Showing papers by "National Health and Family Planning Commission published in 2023"
18 Feb 2023
TL;DR: In this article , the authors dissect an inhibitory projection from the sensory thalamic reticular nucleus (sTRN) to the lateral habenula (LHb), which is activated by acute aversive stimuli.
Abstract: Abstract Chronic stress and chronic pain are two major predisposing factors to trigger depression. Enhanced excitatory input to the lateral habenula (LHb) has been implicated in the pathophysiology of depression. However, the contribution of inhibitory transmission remains elusive. Here, we dissect an inhibitory projection from the sensory thalamic reticular nucleus (sTRN) to LHb, which is activated by acute aversive stimuli. However, chronic restraint stress (CRS) weakens sTRN-LHb synaptic strength, and this synaptic attenuation is indispensable for CRS-induced LHb neural hyperactivity and depression onset. Moreover, artificially inhibiting sTRN-LHb circuit induces depressive-like behaviors in healthy mice, while enhancing this circuit relieves depression induced by both chronic stress and chronic pain. Intriguingly, neither neuropathic pain nor comorbid pain in chronic stress is affected by this pathway. Together, our study demonstrates a novel sTRN-LHb circuit in establishing and modulating depression, thus shedding light on potential therapeutic targets for preventing or managing depression.
1 citations
29 May 2023
TL;DR: In this article , the authors investigated the role of pyruvate metabolism in regulating neurogenesis in the adult brain and found that pyruvic acid metabolism plays a crucial role in specific functions such as pattern separation, learning and memory, and emotional regulation.
Abstract: Neurogenesis declines sharply in adulthood, partly because neural stem and progenitor cells (NSPCs) increasingly return to a dormant state as they age. However, innate NSPC pools are preserved in specific brain regions throughout an individual's lifetime. Petrelli et al.1 recently reported that inhibiting mitochondrial pyruvate import stimulated NSPCs to transition from a quiescent state to an active state, thereby promoting neurogenesis in both young and middle-aged mice. These findings indicate a novel approach for pro-neurogenic treatments. Most neurogenesis in the brain is completed during embryonic development, with only small pools of NSPCs remaining to generate new neurons postnatally. These NSPCs are primarily found in the hippocampal dentate gyrus and the subventricular zone. This biological process, particularly adult hippocampal neurogenesis (AHN), plays a crucial role in specific functions such as pattern separation, learning and memory, and emotional regulation. The pool of NSPCs in the adult brain gradually diminishes but is maintained at a certain level throughout life due to the self-renewal of neural stem cells during symmetric cell division. However, the extent of AHN declines much more sharply compared with the age-dependent depletion of the NSC pool. One of the most significant causes for this decline is the increasing rate at which NSCs in the adult brain transition from an active to a dormant state, remaining quiescent and refusing to proliferate to initiate neurogenesis. Thus, activating these dormant quiescent NSCs is pivotal for restoring neurogenesis. The mitochondrial pyruvate carrier (MPC) on the inner mitochondrial membrane is responsible for transporting the glycolytic end-product pyruvate from the cytosol into the mitochondria, thereby linking glycolysis to the tricarboxylic acid cycle and oxidative phosphorylation. Given that glycolysis plays a critical role in determining the activity state of NSCs, Petrelli et al.1 recently found that MPC expression was highest in quiescent NSPCs, as opposed to those that were active or proliferating. Moreover, both pharmacological blockage of MPC in vitro using the specific membrane-penetrating inhibitor UK5099 and selective deletion of the Mpc1 gene in NSPCs led to the proliferation of these quiescent NSPCs. Subsequently, the authors aimed to investigate the underlying metabolic mechanism. They ruled out the contribution of lactate elevation resulting from MPC loss-of-function as neither lactate supplementation nor downregulation affected the proliferation of NSPCs. Instead, they discovered that the elevated intracellular aspartate, presumed to be due to the upregulation of glutamic-oxaloacetic transaminase activity or enhanced mitochondrial aspartate import, played a significant role in activating quiescent NSPCs. In contrast to quiescent NSPCs, inhibiting MPCs did not affect the proliferation of already active NSPCs or the differentiation of their progeny. Lastly, the authors demonstrated that conditional Mpc1 deletion in NSPCs increased the number of newly generated neurons without affecting the neurite differentiation in one-month-old mice. Importantly, an increase in the number of newly formed neurons was also observed in middle-aged mice (9–11 months of age) with conditional Mpc1 deletion in NSPCs (Figure 1). The inhibition of mitochondrial pyruvate import activates quiescent NSPCs and promotes neurogenesis. The MPC is responsible for transporting pyruvate from the cytosol to mitochondria. Upon MPC loss-of-function, either through conditional knockout (cKO) of the Mpc1 gene or pharmacological inhibition using UK5099, quiescent NSPCs are activated to proliferate. This process leads to increased neurogenesis in the hippocampal dentate gyrus (DG) of both young adult and middle-aged mice. This important study sheds light on the critical role of mitochondrial pyruvate metabolism in regulating the balance between quiescence and activation in NSPCs. It also sparks increased interest in exploring the relationship between metabolism and stem cell biology across various disciplines, including neuroscience, cancer research, and tissue engineering. It has been observed that the total pyruvate dehydrogenase complex increases with age in mice brains.2 However, since pyruvate-involved oxidative activity and glucose metabolism have different effects on neuronal developmental timing in humans and mice,3 it warrants further investigation to determine whether MPC inhibition can also facilitate NSPC activation and neurogenesis in humans. Another question to consider is whether the forced activation of quiescent NSPCs through disrupted pyruvate metabolism might alter the fate of NSPC progeny, shifting them from neurogenesis to astrogliosis, or leading to the accelerated depletion of the adult NSC pool. It has been found that this can result in a temporary increase but ultimately long-term deficits in neurogenesis.4 Although there are numerous challenges, neurogenesis-targeted therapies, either by facilitating innate neurogenesis or engrafting exogenous stem cells, still hold great potential for rejuvenating aging brains and treating neurological disorders characterized by neuron loss or neurodegeneration.5 Considering the critical role of pyruvate metabolism in NSPCs for initiating neurogenesis, MPC inhibitors, whether administered alone or in combination with stem cell transplantation, could represent novel therapies for neurological injuries and neurodegenerative diseases. Yajiao Shi and Jie Zheng conceptualized and wrote the manuscript. You Wan revised the paper. This research was supported by the Peking University Talent Startup Fund (BMU2022YJ003) and the “Fundamental Research Funds for the Central Universities”. The authors declare that they have no conflicts of interest.
TL;DR: Wang et al. as mentioned in this paper detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine.
Abstract: Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene-environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.
TL;DR: Li et al. as discussed by the authors found that an estimated 121 145 cancer cases were diagnosed among children and adolescents in China between 2018 and 2020, and found a positive association between cancer incidence and regional socioeconomic status (p < 0·0001).
TL;DR: In this paper , a stacking machine learning (ML) model was proposed for predicting postoperative refraction errors and calculating EVO-ICL lens power, which is a new challenge in phakic IOL power calculation, especially for those with low and moderate myopia.
Abstract: Abstract Background Implantable collamer lens (ICL) has been widely accepted for its excellent visual outcomes for myopia correction. It is a new challenge in phakic IOL power calculation, especially for those with low and moderate myopia. This study aimed to establish a novel stacking machine learning (ML) model for predicting postoperative refraction errors and calculating EVO-ICL lens power. Methods We enrolled 2767 eyes of 1678 patients (age: 27.5 ± 6.33 years, 18–54 years) who underwent non-toric (NT)-ICL or toric-ICL (TICL) implantation during 2014 to 2021. The postoperative spherical equivalent (SE) and sphere were predicted using stacking ML models [support vector regression (SVR), LASSO, random forest, and XGBoost] and training based on ocular dimensional parameters from NT-ICL and TICL cases, respectively. The accuracy of the stacking ML models was compared with that of the modified vergence formula (MVF) based on the mean absolute error (MAE), median absolute error (MedAE), and percentages of eyes within ± 0.25, ± 0.50, and ± 0.75 diopters (D) and Bland-Altman analyses. In addition, the recommended spheric lens power was calculated with 0.25 D intervals and targeting emmetropia. Results After NT-ICL implantation, the random forest model demonstrated the lowest MAE (0.339 D) for predicting SE. Contrarily, the SVR model showed the lowest MAE (0.386 D) for predicting the sphere. After TICL implantation, the XGBoost model showed the lowest MAE for predicting both SE (0.325 D) and sphere (0.308 D). Compared with MVF, ML models had numerically lower values of standard deviation, MAE, and MedAE and comparable percentages of eyes within ± 0.25 D, ± 0.50 D, and ± 0.75 D prediction errors. The difference between MVF and ML models was larger in eyes with low-to-moderate myopia (preoperative SE > − 6.00 D). Our final optimal stacking ML models showed strong agreement between the predictive values of MVF by Bland-Altman plots. Conclusion With various ocular dimensional parameters, ML models demonstrate comparable accuracy than existing MVF models and potential advantages in low-to-moderate myopia, and thus provide a novel nomogram for postoperative refractive error prediction and lens power calculation.
TL;DR: Wang et al. as mentioned in this paper reported the comprehensive trends in CVD and risk factors in China from 1990 to 2019, and found that the number of CVD incidence, death, and disability-adjusted life years (DALYs) considerably increased by 132.8%, 89.1%, and 52.6%, respectively.
Abstract: Background: Understanding the changing profiles of cardiovascular disease (CVD) and modifiable risk factors is essential for CVD prevention and control. We aimed to report the comprehensive trends in CVD and risk factors in China from 1990 to 2019. Methods: Data on the incidence, death, and disability-adjusted life years (DALYs) of total CVD and its 11 subtypes for China were obtained from the Global Burden of Disease Study 2019. The CVD burden attributable to 12 risk factors was also retrieved. A secondary analysis was conducted to summarize the leading causes of CVD burden and attributable risk factors. Results: From 1990 to 2019, the number of CVD incidence, death, and DALYs considerably increased by 132.8%, 89.1%, and 52.6%, respectively. Stroke, ischemic heart disease, and hypertensive heart disease accounted for over 95.0% of CVD deaths in 2019 and remained the top three causes during the past 30 years. Between 1990 and 2019, the age-standardized rate of stroke decreased significantly (percentage of decreased incidence: -9.3%; death: -39.8%; DALYs: -41.6%), while the rate of ischemic heart disease increased (percentage of increased incidence: 11.5%; death: 17.6%; DALYs: 2.2%). High systolic blood pressure, unhealthy diet, tobacco, and air pollution continued to be the major contributors to CVD deaths and DALYs (attributing to over 70% of the CVD burden), and the high body mass index (BMI)-associated CVD burden had the largest increase between 1990 and 2019. Conclusions: The significant increases in the number of CVD incident cases, deaths, and DALYs suggest that the CVD burden is still a concern. Intensified strategies and policies are needed to maintain promising progress in stroke and to reduce the escalating burden of ischemic heart disease. The CVD burden attributable to risk factors has not yet made adequate achievements; even worse, high BMI has contributed to the increasing CVD burden.
TL;DR: In this paper , a single iridium (III) solvent complex-based electrogenerated chemiluminescence (ECL) and photoluminescent (PL) sensor array was used for the discrimination of bases in oligonucleotides.
TL;DR: Wang et al. as mentioned in this paper investigated the relationship between hair chromium and skin aging among rural housewives in Shanxi Province of northern China, and concluded that skin aging might be positively associated with skin chromium.
29 Mar 2023
TL;DR: Wang et al. as discussed by the authors examined the associations between weight self-misperception and obesity-related knowledge, attitudes, lifestyles and cardio-metabolic markers among Chinese paediatric population.
Abstract: Abstract Objective: The relationships between childhood weight self-misperception and obesity-related factors particularly health markers have not been extensively discussed. This study aims to examine the associations between weight self-misperception and obesity-related knowledge, attitudes, lifestyles and cardio-metabolic markers among Chinese paediatric population. Design: Cross-sectional study. Setting: Data sourced from a national survey in Chinese seven provinces in 2013. Participants: Children and adolescents aged 5–19 years. Results: Of the total 14 079 participants, there were 14·5 % and 2·2 % participants over-estimated and under-perceived their weight, respectively. Multi-variable logistic regression was applied to calculate OR and 95 % CI (95 % Cl) of obesity-related behaviours and cardio-metabolic markers by actual and perceived weight status. Individuals who perceived themselves as overweight/obese were more likely to have prolonged screen time, insufficient dairy intake and over sugar-sweetened beverages consumption (all P < 0·05), regardless of their weight. Furthermore, actual overweight/obese individuals had higher odds of abnormal cardio-metabolic markers, but a smaller magnitude of association was found among weight under-estimators. Among non-overweight/obese individuals, weight over-estimation was positively associated with abdominal obesity (OR: 10·49, 95 % CI: 7·45, 14·76), elevated blood pressure (OR: 1·30, 95 % CI: 1·12, 1·51) and dyslipidemia (OR: 1·43, 95 % CI: 1·29, 1·58). Conclusions: Weight over-perception was more prevalent than under-estimation, particularly in girls. Weight over-estimators tended to master better knowledge but behave more unhealthily; both weight over-perception and actual overweight/obesity status were associated with poorer cardio-metabolic markers. Future obesity intervention programmes should additionally pay attention to the population with inaccurate estimation of weight who were easily overlooked.
TL;DR: In this article , the associations of breast milk leptin with maternal metabolic profiles in pregnancy and dietary patterns during lactation were explored, and only diet quality distance was significantly associated with leptin concentrations in breast milk.
Abstract: Breast milk leptin plays a potential role in preventing childhood obesity. However, the associations of breast milk leptin with maternal metabolism in pregnancy and dietary patterns during lactation are still unclear. We aimed to explore associations of breast milk leptin with maternal metabolic profiles in pregnancy and dietary patterns during lactation. A total of 332 participants were recruited for this retrospective cohort study. Breast milk samples were collected at approximately 6 weeks postpartum. Breast milk leptin and twenty-three metabolic profiles in pregnancy were measured in this study. A semi-quantitative FFQ was used to gather dietary information during lactation. Both principal component analysis and the diet balance index were used to derive dietary patterns. Among twenty-three maternal metabolic profiles, maternal serum glucose (β = 1·61, P = 0·009), γ-glutamyl transferase (β = 0·32, P = 0·047) and albumin (β = -2·96, P = 0·044) in pregnancy were correlated with breast milk leptin. All dietary patterns were associated with breast milk leptin. Given the joint effects of maternal metabolism in pregnancy and dietary patterns during lactation, only diet quality distance was significantly associated with leptin concentrations in breast milk (low level v. almost no diet problem: β = -0·46, P = 0·011; moderate/high level v. almost no diet problem: β = -0·43, P = 0·035). In conclusion, both maternal metabolism in pregnancy and dietary patterns during lactation were associated with breast milk leptin. Maternal diet balance during lactation was helpful to improve breast milk leptin concentration.
01 Jan 2023
TL;DR: In this paper , the authors performed metabolomic analysis in plasma samples from acute venous thrombosis patients and healthy controls and confirmed the results in validation cohorts, and the area under the curve (AUC) for metabolites associated with valine, leucine, and isoleucine biosynthesis was 0.934.
Abstract: Cerebral venous thrombosis (CVT) is a special and easily misdiagnosed or undiagnosed subtype of stroke. To identify specific biomarkers with a high predictive ability for the diagnosis of acute CVT, we performed metabolomic analysis in plasma samples from acute CVT patients and healthy controls and confirmed the results in validation cohorts. In the discovery stage, there were 343 differential metabolites, and the caffeine metabolism pathway and the biosynthesis pathway for the branched chain amino acids (BCAAs) valine, leucine, and isoleucine were two significant pathways between the CVT and healthy cohorts. The area under the curve (AUC) for metabolites associated with valine, leucine, and isoleucine biosynthesis was 0.934. In the validation stage, the BCAA concentrations demonstrated an AUC of 0.935 to differentiate patients with acute CVT from the control cohort. In addition, BCAAs combined with D-dimer levels were used to establish a diagnostic model for CVT, and the AUC was 0.951, showing good diagnostic efficacy of separating CVT patients from the control cohort. BCAAs as plasma biomarkers deserve to be further studied and even developed in clinical CVT management.