Research Progress on the Pathogenesis of Aortic Dissection.

Aortic dissection is a critical cardiovascular disease due to the separation of media and adventitia caused by the rupture of vascular wall intima. The disease has a high mortality rate of about 1%-3% for each additional hour, since the adventitia of the aorta can rupture and bleed to death at any time. Although great progress has been made in clinical treatment of aortic dissection, and the mortality rate has been significantly reduced, the pathogenesis is still not very clear. At present, related studies have confirmed that inflammation of aortic wall promotes the occurrence and development of Aortic dissection. Although the mechanism of aortic dissection is more complicated, some studies have shown that the infiltration of monocytes/macrophages into the aortic wall is the main pathogenic mechanism of the disease. This review introduces the latest research results on the mechanism of macrophage infiltration and plasticity in aortic dissection.

Geochemical characteristics and growth suitability assessment of Scutellaria baicalensis Georgi in the Earth's critical zone of North China.

Geochemical differentiation of soils has a series of consequences on plant and places pressure on the ecological environment. The quantitative evaluation of element migration in the Earth's critical zone is a challenging task. In this study, two demonstration study areas of Scutellaria baicalensis Georgi were selected, and multiple chemical weathering indexes, chemical loss fraction, mass migration coefficients and biological enrichment coefficient method were used to assess the ecological and geochemical suitability. The results show that for the element of Fe, Zn, Se, Cu, Co, Ni, Mo and Ge, the degree of weathering and soil maturation, were greater in the rhyolitic tuff area than in the Plagioclase gneiss area. In both research sites, the heavy metal level of samples in Scutellaria baicalensis Georgi did not exceed the standard limits. The plagioclase gneiss region's surface soil environment was more alkaline, and the content of soil organic matter was lower, resulting in a higher bioenrichment intensity of Ge, Co, Cu, and Se elements in Scutellaria baicalensis Georgi than in the rhyolite-tuff area. The elements of Cd, Nb, Mo, Pb and As are considerably enriched in the soil of the plagioclase gneiss area but lost by leaching in the soil of the rhyolite tuff area, which is connected to the interplay of elemental abundance and human impact in the parent materials. This study provides a good example of how to assess growth suitability of Chinese medicinal materials in the Earth's critical zone.

[Source of Groundwater Nitrate in Luanping Basin Based on Multi-environment Media Nitrogen Cycle and Isotopes].

The multi-environment media of water, surface soil and vadose zone soil samples were collected in the upstream of Miyun Reservoir, in the Luanping Basin of Chengde City, Hebei Province. The aim was to identify the pollution source, ratio, spatial distribution, migration, and transformation characteristics of nitrogen in groundwater. Hydrogeochemistry, soil total nitrogen, and dissolved nitrate nitrogen of vadose zone soil analysis and a multi isotope tracer technique of δ15 N-NO3 and δ18O-NO3, δ34S-SO4 and δ18O-SO4, δ14 C, combined with land-use type analysis and geostatistics, were used in the study. The results showed that nitrate was the main form of nitrogen in the groundwater of the Luanping Basin. The NO3- concentration of groundwater was significantly correlated with the land-use types of residential land and cultivated land where the nitrate pollution of shallow groundwater was mainly distributed. Of the groundwater samples, 13.79% exceeded the National Standard Ⅲ for Groundwater (GB/T 14848-2017) of NO3- concentration value, while the excess multiple was 1.04-3.86, and 37.93% of the groundwater samples exceeded the World Health Organization NO3- concentration standard value. The excess multiple was 1.08-6.83. The spatial variation of groundwater NO3- concentration, soil total nitrogen and surface soil dissolved nitrate nitrogen of vadose zone was affected by the combination of natural structural factors and anthropogenic factors. The source of groundwater nitrate was mainly from livestock manure and domestic sewage, followed by chemical fertilizer leaching. The nitrogen cycle in the aeration zone-groundwater-dominated nitrogen circulation in the groundwater runoff area of the piedmont basin was nitrification. These findings are highly significant for the prevention and remediation of groundwater pollution when viewing the basin system as an independent unit, and for studying the sources and fate of nitrate pollution in the water environment.

Lichen Simplex Chronicus Secondary to Scald Injury and Skin Flap Transplantation.

A 50-year-old woman had suffered from chronic pruritic plaque located on right retroauricular area for around 16 years, which was diagnosed as lichen simplex chronicus. Seventeen years ago, patient had multiple scalded areas distributed throughout the body and underwent autologous skin flap transplantation for the right retroauricular wound. After the wound healed, patient started experiencing paresthesia continuously on the skin grafted area and could not resist scratching. To our knowledge, this is the first reported case of lichen simplex chronicus secondary to scald injury and skin flap transplantation. We successfully treated this patient with dyclonine hydrochloride cream 1% and desonide cream 0.05%.

Progress in Gene Therapy for Chronic Heart Failure.

Chronic heart failure (CHF) is still the leading cause of morbidity and mortality worldwide, and carries with it large economic and social burdens. Although steady and substantial progress has been made in reducing mortality from heart failure using conventional treatments, novel pharmacologic and surgical interventions have not been effective in extending five year survival rates. Therefore, it is necessary to explore new therapies. Gene therapy was introduced in 1970s with the development of recombinant DNA technology. Due to recent progress in the understanding of myocardial metabolism and application of vector based gene transfer strategies in animal models and initial clinical trials, gene therapy possibly affords an ideal treatment alternative for CHF. In last 2 decades, much research has been done on gene therapy, using various genes, signal transduction passages and delivery methods to treat advanced heart failure. Current research in ischemic heart disease (IHD) mainly focuses on stimulating angiogenesis, modifying the coronary vascular environment, and improving the vascular endothelial function with localized gene coated catheters and stents. Compared with standard ischemic heart disease treatment, the main goal of gene therapy for CHF is to inhibit apoptosis, reduce the undesirable remodeling and increase contractility through the most efficient cardiomyocyte transfection [Katz 2012a]. In this paper, we review various gene transfer technologies in ischemic heart disease and heart failure models, and discuss the advantages and disadvantages of these strategies in vector-mediated cardiac gene delivery, with the main focus on the high efficiency approach of a molecular cardiac surgery delivery system.

Induction of Alternative Proinflammatory Cytokines Accounts for Sustained Psoriasiform Skin Inflammation in IL-17C+IL-6KO Mice.

IL-6 inhibition has been unsuccessful in treating psoriasis, despite high levels of tissue and serum IL-6 in patients. In addition, de novo psoriasis onset has been reported after IL-6 blockade in patients with rheumatoid arthritis. To explore mechanisms underlying these clinical observations, we backcrossed an established psoriasiform mouse model (IL-17C+ mice) with IL-6-deficient mice (IL-17C+KO) and examined the cutaneous phenotype. IL-17C+KO mice initially exhibited decreased skin inflammation; however, this decrease was transient and reversed rapidly, concomitant with increases in skin Tnf, Il36α/ß/γ, Il24, Epgn, and S100a8/a9 to levels higher than those found in IL-17C+ mice. A comparison of IL-17C+ and IL-17C+KO mouse skin transcriptomes with that of human psoriasis skin revealed significant correlation among transcripts of skin of patients with psoriasis and IL-17C+KO mouse skin, and confirmed an exacerbation of the inflammatory signature in IL-17C+KO mice that aligns closely with human psoriasis. Transcriptional analyses of IL-17C+ and IL-17C+KO primary keratinocytes confirmed increased expression of proinflammatory molecules, suggesting that in the absence of IL-6, keratinocytes increase production of numerous additional proinflammatory cytokines. These preclinical findings may provide insight into why patients with arthritis being treated with IL-6 inhibitors develop new onset psoriasis and why IL-6 blockade for the treatment of psoriasis has not been clinically effective.

Systemic abnormalities of psoriatic patients: a retrospective study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease related to the metabolic syndrome, cardiovascular disease, and other comorbidities. However, so far there has been no specific research concerning systemic abnormalities in psoriatic patients. OBJECTIVE: A retrospective study was conducted focusing on the detailed systemic abnormalities in psoriatic patients. METHODS: Psoriatic inpatients data was collected from July 2009 to September 2015. The inclusion criteria were first-time hospitalization and without administration of systemic drug therapy or exposure to phototherapy for psoriasis for at least 1 month. Detailed systemic indexes were mainly evaluated. RESULTS: The abnormality rates of blood routine examination, urine examination, blood biochemical examination and chest X-ray of 43 psoriatic patients were significantly higher than those of 44 non-psoriasis controls, and psoriasis patients significantly had higher absolute values of leukocytes and neutrophils, and significantly lower values of lymphocytes. Compared with psoriasis vulgaris, erythrodermic psoriasis had significantly higher abnormality rates of blood biochemical examination and serum electrolyte analysis. Erythrodermic psoriasis had significantly higher absolute values of blood leukocytes, neutrophils, and lower serum calcium compared with those of psoriasis vulgaris. The neutrophil-to-lymphocyte ratio of controls was significantly lower than that of psoriatic patients, and neutrophil-to-lymphocyte ratio of erythrodermic psoriasis was significantly higher in comparison with psoriasis vulgaris. CONCLUSION: This study is the first report in relation to a detailed assessment of systemic abnormalities in psoriatic patients prior to onset of systemic treatment. The systemic condition of psoriatic patients should be observed by clinicians before systemic therapy.

Quality of Life and Cost-Effectiveness of Radiofrequency Ablation versus Open Surgery for Benign Thyroid Nodules: a retrospective cohort study.

This study is to compare the health-related quality of life (HRQoL) and cost-effectiveness of radiofrequency ablation (RFA) and open thyroidectomy (OT) for benign thyroid nodules (BTNs) treatment. HRQoL and utility were assessed for 404 BTN patients immediately before treatments (RFA:OT = 137:267) and at 6-month visit. A cost-effectiveness analysis was performed from societal perspective in the China context. Resource use (hospitalization, sick leaves) was collected. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for RFA and OT. Sensitivity analyses of costs of RFA were performed. At 6-month visit, patients treated with RFA had significantly better HRQoL than patients treated with OT on general health (68.5 versus 66.7, P = 0.029), vitality (71.3 versus 67.5, P < 0.001) and mental health (80.9 versus 79.3, P = 0.038). RFA was more effective than OT in terms of quality-adjusted life-years (QALYs; 0.01QALY/patient) but more expensive (US$823/patient). The probability that RFA would be cost effective at a US$50,000/QALY threshold was 15.5% in China, and it would be increased to 88.4% when price of the RFA device was lowered by 30%. RFA exhibited a significant improvement of HRQoL relative to OT, but is unlikely to be cost effective at its current price in short time.

MiR-23a-depressed autophagy is a participant in PUVA- and UVB-induced premature senescence.

Autophagy is a cellular catabolic mechanism that is activated in response to stress conditions, including ultraviolet (UV) irradiation, starvation, and misfolded protein accumulation. Abnormalities in autophagy are associated with several pathologies, including aging and cancer. Furthermore, recent studies have demonstrated that microRNAs (miRNAs) are potent modulators of the autophagy pathway. As a result, the current study aims to elucidate the role of the autophagy-related miRNA miR-23ain the process of photoaging. Experiments demonstrated that the antagomir-mediated inactivation of miR-23a resulted in the stimulation of PUVA- and UVB-depressed autophagy flux and protected human fibroblasts from premature senescence. Furthermore, AMBRA1 was identified as a miR-23a target. AMBRA1 cellular levels increased following the introduction of miR-23a antagomirs. And a bioinformatics analysis revealed that the AMBRA1 3' UTR contains functional miR-23a responsive sequences. Finally, it was also demonstrated that both AMBRA1 overexpression and Rapamycin treatment were both able to rescue fibroblasts from PUVA and UVB irradiation-induced autophagy inhibition, but that these effects could also be mitigated by miR-23a overexpression. Therefore, this study concludes that miR-23a-regulated autophagy is a novel and important regulator of ultraviolet-induced premature senescence and AMBRA1 is a rate-limiting miRNA target in this pathway.

A 41-gene signature derived from breast cancer stem cells as a predictor of survival.

PURPOSE: The aim of this study was to evaluate the ability of a 41-gene signature derived from breast cancer stem cells (BCSCs) to estimate the risk of metastasis and survival in breast cancer patients. METHODS: The centroid expression of the 41-gene signature derived from BCSCs was applied as the threshold to classify patients into two separate groups--patients with high expression (high-EL) of the prognostic signature and patients with low expression (low-EL). The predictive ability of the 41-gene signature was evaluated by Cox regression model and was compared against other popular tests, such as Oncotype and MammaPrint. RESULTS: Our results showed that the 41-gene prognostic signature was significantly associated with age (P = .0351) and ER status (P = .0095). The analysis indicated that patients in the high-EL group had a worse prognosis than those in the low-EL group in terms of both overall survival (OS: HR, 2.05, P = .009) and distant metastasis-free survival (DMFS: HR, 2.24, P = .002). Additionally, the 41-gene signature was an independent risk factor and separates patients based on estrogen receptor status. While comparable to Oncotype, the analysis demonstrated that the 41-gene signature had a better prognostic value in predicting DMFS and OS than AOL, NPI, St. Gallen, Veridex, and MammaPrint. CONCLUSIONS: This study confirms the utility of the 41-gene signature and adds to the growing evidence that gene expression signatures of BCSCs have clinical potential to predict patient outcome and aid in treatment choice.

The protective effect of baicalin against UVB irradiation induced photoaging: an in vitro and in vivo study.

OBJECTIVE: This study was aimed to evaluate the anti-photoaging effects of baicalin on Ultraviolet B (UVB)-induced photoaging in the dorsal skin of hairless mice and premature senescence in human dermal fibroblasts. METHODS: We established in vivo and in vitro photoaging models by repeated exposures to UVB irradiation. By HE staining, masson staining, immunohistostaing and real-time RT-PCR, we analyzed epidermal thickness, collagen expression and the mRNA and protein levels of type I collagen, type III collagen, interstitial collagenase (MMP-1 and MMP-3) in UVB exposed dorsal mice skin. The aging condition in human dermal fibroblasts was determined by senescence-associated ß-galactosidase (SA-ß-gal) staining. Cell viability was determined using the Cell Counting Kit-8 (CCK-8). The G1 phase cell growth arrest was analyzed by flow cytometry. The senescence-related protein levels of p16INK-4a, p21WAF-1, and p53 and protein levels of phosphorylated histone H2AX were estimated by Western blotting. RESULTS: Topically application of baicalin treatment reduced UVB-induced epidermal thickening of mouse skin and also result in an increase in the production of collagen I and III, and a decrease in the expression of MMP-1 and MMP-3. Compared with the UVB-irradiated group, we found that the irradiated fibroblasts additionally treated with baicalin demonstrated a decrease in the expression of SA-ß-gal, a increase in the cell viability, a decrease in the G1 phase cell proportion, a downregulation in the level of senescence-associated and γ-H2AX proteins. However, Baicalin had no difference in the normal fibroblasts without UVB irradiation and long-term Baicalin incubation of UVB-SIPS fibroblasts gave no effects on the cell proliferation. CONCLUSIONS: Taken together, these results suggest that baicalin significantly antagonizes photoaging induced by UVB in vivo and in vitro, indicating the potential of baicalin application for anti-photoaging treatment.

Effects of local anesthetics on contractions of pregnant and non-pregnant rat myometrium in vitro.

In order to determine whether local anesthetics directly affect the propagation and strength of myometrial contractions, we compared the effects of bupivacaine, ropivacaine, lidocaine and tetracaine on the contractions of myometrium isolated from pregnant and non-pregnant rats. Full-thickness myometrial strips were obtained from 18- to 21-day pregnant and non-pregnant Sprague-Dawley rats and incubated in an organ bath. When spontaneous contractions became regular, strips were exposed to cumulative concentrations of the four local anesthetics ranging from 0.01 to 300 µmol/L and the amplitude and frequency of contraction were recorded. All four compounds caused a concentration-dependent inhibition of the contractility of pregnant and non-pregnant uterine muscle. In pregnant myometrium, the concentration that caused 50% inhibition (IC(50)) was 100 µmol/L for bupivacaine, 157 µmol/L for ropivacaine, > 1000 µmol/L for lidocaine, and 26.3 µmol/L for tetracaine. In non-pregnant myometrium, the IC(50) was 26.9 µmol/L for bupivacaine, 40 µmol/L for ropivacaine, 384 µmol/L for lidocaine, and 7.4 µmol/L for tetracaine. These results suggested that local anesthetics do inhibit myometrial contractions in pregnant and non-pregnant rats in a concentration-dependent manner.

Tissue microarray analysis of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer patients.

The goal of this study was to determine the diagnostic and prognostic potential of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer. We analyzed a tissue microarray comprised of 100 breast cancer cases and 70 matched normal samples. Analysis of an online database, which included 2,977 patients, was also performed. There was a significant difference in cytoplasmic expression of XIAP (XIAP-C) between breast cancer tissue and matched normal (p<0.001). Staining of XIAP-C was defined as negative (breast cancer 8.42% vs. normal 30.91%), slight (40.0 vs. 45.45%), moderate (43.16 vs. 23.64%), or high (8.42 vs. 0%). High XIAP-C protein expression correlated with human epidermal growth factor receptor 2 (HER-2) status (p=0.010) and with human p53 mutant-type (P53) status (p=0.039). We found that XIAP expression did not correlate with disease-free survival (p=0.706) and overall survival (p=0.496) of breast cancer patients. An Internet-based system analysis confirmed our results. In the subgroup analysis, basal-like breast cancer patients with high XIAP levels in the tumor had a significantly increased risk of relapse; thus, the up-regulation of XIAP appeared to be predictive of poor relapse-free survival (p=0.013). Kaplan-Meier curves also identified a significant correlation between distant metastasis-free survival and XIAP expression in patients with lymph-node-negative disease (p=0.030). In summary, expression of XIAP-C was significantly higher in breast cancer compared to normal tissue. XIAP-C expression correlated with HER-2 status and may be considered a prognostic biomarker for basal-like breast cancer patients.

Palmitic acid induces production of proinflammatory cytokines interleukin-6, interleukin-1ß, and tumor necrosis factor-α via a NF-κB-dependent mechanism in HaCaT keratinocytes.

To investigate whether palmitic acid can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with palmitic acid at pathophysiologically relevant concentrations. Secretion levels of interleukin-6 (IL-6), tumor necrosis factor- α (TNF- α), interleukin-1 ß (IL-1 ß), NF- κ B nuclear translocation, NF- κ B activation, Stat3 phosphorylation, and peroxisome proliferator-activated receptor alpha (PPAR α) mRNA and protein levels, as well as the cell proliferation ability were measured at the end of the treatment and after 24 hours of recovery. Pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF- κ B) and goat anti-human IL-6 polyclonal neutralizing antibody were used to inhibit NF- κ B activation and IL-6 production, respectively. Our results showed that palmitic acid induced an upregulation of IL-6, TNF- α , IL-1 ß secretions, accompanied by NF- κ B nuclear translocation and activation. Moreover, the effect of palmitic acid was accompanied by PPAR α activation and Stat3 phosphorylation. Palmitic acid-induced IL-6, TNF- α , IL-1 ß productions were attenuated by NF- κ B inhibitor PDTC. Palmitic acid was administered in amounts able to elicit significant hyperproliferation and can be attenuated by IL-6 blockage. These data demonstrate for the first time that palmitic acid can stimulate IL-6, TNF- α , IL-1 ß productions in HaCaT keratinocytes and cell proliferation, thereby potentially contributing to acne inflammation and pilosebaceous duct hyperkeratinization.

Elevated miR-34c-5p mediates dermal fibroblast senescence by ultraviolet irradiation.

Previous studies showed that several miRNAs can regulate pathways involved in UVB-induced premature senescence and response to ultraviolet irradiation. It has also been reported that miR-34c-5p may be involved in senescence-related mechanisms. We propose that miR-34c-5p may play a crucial role in senescence of normal human primary dermal fibroblasts. Here, we explored the roles of miR-34c-5p in UVB-induced premature senescence on dermal fibroblasts. MiR-34c-5p expression was increased in dermal fibroblasts after repeated subcytotoxic UVB treatments. Underexpression of miR-34c-5p in dermal fibroblasts led to a marked delay of many senescent phenotypes induced by repeated UVB treatments. Furthermore, underexpression of miR-34c-5p in dermal fibroblasts can antagonize the alteration of G1-arrested fibroblasts. Moreover, E2F3, which can inactivate p53 pathway and play a role in cell cycle progression, is a down-stream target of miR-34c-5p. Forced down-expression of miR-34c-5p decreased the expression of UVB-SIPS induced P21 and P53 at both mRNA and protein levels. Our data demonstrated that down-regulation of miR-34c-5p can protect human primary dermal fibroblasts from UVB-induced premature senescence via regulations of some senescence-related molecules.

The effect of conditioned media of adipose-derived stem cells on wound healing after ablative fractional carbon dioxide laser resurfacing.

OBJECTIVE: To evaluate the benefits of conditioned medium of Adipose-derived stem cells (ADSC-CM) on wound healing after fractional carbon dioxide laser resurfacing (FxCR) on human skin. MATERIALS AND METHODS: Nineteen subjects were treated with FxCR on the bilateral inner arms. ADSC-CM was applied on FxCR site of one randomly selected arm. Transepidermal water loss (TEWL), skin color, and gross-elasticity of FxCR site on both arms were measured. Skin samples were taken by biopsy from three subjects 3 weeks after treatment for histopathological manifestations and mRNA expressions of procollagen types I and III, elastin genes were noted. RESULTS: The index of erythema, melanin, and TEWL of the ADSC-CM-treated skin were significantly lower than those of the control side. The mRNA expression of type III procollagen in ADSC-CM-treated group at 3 weeks posttreatment was 2.6 times of that of the control group. CONCLUSION: Application of allograft ADSC-CM is an effective method for enhancing wound healing after FxCR, by reducing transient adverse effects such as erythema, hyperpigmentation, and increased TEWL.

Dihydrotestosterone induces SREBP-1 expression and lipogenesis through the phosphoinositide 3-kinase/Akt pathway in HaCaT cells.

BACKGROUND: The purpose of this study was to investigate the effects and mechanisms of dihydrotestosterone (DHT)-induced expression of sterol regulatory element binding protein-1 (SREBP-1), and the synthesis and secretion of lipids, in HaCaT cells. HaCaT cells were treated with DHT and either the phosphoinositide 3-kinase inhibitor LY294002 or the extracellular-signal-regulated kinase (ERK) inhibitor PD98059. Real time-PCR, Western blot, Oil Red staining and flow cytometry were employed to examine the mRNA and protein expressions of SREBP-1, the gene transcription of lipid synthesis, and lipid secretion in HaCaT cells. FINDINGS: We found that DHT upregulated mRNA and protein expressions of SREBP-1. DHT also significantly upregulated the transcription of lipid synthesis-related genes and increased lipid secretion, which can be inhibited by the addition of LY294002. CONCLUSIONS: Collectively, these results indicate that DHT induces SREBP-1 expression and lipogenesis in HaCaT cells via activation of the phosphoinositide 3-kinase/Akt Pathway.