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HPV16 infections promote the development and progression of cervical cancer. We investigated Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor as new adjuvants to an HPV16 vaccine. C57BL/6 mice were immunized by intramuscular injections of HPV16 E6/E7 plasmids every two weeks, three times in all. An in vivo imaging system was used to observe tumor growth and metastasis. Pathological changes to the heart, liver, spleen, lungs, brain and kidneys were recorded, and the survival rate of the mice was determined. The constructed HPV16 E6/E7 vaccine had no notable side effects in terms of physiological or biochemical indexes. Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor increased the inhibitory effects of the HPV16 E6/E7 vaccine on tumor growth and metastasis in vivo. The HPV16 E6/E7 vaccine enhanced the survival of mice and increased their serum-specific antibody and interferon-γ levels. Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor augmented these effects. In a cytotoxic lymphocyte killing test, Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor improved the ability of splenic lymphocytes from HPV16 E6/E7-vaccinated mice to kill B16 cells. As Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor enhanced the anti-tumor and immune effects of the HPV16 vaccine, these adjuvants should be considered for the treatment of cervical cancer.

OBJECTIVE In recent years, many studies have tried to prove whether Helicobacter pylori (H. pylori) can promote the progression of atherosclerosis (AS), but the reported results are conflicting. Carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), or pulse wave velocity (PWV) are the most commonly used indicators to evaluate the progress of AS. So, we collected and evaluated these three indicators to provide evidence-based medicine for the clinic. MATERIALS AND METHODS We included and evaluated studies on H. pylori infection and CIMT, FMD, or PWV from PubMed, Cochrane trials, and Embase databases before September 1, 2021, and language restrictions: English. Research types include cross-sectional studies, cohort studies, and case-control studies. The MINORS scale was used to evaluate the quality of these studies. For all studies, we choose a random-effects model and calculate the weighted mean difference (WMD) for analysis, and all our analyses use STATA software. RESULTS Meta-analysis shows that H. pylori infection can significantly increase CIMT (WMD = 0.059, 95% CI: 0.039, 0.079, p

Immunotherapy has emerged as a promising strategy for cancer treatment, in which durable immune responses were generated in patients with malignant tumors. In the past decade, biomaterials have played vital roles as smart drug delivery systems for cancer immunotherapy to achieve both enhanced therapeutic benefits and reduced side effects. Hydrogels as one of the most biocompatible and versatile biomaterials have been widely applied in localized drug delivery systems due to their unique properties, such as loadable, implantable, injectable, degradable and stimulus responsible. Herein, we have briefly summarized the recent advances on hydrogel-by-design delivery systems including the design of hydrogels and their applications for delivering of immunomodulatory molecules (e.g., cytokine, adjuvant, checkpoint inhibitor, antigen), immune cells and environmental regulatory substances in cancer immunotherapy. We have also discussed the challenges and future perspectives of hydrogels in the development of cancer immunotherapy for precision medicine at the end.

Qiuyue Guo,1 Yunsheng Xu,2 Jie Li,3 Wenrong An,3 Dan Luo,4 Chengcheng Huang,4 Yanqin Huang4 1Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Endocrinology, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, People’s Republic of China; 3First Clinical Medical College, Jingshi Rd. Campus, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 4Department of Endocrinology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of ChinaCorrespondence: Yanqin Huang Email huangyanqin2020@126.com; 20137125@sdutcm.deu.cnPurpose: To analyze the effect and potential therapeutic targets of liraglutide in type 2 diabetes through miRNA expression profiling.Methods: Ten of 30 SPF Wistar rats, males at 4 weeks old, were randomly selected as the control group and given conventional feed, the other rats adopted high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish a T2DM model. One unsuccessful rat was excluded, and the remaining rats were randomized to the model and the liraglutide group. Liraglutide group was subcutaneously injected with liraglutide 0.11 mg/kg for 8 weeks. The biochemical indicators and staining HE were detected. The expression of miRNA in pancreatic tissue was detected by miRNA sequencing. The intersection of miRNA difference was used to predict the target gene, then functional enrichment was performed to identify its possible biological functions and signal transduction paths. Finally, qRT-PCR was used to verify the results.Results: Compared to the model group, the level of fasting blood glucose (FBG), glucagon and insulin resistance index (HOMA-IR) in the liraglutide group were significantly decreased, fasting insulin (FINS) and insulin sensitivity index (ISI) were increased. Nine differential miRNAs (miR-135a-5p, miR-144-5p, miR-21-3p, miR-215, miR-451-5p, miR-486, miR-122-5p, miR-181d-5p and miR-345-5p) were identified at the intersection through two miRNA sequencing. A total of 3359 related target gene predictions were obtained. GO and pathway analyses demonstrated that differentially expressed genes were closely related to cell proliferation, angiogenesis, and proteolysis. Significant signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway.Conclusion: Liraglutide could improve islet function by regulating nine miRNAs, and the related signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway. Our study provided the basis and direction for further exploring the molecular mechanism of liraglutide on T2DM.Keywords: liraglutide, type 2 diabetes, miRNA expression profile, target gene, signaling pathway

Cervical cancer is acknowledged as the most prevalent gynecological tumor and a severe public issue that threatens female health, resulting from its high incidence and fatality rate. Surging evidence have shown that circular RNAs (circRNAs) play significant roles in the initiation and progression of various malignancies. Although circAMOTL1 has been testified to execute oncogenic properties in breast cancer and prostate cancer, literature on its function and regulatory mechanism in cervical cancer development is still scanty. Using a bioinformatics analysis, we found circ_0004214 was a circular form of AMOTL1. Through qRT-PCR analysis, circAMOTL1 and its host gene AMOTL1 were both upregulated in cervical cancer tissues and closely correlated with poor prognosis of cervical cancer. Gain- or loss-of-function assays and in vivo experiments demonstrated that AMOTL1 promoted cervical cancer cell growth both in vitro and in vivo. Mechanically, circAMOTL1 served as a competing endogenous RNA (ceRNA) to prompt the expression of AMOTL1 through sponging miR-485-5p. Rescue assays revealed that miR-485-5p/AMOTL1 axis was involved in circ_AMOTL1-mediated cervical cancer progression. Our findings provide a better understanding of the molecular mechanism underlying circAMOTL1 in cervical cancer and indicated circAMOTL1/miR-485-5p/AMOTL1 as a promising novel therapeutic strategy for the treatment of this disease.

Myelin-laden macrophages (mye-MΦ), resulting primarily from internalization of myelin debris by infiltrating bone marrow-derived macrophages in spinal cord injury (SCI), trigger inflammatory responses that largely contribute to secondary injury. Adiponectin, which is secreted from adipose tissue, is an important hormone that modulates macrophage inflammation. In the present study, we examined the role of adiponectin on macrophage-mediated neuroinflammation after SCI. We found that in vitro activation of adiponectin receptors (AdipoRs) by their agonist AdipoRon suppressed myelin lipid accumulation in mye-MΦ through APPL1/PPARγ/LXRα/ABCA1-mediated lipid efflux, subsequently inhibiting inflammation and restoring normal function to mye-MΦ. In vivo data further confirmed that intravenous administration of AdipoRon after SCI dampened recruitment of macrophages and reduced myelin lipid accumulation. Accordingly, AdipoRon treatment ameliorated post-SCI tissue damage and astrogliosis, resulting in improved motor function. Although there was no significant pathological exacerbation in adiponectin-null mice subjected to SCI, our work reveals a functional link between adiponectin and hematogenous macrophages in the context of SCI, suggesting that activation of adiponectin signaling is a promising therapeutic approach to mitigate mye-MΦ-mediated neuroinflammation in neurological disorders involving demyelination.

Ethnopharmacological relevance Allium macrostemon Bunge. is an edible Chinese herb traditionally used for the treatment of thoracic pain, stenocardia, heart asthma and diarrhea. Although its biological potential has been extensively proven such as antioxidant activity, antiplatelet aggregation, vasodilation and antidepressant-like activity, there are no reports in the literature regarding its pharmacological analgesic activity. Aim of the study The study was carried out to examine the anti-nociceptive activity of the crude extract of A. macrostemon bulbs and interpret its likely molecular target. Materials and methods The bulbs of A. macrostemon were gathered, dried-up , and extracted with water (AMWD). AMWD was subjected to activity testing, using chemical-induced (acetic acid and formalin test) and heat-induced (hot plate) pain models. To evaluate the likely mechanistic strategy involved in the analgesic effect of AMWD, whole-cell patch clamp recordings were conducted in acutely dissociated dorsal root ganglion (DRG) neurons and human embryonic kidney 293T (HEK293T) cells expressing pain-related receptors. Electrophysiological methods were employed to detect the action potentials of DRG neurons and potential targets of A. macrostemon. Results AMWD showed significant palliative effect in all heat and chemical induced pain assays. Moreover, AMWD significantly reduces the excitability of dorsal root ganglion neurons by reducing the firing frequency of action potentials. Further analysis revealed that voltage-gated sodium channel Nav1.7 is the potential target of A. macrostemon for its analgesic activity. Conclusion This study has brought new scientific evidence of preclinical efficacy of A. macrostemon as an anti-nociceptive agent. Apparently, these effects are involved with the inhibition of the voltage-sensitive Nav1.7 channel contributing to the reduction of peripheral neuronal excitability. Our present study justifies the folkloric usage of A. macrostemon as a remedy for several pain states. Furthermore, A. macrostemon is a good resource for the development of analgesic drugs targeting Nav1.7 channel.

Though widely used in the treatment of coronary heart disease (CHD), the mechanism of traditional Chinese medicine (TCM) is still unclear because of its complex prescription rules. This study prospectively collected 715 prescriptions of TCM for the treatment of CHD. The characteristics of TCM in prescriptions were described and analyzed, and the rules of prescriptions were analyzed by using association rules. Frequency statistics showed that the high-frequency herbs with a frequency of more than 60% were Gan-cao, Huang-qi, Dang-gui, Chuan-xiong, Yan-hu-suo, and San-qi. The high-frequency herb combinations were summarized by using association rules. By using the method of the “Top N groups” to excavate the empirical prescriptions, the basic prescriptions for treating CHD were summarized. We named the intersection herbs of the basic prescriptions and the high frequency herbs as the core herbal prescription. To explore the possible mechanisms underlying the anti-CHD effect of the core herbal prescription, the bioactive components of core herbal prescription and their targets were screened out by using network pharmacology. Molecular docking was performed between the bioactive components and core targets. A total of 28 potential active ingredients and 5 core targets were identified for the treatment of CHD with core herbal prescription. The enrichment analysis results indicated that the mechanism of action mainly involved neuroactive ligand-receptor interaction and calcium signaling pathway. The commonly used herbal pairs for CHD with qi deficiency and blood stasis syndrome were Huang-qi and Dang-gui. The mechanism of action of common herbal pairs was also studied by network pharmacology. This study summarized the prescription rule of TCM in the treatment of CHD and may provide a new idea for the treatment of CHD.

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19–2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06–2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10–0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.

Previous studies evaluating the association of dietary fat and risk of age-related macular degeneration (AMD) yield discrepant results. The objective of this systematic review (SR) and meta-analysis is to establish whether an association exists between dietary fat and AMD. This protocol was developed in line with the quality requirements of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. PubMed and EMBASE will be searched for randomized controlled trials (RCTs), non-randomized trials (NRTs), cross-sectional studies, cohort studies, and case-control studies that evaluate the total incidence of AMD. The data extraction content and quantitative analysis will be carried out systematically. Newcastle-Ottawa Scale (NOS), the Cochrane risk of bias tool, and quality assessment tools will be used for quality assessment. This SR will synthesize evidence to determine if there is an association between dietary fat and AMD. The evidence would provide rationale for future research and serve as a basis for the development of future guidelines. Results are expected to be publicly available in mid 2020. PROSPERO registration number: CRD42019137086.

Myocardial remodeling represents a key factor in chronic heart failure (CHF) development, and is characterized by chronic death of cardiomyocytes. Cardiac function changes may be attributed to inflammation, apoptosis and autophagy. This study assessed the effects of Qi Dan Li Xin Pill (QD) on heart function, inflammatory factors, autophagy and apoptosis in cardiac remodeling in CHF rats upon myocardial infarction (MI) induction. Male SD rats underwent a sham procedure or left anterior descending coronary artery (LADCA) ligation, causing MI. Twenty-eight days after modeling, the animals were treated daily with QD, valsartan and saline for 4 weeks. Echocardiography after 4 weeks of drug intervention revealed substantially improved left ventricular remodeling and cardiac function following QD treatment. As demonstrated by decreased IL-1β, IL-6 and TNF-α amounts, this treatment also inhibited the apoptotic process and protected the viability of the myocardium. These outcomes may be attributed to enhanced autophagy in cardiomyocytes, which further reduced pro-inflammatory and pro apoptotic effects. This process may be achieved by QD regulation of the mTOR/P70S6K signaling pathway, suggesting that the traditional Chinese medicine Qi Dan Li Xin pill is effective in heart protective treatment, and is worth further investigation.

Object. To probe into the target and molecular mechanism of Jianpi Xiaoke (JPXK) prescription in the treatment of type 2 diabetes through high-throughput microRNA (miRNA) sequencing. Methods. Ten of the 31 SPF male Wistar rats were randomly taken as the control group; the remaining rats were fed a high-sugar and high-fat diet, combined with Streptozotocin (STZ, 35 mg/kg) that induced a type 2 diabetes model. The model rats were randomly divided into model groups (n = 11) and the JPXK group (n = 10). After 8 weeks of JPXK intervention, we detected the function of islet cells through HE staining and ELISA. High-pass sequencing technology was adopted to identify the differential expression of miRNA to explore the target of JPXK treatment, assess the relevant target genes, conduct functional analysis, and lastly verify the sequencing data by qRT-PCR. Results. After treatment, FPG, FINS, and HOMA-IR levels of the treatment group improved significantly compared with those of the control group ( P < 0.05 ). Among the miRNAs differentially expressed between the model group and the control group, there were 7 reversals after JPXK treatment, including miR-1-3p, miR-135a-5p, miR-181d-5p, miR-206-3p, miR-215, miR-3473, and miR-547-3p (log2FC ≥ 1 or ≤ −1, P < 0.05 ). Besides, the 1810 target genes associated with these 7 miRNAs were assessed by multiMiR. According to the results of the GO and KEGG analyses, they were associated with biological processes (e.g., glucose transport and fat cell formation), and it covered multiple signaling pathways, capable of regulating islet cell function (e.g., MAPK, PI3K-Akt, Ras, AMPK, and HIF-1 signaling pathways). The PCR verification results were consistent with the sequencing results. Conclusion. This discovery interpreted the potential therapeutic targets and signaling pathways of JPXK prescription against T2DM based on miRNA expression profiling. In conclusion, our research provided novel research insights into traditional Chinese medicine (TCM) treatment of diabetes.

The large yellow croakers (Larimichthys crocea) are mainly present in the Chinese coast and near seas with high economic importance, but vulnerable to many diseases, especially in the breeding and aquaculture. The purpose of this research was to boost the innate immune system of the large yellow croaker by administering bitter peptides into their peritoneal cavity. Total 120 Juvenile of large yellow croakers in very even weight of 60 g were divided into 4 different groups in 200/300 L of water tank, respectively. Fish growth were observed for 3 months before and after different treatments. The bitter peptides from pepsin hydrolysis were applied because they possess the highest bitter sensory scores. The blood of fish from the different groups was collected and tested for different immune parameters to evaluate the effectiveness of bitter peptides as immune stimulants after administration for 8 weeks. The average ratio of leukocytes/total blood cells (%) for control was found at 14.6%, for the low dose of bitter peptides 0.6 mg/fish was at 29.3%, for middle dose of 1.2 mg/fish was at 35%, and high dose of 2.4 mg/fish was at 30%. The lysozyme assay showed that the OD (optical density) units of relative progress lysis activity at 60 min were 0.17, 0.101, 0.307 and 0.198, respectively. Similarly in the same order as in phagocyte assay, most importantly the middle dose (1.2mg/fish) gave the highest survival rate throughout the assay. The results showed that bitter peptides can be used as immune boosters for the yellow croakers and the optimum dose was 1.2 mg/fish due to both leukocytes and lysozyme activity in the treated samples increased significantly compared with the control group. According to the results obtained, we suggest that the incorporation of middle dose of bitter peptides into fish feeds may reduce the fish diseases in aquaculture, at least for large yellow croakers.

MicroRNA-34a (miR-34a) behaves as a tumor suppressor by decreasing the expression of oncogenes involved in multiple carcinogenic pathways. Intravenous delivery of miR-34a mimics has been investigated in clinical trials as a potential treatment for advanced cancers; however, the effect of miR-34a on cancer immune surveillance is controversial. In the current study, we found that miR-34a plays a dual role in the regulation of major histocompatibility complex class I-related sequence B (MICB) protein, a ligand of the NKG2D receptor. MiR-34a could both induce and reduce MICB expression by upregulating ataxia telangiectasia and Rad3-related (ATR) protein kinase and downregulating the transcription factor E2F1, respectively. The net effect of miR-34a on MICB expression depended on endogenous E2F1 levels. Overexpression of miR-34a promoted MICB expression in hepatocytes and hepatocellular carcinoma (HCC) cells that have low E2F1 levels but not in HCC cells that have high E2F1 levels. In HCC patients, the expression of miR-34a and MICB showed positive correlation in paratumor liver tissues, which have low E2F1 levels, but not in HCC tissues, which have high E2F1 levels. We showed that miR-34a overexpression in non-transformed liver cells enhanced cytolysis and interferon-γ production by NK-92MI cells. Furthermore, higher miR-34a expression in tumor and paratumor tissues was associated with positive and negative outcomes, respectively, in HCC patients. Our findings suggest that miR-34a induces MICB expression in paratumor liver tissues, which may cause liver damage and serious cytokine release syndrome, thus disclosing potential side effects of systemic administration of miR-34a in anticancer therapy.

Background Human papillomavirus (HPV) infection and viral proteins expression cause a number of epigenetic alterations leading to cervical carcinogenesis. The recent discovery of a large amount of histone methylation modifiers reveals important roles of these enzymes in regulating tumor progression. Methods The changes in expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E7 in CaSki cells. Lysine-specific demethylase 2A (KDM2A)-regulated microRNAs (miRNAs) in cervical cancer pathogenesis were disclosed using quantitative real-time polymerase chain reaction. The function of KDM2A-miRNAs on cervical cancer was investigated in vitro and in vivo. Results Upregulation of KDM2A induced by HPV16 E7 promotes cervical cancer cell proliferation and invasion and is correlated with poor prognosis in patients with cervical cancer. KDM2A physically interacts with the promoter of miR-132 and suppresses its expression by removing the mono or dimethyl group from H3K36 at the miR-132 locus. Functionally, miR-132 represses cancer cell proliferation and invasion by inhibiting radixin (RDX). Upregulated KDM2A promotes cervical cancer progression by repressing miR-132, which results in a derepression of RDX. Therefore, KDM2A functions as a tumor activator in cervical cancer pathogenesis by binding miR-132 promoter and abrogating its tumor suppressive function. Conclusion Our results suggest a function for KDM2A in cervical cancer progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of cervical cancer.

Background: Diabetic nephropathy (DN) is 1 of the most serious complications of diabetes mellitus and the leading cause of end-stage renal disease in the world. Huangkui capsule, extracted from Abelmoschus manihot (L.) medic (AM), has been widely used to treat DN. However, there is no consensus on the efficacy of Huangkui capsule for DN. This study aims to perform meta-analysis to systematically review the efficacy and safety of Huangkui capsule. Methods: The following 9 electronic databases will be comprehensively searched: PubMed, web of science, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang data, and Chinese BioMedicine Literature Database. The retrieval time is from their inception to May 2021. According to the inclusion and exclusion criteria, 2 reviewers independently completed the study selection, data extraction, risk of bias assessment, and data synthesis. Review Manager Version 5.3 software will be used to conduct meta-analysis. Results: This study provides a high-quality synthesis to assess the efficacy of Huangkui capsule for treating diabetic nephropathy. Conclusion: The result of this systematic review will provide objective evidence-based basis to judge the effectiveness and safety of Huangkui capsule on diabetic nephropathy.

Desk lamp is to be used for reading study and the lamp that design USES, the bulb that general desk lamp USES is incandescent lamp, energy-saving bulb and market popular protect an eye desk lamp, can adjust the direction of height, illumination and brightness, those who use is manual adjust. Children, on the other hand, often don’t know how to adjust and to what extent. In this paper, a smart desk lamp is designed, which can adjust the brightness automatically according to the surrounding brightness when someone is around, and also has the function of correcting the user’s sitting position.

This paper uses a simple portable indoor sleep monitor as the design platform, the sound sensor system and the light sensor system serve as the main sensor module. The sound sensor uses ADC0832 acquisition chip to convert the analog signal detected into digital signal. LM393 comparator and photosensitive resistance are used to compare the signal of ambient light-intensity. DS1302 clock chip is used to provide the system clock with the time of year, month, day, hour, minute and second. STC89C52RC microcontroller is the main control chip of this system, which mainly control the operation of the whole system and realize its corresponding functions. The experimental results show that the performance of the system meets the design requirements.

Tumor boundary delineation using F-FDG PET/CT is a promising tool for radiotherapy applications, but no consensus has been established regarding the optimal delineation method. Time-phase variability of F-FDG PET/CT imaging frequently affects metabolically active volumes and treatment planning for nasopharyngeal carcinoma (NPC). This study aimed to evaluate the time-phase robustness of 8 methods commonly used for tumor volume delineation in NPC.Twenty patients with biopsy-proven NPC were included and underwent multiple time-phase F-FDG PET/CT imaging. Gross tumor volumes (GTVs), absolute SUV, gradient-based watershed segmentation (GTV-GWT), and anatomic biologic contouring (GTV-ABC) values were determined. The volume of overlap between GTV-CT and the 8 PET-based GTVs was enclosed and the overlap fraction (OF-CT) calculated. Color matrix was used to semiquantify the time-phase differences. Gross tumor volume values obtained with different methods were recorded and compared using paired t test. Time-phase differences of GTVs and SUVmax were compared among groups by analysis of variance with Tukey honest significance tests. The coefficients of variation were computed to assess intrapatient time-phase variability. Similarity coefficient was calculated to evaluate similarity.Differences were observed between GTVs obtained at different time points using various delineation procedures. Nonsignificantly higher percentages were obtained for GTV-GWT (88.17%) and GTV-ABC (86.98%) compared with other methods, showing their robustness. GTV-40% (0.81-0.88) and GTV-ABC (0.82-0.88) indicated higher similarity with GTV-MRI than the other methods.PET/CT-based GTV-ABC between 35 and 55 minutes should be the first choice for NPC treatment planning.

Background: At present, the prevalence of type 2 diabetes mellitus (T2DM) has become a major public health issue throughout the world, especially in developing countries. Notably, traditional Chinese patent medicines (TCPMs) are of great significance in the treatment of T2DM combined with conventional Western medicine therapy. However, there is a lack of comparison among all the current common TCPMs for treating T2DM. Therefore, this study intends to explore the efficacy and safety of different TCPMs against T2DM through the Bayesian network meta-analysis (NMA). Methods: We will conduct a comprehensive and systematic search for randomized controlled trials (RCTs) of TCPM for the treatment of T2DM in both Chinese and English databases published till August 2020. Two researchers will be responsible for screening eligible literature, extracting data, and assessing the risk of bias of included studies independently. Then, pairwise meta-analyses and Bayesian network meta-analyses will be conducted to assess all available evidence. In the end, data will be analyzed using STATA15.0 and WinBUGS1.4.3 software. Conclusion: This study will compare the efficacy and safety of different TCPMs against T2DM in detail. Our findings will provide a reliable evidence for selecting clinical treatment program and guideline development of T2DM.

Under the action of low pressure, the wheel pile foundation bears most or even all the downward pressure. When the wheel pile foundation is subjected to uplift force, the uplift force is supported by the short pile, and the ring frame and the 4 flange mainly play the role of transfer pulling force, while the main bearing force is short and short pile. When the wheel pile foundation is subjected to horizontal forces, the horizontal force is mainly borne by the flange and the ring frame. Therefore, only downward pressure and horizontal force should be considered for the ring frame and flange, while uplift force should be considered for the design of thin and short piles. The basic design is simple and the transmission path is clear. The ring frame, flange and short pile of the wheel pile foundation are prefabricated. The foundation can take different prefabricated installation methods with the mechanized construction conditions. It can not only guarantee the quality of the concrete slab, but also speed up the construction speed of the foundation. By comparing with the economic technology of the plate foundation, it is found that under the same geological conditions, the use of wheel pile foundation can reduce the concrete earthwork and the increase of the load, the decrease of concrete is also increased, and the amount of steel is saved, and the economic benefit is remarkable.

Objective. Chromium-containing traditional Chinese medicine Tianmai Xiaoke tablet (TMXKT) is approved for treating newly diagnosed type 2 diabetes mellitus (T2DM) in China. This review aimed to compile the evidence from randomized clinical trials (RCTs) and quantify the effects of TMXKT on newly diagnosed T2DM. Methods. Seven online databases were investigated up to March 20, 2017. The meta-analysis included RCTs investigating the treatment of newly diagnosed T2DM, in which TMXKT combined with conventional therapy was compared with placebo or conventional therapy. The risk of bias was evaluated using the Cochrane Collaboration tool. The estimated mean difference (MD) and the standardized mean difference were within 95% confidence intervals (CI) with respect to the interstudy heterogeneity. The outcomes were measured using fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPG), glycosylated hemoglobin A1c (HbA1c), and body mass index (BMI) levels. Results. TMXKT combined with conventional therapy lowered FBG level (MD=-0.68, 95% CI −0.90 to −0.45, P<0.00001), 2hPG (MD=-1.33, 95% CI −1.86 to −0.79, P<0.00001), HbA1c (MD = −0.46, 95% CI −0.57 to −0.36, P<0.00001), and BMI (MD = −0.77, 95% CI −1.12 to −0.41, P<0.00001). Conclusions. TMXKT combined with conventional therapy is beneficial for patients with newly diagnosed T2DM. However, the effectiveness and safety of TMXKT are uncertain because of the limited number of trials and low methodological quality. Therefore, practitioners should be cautious when applying TMXKT in daily practice. Also, well-designed clinical trials are needed in the future.

Compared with the common angle steel tower, the narrow base steel pipe tower has the advantages of simple structure, beautiful appearance, small floor area and better coordination with the urban environment. In the construction of urban high pressure transmission line, the narrow base tower has its own unique advantages and wide application prospects. It has the advantages of ordinary iron tower processing, transportation, assembly, cost saving, small occupancy of single column steel pipe rod, small line corridor and beautiful beauty. In the optimization design of the narrow tower, how to take the wind vibration coefficient of the tower, how to consider the bending moment of the rod end, the design of the narrow base tower and the structure optimization of the narrow tower tower are all the problems to be solved urgently. In this paper, the modal analysis of a single tower is carried out to determine its vibration mode, and then the wind vibration coefficient of a narrow tower is analyzed. Finally, the influence of x and y direction vibration on the frequency of the tower is obtained.

In this paper, some methods of lightning protection measures are expounded in this paper, and then the influence of grounding resistance on ground resistance with current changing with current is revised by means of incomplete consideration of the influence factors of the impact grounding resistance in the standard.

Cancer is still a clinical challenge, with many efforts invested in order to achieve timely detection. Unexplained elevated blood carcinoembryonic antigen levels are occasionally observed in an asymptomatic population and considered as a risk factor of cancers. The purpose of this study was to determine the validity of 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG-PET/CT) for detecting cancer in an asymptomatic population with an unexplained elevation in blood carcinoembryonic antigen (CEA) levels.This retrospective study included a total of 1920 asymptomatic examinees conducted from August 2011 through September 2013. The participants underwent CEA assay and conventional medical imaging (CEA-conventional), or CEA assay and F-18 FDG-PET/CT (CEA-PET/CT). The validity of conventional medical imaging and CEA-PET/CT scanning for detecting cancer and early-stage cancer in an asymptomatic population with an unexplained elevation in blood CEA levels were evaluated.Sensitivity, specificity, cancer detection rate, missed cancer detection rate, early-stage cancer detection rate, and early-stage cancer ratio using the CEA-PET/CT scanning were 96.6 %, 100 %, 10.4 %, 0.4 %, 3.7 %, and 34.5 %, respectively. In contrast, the corresponding values obtained using the conventional medical imaging were 50.6 % (P 0.0001), 100 % (P 0.9999), 50.6 % (P 0.0001), 99.9 % (P = 0.055), 2.6 % (P 0.0001), 2.5 % (P = 0.04), 0.7 % (P = 0.0004), and 14.5 % (P = 0.002), respectively.The F-18 FDG-PET/CT scanning significantly improved the validity of the cancer detection program in the asymptomatic population with an unexplained elevation in CEA levels.

This paper presents a planar ultra-wideband (UWB) bandpass filter with sharp out-of-band rejection performance. The filter is formed by a folded multiple-mode resonator to realize high performance in an operation band from 3.3 to 10 GHz with a very compact size of 20 mm × 20 mm × 0.5 mm. An extra notched band centered at 5.8 GHz is further accomplished by etching a Hilbert fractal curve slit on the filter without the necessity of readjusting the geometrical parameters. The simulated and measured results are in good agreement.

Summary Background Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of diseases of keratinization, characterized primarily by abnormal skin scaling over the whole body surface. Recently, ARCI has been designated to include the major forms of lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) and harlequin ichthyosis. The first two conditions are the most common major clinical subtypes, and both are caused principally by mutations in the transglutaminase 1 gene, TGM1, although other genes may be responsible in some cases. Aim To identify the genetic mutations underlying LI in a Chinese family with LI, and to review all the known TGM1 mutations in Chinese patients with ARCI. Methods The proband had the severe classic LI phenotype, and was a member of a four-generation family with close blood relationships. We sequenced the DNA of the patients and close relatives. We also reviewed 13 Chinese patients with ARCI from 8 reported families, comprising 10 patients with LI, 2 with CIE and 1 with bathing suit ichthyosis. Results We characterized 14 different TGM1 mutations. Six of these were reported in other ethnic groups initially and later in Chinese patients, while the remaining eight were first described in Chinese patients. Of the latter, five have been reported only in Chinese patients, while the remaining three have also been reported in other ethnic groups. Conclusion This study expands the current spectrum on TGM1 mutation and increases the knowledge of TGM1 mutation characteristics.

We describe an unusual case of subacute cutaneous lupus erythematosus concurrent with hand-foot syndrome, apparently associated with capecitabine treatment. We hypothesise that subacute cutaneous lupus erythematosus and hand-foot syndrome may occur in a novel overlap syndrome.

] Suenaga M. Genetical studies on skin diseases. VII. Dyschromatosis universalis hereditaria in five generations. Tohoku J Exp Med 1952;55:373–6. ] Urabe K, Hori Y, Dyschromatosis. Semin Cutan Med Surg 1997;16:81–5. Chaoxia Lu, Jie Liu, Fang Liu, Yaping Liu, Donglai Ma*, Xue Zhang** McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100073, China

Spinal cord injury (SCI) causes functional impairment as a result of the initial injury followed by secondary injury mechanism. SCI provokes an inflammatory response that causes secondary tissue damage and neurodegeneration. While the use of neural stem cell (NSC) engraftment to mitigate secondary injury has been of interest to many researchers, it still faces several limitations. As such, we investigated if NSC-conditioned medium (NSC-M) possesses therapeutic potential for the treatment of SCI. It has been proposed that many of the beneficial effects attributed to stem cell therapies are due to secreted factors. Utilizing primary cell culture and murine models of SCI, we determined that systemic treatment with NSC-M was able to significantly improve motor function and lesion healing. In addition, NSC-M demonstrated significant anti-inflammatory potential in vitro and in vivo, reducing inflammatory cytokine expression in both activated macrophages and injured spinal cord tissues. NSC-M was also able to reduce the expression of inducible nitric oxide synthase (iNOS) within the spleen of injured animals, indicating an ability to reduce systemic inflammation. Thus, we believe that NSC-M offers a possible alternative to direct stem cell engraftment for the treatment of SCI.

Background Macrophages play an important role in the inflammatory responses involved with spinal cord injury (SCI). We have previously demonstrated that infiltrated bone marrow-derived macrophages (BMDMs) engulf myelin debris, forming myelin-laden macrophages (mye-Mϕ). These mye-Mϕ promote disease progression through their pro-inflammatory phenotype, enhanced neurotoxicity, and impaired phagocytic capacity for apoptotic cells. We thus hypothesize that the excessive accumulation of mye-Mϕ is the root of secondary injury, and that targeting mye-Mϕ represents an efficient strategy to improve the local inflammatory microenvironment in injured spinal cords and to further motor neuron function recovery. In this study, we administer murine embryonic stem cell conditioned media (ESC-M) as a cell-free stem cell based therapy to treat a mouse model of SCI. Results We showed that BMDMs, but not microglial cells, engulf myelin debris generated at the injury site. Phagocytosis of myelin debris leads to the formation of mye-Mϕ in the injured spinal cord, which are surrounded by activated microglia cells. These mye-Mϕ are pro-inflammatory and lose the normal macrophage phagocytic capacity for apoptotic cells. We therefore focus on how to trigger lipid efflux from mye-Mϕ and thus restore their function. Using ESC-M as an immune modulating treatment for inflammatory damage after SCI, we rescued mye-Mϕ function and improved functional locomotor recovery. ESC-M treatment on mye-Mϕ resulted in improved exocytosis of internalized lipids and a normal capacity for apoptotic cell phagocytosis. Furthermore, when ESC-M was administered intraperitoneally after SCI, animals exhibited significant improvements in locomotor recovery. Examination of spinal cords of the ESC-M treated mice revealed similar improvements in macrophage function as well as a shift towards a more anti-inflammatory environment at the lesion and parenchyma. Conclusions The embryonic stem cell conditioned media can be used as an effective treatment for SCI to resolve inflammation and improve functional recovery while circumventing the complications involved in whole cell transplantation.

To warrant potential clinical testing, the equine anti-SARS-CoV F(ab')(2) requires evaluation in as many animal models as possible and a safety test in a primate model. In this study, we evaluated the pharmacokinetics, tolerance and immunity of this kind of antibody in macaques and rats. Results showed that the F(ab')(2) fragments had a normal metabolism in injected animals. The general physiological indexes did not differ between animals injected with anti-SARS-CoV F(ab')(2) or saline. However, a mild inflammatory response in local injection site and a moderate immune response against this antibody in the successively injected animals were observed, which however recovered 3 weeks after the last injection. The antibody titring from 1:100 to 400 against the equine anti-SARS-CoV F(ab')(2) in the inoculated hosts could be detected at week 2 during the successive injections of the equine F(ab')(2). The considerable safety of this antibody used in primates and the fact that the immune system of the host can be motivated by post-injection of the F(ab')(2) indicate that this type of anti-SARS-CoV antibody can be used for prevention and treatment of SASR, especially at the early stage of this virus infection. In addition, it can also provide the precious time for the combined use of other anti-SARS-CoV agents such as antiviral drug and vaccine.

ejd.2013.2121 Auteur(s) : XueQi Zhang tigar@aliyun.com, JingJing Liu, XiaoHong Shao, JianFeng Cai, ShenMeng Gao, XiaoHua Lin, YueYue Yuan, ZhiMing Li, BingXu Li, YunSheng Xu First Affiliated Hospital, Wenzhou Medical College, No 1 Fuxue lane, 325000 Wenzhou, Zhejiang, China We report a 19-year-old patient (III10) from a four-generation Chinese pedigree with desquamation covering almost all the body since about 10 months of age. The development of cutaneous lesions initially occurred on the extremities [...]

Background : It is well known that both heat shock protein (HSP) and Toll-like receptor (TLR)3 agonist polyinosinic:polycytidylic acid (poly(I:C)) are capable of promoting the antigen-specific immune responses. In the current study, we assessed whether the anti-tumor effects of the HPV16E7 49–57 -based vaccine can be elevated by combined applications of poly(I:C) and oxygen-regulated protein 150 (ORP150) in a mouse cervical cancer model. Methods : Recombinant mouse ORP150 and HPV E7 49–57 peptide were combined to passively form the ORP150–E7 49–57 complex under heat shock conditions. The effects of ORP150–E7 49–57 complex plus poly(I:C) adjuvant on lymphocyte proliferation and functional cytotoxic T cells were investigated by methyl thiazolyl tetrazolium (MTT), ELISPOT, and non-radioactive cytotoxicity assays. Finally, the complex's therapeutic anti-tumor effects with and without adjuvant therapy were observed in a tumor challenge experiment. Results : This combination vaccine approach significantly enhanced the proliferation of splenocytes and induced strong E7 49–57 -specific CTL responses. More importantly, the ORP150–E7 49–57 complex plus poly(I:C) vaccine format demonstrated more potent anti-tumor effects than ORP150–E7 49–57 complex alone or E7 49–57 plus poly(I:C) in TC-1 tumor-bearing mice. Conclusion : Both poly(I:C) and ORP150 chaperone can synergistically enhance the anti-tumor effects of the HPV16E7 49–57 -based vaccine in vitro and in vivo. This strategy provides a platform for the design of a tumor therapeutic vaccine capable of inducing an effective anti-tumor immune response.

Similarity measure formula between Vague set A and B is put forward: (, ) 1 1 22 ii i i i i i i mm m m m m m m n ab a b a b a b m i

The Vague optimization method sorted out is a special case of the pattern recognition method of the Vague set. Its specific application steps are as follows: 1 the set-up of characters to determine the evaluation; 2 the establishment of a collection of new varieties of wheat to be optimized; 3 the extract of the ideal set of new wheat varieties ; 4 the construction of Vague environment to collect all varieties of Vague sets; 5 the Vague optimization: to calculate similarity measures between Vague sets to obtain the new wheat varieties based on numerical similarity measures and to propose the similarity measures formula between the Vague sets. This optimization formula is supported by Vague class techniques. Breeding new varieties of wheat with comprehensive quality traits is one of the directions in wheat breeding. It is a new attempt to study the wheat assessment of the new wheat varieties with the application of optimization methods. The wheat assessment case of the new wheat varieties shows that both the formula and the method are practical.

A new method to measure the radiative heat transfer in fluidized beds was presented. Experiments were carried out on a 0.8 th−1 fluidized bed combustion boiler. The residual slag of fired coal was operated in a fluidized bed at room temperature. As the radiative heat transfer at room temperature is insignificant, its contribution at high temperatures might be obtained by the comparison of experimental results at high and low temperatures. On experimental study, a radiative contribution was given as a function of bed temperature and particle size. The results were compared with those in other references.