Ubiquitous coexisting electron-mode couplings in high-temperature cuprate superconductors.

In conventional superconductors, electron-phonon coupling plays a dominant role in generating superconductivity. In high-temperature cuprate superconductors, the existence of electron coupling with phonons and other boson modes and its role in producing high-temperature superconductivity remain unclear. The evidence of electron-boson coupling mainly comes from angle-resolved photoemission (ARPES) observations of [Formula: see text]70-meV nodal dispersion kink and [Formula: see text]40-meV antinodal kink. However, the reported results are sporadic and the nature of the involved bosons is still under debate. Here we report findings of ubiquitous two coexisting electron-mode couplings in cuprate superconductors. By taking ultrahigh-resolution laser-based ARPES measurements, we found that the electrons are coupled simultaneously with two sharp modes at [Formula: see text]70meV and [Formula: see text]40meV in different superconductors with different dopings, over the entire momentum space and at different temperatures above and below the superconducting transition temperature. These observations favor phonons as the origin of the modes coupled with electrons and the observed electron-mode couplings are unusual because the associated energy scales do not exhibit an obvious energy shift across the superconducting transition. We further find that the well-known "peak-dip-hump" structure, which has long been considered a hallmark of superconductivity, is also omnipresent and consists of "peak-double dip-double hump" finer structures that originate from electron coupling with two sharp modes. These results provide a unified picture for the [Formula: see text]70-meV and [Formula: see text]40-meV energy scales and their evolutions with momentum, doping and temperature. They provide key information to understand the origin of these energy scales and their role in generating anomalous normal state and high-temperature superconductivity.

Blocking exosomal secretion aggravated 1,4-benzoquinone-induced cytotoxicity.

Benzene exposure inhibits the hematopoietic system and leads to the occurrence of various types of leukemia. However, the mechanism underlying the hematotoxicity of benzene is still largely unclear. Emerging evidence has shown that exosomes are involved in toxic mechanisms of benzene. To understand the effect of 1,4-benzoquinone (PBQ; an active metabolite of benzene in bone marrow) on the exosomal release characteristics and role of exosomal secretion in PBQ-induced cytotoxicity. Exosomes were isolated from PBQ-treated HL-60 cells, purified by ultracentrifugation, and verified by transmission electron microscopy, nanoparticle tracking analysis and the presence of specific biomarkers. Our results showed that PBQ increased exosomal secretion in a dose-dependent manner, reaching a peak in 3 h at 10 µM PBQ treatment and then slowly decreasing in HL-60 cells. The exosomes contained miRNAs, which have been reported to be associated with benzene exposure or benzene poisoning. In particular, mir-34a-3p and mir-34A-5p were enriched in exosomes derived from PBQ-treated cells. In addition, the inhibition of exosomal release by GW4869 (an inhibitor of exosomal release) exacerbated PBQ-induced cytotoxicity, including increased intracellular reactive oxygen species levels, decreased mitochondrial membrane potential, and increased the apoptosis rate. Our findings illustrated that exosomes secretion plays an important role in antagonizing PBQ-induced cytotoxicity and maintaining cell homeostasis.

Association of placental PPARα/γ and miR-27b expression with macrosomia in healthy pregnancy.

BACKGROUND: Peroxisomal proliferator-activated receptors (PPARs) and microRNAs (miRNAs) play important roles in the development of fetuses, whereas expression changes of PPARs and three miRNAs (miR-17, miR-27b and miR-34a) and whether these miRNAs regulate PPARs in non-GDM macrosomia placenta is unclear. METHODS: A case-control study was performed to collect information and placental tissues on mothers and newborns of non-GDM macrosomia and normal-birth-weight infants. In vitro HTR8-SVneo cellular model was used to detect the effects of miRNAs on PPARs expression. Quantitative real-time PCR (qRT-PCR) and western blot was applied to examine the expression levels of PPARs, miR-17, miR-27b, and miR-34a in placental tissues and cells. RESULTS: The PPARα/γ mRNA and protein levels were significantly up-regulated and miR-27b was down-regulated in the placenta of macrosomia group compared with in the control group, while no difference was observed in PPARß, miR-17, and miR-34a. After adjusting for confounding factors, low miR-27b and high PPARα/γ mRNA expression still increased the risk of macrosomia. The PPARα/γ protein levels presented a corresponding decrease or increase when cells were transfected with miR-27b mimic or inhibitor. CONCLUSIONS: Placental PPARα/γ and miR-27b expression were associated with non-GDM macrosomia and miR-27b probably promotes the occurrence of non-GDM macrosomia by regulating PPARα/γ protein. IMPACT: Low miR-27b and high PPARα/γ mRNA expression in the placenta were associated with higher risk of macrosomia. In vitro HTR8-SVneo cell experiment supported that miR-27b could negatively regulate the expression of PPARα and PPARγ protein. MiR-27b was probably involved in non-GDM macrosomia through negative regulation of PPARα/γ protein.

Ultrapulse carbon dioxide dot matrix laser for facial scar treatment: A meta-analysis.

A meta-analysis was performed to investigate the efficacy of ultrapulse carbon dioxide dot matrix laser treatment for patients with facial scars. PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Literature Database, and Wanfang Database were systematically searched for randomised controlled trials (RCTs) investigating ultrapulse carbon dioxide dot matrix laser treatment for facial scars, and the search was conducted from the time of database inception to July 2023. The retrieved literature was screened independently by two researchers, and data extraction and quality assessments were performed. The meta-analysis was conducted using RevMan 5.4 software. Outcome metrics included overall treatment effectiveness, complication rate, and Echelle d'évaluation clinique des cicatrices d'acné (ECCA) scores. Seventeen RCTs comprising 3703 patients were included, with 1853 patients in the experimental group and 1850 in the control group. The results showed that the experimental group had significantly increased overall treatment efficacy rates (odds ratio [OR]: 3.84, 95% confidence interval [CI]: 3.02-4.90, p < 0.001), reduced complication rates (OR: 0.35, 95% CI: 0.27-0.44, p < 0.001), and improved ECCA scores (standardised mean difference: -1.79, 95% CI: -2.53 to -1.05, p < 0.001) compared with the control group. In conclusion, as the primary treatment modality for facial acne depression scars, ultrapulse carbon dioxide dot matrix laser can significantly increase the overall treatment efficacy rate and ECCA scores and reduce the incidence of complications; however, higher-quality studies are needed for further validation.

Blocking exosomal secretion aggravates 1,4-benzoquinone-induced mitochondrial fission activated by the AMPK/MFF/Drp1 pathway in HL-60 cells.

There is in vivo and in vitro evidence that exposure to benzene or its metabolites could affect the mitochondrial function. However, the underlying molecular mechanism of mitochondrial damage remains to be elucidated. In this study, exposure of human promyelocytic leukemia cells (HL-60) to 1,4-benzoquinone (1,4-BQ; an active metabolite of benzene) increased the intracellular reactive oxygen species levels, decreased the mitochondrial membrane potential, adenosine triphosphate production and mitochondrial DNA (mtDNA) copy number, up-regulated the expression of mitochondrial fission proteins Drp1 and Fis1, and down-regulated the expression of mitochondrial fusion proteins Mfn2 and Opa1. Further study showed that 1,4-BQ mediated mitochondrial fission through activation of the AMP-activated protein kinase/mitochondrial fission factor/dynamin-related protein 1 pathway. Additionally, we also examined the role of exosomal secretion in mitochondrial damage under 1,4-BQ treatment. Results showed that 1,4-BQ increased the total protein level and mtDNA content in exosomes. Upon pre-treatment with the mitochondria-targeted antioxidant SS-31, there was attenuation of the mitochondrial damage induced by 1,4-BQ, accompanied by a change in the exosome release characteristics, while inhibition of exosomal secretion using GW4869 aggravated the 1,4-BQ-mediated mitochondrial fission. We concluded that exosomal secretion may serve as a self-protective mechanism of cells against 1,4-BQ-induced mitochondria damage and mitochondrial dynamics interference.

Ethanol-Induced Neuronal and Cognitive/Emotional Impairments are Accompanied by Down-Regulated NT3-TrkC-ERK in Hippocampus.

AIMS: Ethanol ingestion affects cognition and emotion, which have been attributed to the dysfunction of specific brain structures. Studies of alcoholic patients and animal models consistently identify reduced hippocampal mass as a key ethanol-induced brain adaptation. This study evaluated how neuroadaptation in the hippocampus (Hip) produced by ethanol contributed to related behavioral deficits in male and female rats. METHODS: Effects of acute, short-term and long-term ethanol exposure on the anxiety-like behavior and recognition memory on adult male and female Sprague-Dawley rats were assessed using elevated plus maze test and novel object recognition test, respectively. In addition, in order to investigate the direct effect of ethanol on hippocampal neurons, primary culture of hippocampal neurons was exposed to ethanol (10, 30 and 90 mM; 1, 24 and 48 h), and viability (CCK-8) and morphology (immunocytochemistry) were analyzed at structural levels. Western blot assays were used to assess protein levels of NT3-TrkC-ERK. RESULTS: Acute and short-term ethanol exposure exerted anxiolytic effects, whereas long-term ethanol exposure induced anxiogenic responses in both sexes. Short-term ethanol exposure impaired spatial memory only in female rats, whereas long-term ethanol exposure impaired spatial and recognition memory in both sexes. These behavioral impairments and ethanol-induced loss of hippocampal neurons and decreased cell viability were accompanied by downregulated NT3-TrkC-ERK pathway. CONCLUSION: These results indicate that NT3-TrkC-ERK signaling in the Hip may play an important role in ethanol-induced structural and behavioral impairments.

The correlation between cytokine levels in the aqueous humor and the prognostic value of anti-vascular endothelial growth factor therapy for treating macular edema resulting from retinal vein occlusion.

PURPOSE: To determine the correlation between aqueous humor cytokine levels and the prognostic value of anti-vascular endothelial growth factor (VEGF) therapy for treating macular edema resulting from retinal vein occlusion (RVO-ME). METHODS: This prospective study included 47 RVO-ME and 32 senile cataract cases. Aqueous humor collection was performed in patients with RVO-ME before intravitreal injection of ranibizumab and in patients before cataract surgery. VEGF, monocyte chemotactic protein 1 (MCP-1), interleukin (IL)-8, IL-6, basic fibroblast growth factor (b-FGF), and tumor necrosis factor-α (TNF-α) levels were measured in the aqueous humor. Central retinal thickness (CRT) was measured before ranibizumab treatment and during each follow-up visit. The recovery rate following ranibizumab treatment was calculated as (CRTBT-CRTAT1W)/CRTBT, in which CRTBT was the CRT measured before treatment and CRTAT1W was measured 1 week after treatment. The recurrence time of RVO-ME was recorded. RESULTS: VEGF, MCP-1, IL-8, and IL-6 levels in the aqueous humor of patients with RVO-ME were significantly higher compared with control and were positively correlated with the CRTBT. Ranibizumab significantly reduced CRT, and VEGF levels positively correlated with the recovery rate. The mean recurrence time of RVO-ME was 43.5 days. IL-6 levels negatively correlated with the recurrence time of ME. CONCLUSION: VEGF, MCP-1, IL-8, and IL-6 levels were significantly increased in patients with RVO-ME and were positively correlated with ME. Higher VEGF levels were indicative of CRT recovery, and higher IL-6 levels were indicative of ME recurrence after ranibizumab treatment.

Suppression of long noncoding RNA MALAT1 inhibits the development of uveal melanoma via microRNA-608-mediated inhibition of HOXC4.

This study explored the effects of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the development of uveal melanoma. Moreover, the role of the MALAT1/microRNA-608 (miR-608)/homeobox C4 (HOXC4) axis was assessed by evaluating the proliferation, invasion, and migration, as well as the cell cycle distribution of uveal melanoma in vitro after knocking down MALAT1 or HOXC4 and/or overexpression of miR-608 in uveal melanoma cells (MUM-2B and C918). Moreover, the effects of the MALAT1/miR-608/HOXC4 axis in uveal melanoma in vivo were further evaluated by injecting the C918 cells into the NOD/SCID mice. HOXC4 was found to be a gene upregulated in uveal melanoma, while knockdown of its expression resulted in suppression of uveal melanoma cell migration, proliferation, and invasion, as well as cell cycle progression. In addition, the upregulation of miR-608 reduced the expression of HOXC4 in the uveal melanoma cells, which was rescued by overexpression of MALAT1. Hence, MALAT1 could upregulate the HOXC4 by binding to miR-608. The suppressed progression of uveal melanoma in vitro by miR-608 was rescued by overexpression of MALAT1. Additionally, in vivo assays demonstrated that downregulation of MALAT1 could suppress tumor growth through downregulation of HOXC4 expression via increasing miR-608 in uveal melanoma. In summary, MALAT1 downregulation functions to restrain the development of uveal melanoma via miR-608-mediated inhibition of HOXC4.

Neuroprotective Effects of Grape Seed Procyanidins on Ethanol-Induced Injury and Oxidative Stress in Rat Hippocampal Neurons.

AIMS: Ethanol is a small molecule capable of interacting with numerous targets in the brain, the mechanisms of which are complex and still poorly understood. Studies have revealed that ethanol-induced hippocampal neuronal injury is associated with oxidative stress. Grape seed procyanidin (GSP) is a new type of antioxidant that is believed to scavenge free radicals and be anti-inflammatory. This study evaluated the ability and mechanism by which the GSP improves ethanol-induced hippocampal neuronal injury. METHODS: Primary cultures of hippocampal neurons were exposed to ethanol (11, 33 and 66 mM, 1, 4, 8, 12 and 24 h) and the neuroprotective effects of GSP were assessed by evaluating the activity of superoxide dismutase (SOD), the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and cell morphology. RESULTS: Our results indicated that GSP prevented ethanol-induced neuronal injury by reducing the levels of MDA and LDH, while increasing the activity of SOD. In addition, GSP increased the number of primary dendrites and total dendritic length per cell. CONCLUSION: Together with previous findings, these results lend further support to the significance of developing GSP as a therapeutic tool for use in the treatment of alcohol use disorders.

A new dynamic culture device suitable for rat skin culture.

Cultured skin has been used extensively for testing therapeutic drugs because it replicates the physical and biochemical properties of whole skin. However, traditional static culture cannot fully maintain cell viability and skin morphology because of the limitations involved with nutrient transmission. Here, we develop a new dynamic perfusion platform for skin culture and compare it with a static culture device. Rat skins were cultured in either static or dynamic condition for 0, 3, 6, 9 and 12 days. H&E, periodic acid-Schiff (PAS) and picrosirius red (PSR) staining were used for skin morphology detection, immunostaining against cytokeratin 10 (CK10) for differentiation detection, immunostaining against proliferating cell nuclear antigen (PCNA) for cell proliferation detection and TUNEL staining for apoptosis detection. After culturing for 12 days, the epidermis, basement membrane, hair follicles and connective tissue were disrupted in the static group, whereas these features were preserved in the dynamic group. Moreover, compared to the static group, proliferation in the epidermis and hair follicles was significantly improved and apoptosis in dermis was significantly decreased in the dynamic group. These findings suggest that our device is effective for extending the culture period of rat skin to maintain its characteristics and viability in vitro.

Cord blood leptin DNA methylation levels are associated with macrosomia during normal pregnancy.

BACKGROUND: We previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia. METHOD: We carried out a case-control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500-3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Average cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns (P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72-4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99-27.75), long gestational age (AOR = 3.18, 95% CI: 1.74-5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34-3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31-11.69) significantly increased the risk of macrosomia. CONCLUSIONS: Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.

Ultrasonic/CT image fusion guidance facilitating percutaneous catheter drainage in treatment of acute pancreatitis complicated with infected walled-off necrosis.

BACKGROUND: As the firs-line treatment for acute pancreatitis (AP) related infectious walled-off necrosis (WON), percutaneous catheter drainage (PCD) are usually accomplished under CT or US guidance, either of which has certain disadvantages. It is necessary to verify the clinical effects of using US and CT images fusion as guidance of PCD. METHODS: The total 94 consecutive AP patients with infected WON from January of 2013 to January of 2017 were included. Among these patients with infected WON, 48 received PCD under simple US guidance (US-PCD) and 46 under US/CT images fusion guidance (US/CT-PCD). The clinical data consisting of puncture data, drainage effectiveness indicators, intervention complications were collected. RESULTS: The demographic characteristics and disease related characteristics of two groups were comparable. After 48 h of PCD treatment, the US/CT-PCD group achieved a significantly higher imaging effective rate, and significantly lower inflammatory response indexes and severity score, than the US-PCD group (P < 0.05). The US/CT-PCD group required fewer puncture times and drainage tubes and lower rate of advanced treatment, showing higher operational success rate than the US-PCD group (P < 0.05). Moreover, the US/CT-PCD group exhibited significantly fewer puncture related complications, lower hospital stay, intubation time, and hospitalization expenses than the US-PCD group (P < 0.05). CONCLUSION: PCD treatment under the US/CT images fusion guidance is a reliable intervention with definite clinical effects for AP complicated with infected WON.

Benzoquinone induces ROS-dependent mitochondria-mediated apoptosis in HL-60 cells.

Benzene exposure affects the hematopoietic system and leads to the occurrence of various types of leukemia and hematotoxicity. It has been confirmed that active metabolites of benzene, including 1,4-benzoquinone (1,4-BQ), can induce reactive oxygen species (ROS) and apoptosis in the bone marrow, and recent studies have also suggested that benzene exposure can affect mitochondrial function in both experimental animals and cell lines. However, the potential relationship among ROS production, mitochondrial damages, and subsequent apoptosis following benzene exposure has not been well studied in detail. In the present study, we utilized HL-60 cells, a well-characterized human myeloid cell line, as an in vitro model and examined the effects of 1,4-BQ on intracellular ROS formation, mitochondria damage, and the occurrence of apoptotic events with or without using the ROS scavenger N-acetyl-l-cysteine (NAC). The results demonstrated that 1,4-BQ could dose-dependently induce production of ROS and mitochondrial damage as characterized by mitochondrial membrane potential disruption, mitochondrial ultrastructure alteration, and induced apoptosis and activated caspase-3 and caspase-9. Preincubation of HL-60 cells with NAC prior to 1,4-BQ treatment could block 1,4-BQ-induced production of ROS and the occurrence of apoptosis. These results demonstrated that 1,4-BQ induced apoptosis in HL-60 cells through a ROS-dependent mitochondrial-mediated pathway.

Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

PURPOSE: To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. METHODS: This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. RESULTS: Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P < 0.001), but not in macrosomic neonates. Cord blood BDNF was positively associated with placental BDNF relative expression (r s = 0.245, P = 0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). CONCLUSIONS: Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

12-O-tetradecanoylphorbol-13-acetate activates hair follicle melanocytes for hair pigmentation via Wnt/ß-catenin signaling.

Melanocyte stem cells (McSCs) undergo cyclical activation and quiescence together with hair follicle stem cells (HFSCs). This process is strictly controlled by the autonomous and extrinsic signaling environment. However, the modulation of factors important for the activation of McSCs for hair pigmentation remains unclear. 12-O-tetradecanoylphorbol-13-acetate (TPA) mimics vital signaling pathways involved in melanocyte growth and melanogenesis in vitro. To investigate whether TPA regulates quiescent McSCs for hair pigmentation, we topically smeared TPA on 7-week-old mouse dorsal skin and found that TPA stimulated hair growth and hair matrix pigmentation. These changes were associated with a significant increase in the number of hair bulb melanocytes. Moreover, in the TPA-treated group, hair bulge McSCs and hair bulb melanoblasts actively proliferated. At the molecular level, nuclear ß-catenin, a key factor of Wnt/ß-catenin signaling, was highly synthesized in melanocytes and keratinocytes in TPA-induced hair bulbs. Inhibition of Wnt/ß-catenin signaling by injecting Dickkopf1 plasmids into TPA-treated skin decreased hair matrix pigmentation and inhibited the proliferation and differentiation of McSCs. Our findings suggest that the topical application of TPA stimulates the proliferation and differentiation of McSCs and their progeny for hair matrix pigmentation by activating Wnt/ß-catenin signaling. This might provide a useful experimental model for the study of signals controlling the activation of McSCs.

Hoxc13 is a crucial regulator of murine hair cycle.

Hair follicles undergo cyclical growth and regression during postnatal life. Hair regression is an apoptosis-driven process strictly controlled by micro- and macro-environmental signals. However, how these signals are controlled remains largely unknown. Hoxc13, a member of the Hox gene family, is reported to play an important role in hair follicle differentiation. In the present study, we observed that Hoxc13 was highly expressed in the outer root sheath, matrix, medulla and inner root sheath of hair follicles in a hair cycle-dependent manner. We therefore investigated the role of Hoxc13 in hair follicle cycling. Injection of ShRNA (ShHoxc13) to suppress Hoxc13 in early anagen promoted premature catagen entry, shown by significantly decreased hair length and hair bulb size, increased percentage of catagen hair follicles, hair cycle score and TUNEL+ cells and inhibited proliferation. In contrast, local injection of recombinant Hoxc13 polypeptide (rhHoxc13) during the late anagen phase prolonged the anagen phase. Additionally, rhHoxc13 injections during the telogen phase significantly promoted hair growth and induced the anagen progression. At the molecular level, the expression of phosphorylated smad2 (p-smad2), a key factor of active TGF-ß1 signaling, was up-regulated in the ShHoxc13-treated hair follicles and down-regulated in rhHoxc13-treated hair follicles, suggesting that Hoxc13 might block anagen-catagen transition by inhibiting the TGF-ß1 signaling. Taken together, our data strongly suggest that Hoxc13 is a novel and crucial regulator of the hair cycle. This might also provide an understanding of the mechanism of the 'hair cycle clock' and the development of alopecia treatments.

A 21-35 kDa Mixed Protein Component from Helicobacter pylori Activates Mast Cells Effectively in Chronic Spontaneous Urticaria.

BACKGROUND: Helicobacter pylori (H. pylori) seem to involve in the etiology of chronic spontaneous urticaria (CSU). But studies of the pathogenic mechanism are very little. METHODS: In this study, we detected the serum-specific anti-H. pylori IgG and IgE antibodies in 211 CSU and 137 normal subjects by enzyme-linked immunosorbent assay (ELISA), evaluated the direct activation effects of H. pylori preparations and its protein components on human LAD2 mast cell line in vitro, and analyzed the specific protein ingredients and functions of the most effective H. pylori mixed protein component using liquid chromatography-mass spectrometry and ELISA assay. RESULTS: In CSU patients, the positive rate of anti-H. pylori IgG positive rate was significantly higher than that in normal controls, and the anti-H. pylori IgE levels had no statistical difference between H. pylori-infected patients with and without CSU. Further studies suggested that H. pylori preparations can directly activate human LAD2 mast cell line in a dose-dependent manner and its most powerful protein component was a mixture of 21-35 kDa proteins. Moreover, the 21-35 kDa mixed protein component mainly contained 23 kinds of proteins, which can stimulate the release of histamine, TNF-a, IL-3, IFN-γ, and LTB4 by LAD2 cells in a dose-dependent or time-dependent manner. CONCLUSIONS: A 21-35 kDa mixed protein component should be regarded as the most promising pathogenic factor contributing to the CSU associated with H. pylori infection.

Outcome benefit of abdominal paracentesis drainage for severe acute pancreatitis patients with serum triglyceride elevation by decreasing serum lipid metabolites.

BACKGROUND: Our previous reports demonstrated that abdominal paracentesis drainage (APD) exerts a beneficial effect on severe acute pancreatitis (SAP) patients. However, the underlying mechanisms for this effectiveness are not well understood. METHODS: A retrospective cohort of 132 consecutive non-hypertriglyceridemia (HTG)-induced SAP patients with triglyceride (TG) elevation and pancreatitis-associated ascitic fluid (PAAF) was recruited from May 2010 to May 2015 and included in this study. The patients were divided into two groups: the APD group (n = 68) and the non-APD group (n = 64). The monitored parameters mainly included mortality, hospital stay, the incidence of further intervention, levels of serum lipid metabolites and inflammatory factors, parameters related to organ failure and infections, and severity scores. RESULTS: The demographic data and severity scores were comparable between the two groups. Compared with the non-APD group, the primary outcomes (including mortality, hospital stay and the incidence of percutaneous catheter drainage) in the APD group were improved. The serum levels of lipid metabolites were significantly lower in the APD group after 2 weeks of treatment than in the non-APD group. Logistic regression analysis indicated that the decreased extent of free fatty acid (FFA)(odds ratio, 1.435; P = 0.015) was a predictor of clinical improvement after 2 weeks of treatment. CONCLUSION: Treatment with APD benefits non-HTG-induced SAP patients with serum TG elevation by decreasing serum levels of FFA.

Abdominal paracentesis drainage ahead of percutaneous catheter drainage benefits patients attacked by acute pancreatitis with fluid collections: a retrospective clinical cohort study.

OBJECTIVE: The efficacy and safety of ultrasound-guided abdominal paracentesis drainage ahead of percutaneous catheter drainage as the new second step of a step-up approach are evaluated. DESIGN: The observed parameters were compared between groups including mortality, infection, organ failure, inflammatory factor levels, indexes of further interventions, and drainage-related complications. PATIENTS: This retrospective study included 102 consecutive patients with acute pancreatitis from June 2009 to June 2011. INTERVENTIONS: In this step-up approach, all patients subsequently received medical management, percutaneous catheter drainage (with or without previous abdominal paracentesis drainage), and necrosectomy if necessary according to indications. The patients were divided into two groups: 53 cases underwent abdominal paracentesis drainage followed by percutaneous catheter drainage (abdominal paracentesis drainage + percutaneous catheter drainage group) and 49 cases were managed only with percutaneous catheter drainage (percutaneous catheter drainage-alone group). MEASUREMENTS AND MAIN RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the abdominal paracentesis drainage + percutaneous catheter drainage group (0%) than the percutaneous catheter drainage-alone group (8.2%) (p = 0.050). Compared with the percutaneous catheter drainage-alone group, the laboratory variables of the abdominal paracentesis drainage + percutaneous catheter drainage group decreased more rapidly, the mean number of failed organs was lower, and the interval from the onset of disease to further interventions was much longer. However, there was no significant difference in the prevalence and duration of infections between the two groups. CONCLUSION: Application of abdominal paracentesis drainage ahead of percutaneous catheter drainage is safe and beneficial to patients by reducing inflammatory factors, postponing further interventions, and delaying or avoiding multiple organ failure.

SCF/c-kit signaling is required in 12-O-tetradecanoylphorbol-13-acetate-induced migration and differentiation of hair follicle melanocytes for epidermal pigmentation.

Hair follicle melanocyte stem cells (McSCs) are responsible for hair pigmentation and also function as a major melanocyte reservoir for epidermal pigmentation. However, the molecular mechanism promoting McSCs for epidermal pigmentation remains elusive. 12-O-tetradecanoylphorbol-13-acetate (TPA) mimics key signaling involved in melanocyte growth, migration and differentiation. We therefore investigated the molecular basis for the contribution of hair follicle McSCs to epidermal pigmentation using the TPA induction model. We found that repetitive TPA treatment of female C57BL/6 mouse dorsal skin induced epidermal pigmentation by increasing the number of epidermal melanocytes. Particularly, TPA treatment induced McSCs to initiate proliferation, exit the stem cell niche and differentiate. We also demonstrated that TPA promotes melanoblast migration and differentiation in vitro. At the molecular level, TPA treatment induced robust expression of stem cell factor (SCF) in keratinocytes and c-kit in melanoblasts and melanocytes. Administration of ACK2, a neutralizing antibody against the Kit receptor, suppressed mouse epidermal pigmentation, decreased the number of epidermal melanocytes, and inhibited melanoblast migration. Taken together, our data demonstrate that TPA promotes the expansion, migration and differentiation of hair follicle McSCs for mouse epidermal pigmentation. SCF/c-kit signaling was required for TPA-induced migration and differentiation of hair follicle melanocytes. Our findings may provide an excellent model to investigate the signaling mechanisms regulating epidermal pigmentation from mouse hair follicle McSCs, and a potential therapeutic option for skin pigmentation disorders.