Effect Evaluation of Platelet-Rich Plasma Combined with Vacuum Sealing Drainage on Serum Inflammatory Factors in Patients with Pressure Ulcer by Intelligent Algorithm-Based CT Image.

This work was to explore the efficacy of intelligent algorithm-based computed tomography (CT) to evaluate platelet-rich plasma (PRP) combined with vacuum sealing drainage (VSD) in the treatment of patients with pressure ulcers. Based on the u-net network structure, an image denoising algorithm based on double residual convolution neural network (Dr-CNN) was proposed to denoise the CT images. A total of 84 patients who were hospitalized in hospital were randomly divided into group A (without any intervention), group B (PRP treatment), group C (VSD treatment), and group D (PRP+VSD treatment). Procalcitonin (PCT) was detected by enzyme-linked immunosorbent assay (ELISA) combined with immunofluorescence method, C-reactive protein (CRP) was detected by rate reflectance turbidimetry (RRT), and interleukin-6 (IL-6) was detected by electrochemiluminescence method. The results showed that after treatment, 44 cases (52.38%) of pressure ulcers patients recovered, 24 cases (28.57%) had no change in stage, and 16 cases (19.04%) developed pressure ulcers. The pain scores of group D at 1 week (3.35 ± 0.56 points) and 2 weeks (2.76 ± 0.55 points) after treatment were significantly lower than those in group C (7.77 ± 0.58 points and 6.34 ± 0.44 points, respectively). The time of complete wound healing in group D (24.5 ± 2.32) was obviously lower in contrast to that in groups A, B, and C (35.54 ± 3.22 days, 30.23 ± 2 days, and 29.34 ± 2.15 days, respectively). In addition, the medical satisfaction of group D (8.74 ± 0.69) was significantly higher than that of groups A, B, and C (4.69 ± 0.85, 5.22 ± 0.31, and 5.18 ± 0.59, respectively). The levels of IL-6 and PCT in group D were lower than those in groups A, B, and C, and the differences were statistically significant (P < 0.01). The average values of peak signal to noise ratio (PSNR) and structural similarity index measure (SSIM) of the Dr-CNN network model were 37.21 ± 1.09 dB and 0.925 ± 0.01, respectively, which were higher than other algorithms. The mean values of root mean square error (MSE) and normalized mean absolute distance (NMAD) of the Dr-CNN network model were 0.022 ± 0.002 and 0.126 ± 0.012, respectively, which were significantly lower than other algorithms (P < 0.05). The experimental results showed that PrP combined with VSD could significantly reduce the inflammatory response of patients with pressure ulcers. PRP combined with VSD could significantly reduce the pain of dressing change for patients. Moreover, the performance model of image denoising algorithm based on double residual convolutional neural network was better than other algorithms.

Edaravone attenuates smoke inhalation injury in rats by the Notch pathway.

OBJECTIVE: To explore the protective effect of inhaled edaravone (EDA) on inflammation, oxidative stress (OS), and pulmonary function (PF) in rats after smoke inhalation injury (SII), as well as its mechanisms. METHODS: Twenty-four rats were designated as group A (model group), group B (EBA prevention group), group C (low-dose group) and group D (high-dose group) (n=6 for each group). SII models were induced in all groups. After successful modeling, rats in each group were treated accordingly. After 6 hours of modeling, assessments of PF, oxygenation index (OI), inflammatory cytokine expression, oxidative stress index (OSI), wet/dry weight ratio (W/D), total lung water (TLW), and the expression of Notch markers were carried out. RESULTS: Compared with group A, the remaining groups had higher peak respiratory velocity (PEF), forced expiratory volume in the first second (FEV1), FEV1/forced vital capacity (FVC) and OI, as well as lower W/D and TLW; levels of serum superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 decreased, and those of serum myeloperoxidase (MPO) and IL-10 increased. Levels of PEF, FEV1, FVC, OI, MPO, and IL-10 were higher in group A than in groups C and D, and those of W/D, TLW, SOD, MDA, TNF-α, and IL-6 were lower. Levels of Notch markers NICD, Hes1 and Hes5 were downregulated in groups B, C, and D, and in group B were lower than those in groups C and D. CONCLUSION: Inhaled EDA is able to alleviate inflammation and OS and effectively improve PF in rats after SII, possibly by inhibiting the Notch pathway.

Aerosol inhalation of edaravone can improve inflammation, oxidative stress and pulmonary function of rats with smoke inhalation injury by down-regulating miR-320.

OBJECTIVE: To explore the protective effects and related mechanism of aerosol inhalation of edaravone on inflammation, oxidative stress and pulmonary function (PF) in rats with smoke inhalation injury. METHODS: Twenty-four rats were stochastically and equally divided into four groups: group A (edaravone-preventing group), group B (model group), group C (low-dose group) and group D (high-dose group). The serum of rats was collected to determine the expression of miR-320, inflammatory mediators (TNF-α, IL-6, IL-10), oxidative stress indexes (MDA, SOD, MPO) and oxygenation index (OI). Pulmonary tissues of rats were collected to determine the total lung water (TLW), wet-to-dry ratio (W/D) and other parameters. HE staining was adopted for pathological evaluation. RESULTS: Compared with group B, the levels of miR-320, TNF-α, IL-6, MDA, MPO, TLW and W/D in group A were significantly down-regulated, while IL-10, SOD and OI levels were significantly up-regulated, and the trend of this change was more obvious than that in group C and group D, with notably better improvement degree in group D than group C. In HE staining, the pulmonary tissue structure was basically normal in group A, and was better than that of the other three groups. In group B, the pulmonary tissue was seriously damaged, accompanied by a large number of inflammatory cells infiltration and alveolar wall thickening. The pathological condition of group C was notably ameliorated, the extent of this improvement was more pronounced in group D, and the degree of pathological improvement in group D was superior to that in group C. CONCLUSION: Aerosol inhalation of edaravone in advance can reduce the levels of inflammatory factors and oxidative stress indexes in serum of smoke inhalation injury rats, thus protecting PF, which may be related to the down-regulation of miR-320 by edaravone.

MicroRNA-185 inhibits the proliferation and migration of HaCaT keratinocytes by targeting peroxisome proliferator-activated receptor ß.

Proliferation and migration of keratinocytes are major processes of skin wound repair after injury. It has been indicated that microRNAs (miRNAs/miRs) are associated with the proliferation and migration of keratinocytes. However, the mechanism by which miR-185 affects these processes in keratinocytes remains unclear. In the present study, the expression level of miR-185 and peroxisome proliferator-activated receptor ß (PPARß) was examined by reverse transcription-quantitative PCR in HaCaT keratinocytes. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. Western blot analysis was used to detect the levels of cell proliferation, migration and PI3K/AKT signaling pathway-associated proteins. In addition, the migratory capacity of the cells was determined using Transwell assay. The target gene of miR-185 was verified using dual-luciferase reporter assay. The results indicated that overexpression of miR-185 inhibited proliferation, migration and activation of the PI3K/AKT signaling pathway in HaCaT keratinocytes. PPARß was indicated to be a target of miR-185 and its overexpression promoted the proliferation and migration of HaCaT keratinocytes, while its knockdown exhibited the adverse effects. Furthermore, PI3K inhibitor LY294002 inhibited activation of the PI3K/AKT signaling pathway and decreased the proliferation and migration of HaCaT keratinocytes. In addition, overexpressed PPARß reversed the suppressive effects of miR-185 overexpression on proliferation, migration and activation of the PI3K/AKT signaling pathway. In conclusion, the results of the present study demonstrated that miR-185 suppressed activation of the PI3K/AKT signaling pathway via targeting PPARß, thereby regulating proliferation and migration in HaCaT keratinocytes. The present study provided a novel theoretical basis for the use of miR-185 as a target in wound repair.

NEAT1 Knockdown Inhibits Keloid Fibroblast Progression by miR-196b-5p/FGF2 Axis.

BACKGROUND: Keloid is a benign fibroproliferative tumor of the skin caused by abnormal wound healing process after skin injury. Long noncoding RNAs have been reported to be involved in the development of keloid. However, the role and mechanism of nuclear enriched abundant transcript 1 (NEAT1) in keloid are still unknown. METHODS: Quantitative real-time polymerase chain reaction was performed to detect the expression of NEAT1, miR-196b-5p, and fibroblast growth factor 2 (FGF2). Western blot was conducted to measure the levels of collagen I, α-smooth muscle actin, fibronectin, and FGF2. Cell Counting Kit-8 assay and transwell assay were used to evaluate cell viability and migration, respectively. Dual-luciferase reporter assay was conducted to verify the targeting relationship between miR-196b-5p and NEAT1 or FGF2. RESULTS: NEAT1 was increased and miR-196b-5p was decreased in keloid tissues and fibroblasts. NEAT1 knockdown or miR-196b-5p overexpression suppressed cell viability, migration, and extracellular matrix (ECM) component production in keloid fibroblasts. MiR-196 b-5p was a target of NEAT1, and NEAT1 overexpression reversed the effect of miR-196b-5p on keloid fibroblast progression. Moreover, we found that miR-196b-5p directly targeted FGF2. FGF2 knockdown suppressed keloid fibroblast viability, migration, and ECM protein production. FGF2 overexpression abolished the effect of miR-196b-5p overexpression on keloid fibroblast development. CONCLUSIONS: NEAT1 silencing suppressed cell viability, migration, and ECM expression in keloid fibroblasts by regulating miR-196b-5p/FGF2 axis, indicating a promising strategy for keloid treatment.

Loganin attenuates intestinal injury in severely burned rats by regulating the toll-like receptor 4/NF-κB signaling pathway.

Severe burns may lead to intestinal inflammation and oxidative stress, resulting in intestinal barrier damage and gut dysfunction. Loganin, an iridoid glycoside compound, has been isolated from Cornus officinalis Sieb. et Zucc; however, its role in the treatment of burn injury is yet to be fully elucidated. Therefore, the present study examined the effect of loganin administration on burn-induced intestinal inflammation and oxidative stress after severe burns in male Sprague-Dawley rats. Histological injury was assessed by hematoxylin and eosin staining. Furthermore, cytokine expression in intestinal tissues was measured by ELISA and reverse transcription-quantitative PCR. Antioxidative activities were assessed by determining the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). Apoptosis was detected by flow cytometry. Apoptosis-related proteins, toll-like receptor 4 (TLR4) protein and NF-κB translocation were examined by western blotting. Immunohistochemical staining was used to observe TLR4 and NF-κB p65 expression in intestinal tissues. The present study suggested that loganin administration significantly reduced burn injury-induced intestinal histological changes, tumor necrosis factor-α, interleukin (IL)-6 and IL-1ß production and oxidative stress, evidenced by decreased ROS levels and MDA content (P<0.05). Furthermore, loganin increased SOD, CAT and GSH-Px levels and intestinal epithelial cell apoptosis. Loganin treatment also significantly inhibited activation of the TLR4/NF-κB signaling pathway in the intestine of severely burned rats (P<0.05). In conclusion, loganin reduced burns-induced intestinal inflammation and oxidative stress, potentially by regulating the TLR4/NF-κB signaling pathway.

Traditional Chinese Medicine syndrome elements of male infertility revealed by latent tree model analysis.

OBJECTIVE: To explore the features of Traditional Chinese Medicine (TCM) syndromes in male infertility using computer-based analyses. METHODS: Latent class analysis was used to analyze the TCM syndrome data from 813 patients with male infertility and establish a latent tree model. RESULTS: A latent tree model with a Bayesian information criterion score of -11 263 was created. This model revealed that the characteristics of basic TCM syndromes in patients with male infertility were kidney Yang deficiency, kidney Qi deficiency, spleen Yang deficiency, liver Qi stagnation, Qi stagnation and blood stasis, and dump-heat; moreover, most patients with male infertility had complex syndromes (spleen-kidney Yang deficiency and liver Qi stagnation) rather than simple single syndromes. CONCLUSION: The hidden tree model analysis revealed the objective and quantitative complex relationships between the TCM symptoms of male infertility, and obtained the quantification and objective evidence of TCM syndromes in male infertility.

Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway.

Prostate cancer is one of the most common malignancies in men, and it urgently demands precise interventions that target the signaling pathways implicated in its initiation, progression, and metastasis. The Notch-1 signaling pathway is closely associated with the pathophysiology of prostate cancer. This study investigated the antitumor effects and mechanisms of curcumin, which is a well-known natural compound from curcuminoids, in prostate cancer cells. Viability, proliferation, and migration were analyzed in two prostate cancer cell lines, DU145 and PC3, after curcumin treatment. Whether the Notch-1 signaling pathway is involved in the antitumor effects of curcumin was examined. Curcumin inhibited the survival and proliferation of PC3 and DU145 cells in a dose- and time-dependent manner and inhibited DU145 migration. Curcumin did not affect the expression of Notch-1 or its active product NICD, but it did inhibit the expression of MT1-MMP and MMP2 proteins in DU145 cells. We found that curcumin inhibited the DNA-binding ability of NICD in DU145 cells. In conclusion, curcumin inhibited the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway.

A comparison of drug resistances of targeted drugs for advanced renal cell cancer approved by the Food and Drug Administration: A meta-analysis of randomized clinical trials.

PURPOSE: The purpose of this study was to conduct network meta-analysis to assess drug resistances of the Food and Drug Administration-approved drugs for advanced renal cell carcinoma. MATERIALS AND METHODS: Database searches were conducted to identify randomized controlled trials reporting results for eligible treatments. After searching for PubMed, MEDLINE, EMBASE, and ISI Web of Science, 22 studies (n = 7854 patients) were included for the comparison of drug resistance in the present meta-analysis. RESULTS: For overall present, the mean 6-month progression-free survival rates were 65.4%, 49.3%, 60.6%, 70.3%, 62.6%, 41.6%, 38.2%, 66.1%, 43.1%, and 17.9% for sunitinib, sorafenib, pazopanib, axitinib, bevacizumab plus interferon (IFN)-a, everolimus, temsirolimus, temsirolimus plus bevacizumab, IFN-a, and placebo, respectively. For indirect comparison, two combined therapies (bevacizumab plus IFN-a and temsirolimus plus bevacizumab) and sunitinib were of less ability of drug resistance. The risk ratio of sunitinib therapy was 3.64 (95% confidence interval [CI] [3.12, 4.25]), the risk ratio of temsirolimus plus bevacizumab therapy was 3.68 (95% CI [3.14, 4.33]), and the risk ratio of bevacizumab plus IFN-a therapy was 3.49 (95% CI [2.99, 4.06]). CONCLUSIONS: Our results support that combination of targeted therapies might be a novel strategy against advanced renal cell carcinomas.

The organochlorine pesticides residues in the invasive ductal breast cancer patients.

Investigation of organochlorine pesticides residues (important environmental contamination causing malignant transformation) in breast cancer patients is valuable to understanding their roles in breast cancer. 75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of ß-HCH and PCTA were higher in IDC than those in both controls (both p<0.05), and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of ß-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of ß-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC (all p<0.05). The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.

Iptakalim confers an antidepressant effect in a chronic mild stress model of depression through regulating neuro-inflammation and neurogenesis.

Depression is a serious mental disorder in the world, but the underlying mechanisms remain unclear and the effective cures are scarce. Iptakalim (Ipt), an ATP-sensitive potassium (K-ATP) channel opener that can cross the blood-brain barrier freely, has been demonstrated to inhibit neuro-inflammation and enhance adult hippocampal neurogenesis. But it is unknown whether Ipt is beneficial to therapy of depression by modulating neurogenesis and neuro-inflammation. This study aimed to determine the potential antidepressant efficacy of Ipt in a chronic mild stress (CMS) mouse model of depression. We showed that treatment with Ipt (10 mg/kg/day, i.p) for 4 wk restored the decrease of sucrose preference and shortened the immobile time in forced swimming tests (FST) and tail suspension tests (TST) in CMS model mice. We further found that Ipt reversed the CMS-induced reduction of the adult hippocampal neurogenesis and improved cerebral insulin signalling in the CMS mice. Furthermore, Ipt negatively regulated nod-like receptor protein 3 (NLRP3) expression and, in turn, inhibited microglia-mediated neuro-inflammation by suppressing the activation of NLRP3-inflammasome/caspase-1/interleukin 1ß axis in the hippocampus of CMS mice. Taken together, our findings demonstrate that Ipt plays a potential antidepressant role in CMS model mice through regulating neuro-inflammation and neurogenesis, which will provide potential for Ipt in terms of opening up novel therapeutic avenues for depression.

Iptakalim enhances adult mouse hippocampal neurogenesis via opening Kir6.1-composed K-ATP channels expressed in neural stem cells.

BACKGROUND AND PURPOSE: Emerging evidence indicates that stimulating adult neurogenesis provides novel strategies for central nervous system diseases. Iptakalim (Ipt), a novel ATP-sensitive potassium (K-ATP) channel opener, has been demonstrated to play multipotential neuroprotective effects in vivo and in vitro. However, it remains unknown whether Ipt could regulate the adult neurogenesis. METHODS AND RESULTS: Based on the finding that adult neural stem cells (ANSCs) in hippocampus expressed Kir6.1/SUR1-composed K-ATP channel, Kir6.1 heterozygotic (Kir6.1(+/-) ) mice were used to investigate whether and how Ipt regulates adult hippocampal neurogenesis. We showed that administration of Ipt (10 mg/kg) or fluoxetine (Flx, 10 mg/kg) for 4 weeks significantly increased newborn ANSCs in subgranular zone (SGZ) of Kir6.1(+/+) mice but failed to affect those of Kir6.1(+/-) mice. Meanwhile, ANSCs in Kir6.1(+/-) mice exhibited decreased survival rate and impaired ability of differentiation into astrocytes. We further found that Kir6.1(+/-) mice showed lower level of brain-derived neurotrophic factor (BDNF) in hippocampus compared with Kir6.1(+/+) mice. Furthermore, Ipt increased the levels of BDNF and basic fibroblast growth factor (FGF-2) throughout the hippocampus in Kir6.1(+/+) mice but not in Kir6.1(+/-) mice. Moreover, Ipt and Flx enhanced the phosphorylation of Akt and CREB in the hippocampus of Kir6.1(+/+) mice. Notably, these effects were completely abolished in Kir6.1(+/-) mice. CONCLUSIONS: Our findings demonstrate that Ipt stimulates the adult hippocampal neurogenesis via activation of Akt and CREB signal following the opening of Kir6.1-composed K-ATP channels, which gives us an insight into the therapeutic implication of Ipt in the diseases with adult neurogenesis deficiency, such as major depression.