Five days of integrative body-mind training (IBMT) improves attention and self-regulation in comparison with the same amount of relaxation training. This paper explores the underlying mechanisms of this finding. We measured the physiological and brain changes at rest before, during, and after 5 days of IBMT and relaxation training. During and after training, the IBMT group showed significantly better physiological reactions in heart rate, respiratory amplitude and rate, and skin conductance response (SCR) than the relaxation control. Differences in heart rate variability (HRV) and EEG power suggested greater involvement of the autonomic nervous system (ANS) in the IBMT group during and after training. Imaging data demonstrated stronger subgenual and adjacent ventral anterior cingulate cortex (ACC) activity in the IBMT group. Frontal midline ACC theta was correlated with highfrequency HRV, suggesting control by the ACC over parasympathetic activity. These results indicate that after 5 days of training, the IBMT group shows better regulation of the ANS by a ventral midfrontal brain system than does the relaxation group. This changed state probably reflects training in the coordination of body and mind given in the IBMT but not in the control group. These results could be useful in the design of further specific interventions.anterior cingulate cortex ͉ body-mind interaction ͉ IBMT I n a previous study (1, 2), 80 Chinese undergraduates were randomly assigned to an experimental group (integrative body-mind training, IBMT) or to a control group (relaxation training) for 5 days of short-term training (20 min per day). Before training, no differences were found for behavioral, endocrine, and immune measures between the 2 groups. After 5 days of training, the IBMT group showed significantly greater improvement of performance in executive attention and positive mood, significantly reduced stress as measured by cortisol secretion following a stressful experience, and increased immunoreactivity compared to participants with the same amount of relaxation training.IBMT was adopted from traditional Chinese medicine and incorporates aspects of meditation and mindfulness training. Cooperation between the body and the mind is emphasized in facilitating and achieving a meditative state (1, 3). Combined use of body and mind training is consistent with studies in which changes in the body influence and facilitate emotional and cognitive processing (4-7). Relaxation training, on the other hand, requires voluntary control in progressive relaxation of the muscles of the body, sending feedback to influence the mind (8, 9). During relaxation training, thinking about control operations could interfere with training effects (1, 3), leading to different results between the IBMT and the relaxation groups.To test the mechanisms of training, this study used random assignment of 86 Chinese undergraduates to 2 experimental (IBMT) or control (relaxation) groups. Forty-six subjects participated in experiment I using brain imaging and physiologica...

Interleukin-17 (IL-17)-producing CD4M ore than 350 million people worldwide suffer from persistent infection with hepatitis B virus (HBV) and are at risk for developing liver cirrhosis and hepatocellular carcinoma. 1 HBV itself is noncytopathic, but immune-mediated liver damage often occurs in patients with both acute and chronic HBV infection. Such damage has conventionally been attributed to killing of infected hepatocytes by virus-specific cytotoxic CD8 ϩ T cells. [2][3][4] Increasing evidence, however, suggests that non-HBV-specific inflammatory infiltration into the liver is likely responsible for hepatic pathology in patients with chronic hepatitis B (CHB). 5,6 For example, in HBV infection activated HBV-specific CD8 ϩ T cells are often present at high levels in the livers of patients without evident liver inflammation; by contrast, nonantigen-specific lymphocytes were found to be massively infiltrated into the livers of patients with hepatic inflammation. 7 An HBV transgenic mouse model further reinforced the concept that liver inflammation initiated by virus-specific CD8 ϩ T cells is amplified by other lymphocytes. 4,8 Indeed, a large number of immune cells, including myeloid dendritic cells (mDCs), plasmacytoid dendritic cells, and FoxP3-positive regulatory T cells can

Importance In China diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes. Objective To assess the proportional excess mortality associated with diabetes, and to estimate the diabetes-related absolute excess mortality in rural and urban China. Design, setting, and participants A 7-year nationwide prospective study of 512,869 adults aged 30-79 years from 10 (5 rural, 5 urban) localities across China, recruited from 6/2004 to 7/2008 and followed until 1/2014. Exposure Diabetes (previously diagnosed or screen-detected) recorded at baseline. Main outcome measures All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratios (RRs) comparing those with versus without diabetes at baseline. Results Overall, the mean (SD) age was 51.5 (10.7) years, 59% (n=302,618) were women, and 5.9% (n=30,280) had diabetes (rural 4.1%, urban 8.1%, men 5.8%, women 6.1%, previously diagnosed 3.1%, screen-detected 2.8%). During 3.64 million person-years of follow-up, there were 24,909 deaths, including 3,384 among individuals with diabetes. Compared to adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100,000; adjusted RR, 2.00 [95%CI, 1.93 to 2.08]), which was higher in rural than urban areas (rural RR, 2.17 [95%CI 2.07 to 2.29]; urban RR, 1.83 [95%CI, 1.73 to 1.94]). Presence of diabetes was associated with increased mortality from ischaemic heart disease (3287 deaths; RR, 2.40 [95%CI, 2.19 to 2.63]), stroke (4444 deaths; RR, 1.98 [95%CI, 1.81 to 2.17]), chronic liver disease (481 deaths; RR, 2.32 [95%CI, 1.76 to 3.06]), infections (425 deaths; RR, 2.29 [95%CI, 1.76 to 2.99]), and cancer of the liver (1325 deaths; RR, 1.54 [95%CI 1.28 to1.86]), pancreas (357 deaths; RR, 1.84 [95%CI, 1.35 to 2.51]), female breast (217 deaths; RR, 1.84 [95%CI, 1.24 to 2.74]), and female reproductive system (210 deaths; RR, 1.81 [95%CI, 1.20 to 2.74]). For chronic kidney disease (365 deaths), the RR was higher in rural than urban areas (18.69 [95%CI, 14.22 to 24.57] versus 6.83 [95%CI, 4.73 to 9.88]). Among those with diabetes, 10% of all deaths (rural 16%, urban 4%) were due to definite or probable diabetic ketoacidosis or coma (408 deaths). Conclusions and relevance Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and non-cardiovascular diseases. Although diabetes was more common in urban areas, it was associated with a greater excess mortality in rural areas.

Programmed death 1 (PD-1) and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of cytotoxic CD8 1 T lymphocytes, the main effector cells in hepatocellular and blocking PD-L1 reversed this effect. Therefore, this study extends our knowledge of the role of the PD-1/PD-L1 pathway in tumor evasion and provides evidence for a new therapeutic target in HCC patients.

In adult Chinese, physical activity varies substantially by occupation, and lack of physical activity and excess sedentary leisure time are independently and jointly associated with greater adiposity.

Nasopharyngeal carcinoma (NPC) has a particularly high prevalence in southern China, southeastern Asia and northern Africa. Radiation resistance remains a serious obstacle to successful treatment in NPC. This study aimed to explore the metabolic feature of radiation-resistant NPC cells and identify new molecular-targeted agents to improve the therapeutic effects of radiotherapy in NPC. Methods: Radiation-responsive and radiation-resistant NPC cells were used as the model system in vitro and in vivo. Metabolomics approach was used to illustrate the global metabolic changes. 13C isotopomer tracing experiment and Seahorse XF analysis were undertaken to determine the activity of fatty acid oxidation (FAO). qRT-PCR was performed to evaluate the expression of essential FAO genes including CPT1A. NPC tumor tissue microarray was used to investigate the prognostic role of CPT1A. Either RNA interference or pharmacological blockade by Etomoxir were used to inhibit CPT1A. Radiation resistance was evaluated by colony formation assay. Mitochondrial membrane potential, apoptosis and neutral lipid content were measured by flow cytometry analysis using JC-1, Annexin V and LipidTOX Red probe respectively. Molecular markers of mitochondrial apoptosis were detected by western blot. Xenografts were treated with Etomoxir, radiation, or a combination of Etomoxir and radiation. Mitochondrial apoptosis and lipid droplets content of tumor tissues were detected by cleaved caspase 9 and Oil Red O staining respectively. Liquid chromatography coupled with tandem mass spectrometry approach was used to identify CPT1A-binding proteins. The interaction of CPT1A and Rab14 were detected by immunoprecipitation, immunofluorescence and in situ proximity ligation analysis. Fragment docking and direct coupling combined computational protein-protein interaction prediction method were used to predict the binding interface. Fatty acid trafficking was measured by pulse-chase assay using BODIPY C16 and MitoTracker Red probe. Results: FAO was active in radiation-resistant NPC cells, and the rate-limiting enzyme of FAO, carnitine palmitoyl transferase 1 A (CPT1A), was consistently up-regulated in these cells. The protein level of CPT1A was significantly associated with poor overall survival of NPC patients following radiotherapy. Inhibition of CPT1A re-sensitized NPC cells to radiation therapy by activating mitochondrial apoptosis both in vitro and in vivo. In addition, we identified Rab14 as a novel CPT1A binding protein. The CPT1A-Rab14 interaction facilitated fatty acid trafficking from lipid droplets to mitochondria, which decreased radiation-induced lipid accumulation and maximized ATP production. Knockdown of Rab14 attenuated CPT1A-mediated fatty acid trafficking and radiation resistance. Conclusion: An active FAO is a vital signature of NPC radiation resistance. Targeting CPT1A could be a beneficial regimen to improve the therapeutic effects of radiotherapy in NPC patients. Importantly, the CPT1A-Rab14 interaction plays roles in CPT1A-mediated radiation...

SummaryBackgroundThe age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China.Methods512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure.FindingsDuring a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually.InterpretationAmong adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality.FundingUK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China.

Mitochondria are the major cellular energy‐producing organelles and intracellular source of reactive oxygen species. These organelles are responsible for driving cell life and death through mitochondrial network structure homeostasis, which is determined by a balance of fission and fusion. Recent advances revealed that a number of components of the fission and fusion machinery, including dynamin‐related protein 1 (Drp1), mitofusin1/2 (Mfn1/2) and Optic atrophy 1 (OPA1), that have been implicated in mitochondrial shape changes are indispensible for autophagy, apoptosis and necroptosis. Drp1 is the main regulator of mitochondrial fission and has become a key point of contention. The controversy focuses on whether Drp1 is directly involved in the regulation of cell death and, if involved, whether is it a stimulator or a negative regulator of cell death. Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Thus, the fragmented ratio can reflect tumor progression that predicts prognosis and therapeutic response. In addition, we investigate whether the targeting of the mitochondrial fission protein Drp1 could be a novel therapeutic approach.