Circulating acetylcholine serves as a potential biomarker role in pulmonary hypertension.

BACKGROUND: An increased acetylcholine (ACh) level in the right ventricle tissue of pulmonary hypertension (PH) was revealed, which indicated the important role of ACh in disease pathogenesis. However, the relationship between plasma ACh levels and disease conditions and patients' prognosis has not been investigated. We aimed to explore the association between plasma ACh levels and the prognosis of patients with PH. We also discussed the feasibility of plasma ACh as a biomarker, which may contribute to the management of PH patients in the future. METHODS: Patients with confirmed PH in Fuwai Hospital from April 2019 to August 2020 were enrolled. The primary clinical outcome in this study was defined as a composite outcome, including death/lung transplantation, heart failure, and worsening of symptoms. Fasting plasma was collected to detect the ACh levels. The association between ACh levels and patients' prognosis was explored. RESULTS: Finally, four hundred and eight patients with PH were enrolled and followed for a mean period of 2.5 years. Patients in the high ACh group had worse World Health Organization Functional Class (WHO-FC), lower 6-minute walk distance (6 MWD), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP). Notably, echocardiographic and hemodynamic parameters in the high metabolite group also suggested a worse disease condition compared with the low ACh group. After adjusting for confounders, compared with low ACh patients, those with high metabolite levels still have worse prognoses characterized as elevated risk of mortality, heart failure, and symptoms worsening. CONCLUSION: High circulating ACh levels were associated with severe PH conditions and poor prognosis, which might serve as a potential biomarker in PH.

Adaptation strategies of leaf traits and leaf economic spectrum of two urban garden plants in China.

BACKGROUND: Previous studies of the relationships between traits have focused on the natural growth conditions of wild plants. Urban garden plants exhibit some differences in plant traits due to environmental interference. It is unknown whether the relationships between the leaf traits of urban garden plants differ under distinct climates. In this study, we revealed the variation characteristics of the leaf functional traits of trees, shrubs, and vines in two urban locations. Two-way ANOVA was used to reveal the response of plant leaf traits to climate and life forms. Pearson correlation analysis and principal component analysis were used to calculate the correlation coefficient between the leaf functional traits of plants at the two locations. RESULTS: Leaf dry matter content (LDMC) and vein density (VD) of different life forms in Mudanjiang were higher than those in Bozhou (P < 0.05), and the relative water content (RWC) in Bozhou was higher, whereas vein density (VD) of trees and shrubs in the two urban locations was significant (P < 0.05), but the vines were not significant. The photosynthetic pigments of tree and shrub species were larger in Mudanjiang, but the opposite was true for the vines. Both leaf vein density (VD) and stomatal density (SD) showed a very significant positive correlation in the two urban locations (P < 0.01), and both were significantly positively correlated with specific leaf area (SLA) (P < 0.05); and negatively correlated with leaf thickness (LT), and the relationship between pigment content were closer. CONCLUSION: The response to climate showed obvious differences in leaf traits of different life forms species in urban area, but the correlations between the traits showed convergence, which reflects that the adaptation strategies of garden plant leaves to different habitats are both coordinated and relatively independent.

Possible sarcopenia and risk of new-onset type 2 diabetes mellitus in older adults in China: a 7-year longitudinal cohort study.

BACKGROUND: Previous studies have shown that type 2 diabetes mellitus (T2DM) can cause sarcopenia; however, these conditions may have a bidirectional association. This study aimed to explore the longitudinal association between possible sarcopenia and new-onset T2DM. METHODS: We conducted a population-based cohort study using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). This study included participants aged ≥ 60 years who were free of diabetes during the baseline survey of CHARLS (2011 to 2012) and were followed up until 2018. Possible sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Cox proportional hazards regression models were used to evaluate the effect of possible sarcopenia on new-onset T2DM. RESULTS: In total, 3,707 individuals were enrolled in this study, with a median age of 66 years; the prevalence of possible sarcopenia was 45.1%. During the 7-year follow-up, 575 cases (15.5%) of incident diabetes were identified. Participants with possible sarcopenia were more likely to have new-onset T2DM than those without possible sarcopenia (hazard ratio: 1.27, 95% confidence interval: 1.07-1.50; p = 0.006). In subgroup analysis, we found a significant association between possible sarcopenia and T2DM in individuals aged < 75 years or with a BMI < 24 kg/m². However, this association was not significant in individuals aged ≥ 75 years or with a BMI ≥ 24 kg/m². CONCLUSIONS: Possible sarcopenia is associated with an increased risk of new-onset T2DM in older adults, especially in individuals who are not overweight and aged 75 years or younger.

Circulating choline levels are associated with prognoses in patients with pulmonary hypertension: a cohort study.

BACKGROUNDS: Mounting evidences have highlighted the association between metabolites and cardiovascular diseases. Our previous works have demonstrated that circulating metabolite, trimethylamine oxide, was associated with prognosis of patients with pulmonary hypertension (PH). Choline is a precursor of trimethylamine oxide and its role in PH remains unknown. Here, we aimed to validate the hypothesis that circulating choline levels were associated with prognoses in patients with PH. METHODS: Inpatients diagnosed with PH-defined as mean pulmonary arterial pressure ≥ 25 mmHg by right heart catheterisation-from Fuwai Hospital were enrolled after excluding relative comorbidities. Fasting blood samples were obtained to assess choline levels and other clinical variables. The primary endpoints were defined as death, escalation of targeted medication, rehospitalization due to heart failure, PH deterioration. The follow-up duration was defined as the time from the choline examination to the occurrence of outcomes or the end of the study. The associations between circulating choline levels and disease severity and prognoses were explored. RESULTS: Totally, 272 inpatients with PH were enrolled in this study. Patients were divided into high and low choline groups according to the 50th quartile of circulating choline levels, defined as 12.6 µM. After confounders adjustment, the high circulating choline levels were still associated with poor World Health Organization functional class, elevated N-terminal pro-B-type natriuretic peptide, and decreased cardiac output index indicating the severe disease condition. Moreover, elevated choline levels were associated with poor prognoses in PH patients even after adjusting for confounders (hazard ratio = 1.934; 95% CI, 1.034-3.619; P = 0.039). Subgroup analyses showed that choline levels predicted the prognosis of patients with pulmonary arterial hypertension but not chronic thromboembolic pulmonary hypertension. CONCLUSIONS: Choline levels were associated with disease severity and poor prognoses of patients with PH, especially in pulmonary arterial hypertension suggesting its potential biomarker role.

Using a New Deep Learning Method for 3D Cephalometry in Patients With Hemifacial Microsomia.

ABSTRACT: Deep learning algorithms based on automatic 3D cephalometric marking points about people without craniomaxillofacial deformities have achieved good results. However, there has been no previous report about hemifacial microsomia (HFM). The purpose of this study is to apply a new deep learning method based on a 3D point cloud graph convolutional neural network to predict and locate landmarks in patients with HFM based on the relationships between points. The authors used a PointNet++ model to investigate the automatic 3D cephalometry. And the mean distance error (MDE) of the center coordinate position and the success detection rate (SDR) were used to evaluate the accuracy of systematic labeling. A total of 135 patients were enrolled. The MDE for all 32 landmarks was 1.46 ± 1.308 mm, and 10 landmarks showed SDRs at 2 mm over 90%, and only 4 landmarks showed SDRs at 2 mm under 60%. Compared with the manual reproducibility, the standard distance deviation and coefficient of variation values for the MDE of the artificial intelligence system was 0.67 and 0.43, respectively. In summary, our training sets were derived from HFM computed tomography to achieve accurate results. The 3D cephalometry system based on the graph convolutional network algorithm may be suitable for the 3D cephalometry system in HFM cases. More accurate results may be obtained if the HFM training set is expanded in the future.

Reliability and Validity Evaluation of the Chin Augmentation With Medpor Using FACE-Q Scales Effectiveness.

BACKGROUND: Chin augmentation (CA) is important treatment modality for microgenia. The use of implantable alloplastic biomaterials in CA grows in popularity, and there is no verifiable documentation of patients' satisfaction about CA with Medpor (CAWM) exists in the literature, this study examined effectiveness of CAWM by analyzing patient satisfaction. METHODS: Patients had undergone CAWM were followed up postoperatively. Occurrence of complications was collected, patients' satisfactions with chin shape and surgical decision were analyzed using FACE-Q scales, the reliability of operation was studied through analyzing the statistics, and the influences of sex and follow-up time on satisfaction were compared. RESULTS: One hundred ten patients who had undergone CAWM received FACE-Q scales and 64 valid questionnaires were collected. 61 (95.3%) showed high satisfaction with chin shape after CAWM (Cronbach α coefficients were all above 0.8), the median values of satisfaction of chin shape and decision making were 85 (67, 100) and 100 (75,100), respectively. The median chin satisfactions of females and males were 87 (67, 100), 79 (61,100). The median chin satisfactions of patients had surgery before 2 years ago and within 2 years were 81 (67, 100), 87 (64,100), respectively. During the follow-up, among 110, 1 (0.91%) developed graft-related infection and 1 (0.91%) developed an allergic reaction, 1 (0.91%) underwent prosthesis removal because dissatisfaction with chin shape. CONCLUSIONS: Chin augmentation with prothesis is a safe and efficacious way to improve microgenia. Medpor is the desired implant material with less infection, displacement and bone absorption, which is worthy of promotion and further study in CA surgery.

Bioinformatics Analysis of Hub Genes Involved in Smoke-Induced Hemifacial Microsomia Pathogenesis.

OBJECTIVE: Tobacco smoke is a recognized teratogen, which increases the risk for hemifacial microsomia (HFM) of the fetus during maternal pregnancy. The present study aimed to explore potential mechanisms and verify hub genes of HFM associated with smoke and tobacco smoke pollution (TSP) via bioinformatics methods. METHODS: Hemifacial microsomia and smoke and TSP pathogenic genes were obtained. A protein-protein interactional (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were performed by Metascape. Finally, we used the cytoHubba plug-in to screen the hub genes. RESULTS: A total of 43 HFM genes and 50 optimal smoke candidate genes were selected. Functional enrichment analysis largely focused on tissue morphogenesis and development. Two modules were identified from the PPI network, and 10 hub genes were screened out. The genes most relevant to smoke-induced HFM pathogenesis included TP53 , ESR1 , ESR2 , and HNRNPL. CONCLUSIONS: This study identified some significant hub genes, pathways, and modules of HFM related to smoke by bioinformatics analyses. Our results suggest that the TP53 , ESR1 , ESR2 , and HNRNPL gene subfamilies may have played a major role in HFM induced by smoke and TSP.

Using a New Deep Learning Method for 3D Cephalometry in Patients With Cleft Lip and Palate.

Deep learning algorithms based on automatic 3-dimensional (D) cephalometric marking points about people without craniomaxillofacial deformities has achieved good results. However, there has been no previous report about cleft lip and palate. The purpose of this study is to apply a new deep learning method based on a 3D point cloud graph convolutional neural network to predict and locate landmarks in patients with cleft lip and palate based on the relationships between points. The authors used the PointNet++ model to investigate the automatic 3D cephalometric marking points. And the mean distance error of the center coordinate position and the success detection rate (SDR) were used to evaluate the accuracy of systematic labeling. A total of 150 patients were enrolled. The mean distance error for all 27 landmarks was 1.33 mm, and 9 landmarks (30%) showed SDRs at 2 mm over 90%, and 3 landmarks (35%) showed SDRs at 2 mm under 70%. The automatic 3D cephalometric marking points take 16 seconds per dataset. In summary, our training sets were derived from the cleft lip with/without palate computed tomography to achieve accurate results. The 3D cephalometry system based on the graph convolutional neural network algorithm may be suitable for 3D cephalometry system in cleft lip and palate cases. More accurate results may be obtained if the cleft lip and palate training set is expanded in the future.

A Novel Method for one-Stage Repair of the lip Vermilion Defects in Progressive Hemifacial Atrophy.

BACKGROUND: Progressive hemifacial atrophy often causes lip vermilion defects in patients. In this study, we described a one-stage repair method for lip defects in progressive hemifacial atrophy using a lip vermilion mucosal flap or combined dermal fat flap graft. PATIENTS AND METHODS: Patients diagnosed with progressive hemifacial atrophy with lip vermilion defects from 2010 to 2022 were included in this study. Based on the severity and location of the patient's lip defect, a lip vermilion mucosal flap was designed and transferred to the lip defect or combined with a hip dermal fat flap for one-stage repair of the lip morphology. Lip morphology and function of patients were followed up after surgery. RESULTS: A total of 22 patients were enrolled in this study, including 15 patients with lip defects on the upper lip alone and 7 patients with both upper and lower lip defects. Follow-up six months to two years postoperatively, all patients recovered uneventfully without complications. The repaired lips of the patient had a full and symmetrical morphology with no visible scarring. Two patients experienced transient dysesthesia of the lips postoperatively and both returned to normal after three months. All patients had good lip closure with normal dietary and speech function. CONCLUSIONS: The method we described for repairing lip defects in progressive hemifacial atrophy can achieve satisfactory aesthetic and functional lip results. The distinct advantage of this approach is that the patients undergo only one-stage operation and it can be used to repair both upper and lower lip defects.

Analysis of Obstructive Sleep Apnoea in Craniofacial Microsomia Based on Polysomnography.

OBJECTIVE: This study aimed to investigate the prevalence of obstructive sleep apnoea (OSA) in patients with craniofacial microsomia (CFM) through polysomnography (PSG) and the relationship with the severity of CFM. METHODS: This study reviewed patients of CFM with pre-operative PSG data between January 2005 and September 2023. Patients were grouped according to the Pruzansky-Kaban classification. OSA was diagnosed and severity was assessed by the obstructive apnea-hypopnea index. The Pediatric Sleep Questionnaire was used to investigate OSA-related signs and symptoms. The χ 2 test and Fisher's exact test were used to compare between groups. Univariate logistic regression was used to identify risk factors associated with OSA. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 121 patients with CFM were included in the study with 3 bilateral and 118 unilateral patients. In total, 86 patients (71.07%) were diagnosed with OSA. The prevalence of OSA in type IIa, type IIb and type III was 72.97%, 78.33%, and 47.62%. There was no statistically significant difference in the prevalence of OSA between type IIa and type IIb (p > .05). The difference in the prevalence of OSA between type III and type II was statistically significant (p < .05). Snoring was the most common symptom among the patients of CFM with OSA. CONCLUSIONS: Patients with CFM have a higher incidence of OSA based on PSG in type II and type III patients. The incidence of OSA did not correlate positively with the severity of CFM, with type III patients having certain particularities.

Higher circulating Trimethylamine N-oxide levels are associated with worse severity and prognosis in pulmonary hypertension: a cohort study.

BACKGROUND: Trimethylamine N-oxide (TMAO), the gut microbiota-dependent metabolite, is a potential biomarker in several cardiovascular diseases. However, no study has investigated its value in pulmonary hypertension (PH). Therefore, this study aimed to explore the association between plasma TMAO levels and prognosis in patients with PH. METHODS: Inpatients with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH), PAH associated with congenital heart disease (CHD-PAH), and chronic thromboembolic pulmonary hypertension (CTEPH) at Fuwai Hospital were enrolled after excluding those with relative comorbidities. The endpoint was defined as a composite outcome including death, rehospitalisation due to heart failure, and at least 15% decreased 6-min walk distance from the baseline. Fasting blood samples were collected to measure plasma levels of TMAO and other clinical indicators. The associations between TMAO levels with disease severity and patients' prognosis were investigated. RESULTS: In total, 163 patients with PH were included, with a mean follow-up duration of 1.3 years. After adjusting for confounding factors, elevated TMAO levels were still associated with severe disease conditions. TMAO levels dynamically decreased in stable and improved patients after treatment [ΔTMAO = - 0.2 (- 1.6, 0.7) µmol/L, P = 0.006]. Moreover, high plasma TMAO levels predicted a poor prognosis in the PH cohort (P < 0.001), and the association remained significant after adjusting the confounders, including treatment, risk stratification, and PH subtypes. CONCLUSION: Elevated plasma TMAO levels were associated with severe disease conditions and poor prognosis in patients with PH, indicating its potential biomarker role in PH.

Systematic review on factors associated with self-perceived burden among cancer patients.

INTRODUCTION: Cancer is the leading cause of death in the world. There was a high prevalence of high self-perceived burden (SPB) among cancer patients and this could bring adverse consequences to the physical and mental health of cancer patients, which can lead to suicide if not treated well. This review aims to determine the prevalence of SPB among cancer patients and its risk factors. METHODS: Published journals before September 2021, from five databases (PubMed, ScienceDirect, Springer, Cochrane, and CNKI) were retrieved according to the keywords. The keywords used included cancer patients, terminally ill patients, cancer, SPB, self-perceived burden, self-burden, self-perceived, factor, predictor, associated factor, determinants, risk factor, prognostic factor, covariate, independent variable, and variable. The quality of the inclusion and exclusion criteria was independently reviewed by three researchers. RESULTS: Out of 12,712 articles, there are 22 studies met the eligibility criteria. The prevalence of SPB among cancer patients ranged from 73.2 to 100% in Malaysia, China, and Canada. Most of them had moderate SPB. Out of the reported factors, age, gender, marital status, ethnicity, residence, educational level, occupational status, family income, primary caregiver, payment methods, disease-related factors, psychological factors, and physical factors were mostly reported across the studies. CONCLUSIONS: In conclusion, SPB prevalence is high in cancer patients. Therefore, hospitals, non-governmental organizations, relevant policymakers, and communities can provide special programs for high-risk groups to provide psychological guidance or design corresponding interventions to reduce the SPB level of patients and improve the quality of life.

Identification of Hub Genes in Hemifacial Microsomia: Evidence From Bioinformatic Analysis.

OBJECTIVE: This thesis addresses a neglected aspect of bioinformatics research of hemifacial microsomia (HFM). Existing research stops short of prediction based on big data. This study combines multiple databases to explore underlying pathogenesis using bioinformatic approach. METHODS: The research consisted of multiple bioinformatic methods, included pathogenic genes analyses, protein-protein interaction network construction, functional enrichment, and mining target genes related miRNA, for studying pathogenic genes of HFM. RESULTS: Total of 140 genes were identified as potential genes in the study. The protein-protein interaction networks for pathogenic genes were constructed, which contained 138 nodes and 243 edges with RAF1, MAP2K1, MAP2K2, MAPK3, MAPK1, EGFR, BRAF, LMNA, ESPR1, and SFN as the hub genes. These genes were discovered significantly enriched in MAPK pathway. Besides, the whole of interactions between miRNAs and the top 5 hub genes were revealed. CONCLUSIONS: Our results indicated that occurrence of HFM is attributed to a variety of genes. Furthermore, the interactions of pathogenic genes were further elucidated by using bioinformatics approach. It reveals the MAPK pathway play an essential role in its pathogenesis. It may provide a novel perspective on better understanding the pathogenesis and more accurate early screening of HFM.

Bioinformatics Analysis of Hub Genes Involved in Alcohol-Related Hemifacial Microsomia Pathogenesis.

OBJECTIVE: Alcohol is a recognized teratogen, and alcohol exposure increases the risk for hemifacial microsomia (HFM) of the fetus during maternal pregnancy. The present study aimed to explore potential mechanisms and verify hub genes of HFM associated with alcohol by bioinformatics methods. METHODS: First, HFM and alcohol pathogenic genes were obtained. Thereafter, a protein-protein interactional (PPI) network was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were performed by Metascape. Finally, we used the cytoHubba plugin to screen the hub genes. RESULTS: A total of 43 HFM genes and 50 optimal alcohol candidate genes were selected. The PPI networks for pathogenic genes contained 93 nodes and 503 edges. Functional enrichment analysis largely focused on tissue formation and development. Two modules were identified from the PPI network, and 10 hub genes were screened out. The genes most relevant to alcohol-induced HFM pathogenesis included CTNNB1, TP53, MYC, HDAC1, and SOX2. CONCLUSIONS: This study identified some significant hub genes, pathways, and modules of HFM related to alcohol by bioinformatics analyses. Our results suggest that the CTNNB1, TP53, MYC, HDAC1, and SOX B1 gene subfamilies may have played a major role in alcohol-induced HFM.

Mandibular Distraction Osteogenesis First for Children With Severe Unilateral Hemifacial Microsomia: Treatment Strategy and Outcomes.

ABSTRACT: The treatment for severe hemifacial microsomia (HFM), especially type III case, is extremely difficult. Mandibular distraction osteogenesis (MDO) was rarely used as the primary choice in the treatment of severe type cases. The authors sought to observe the short-term therapeutic outcomes of patients with severe unilateral HFM who underwent MDO first.A retrospective study of children underwent MDO or later received costochondral graft (CCG) for severe unilateral HFM from 2009 to 2019 was conducted. Cephalometric measurements and clinical variables were analyzed to evaluate the effectiveness of MDO first strategy for severe cases and compare disparity between Pruzansky-Kaban classification type IIb and type III groups.Thirty-six patients (23 males and 13 females) underwent MDO first for severe HFM were included for analysis in the present study. The average age at MDO was 8.33 ±â€Š2.03 years. At the last follow-up, MDO acquired significant improvement in mandibular height, maxillary cant, chin deviation, lip commissural line tilt, and clinical chin deviation (P < 0.05). Distraction results were stable during the short-term follow-up in terms of the mandibular height ratio and maxillary cant (P > 0.05).MDO is a proper primary method for suitable type IIb and type III HFM cases. MDO can immediately and significantly improve the facial skeleton deficiency, extend the associated soft tissue at the same time, and lay foundation for secondary surgery. MDO can achieve the downgrade of HFM deficiency severity. MDO followed by costochondral graft can get satisfactory esthetic and structural consequence for type III patients.

Responses of greenhouse gas emissions to residue returning in China's croplands and influential factors: A meta-analysis.

Climate change is a global issue threatening agricultural production and human survival. However, agriculture sector is a major source of global greenhouse gases (GHGs), especially CH4 and N2O. Crop residue returning (RR) is an efficient practice to sequestrate soil carbon and increase crop yields. However, the efficiency of RR to mitigate climate change and maintain food security will be affected by the response of GHG emissions at both per area-scale and per yield-scale. Therefore, a national meta-analysis was conducted using 309 comparisons from 44 publications to assess the responses of GHG emissions to RR in China's croplands. The results indicated that little response of GWP to RR was observed with conditions under lower nitrogen fertilizer input rates (0-120 kg ha-1), mulch retention, returning one time in double cropping systems, returning with half residue, weakly acidic soil (pH 5.5-6.5), initial SOC contents >20 g kg-1, or mean annual precipitation <1000 mm. In order to mitigate climate change and sustain food security, RR combined with paddy-upland rotation, nitrogen fertilizer input rates of 240-360 kg ha-1, and neutral soil (pH 6.5-7.5) could decrease GWP at per unit of crop yield, which ultimately leads to a lower effect on GHGI and a higher crop production efficiency. In-depth studies should be conducted in the future to explore the interactions between various factors influencing GHG emissions under RR conditions. Overall, optimizing the interactions with management and site-specific conditions, potential for regulating GHGs emissions of RR can be enhanced.

d-Allulose Ameliorates Skeletal Muscle Insulin Resistance in High-Fat Diet-Fed Rats.

BACKGROUND: d-Allulose is a rare sugar with antiobesity and antidiabetic activities. However, its direct effect on insulin sensitivity and the underlying mechanism involved are unknown. OBJECTIVE: This study aimed to investigate the effect of d-allulose on high-fat diet (HFD)-induced insulin resistance using the hyperinsulinemic-euglycemic (HE)-clamp method and intramuscular signaling analysis. METHODS: Wistar rats were randomly divided into three dietary groups: chow diet, HFD with 5% cellulose (HFC), and HFD with 5% d-allulose (HFA). After four weeks of feeding, the insulin tolerance test (ITT), intraperitoneal glucose tolerance test (IPGTT), and HE-clamp study were performed. The levels of plasma leptin, adiponectin, and tumor necrosis factor (TNF)-α were measured using the enzyme-linked immunosorbent assay. We analyzed the levels of cell signaling pathway components in the skeletal muscle using Western blotting. RESULTS: d-allulose alleviated the increase in HFD-induced body weight and visceral fat and reduced the area under the curve as per ITT and IPGTT. d-Allulose increased the glucose infusion rate in the two-step HE-clamp test. Consistently, the insulin-induced phosphorylation of serine 307 in the insulin receptor substrate-1 and Akt and expression of glucose transporter 4 (Glut-4) in the muscle were higher in the HFA group than HFC group. Furthermore, d-allulose decreased plasma TNF-α concentration and insulin-induced phosphorylation of stress-activated protein kinase/Jun N-terminal kinase in the muscle and inhibited adiponectin secretion in HFD-fed rats. CONCLUSIONS: d-allulose improved HFD-induced insulin resistance in Wistar rats. The reduction of the proinflammatory cytokine production, amelioration of adiponectin secretion, and increase in insulin signaling and Glut-4 expression in the muscle contributed to this effect.

mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

It is growingly concerned about methamphetamine (MA)-induced lung toxicity. IMP1 is identified as a key molecule for cell life processes, but the role of IMP1 in MA-induced senescence remains unclear. The purpose of this study was to investigate whether chronic exposure to MA can cause autophagy and senescence of the lungs, whether there are interactions between Mammalian target of rapamycin (mTOR) and IMP1 and whether IMP1 is involved in pulmonary senescence promoted by mTOR-autophagy. The rats were randomly divided into control group and MA group, following by H&E staining, immunohistochemistry staining and Western blot. The alveolar epithelial cells were proceeded by ß-galactosidase staining, cell cycle detection, transfection and co-immunoprecipitation. Long-term exposure to MA led to the thickening of alveolar septum and more compact lungs. MA promoted the conversion of LC3-I to LC3-II and inhibited the activation of mTOR to induce autophagy. Bioinformatics and co-immunoprecipitation results presented the interactions between IMP1 and mTOR. MA induced cell senescence by decreasing IMP1, up-regulating p21 and p53, arresting cell cycle and increasing SA-ß-gal. Overexpression of IMP1 reduced p21 and SA-ß-gal to inhibit the senescence of alveolar epithelial cells. These results demonstrated that mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

Clinical characteristics and survival of Chinese patients diagnosed with pulmonary arterial hypertension who carry BMPR2 or EIF2KAK4 variants.

BACKGROUND: Variants in the gene encoding bone morphogenetic protein receptor type II (BMPR2) are the most common genetic cause of pulmonary arterial hypertension (PAH), whereas biallelic variants in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH). Racial background may influence the clinical characteristics of patients diagnosed with PAH or PVOD/PCH. Here, we compared the clinical characteristics and survival between patients with BMPR2 variants or EIF2AK4 variants in a Chinese population. METHODS: Heterozygous variants in BMPR2 and homozygous or compound heterozygous biallelic EIF2AK4 variants predicted to be deleterious were identified as potentially causal. Clinical and radiological data were collected and analysed. The primary outcomes were death or lung transplantation. Hazard ratios (HRs) for death or transplantation associated with the presence of BMPR2 or biallelic EIF2AK4 variants were calculated using Cox proportional hazards models to analyse patient survival. RESULTS: Two hundred thirty-two patients with PAH were enrolled for genetic testing, and PAH patients with associated conditions were excluded from the study. Forty-five patients with BMPR2 variants and 11 patients with biallelic EIF2AK4 variants were recruited. PAH patients with BMPR2 or biallelic EIF2AK4 variants presented symptoms at the ages of 25.57 ± 10.17 years and 31.6 ± 9.38 years, respectively. The whole group of patients showed female dominance either with BMPR2 variants or biallelic EIF2AK4 variants. Specific radiological abnormalities are more prominent in EIF2AK4 variant carriers but can also be found in some patients with BMPR2 variants. Biallelic EIF2AK4 variant carriers had worse survival than BMPR2 variant carriers (p < 0.0001). CONCLUSIONS: Clinical pictures of PAH patients with BMPR2 and biallelic EIF2AK4 variants in the Chinese population differ from other populations by a younger age at diagnosis and demonstrate female dominance in the whole patient group. High-resolution chest CT can help assist in differentiating PAH with PVOD/PCH. BMPR2 variants and biallelic EIF2AK4 variants are associated with adverse outcomes, but the survival of patients with biallelic EIF2AK4 variants is dismal.

[The Clinical Value of the Pathophysiology Oriented Critical Care Ultrasound Exam (POCCUE) Protocol in Acute Respiratory and Circulatory Compromise of Critically Ill Patients].

OBJECTIVE: The aim of this study is to explore the diagnostic and therapeutic accuracy of pathophysiology and clinic oriented critical care ultrasound exam (POCCUE) protocol in acute respiratory and circulatory compromise of critically ill patients. METHODS: Prospectively included patients with acute respiratory and circulatory compromise from ICU of West China Hospital of Sichuan University from March to April 2018. The POCCUE protocol designed according to the pathophysiological changes of acute respiratory and circulatory disorders includes: the first part is the acquiring an ultrasound section and measuring corresponding indicators including pulmonary and echocardiographic indicators; the second part is a comprehensive analysis according to the former examination which evaluates the pathophysiological changes of acute respiratory and circulatory disorders, and then establish the initial etiology diagnosis and start treatment. The clinical value of the POCCUE protocol, including the accuracy of diagnosis, and the differences in treatment was verified by comparing the clinical outcome with the traditional treatment group. RESULTS: A total of 82 subjects were used for statistics. Compare with the traditional group, POCCUE can notably increase the diagnostic and therapeutic accuracy of clinic and pathophysiology (diagnostic accuracy: 93.90% vs. 68.29%, P < 0.01; therapeutic accuracy: 93.90% vs. 62.20%, P < 0.01). CONCLUSION: The POCCUE has a higher accuracy of diagnosis and treatment for patients with acute respiratory and circulatory compromise.