the 989 AUGIB patients enrolled, 10.2% (101/989) developed myocardial injury. Logistic regression analysis showed that the strong predictors of myocardial injury were a history of hypertension (OR: 4.252, 95% CI: 1.149-15.730, P = 0.030), blood urea nitrogen (BUN) (OR: 1.159, 95% CI: 1.026-1.309, P = 0.018) and left ventricular ejection fraction (LVEF) <68% (OR: 3.667, 95% CI: 1.085-12.398, P = 0.037). The patients with a tumor history (digestive system tumors and non-digestive system tumors) had no significant difference between the myocardial injury group and the control group (P = 0.246). A prognostic nomogram model was established based on these factors with an area under the receiver operator characteristic curve of 0.823 (95% CI: 0.730-0.916). The patients with myocardial injury had a much higher in-hospital mortality rate (10.9% vs. 2.0%, P < 0.001), and an elevated D-dimer level was related to in-hospital mortality among the AUGIB patients with myocardial injury (OR: 1.273, 95% CI: 1.085-1.494, P = 0.003). Conclusion: A history of hypertension, renal dysfunction, and cardiac function with LVEF <68% were strong predictors of myocardial injury. Coagulopathy was found to be associated with poor prognosis in AUGIB patients with myocardial injury.

Integrative Functional Transcriptomic Analyses Implicate Shared Molecular Circuits in Sensorineural Hearing Loss.

Sensorineural hearing loss (SNHL) is referred to as the most common type of hearing loss and typically occurs when the inner ear or the auditory nerve is damaged. Aging, noise exposure, and ototoxic drugs represent three main causes of SNHL, leading to substantial similarities in pathophysiological characteristics of cochlear degeneration. Although the common molecular mechanisms are widely assumed to underlie these similarities, its validity lacks systematic examination. To address this question, we generated three SNHL mouse models from aging, noise exposure, and cisplatin ototoxicity, respectively. Through constructing gene co-expression networks for the cochlear transcriptome data across different hearing-damaged stages, the three models are found to significantly correlate with each other in multiple gene co-expression modules that implicate distinct biological functions, including apoptosis, immune, inflammation, and ion transport. Bioinformatics analyses reveal several potential hub regulators, such as IL1B and CCL2, both of which are verified to contribute to apoptosis accompanied by the increase of (ROS) in in vitro model system. Our findings disentangle the shared molecular circuits across different types of SNHL, providing potential targets for the broad effective therapeutic agents in SNHL.

The interaction between multiplex community networks.

Multiplex community networks, consisting of several different types of simplex networks and interconnected among them, are ubiquitous in the real world. In this paper, we carry out a quantitative discussion on the interaction among these diverse simplex networks. First, we define two measures, mutual-path-strength and proximity-node-density, based on twoplex community networks and then propose an impact-strength-index (ISI) to describe the influence of a simplex network on the other one. Finally, we apply the measure ISI to make an explanation for the challenge system of social relations from the viewpoint of network theory. Numerical simulations show that the measure ISI can describe the interaction between multiplex community networks perfectly.

Exponential synchronization of chaotic systems with time-varying delays and parameter mismatches via intermittent control.

This paper studies the synchronization of coupled chaotic systems with time-varying delays in the presence of parameter mismatches by means of periodically intermittent control. Some novel and useful quasisynchronization criteria are obtained by using the methods which are different from the techniques employed in the existing works, and the derived results are less conservative. Especially, a strong constraint on the control width that the control width should be larger than the time delay imposed by the current references is released in this paper. Moreover, our results show that the synchronization criteria depend on the ratio of control width to control period, but not the control width or the control period. Finally, some numerical simulations are given to show the effectiveness of the theoretical results.

Analysis of MCM Proteins' Role as a Potential Target of Statins in Patients with Acute Type A Aortic Dissection through Bioinformatics.

Acute aortic dissection is one of the most severe vascular diseases. The molecular mechanisms of aortic expansion and dissection are unclear. Clinical studies have found that statins play a protective role in aortic dissection development and therapy; however, the mechanism of statins' effects on the aorta is unknown. The Gene Expression Omnibus (GEO) dataset GSE52093, GSE2450and GSE8686 were analyzed, and genes expressed differentially between aortic dissection samples and normal samples were determined using the Networkanalyst and iDEP tools. Weight gene correlation network analysis (WGCNA), functional annotation, pathway enrichment analysis, and the analysis of the regional variations of genomic features were then performed. We found that the minichromosome maintenance proteins (MCMs), a family of proteins targeted by statins, were upregulated in dissected aortic wall tissues and play a central role in cell-cycle and mitosis regulation in aortic dissection patients. Our results indicate a potential molecular target and mechanism for statins' effects in patients with acute type A aortic dissection.

Association of biomarkers related to preoperative inflammatory and coagulation with postoperative in-hospital deaths in patients with type A acute aortic dissection.

The aim of this study was to analyze the role of blood biomarkers regarding preoperative inflammation and coagulation in predicting the postoperative in-hospital mortality of patients with type A acute aortic dissection (AAD). A total of 206 patients with type A AAD who had received surgical treatment were enrolled in this study. Patients were divided into two groups: the death group (28 patients who died during hospitalization) and the survival group (178 patients). Peripheral blood samples were collected before anesthesia induction. Preoperative levels of D-dimer, fibrinogen (FIB), platelet (PLT), white blood cells (WBC) and neutrophil (NEU) were compared between the two groups. Univariable and multivariable logistic regression analysis were utilized to identify the independent risk factors for postoperative in-hospital deaths of patients with type A AAD. Receiver operating characteristic (ROC) curve were used to analyze the predictive value of these indices in the postoperative in-hospital mortality of the patients. Univariable logistic regression analysis showed that the P values of the five parameters including D-dimer, FIB, PLT, WBC and NEU were all less than 0.1, which may be risk factors for postoperative in-hospital deaths of patients with type A AAD. Further multivariable logistic regression analysis indicated that higher preoperative D-dimer and WBC levels were independent risk factors for postoperative in-hospital mortality of patients with type A AAD. ROC curve analysis indicated that application of combining FIB and PLT could improve accuracy in prediction of postoperative in-hospital mortality in patients with type A AAD. Both preoperative D-dimer and WBC in patients with type A AAD may be used as independent risk factors for the postoperative in-hospital mortality of such patients. The combination of FIB and PLT may improve the accuracy of clinical prognostic assessment.

[Evaluation of immune status of kidney transplant recipients by combined HLA-G5 and sCD30].

OBJECTIVE: to study the relationship between the expression of serum human leucocyte antigen-G5 (HLA-G5)/soluble CD30 (sCD30) and the function of renal graft in kidney transplant recipients and investigate the immune status of recipients with combined HLA-G5 and sCD30. METHODS: from January 2002 to November 2008, a total of 66 kidney transplant recipients in our centre were selected as subjects and divided into three groups: stable function of renal graft (n = 38), acute rejection (n = 15) and chronic rejection (n = 13). The expressions of serum HLA-G5 and sCD30 were detected. There were two different immune conditions with acute/chronic allograft rejection and normal renal graft in kidney transplant recipients as evaluated by combined HLA-G5 and sCD30. The sensitivity, specificity and critical value of the method were analyzed by the curve of receiver operating characteristic. RESULTS: the levels of HLA-G5 and sCD30 were significantly correlated with serum creatinine (r = -0.493, 0.691, both P < 0.01). Within the first year post-transplantation, the sensitivity was 78.6% and the specificity 85.7% when HLA-G5 critical value 82 microg/L and sCD30 critical value 12.2 microg/L. After one year post-transplantation: the sensitivity was 92.3% and the specificity 84.6% when HLA-G5 critical value 141 microg/L and sCD30 critical value 10.3 microg/L. CONCLUSION: the immune state of recipients are evaluated by combine HLA-G5 and sCD30 which may be a simple and valid method.