USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling.

Despite recent advances in systemic therapy for hepatocellular carcinoma (HCC), the prognosis of hepatitis B virus (HBV)-induced HCC patients remains poor. By screening a sgRNA library targeting human deubiquitinases, we find that ubiquitin-specific peptidase 26 (USP26) deficiency impairs HBV-positive HCC cell proliferation. Genetically engineered murine models with Usp26 knockout confirm that Usp26 drives HCC tumorigenesis. Mechanistically, we find that the HBV-encoded protein HBx binds to the promoter and induces the production of USP26, which is an X-linked gene exclusively expressed in the testis. HBx consequently promotes the association of USP26 with SIRT1 to synergistically stabilize SIRT1 by deubiquitination, which promotes cell proliferation and impedes cell apoptosis to accelerate HCC tumorigenesis. In patients with HBV-positive HCC, USP26 is robustly induced, and its levels correlate with SIRT1 levels and poor prognosis. Collectively, our study highlights a causative link between HBV infection, deubiquitinase induction and development of HCC, identifying a druggable target, USP26.

Noninvasive Transdermal Administration of mRNA Vaccines Encoding Multivalent Neoantigens Effectively Inhibits Melanoma Growth.

It is difficult to obtain specific tumor antigens, which is one of the main obstacles in the development of tumor vaccines. The vaccines containing multivalent antigens are thought to be more effective in antitumor therapy. In this study, a mRNA encoding three neoantigens of melanoma were prepared and encapsulated into the mannosylated chitosan-modified ethosomes (EthsMC) to obtain a multivalent mRNA vaccine (MmRV) for transcutaneous immunization (TCI). MmRV can effectively induce maturation of dendritic cells, with a better performance than mRNA of a single neoantigen. TCI patches (TCIPs) loading MmRV or siRNA against PDL1 (siPDL1) were prepared and applied to the skin of melanoma-bearing mice. The results showed that TCIPs significantly increase the levels of TNF-α, IFN-γ, and IL-12 in both plasma and tumor tissues, inhibit tumor growth, as well as promote infiltration of CD4+ and CD8+ T cells in the tumor tissues. Furthermore, the combination of MmRV and siPDL1 showed much better antitumor effects than either monotherapy, suggesting a synergistic effect between the vaccine and PDL1 blocker. In addition, the treatment with the TCIPs did not cause damage to the skin, blood, and vital organs of the mice, showing good biosafety. To the best of our knowledge, this work is the first to construct a noninvasive TCI system containing MmRV and siPDL1, providing a convenient and promising approach for tumor treatment.

Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence.

Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8+ T cell senescence, driven by atypical chemokine receptor 2 (ACKR2)+ CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2+ tumor cells are induced to produce transforming growth factor ß to drive CD8+ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8+ T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2+ tumor cells driving CD8+ T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8+ T cell senescence for chemoradiotherapy recurrence.

An immune sandwich electrochemical biosensor based on triple-modified zirconium derivatives for detection of CD146 in serum.

CD146, also known as melanoma cell adhesion molecule (MCAM), is overexpressed in various cancer patients, making it a valuable predictor for early diagnosis. In this work, an immune sandwich electrochemical biosensor is proposed for sensitive and non-invasive quantitative detection of CD146 in serum. Zirconium-based MOF (UIO-66) was modified by simultaneous copper atom doping, in situ growth carbon-based support and physical embedding of platinum nanoparticles (PtNPs). Triple-modified Cu-UIO-66@SWCNT/PtNPs nanocomposites with high stability and excellent electrochemical properties, serve as surface modification materials for glassy carbon electrodes. Anti-CD146 antibody (Ab1) was grafted onto the electrode surface via Pt-S bond. Meanwhile, the secondary antibody (Ab2) was conjugated with silver nanoparticles (AgNPs) to cooperate for CD146 capture and achieve secondary electrical signal amplification. Under optimal conditions, square wave voltammetry was employed to determine CD146 in the concentration range of 10-9-10-4 mg/mL and a limit of detection of 12 fg/mL was obtained. Finally, it was successfully applied to the analysis of CD146 in lung and liver cancer patients' serum samples.

Whole-genome sequencing in medicinal plants: current progress and prospect.

Advancements in genomics have dramatically accelerated the research on medicinal plants, and the development of herbgenomics has promoted the "Project of 1K Medicinal Plant Genome" to decipher their genetic code. However, it is difficult to obtain their high-quality whole genomes because of the prevalence of polyploidy and/or high genomic heterozygosity. Whole genomes of 123 medicinal plants were published until September 2022. These published genome sequences were investigated in this review, covering their classification, research teams, ploidy, medicinal functions, and sequencing strategies. More than 1,000 institutes or universities around the world and 50 countries are conducting research on medicinal plant genomes. Diploid species account for a majority of sequenced medicinal plants. The whole genomes of plants in the Poaceae family are the most studied. Almost 40% of the published papers studied species with tonifying, replenishing, and heat-cleaning medicinal effects. Medicinal plants are still in the process of domestication as compared with crops, thereby resulting in unclear genetic backgrounds and the lack of pure lines, thus making their genomes more difficult to complete. In addition, there is still no clear routine framework for a medicinal plant to obtain a high-quality whole genome. Herein, a clear and complete strategy has been originally proposed for creating a high-quality whole genome of medicinal plants. Moreover, whole genome-based biological studies of medicinal plants, including breeding and biosynthesis, were reviewed. We also advocate that a research platform of model medicinal plants should be established to promote the genomics research of medicinal plants.

Prevalence and the age of onset patterns of stroke in Jiangsu Province, China.

OBJECTIVES: Little was known regarding the current age of onset patterns of stroke. This study aimed to examine the prevalence of stroke and explore the age of onset patterns of stroke in Jiangsu Province, China. MATERIALS AND METHODS: Participants were recruited from April 2012 to April 2013 in Jiangsu Province, China. Survival analysis models were used to evaluate the hazards of stroke by a single year of age. Kaplan-Meier analysis and the log-rank test were used to explore the disparities of the age of onset patterns of stroke. RESULTS: This population-based study was conducted among 39,887 participants aged ≥ 18 years in Jiangsu Province, China. Of the 740 (1.9%) events of stroke, 13.2% suffered from hemorrhagic stroke (HS) and 86.8% suffered from ischemic stroke (IS). The prevalence of HS and IS were 0.3% and 1.7%, respectively. The estimated mean age of onset of stroke was 71.98 (95% CI: 71.97-71.99) years by the survival model. Up to age of 45 years, the estimated hazards of stroke onset were at a relatively low level. From the age of 45 years, the increases in hazards accelerated and peaked at age 75 years. Urban, smoking, and drinking males had a higher risk of stroke than their counterparts (P < 0.05). However, no such difference was found among females. CONCLUSIONS: The findings emphasize the importance of implementing stroke prevention interventions in Jiangsu Province, China, especially for urban, smoking, and drinking males. It is of great significance to strengthen comprehensive management of health-related behaviors, including smoking cessation and moderate consumption of alcohol to have sustained beneficial effects on stroke risk. Chenlu He and Qian Chen contributed equally to this work.

RAB21 controls autophagy and cellular energy homeostasis by regulating retromer-mediated recycling of SLC2A1/GLUT1.

The endosomal system maintains cellular homeostasis by coordinating multiple vesicular trafficking events, and the retromer complex plays a critical role in endosomal cargo recognition and sorting. Here, we demonstrate an essential role for the small GTPase RAB21 in regulating retromer-mediated recycling of the glucose transporter SLC2A1/GLUT1 and macroautophagy/autophagy. RAB21 depletion mis-sorts SLC2A1 to lysosomes and affects glucose uptake, thereby activating the AMPK-ULK1 pathway to increase autophagic flux. RAB21 depletion also increases lysosome function. Notably, RAB21 depletion does not overtly affect retrograde transport of IGF2R/CI-M6PR or WLS from endosomes to the trans-Golgi network. We speculate that RAB21 regulates fission of retromer-decorated endosomal tubules, as RAB21 depletion causes accumulation of the SNX27-containing retromer complex on enlarged endosomes at the perinuclear region. Functionally, RAB21 depletion sensitizes cancer cells to energy stress and inhibits tumor growth in vivo, suggesting an oncogenic role for RAB21. Overall, our study illuminates the role of RAB21 in regulating endosomal dynamics and maintaining cellular energy homeostasis and suggests RAB21 as a potential metabolic target for cancer therapy.

Elevated Admission Cardiac Troponin I Predicts Adverse Outcomes of Acute Type B Aortic Dissection after Endovascular Treatment.

Background: There is a lack of evidence about the predictive role of serum cardiac troponin I (cTnI) on the long-term adverse outcomes of acute type B aortic dissection (aTBAD) patients after thoracic endovascular aortic repair (TEVAR). In this study, we identified whether cTnI was an independent risk factor of 5-year adverse outcomes for aTBAD patients after TEVAR. Methods: We reviewed consecutive aTBAD patients without previous heart disease who were admitted for TEVAR. The total study population was divided into the cTnI(+) group (≥0.03 ng/mL) and the cTnI(-) group (<0.03 ng/mL) according to the time-dependent receiver operating characteristic curve analysis. The differences in clinical characteristics, operative details and clinical outcomes were compared between the two groups. Results: There was no difference in age and male prevalence between the two groups. Compared with the cTnI(-) group, the incidence of chronic kidney disease was higher in patients with cTnI ≥0.03 ng/mL. In addition, the cTnI(+) group presented with more frequent premature beats and non-myocardial-infarction ST-T segment changes. In terms of laboratory examinations, white blood cell counts, neutrophil counts, serum D-dimer and serum fibrin degradation products showed an increase in the cTnI(+) group, while lymphocyte and platelet counts showed a decrease in these patients. Patients with elevated cTnI suffered from increased risks of 5-year aortic-related adverse events (hazard ratio, HR = 1.822, 95% confidence interval, CI: 1.094-3.035; p = 0.021) and all-cause mortality (HR = 4.009, 95% CI: 2.175-7.388; p < 0.001). Conclusion: Among aTBAD patients without previous heart disease, preoperative elevated cTnI identified patients at an increased risk of long-term adverse outcomes after TEVAR.

Ezh2 competes with p53 to license lncRNA Neat1 transcription for inflammasome activation.

Inflammasome contributes to the pathogenesis of various inflammatory diseases, but the epigenetic mechanism controlling its activation remains elusive. Here, we found that the histone methyltransferase Ezh2 mediates the activation of multiple types of inflammasomes in macrophages/microglia independent of its methyltransferase activity and thus promotes inflammasome-related pathologies. Mechanistically, Ezh2 functions through its SANT2 domain to maintain the enrichment of H3K27 acetylation in the promoter region of the long noncoding RNA (lncRNA) Neat1, thereby promoting chromatin accessibility and facilitating p65-mediated transcription of Neat1, which is a critical mediator of inflammasome assembly and activation. In addition, the tumour suppressor protein p53 competes with Ezh2 for the same binding region in the Neat1 promoter and thus antagonises Ezh2-induced Neat1 transcription and inflammasome activation. Therefore, loss of Ezh2 strongly promotes the binding of p53, which recruits the deacetylase SIRT1 for H3K27 deacetylation of the Neat1 promoter and thus suppresses Neat1 transcription and inflammasome activation. Overall, our study demonstrates an epigenetic mechanism involved in modulating inflammasome activation through an Ezh2/p53 competition model and highlights a novel function of Ezh2 in maintaining H3K27 acetylation to support lncRNA Neat1 transcription.

Long-Term Outcomes of Endovascular Treatment for Type B Aortic Dissection with Simple Renal Cysts: A Multicenter Retrospective Study.

Background: Few studies have investigated the characteristics and long-term outcomes of type B aortic dissection (BAD) patients with simple renal cysts (SRC) after thoracic endovascular aortic repair (TEVAR). Methods: A multi-center retrospective cohort study was performed, including 718 BAD patients undergoing TEVAR from 2003 to 2016. The prevalence of SRC was 34.5% (n = 248). After propensity score matching, 214 matched pairs were selected for further analysis. Primary outcomes were long-term aortic-related adverse events (ARAEs). The effects of SRC in each subgroup of interest and their interactions were analyzed. Results: BAD patients with SRC were older and had a greater prevalence of comorbidities, including hypertension, coronary artery disease and chronic occlusive pulmonary disease. In addition, the SRC group presented a greater proportion of pleural effusion and aortic calcification. Compared with the non-SRC group, a significantly higher maximal diameter of ascending aorta was observed in the SRC group. Apart from the timing of the operation, no differences were found in the medication regime or intra-operative parameters. In the matched population, patients with SRC were at a higher risk of ARAEs in the long term. The multivariable Cox model indicated that SRC was an independent predictor of long-term ARAEs (hazard ratio: 1.84, 95% confidence interval: 1.13-3.00). The interaction between SRC and hypertension on rupture after TEVAR was statistically significant (p = 0.023). Conclusions: Compared with the non-SRC group, BAD patients with SRC experienced a higher risk of long-term ARAEs after TEVAR. Among the SRC subgroup, hypertensive patients had the highest risk of rupture after TEVAR.

Cytoplasmic DNA sensing by KU complex in aged CD4+ T cell potentiates T cell activation and aging-related autoimmune inflammation.

Aging is associated with DNA accumulation and increased homeostatic proliferation of circulating T cells. Although these attributes are associated with aging-related autoimmunity, their direct contributions remain unclear. Conventionally, KU complex, the regulatory subunit of DNA-dependent protein kinase (DNA-PK), together with the catalytic subunit of DNA-PK (DNA-PKcs), mediates DNA damage repair in the nucleus. Here, we found KU complex abundantly expressed in the cytoplasm, where it recognized accumulated cytoplasmic DNA in aged human and mouse CD4+ T cells. This process enhanced T cell activation and pathology of experimental autoimmune encephalomyelitis (EAE) in aged mice. Mechanistically, KU-mediated DNA sensing facilitated DNA-PKcs recruitment and phosphorylation of the kinase ZAK. This activated AKT and mTOR pathways, promoting CD4+ T cell proliferation and activation. We developed a specific ZAK inhibitor, which dampened EAE pathology in aged mice. Overall, these findings demonstrate a KU-mediated cytoplasmic DNA-sensing pathway in CD4+ T cells that potentiates aging-related autoimmunity.

Transdermal delivery of interleukin-12 gene targeting dendritic cells enhances the anti-tumour effect of programmed cell death protein 1 monoclonal antibody.

Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody (aPD-1) depends on the expression of interleukin-12 (IL-12) by dendritic cells (DCs). Since DCs are abundant in skin tissues, transdermal delivery of IL-12 targeting DCs may significantly improve the anti-tumour effect of aPD-1. In this study, a novel mannosylated chitosan (MC)-modified ethosome (Eth-MC) was obtained through electrostatic adsorption. The Eth-MC loaded with plasmid containing the IL-12 gene (pIL-12@Eth-MC) stimulated DCs to express mature-related molecular markers such as CD86, CD80, and major histocompatibility complex-II in a targeted manner. The pIL-12@Eth-MC was then mixed with polyvinyl pyrrolidone solution to make microspheres using the electrospray technique, and sprayed onto the surface of electrospun silk fibroin-polyvinyl alcohol nanofibres to obtain a PVP-pIL-12@Eth-MC/silk fibroin-polyvinyl alcohol composite nanofibrous patch (termed a transcutaneous immunization (TCI) patch). The TCI patch showed a good performance on transdermal drug release. Animal experiments on melanoma-bearing mice showed that topical application of the TCI patches promoted the expression of IL-12 and inhibited the growth of tumour. Furthermore, combined application of the TCI patch and aPD-1 showed a stronger anti-tumour effect than aPD-1 monotherapy. The combination therapy significantly promoted the expression of IL-12, interferon-γ and tumour necrosis factor-α, the infiltration of CD4+ and CD8+ T cells into tumour tissues, and thus promoted the apoptosis of tumour cells. The present study provides a convenient and non-invasive strategy for improving the efficacy of immune checkpoint inhibitor therapy. This study was approved by the Institutional Animal Care and Use Committee at Donghua University (approval No. DHUEC-NSFC-2020-11) on March 31, 2020.

The Mini-Cross Prefenestration for Endovascular Repair of Aortic Arch Pathologies.

Objective: To examine the feasibility, integrity, efficacy, and safety of endovascular repair of the aortic arch pathologies with the mini-cross prefenestration (MCPF) on stent grafts. Methods: First, to prove the feasibility of the MCPF, an in-vitro prefenestration experiment was conducted. Second, to examine the integrity of the MCPF stent grafts, a fatigue test was conducted. Then, the membranes and metal structures of stent grafts were examined by light microscopy and scanning electron microscopy (SEM). Third, a clinical experiment was conducted to investigate the efficacy and safety of this novel technique (ClinicalTrials.gov Identifier: NCT04544579). Results: All the 12 branch stents were successfully implanted and flared in vitro. After the fatigue test stimulating a 5-year cardiac cycle, no obvious disintegration or fracture was found in light microscopy or SEM. From December 2017 to February 2020, 26 patients with left subclavian arteries and/or left common carotid arteries involved received the novel technique. The endovascular repair with the MCPF was successfully performed on all the 26 (100%) patients. Eighteen (69.2%) patients underwent the reconstruction of the left subclavian artery (LSCA) only. The fenestrations of both the LSCA and left common carotid artery (LCCA) were conducted in 8 (30.8%) patients. Median operative time was 120 [interquartile range (IQR), 95-137.5] min and median revascularization time of the LSCA and LCCA was 30.5 (IQR, 22.8-42.0) s and 20.0 (IQR, 18.0-32.0) s separately. During the median follow-up duration of 38.9 (range, 18.8-44.2) months, one case needed an open surgery because of retrograde type A aortic dissection 3 months after implantation and no other complications or mortality occurred. The maximum aortic diameters were significantly decreased in patients with thoracic aortic dissection and thoracic aortic aneurysm (p < 0.05). Conclusion: The existing evidence demonstrated the safety, rapid branch artery revascularization, and positive aortic remodeling of the novel technique. Long-term observation is warranted to prove the durability.

Impact of high blood pressure variability on the occurrence of acute type B aortic dissection.

BACKGROUND: Acute type B aortic dissection is a life-threatening medical emergency, and hypertension is believed to be an important predictor of aortic dissection; the impact of blood pressure variability on the onset and development of aortic dissection has attracted increasing attention. METHODS: A total of 120 acute type B aortic dissection patients and 57 hypertensive patients without aortic dissection were consecutively enrolled and retrospectively reviewed between January 2013 and November 2015. There were 60 acute type B aortic dissection patients in both high and low blood pressure variability groups. RESULTS: Blood pressure variability showed higher diagnostic value than hypertension in aortic dissection, and the best threshold of blood pressure variability is 5.71 mmHg. By performing multivariable logistic regression, we found that the history of hypertension was likely to be a risk factor of blood pressure variability (95% CI: 1.155-6.422, P = 0.022). Nine patients from high blood pressure variability group and two from low blood pressure variability group (χ2 = 4.90, P = 0.027) received emergency surgery within 24 hours after admission. The presence of multiple tears (>2, 55.0% vs. 45.0%, P = 0.001), configuration of the false lumen (spiral false lumen) (50.0% vs. 21.7%, P = 0.001), the diameter of the false lumen (49.6 ± 15.0 mm vs. 37.6 ± 10.8 mm, P < 0.001), the false/true lumen ratio (1.53 ± 1.02 vs. 0.929 ± 0.733, P < 0.001), and the number of visceral arteries involved (1.75 ± 0.942 vs. 0.800 ± 0.927, P < 0.001) showed significant differences between high and low blood pressure variability groups. Nine (30%) patients from the high blood pressure variability group showed a maximum diameter of false lumen over 60 mm, while none was found in the low blood pressure variability group. CONCLUSIONS: High blood pressure variability, the presence of multiple tears (>2), the configuration of false lumen, the diameter of the false lumen, false/true lumen ratio, and the number of visceral arteries involved were independent risk factors for acute type B aortic dissection.

Phospholipase C inhibits apoptosis of porcine primary granulosa cells cultured in vitro.

Phospholipase C (PLC) can participate in cell proliferation, differentiation and aging. However, whether it has a function in apoptosis in porcine primary granulosa cells is largely uncertain. The objective of this study was to examine the effects of PLC on apoptosis of porcine primary granulosa cells cultured in vitro. The mRNA expression of BAK, BAX and CASP3, were upregulated in the cells treated with U73122 (the PLC inhibitor). The abundance of BCL2 mRNA, was upregulated, while BAX and CASP3 mRNA expression was decreased after treatment with m-3M3FBS (the PLC activator). Both the early and late apoptosis rate were maximized with 0.5 µM U73122 for 4 h. The rate of early apoptosis was the highest at 4 h and the rate of late apoptosis was the highest at 12 h in the m-3M3FBS group. The protein abundance of PLCß1, protein kinase C ß (PKCß), calmodulin-dependent protein kinaseII α (CAMKIIα) and calcineurinA (CalnA) were decreased by U73122, and CAMKIIα protein abundance was increased by m-3M3FBS. The mRNA expression of several downstream genes (CDC42, NFATc1, and NFκB) was upregulated by PLC. Our results demonstrated that apoptosis can be inhibited by altering PLC signaling in porcine primary granulosa cells cultured in vitro, and several calcium-sensitive targets and several downstream genes might take part in the processes.

Data Fusion of Fourier Transform Mid-Infrared (MIR) and Near-Infrared (NIR) Spectroscopies to Identify Geographical Origin of Wild Paris polyphylla var. yunnanensis.

Origin traceability is important for controlling the effect of Chinese medicinal materials and Chinese patent medicines. Paris polyphylla var. yunnanensis is widely distributed and well-known all over the world. In our study, two spectroscopic techniques (Fourier transform mid-infrared (FT-MIR) and near-infrared (NIR)) were applied for the geographical origin traceability of 196 wild P. yunnanensis samples combined with low-, mid-, and high-level data fusion strategies. Partial least squares discriminant analysis (PLS-DA) and random forest (RF) were used to establish classification models. Feature variables extraction (principal component analysis-PCA) and important variables selection models (recursive feature elimination and Boruta) were applied for geographical origin traceability, while the classification ability of models with the former model is better than with the latter. FT-MIR spectra are considered to contribute more than NIR spectra. Besides, the result of high-level data fusion based on principal components (PCs) feature variables extraction is satisfactory with an accuracy of 100%. Hence, data fusion of FT-MIR and NIR signals can effectively identify the geographical origin of wild P. yunnanensis.

LncRNA XIST mediates bovine mammary epithelial cell inflammatory response via NF-κB/NLRP3 inflammasome pathway.

OBJECTIVES: The correlations between long non-coding RNAs (lncRNAs) and diverse mammal diseases have been clarified by many researches, but the cognition about bovine mastitis-related lncRNAs remains limited. This study aimed to investigate the potential role of lncRNA X-inactive specific transcript (XIST) in the inflammatory response of bovine mammary epithelial cells. MATERIALS AND METHODS: Two inflammatory bovine mammary alveolar cell-T (MAC-T) models were established by infecting the cells with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The expressions of pro-inflammatory cytokines were measured, and the proliferation, viability and apoptosis of the inflammatory cells were evaluated after XIST was knocked down by an siRNA. The relationship among XIST, NF-κB pathway and NOD-like receptor protein 3 (NLRP3) inflammasome was investigated using an inhibitor of NF-κB signal pathway. RESULTS: The expression of XIST was abnormally increased in bovine mastitic tissues and inflammatory MAC-T cells. Silencing of XIST significantly increased the expression of E. coli or S. aureus-induced pro-inflammatory cytokines. Additionally, knockdown of XIST could inhibit cell proliferation, suppress cell viability and promote cell apoptosis under inflammatory conditions. Furthermore, XIST inhibited E. coli or S. aureus-induced NF-κB phosphorylation and the production of NLRP3 inflammasome. CONCLUSIONS: The expression of XIST was promoted by activated NF-κB pathway and, in turn, XIST generated a negative feedback loop to regulate NF-κB/NLRP3 inflammasome pathway for mediating the process of inflammation.

Comparison and Identification for Rhizomes and Leaves of Paris yunnanensis Based on Fourier Transform Mid-Infrared Spectroscopy Combined with Chemometrics.

Paris polyphylla, as a traditional herb with long history, has been widely used to treat diseases in multiple nationalities of China. Nevertheless, the quality of P. yunnanensis fluctuates among from different geographical origins, so that a fast and accurate classification method was necessary for establishment. In our study, the geographical origin identification of 462 P. yunnanensis rhizome and leaf samples from Kunming, Yuxi, Chuxiong, Dali, Lijiang, and Honghe were analyzed by Fourier transform mid infrared (FT-MIR) spectra, combined with partial least squares discriminant analysis (PLS-DA), random forest (RF), and hierarchical cluster analysis (HCA) methods. The obvious cluster tendency of rhizomes and leaves FT-MIR spectra was displayed by principal component analysis (PCA). The distribution of the variable importance for the projection (VIP) was more uniform than the important variables obtained by RF, while PLS-DA models obtained higher classification abilities. Hence, a PLS-DA model was more suitably used to classify the different geographical origins of P. yunnanensis than the RF model. Additionally, the clustering results of different geographical origins obtained by HCA dendrograms also proved the chemical information difference between rhizomes and leaves. The identification performances of PLS-DA and the RF models of leaves FT-MIR matrixes were better than those of rhizomes datasets. In addition, the model classification abilities of combination datasets were higher than the individual matrixes of rhizomes and leaves spectra. Our study provides a reference to the rational utilization of resources, as well as a fast and accurate identification research for P. yunnanensis samples.

Comparison of open surgery and endovascular procedures as a therapeutic choice for visceral artery aneurysms.

Objectives Visceral arterial aneurysms may be treated using open surgery or endovascular repair, but the best approach remains controversial. This was a retrospective study aiming to compare open surgery and endovascular treatment strategies for visceral arterial aneurysms. Methods The study included all 93 patients who were admitted with visceral artery aneurysms between January 2001 and January 2011 at the Department of Vascular Surgery, Changhai Hospital, Shanghai, China. All cases underwent either open or endovascular procedures. Overall survival and adverse events were compared between the groups. Success rate, blood loss, length of surgery, and length of hospital stay were also compared. The patients were followed up at three, six, and 12 months then every year until April 2014. Results Open surgery was performed on 34 patients and endovascular procedures on 59. There were no differences in characteristics of the patients between the open surgery and endovascular groups. The perioperative complication rate was 52.9 and 13.6% in the open surgery and endovascular groups, respectively. Mean follow-up was 36.8 months (range: 11 months to 10 years). The one- and five-year survival rates were 100 and 60.6%, respectively, in the open surgery group, compared to 100 and 84.5% in the endovascular group. Multivariate analysis for factors related to overall survival showed that there was a significant relationship with the treatment approach (HR = 0.479, 95%CI: 0.278-0.825; P = 0.008) and the presence of false aneurysm (HR = 2.929, 95%CI: 1.388-6.180, P = 0.005). Conclusions Endovascular repair could be considered as an effective method for visceral artery aneurysm. Endovascular repair showed lower perioperative complication rates and better long-term survival.

Outcomes of Endovascular Repair of Ascending Aortic Dissection in Patients Unsuitable for Direct Surgical Repair.

BACKGROUND: Stent grafting is a therapeutic option for patients who are unable to undergo urgent surgical repair of ascending aortic dissections. However, follow-up regarding outcomes is limited. OBJECTIVES: This study reports mid-term outcomes with endovascular repair for ascending aortic dissections in patients deemed high risk for open repair. METHODS: Between May 1, 2009 and January 31, 2011, 15 ascending aortic dissection patients (ages 45 to 78 years) ineligible for direct surgical repair underwent endovascular repair (1 acute dissection, 7 subacute dissections, and 7 chronic dissections) and were closely followed up for a median of 72 months (range 61 to 81 months). RESULTS: The mean interval between aortic dissection onset and treatment was 25.5 (range 6 to 353) days. Technical success was achieved in all patients. No major morbidity or deaths occurred perioperatively. During the follow-up period, there were no deaths, 8 complications occurred, and there were 4 reinterventions. A new dissection in the aortic arch was treated with a branched endograft. One patient developed retrograde aortic dissection and a left ventricular pseudoaneurysm was successfully treated with open surgery. One cardiovascular ischemia was treated with stenting and 1 supraventricular tachycardia was treated with radiofrequency ablation. Other morbidities included perigraft endoleak, a bird-beak sign, a temporary pericardial effusion, and a left kidney atrophy. Significant enlargements of true lumens and shrinkage of false lumens and overall thoracic aorta were observed at 12 months. No significant changes were detected subsequently. Minimal impact on aortic valve function was recorded over time. CONCLUSIONS: Our results with the novel endovascular procedure appear acceptable. Additional evidence and studies with larger sample size and longer follow-up are needed to support the durability of this new technique.