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Abstract The aim of this study was to investigate whether triglyceride glucose-body mass index (TyG-BMI) plays a mediating role between obstructive sleep apnoea syndrome (OSAS) and hypertension. The study analyzed clinical data from a total of 840 OSAS patients at Wuhan Union Hospital between January 2020 to December 2023. The association between TyG-BMI and hypertension was examined using restricted cubic spline regression and logistic regression. Mediation effect analysis was conducted to explore the relationship between OSAS, TyG-BMI, and the risk of hypertension. Severe OSAS was associated with a significantly increased risk of hypertension compared to mild OSAS (OR = 1.752, p = 0.013). There was a positive linear relationship between TyG-BMI and the risk of hypertension (P-non-linear = 0.535). The risk of hypertension increased with increasing TyG-BMI, with a significantly higher risk of hypertension in the fourth quartile (OR = 3.407, p

To effectively replace diseased and damaged thoracic vertebrae, a series of three-dimensional (3D) printed titanium (Ti) alloy (Ti6Al4V) thoracic fusion cages with varying volume ratio of reinforced scaffolds are designed, and their structure-function relationships are investigated systematically. It is demonstrated that the mechanical strength of fusion cage is gradually enhanced as the scaffold volume increases, which may be attributed to its textural transformation from α phase to β phase. The compressive, shear, and fatigue of fusion cages successfully attain the International Organization for Standardization (ISO 23089), when the scaffold volume ratio exceeds 15%. Furthermore, the biomechanical analyses, including stress distributions and subsidence in flexion, extension, axial rotation, and lateral bending sections of fusion cages, further shed light on their potential clinical applications. This work deeply deciphers the intrinsic connection between biomechanical property and material texture of the thoracic fusion cages, offering valuable insights into their strengthening mechanism, which providing a guidance for the precise design and quick synthesis of other 3D-printed Ti6Al4V implants.

Excessive fructose diet is closely associated with colorectal cancer (CRC) progression. Nevertheless, fructose's specific function and precise mechanism in colorectal cancer liver metastasis (CRLM) is rarely known. Here, this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM, and the expression of KHK-A, not KHK-C, in liver metastasis was higher than in paired primary tumors. Furthermore, KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at Ser37. PKM2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of PKM2. EMT and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells' migration ability and anoikis resistance during CRLM progression. TEPP-46 treatment, targeting the phosphorylation of PKM2, inhibited the pro-metastatic effect of KHK-A. Besides, c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A, forming a positive feedback loop.

Abstract Elevated levels of tumor‐associated macrophages and microglia in the immune microenvironment of malignant gliomas promote tumor growth and progression. Although immune evasion has been implicated in these processes, the mechanisms underlying the regulation of CD47‐SIRPα‐mediated immune evasion under hypoxic conditions remain unclear. Therefore, this study aimed to explore the mechanisms through which CD47‐SIRPα modulates immune evasion in a cobalt chloride (CoCl2)‐induced hypoxic microenvironment of malignant gliomas. Human and mouse glioma cell lines were used to investigate immune evasion in vitro. After membrane protein extraction and nucleoplasmic isolation, we downregulated the expression levels of transport receptors to elucidate the regulation of CD47‐SIRPα transport. The CoCl2‐induced hypoxic microenvironment attenuated microglial phagocytosis in glioma cells. Enhanced CD47‐SIRPα interaction promoted immune evasion, which negatively affected tumor clearance. In addition, the intracellular transport of CD47 was promoted in the CoCl2‐induced hypoxic state. This process was regulated by regulator of chromosome condensation 1 (RCC1) and sortilin in the nuclear cytoplasm and cytoplasmic membrane, respectively. These results demonstrate the CD47‐SIRPα‐mediated immune escape mechanism of the CoCl2‐induced glioma hypoxic environment, which is associated with enhanced intracellular transport of CD47. Our findings provide a theoretical basis for the potential development of novel therapies targeting CD47‐SIRPα.

To compare the impact of nanoselenium and sodium selenite on the performance, blood indices, and milk metabolites of dairy cows during the peak lactation period, two groups of dairy cows under the same conditions were selected as the control group (CON group) and treatment group (NSe group) for a 38-day (10 days for adaptation and 28 days for sampling) experiment. The control group (CON) was provided a basal diet +3.3 g/d of sodium selenite (purity1%), whereas the nanoselenium group (NSe) was offered the same diet +10 mL/d of nanoselenium (selenium concentration 1,500 mg/L). The results showed that NSe significantly increased the milk yield, milk selenium content, and feed efficiency (p 0.05). NSe significantly increased blood urea nitrogen (BUN) and alkaline phosphatase (ALP) (p 0.05). In addition, the nontargeted metabolomics of the milk was determined by LC–MS technology, and the differentially abundant metabolites and their enrichment pathways were screened. According to these findings, NSe considerably increased the contents of cetylmannoside, undecylenoic acid, 3-hydroxypentadecanoic acid, 16-hydroxypentadecanoic acid, threonic acid, etc., but decreased the contents of galactaric acid, mesaconic acid, CDP-glucose etc. Furthermore, the enriched metabolic pathways that were screened with an impact value greater than 0.1 included metabolism of niacin and niacinamide, pyruvate, citrate cycle, riboflavin, glycerophospholipid, butanoate and tyrosine. Pearson correlation analysis also revealed a relationship between different milk metabolites and blood selenium, as well as between milk selenium and blood biochemical indices. In conclusion, compared with sodium selenite, nanoselenium improves the milk yield, feed efficiency, and milk selenium content of dairy cows and regulates milk metabolites and related metabolic pathways in Holstein dairy cows during the peak lactation period, which has certain application prospects in dairy production.

ObjectiveThis study aimed to investigate the biomechanical characteristics of the tandem spinal external fixation (TSEF) for treating multilevel noncontiguous spinal fracture (MNSF) using finite element analysis and provide a theoretical basis for clinical application.MethodsWe constructed two models of L2 and L4 vertebral fractures that were fixed with the TSEF and the long-segment spinal inner fixation (LSIF). The range of motion (ROM), maximum stresses at L2 and L4 vertebrae, the screws and rods, and the intervertebral discs of the two models were recorded under load control. Subsequently, the required torque, the maximum stress at L2 and L4 vertebrae, the screws and rods, and the intervertebral discs were analyzed under displacement control.ResultsUnder load control, the TSEF model reserved more ROM than the LSIF model. The maximum stresses of screws in the TSEF model were increased, while the maximum stresses of rods were reduced compared to the LSIF model. Moreover, the maximum stresses of L2 and L4 vertebrae and discs in the TSEF model were increased compared to the LSIF model. Under displacement control, the TSEF model required fewer moments (N·mm) than the LSIF model. Compared to the LSIF model, the maximum stresses of screws and rods in the TSEF model have decreased; the maximum stresses at L2 and L4 in the TSEF model were increased. In the flexion condition, the maximum stresses of discs in the TSEF model were less than the LSIF model, while the maximum stresses of discs in the TSEF model were higher in the extension condition.ConclusionCompared to LSIF, the TSEF has a better stress distribution with higher overall mobility. Theoretically, it reduces the stress concentration of the connecting rods and the stress shielding of the fractured vertebral bodies.

Abstract Colorectal cancer (CRC) is a global health challenge, and patient education plays a crucial role in its early detection and treatment. Despite progress in AI technology, as exemplified by transformer-like models such as ChatGPT, there remains a lack of in-depth understanding of their efficacy for medical purposes. We aimed to assess the proficiency of ChatGPT in the field of popular science, specifically in answering questions related to CRC diagnosis and treatment, using the book “Colorectal Cancer: Your Questions Answered” as a reference. In general, 131 valid questions from the book were manually input into ChatGPT. Responses were evaluated by clinical physicians in the relevant fields based on comprehensiveness and accuracy of information, and scores were standardized for comparison. Not surprisingly, ChatGPT showed high reproducibility in its responses, with high uniformity in comprehensiveness, accuracy, and final scores. However, the mean scores of ChatGPT’s responses were significantly lower than the benchmarks, indicating it has not reached an expert level of competence in CRC. While it could provide accurate information, it lacked in comprehensiveness. Notably, ChatGPT performed well in domains of radiation therapy, interventional therapy, stoma care, venous care, and pain control, almost rivaling the benchmarks, but fell short in basic information, surgery, and internal medicine domains. While ChatGPT demonstrated promise in specific domains, its general efficiency in providing CRC information falls short of expert standards, indicating the need for further advancements and improvements in AI technology for patient education in healthcare.

The aim of this study was to investigate the effects of Lentilactobacillus plantarum (LP), cellulase (CE), and xylanase (XE) supplementation on the fermentation quality, chemical composition, and bacterial community of Caragana korshinskii Kom. silage. Four groups were designed for the study. No additives were used in the control group (CK), and LP (1 × 106 cfu/g), CE (1 × 104 IU/g) and XE (2 × 105 IU/g) were added to the experimental groups on a fresh matter basis, with three replicates per group. To promote fermentation, 5% molasses was added to all of the groups. On days 15 and 60, fermentation quality, chemical composition and the bacterial community were analysed. The pH of groups CE and XE was lower than that of the CK group at 60 days. During ensiling, the lactic acid (LA) content in the experimental groups and the acetic acid (AA) content in the CK and LP groups increased. At 60 days, the dominant genera in the CK and LP groups was Weissella and the dominant genera in the CE and XE groups was Lentilactobacillus. At different times during silage, nucleotide metabolism was enhanced, whereas the metabolism of carbohydrate, amino acids, energy, cofactors and vitamins was inhibited in the LP group. However, the metabolism of amino acids, energy, cofactors and vitamins in the CE and XE groups was increased, whereas the metabolism of nucleotides was inhibited. In conclusion, LP, CE and XE could exert a positive effect on the fermentation quality of C. korshinskii Kom. silage by shifting the bacterial community composition.

As biodegradable materials, zinc (Zn) and zinc-based alloys have attracted wide attention owing to their great potential in biomedical applications. However, the poor strength of pure Zn and binary Zn alloys limits their wide application. In this work, a stir casting method was used to prepare the Zn-1Fe-xSr (x = 0.5, 1, 1.5, 2 wt.%) ternary alloys, and the phase composition, microstructure, tensile properties, hardness, and degradation behavior were studied. The results indicated that the SrZn13 phase was generated in the Zn matrix when the Sr element was added, and the grain size of Zn-1Fe-xSr alloy decreased with the increase in Sr content. The ultimate tensile strength (UTS) and Brinell hardness increased with the increase in Sr content. The UTS and hardness of Zn-1Fe-2Sr alloy were 141.65 MPa and 87.69 HBW, which were 55.7% and 58.4% higher than those of Zn-1Fe alloy, respectively. As the Sr content increased, the corrosion current density of Zn-1Fe-xSr alloy increased, and the charge transfer resistance decreased significantly. Zn-1Fe-2Sr alloy had a degradation rate of 0.157 mg·cm−2·d−1, which was 118.1% higher than the degradation rate of Zn-1Fe alloy. Moreover, the degradation rate of Zn-1Fe-xSr alloy decreased significantly with the increase in immersion time.

ABSTRACT: Pulmonary artery remodeling is a characteristic feature of broiler ascites syndrome (BAS). Pulmonary artery endothelial cells (PAECs) regulated by HIF-1α play a critical role in pulmonary artery remodeling, but the underlying mechanisms of HIF-1α in BAS remain unclear. In this experiment, primary PAECs were cultured in vitro and were identified by coagulation factor VIII. After hypoxia and RNA interference, the mRNA and protein expression levels of HIF-1α and VEGF were determined by qPCR and Western blotting. The transcriptome profiles of PAECs were obtained by RNA sequencing. Our results showed that the positive rate of PAECs was more than 90%, hypoxia-induced promoted the proliferation and apoptosis of PAECs, and RNA interference significantly downregulated the expression of HIF-1α, inhibited the proliferation of PAECs, and promoted the apoptosis of PAECs. In addition, transcriptome sequencing analysis indicated that HIF-1α may regulate broiler ascites syndrome by mediating COL4A, vitronectin, vWF, ITGα8, and MKP-5 in the ECM, CAMs and MAPK pathways in PAECs. These studies lay the foundation for further exploration of the mechanisms of pulmonary artery remodeling, and HIF-1α may be a potentially effective gene for the prevention and treatment of BAS.

The objective of this experiment was to investigate the effects of Lactobacillus plantarum and molasses on the nutrient composition, fermentation quality, bacterial count, aerobic stability, and microflora of alfalfa silage in sandy grasslands. The experimental treatments included control (CK), 106 CFU/g Lactobacillus plantarum (L), 5% molasses (M), and 106 CFU/g Lactobacillus plantarum + 5% molasses (LM). The nutrient composition, fermentation quality, bacterial count, aerobic stability, and microflora were determined after 14 days and 56 days of ensiling, respectively. The results showed that the addition of L, M, and LM reduced dry matter loss (DM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) content, and increased water-soluble carbohydrates (WSC) and ether extract (EE) content, compared to the CK group. Meanwhile, more lactic acid (LA) and accelerated fermentation were observed, causing the pH value to drop below 4.5 in the L, M, and LM groups after 56 days of ensiling. The addition of L, M, and LM promoted lactic acid bacteria (LAB), and inhibited yeast. The addition of L significantly increased the content of acetic acid (AA). In terms of microflora, the addition of L, M, and LM made Firmicutes become the dominant bacterial phylum earlier, while Lactobacillus, Weissella, and Pediococcus had a higher abundance. According to the result of Pearson's correlation, there is a very significant negative correlation between pH value and Lactobacillus (P < 0.01) and a very significant positive correlation between pH value and Lactococcus, Enterobacter, Enterococcus, and Leuconostoc (P < 0.01), which may be inhibited by Lactobacillus under the decreased pH value. The results of the prediction of microbial genes indicated that the addition of M could enhance the carbohydrate metabolism and membrane transport metabolism, which may contribute to LA production by LAB metabolism. In general, L, M and LM all improved the fermentation quality and reduced the loss of nutrients to varying degrees, but considering the fermentation quality, the overall effects of M and LM were better than L. M and LM are recommended to be used as silage additives in the process of alfalfa silage in sandy grasslands to improve the quality.

Abstract Tumor‐associated macrophages (TAMs) play a crucial role in promoting tumor growth and dissemination, motivating a search for key targets to interfere with the activation of TAMs or reprogram TAMs into the tumor‐suppressive type. To gain insight into the mechanisms of macrophage polarization, a designed co‐culture system is established, allowing for the education of macrophages in a manner that closely mimics the intricacies of TAMs in the tumor immune microenvironment (TIME). Through database mining, exosomal miR‐1246 is identified and is then validated. Exosomal miR‐1246‐driven polarization of TAMs disrupts the infiltration and function of CD8+ T cells. Mechanically, the amassment of exosomal miR‐1246 stems from TUT7‐mediated degradation of small noncoding RNA, a process stabilized by SNRPB, but not the precursor of miR‐1246. Moreover, an Exo‐motif is present in the exosomal miR‐1246 sequence, enabling it to bind with the exosomal sorting protein hnRNPA2B1. RNA‐seq analysis reveals that exogenous miR‐1246 modulates the polarization of TAMs at a post‐transcriptional level, emphasizing the pivotal role of the NLRP3 in macrophage polarization. In conclusion, the findings underscore the importance of exosomal miR‐1246 as a trigger of macrophage reprogramming and uncover a novel mechanism for its enhanced presence in the TIME.

Abstract Background The ZJU index, a novel calculation that combines body mass index, triglycerides, fasting blood glucose and the ratio of alanine aminotransferase to aspartate aminotransferase, is a closely related measure of obesity and insulin resistance. Studies of the ZJU index in relation to obstructive sleep apnea syndrome (OSAS) have not been reported. This study assessed the correlation between the ZJU values and OSAS risk. Methods A total of 2,130 participants who underwent polysomnographic monitoring were included in the study. The participants’ basic information and laboratory biochemical indicators were collected, and the ZJU index was computed. The ZJU index was divided into quartiles. The correlation between the different ZJU index levels and OSAS risk was assessed using logistic regression. Drew a receiver operating characteristic (ROC) relationship curve, with prediction efficacy judged by the area under the curve (AUC), and found the optimum cut-off point for ZJU index to predict OSAS. Relative risks were presented as odds ratios (OR). The range of OR values is expressed in the form of 95% confidence intervals (95% CI). Results The number of patients diagnosed with OSAS increased progressively with increasing ZJU index (T1: 9.4%; T2: 20.6%; T3: 28.3%; T4: 41.7%; P

Abstract Background Aortic diseases remain a highly perilous macrovascular condition. The relationship between circulating aldosterone and aortic diseases is rarely explored, thus we investigated the difference in plasma aldosterone concentration (PAC) between patients with and without aortic disease in hypertensive people. Methods We analyzed 926 patients with hypertension, ranging in age from 18 to 89 years, who had their PAC measured from the hospital's electronic database. The case group and control group were defined based on inclusion and exclusion criteria. The analysis included general information, clinical data, biochemical data, and medical imaging examination results as covariates. To further evaluate the difference in PAC between primary hypertension patients with aortic disease and those without, we used multivariate logistic regression analysis and also employed propensity score matching to minimize the influence of confounding factors. Results In total, 394 participants were included in the analysis, with 66 individuals diagnosed with aortic diseases and 328 in the control group. The participants were predominantly male (64.5%) and over the age of 50 (68.5%), with an average PAC of 19.95 ng/dL. After controlling for confounding factors, the results showed hypertension patients with aortic disease were more likely to have high PAC levels than those without aortic disease (OR = 1.138, 95% CI [1.062 to 1.238]). Subgroup analysis revealed consistent relationship between PAC and primary hypertensive patients with aortic disease across the different stratification variables. Additionally, hypertensive patients with aortic disease still have a risk of higher PAC levels than those without aortic disease, even after propensity score matching. Conclusions The results of this study suggest that primary hypertensive patients with aortic diseases have elevated levels of PAC, but the causal relationship between PAC and aortic disease requires further study.

Abstract Background The geographic information science-based interactive map provided good prospects for the public health to study disease prevalence. The purpose of this study is to understand global spatial–temporal trends of childhood overweight and obesity and underlying causes help formulating intervention strategies. Methods This multiple cross-sectional study included data on childhood overweight and obesity prevalence, gross national income per capita, and urbanization rate for 191 countries from 1975–2016. Autoregressive integrated moving average model, standard deviational ellipse model and mixed-effects models were used to explore spatial–temporal trends of childhood overweight and obesity and associations with gross national income per capita and urbanization rate. Results Globally, childhood overweight and obesity rate would reach 30.0% in 2030 (boys: 34.2%, girls: 27.4%). By 2030, it would reach 58.3% in middle- and high-income countries and 68.1% in Western Pacific region. Spatial–temporal trendline for childhood overweight and obesity in 1975–2030 exhibited a “C” shape, migrating from 1975 (15.6。E, 24.6。N) to 2005 (10.6。E, 21.7。N), then to 2030 (14.8。E, 17.4。N). The trendline for urbanization rate was also an irregular "C", and the turning point appeared five years earlier than childhood overweight and obesity. Conclusions Globally, childhood overweight and obesity prevalence will continue to increase. Its weight mean center migrated from western countries to Asia and Africa following economic development.

Abstract Background Hyperuricemia and sarcopenia are both strongly linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD), and this study was designed to look into the interactive effects of hyperuricemia on ASCVD risk. Methods This study collected information from patients (N = 2647) who underwent health check-ups at the Health Care Building of Wuhan Union Hospital between January 2019 and December 2020. Skeletal muscle mass was measured using bioelectrical impedance methods. The Asian Working Group on Sarcopenia diagnostic criteria were used to classify patients with sarcopenia. ASCVD risk was calculated using the Framingham Heart Study, and ASCVD risk ≥ 20% was considered high risk ASCVD. IBM SPSS 25.0 and GraphPad prism 8.0 software were used for data analysis and graphing. Results The prevalence of hyperuricemia and sarcopenia was 23.57% and 15.34%, respectively. The occurrence of cardiovascular risk factors such as obesity, hypertension, diabetes mellitus, chronic kidney disease, and low HDL-Cemia was significantly higher in subjects with hyperuricemia combined with sarcopenia (OR = 1.734, 3.064, 1.61, 8.77 and 1.691 respectively, p

This study addresses the issue of a significant amount of unmelted powder adhering to the surface of Laser Powder Bed Fusion (LPBF) porous titanium alloy scaffolds, and the current inability of existing technologies to effectively handle such surface defects. Porous titanium alloy scaffolds with a triple periodical minimal surface (TPMS) Gyroid structure were prepared using powder bed fusion technology for dynamic chemical polishing. The spatial and surface morphology, as well as the mechanical properties of the scaffolds, were evaluated before and after treatment. Concurrently, fluid finite element simulation was employed to analyze the flow state of the solution inside the porous scaffold during dynamic chemical polishing. Cell culture samples were prepared and subjected to dynamic chemical polishing to study the specific effects of scaffold surface morphology on cell activity. The results indicate that the surface treatment effect, internal and external homogeneity, and dynamic and static mechanical properties of the porous scaffolds with a Gyroid structure are significantly improved after dynamic chemical polishing. Additionally, it was found that dynamic chemical polishing could effectively reduce the micrometer roughness and increase the nanometer roughness of the sample surface, thereby enhancing the adhesion, proliferation, and differentiation activities of Human Bone Mesenchymal Stem cells.

Objectives Sarcopenia is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Studies evaluating the association between the fat-to-muscle ratio (FMR) and NAFLD are limited. Therefore, the aim of our study was to investigate the association between FMR and NAFLD.Design A retrospective study was conducted on individuals who underwent health examination at Wuhan Union Hospital between January 2020 and November 2021. Clinical data were collected from electronic medical records.Setting Wuhan Union Hospital, Wuhan, China.Participants 1592 participants aged ≥40 years who underwent body composition analysis and liver ultrasonography were retrospectively reviewed.Outcome measures Liver ultrasonography was used to assess liver steatosis, and the fibrosis-4 index was used to calculate the risk scores for liver fibrosis. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction model was used to calculate ASCVD risk scores.Results The FMR was significantly higher in individuals with NAFLD than in those without NAFLD (p

This paper proposes a new optimal control method to solve traffic accidents such as vehicle collisions during driver’s conscious lane changing under the dangerous state of highway driving and meet the requirements of safety and comfort during vehicle lane changes. First, by directly analyzing the interpolation error and slope of discrete nodes, a new mesh refinement method was used to solve the vehicle optimal lane-changing problem. Then, a simulation of vehicle emergency left and right lane changes was established to verify the proposed method based on a nonlinear 7-DOF vehicle model. Finally, a virtual test using the CarSim software was conducted to verify the feasibility of the simulated results. The simulation results show that the mesh generated by the method in this study is smaller and requires fewer grid iterations, which can quickly and accurately solve the vehicle optimal lane-changing problem with constant components of the optimal control variables and fewer mesh iteration times and node numbers with high accuracy. And also, compared with the traditional Gaussian pseudospectral method(GPM), the solution accuracy of the mesh refinement method is higher than that of the traditional Gaussian pseudospectral method, indicating the superiority of the proposed method.

Abstract Background N4-acetylcytidine (ac4C) as a significant RNA modification has been reported to maintain the stability of mRNA and to regulate the translation process. However, the roles of both ac4C and its ‘writer’ protein N-acetyltransferase 10 (NAT10) played in the disease especially colorectal cancer (CRC) are unclear. At this point, we discover the underlying mechanism of NAT10 modulating the progression of CRC via mRNA ac4C modification. Methods The clinical significance of NAT10 was explored based on the TCGA and GEO data sets and the 80 CRC patients cohort of our hospital. qRT-PCR, dot blot, WB, and IHC were performed to detect the level of NAT10 and ac4C modification in CRC tissues and matched adjacent tissues. CCK-8, colony formation, transwell assay, mouse xenograft, and other in vivo and in vitro experiments were conducted to probe the biological functions of NAT10. The potential mechanisms of NAT10 in CRC were clarified by RNA-seq, RIP-seq, acRIP-seq, luciferase reporter assays, etc. Results The levels of NAT10 and ac4C modification were significantly upregulated. Also, the high expression of NAT10 had important clinical values like poor prognosis, lymph node metastasis, distant metastasis, etc. Furthermore, the in vitro experiments showed that NAT10 could inhibit apoptosis and enhance the proliferation, migration, and invasion of CRC cells and also arrest them in the G2/M phase. The in vivo experiments discovered that NAT10 could promote tumor growth and liver/lung metastasis. In terms of mechanism, NAT10 could mediate the stability of KIF23 mRNA by binding to its mRNA 3’UTR region and up-regulating its mRNA ac4c modification. And then the protein level of KIF23 was elevated to activate the Wnt/β-catenin pathway and more β-catenin was transported into the nucleus which led to the CRC progression. Besides, the inhibitor of NAT10, remodelin, was applied in vitro and vivo which showed an inhibitory effect on the CRC cells. Conclusions NAT10 promotes the CRC progression through the NAT10/KIF23/GSK-3β/β-catenin axis and its expression is mediated by GSK-3β which forms a feedback loop. Our findings provide a potential prognosis or therapeutic target for CRC and remodelin deserves more attention. Graphical Abstract

Abstract Background Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA. Methods Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis. Results The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p

Objectives: Compare the differences between the intervention and control groups in changes of primary outcomes (body mass index [BMI] and waist-to-height ratio [WHtR]) and secondary outcomes (nutrition knowledge of children and parents), from baseline to the 6- and 12-month follow-ups; examine the associations of changes in nutrition knowledge of children and their parents with children's changes in BMI and WHtR. Data sources: Data collected from four schools in two poverty-stricken counties in northern Shaanxi Province in 2020‒2021. Methods: A multifaced intervention program targeted children (promoting healthy diet and nutrition education) and their parents (promoting nutrition knowledge) was conducted in the interventional group. Four schools, with two in each group, were randomly allocated to the intervention or control group, with 814 eligible children aged 7.1 to 12.8 years. The control group conducted myopia promotion. Differences in changes of BMI and WHtR between groups were compared with t-test. Mixed-effects model was used to examine the associations between changes in nutrition knowledge of children and parents with changes in children's BMI and WHtR. Results: At the 6-month follow-up, the difference in changes in BMI between the intervention and control groups was 0.4 kg/m 2 (P < 0.001). At the 12-month follow-up, the difference in changes in BMI and WHtR between intervention and control groups was 0.1 kg/m2 (P < 0.001) and 0.01 kg/m2 (P < 0.001). In the intervention group, the nutrition knowledge awareness rate of children increased from 16.9% (69/409) at baseline to 21.3% (87/409) at 6-month, and 22.7% (93/409) at 12-month. The awareness rate of nutrition knowledge of parents also fluctuated, from 5.6% (23/409) to 6.6% (27/409) and 5.4% (22/409). However, the difference in changes in nutrition knowledge between intervention and control groups was non-significant. The 6-month follow-up changes in children's nutrition knowledge scores were negatively associated with changes in BMI in girls (β = −0.26, 95% confidence interval [CI]: −0.38 to −0.14, P < 0.001), while positively associated with changes in WHtR in boys (β = 0.003, 95% CI: −0.0002 to 0.005, P = 0.035). The 12-month follow-up changes in children's nutrition knowledge scores were positively associated with changes in children's WHtR (β = 0.003, 95% CI: 0.0004 to 0.01, P = 0.018). Conclusions: The intervention strategies did not reduce the BMI and WHtR of children, and the nutrition knowledge of children and parents increased after the intervention in intervention group. Changes in nutrition knowledge of children and their parents are associated with changes in children's BMI or WHtR. Interventions with a new focus on obesity are needed to help improve children's nutritional status in poverty-stricken areas in Shaanxi Province of China.

Obesity has become a serious public health problem globally. China has the world's largest number of people with obesity or overweight. More than 50% of adults and about 20% of children and adolescents in China are overweight or obese. Over the past 20 years, China has made many efforts in obesity intervention, while obesity rates continued rising. In recent years, China has taken more actions for obesity prevention. The World Obesity Day (WOD) was established in 2015 by the World Obesity Federation, and is a unified day of action calling for a cohesive, cross-sector response to fight obesity. WOD has drawn increasing attention in recent years. China formally joined the WOD activities this year, promoted by The Obesity Prevention and Control Section of Chinese Nutrition Society, which cooperated closely with other organizations in carrying out a series of activities during the 2022 WOD. These efforts aimed to encourage the whole society to pay attention to the obesity problem and take more practical actions. The activities include: (1) The 2022 “World Obesity Day” China Summit; (2) a specifically developed WOD obesity prevention education video; and (3) the launch of The Expert Consensus on Obesity Prevention and Treatment in China. These can serve as examples for other organizations and countries to consider in future intervention efforts. To fight the global obesity epidemic, all counties and people need to act. Countries can learn from each other's successful practices.

Abstract Ariadne homolog 2 (ARIH2) is a key member of the RING-between-RING (RBR) E3 ligase family, which is characterized by an RBR domain involved in the polyubiquitination process. However, the molecular mechanism and biological function of ARIH2 in the pathogenesis of gastric cancer remain unclear. In this paper, we found that high ARIH2 expression is correlated with poor prognosis in gastric cancer patients and that ARIH2 can significantly promote the proliferation of gastric cancer cells. The effect of ARIH2 knockdown on colony formation and tumorigenesis of gastric cancer cells was also shown both in vivo and in vitro. Further mechanistic investigations revealed that ARIH2 interacts with p21 and induces p21 ubiquitination, and that the K48 residue of ubiquitin and the K161 residue of p21 play key roles in ARIH2-mediated p21 ubiquitination. We identified ARIH2 as an E3 ligase of p21 by an in vitro ubiquitination assay. In addition, ARIH2 knockdown induced DNA damage, and then induced cell apoptosis and regulated the chemosensitivity of gastric cancer cells after combined treatment with 5-fluorouracil. Generally, our results indicated that ARIH2 promotes the proliferation of gastric cancer cells and regulates p21 expression. These data demonstrate the need to further evaluate the potential therapeutic implications of ARIH2 in gastric cancer.

Abstract GPR176 belongs to the G protein‐coupled receptor superfamily, which responds to external stimuli and regulates cancer progression, but its role in colorectal cancer (CRC) remains unclear. In the present study, expression analyses of GPR176 are performed in patients with colorectal cancer. Genetic mouse models of CRC coupled with Gpr176‐deficiency are investigated, and in vivo and in vitro treatments are conducted. A positive correlation between GPR176 upregulation and the proliferation and poor overall survival of CRC is demonstrated. GPR176 is confirmed to activate the cAMP/PKA signaling pathway and modulate mitophagy, promoting CRC oncogenesis and development. Mechanistically, the G protein GNAS is recruited intracellularly to transduce and amplify extracellular signals from GPR176. A homolog model tool confirmed that GPR176 recruits GNAS intracellularly via its transmembrane helix 3‐intracellular loop 2 domain. The GPR176/GNAS complex inhibits mitophagy via the cAMP/PKA/BNIP3L axis, thereby promoting the tumorigenesis and progression of CRC.

The current database has no information on the infiltration of glioma samples. Here, we assessed the glioma samples’ infiltration in The Cancer Gene Atlas (TCGA) through the single-sample Gene Set Enrichment Analysis (ssGSEA) with migration and invasion gene sets. The Weighted Gene Co-expression Network Analysis (WGCNA) and the differentially expressed genes (DEGs) were used to identify the genes most associated with infiltration. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the major biological processes and pathways. Protein–protein interaction (PPI) network analysis and the least absolute shrinkage and selection operator (LASSO) were used to screen the key genes. Furthermore, the nomograms and receiver operating characteristic (ROC) curve were used to evaluate the prognostic and predictive accuracy of this clinical model in patients in TCGA and the Chinese Glioma Genome Atlas (CGGA). The results showed that turquoise was selected as the hub module, and with the intersection of DEGs, we screened 104 common genes. Through LASSO regression, TIMP1, EMP3, IGFBP2, and the other nine genes were screened mostly in correlation with infiltration and prognosis. EMP3 was selected to be verified in vitro. These findings could help researchers better understand the infiltration of gliomas and provide novel therapeutic targets for the treatment of gliomas.

Polyoxometalates (POMs) have shown promising antitumor activities attributed to their virtue of incomparable structural versatility and interesting redox properties. However, the clinical application of POM drugs is limited by their poor stability and low anticancer specificity. To overcome these shortcomings, a multifunctional platform based on POMs (the tetrabutylammonium salts of [PW12O40]3−, [V10O28H3]3− and [Mo6O19]2−) and MIL-100 (Fe) was successfully developed for combined chemical and chemodynamic therapy, ultimately inducing cancer cell apoptosis. The prepared POMs@MIL-100 (Fe) composites showed great efficiency in killing MCF-7 and 4T1 cells while with a low toxicity to normal MCF-10A and C2C12 cells.

Background. Currently, both metabolic syndrome and hyperuricaemia have attracted extensive attention in public health. The correlation between uric acid and metabolic syndrome is controversial. Research on the relationship between uric acid and metabolic syndrome in community-dwelling elderly people is relatively lacking. The purpose of this study is to explore the relationship between uric acid and metabolic syndrome in the community-dwelling elderly people. Design. Cross-sectional study. Methods. We collected the physical examination data of 1,267 elderly people in Gutian community in Wuhan and used SPSS IBM 25.0 for data analysis. Correlation and logistic regression analyses were performed, and ROC curves were drawn. Results. The uric acid level of the nonmetabolic syndrome group was lower than that of the metabolic syndrome group (337.31 vs. 381.91 µmol/L; P

BackgroundNon-communicable diseases (NCDs) including risk factors, e.g., obesity, are the major causes of preventable deaths in China, yet NCD disparities in China remain under-studied.ObjectiveThis study aimed to compare the determinants and burden of NCDs within four selected provinces in mainland China: the least developed Qinghai-Tibet Plateau group (PG, Tibetan Autonomous Region [TAR] and Qinghai Province) and most developed megacity group (MCG, Shanghai, and Beijing).MethodsStudies, reports, and other official sources with comparable data for NCD burden and related determinants for the four provinces were searched. Geographic, demographic, socioeconomic, and dietary characteristics and selected health indicators (e.g., life expectancy) were extracted from the China Statistical Yearbook and China Health Statistics Yearbook. Data on NCD burdens were extracted from the National Chronic Disease and Risk Factor Surveillance Study and other nationally representative studies.ResultsThe overall NCD mortality rates and prevalence of metabolic risk factors including obesity, hypertension, and diabetes in mainland China have increased in the past 20 years, and this trend is expected to continue. The PG had the highest level of standardized mortality rates (SMRs) on NCDs (711.6–896.1/100,000, 6th/6-level); the MCG had the lowest (290.6–389.6/100,000, 1st/6-level) in mainland China. The gaps in SMRs were particularly high with regard to chronic respiratory diseases (PG 6th/6-level, MCG 1st/6-level) and cardiovascular diseases (6th/6 and 4th/6 in TAR and Qinghai; 1st/6-level and 2nd/6-level in Shanghai and Beijing). In contrast, the prevalence rates of obesity, hypertension, and diabetes were generally higher or comparable in MCG compared to PG. Diabetes prevalence was particularly high in MCG (5th/5-level, 13.36–14.35%) and low in PG (1st/5-level, 6.20–10.39%). However, awareness, treatment, and control of hypertension were poor in PG. Additionally, PG had much lower and severely inadequate intakes of vegetables, fruits, and dairy products, with additional indicators of lower socioeconomic status (education, income, etc.,) compared with MCG.ConclusionEvidence showed large disparities in NCD burden in China's provinces. Socioeconomic disparity and dietary determinants are probably the reasons. Integrated policies and actions are needed.

Bioengineered porous bone tissue materials based on additive manufacturing technology have gradually become a research hotspot in bone tissue-related bioengineering. Research on structural design, preparation and processing processes, and performance optimization has been carried out for this material, and further industrial translation and clinical applications have been implemented. However, based on previous studies, there is controversy in the academic community about characterizing the pore structure dimensions of porous materials, with problems in the definition logic and measurement method for specific parameters. In addition, there are significant differences in the specific morphological and functional concepts for the pore structure due to differences in defining the dimensional characterization parameters of the pore structure, leading to some conflicts in perceptions and discussions among researchers. To further clarify the definitions, measurements, and dimensional parameters of porous structures in bioengineered bone materials, this literature review analyzes different dimensional characterization parameters of pore structures of porous materials to provide a theoretical basis for unified definitions and the standardized use of parameters.

Abstract Background The clinical characteristics of patients with chronic cough are reported only in single-center survey in China, being significantly different from that in western countries. Here, we performed a multicenter study to describe the clinical characteristics of chronic cough patients. Methods A cross-sectional observational survey was conducted in thirteen tertiary hospitals of Guangdong, South China. Relevant data were recorded using a standardized questionnaire and analyzed, including demographics, educational attainment, cough features, and concomitant symptoms. Results Of 933 patients in this study, the median age was 40.0 (IQR 31.0–52.0) years with a peaked age of 30–39 years. The proportion of females (487, 52.2 %) was comparable to that of males (446, 47.8 %). Up to 81.9 % of the patients were non-smokers. More than two-thirds of the subjects with chronic cough had a low educational level. The median cough duration was 6.0 (IQR 3.0–24.0) months, and 73.0 % of chronic cough patients presented with dry cough. Laryngeal paresthesia was the most common concomitant symptom (704, 75.5 %), followed by rhinitis/sinusitis-related (350, 37.5 %) and respiratory symptoms (322, 34.5 %). Rhinitis/sinusitis-related symptoms more frequently occurred in patients with productive cough than in those with dry cough (49.0 % vs. 33.0 %, P

As a deeply processing product of kiwifruit, kiwifruit wine (KW) has also shown promising commercial development prospects. In this study, the color and aroma characteristics of 14 commercially available KW were evaluated using intelligent sensory technologies (electronic nose (E-nose) and colorimeter) and gas chromatography-mass spectrometry (GC–MS). Different types of KW had similar color trends, namely, yellow-green or yellow; however, individual samples showed a bright green color and had a high transparency. E-nose and GC–MS reached a relatively consistent conclusion that fermented wine and Lu Jiu were closer and significantly differed from those of distilled wine and beer. A total of 215 volatile organic compounds were identified in all KW. 50 key odor-active compounds were identified, of which ethyl caprylate, which had high OAVs in all samples (30–565.17), was considered the key odor-active compound of KW; likewise, damascenone also made a prominent aroma contribution in the different types of KW. Moreover, β-ionone, ethyl undecanoate, ethyl 2-methylvalerate were outstanding in different fermented wines. Acids and terpenoids were prominent in beer. The study could provide a data support and market information for the quality control, research, production and development of KW.

Accurate tracking of a given path is one of the primary factors in the maneuverability of a vehicle and is also an important topic in autonomous vehicle research. To solve the problem of vehicle path tracking, the problem must first be transformed into an optimal control problem. Then, a symplectic pseudospectral method (SPM) based on the third-generation function of symplectic theory and pseudospectral discretization is proposed to efficiently solve the nonlinear optimal control problems. Finally, the results obtained by the proposed algorithm are compared with those obtained by the Gauss pseudospectral method (GPM). The simulation results show that the proposed method can effectively solve the vehicle path tracking problem. Furthermore, the vehicle can track the given path controlled by the proposed algorithm with higher accuracy and greater applicability than other methods.

(1) Background: We investigated the effects of a 12-week exercise intervention with or without vitamin D supplementation on insulin resistance and the plasma lipidome of participants with type 2 diabetes. We further explored whether the effects of the intervention on glycemic parameters could be associated with the baseline lipidome. (2) Methods: Sixty-one participants were randomly allocated to control (Con), exercise (EX), vitamin D (VD), and EX + VD groups. Multiple glycemic and anthropometric parameters were evaluated before and after intervention. The homeostasis model assessment of insulin resistance (HOMA-IR) was the primary outcome. The plasma lipidome was analyzed before, after, and at an additional 12-week follow-up. Machine learning was applied to establish prediction models for responsiveness of glycemic control. (3) Results: Our interventions failed to improve the HOMA-IR index while fasting glucose was reduced in the EX + VD group (change%, −11.9%; effect size, 0.65; p < 0.05). Both EX and VD interventions altered the plasma lipidome, with EX + VD intervention considerably affecting levels of lyso-phosphatidylcholines and triglycerols containing long-chain unsaturated fatty acids. Such effects could last until 12 weeks after intervention. Notably, there was high inter-individual variability in glycemic parameters including HOMA-IR in response to the interventions, which could be predicted with great accuracy using an optimal panel of baseline lipid predictors alone or in combination with clinical indices, as assessed by an area under the receiver operating characteristic curve value of over 0.9. (4) Conclusions: Although substantial alterations were observed in the plasma lipidome related to glycemic control, our intervention failed to improve HOMA-IR scores, which may have been predominately due to the large inter-individual variability in responses. Basal plasma lipid levels could potentially predict an individual’s response to intervention, highlighting the necessity of personalized nutrition.

Abstract Background Recent studies have investigated the role of circular RNAs (circRNAs) as significant regulatory factors in multiple cancer progression. Nevertheless, the biological functions of circRNAs and the underlying mechanisms by which they regulate colorectal cancer (CRC) progression remain unclear. Methods A novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of in vitro and in vivo phenotype experiments were performed to investigate the role of circ-GALNT16 in CRC. The FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were performed to investigate the molecular mechanisms of circ-GALNT16 in CRC progression. Results Circ-GALNT16 was downregulated in CRC and was negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastatic ability of CRC cells in vitro and in vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which promoted the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the formation of the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO-specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex. Conclusions Circ-GALNT16 suppressed CRC progression by inhibiting Serpine1 expression through regulating the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might function as a biomarker and therapeutic target for CRC.

ABSTRACT With the demographic changes, more and more elderly people have chosen to spend their retirement life in a senior care facility. The elderly people in senior care facility are commonly suffering from various geriatric syndromes, including declined daily living activities, cognitive dysfunction, frailty, comorbidities, and polypharmacy, which make them vulnerable to adverse effects, like hypoglycemia and fall. Therefore, layered management is necessary for this population with group disparities. However, the staff in senior care facility vary greatly in concepts and skills on management of senile diabetic population, which needs urgently to be standardized and improved. For this purpose, based on literature review and panel discussion, 28 recommendations are proposed in respect of the standardized management of blood glucose, covering the comprehensive assessment, layered management and grouping, exercise, nutrition, glucose monitoring, identification and treatment of severe hyperglycemia, identification of macrovascular and microvascular complications, management of hypoglycemic drugs, falls and choking and other common problems, blood glucose screening, hypoglycemia prevention, and blood glucose management in major public health events or serious natural disasters. This guideline aims to standardize management skills of medical staff and caregivers in senior care facility for the blood glucose of elderly people and improve their quality of life.

Objective: The data in regard of the clinical characteristics and diagnosis of somatic cough syndrome in adults were limited. The aim of this study was to fill that gap. Methods: This was a retrospective analysis of patients with somatic cough syndrome. We described clinical characteristics of adult patients with somatic cough syndrome. Results: Twenty-three somatic cough syndrome patients were identified in 543 adult patients with chronic cough. Psychiatric disorder of these patients was identified as anxiety ( n = 8), obsessive-compulsive ( n = 7), somatoform ( n = 6), depression ( n = 3), and cognitive bias ( n = 1). Twelve patients showed abnormal results of investigations related with common causes of chronic cough, including gastroesophageal reflux, sputum eosinophilia, bronchial hyper-responsiveness, or signs of sinusitis but did not respond to the treatments directed to those conditions. All these patients were ever misdiagnosed as other causes of chronic cough. Compared to 520 non-somatic cough syndrome patients, patients with somatic cough syndrome were younger (32 (29.0–43.0) vs 42.0 (32.0–55.0) years, p = 0.013), longer disease duration (48.0 (19.5–102.0) vs 24.0 (9.0–72.0) months, p = 0.037), more common in dry cough (100% vs 57.6%, p

White spot syndrome is an epidemic disease caused by the highly contagious and lethal white spot syndrome virus (WSSV), resulting in huge economic losses to the global aquaculture industry. VP28 is the main structural protein in the capsule of WSSV and is important in the early stage of infection. Under an excitation wavelength of 548 nm, the mOrange fluorescent protein releases a 562 nm emission wavelength, which is different from the autofluorescence of cyanobacteria. Therefore, using this characteristic combined with the receptor system of Synechococcus elongatus PCC 7942, we constructed transgenic S. elongatus to express the recombinant protein VP28-mOrange. In addition, PCR and western blotting were used to confirm the stable expression of the target gene in cyanobacteria. Using mOrange tracer features, we explored the recombinant protein VP28-mOrange in the metabolic cycle of young Litopenaeus Vannamei after feeding. After the young shrimp had stopped consuming transgenic cyanobacteria, the 24 to 33 h fluorescence signal in the intestine was very weak, and almost disappeared after 36 h. We explored the protective effect of transgenic vp28-mOrange S. elongatus within 48 h of being ingested by L. vannamei and set WSSV challenges at 2, 12, 24, and 48 h post-immunization. However, the survival rate of L. vannamei decreased as the time of the WSSV challenge increased. The survival rate on the seventh day was 81%, 52%, 45.5%, and 33.3% for shrimps challenged for 2, 12, 24, and 48 h, respectively. Enzyme activity can also support this conjecture, the enzyme activity indexes of the experimental groups were significantly reduced compared to positive and wild-type controls. Therefore, this immune agent functioned as a preventive agent. Compared with the traditional method, this method was easy to detect and can visualize the digestion of transgenic cyanobacteria in the Litopenaeus vannamei intestine.

BackgroundDelayed treatment of acute aortic dissection (AAD)-related acute kidney injury (AKI) significantly increases the burden of chronic kidney disease (CKD) and mortality. Lysophosphatidic acid (LPA) is a shared mediator of kidney disease and AAD. Here, we evaluated the relationship between LPA and kidney injury in AAD patients.MethodsWe measured the plasma concentration of LPA in a cohort of 80 patients with AAD. Least Absolute Shrinkage and Selection Operator (LASSO) regression and Logistic regression were used to evaluate the effect and interaction of LPA on AKI. Additive generalized model and penalized spline method were used to describe the non-linear association. Multivariable analyses with the Cox proportional-hazards model were used for subgroup analysis and interaction in LPA and subsequent CKD.ResultsThe participant’s average age was 54.27 ± 11.00 years, 68.75% of them were males, and the incidence of AKI was 43.75%. Patients with AKI had higher levels of LPA on admission, and the more significant the increase, the higher the risk of AKI. There was a non-linear positive correlation between admission LPA and AKI, and the premeditated inflection point was 346.33 (μg/dL) through two-piecewise linear regression and recursive algorithm. Subgroup analysis identified a stronger association between admission LPA and AKI in the elder, female and medically treated patients. The incidence of CKD was 22.67% in the 2-year follow-up. Patients with subsequent CKD had higher LPA levels on admission in the follow-up cohort, and a similar interaction trend was also observed through Cox proportional—hazards model.ConclusionAdmission LPA levels show a non-linear positive correlation with AKI and increase the risk of subsequent CKD, which is more pronounced in elderly, female, and medically treated patients.

Abstract Background Immune cells account for a large proportion of the tumour microenvironment in anaplastic thyroid carcinomas (ATCs). However, the expression pattern of immune-related genes (IRGs) in ATCs is unclear. Our study aimed to identify an immune-related signature indicating the dedifferentiation of thyroid cells. Methods We compared the differences in thyroid differentiation score (TDS), infiltration of immune cells and enriched pathways between ATCs and papillary thyroid carcinomas (PTCs) or normal thyroid tissues in the Gene Expression Omnibus database. Univariate and multivariable Cox analyses were used to screen prognosis-associated IRGs in The Cancer Genome Atlas database. After constructing a risk score, we investigated its predictive value for differentiation and survival by applying receiver operating characteristic and Kaplan–Meier curves. We further explored its associations with important immune checkpoint molecules, infiltrating immune cells and response to immunotherapy. Results Compared with PTCs or normal thyroid tissues, ATCs exhibited lower TDS values and higher enrichment of immune cells and activation of the inflammatory response. The quantitative analyses and immunohistochemical staining validated that most ATC cell lines and ATC tissues had higher expression of MMP9 and lower expression of SDC2 than normal thyroid samples and PTC. Higher risk scores indicates dedifferentiation and a worse prognosis. Additionally, the risk score was positively correlated with the immune checkpoint molecules PDL1, CTLA4, IDO1, and HAVCR2 and infiltration of multiple immune cells. Importantly, we found that the samples with higher risk scores tended to have a better response to immunotherapy than those with lower scores. Conclusion Our findings indicate that the risk score may not only contribute to the determination of differentiation and prognosis of thyroid carcinomas but also help the prediction of immune cells infiltration and immunotherapy response.

Abstract Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly correlated with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. In conclusion, the circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.

Little is known about the longitudinal association between dietary patterns (DPs) and metabolic disorders in people living at high altitude areas, such as Tibetans. We constructed the first open cohort, with 1832 Tibetans, and collected data in 2018 and in 2022. The metabolic syndrome (MetS) prevalence was 30.1% (32.3% in men and 28.3% in women). Three different DPs were identified: modern DP (pulses, poultry, offal, and processed meat), urban DP (vegetables, refined grain, beef/mutton, and eggs), and pastoral DP (Tibetan cheese, tsamba, butter/milk tea, and desserts). Participants within the third tertile of the urban DP had a 3.42-fold (95% CI 1.65–7.10) higher risk of MetS than those with the first tertile. Modern DP was positively associated with elevated blood pressure (BP) and elevated triglycerides (TAG), while it was inversely associated with low HDL-C. The urban DP was associated with a higher risk of low HDL-C, but a lower risk of impaired fasting blood glucose (FBG). The pastoral DP was a risk factor for impaired FBG, but protective for central obesity and elevated BP. Associations of modern DP with elevated BP, and pastoral DP with low HDL-C, were modified by altitude. In conclusion, among Tibetan adults, DPs were associated with MetS and its components, and the associations were modified by altitude among Tibetans.

Abstract Colorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the specific mechanism of CRLM (colorectal cancer with liver metastasis) is not fully understood. LZTS1 has been found dysregulated in many cancers, especially in CRC. Theories suggested that hypermethylation of the promoter regions of LZTS1 was responsible for LZTS1 abnormal expression in multiple malignant tumors. Although the role of LZTS1 in CRC cell proliferation has been reported, its role in CRLM remains unclear. Numerous studies reported Long non-coding RNA (lncRNA) could regulate the gene expression level by regulating gene methylation status in many tumors. However, whether there were lncRNAs could change the methylation status of LZTS1 or not in CRLM was unknown. In this study, we aimed to investigate whether there are lncRNAs can regulate the expression of LZTS1 through affecting DNA methylation in CRLM. We found that upregulated Lnc-LALC in CRC was negatively correlated with LZTS1 expression, and Lnc-LALC could regulate LZTS1 expression in both mRNA and protein level in our study. Functionally, Lnc-LALC enhanced the CRC cells metastasis ability in vitro and vivo through inhibiting the expression of LZTS1. Furthermore, the precise mechanisms exploration showed that lnc-LALC could recruit DNA methyltransferases (DNMTs) to the LZTS1 promoter by combining with Enhancer of zeste homolog 2(EZH2) and then altered the expression of LZTS1 via DNMTs-mediated DNA methylation. Collectively, our data demonstrated the important role of Lnc-LALC/ LZTS1 axis in CRLM development.

Our previous studies shown that syndecan-1 (SDC1) may be a novel class of biomarkers for the diagnosis and treatment of glioma, but its specific roles and the in-depth molecular mechanism remain elusive. Here, we used Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithms and single-sample Gene Set Enrichment Analysis (ssGSEA) algorithms to evaluate the immune score of tumor samples and quantify the relative infiltration of immune cells in the tumor microenvironment (TME), respectively, in different data sets obtained from the Chinese Glioma Genome Atlas and The Cancer Gene Atlas. Next, we calculate the correlation of the immune score and immune cells with SDC1, respectively. To identify the specific process regulated by SDC1, the differentially expressed genes (DEGs) analysis between the high and low expression of SDC1 of glioma samples were used to discover the hub genes through Weighted Gene Coexpression Network Analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed cardinal biological processes and pathways involved in genes and tumor grade correlation and survival analysis verified its significance in glioma. The results show that SDC1 is associated with the immune infiltration of glioma in the TME, especially activated CD4+T cells and CD8+T cells. The three data sets filter 8,887 DEGs, the genes in the blue modules were selected as hub genes in WGCNA. GO and KEGG analysis found eight genes in the blue modules involved in antigen processing and presentation in T cells in glioma. Kaplan–Meier estimator and log-rank test statistic determined that the introduced genes are associated with poor prognosis in glioma. Protein–protein network interaction analysis showed that SDC1 may regulate antigen processing and presentation through CTSL or CD4 in glioma. Finally, this study provided insights and clues for the next research direction of SDC1 and identified the key pathways and genes that might participate in the immune escape of glioma. These results might provide a new insight on the study of immune infiltration of glioma in the future.

Abstract Background Several randomized controlled trials (RCTs) compared the effects of laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC), but the results have remained inconsistent. Hence, a meta-analysis and a systematic review of these treatment modalities are necessary to evaluate their efficacy and safety for HCC treatment. Methods From the inception of this meta-analysis and review until August 31, 2019, we searched Medline, PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and China Biomedical Literature Database for RCTs involving LH and RFA treatments of patients with HCC. The studies were screened and the data from these articles were extracted independently by two authors. Summary odd ratios (OR) or mean differences (MD) with 95% confidence intervals (CI) were calculated for each outcome with a fixed- or random-effect model. The outcomes for effectiveness evaluations included duration of surgery, estimated bleeding volume, incidence of blood transfusion during surgery, duration of hospital stay, and the outcome for safety included the incidence of cancer recurrence. Results Seven RCTs with a total of 615 patients were identified, 312 and 303 of which underwent RFA and LH treatments, respectively. The duration of surgery (MD = −99.04; 95% CI: −131.26–−66.82), estimated bleeding volume (MD = −241.97; 95% CI: −386.93–−97.02), incidence of blood transfusion during surgery (OR = 0.08; 95% CI: 0.02–0.37), and duration of hospital stay (MD = −3.4; 95% CI: −5.22–−1.57) in RFA treatment were significantly lower than those of LH treatment. However, the incidence of cancer recurrence was significantly higher for RFA treatment compared with LH treatment (OR = 2.68; 95% CI: 1.72–4.18). Conclusions LH treatment is preferred over RFA treatment with a better radical effect, but RFA treatment is more beneficial with smaller trauma, development of less complications, and shorter operating time when compared with HCC treatment.

In December 2019, novel coronavirus pneumonia-19 (COVID-19) was discovered in the viral pneumonia cases that occurred in Wuhan, China, and then quickly spread around the world. This report described the clinical course of two COVID-19 patients and the purpose of the study was to discuss the combination of chest CT and clinical features for diagnosis of COVID-19. The first case was a typical COVID-19 case. A 66-year-old female presented to our hospital with a 3-day history of fever. She had contact with a COVID-19 patient. Chest CT showed a typical COVID-19 appearance. She was diagnosed with COVID-19 by a positive nucleic acid test. The second case was a 50-year-old male with a 2-day history of fever. He denied having been to Wuhan. Chest CT also showed typical features of COVID-19 pneumonia. COVID-19 nucleic acid tests were repeated up to seven times and the results remained controversial. Eventually, he was diagnosed with COVID-19. Our study shows that chest CT has high sensitivity for diagnosis of COVID-19 in clinical practice, particularly when the nucleic acid test is negative. The chest CT should be considered as a diagnostic tool for the COVID-19 screening, comprehensive evaluation, and follow-up and patients would benefit from effective treatments in time.

IntroductionTransanal endoscopic microsurgery (TEM) is an organ-preserving treatment alternative for patients with early rectal cancer. However, TEM alone is associated with greater risk of local recurrence and inferior survival in comparison with total meso-rectal excision (TME). As an important adjuvant therapy, radiotherapy can effectively reduce the local recurrence rate of rectal cancer. This study aimed to investigate whether TEM followed by radiotherapy can be a valid alternative to TME in T2N0M0 distal rectal cancer treatment.MethodsWe plan to recruit 168 participants meeting established inclusion criteria. Following informed consent, participants will randomly receive treatment protocols of TEM followed by radiotherapy (a total dose of 45–50.4 Gy given in 25–28 factions) or TME. Depending on post-operative pathology, the participants will receive either long-term follow-up or further treatment. The primary endpoint of this trial is 3-year local recurrence rate. The secondary end points include 3-year disease-free survival rate, 3-year overall survival rate, 3-year mortality rate, post-operative quality of life, post-operative safety index, intraoperative evaluation index and post-operative short-term evaluation index.DiscussionThis trial is the first prospective randomized trial to investigate the rectum preserving treatment by using transanal local excision followed by radiotherapy.Clinical trial registrationThe trial was prospectively registered at ClinicalTrials.gov NCT04098471 on September 20, 2019.