The relationship between psychological distress and weight maintenance in weight cycling: mediating role of eating behavior.

BACKGROUND: Obesity is a global public health concern. The goal of this study was to see if eating habits could mediate the relationship between psychological distress and weight maintenance in a population with a history of weight cycling. METHODS: A 3-month outpatient intervention consisting of a diet and exercise program was provided to 153 participants. Psychological distress, appetite, and behavior were assessed at the beginning and end of the study. Anthropometric measurements were taken at baseline and six months. RESULTS: After the structural equation model was developed, it was discovered that the psychological status of people with obesity and weight cycling histories correlated with the weight loss outcome effect (three and six months). This effect was mediated by factors related to eating behavior. Associative psychological factors had a direct effect on eating behavior (three months: ß = 0.181, 95% CI: 0.055-0.310; six months: ß = 0.182, 95% CI: 0.039-0.332) and appetite had a direct effect on eating behavior (three months: ß = 0.600, 95% CI: 0.514-0.717; six months: ß = 0.581, 95% CI: 0.457-0.713), both of which were significant (p < 0.01). At three months, psychological distress has a more substantial positive impact on weight change, with eating behavior acting as a partial mediator. At six months, there was no support for appetite's moderating role in eating behavior. CONCLUSIONS: The findings suggest that psychological interventions should be strengthened to improve weight loss effectiveness, particularly in participants with a history of weight cycling, making weight loss more complicated and prone to rebound. CLINICAL TRIAL REGISTRATION: The study has been registered in Clinical Trials (NCT05311462).

Effect of supervised exercise training on cardiovascular function in patients with intermittent claudication: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to determine the effect of supervised exercise training (SET) on cardiovascular function in patients with intermittent claudication (IC). A systematic search in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was conducted. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), rate pressure product (RPP), cardiac output (CO), peak oxygen consumption (VO2peak), and heart rate variability (HRV). Secondary outcomes were maximum walking distance (MWD) and pain-free walking distance (PFWD). Outcomes were reported as weighted mean difference (WMD) between the SET group and the control group and synthesized by using the random-effects model. Seventeen RCTs with a total of 936 patients were included in this review. SET resulted in significant improvements of SBP (WMD = - 7.40, 95% CI - 10.69 ~ - 4.11, p < 0.001, I2 = 15.2%), DBP (WMD = - 1.92, 95% CI - 3.82 ~ - 0.02, p = 0.048, I2 = 0.0%), HR (WMD = - 3.38, 95% CI - 6.30 ~ - 0.46, p = 0.023, I2 = 0.0%), RPP (WMD = - 1072.82, 95% CI - 1977.05 ~ - 168.59, p = 0.020, I2 = 42.7%), and VO2peak with plantar flexion ergometer exercise (WMD = 5.57, 95% CI 1.66 ~ 9.49, p = 0.005, I2 = 62.4%), whereas CO and HRV remained statistically unaltered. SET also improved MWD (WMD = 139.04, 95% CI 48.64 ~ 229.44, p = 0.003, I2 = 79.3%) and PFWD (WMD = 40.02, 95% CI 23.85 ~ 56.18, p < 0.001, I2 = 0.0%). In conclusion, SET is effective in improving cardiovascular function in patients with IC, which was confirmed on outcomes of cardiovascular function associated with exercise ability. The findings hold out that the standard therapy of SET can improve not only walking distance but also cardiovascular function in patients with IC.

Chimeric antigen receptor T cell and regulatory T cell therapy in non-oncology diseases: A narrative review of studies from 2017 to 2023.

Recently, the remarkable success of chimeric antigen receptor T cell (CAR-T) therapy in treating certain tumors has led to numerous studies exploring its potential application to treat non-oncology diseases. This review discusses the progress and evolution of CAR-T cell therapies for treating non-oncology diseases over the past 5 years. Additionally, we summarize the advantages and disadvantages of CAR-T cell therapy in treating non-oncological diseases and identify any difficulties that should be overcome. After conducting an in-depth analysis of the most recent studies on CAR-T technology, we discuss the key elements of CAR-T therapy, such as developing an effective CAR design for non-oncological diseases, controlling the rate and duration of response, and implementing safety measures to reduce toxicity. These studies provide new insights into different delivery strategies, the discovery of new target molecules, and improvements in the safety of CAR-T therapy for non-oncological diseases.

The effect of various urea-in-water solution types on exhaust particle number emission.

In order to qualitatively evaluate the impact of urea-in-water solution on the particle number emission, five different urea types were chosen under diesel engine bench test. The results show that compared to the instantaneous particle concentrations without injection, the instantaneous particle concentrations with injection increase distinctly, which are larger around 0.3-1.2 times than that without urea-in-water solution. At high speed phase, the instantaneous particle concentrations with urea-in-water solution injection rise obviously, especially for C and E solutions. In addition, the particle size distribution characteristic does not change with the urea-in-water solution dosing. The PN emission factors follow the sequence of C solution > E solution > A solution > B solution > D solution. It is deduced that the metallic element contents in the urea-in-water solution play a key role for the PN emission factor. In the future, the particle formation due to urea-in-water solution injection should be given more attention.

Identifying Ferroptosis-Related Genes Associated with Weight Loss Outcomes and Regulation of Adipocyte Microenvironment.

SCOPE: The study is about the influence of ferroptosis-related genes combined with the immune microenvironment exerted on weight control outcomes and systematic analysis. METHODS AND RESULTS: Subcutaneous adipose tissue (sWAT) samples from 11 subjects with good outcome and 10 subjects with poor outcome in weight management are obtained from the Gene Expression Omnibus database. The results are validated in vivo in animal models with different weight loss outcomes. The CIBERSORT algorithm is used to evaluate the differences in immune cell infiltration in each sample. Patients with poor outcome have higher levels of ferroptosis in the adipose tissue. Remarkable differences in cytokine production, nuclear factor kappa-B(NF-κB) transcription factor activity, leukocyte migration involved in the inflammatory response, and other biological processes are also observed compared to that in the well-controlled group. Aldo-keto reductase family 1-member C1(AKR1C1), nuclear receptor coactivator 4(NCOA4), and glutamate-cysteine ligase catalytic subunit(GCLC) are identified as core predictive markers and their expression patterns are confirmed in animal models. CONCLUSIONS: Ferroptosis and its mediated inflammation play an important role in long-term weight control, and analyses of the role of ferroptosis-related genes(FRGs) in weight control may provide new potential therapeutic targets for long-term weight control. Anti-inflammatory diets that mitigate inflammatory responses and affect ferroptosis may be considered in the future to improve weight control.

Identifying oxidative stress-related biomarkers in idiopathic pulmonary fibrosis in the context of predictive, preventive, and personalized medicine using integrative omics approaches and machine-learning strategies.

Background: Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease with a poor prognosis that currently lacks effective treatment methods. Preventing the acute exacerbation of IPF, identifying the molecular subtypes of patients, providing personalized treatment, and developing individualized drugs are guidelines for predictive, preventive, and personalized medicine (PPPM / 3PM) to promote the development of IPF. Oxidative stress (OS) is an important pathological process of IPF. However, the relationship between the expression levels of oxidative stress-related genes (OSRGs) and clinical indices in patients with IPF is unclear; therefore, it is still a challenge to identify potential beneficiaries of antioxidant therapy. Because PPPM aims to recognize and manage diseases by integrating multiple methods, patient stratification and analysis based on OSRGs and identifying biomarkers can help achieve the above goals. Methods: Transcriptome data from 250 IPF patients were divided into training and validation sets. Core OSRGs were identified in the training set and subsequently clustered to identify oxidative stress-related subtypes. The oxidative stress scores, clinical characteristics, and expression levels of senescence-associated secretory phenotypes (SASPs) of different subtypes were compared to identify patients who were sensitive to antioxidant therapy to conduct differential gene functional enrichment analysis and predict potential therapeutic drugs. Diagnostic markers between subtypes were obtained by integrating multiple machine learning methods, their expression levels were tested in rat models with different degrees of pulmonary fibrosis and validation sets, and nomogram models were constructed. CIBERSORT, single-cell RNA sequencing, and immunofluorescence staining were used to explore the effects of OSRGs on the immune microenvironment. Results: Core OSRGs classified IPF into two subtypes. Patients classified into subtypes with low oxidative stress levels had better clinical scores, less severe fibrosis, and lower expression of SASP-related molecules. A reliable nomogram model based on five diagnostic markers was constructed, and these markers' expression stability was verified in animal experiments. The number of neutrophils in the immune microenvironment was significantly different between the two subtypes and was closely related to the degree of fibrosis. Conclusion: Within the framework of PPPM, this work comprehensively explored the role of OSRGs and their mediated cellular senescence and immune processes in the progress of IPF and assessed their capabilities aspredictors of high oxidative stress and disease progression,targets of the vicious loop between regulated pulmonary fibrosis and OS for targeted secondary and tertiary prevention, andreferences for personalized antioxidant and antifibrotic therapies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00334-4.

A systematic review and meta-analysis of cold exposure and cardiovascular disease outcomes.

Background: Cold exposure has been considered an essential risk factor for the global disease burden, while its role in cardiovascular diseases is still underappreciated. The increase in frequency and duration of extreme cold weather events like cold spells makes it an urgent task to evaluate the effects of ambient cold on different types of cardiovascular disease and to understand the factors contributing to the population's vulnerability. Methods: In the present systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane. We included original research that explored the association between cold exposure (low temperature and cold spell) and cardiovascular disease outcomes (mortality and morbidity). We did a random-effects meta-analysis to pool the relative risk (RR) of the association between a 1°C decrease in temperature or cold spells and cardiovascular disease outcomes. Results: In total, we included 159 studies in the meta-analysis. As a result, every 1°C decrease in temperature increased cardiovascular disease-related mortality by 1.6% (RR 1.016; [95% CI 1.015-1.018]) and morbidity by 1.2% (RR 1.012; [95% CI 1.010-1.014]). The most pronounced effects of low temperatures were observed in the mortality of coronary heart disease (RR 1.015; [95% CI 1.011-1.019]) and the morbidity of aortic aneurysm and dissection (RR 1.026; [95% CI 1.021-1.031]), while the effects were not significant in hypertensive disease outcomes. Notably, we identified climate zone, country income level and age as crucial influential factors in the impact of ambient cold exposure on cardiovascular disease. Moreover, the impact of cold spells on cardiovascular disease outcomes is significant, which increased mortality by 32.4% (RR 1.324; [95% CI 1.2341.421]) and morbidity by 13.8% (RR 1.138; [95% CI 1.015-1.276]). Conclusion: Cold exposure could be a critical risk factor for cardiovascular diseases, and the cold effect varies between disease types and climate zones. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022347247.

Weight cycling based on altered immune microenvironment as a result of metaflammation.

As a result of the obesity epidemic, more people are concerned about losing weight; however, weight regain is common, leading to repeated weight loss and weight cycling. The health benefits of early weight loss are nullified by weight regain after weight cycling, which has much more severe metabolic consequences. Weight cycling alters body composition, resulting in faster fat recovery and slower muscle reconstruction. This evident fat accumulation, muscle loss, and ectopic fat deposition destroy the intestinal barrier, increase the permeability of the small intestinal epithelium, and cause the lipotoxicity of lipid metabolites and toxins to leak into extraintestinal tissues and circulation. It causes oxidative stress and hypoxia in local tissues and immune cell infiltration in various tissues, all contributing to the adaptation to this metabolic change. Immune cells transmit inflammatory responses in adipose and skeletal muscle tissue by secreting cytokines and adipokines, which mediate immune cell pathways and cause metaflammation and inefficient metabolic degradation. In this review, we focus on the regulatory function of the immunological microenvironment in the final metabolic outcome, with a particular emphasis on the cellular and molecular processes of local and systemic metaflammation induced by weight cycling-induced changes in body composition. Metaflammation in adipose and muscle tissues that is difficult to relieve may cause weight cycling. As this chronic low-grade inflammation spreads throughout the body, metabolic complications associated with weight cycling are triggered. Inhibiting the onset and progression of metabolic inflammation and enhancing the immune microenvironment of adipose and muscle tissues may be the first step in addressing weight cycling.

Effect of malnutrition and nutritional support to reduce infections in elderly hospitalized patients with cancer: A multicenter survey in China.

OBJECTIVES: Malnutrition is common among elderly patients with cancer, and greatly affects patients' quality of life. Malnutrition is a key factor in the development of systemic, chronic, low-grade inflammation that can exacerbate. METHODS: A total of 633 elderly patients with cancer from 29 tertiary public hospitals in 14 cities in China were selected as the research subjects. Physical examination, questionnaire survey, medical history collection, and blood index detection were performed on the research subjects to analyze the relationship between malnutrition, nutritional support, and infection status. RESULTS: There was no significant difference in infection rate among elderly hospitalized patients with cancer and different cancer types, cancer stages, or therapy methods (P > 0.05). The proportion of vomiting, loss of appetite, depression, and physical fatigue in patients with good nutritional status were lower than in patients with moderate or severe malnutrition (P < 0.05). Nutritional support is crucial for the nutritional status of elderly patients with cancer, and patients without special nutritional guidance are more likely to develop infection (P < 0.05). After adjusting for confounding variables, the results of the logistic regression analysis showed that oral nutritional supplements (odds ratio [OR]: 0.088; 95% confidence interval [CI], 0.015-0.514), parenteral nutrition (OR: 0.091; 95% CI, 0.011-0.758), and individualized nutritional guidance (OR: 0.026; 95% CI, 0.003-0.202) were all protective factors associated with cancer infection. CONCLUSIONS: Many elderly hospitalized patients with cancer have local or systemic infections, and good nutrition is associated with lower rates of infection. Receiving nutritional guidance or support is associated with lower infection rates in elderly patients with cancer.

Tiny Drosophila intestinal stem cells, big power.

The signaling pathways are highly conserved between Drosophila and mammals concerning intestinal development, regeneration, and disease. The powerful genetic tools of Drosophila make it a valuable and convenient alternative to answer basic biological questions that can not be addressed using mammalian models. In this review, we discuss recent advances in how we use fly midgut to answer the following key questions: (1) How intestine stem cell niches are established; (2) which factors control asymmetric division of stem cells; (3) how intestinal cells interact with environmental factors, such as tissue damage, microbiota, and diet; (4) how to screen aging/cancer-related factors or drugs by fly intestine stem cells.

Ag85a-S2 Activates cGAS-STING Signaling Pathway in Intestinal Mucosal Cells.

Brucellosis is a zoonotic disease caused by Gram-negative bacteria. Most of the brucellosis vaccines in the application are whole-bacteria vaccines. Live-attenuated vaccines are widely used for brucellosis prevention in sheep, goats, pigs, and cattle. Thus, there is also a need for an adjuvanted vaccine for human brucellosis, because the attenuated Brucella vaccines now utilized in animals cause human illness. Here, we developed a live-attenuated Brucella suis strain 2 vaccine (S2) adjuvanted with Ag85a (Ag85a-S2). We found that Ag85a-S2 activated cGAS-STING pathways both in intestinal mucosal cells in vivo and in the BMDM and U937 cell line in vitro. We demonstrated that the cGAS knockout significantly downregulated the abundance of interferon and other cytokines induced by Ag85a-S2. Moreover, Ag85a-S2 triggered a stronger cellular immune response compared to S2 alone. In sum, Ag85a-S2-mediated enhancement of immune responses was at least partially dependent on the cGAS-STING pathway. Our results provide a new candidate for preventing Brucella pathogens from livestock, which might reduce the dosage and potential toxicity compared to S2.

Iron metabolism-related genes reveal predictive value of acute coronary syndrome.

Iron deficiency has detrimental effects in patients with acute coronary syndrome (ACS), which is a common nutritional disorder and inflammation-related disease affects up to one-third people worldwide. However, the specific role of iron metabolism in ACS progression is opaque. In this study, we construct an iron metabolism-related genes (IMRGs) based molecular signature of ACS and to identify novel iron metabolism gene markers for early stage of ACS. The IMRGs were mainly collected from Molecular Signatures Database (mSigDB) and two relevant studies. Two blood transcriptome datasets GSE61144 and GSE60993 were used for constructing the prediction model of ACS. After differential analysis, 22 IMRGs were differentially expressed and defined as DEIGs in the training set. Then, the 22 DEIGs were trained by the Elastic Net to build the prediction model. Five genes, PADI4, HLA-DQA1, LCN2, CD7, and VNN1, were determined using multiple Elastic Net calculations and retained to obtain the optimal performance. Finally, the generated model iron metabolism-related gene signature (imSig) was assessed by the validation set GSE60993 using a series of evaluation measurements. Compared with other machine learning methods, the performance of imSig using Elastic Net was superior in the validation set. Elastic Net consistently scores the higher than Lasso and Logistic regression in the validation set in terms of ROC, PRC, Sensitivity, and Specificity. The prediction model based on iron metabolism-related genes may assist in ACS early diagnosis.

The interleukin-enhanced binding factor 3-mediated inhibition of nitric oxide production via phosphoinositide 3-kinase/protein kinase B pathway contributes to central cardiovascular regulation in the rostral ventrolateral medulla in hypertension.

Hypertension is characterized by sympathetic hyperactivity, which is related to the overexcitation of the presympathetic neurons in the rostral ventrolateral medulla (RVLM). Nitric oxide (NO) has been reported to be a vital neuromodulator involved in central cardiovascular regulation. However, the mechanism of interleukin-enhanced binding factor 3 (ILF3) participating in blood pressure (BP) regulation is still unclear. Therefore, this study aims to clarify the role of ILF3 within the rostral ventrolateral medulla (RVLM) in regulating NO in hypertension. It was found that the expression level of ILF3 was significantly increased in the RVLM of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats through microarray gene expression analysis, Western blot, and immunofluorescence. Overexpression of ILF3 by injecting constructed adenovirus into the RVLM increased the BP and renal sympathetic nerve activity (RSNA) of the WKY rats, significantly decreasing NO production and neuronal nitric oxide synthase (nNOS) expression. Knockdown of ILF3 in the RVLM of SHR significantly reduced BP but increased NO production and the neuronal nitric oxide synthase (nNOS) expression. Furthermore, it was found that the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was activated via Western blotting in the RVLM after overexpression of ILF3, whereas it was attenuated after knockdown of ILF3 in SHR. In addition, inhibition of PI3K by intracisternal infusion of the PI-103 attenuated the increase in Akt phosphorylation and decrease in nNOS expression and NO production caused by overexpressing ILF3, which ultimately blunted high BP induced by overexpressing ILF3. Taken together, this current study suggests that ILF3 participates in high BP via reducing NO production in the RVLM through PI3K/Akt pathway.

Identification and immune characteristics of molecular subtypes related to fatty acid metabolism in idiopathic pulmonary fibrosis.

Background: Although fatty acid metabolism has been confirmed to be involved in the pathological process of idiopathic pulmonary fibrosis (IPF), systematic analyses on the immune process mediated by fatty acid metabolism-related genes (FAMRGs) in IPF remain lacking. Methods: The gene expression data of 315 patients with IPF were obtained from Gene Expression Omnibus database and were divided into the training and verification sets. The core FAMRGs of the training set were identified through weighted gene co-expression network analysis. Then, the fatty acid metabolism-related subtypes in IPF were identified on the basis of k-means unsupervised clustering. The scores of fatty acid metabolism and the expression of the fibrosis biomarkers in different subtypes were compared, and functional enrichment analysis was carried out on the differentially expressed genes between subtypes. A random forest model was used to select important FAMRGs as diagnostic markers for distinguishing between subtypes, and a line chart model was constructed and verified by using other datasets and rat models with different degrees of pulmonary fibrosis. The difference in immune cell infiltration among subtypes was evaluated with CIBERSORT, and the correlation between core diagnostic markers and immune cells were analyzed. Results: Twenty-four core FAMRGs were differentially expressed between the training set and normal samples, and IPF was divided into two subtypes. Significant differences were observed between the two subtypes in biological processes, such as linoleic acid metabolism, cilium movement, and natural killer (NK) cell activation. The subtype with high fatty acid metabolism had more severe pulmonary fibrosis than the other subtype. A reliable construction line chart model based on six diagnostic markers was constructed, and ABCA3 and CYP24A1 were identified as core diagnostic markers. Significant differences in immune cell infiltration were found between the two subtypes, and ABCA3 and CYP24A1 were closely related to NK cells. Conclusion: Fatty acid metabolism and the immune process that it mediates play an important role in the occurrence and development of IPF. The analysis of the role of FAMRGs in IPF may provide a new potential therapeutic target for IPF.

Contribution of cyclooxygenase-2 overexpression to enhancement in tonically active glutamatergic inputs to the rostral ventrolateral medulla in hypertension.

OBJECTIVE: Cyclooxygenase (COX) is critical in regulating cardiovascular function, but its role involved in the central control of blood pressure (BP) is uncovered. The tonic glutamatergic inputs to the rostral ventrolateral medulla (RVLM) are enhanced in hypertension. Here, the present study was designed to investigate the effect and mechanism of central COX on tonic glutamatergic inputs to the RVLM and BP regulation. METHODS: Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) received RVLM microinjection of adeno-associated viral vectors to promote or inhibit the COX2 expression were subjected to subsequent experiments. Glutamate level and glutaminase expression were detected by ELISA and western blot, respectively. The function of tonic glutamatergic inputs was assessed by BP response to microinjection of the glutamate receptor antagonist into the RVLM. PC12 cells were used to detect the underlying signal pathway. RESULTS: The RVLM COX2 expression and prostaglandin E2 level were significant higher in SHRs than in WKY rats. Overexpression of COX2 in the RVLM produced an increase in basal BP, RVLM glutamate level, and glutaminase expression in WKY rats, while they were significantly reduced by interfering with COX2 expression in SHRs. Microinjections of the glutamate receptor antagonist into the RVLM produced a significant BP decrease in WKY rats with COX2 overexpression pretreatment. Furthermore, the increased levels of BP, glutamate content, and glutaminase activity in the RVLM evoked by central infusion of angiotensin II were attenuated in COX2 knockout mice. It was also found that prostaglandin E2 increased supernatant glutamate level and phosphorylation of signal transducer and activator of transcription 3 in PC12 cells. CONCLUSION: Our findings suggest that upregulated COX2 expression enhances the tonically active glutamatergic inputs to the RVLM, which is associated with cardiovascular regulation in hypertension.

Identification of pyroptosis-related subtypes and establishment of prognostic model and immune characteristics in asthma.

Background: Although studies have shown that cell pyroptosis is involved in the progression of asthma, a systematic analysis of the clinical significance of pyroptosis-related genes (PRGs) cooperating with immune cells in asthma patients is still lacking. Methods: Transcriptome sequencing datasets from patients with different disease courses were used to screen pyroptosis-related differentially expressed genes and perform biological function analysis. Clustering based on K-means unsupervised clustering method is performed to identify pyroptosis-related subtypes in asthma and explore biological functional characteristics of poorly controlled subtypes. Diagnostic markers between subtypes were screened and validated using an asthma mouse model. The infiltration of immune cells in airway epithelium was evaluated based on CIBERSORT, and the correlation between diagnostic markers and immune cells was analyzed. Finally, a risk prediction model was established and experimentally verified using differentially expressed genes between pyroptosis subtypes in combination with asthma control. The cMAP database and molecular docking were utilized to predict potential therapeutic drugs. Results: Nineteen differentially expressed PRGs and two subtypes were identified between patients with mild-to-moderate and severe asthma conditions. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes. Poor control subtypes were closely related to glucocorticoid resistance and airway remodeling. BNIP3 was identified as a diagnostic marker and associated with immune cell infiltration such as, M2 macrophages. The risk prediction model containing four genes has accurate classification efficiency and prediction value. Small molecules obtained from the cMAP database that may have therapeutic effects on asthma are mainly DPP4 inhibitors. Conclusion: Pyroptosis and its mediated immune phenotype are crucial in the occurrence, development, and prognosis of asthma. The predictive models and drugs developed on the basis of PRGs may provide new solutions for the management of asthma.

Nano Carbon Tracing-based Treatment of Breast Cancer Lymphadenectomy and Nursing Intervention of Postoperative Lymphedema.

to investigate the tracing and therapeutic effects of carbon nanoparticles epirubicin (CNP-EPI) on axillary lymphadenectomy for breast cancer and postoperative lymphedema nursing intervention, a total of 60 breast cancer patients in Harbin Medical University Cancer Hospital were selected as the study subjects and randomly divided into group A (n=30) and group B (n=30). They were subcutaneously injected with 1 mL of CNP-EPI 1 day before surgery and 3 days before surgery, respectively, and underwent axillary lymph node dissection. Lymphedema nursing intervention and routine care were implemented in groups A and B, respectively. After adsorption of 2 mL of 6 mg/mL epirubicin by 1 mL carbon nanoparticles, epirubicin could be slowly released with a cumulative release rate of 64.7 %. The black staining rate was 80.2 % (341/425) in group A and 57.7 % (217/376) in group B, and the difference was statistically significant (P < 0.05). The black staining rate in metastatic lymph nodes was 73.1 % (23/52) in group A and 65.9 % (27/41) in group B (P > 0.05). The incidence rate of edema at 1, 3, and 6 months after operation in group A was significantly lower than that in group B (P < 0.05). Carbon nanoparticles have strong adsorption properties and slow drug release ability; subcutaneous injection of CNP-EPI axillary lymph nodes around the areola 1 day before surgery has a better lymphatic tracing effect; lymphedema nursing intervention can effectively reduce the incidence of prognostic lymphedema.

The Peripheral Circulating Exosomal microRNAs Related to Central Inflammation in Chronic Heart Failure.

Sympathetic hyperactivity plays an important role in the progression of chronic heart failure (CHF). It is reported that inflammation in the rostral ventrolateral medulla (RVLM), a key region for sympathetic control, excites the activity of neurons and leads to an increase in sympathetic outflow. Exosome, as the carrier of microRNAs (miRNAs), has the function of crossing the blood-brain barrier. The present study was designed to investigate the effect of exosomal miRNAs on central inflammation via peripheral-central interaction in CHF. The miRNA microarray detection was performed to compare the difference between circulating exosomes and the RVLM in CHF rats. It was shown that the expression of miR-214-3p was significantly up-regulated, whereas let-7g-5p and let-7i-5p were significantly down-regulated in circulating exosomes and the RVLM. Further studies in PC12 cells revealed that miR-214-3p enhanced the inflammatory response, while let-7g-5p and let-7i-5p reduced the neuroinflammation. The direct interaction between the miRNA and its inflammatory target gene (miR-214-3p, Traf3; let-7g-5p, Smad2; and let-7i-5p, Mapk6) was confirmed by the dual-luciferase reporter assay. These results suggest that the circulating exosomes participate in the enhancement of inflammatory response in the RVLM through their packaged miRNAs, which may further contribute to sympathetic hyperactivity in CHF.

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment.

Background: Autophagy has been proven to play an important role in the pathogenesis of asthma and the regulation of the airway epithelial immune microenvironment. However, a systematic analysis of the clinical importance of autophagy-related genes (ARGs) regulating the immune microenvironment in patients with asthma remains lacking. Methods: Clustering based on the k-means unsupervised clustering method was performed to identify autophagy-related subtypes in asthma. ARG-related diagnostic markers in low-autophagy subtypes were screened, the infiltration of immune cells in the airway epithelium was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. On the basis of the expression of ARGs and combined with asthma control, a risk prediction model was established and verified by experiments. Results: A total of 66 differentially expressed ARGs and 2 subtypes were identified between mild to moderate and severe asthma. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes, and the low-autophagy subtype was closely associated with severe asthma, energy metabolism, and hormone metabolism. The autophagy gene SERPINB10 was identified as a diagnostic marker and was related to the infiltration of immune cells, such as activated mast cells and neutrophils. Combined with asthma control, a risk prediction model was constructed, the expression of five risk genes was supported by animal experiments, was established for ARGs related to the prediction model. Conclusion: Autophagy plays a crucial role in the diversity and complexity of the asthma immune microenvironment and has clinical value in treatment response and prognosis.