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Interleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated.To investigate whether and how IL-34 affects the proliferation of GC cells and EMT.Using immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting.Expression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice.IL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC.

Cannabinoid receptors belong to the large family of G-protein-coupled receptors, which can be divided into two receptor types, cannabinoid receptor type-1 (CB1) and cannabinoid receptor type-2 (CB2). Marinol, Cesamet and Sativex are marketed CB1 drugs which are still in use and work well, but the central nervous system side effects caused by activation CB1, which limited the development of CB1 ligands. So far, no selective CB2 ligand has been approved for marketing, but lots of its ligands in the clinical stage and pre-clinical stage have positive effects on the treatment of some disease models and have great potential for development. Most selective CB2 agonists are designed and synthesized based on non-selective CB2 agonists through the classical med-chem strategies

A comprehensive evaluation system for a camouflage design combining local effect evaluation and global sampling is developed. Different from previous models, this method can sample and evaluate target camouflage in a wide range of combat areas, thereby obtaining a comprehensive evaluation effect. In evaluating local effects, the Gaussian pyramid model is adopted to decompose the image on a multi-scale so that it can conform to the multi-resolution property of human eyes. The Universal Image Quality Index (UIQI) conforming to features of eye movements is then adopted to measure the similarities between multi-scale targeted and background brightness, color and textural features. In terms of the imitation camouflage pattern design algorithm, uniform sampling is used to obtain the evaluation distribution in the background; while for the deformation camouflage pattern, the sampling distribution is improved to make it conform to the movement rule of the target in the background. The evaluation results of the model for different designs were investigated. It is suggested by the experimental results that the model can compare and evaluate the indicators involved in the process of camouflage design, including integration, polychromatic adaptability and algorithm stability. This method can be applied in the evaluation and contrast of camouflage pattern design algorithms, in parameter optimisation of camouflage design and in scheme comparison in engineering practice, and can provide support of evaluation methodology for camouflage design theories.

Hen eggs (HEs) provide valuable nutrients for humans, including proteins, carbohydrates, lipids and vitamins. Recent studies revealed a number of novel egg-derived proteins/peptides (EDPs), and EDPs may play a crucial role in food industry and medical therapy. First, these EDPs were purified from the enzyme-catalyzed hydrolysates of egg proteins and were characterized by biochemical assays such as gel electrophoresis, HPLC, mass spectrometry, proteomic and peptideomic analysis, etc. Second, some EDPs can be used as nontoxic bio-preservatives and functional nutraceuticals for replacing harmful sodium nitrite, inhibiting foodborne pathogens, promoting metal-ion absorption and improving meat-product quality, and these new features will be widely used in the field of food production. Third, novel medical properties of EDPs comprise anti-oxidative, anti-microbial, anti-inflammatory and anti-nociceptive activities, which will benefit prevention of cardiovascular diseases, cancers, diabetic mellitus, immune disorders, etc. In summary, this review gives a real insight into the novel nutritional, biological and medical functions of EDPs, predictably facilitating the applications of EDPs in production of nutritive supplements, functional nutraceuticals and therapeutic medicines.

Coronavirus Disease 2019 (COVID-19) infected by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a public health emergency of international concerns. Cytokine storm syndrome (CSS) is a critical clinical symptom of severe COVID-19 patients, and the macrophage is recognized as the direct host cell of SARS-CoV-2 and potential drivers of CSS. In the present study, peramivir was identified to reduce TNF-α by partly intervention of NF-κB activity in LPS-induced macrophage model. In vivo, peramivir reduced the multi-cytokines in serum and bronchoalveolar lavage fluid (BALF), alleviated the acute lung injury and prolonged the survival time in mice. In human peripheral blood mononuclear cells (hPBMCs), peramivir could also inhibit the release of TNF-α. Collectively, we proposed that peramivir might be a candidate for the treatment of COVID-19 and other infections related CSS.

Objective: The efficacy and safety of adjunctive magnetic seizure therapy (MST) for patients with schizophrenia are unclear. This systematic review was conducted to examine the efficacy and safety of adjunctive MST for schizophrenia.Methods: Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO, and the Cochrane Library) databases were systematically searched.Results: Two open-label self-controlled studies (n = 16) were included and analyzed in this review. In these studies, the Positive and Negative Syndrome Scale (PANSS) total scores and Brief Psychiatric Rating Scale (BPRS) total scores significantly decreased from baseline to post-MST (all Ps < 0.05), without serious adverse neurocognitive effects. Mixed findings on the neurocognitive effects of adjunctive MST for schizophrenia were reported in the two studies. A discontinuation rate of treatment of up to 50% (4/8) was reported in both studies. The rate of adverse drug reactions (ADRs) was evaluated in only one study, where the most common ADRs were found to be dizziness (25%, 2/8) and subjective memory loss (12.5%, 1/8).Conclusion: There is inconsistent evidence for MST-related adverse neurocognitive effects and preliminary evidence for the alleviation of psychotic symptoms in schizophrenia.

Eleven novel NNN Cu(II) complexes supported by a tridentate bis(imidazo[1,2-α]pyridin-2-yl)pyridine ligand were synthesized and characterized by elemental analysis, HRMS, and X-ray determination. Target prediction and docking studies indicated that these pincer complexes formed hydrogen bonds with Asp33 and Gly35 of Cathepsin D protein, which is highly associated with prognosis of advanced prostate cancer. Furthermore, they exhibited anti-proliferation activity in both androgen-sensitive and androgen-insensitive prostate cancer cells according to WST-1 assay results. Mechanistic study showed that pincer complexes arrested cell cycle progression at G0/G1 phase and inhibited Cathepsin D regulated signaling pathways. Most importantly, new pincer copper complexes significantly inhibited xenograft prostate cancer growth along with a promising in vivo safety profile. In summary, these results suggest the applicability of the developed novel pincer copper complexes as promising anticancer agents for prostate cancer treatment.

Background:Members of the integrin β superfamily(ITGBs) have been shown to be aberrantly expressed in various human cancers and involved in tumorigenesis and progression. However, the diverse expression patterns and prognostic values of the entire ITGB family members in gastric cancer(GC) has not been systematically investigated.Methods:In the current study, Oncomine, GEPIA, Kaplan Meier plotter, TIMER, GeneMANIA, STRING and Metascape database were employed to explore the transcriptional and survival data of ITGB superfamily members in GC. Moreover, we confirmed the mRNA expression levels of ITGB superfamily members in GC cell lines by qRT-PCR.Results:The mRNA expression level of ITGB1/2/4/5/8 was upregulated in GC, while the expression level of ITGB7 was downregulated. Higher expression of ITGB2/7 was significantly associated with the tumor stage of patients with GC. However, we found that the expression level of ITGB1/2/4/5/6/7/8 was remarkably increased in GC cell lines compared to stomach normal cell lines, while ITGB3 expression was decreased in the former than in the latter. Meanwhile,higher expression levels of ITGB2/6/7 were closely correlated with better overall clinical survival (OS) and recurrence-free survival (RFS) in GC patients, while higher ITGB3/4/5 expression were strongly associated with poorer OS and RFS.We also discovered that the functions of ITGBs and their adjacent genes are mainly related to protein complexes involved in cell adhesion. the functions of ITGBs and their adjacent proteins are mainly related to focal adhesion, cell adhesion molecules, proteoglycans in cancer, small cell lung cancer, rap1 signaling pathway, IgA production by intestinal immune network, and microRNAs in cancer.In addition, the expression of ITGBs was significantly correlated with the infiltration of multiple immune cells, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells.Conclusions:Our results suggested that abnormal expression of ITGBs plays a key role in the progression of GC and that ITGBs may be potential prognostic biomarkers and therapeutic targets for GC.

The efficacy and safety of adjunctive nonconvulsive electrotherapy (NET) for patients with depression are undetermined. This systematic review was conducted to examine the efficacy and safety of adjunctive NET for patients with depression. Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO and the Cochrane Library) databases were systematically searched from their inception until Jan 27, 2021 by three independent investigators. One randomized controlled trial (RCT) with 3 treatment arms (n = 108) and two observational studies (single-group, before-after design, n = 31) were included. In the RCT, the antidepressant efficacy of NET on depression was similar to that of electroconvulsive therapy (ECT) (P > 0.05) but with significantly fewer neurocognitive impairments as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (P

Schizophrenia is associated with an increased risk of metabolic syndrome (MetS), which is an important risk factor for developing cognitive impairment in the general population. A few case-control studies have explored the relationship between MetS and cognitive deficits in individuals with schizophrenia but with inconsistent findings. This meta-analysis of case-control studies was carried out to explore the association between MetS and cognitive performance in patients with schizophrenia. Only case-control studies assessing the association of cognitive function and MetS in patients with schizophrenia were identified. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale. Six case-control studies (n = 992) comparing cognition between patients with schizophrenia with MetS (n = 426) and those without MetS (n = 566) using the RBANS were identified. Compared to patients with schizophrenia without MetS, patients with schizophrenia and MetS had significantly more impairments in RBANS total scores [standardized mean difference (SMD) = −0.26, 95% confidence interval (CI): −0.51 to −0.02; I2 = 72%; p = 0.03], immediate memory (SMD = -0.32, 95% CI: −0.54 to −0.10; I2 = 66%; p = 0.005), attention (SMD = -0.29, 95% CI: −0.56 to −0.02; I2 = 77%; p = 0.03), and delayed memory (SMD = -0.24, 95% CI: −0.46 to −0.03; I2 = 64%; p = 0.03). No group difference was found regarding visuospatial skills and language (p > 0.05). This meta-analysis found that schizophrenia patients with MetS had worse performance on certain cognitive tasks than non-MetS patients.

This study aimed to improve the biological effectiveness and pharmacokinetic properties of chlorin e

A series of novel bis-naphalenyl compounds with different diamine linkers were synthesized and characterized by 1H NMR, 13C NMR, and HR-MS. The DNA binding abilities of the compounds were studied by using flourescence titration, DNA thermal denaturation experiments, viscosity titration, and NMR studies. The DNA binding abilities of all the bis-naphalenyl compounds were on the same order of magnitude. Compared with the groove binding mode of the monomer, the bis-naphalenyl compounds exhibited partial intercalating binding mode. The cytotoxicity activities of the compounds were evaluated by MTT assay in vitro. According to the results of MTT assay, bis-naphalenyl compound 3c with hexamethylenediamine linker, and 3d with p-xylylenediamine linker were found to be more toxic against BGC823 cells. The IC50 values of the two compounds were similar to that of the control drug (5-Fluorouracil) on BGC823 cells. Compared with the results on BGC823 cells, better results were found on SW480 cells. Compounds 3c and 3d exhibited smaller IC50 values than that of control drug (5-Fluorouracil). The IC50 values of 3c, 3d, and 5-Fluorouracil were 52.01, 66.09, and 230.11 μM, respectively.

Background Rapid demographic and economic changes have made chronic disease the number one health issue in China, contributing to more than 80% of the country’s 10.3 million annual deaths and nearly 70% of its total disease burden (Wang et al., Toward a Healthy and Harmonious Life in China: Stemming the Rising Tide of Non-Communicable Diseases, 2011; Yip and Hsiao, Lancet 384: 805-18, 2014). Diabetes is a major contributor to the chronic disease burden and is experienced by nearly 11% of the adult population of China (Yang et al., N Engl J Med 362:1090-101, 2010). In response to the challenges of chronic disease, the Chinese government initiated comprehensive health care reforms nationwide in 2009. A key measure was a hierarchical diagnosis and treatment system for monitoring and reducing chronic diseases and improving the community health service system (Barber et al., Health Policy Plan 29:367-78, 2014). Primary hospitals, such as community health service centers, are the main gatekeepers for management of diabetes and other chronic diseasesin China. In recognition of the need for a more patient-centered approach, the Chinese government has piloted a program incorporating methods of diabetes self-management for chronic care: the Happy Life Club (Browning et al., Front in Public Health 2:181, 2015). This program is modeled on a similar program developed in Australia (Kelly et al., Aust J Prim Health 9:186-9, 2003). The ICDMS is an important tool in the implementation of patient-centered programs targeting chronic health issues, and its success is determined by factors, such as frequent contact between patients and doctors and effective website training for patients. This retrospective study used de-identified data from the Fangzhuang (Beijing) intelligent chronic disease management system (ICDMS) database to evaluate the effect of an intelligent chronic disease management system on selected Beijing community patients who have type 2 diabetes mellitus (T2DM). Methods A comparative study before and after ICDMS implementation was performed to evaluate the effect of ICDMS on the rates of follow-up and laboratory examinations, measurement rates of blood glucose and lipids, glycosylated hemoglobin (HbA1c) and blood lipid levels, as well as the corresponding health parameters. Continuous variables and categorical variables were analyzed using paired t-test and McNemar’s tests, respectively. Results A total of 2451 T2DM patients met inclusion/exclusion criteria. Compared with the pre-index period, the laboratory examination, rates of blood glucose and blood lipids increased significantly in the post-index period (p

Objective: To evaluate the effect of an intelligent Internet-based information system upon optimising the management of patients diagnosed with type 2 diabetes mellitus (T2DM). Methods: In 2015, a T2DM information system was introduced to optimise the management of T2DM patients for 1 year in Fangzhuang community of Beijing, China. A total of 602 T2DM patients who were registered in the health service centre of Fangzhuang community were enrolled based on an isometric sampling technique. The data from 587 patients were used in the final analysis. The intervention effect was subsequently assessed by statistically comparing multiple parameters, such as the prevalence of glycaemic control, standard health management and annual outpatient consultation visits per person, before and after the implementation of the T2DM information system. Results: In 2015, a total of 1668 T2DM patients were newly registered in Fangzhuang community. The glycaemic control rate was calculated as 37.65% in 2014 and significantly elevated up to 62.35% in 2015 ( p < 0.001). After application of the Internet-based information system, the rate of standard health management was increased from 48.04% to 85.01% ( p < 0.001). Among all registered T2DM patients, the annual outpatient consultation visits per person in Fangzhuang community was 24.88% in 2014, considerably decreased to 22.84% in 2015 ( p < 0.001) and declined from 14.59% to 13.66% in general hospitals ( p < 0.05). Conclusion: Application of the T2DM information system optimised the management of T2DM patients in Fangzhuang community and decreased the outpatient numbers in both community and general hospitals, which played a positive role in assisting T2DM patients and their healthcare providers to better manage this chronic illness.

Vast changes have occurred in China in the last five years since the decision of the Chinese Government to reform its health system. Many district and community hospitals in the city have been converted into community health centers. The hospital-based doctors who used to work in these centers are being retrained to become general practitioners (GPs). The reform had encountered many problems. The community has not embraced the concept of general practice readily. Lack of fair remuneration and lack of recognition of the importance of the reform by bureaucrats of local government are other problems encountered. The Ministry of Health meanwhile has also introduced a system of retraining hospital-based doctors to become GPs. A medical education curriculum for GPs has been developed. A nationwide network of GP training centers is progressively being formed. The GP training program has also extended to undergraduate medical students. Despite the progress made, many difficulties remained especially in regional areas. The speed and quality of GP training in wealthy, developed places is better than poorer regional areas. The issuing of national license and registration examinations for GPs has not been synchronized with GP training, leading to uneven standard of GP practice. Staff morale is also poor due to the lack of chance for promotion and professional development. Although a number of strategies have been proposed to improve the situation, problems are enormous that China may welcome international collaboration.

Human neutrophil elastase (HNE) has been identified as a potential therapeutic target for the discovery of anti-inflammatory drugs for decades. However, little progress has been made on assays measuring the activity of HNE, especially on synthetic substrates which play essential role in determination of HNE activity. Herein, a small-molecule compound, 2,2,3,3,3-pentafluoro-N-(2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl)-propanamide (compound 4), has been successfully designed as the first ever non-peptide-based fluorogenic substrate for HNE. A "turn-on" fluorometric assay based on 4 has been successfully developed for rapid determination of HNE activity and the inhibitory kinetic study. Most importantly, the probe 4 shows highly specific response for HNE among seven tested hydrolases or proteins and can be directly used to detect the elevated HNE activity in the serum of chronic obstructive pulmonary disease (COPD) patients compared to that of healthy controls. This specific and cost-effective probe will facilitate future high-throughput discovery of HNE inhibitors and clinical diagnosis of elastase-related diseases.

Primer sequences used for reverse transcriptase (RT)-PCR analysis of C-repeat binding factors (CBFs), ABA biosynthesis and signaling, and certain tomato invertase and invertase inhibitor genes. Figure S1. Phenotypic responses of INVINH1 RNAi line 2&8 and wildtype plant under cold stress. (A) Water loss rate of the leaves from The first mature leaf from 60-d INVINH1 RNAi and wildtype plant, which were recovered at 25 °C for 2 h after treated at 4 °C for 48 h. (B) The proline content of the first mature leaf from 60-d INVINH1 RNAi and wildtype plant before and after treated at 4 °C for 24 h. (C) The POD activity of the first mature leaf from 60-d INVINH1 RNAi and wildtype plant before and after treated at 4 °C for 24 h. (POD activity: 1 U = OD•min−1•g−1FW). Each value is mean ± SE of at least ten biological replicates. Lowercase letters indicate values significantly different at P

Primer sequences used for reverse transcriptase (RT)-PCR analysis of C-repeat binding factors (CBFs), ABA biosynthesis and signaling, and certain tomato invertase and invertase inhibitor genes. Figure S1. Phenotypic responses of INVINH1 RNAi line 2&8 and wildtype plant under cold stress. (A) Water loss rate of the leaves from The first mature leaf from 60-d INVINH1 RNAi and wildtype plant, which were recovered at 25 °C for 2 h after treated at 4 °C for 48 h. (B) The proline content of the first mature leaf from 60-d INVINH1 RNAi and wildtype plant before and after treated at 4 °C for 24 h. (C) The POD activity of the first mature leaf from 60-d INVINH1 RNAi and wildtype plant before and after treated at 4 °C for 24 h. (POD activity: 1 U = OD•min−1•g−1FW). Each value is mean ± SE of at least ten biological replicates. Lowercase letters indicate values significantly different at P

The volatile components of the Hui formula "Ha Hei Lili" were extracted by steam distillation extraction (SD) and supercritical CO2 fluid extraction, and the structures were analyzed and identified by GC-MS.The GC-MS conditions were set as follows: Rxi-5Sil MS quartz capillary column (30 m x 0.25 mm, 0.25 μm), the initial temperature of 50 degrees C to keep 1 min, to 10 degrees C/min heating to 120 degrees C, maintained 3 min, then to 3 degrees C/min heating to 200 degrees C, maintained 3 min, and then to 5 degreesC/min heating to 290 degrees C, maintained until completion of analysis; helium as the carrier gas, column flow rate 1.0 ml/min, split ratio 25: 1, inlet temperature 250 degrees C, EI ionization source 70 eV, ion source temperature 230 degrees C, scan range of m/z 35 - 500.Yield of volatile oil were 0.21% and 5.44% extracted by SD and SFE methods, respectively; and for SD method, 36 kinds of compounds were identified, accounted for 87.02% of total mass of volatile oil; for SFE method, 38 kinds of constituents were identified, accounted for 97.47% of total mass of volatile oil.The type of constituents contained in the volatile oil extracted by SD and SFE methods are totally different; and GC-MS can be used to identify the structures and relative content of volatile components, the results of this study can provide an experimental basis for development and utilization of Hui formula "Ha Hei Lili".

Annealing control primer (ACP) system was applied to find candidate genes related to lipidosis in muscle of Yanbian yellow cattle by screening differentially expressed genes (DEGs) in Longissimus dorsi, which had significant difference on intramuscular fat (IMF) content. Thirty steers, aged at 28 month-bullocks were selected to measure the IMF content in L. dorsi. Two groups of bullocks (three heads per group) with the highest and the lowest contents of IMF were selected to build a RNA pool, and DEGs of two groups were analyzed by ACP system. Twelve DEGs were identified and sequenced by amplification with 20 arbitrary primers (fragment sizes were 200-890 bp). In these genes, eight were already known as functional groups of cytoskeleton, cytokine signal transduction, protein synthesis, energy metabolism, and others, four were unknown. All the 12 ESTs were screened by ACP system, which may participated in regulating on lipidosis in muscle. This study established a foundation for further screening of lipidosis related genes.

Summary Objective To review the severe acute respiratory syndrome (SARS) epidemic in Beijing using basic epidemiological principles omitted from the original analysis. Study design Analysis of Prospective surveillance data for Beijing collected during the outbreak. Methods Surveillance data were reclassified according to World Health Organization criteria. Cases previously excluded without date of onset of illness were included in the epidemic curve from estimates using the average time between date of onset and date of hospitalization for cases with both dates. Cases who failed to give a contact history were now included; 7% ( n = 5 ) of cases during the import phase and 61% ( n = 365 ) during the peak phase. Previously excluded cases were included for plotting on an epidemic curve, and basic spot mapping for distribution of cases was used from attack rates recalculated for age, gender, occupation, residential location, date of onset of illness and demographics. Results The spot map effectively illustrated clusters by residency, with the inner-city sustaining the highest attack rate (33.42 per 100,000), followed by an easterly distribution 5–30 km away (21.62 per 10,000), and lowest in districts 60–160 km away (9.21 per 100,000). The new epidemic curve shows the outbreak commencing 10 days earlier than initially reported, with a three-fold greater increase in cases during the escalation phase than previously estimated. Conclusion In hindsight, the investigation of the Beijing SARS would have benefited from the use of spot maping as an essential outbreak tool for early identification of specific geographical area(s) for quarantining. If a spot map of incidence density rates was used during the early phase of the outbreak, the inner city might have been identified as a major risk factor requiring rapid quarantining. Contact history became uncommon as the outbreak progressed, suggesting that hospitals were over-burdened or pathogenesis and environment risk factors changed, strengthening the usefulness of early spot mapping and the need to modify risk factors included as contact history as the epidemic progresses.

Toll-interacting protein (Tollip) is an endogenous inhibitor of toll-like receptors, a superfamily that plays a pivotal role in various pathological conditions, including myocardial infarction (MI). However, the exact role of Tollip in MI remains unknown.MI models were established in Tollip knockout (KO) mice, mice with cardiac-specific overexpression of human Tollip gene and in their Tollip(+/+) and non-transgenic controls respectively. The effects of Tollip on MI were evaluated by mortality, infarct size and cardiac function. Hypoxia-induced cardiomyocyte damage was investigated in vitro to confirm the role of Tollip in heart damage.Tollip expression was dramatically up-regulated in human ischaemic hearts and infarcted mice hearts. MI-induced mortality, infarct size and cardiac dysfunction were decreased in Tollip-KO mice compared with Tollip(+/+) controls. Ischaemic hearts from Tollip-KO mice exhibited decreased inflammatory cell infiltration and reduced NF-κB activation. Tollip depletion also alleviated myocardial apoptosis by down-regulating pro-apoptotic protein levels and up-regulating anti-apoptotic protein expressions in infarct border zone. Conversely, MI effects were exacerbated in mice with cardiac-specific Tollip overexpression. This aggravated MI injury by Tollip in vivo was confirmed with in vitro assays. Inhibition of Akt signalling was associated with the detrimental effects of Tollip on MI injury; activation of Akt largely reversed the deleterious effects of Tollip on MI-induced cardiomyocyte death.Tollip promotes inflammatory and apoptotic responses after MI, leading to increased mortality and aggravated cardiac dysfunction. These findings suggest that Tollip may serve as a novel therapeutic target for the treatment of MI.

This study was performed to determine airborne manganese levels during welding practice and to establish the relationship between long-term, low-level exposure to manganese and altered serum concentrations of manganese, iron, and proteins associated with iron metabolism in career welders. Ninety-seven welders (average age of 36 years) who have engaged in electric arc weld in a vehicle manufacturer were recruited as the exposed group. Welders worked 7-8h per day with employment duration of 1-33 years. Control subjects consisted of 91 employees (average age of 35 years) in the same factory but not in the welding profession. Ambient manganese levels in welders' breathing zone were the highest inside the vehicle (1.5 +/- 0.7 mg/m3), and the lowest in the center of the workshop (0.2 +/- 0.05 mg/m3). Since the filter size was 0.8 microm, it is possible that these values may be likely an underestimation of the true manganese levels. Serum levels of manganese and iron in welders were about three-fold (p < 0.01) and 1.2-fold (p < 0.01), respectively, higher than those of controls. Serum concentrations of ferritin and transferrin were increased among welders, while serum transferrin receptor levels were significantly decreased in comparison to controls. Linear regression analyses revealed a lack of association between serum levels of manganese and iron. However, serum concentrations of iron and ferritin were positively associated with years of welder experience (p < 0.05). Moreover, serum transferrin receptor levels were inversely associated with serum manganese concentrations (p < 0.05). These findings suggest that exposure to welding fume among welders disturbs serum homeostasis of manganese, iron, and the proteins associated with iron metabolism. Serum manganese may serve as a reasonable biomarker for assessment of recent exposure to airborne manganese.

The antifungal activity of ZJ-522, a new triazole antifungal agent restructured from fluconazole and butenafine, was compared to that of fluconazole and butenafine against 43 strains of fungi representing 13 fungal species. MICs were determined by using the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth microdilution method for yeasts, which was modified for filamentous fungi. ZJ-522 was about 50-fold and 2 to 16-fold more potent than fluconazole against yeasts and filamentous fungi respectively, but it was less active than butenafine against filamentous fungi, although butenafine was inactive against most yeasts. Thus, the fashion of ZJ-522 antifungal activity more similar to that of fluconazole than that of butenafine indicates that ZJ-522 should be an inhibitor of lanosterol 14alpha-demethylase but not of squalene epoxidase, and should be a candidate for clinical development.

No abstract.

Nine racemic homocamptothecin derivatives were synthesized and in vitro antitumor activities were evaluated by standard MTT method. The results showed that some of the compound had higher antitumor activity than iritecan.

To examine the antifungal effect of different extract of Dryopteris fragrans (L.) Schott. in vitro, and screen the effective fraction from those extracts.Separated the Dryopteris fragrans extract and got four parts by refluxing extraction,and determined the contents of total phloroglucinol. Disc agar diffusion method and solid agar dilution method were used to determine inhibitory effect. Minimum inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of different parts of Dryopteris fragrans extract against four strains of common clinical dermatophytes were investigated.The data showed that the contents sequence of total phloroglucinol was in the following order: 95% -ethanol extractwater extractdiethyl ether extractpetroleum ether extract, and the antimicrobial activities against the four dermatophytes were as following order: 95% -ethanol extractwater extractdi-ethyl ether extractpetroleum ether extract.The contents of total phloroglucinol in 95% -ethanol extract of Dryopteris fragrans is the highest, and the antifungal activity against dermatophytes in vitro is the strongest. The effective fraction of Dryopteris fragrans is the 95%-ethanol extract.

Background Primary care medical staffs’ knowledge, attitude and behavior about health emergency and the response capacity are directly related to the control and prevention of public health emergencies. Therefore, it is of great significance for improving primary care to gain in-depth knowledge about knowledge, attitude and behavior and the response capacity of primary care medical staffs. The main objective of this study is to explore knowledge, attitude and behavior, and the response capacity of primary care medical staffs of Guangdong Province, China. Methods Stratified clustered sample method was used in the anonymous questionnaire investigation about knowledge, attitude and behavior, and the response capacity of 3410 primary care medical staffs in 15 cities of Guangdong Province, China from July, 2010 to October 2010. The emergency response capacity was evaluated by 33 questions. The highest score of the response capacity was 100 points (full score), score of 70 was a standard. Results 62.4% primary care medical staffs believed that public health emergencies would happen. Influenza (3.86 ± 0.88), food poisoning (3.35 ± 0.75), and environmental pollution events (3.23 ± 0.80) (the total score was 5) were considered most likely to occur. Among the 7 public health emergency skills, the highest self-assessment score is “public health emergency prevention skills” (2.90 ± 0.68), the lowest is “public health emergency risk management (the total score was 5)” (1.81 ± 0.40). Attitude evaluation showed 66.1% of the medical staffs believed that the community awareness of risk management were ordinary. Evaluation of response capacity of health emergency showed that the score of primary care medical staffs was 67.23 ± 10.61, and the response capacity of senior physicians, public health physicians and physicians with relatively long-term practice were significantly better (P Conclusions The knowledge, attitude and behavior about public health emergencies and the response capacity of primary care medical staffs of Guangdong Province (China) were poor. Health administrative departments should strengthen the training of health emergency knowledge and skills of the primary care medical staffs to enhance their health emergency response capabilities.

Background Procedural burn pain is the most intense acute pain and most likely type of burn injury pain to be undertreated due to the physician’s fear of the adverse effect of analgesia and lack of anesthetist present. At our institution, in most of the cases, local burn detersion and debridement were performed at the ward level without any analgesics. This article describes a study designed to test the analgesia effect of a fixed nitrous oxide/oxygen mixture on burn dressing pain. Methods/design The experiment was carried out in three centers. The patients were given a number from 1 to 240. A randomization list was produced by a statistician according to our preliminary study. Due to the severity of the pain suffered, ethically it was decided to help as many as possible, so patients given the letters A, B or C were treated using a canister with the appropriate letter containing preprepared nitrous oxide/oxygen mixture (NOOM). Those with D were given oxygen only, from an identical-looking canister labeled D. Neither patients, nor doctors, nor nurses, nor data collector knew what was in each canister, thus they were all blind. The nursing officer who implemented the intervention handed the doctors envelopes containing the patients’ name and allocation of A, B, C or D. Thus, patients receiving NOOM or oxygen were in the ratio 3:1. Parameters, including pain severity, blood pressure, heart rate, digital oxygen saturation and the Chinese version of the burn specific pain anxiety scale (C-BSPAS), were taken before, during and after dressing for each group. A video and audio record was taken individually for later communication coding and outcome analysis. Rescue analgesic was recorded. Discussion Based on the findings from our previous qualitative study that physician’s reluctance to order narcotic analgesia is due to its adverse effect and from our pilot experiment, this study aims to test the hypothesis that a fixed nitrous oxide/oxygen mixture will promote better burn dressing pain alleviation and outcomes. Analyses will focus on the effects of the experimental intervention on pain severity during dressing (primary outcomes); physiological parameters, C-BSPAS and acceptance of both health care professionals and patients (secondary outcomes). If this model of analgesia for burn pain management implemented by nurses proves successful, it could potentially be implemented widely in hospital and prehospital settings and improve patients’ satisfaction and quality of life. Trial registration (Clinical Trials Identifier: CHICTR-TRC11001690).

This study investigated the protective effects of Lycium barbarum polysaccharide (LBP) on alleviating injury from oxygen-glucose deprivation/reperfusion (OGD/RP) in primary cultured rat hippocampal neurons. Cultured hippocampal neurons were exposed to oxygen-glucose deprivation (OGD) for 2 h followed by a 24 h re-oxygenation. The MTT assay and the lactate dehydrogenase (LDH) release were used to determine the neuron viability. Superoxide dismutase (SOD), Glutathione peroxidase (GSH-PX), malondialdehyde (MDA) were determined by spectrophotometry using commercial kits. Mitochondrial membrane potential (MMP) and the intracellular free calcium concentration ([Ca(2+)](i)) in hippocampal neurons were measured using the confocal laser scanning microscope (CLSM). Treatment with LBP (10-40 mg/l) significantly attenuated neuronal damage and inhibited LDH release in a dose-dependent manner. Furthermore, LBP enhanced activities of SOD and GSH-PX but it decreased their MDA content, inhibited [Ca(2+)](i) elevation and decrease of MMP in ischemia-reperfusion treated hippocampal neurons. These findings suggested that LBP may be a potential neuroprotective agent for cerebral ischemia-reperfusion injury.

Annealing control primer (ACP) system was applied to find candidate genes related to lipidosis in muscle of Yanbian yellow cattle by screening differentially expressed genes (DEGs) in Longissimus dorsi, which had significant difference on intramuscular fat (IMF) content. Thirty steers, aged at 28 month-bullocks were selected to measure the IMF content in L. dorsi. Two groups of bullocks (three heads per group) with the highest and the lowest contents of IMF were selected to build a RNA pool, and DEGs of two groups were analyzed by ACP system. Twelve DEGs were identified and sequenced by amplification with 20 arbitrary primers (fragment sizes were 200-890 bp). In these genes, eight were already known as functional groups of cytoskeleton, cytokine signal transduction, protein synthesis, energy metabolism, and others, four were unknown. All the 12 ESTs were screened by ACP system, which may participated in regulating on lipidosis in muscle. This study established a foundation for further screening of lipidosis related genes.

In recent years, the incidence and mortality rate of invasive fungal infection have increased dramatically, and it is of great significance to develop novel antifungal agents with new chemical structure and new mode of action. In this review, novel antifungal lead compounds reported from 2007 to 2009 are reviewed. Moreover, their chemical structures, antifungal activities and structure-activity relationships have been summarized, which can provide useful information for future study of antifungal agents.

Background Soft tissue injury imposes major public health burdens worldwide. The positive effect of China's Tibetan medicine and the Lamiophlomis rotata-based herbal Pain Relieving Plaster (PRP) on healing closed soft tissue injury (CSTI) has been reported. The herbs contained in Plaster are also referred as 'blood-activating and stasis-dispelling' in herbal medicine. The formula of the plaster contains four China's Tibetan medical herbs, including Lamiophlomis rotata, Oxytropis falcate Bunge, Curcuma longa Linn, and Myricaria bracteata. Two of these herbs (Lamiophlomis rotate; Curcuma longa Linn) are commonly used in different formulae of Chinese medicine. The objective of this study is to use an interdisciplinary approach to test the hypothesis that the formula and its components influence the process of CSTI. Methods In vivo models have been established in 30 rabbit ear pinnae and studied for: (1) blood flow velocity (BFV) which was affected by pressure of 21.2 kg/cm2 for 30 second over the local rabbit ear tissue; (2) edema formation of the closed soft tissue injury; (3) in vivo local temperature change. Results The results of in vivo studies indicated that CSTI significantly increased the velocity of blood flow and increased edema formation within the control group. The PRP extracts for 5 hours significantly slowed down the BFV of CSTI in rabbit ears, markedly decreased the elevated edema level from the 3rd to the 5th day. Conclusion The ingredients contained in the formula have positive effects in healing CSTI and further study is worth exploring.

In recent years, the incidence of infections caused by invasive fungal pathogens has increased dramatically. However, most antifungal agents used in clinic have many drawbacks and cannot meet the demand of the clinical use. Therefore, for the development of new generation of antifungal agents, it is of great significance to find antifungal lead compounds with novel chemical scaffolds and new mode of action. Novel antifungal lead compounds reported in recent years are reviewed. Their chemical structures, antifungal activity and structure-activity relationship are discussed in detail, and current problems and trends in future research are also emphasized.

To explore the association between polymorphism in the ACE I/D gene and blood pressure-lowering response to hydrochlorothiazide (HCTZ) in 829 patients.HCTZ 12.5 mg was taken once a day for six weeks. The blood pressure reduction and ratio reaching target blood pressure were compared in different ACE genotype groups.The reduction in SBP of patients carrying DD was greater than that in other groups carrying II or ID (12.2 mmHg versus 5.4 mmHg, 12.2 mmHg versus 4.4 mmHg, respectively, P0.05). The reduction in MAP of patients carrying DD was also greater than that in other groups carrying II or ID (6.9 mmHg versus 3.9 mmHg, 6.9 mmHg versus 3.6 mmHg, respectively, P0.05). The ratio reaching target blood pressure in DD groups was significantly higher than that in II or ID groups (P0.05). The pre-treatment SBP, DD genotype, aldosterone levels entered the multi-linear regression model significantly and might affect the reduction of SBP. The pre-treatment DBP, aldosterone levels, DD genotype entered the multi-linear regression model significantly and might affect the reduction of DBP. The pre-treatment MAP, DD genotype, aldosterone levels entered the multi-linear regression model significantly and might affect the reduction of MAP.ACE genotyping is associated with blood pressure-lowering response to HCTZ. Specific genotypes might be associated with the response to specific antihypertensive treatment.

To assess and explore the quality of life and related factors among 291 outpatient adults with epilepsy.From July, 2005 to July, 2006, eligible outpatient epilepsy in a hospital was evaluated by the scale on quality of life in epilepsy-31 (Chinese version).The total scores of quality of life was low (56.46 +/- 16.58). The scores of quality of life in each item were as follows: seizure worry (45.01 +/- 25.25); overall quality of life (56. 12 +/- 16.37); emotional well-being (59.35 +/- 19.56); cognitive function (58.58 +/- 22.41); energy/fatigue (59.12 +/- 18.98); medication effects (40.45 +/- 24.44) and social function (53.00 +/- 26.36). The quality of life of patients with different education background, drug intake and side effects was different significantly (P0.05). Data on Multi-linear regression showed that education background, side effects would affect the quality of life.The quality of life of outpatient adults with epilepsy was low with education background, while side effects and drugs intake might serve as important factors affecting the quality of life with epilepsy.

To clarify the important functional residues in the active site of N-myristoyltransferase (NMT), a novel antifungal drug target, and to guide the design of specific inhibitors, multiple sequence alignments were performed on the NMT family and thus evolutionary trace was constructed. The important functional residues in myristoyl CoA binding site, catalytic center and inhibitor binding site of NMT family were identified by ET analysis. The trace residues were mapped onto the active site of CaNMT. Trpl26, Asn175 and Thr211 are highly conserved trace residues and do not interact with current NMT inhibitors, which are potential novel drug binding sites for the novel inhibitor design. Pro338, Leu350, Ile352 and Ala353 are class-specific trace residues, which are important for the optimization of current NMT inhibitors. The trace residues identified by ET analysis are of great importance to study the structure-function relationship and also to guide the design of specific inhibitors.

To summarize lessons learned from an outbreak of severe acute respiratory syndrome (SARS) in China during the spring of 2004.Data of SARS cases were officially reported by Beijing Municipal Center for Disease Control and Prevention (BCDC) and Anhui Provincial Center for Disease Control and Prevention (APCDC) and results of epidemiological investigations were collected and analyzed.Three generations of 11 cases of SARS were identified during the outbreak. Initial two cases were most likely to be infected in Diarrhea Virus Laboratory of National Institute of Virology, China Centers for Disease Control and Prevention and main mode of transmission was direct contact with SARS patients. Delay in detecting initial case resulted in spread of the illness at hospitals and communities with two generations of secondary cases.SARS outbreak in 2004 has yielded following lessons for public health globally. (1) Lab bio-safety programs should be made and should be strictly abided by. Studies in highly pathogenic viruses such as SARS coronavirus should be utmost cautious. (2) Management systems of occupational exposure to virus and disease surveillance need to be strengthened to take all risk factors into account so as to detect potential patients with infectious disease as early as possible.

To study the potential risk factors for severe acute respiratory syndromes (SARS)-related deaths in Beijing.Epidemiological data were collected among the confirmed SARS patients officially reported by Beijing Centers for Disease Control and Prevention (BCDC), and information was also supplemented by a follow-up case survey. Chi-square test and multivariate stepwise logistic regression analysis were performed.Old age (over 60 years) was found to be significantly associated with SARS-related deaths in the univariate analysis. Also, history of contacting SARS patients within 2 weeks prior to the onset of illness, health occupation, and inferior hospital ranking as well as longer interval of clinic consulting (longer than 1 day) were the risk factors for SARS-related deaths. Multivariate stepwise logistic regression analysis found four risk factors for SARS-related deaths.Old age (over 60 years) is the major risk factor for SARS-related deaths. Moreover, hospital health workers, the designated hospitals for SARS clinical services and the interval of consulting doctors (less than 1 day) are protective factors for surviving from SARS.

To investigate the systemic changes of iron metabolism following manganese exposure.Ninety-seven welders and 91 workers with no history of exposure to manganese were recruited from the same factory in Beijing serving as the exposure group and the control group respectively. The welding rods used were type J422. The concentration of the manganese in the air of the work place was determined respectively with the national standard method. The serum iron and manganese, ferritin, transferrin and transferrin receptors were measured with the graphite furnace atomic absorption spectrophotometry and ELISA in both groups.The permissible concentration-STEL of ambient Mn in welders' breathing zone ranged from 0.53 mg/m(3) to 2.19 mg/m(3), while the permissible concentration-TWA of ambient Mn was between 0.29 mg/m(3) and 0.92 mg/m(3) in the breathing zone of the workplace. Serum Mn and Fe concentrations in welders were about 1.40 times (P0.0l) and 1.2 times (P0.01), respectively, higher than those of control subjects. At the same time, the transferrin concentrations in serum were significantly higher (about 1.2 times, P0.05) in welders than in controls. In contrast, transferrin receptors were significantly lower (about 1.2 times) in exposed subjects than controls (P = 0.001). There was no difference in serum ferritin between the two groups (P = 0.112). Although there was no significant trend, the serum ferritin level was increased by 18% in comparison with that of the control. The abnormal percentage of serum Fe and Serum Mn in welders were 55.67% and 67.01% respectively, higher than those of control subjects. In addition, the correlations between all indicators and the duration of employment were not observed.The long term exposure to the manganese can induce the disorder of the iron metabolism, which is found in the expression of increase of the serum iron and transferrin as well as the decrease of transferrin receptors.

To describe the epidemiologic features of an outbreak of severe acute respiratory syndrome (SARS) in urban and suburb areas in Beijing and to explore their differences between these two areas.Data of SARS cases were collected from daily notification of China Ministry of Health and a database of infectious diseases was established by the Beijing Municipal Center for Disease Prevention and Control (BCDC). All the data were put into dataset files by Microsoft Excel-2000 and analyzed with SPSS version 10.0 software.The respective urban incidence and mortality rate were 29.06 and 2.21 per 100,000, while the case fatality rate was 7.62%. In contrast, the respective suburb incidence and mortality rate were 10.61 and 0.78 per 100,000, and the case fatality rate was 7.32%. No significant differences were found in demographic characteristics between the urban and suburb areas.Beijing urban area suffered a more serious SARS epidemic than the suburb area in 2003.

To describe the case fatality rate of SARS in Beijing.Data of SARS cases notified from Beijing Center for Disease Control and Prevention (BCDC) and supplemented by other channels were collected. The data were analyzed by rate calculation.The case fatality rate of SARS in Beijing was 7.66%, and had an ascending trend while the age of cases was getting older, and a descending trend while the epidemic development. The case fatality rate in Beijing was lower than that in other main epidemic countries or regions.The risk of death increases with the increment of age of SARS patients. Beijing is successful in controlling and treating SARS.

To assess the impacts of public health interventions on the outbreak of SARS in Beijing by analyzing the intervals between symptom onset, hospital admission and notification of its cases.Data of SARS cases reported from the Beijing Municipal Centers for Disease Prevention and Control (BCDC) were collected and analyzed by descriptive epidemiology.In the early epidemic period, the intervals between the disease onset and the hospital admission seemed irregular, so was the intervals between the hospital admission and the notification. After the middle ten days of April, the intervals turned out to be more regular, and the disordered situation in terms of the hospital admission and the case notification was gradually brought under control.Public health interventions against SARS has revealed positive impacts on SARS control program in Beijing. The timing and sensitivity of epidemic information reporting systems has been greatly improved in Beijing as a result of successful fight against this disease.