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Enhanced liver but not muscle OXPHOS in diabetes and reduced glucose output by complex I inhibition
Mitochondrial function is critical in energy metabolism. To fully capture how the mitochondrial function changes in metabolic disorders, we investigated mitochondrial function in liver and muscle of animal models mimicking different types and stages of diabetes. Type 1 diabetic mice were induced by streptozotocin (STZ) injection. The db/db mice were used as type 2 diabetic model. High‐fat diet‐induced obese mice represented pre‐diabetic stage of type 2 diabetes. Oxidative phosphorylation (OXPHOS) of isolated mitochondria was measured with Clark‐type oxygen electrode. Both in early and late stages of type 1 diabetes, liver mitochondrial OXPHOS increased markedly with complex IV‐dependent OXPHOS being the most prominent. However, ATP, ADP and AMP contents in the tissue did not change. In pre‐diabetes and early stage of type 2 diabetes, liver mitochondrial complex I and II‐dependent OXPHOS increased greatly then declined to almost normal at late stage of type 2 diabetes, among which alteration of complex I‐dependent OXPHOS was the most significant. In contrast, muscle mitochondrial OXPHOS in HFD, early‐stage type 1 and 2 diabetic mice, did not change. In vitro, among inhibitors to each complex, only complex I inhibitor rotenone decreased glucose output in primary hepatocytes without cytotoxicity both in the absence and presence of oleic acid (OA). Rotenone affected cellular energy state and had no effects on cellular and mitochondrial reactive oxygen species production. Taken together, the mitochondrial OXPHOS of liver but not muscle increased in obesity and diabetes, and only complex I inhibition may ameliorate hyperglycaemia via lowering hepatic glucose production.
Journal Article
Frequency and mortality of sepsis and septic shock in China: a systematic review and meta-analysis
Background
Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China.
Methods
We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock.
Results
Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I
2
= 99.2%; p < 0.001), and the pooled mortality of sepsis, severe sepsis and septic shock were 29.0% (95% CI 25.3%–32.8%, I
2
= 92.1%; p = 0), 31.1% (95% CI 25.3% to 36.9%, I
2
= 85.8%; p < 0.001) and 37.3% (95% CI 28.6%–46.0%, I
2
= 93.5%; p < 0.001). There was significant heterogeneity between studies. With a small number of included studies and the changing definition of sepsis, trends in sepsis frequency and mortality were not sufficient for analysis. Epidemiological data on sepsis in the emergency department (ED) are severely lacking, and more research is urgently needed in this area is urgently needed
.
Conclusions
Our findings indicated that the frequency and mortality of sepsis and septic shock in China were much higher than North America and Europe countries. Based on our results, an extremely high incidence and mortality of sepsis and septic shock in China's mainland requires more healthcare budget support. Epidemiological data on sepsis and septic shock in ED are severely lacking, and more research is urgently needed in this area.
Trial registration
This systematic review was conducted according to the statement of the preferred reporting items for systematic review (PROSPERO CRD42021243325) and the meta-analysis protocols (PRISMA-P).
Journal Article
Sepsis-Induced Cardiomyopathy: Mechanisms and Treatments
Sepsis is a lethal syndrome with a high incidence and a weighty economy burden. The pathophysiology of sepsis includes inflammation, immune dysfunction, and dysfunction of coagulation, while sepsis-induced cardiomyopathy (
), defined as a global but reversible dysfunction of both sides of the heart induced by sepsis, plays a significant role in all of the aspects above in the pathogenesis of sepsis. The complex pathogenesis of
involves a combination of dysregulation of inflammatory mediators, mitochondrial dysfunction, oxidative stress, disorder of calcium regulation, autonomic nervous system dysregulation, and endothelial dysfunction. The treatments for
include the signal pathway intervention, Chinese traditional medicine, and other specific therapy. Here, we reviewed the latest literatures on the mechanisms and treatments of
and hope to provide further insights to researchers and create a new road for the therapy of sepsis.
Journal Article
Systemic immune-inflammation index and all-cause and cause-specific mortality in sarcopenia: a study from National Health and Nutrition Examination Survey 1999-2018
Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort.
We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness.
Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models.
Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.
Journal Article
A novel efficient strategy to generate liver sinusoidal endothelial cells from human pluripotent stem cells
Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as
EPAS1, LIFR, and NID1
, as well as several previously revealed markers, such as
CLEC4M, CLEC1B, CRHBP
and
FCN3
. These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.
Journal Article
Multi-User Opportunistic Spectrum Access for Cognitive Radio Networks Based on Multi-Head Self-Attention and Multi-Agent Deep Reinforcement Learning
Aiming to address the issue of multi-user dynamic spectrum access in an opportunistic mode in cognitive radio networks leading to low sum throughput, we propose a multi-user opportunistic spectrum access method based on multi-head self-attention and multi-agent deep reinforcement learning. First, an optimization model for joint channel selection and power control in multi-user systems is constructed based on centralized training with a decentralized execution framework. In the training phase, the decision-making policy is optimized using global information, while in the execution phase, each agent makes decisions according to its observations. Meanwhile, a multi-constraint dynamic proportional reward function is designed to guide the agent in selecting more rational actions by refining the constraints and dynamically adjusting the reward proportion. Furthermore, a multi-head self-attention mechanism is incorporated into the critic network to dynamically allocate attention weights to different users, thereby enhancing the ability of the network to estimate the joint action value. Finally, the proposed method is evaluated in terms of convergence, throughput, and dynamic performance. Simulation results demonstrate that the proposed method significantly improves the sum throughput of secondary users in opportunistic spectrum access.
Journal Article
A Self-Adaptive Thresholding Approach for Automatic Water Extraction Using Sentinel-1 SAR Imagery Based on OTSU Algorithm and Distance Block
As an indispensable material for animals, plants and human beings, obtaining accurate water body information rapidly is of great significance to maintain the balance of ecosystems and ensure normal production and the life of human beings. Due to its independence of the time of day and the weather conditions, synthetic aperture radar (SAR) data have been increasingly applied in the extraction of water bodies. However, there is a great deal of speckle noise in SAR images, which seriously affect the extraction accuracy of water. At present, most of the processing methods are filtering methods, which will cause the loss of detailed information. Based on the characteristic of side-looking SAR, this paper proposed a self-adaptive thresholding approach for automatic water extraction based on an OTSU algorithm and distance block. In this method, the whole images were firstly divided into uniform image blocks through a distance layer which was produced by the distance to the orbit. Then, a self-adaptive processing was conducted for merging blocks. The OTSU algorithm was used to obtain a threshold for classification and the Jeffries–Matusita (JM) distance was calculated with the classification result. The merge processing continued until the separability of image blocks reached the maximum. Subsequently, we started from the next block to repeat the merger, and so on until all blocks were processed. Ten study areas around the world and the local Dongting Lake area were applied to test the feasibility of the proposed method. In comparison with five other global threshold segmentation algorithms such as the traditional OTSU, MOMENTS, MEAN, ISODATA and MINERROR, the proposed method obtains the highest overall accuracy (OA) and kappa coefficient (KC), while this approach also demonstrates greater robustness in the analysis of time series. The findings of this study offer an effective method to improve water detection accuracy as well as reducing the influence of speckle noise and retaining details in the image.
Journal Article
Association between self-care disability and depressive symptoms among middle-aged and elderly Chinese people
In the context of an increased focus on geriatric depression in recent years, this study examined the associations between different types of self-care disability, the number of self-care disabilities, and depressive symptoms among middle-aged and elderly Chinese people.
The data for this study were extracted from the follow-up survey (conducted in 2018) of the China Health and Retirement Longitudinal Study (CHARLS). The sample comprised 10808 participants aged 45 years and older. The Activities of Daily Living (ADL) scale and the Center for Epidemiological Studies Depression (CESD-10) Scale were used to assess self-care disability and depressive symptoms, respectively.
The prevalence of depressive symptoms and self-care disability among the surveyed residents was 45.1% and 23.4%, respectively. Overall, there was a significant positive association between self-care disability and depressive symptoms. Participants who reported having a self-care disability in relation dressing, bathing, transferring in and out of bed, using the toilet, and controlling urination and defecation were found to have a significantly higher risk of depressive symptoms. In addition, participants with a greater cumulative quantity of self-care disabilities had a higher risk of depressive symptoms, and higher CESD-10 scores.
Self-care disability is a risk factor for depressive symptoms among middle-aged and elderly Chinese people. A positive correlation between the number of self-care disabilities and the risk of depressive symptoms was found.
Journal Article
The efficacy of ileostomy after laparoscopic rectal cancer surgery: a meta-analysis
Background
Protective ileostomy is always applied to avoid clinically significant anastomotic leakage and other postoperative complications for patients receiving laparoscopic rectal cancer surgery. However, whether it is necessary to perform the ileostomy is still controversial. This meta-analysis aims to analyze the efficacy of ileostomy on laparoscopic rectal cancer surgery.
Methods
Cochrane Library, EMBASE, Web of Science, and PubMed were applied for systematic search of all relevant literature, updated to May 07, 2021. Studies compared patients with and without ileostomy for laparoscopic rectal cancer surgery. We applied Review Manager software to perform this meta-analysis. The quality of the non-randomized controlled trials was assessed using the Newcastle-Ottawa scale (NOS), and the randomized studies were assessed using the Jadad scale.
Results
We collected a total of 1203 references, and seven studies were included using the research methods. The clinically significant anastomotic leakage rate was significantly lower in ileostomy group (27/567, 4.76%) than that in non-ileostomy group (54/525, 10.29%) (RR = 0.47, 95% CI 0.30–0.73,
P
for overall effect = 0.0009,
P
for heterogeneity = 0.18,
I
2
= 32%). However, the postoperative hospital stay, reoperation, wound infection, and operation time showed no significant difference between the ileostomy and non-ileostomy groups.
Conclusion
The results demonstrated that protective ileostomy could decrease the clinically significant anastomotic leakage rate for patients undergoing laparoscopic rectal cancer surgery. However, ileostomy has no effect on postoperative hospital stay, reoperation, wound infection, and operation time. The efficacy of ileostomy after laparoscopic rectal cancer surgery: a meta-analysis.
Journal Article