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MLL3 is a histone H3K4 methyltransferase that is frequently mutated in cancer, but the underlying molecular mechanisms remain elusive. Here, we found that MLL3 depletion by CRISPR/sgRNA significantly enhanced cell migration, but did not elevate the proliferation rate of cancer cells. Through RNA-Seq and ChIP-Seq approaches, we identified TNS3 as the potential target gene for MLL3. MLL3 depletion caused downregulation of H3K4me1 and H3K27ac on an enhancer ~ 7 kb ahead of TNS3. 3C assay indicated the identified enhancer interacts with TNS3 promoter and repression of enhancer activity by dCas9-KRAB system impaired TNS3 expression. Exogenous expression of TNS3 in MLL3 deficient cells completely blocked the enhanced cell migration phenotype. Taken together, our study revealed a novel mechanism for MLL3 in suppressing cancer, which may provide novel targets for diagnosis or drug development. more...

The influence of national health level in the stability and sustainable development of national society is increasingly prominent. The purpose of this study is to examine whether, when, and how national fitness policies exert influence on national health. Panel data from 2008 to 2017 of 30 Chinese provinces (cities) (except the Tibet autonomous region) were used to systematically reveal the direct impact of national fitness policies on national health and its characteristics in different regions, as well as the interaction mechanisms of human capital and finance health expenditures in public sports. This study found that first, national fitness policies had a positive effect on adult health. Second, sports human capital weakens the health effect of national fitness policies, while public finance health expenditures strengthen this effect. Lastly, the health effect of national fitness policies varies significantly across regions due to uneven regional economic development, and the differences in the effects on different age groups (adults and children) are equally pronounced. This study suggests that national fitness public service system and diverse national fitness plans improving national health level are important for a new dynamic balance and high quality coordinated development in both Chinese economic growth and social welfare. more...

ObjectivesObesity is a well-recognised risk factor for osteoarthritis (OA). Our aim is to characterise body mass index (BMI)-associated pathological changes in the osteochondral unit and determine if obesity is the major causal antecedent of early joint replacement in patients with OA.MethodsWe analysed the correlation between BMI and the age at which patients undergo total knee replacement (TKR) in 41 023 patients from the Australian Orthopaedic Association National Joint Replacement Registry. We then investigated the effect of BMI on pathological changes of the tibia plateau of knee joint in a representative subset of the registry.Results57.58% of patients in Australia who had TKR were obese. Patients with overweight, obese class I & II or obese class III received a TKR 1.89, 4.48 and 8.08 years earlier than patients with normal weight, respectively. Microscopic examination revealed that horizontal fissuring at the osteochondral interface was the major pathological feature of obesity-related OA. The frequency of horizontal fissure was strongly associated with increased BMI in the predominant compartment. An increase in one unit of BMI (1 kg/m2) increased the odds of horizontal fissures by 14.7%. 84.4% of the horizontal fissures were attributable to obesity. Reduced cartilage degradation and alteration of subchondral bone microstructure were also associated with increased BMI.ConclusionsThe key pathological feature in OA patients with obesity is horizontal fissuring at the osteochondral unit interface. Obesity is strongly associated with a younger age of first TKR, which may be a result of horizontal fissures. more...

The impact and working mechanism of the national Healthy Cities pilot policy on the upgrading of the industrial structure remain foggy. This study takes China’s first batch of Healthy Cities under the pilot policy in 2016 as a natural experiment and builds a DID model based on the panel data of 280 prefecture-level cities from 2012 to 2019 to explore the impact of the Healthy Cities pilot policy on the industrial structure, wherein the impact tests and regional heterogeneity analysis are carried out accordingly. It is found through the study that the Healthy Cities pilot policy significantly contributes to industrial structure upgrading, especially for cities in the eastern and central regions. Further research on the impact mechanism shows that the Healthy Cities pilot policy facilitates industrial structure upgrading through technological innovation and green total factor productivity. Supported by the research results, this study argues that it bears great significance on the sustainable development of China’s economy as well as the health and well-being of the people to continually carry out the Healthy Cities pilot work and fully explore the mediating mechanism of the multi-faceted pilot policy on the optimization and upgrading of industrial structure, so as to promote the transformation of the health industry in different regions according to respective local conditions. more...

Objective We aimed to investigate practices of nasogastric tube (NGT) intubation and feeding for adults by clinical nurses in China. Methods A self-designed and validated questionnaire comprising 30 questions was distributed to 560 clinical nurses in three comprehensive hospitals of Xiamen, China. The questionnaire covered participants’ demographic characteristics, NGT placement, administration of enteral nutrition (EN), and monitoring or management of feeding intolerance. Results A total 464 (82.9%) questionnaires were completed; 36.2% of nurses used nose–ear–xiphoid and 79.5% forehead–xiphoid measurement to define the internal length of the NGT. Many participants still used traditional methods to confirm NGT placement (auscultation of injected air 50.2%, bubble test 34.7% and observing feeding tube aspirate 34.3%). Bolus feeding was the most commonly used technique to administer EN. A total 97.0% of all nurses used syringes to measure gastric residual volume (GRV), and 62.7% measured GRV every 4–8 hours. The most frequently used GRV threshold values were 200 mL (44.6%) and 150 mL (25.2%). Most nurses stopped feeding immediately when encountering high GRV (84.3%) or diarrhea (45.0%). The nasogastric feeding practices of many clinical nurses were not consistent with international guidelines. Conclusions Our study can provide an impetus for nursing administrators to revise their nasogastric feeding procedures, to promote compliance with evidence-based guidelines. more...

Summary Obesity-related osteoarthritis (OA) is a complex, multifactorial condition that can cause significant impact on patients’ quality of life. Whilst chronic inflammation, adipocytokines and metabolic factors are considered to be important pathogenic factors in obesity related OA, there has been limited investigation into the biomechanical impact of obesity on OA development. This review aims to demonstrate that mechanical factors are the major pathological cause of obesity-related OA. The effect of obesity on pathological changes to the osteochondral unit and surrounding connective tissues in OA is summarized, as well as the impact of obesity-related excessive and abnormal joint loading, concomitant joint malalignment and muscle weakness. An integrated therapeutic strategy based on this multi-factorial presentation is presented, to assist in the management of obesity related OA. The translational potential of this article Despite the high prevalence of obesity-related OA, there is no specific guideline available for obesity-related OA management. In this review, we demonstrated the pathological changes of obesity-related OA and summarized the impact of biomechanical factors by proposing a hypothetical model of obesity-related OA change. Therapeutic strategies based on adjusting abnormal mechanical effects are presented to assist in the management of obesity-related OA. more...

OBJECTIVES The management of non-small cell lung cancer (NSCLC) relies on the tumour-node-metastasis (TNM) stage, and the treatment regimen differs based on the N status. Positron emission tomography-computed tomography (PET-CT) has emerged as a powerful imaging tool for the detection of various cancers with a relatively low false-negative rate. We explored predictors to identify false-negative N2 disease in PET-CT. METHODS A total of 284 consecutive cN0 patients with peripheral NSCLC who underwent PET-CT scans followed by curative intent resections were enrolled as a training set to identify predictors of occult N2 metastases by multivariable analysis. The accuracy and cut-off values for the predictors were calculated using a receiver operating characteristic curve. Clinical and pathological data were analysed retrospectively. An additional 151 patients were collected as a test set to validate the results, including the occult N2 rate and accuracy. RESULTS In total, 8.5% (24/284) PET-CT-diagnosed N0 NSCLC cases had pathologically diagnosed N2 metastases. The SUVmax of the primary tumour was a unique independent risk factor for occult N2 NSCLC [P = 0.003, 95% confidence interval = 0.81-0.96, odds ratio (OR) = 0.88]. Occult N2 metastases occurred more frequently in the subcarinal (16/24) and right lower paratracheal lymph nodes (12/24). Accordingly, we divided the patients into two groups by SUVmax: the occult N2 rates in the SUVmax of more...

The ultimate goal of tissue engineering is to regenerate and/or replace fully functional tissue, or to stimulate the body to regenerate its own fully functional tissue (Vacanti and Langer in Lancet 354:SI32–SI34, 1999). This technology is of particular use in orthopaedics where various reconstructive operations are conducted throughout the musculoskeletal system. Many tissue engineering techniques utilize specific combinations of living cells, manufactured macromolecular biomaterials (matrices), and bioactive factors (cytokines and/or growth factors) to direct synthesis and organization of tissues (Fodor in Reproductive Biology and Endocrinology 1:102, 2003). The architecture and biochemical nature of matrices is a key aspect of cell-based tissue engineering. The matrix provides a vehicle for delivery of stem cells and progenitors to a desired site, and provides surfaces that facilitate the attachment, survival, migration, proliferation and differentiation of these cells. The ideal scaffold requirements for bone tissue engineering include biocompatibility, osteoconductive or osteoinductive capacity, high porosity that enables nutrient transport, infiltration of cells, degradability over suitable time scales, and interstitial flow of fluid (Bruder and Fox in Clinical Orthopaedics and Related Research 367:S68–83, 1999). The skeletons of Porifera appear to have unique properties that may provide for potential bioscaffolds in cell-based bone tissue engineering. These properties include the collagenous composition of the fiber skeleton, its ability to hydrate to a high degree, and the possession of open interconnected channels created by the fiber network (Green et al. in Tissue Engineering 9:1159–1166, 2003). In addition to this, the phylum has a tremendous diversity of skeletal architecture within the 8000 extant species currently described, many of which are readily available for use (Hooper and Van Soest in Systema Porifera: a guide to the classification of sponges. Academic/Plenum, New York, 2002). more...

High performance thermal insulating ethylene-propylene-diene monomer (EPDM) composites were obtained with the addition of hollow phenolic micro-sphere. The effects of the pretreatment and content of micro-sphere on various properties of EPDM composites were evaluated. Experimental results showed that thermal conductivity and specific gravity of EPDM composites significantly decreased, which was due to the intact and uniform dispersion of pretreated micro-sphere throughout the EPDM matrix. With the content increasing of pretreated micro-sphere, the specific gravity of EPDM composites linearly decreased while the thermal stability increased. Specifically, EPDM composites showed the three-layer structure after ablation and the addition of pretreated micro-sphere distinctively enhanced thermal insulating properties of EPDM composites, which was attributed to multi-type heat conductivity resulted from hollow micro-spheres. Hollow phenolic micro-sphere exhibited great potential in preparing new generation of light-weight and high thermal insulating materials. more...

Background Epigenetic regulation has emerged to be the critical steps for tumorigenesis and metastasis. Multiple histone methyltransferase and demethylase have been implicated as tumor suppressors or oncogenes recently. But the key epigenomic events in cancer cell transformation still remain poorly understood. Methods A breast cancer transformation model was established via stably expressing three oncogenes in primary breast epithelial cells. Chromatin immunoprecipitation followed by the next-generation sequencing of histone methylations was performed to determine epigenetic events during transformation. Western blot, quantitative RT-PCR, and immunostaining were used to determine gene expression in cells and tissues. Results Histones H3K9me2 and me3, two repressive marks of transcription, decrease in in vitro breast cancer cell model and in vivo clinical tissues. A survey of enzymes related with H3K9 methylation indicated that KDM3A/JMJD1A, a demethylase for H3K9me1 and me2, gradually increases during cancer transformation and is elevated in patient tissues. KDM3A/JMJD1A deficiency impairs the growth of tumors in nude mice and transformed cell lines. Genome-wide ChIP-seq analysis reveals that the boundaries of decreased H3K9me2 large organized chromatin K9 modifications (LOCKs) are enriched with cancer-related genes, such as MYC and PAX3. Further studies show that KDM3A/JMJD1A directly binds to these oncogenes and regulates their transcription by removing H3K9me2 mark. Conclusions Our study demonstrates reduction of histones H3K9 me2 and me3, and elevation of KDM3A/JMJD1A as important events for breast cancer, and illustrates the dynamic epigenomic mechanisms during breast cancer transformation. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0201-x) contains supplementary material, which is available to authorized users. more...

To observe the intervention of Shenfu Injection (SFI) on the hemodynamics and circulatory function during induction of general anesthesia for aged people, in order to optimize the medication of anesthesia inductive phase in aged people.Sixty aged patients scheduled to receive general anesthesia were equally randomized into 2 groups, the SFI group and the control group. SFI via intravenous drip (1 mL/kg diluted with 5 mL/kg saline) was administered to the SFI group 15 min before anesthesia induction and to the control group, normal saline was administered instead. Then the induction and intubation were implemented. The systolic blood pressure (SBP), diastolic pressure (DBP), heart rate (HR), central venous pressure (CVP), pulse saturation oxygen (SpO2), and the ST segment of ECG were observed at the different time points of induction, i.e. at the time of entry into the operating room (T1), ending the medication (T2), before the induction (T3), showing the lowest SBP in induction (T4), before and after intubation (T5 and T5). The dose and frequency of atropine and ephedrine applied in the inductive phase were observed as well.As compared with the baseline values measured at T1, CVP elevated at T2, T3, and T6 (P0.05), SBP and DBP descended at T4, T5, T6 in both groups; HR accelerated at T2, T3, and T6 in the control group; and HR at T4, T5 and T6 in both groups were significantly different (P0.05 or P0.01). Inter-group comparisons showed significant difference between groups in CVP at T2 (P0.05); so did SBP, DBP and HR at T4, T5 and T6 (P0.05 or P0.01).Application of SFI in the inductive phase of general anesthesia in aged people could evidently reduce the fluctuation of hemodynamics to prevent the occurrence of myocardial ischemia and improve it definitely. more...