British medical journal
The relationship between adult weight change and all-cause and specific factor mortality.
Professor Pan An from Huazhong University of Science and Technology analyzed the relationship between adult weight change and all-cause and specific factor mortality. 20 19, 10 On June 6th, the British Medical Journal published this achievement online.
This prospective cohort study analyzed the data from the National Health and Nutrition Survey of the United States during 1988- 1994 and 1999-20 14 years. * * A total of 3605 1 participants, all over 40 years old, measured their baseline weight and height, and recalled their 25 years old and 65438 years old.
The average follow-up was 12.3 years, and 10500 people died. Compared with participants who maintain normal weight, the all-cause mortality and heart disease mortality of participants who gain weight from youth to middle age are 22% and 49% higher, respectively, and the risk ratios are 1.22 and 1.49, while the participants who gain weight from youth to middle age have nothing to do with the risk of death.
Participants who changed from fat to not fat from middle age to old age had an increased risk of all-cause death and heart disease death, and the risk ratios were 1.30 and 1.48, respectively, while participants who became fat from middle age to old age had no relationship with the risk of death.
Obese participants throughout adulthood are always related to the increase of all-cause mortality: the risk ratio from youth to middle age is 1.72, from youth to old age is 1.6 1, and from middle age to old age is 1.20.
The correlation between maximum overweight and adult mortality is weak or zero. There is no significant correlation between different weight change patterns and cancer mortality.
In short, obesity in adulthood, weight gain in youth to middle age and weight loss in middle age to old age are all related to the increase in mortality. It is very important to prevent premature death in old age if we maintain a normal weight throughout adulthood, especially in youth.
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● The study found that the prognosis of very premature infants who were transferred to another hospital after delivery was very poor.
Recently, Chris Gale of Imperial College London, London, UK and his team studied the relationship between premature infants' delivery in non-tertiary hospitals, early metastasis and mortality after birth, and severe brain injury. This research result was published online in the British Medical Journal on June 6th, 2065438+2009+65438.
The research team analyzed the population data from 2008 to 20 15 in the British National Neonatal Research Database. * * * Very premature infants 17577 cases born less than 28 weeks were divided into two groups according to the hospital of birth and the transfer within 48 hours after birth: upward transfer group 2 158 cases were transferred from non-tertiary hospitals to tertiary hospitals; 2668 cases in non-tertiary nursing group were born in non-tertiary hospitals and did not transfer to other hospitals; Control group 10866 cases were born in a tertiary hospital and were not transferred; 305 cases were transferred between horizontal transfer group and tertiary hospitals. These babies were matched with the propensity score to eliminate the differences in general data.
Compared with the control group, the mortality rate of infants in the upward transfer group was similar before discharge, but the probability of severe brain injury increased significantly, and the survival rate without severe brain injury decreased significantly. The infant mortality rate in the non-tertiary nursing group was significantly higher than that in the control group, but the survival rate with or without severe brain injury was similar.
Compared with the upward transfer group, the infant mortality rate in the non-tertiary care group was similar before discharge, but the incidence of severe brain injury was significantly reduced and the survival rate without severe brain injury was significantly improved. There was no significant difference in prognosis between horizontal metastasis group and control group.
In short, the prognosis of very premature infants who gave birth in a non-tertiary hospital and were transferred within 48 hours is worse than that in a tertiary hospital. The research group suggested that perinatal services should be provided, so that very premature babies could give birth in tertiary hospitals as much as possible, rather than being transferred to other hospitals after delivery.
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New England Journal of Medicine
● 20-year follow-up of statin therapy in children with familial hypercholesterolemia
The research team of John J.P. Kastelein of the University Medical Center in Amsterdam, the Netherlands, recently published the results of their 20-year follow-up of children with familial hypercholesterolemia taking statins. This research result was published in the New England Journal of Medicine, 5438+09, 17, published in October 2006.
Familial hypercholesterolemia is characterized by a serious increase in the level of low-density lipoprotein cholesterol and the premature occurrence of cardiovascular diseases. Children who take statins have a good short-term effect, but there is little long-term follow-up on their cardiovascular risk changes.
The research team followed up the children who received statins for 20 years. * * * 2 14 patients with familial hypercholesterolemia and 95 healthy brothers and sisters were followed up.
These patients have participated in a placebo-controlled trial on the efficacy and safety of pravastatin two years ago. All participants filled out questionnaires, provided blood samples and measured carotid intima-media thickness.
The follow-up results showed that the average LDL level of patients decreased from 237.3 mg/dL to 160.7 mg/dL, a decrease of 32%. 37 patients achieved the treatment goal, that is, the LDL level was lower than 100 mg/dL.
During the whole follow-up period, the average progression of carotid intima-media thickness in patients with familial hypercholesterolemia was 0.0056 mm, while that in healthy compatriots was 0.0057 mm.
At the age of 39, the cumulative incidence of cardiovascular events and the death caused by cardiovascular causes in patients with familial hypercholesterolemia were 65,438 0% and 0%, respectively, which were significantly lower than those in their parents with the same disease.
In a word, statin therapy for patients with familial hypercholesterolemia from childhood can slow down the progress of carotid intima-media thickness and reduce the risk of cardiovascular disease in adulthood.
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cellular metabolism
Ketosis can improve polycystic kidney.
Thomas Weimbs, a research group at the University of California, Santa Barbara, has made new progress. They found that ketosis can improve the growth of renal cysts in polycystic kidney disease. 20 19, 10 On June 7th, the internationally renowned academic journal Cell-Metabolism published this achievement online.
Recent studies have shown that a slight reduction in food intake will slow down the progress of PKD in mouse models, but it is not clear whether this effect is only due to calorie reduction or other aspects of diet.
The researchers found that this benefit is due to the induction of ketosis. In PKD rat model, limiting food intake without reducing calories can strongly inhibit mTOR signal transduction, proliferation and fibrosis of affected kidneys. Ketogenic diet has a similar effect and leads to the regression of renal cystic burden.
Acute fasting in PKD models of rats, mice and cats can lead to rapid reduction of cyst volume, while oral administration of β -hydroxybutyrate ketone in rats can strongly inhibit the progress of PKD.
These results show that the cystic cell metabolism of PKD is inelastic and can be utilized by dietary intervention or BHB supplementation, which indicates a new method to treat PKD.
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cancer cell
Neuroblastoma subtypes with low atrx gene mutation are sensitive to EZH2 inhibitors.
Emily Bernstein's research team in icahn school of medicine at mount sinai, USA, found that neuroblastoma fused with mutation in the ATRX gene framework is very sensitive to EZH2 inhibition, which is achieved by regulating the characteristic genes of neurons. Related papers were published online in Cancer Cell on 20 19- 10/7.
The researchers found that the fusion protein in the reading frame of ATRX redistributed from the chromatin rich in H3K9me3 to the promoter that activated the gene, and identified the other genes as the target of ATRX IFF, whose activation promoted the silencing of the neuron differentiation gene.
The researchers further showed that ATRX IFF cells were sensitive to EZH2 inhibitors due to the inhibition of neurogenic genes.
Therefore, the researchers proved that the structural change of ATRX is not a loss of function, and proposed EZH2 inhibitors as a potential therapy for ATRX IFF neuroblastoma.
It is reported that ATRX gene changes frequently occur in neuroblastoma of adolescents and young people. It is particularly interesting that deleting the large N-terminal fragment of ATRX can produce IFF protein without key chromatin interaction domain, while retaining SWI/SNF-like helicase region.
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Cell stem cells
● The research reveals the regulatory elements that drive nerve induction.
Nir Yosef of the University of California, Berkeley and Nadav Ahituv of the University of San Francisco collaborated to identify and characterize the regulatory elements that drive neural induction. The results of this study were published in the journal Cell-Stem Cells from June to October, 2009.
Taking the neural induction of human pluripotent stem cells as an example, the researchers tested seven time points in the process of early neural differentiation by using RNA sequencing, chromatin immunoprecipitation sequencing and transposase accessible chromatin sequencing.
The researchers found that the change of DNA accessibility preceded H3K27ac, followed by the change of gene expression. By testing the activities of 2464 candidate regulatory sequences at all seven time points using large-scale parallel reporter gene analysis, the researchers showed that many of these sequences had temporal activity patterns related to endogenous gene expression and chromatin changes in their respective cells.
By combining the prioritization method of all genomes and MPRA data, the researchers further identified the key transcription factors that drive the fate of nerves.
These results provide a comprehensive resource of genes and regulatory elements, that is, these genes and regulatory elements can coordinate neural induction and clarify the time frame in the process of differentiation.
It is known that epigenetic regulation and lineage-specific gene expression jointly drive cell differentiation, but the time sequence interaction between these processes is largely unknown.
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Cell: Volume 3 179
● New progress has been made in somatic cell reprogramming.
Wu Jun of the Southwest Medical Center of the University of Texas and Juan Carlos Izpisua Belmont of the Salk Institute of Biology collaborated to induce blastocyst-like structures from mouse embryos or adult cells. The research results were published in the issue of Cell in 20 19, 17 10.
From a single stem cell type to pluripotent stem cells with expansion potential, researchers have established a 3D differentiation system, which can generate blastocyst-like structures through pedigree separation and self-organization.
EPS- blastocyst is similar to blastocyst in morphology and cell type, which simulates the key morphogenetic events in the early development of embryos before and after in vitro implantation. After transplantation, some EPS blastocysts were implanted, which caused decidualization of endometrium and produced living tissue in uterus.
Single cell RNA sequencing analysis showed that EPS blastocyst contained all three blastocyst cell types, and its transcription level was similar to that of normal blastocyst. The evidence provided by the study shows that EPS blastocysts can be produced by adult cells through cell reprogramming.
EPS blastocyst provides a unique platform for studying early embryogenesis and paves the way for creating feasible synthetic embryos by using cultured cells.
It is understood that a single mouse blastomere from embryo to 8-cell stage can produce the whole blastocyst. Whether the cells cultured in the laboratory retain similar totipotency is unknown.
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science
● Discover the temporal and spatial expansion of the developing cerebellar ancestral area.
Kathleen J. Millen's team at Seattle Children's Institute in the United States found that the temporal and spatial expansion of the primary ancestral area of the developing human cerebellum. The research results were published online in Science on 20 19 10 6 17.
They put forward the histological and molecular analysis of human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include temporal and spatial expansion of primary progenitor cells in the ventricles and rhomboid lips to include the subventricular region containing basal progenitor cells.
Through the development of cerebellum, the human rhomboid lip lasts longer than that of mice, and changes in morphology, forming progenitor cells in the posterior lobule, which is not found in other organisms or even non-human primate macaques.
The developmental retardation of human rhomboid lip is related to cerebellar vermis hypoplasia and Dandy-Walker malformation. The existence of neural progenitor cells of these specific species has improved our understanding of human cerebellar developmental disorders.
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● Research found adaptive ancient human genes.
The research team of Evan E. Eichler of the University of Washington in the United States has made progress in this research. They found that the change of copy number adapted to the infiltration of ancient genes and previously unknown human genes. This research was published in the journal Science on June 8th, 2006, 5438+09, 10.
The researchers found that the stratified CNV was significantly correlated with the positive selection characteristics of melanesians, and provided evidence for the adaptive infiltration of a large number of CNVs on chromosomes16p1.2 and 8p2 1.3 from Denisova and Neanderthals respectively.
Using long reading sequence data, the researchers reconstructed the structure and complex evolutionary history of these polymorphisms, and showed that both genes encoded positive selection genes that most people did not have.
The results of this study show that a large number of CNV originated from ancient humans and infiltrated into modern humans have played an important role in the adaptation of the local population, and represent the source of large-scale genetic variation that has not been fully studied.
According to reports, CNV bears greater selection pressure than single nucleotide variation, but its role in ancient gene penetration and adaptation has not been systematically studied.
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Science: Volume 366, No.6463
● Scientists reveal changes in marine and terrestrial biodiversity.
Researchers such as Shane A. Blowes of the German Biodiversity Research Center, Sarah R. Supp of Dennison University in the United States and Maria Dornelas of St Andrews University in the United Kingdom have made new achievements. Their research reveals the changes of marine and terrestrial biodiversity. This achievement was published in the June 2019/kloc-0+08 issue of Science.
Using more than 50,000 time series of biodiversity in 239 studies, the researchers studied the spatial changes of species richness and composition changes, and found obvious geographical changes of biodiversity changes. It is a common phenomenon that the composition changes rapidly, the marine biota exceeds the overall trend, and the terrestrial biota lags behind the overall trend.
Although it is found in some marine studies that the annual increase or decrease of population richness is as high as 20%, its average richness has not changed. On the local scale, extensive composition recombination is usually decoupled from the change of richness, and the change of biodiversity in the ocean is the strongest and greatest.
Researchers say that human activities have fundamentally changed biodiversity. The prediction of global decline is contrary to the trend of local height change, indicating that the change of biodiversity may have spatial structure.
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