Targeting ERBB2 and PIK3R1 as a therapeutic strategy for dilated cardiomyopathy: A single-cell sequencing and mendelian randomization analysis.

Background: Dilated cardiomyopathy (DCM) is widely recognized as a significant contributor to heart failure. Nevertheless, the absence of pharmaceutical interventions capable of reversing disease progression and improving prognosis underscores the imperative for additional research in this area. Methods: First, we identified and evaluated three gene sets, namely "SC-DCM", "EP-DCM" and "Drug", using big data and multiple bioinformatics analysis methods. Accordingly, drug-treatable ("Hub") genes in DCM were identified. Following this, four microarray expression profile datasets were employed to authenticate the expression levels and discriminatory efficacy of "Hub" genes. Additionally, mendelian randomization analysis was conducted to ascertain the causal association between the "Hub genes" and heart failure. Finally, the "DGIdb" was applied to identify "Hub" genes-targeted drugs. The "ssGSEA" algorithm assessed the level of immune cell infiltration in DCM. Results: Enrichment analysis showed that the "SC-DCM" and "EP-DCM" gene sets were closely associated with DCM. PIK3R1 and ERBB2 were identified as drug-treatable genes in DCM. Additional analysis using MR supported a causal relationship between ERBB2 and heart failure, but not PIK3R1. Moreover, PIK3R1 was positively correlated with immune activation, while ERBB2 was negatively correlated. We found that everolimus was a pharmacological inhibitor for both PIK3R1 and ERBB2. However, no pharmacological agonist was found for ERBB2. Conclusion: PIK3R1 and ERBB2 are drug-treatable genes in DCM. ERBB2 has a causal effect on heart failure, and its normal expression may play a role in preventing the progression of DCM to heart failure. In addition, there is a cross-expression of PIK3R1 and ERBB2 genes in both DCM and tumors. The adaptive immune system and PIK3R1 may be involved in DCM disease progression, while ERBB2 exerts a protective effect against DCM.

Clinical values of circulating tumor cells count in localized renal cell carcinoma.

Background: Renal cancer is one of the most common malignant tumors of the urinary system, with distant metastasis occurring 30% of patients. Therefore, early detection and monitoring of tumor progression are of great significance in the diagnosis and treatment of renal cancer. However, current biomarkers used to diagnose, monitor recurrence and assess prognosis of renal cancer are still uncertain. Circulating tumor cells (CTCs) are tumor cells detached from the primary tumor or metastasis, invaded and existing in the peripheral blood, and are one of the most promising liquid biopsy targets because they can provide complete cell biological information. Microfluidic chip has advantages of miniaturization, high integration, and fast analysis, which has advantages in CTC separation and enrichment. Methods: In this study, 1 mL peripheral blood of each 30 patients with early localized renal cancer was collected before and 1 day after surgery. CTC enrichment was performed by microfluidic chip and CTCs were identified by immunofluorescence staining. All patients were followed up for a median of 17 months. Results: The number of CTCs before surgery was higher than that after surgery (P<0.001), and the number was positively correlated with tumor-node-metastasis (TNM) stage and International Society of Urological Pathology (ISUP) grade. Patients in group CTC ≤2 had a longer progression-free survival (PFS) than those in group CTC ≥3 (P<0.05). Conclusions: Surgical treatment can remarkably reduce the number of CTCs in patients, and CTC counts can also play a role in monitoring tumor load and predicting prognosis in renal cancer.

A plasma proteomic approach in patients with heart failure after acute myocardial infarction: insights into the pathogenesis and progression of the disease.

Aims: The pathogenesis of disease progression targets for patients with heart failure after acute myocardial infarction was investigated by using plasma proteomics. Methods: The plasma proteomes of acute myocardial infarction patients with (MI-HF) and without (MI-WHF) heart failure were compared. Each group consisted of 10 patients who were matched for age and sex. The peptides were analyzed by 2-dimensional liquid chromatography coupled to tandem mass spectrometry in a high definition mode. Parallel reaction monitoring (PRM) verified the selected target proteins. Results: We identified and quantified 2,589 and 2,222 proteins, respectively, and found 117 differentially expressed proteins (DEPs) (≥1.5-fold), when the MI-HF and MI-WHF groups were compared. Of these 51 and 66 were significantly up-regulated and down-regulated, respectively. The significant DEPs was subjected to protein-protein interaction network analysis which revealed a central role of the NF-κB signaling pathway in the MI-HF patients. PRM verified that MB, DIAPH1, VNN1, GOT2, SLC4A1, CRP, CKM, SOD3, F7, DLD, PGAM2, GOT1, UBA7 and HYOU1 were 14 proteins which were highly expressed in MI-HF patients. Conclusions: These findings showed a group of proteins related to the NF-κB signaling pathway in the pathogenesis of patients with poor outcomes after experiencing MI-HF. These proteins may be useful candidate markers for the diagnosis of MI-HF as well as help to elucidate the pathophysiology of this major cause of mortality in older patients.

Has new rural pension system reduced the intake of junk food among rural older adults? Evidence from China.

At present, China has become one of the fastest growing countries in terms of junk food consumption. However, there has been less previous evidence for the effect of endowment insurance on dietary health. Using the data China Family Panel Studies (CFPS) from 2014, this paper exploits a policy, the New Rural Pension System (NRPS), that only the older adults who have reached 60 years old can receive pensions and conduct a fuzzy regression discontinuity (FRD) to address endogeneity and examine the causal effect of the NRPS on the intake of junk food among rural older adults in China. We find that the NRPS can significantly reduce junk food intake among them, which remains robust after a series of robustness tests. In addition, heterogeneity analysis shows that the female, low-educated, unemployed, and low-income groups are more sensitive to the pension shock from the NRPS. The result of our study provides insights to effectively improve people's dietary quality and related policy formulation.

Association of the awareness of the epidemic, mental health status with mobile phone screen use time in Chinese college students during COVID-19 isolation and control.

OBJECTIVE: This study aimed to investigate the awareness of the epidemic among college students and their mental health as well as to explore the association between their awareness of the epidemic mental health and the daily mobile phone screen use time, in order to provide guidance for the publicity of school epidemic prevention and control knowledge and the psychological counseling of students. METHODS: A cross-sectional design was employed among 780 college students, The Pandemic Fatigue Questionnaire, epidemic prevention and control knowledge and the mental health Scale were used to collect data through an online survey. RESULTS: 1. Awareness rate of the transmission routes and protective measures of COVID-19 among college students is higher when the daily mobile screen use time is 3-7 hours. 2. 21.79% of the 780 college students felt stressed; 24.87% felt anxious; 19.23% showed depression. 3. The scores of each subscale in the daily mobile phone screen use time of 3-7 hours and more than 7 hours were higher, and the scores of each subscale in the group of more than 7 hours were the highest. Further correlation analysis found that the time spent on mobile phone screens was positively correlated with stress, anxiety, and depression scores (r = 0.155, 0.180, 0.182, P<0.01). CONCLUSION: During the COVID-19 isolation and control period, college students with different mobile screen usage time have different understandings of the epidemic. Long-term mobile screen use is related to the occurrence of psychological problems such as stress, anxiety, and depression. Therefore, education departments and schools should pay attention to college students' mobile phone use time to reduce the occurrence of bad psychological state of students.

Common molecular mechanism and immune infiltration patterns of thoracic and abdominal aortic aneurysms.

Background: Aortic disease (aortic aneurysm (AA), dissection (AD)) is a serious threat to patient lives. Little is currently known about the molecular mechanisms and immune infiltration patterns underlying the development and progression of thoracic and abdominal aortic aneurysms (TAA and AAA), warranting further research. Methods: We downloaded AA (includes TAA and AAA) datasets from the GEO database. The potential biomarkers in TAA and AAA were identified using differential expression analysis and two machine-learning algorithms. The discrimination power of the potential biomarkers and their diagnostic accuracy was assessed in validation datasets using ROC curve analysis. Then, GSEA, KEGG, GO and DO analyses were conducted. Furthermore, two immuno-infiltration analysis algorithms were utilized to analyze the common immune infiltration patterns in TAA and AAA. Finally, a retrospective clinical study was performed on 78 patients with AD, and the serum from 6 patients was used for whole exome sequencing (WES). Results: The intersection of TAA and AAA datasets yielded 82 differentially expressed genes (DEGs). Subsequently, the biomarkers (CX3CR1 and HBB) were acquired by screening using two machine-learning algorithms and ROC curve analysis. The functional analysis of DEGs showed significant enrichment in inflammation and regulation of angiogenic pathways. Immune cell infiltration analysis revealed that adaptive and innate immune responses were closely linked to AA progression. However, neither CX3CR1 nor HBB was associated with B cell-mediated humoral immunity. CX3CR1 expression was correlated with macrophages and HBB with eosinophils. Finally, our retrospective clinical study revealed a hyperinflammatory environment in aortic disease. The WES study identified disease biomarkers and gene variants, some of which may be druggable. Conclusion: The genes CX3CR1 and HBB can be used as common biomarkers in TAA and AAA. Large numbers of innate and adaptive immune cells are infiltrated in AA and are closely linked to the development and progression of AA. Moreover, CX3CR1 and HBB are highly correlated with the infiltration of immune cells and may be potential targets of immunotherapeutic drugs. Gene mutation research is a promising direction for the treatment of aortic disease.

Social exclusion, thwarted belongingness, and perceived burdensomeness: construct validity and psychometric properties of the Interpersonal Needs Questionnaire among patients with sexually transmitted infections in Shanghai, China.

BACKGROUND: Sexually transmitted infections (STIs) are a serious public health problem worldwide. Patients with STIs have a high rate of psychosocial problems and may perceive unmet interpersonal needs, which is considered a proximal and sufficient cause of suicidal thoughts and behaviors. The present study examined the construct validity and psychometric properties of the 15-item Interpersonal Needs Questionnaire among patients with STIs in Shanghai, China. METHODS: We recruited 910 patients with STIs (438 males and 472 females; mean age = 38.72, standard deviation [SD] = 13.034) from the Shanghai Skin Disease Hospital using accidental sampling. Baseline descriptive statistics were calculated using R 4.0.0, and a latent variable model was developed using Mplus 7.4. RESULTS: The construct validity results supported a latent variable measurement model with three distinct but related constructs (thwarted belongingness, perceived burdensomeness, and social exclusion) (p < 0.001, χ2/df = 2.475, root mean square error of approximation = 0.057, comparative fit index = 0.931, Tucker-Lewis index = 0.916, standardized root mean residual = 0.044). The Cronbach's α and McDonald's ω values were 0.849 and 0.767 for the total scale, 0.888 and 0.889 for perceived burdensomeness, 0.764 and 0.777 for social exclusion, and 0.892 and 0.893 for thwarted belongingness. Interpersonal needs were significantly associated with low self-esteem (r = 0.539), loneliness (r = 0.573), depression (r = 0.338), entrapment (r = 0.420), defeat (r = 0.579), and low perceived social support (r = 0.424). CONCLUSIONS: This was the first study to highlight social exclusion as a distinct but related dimension of interpersonal needs. This finding indicates that patients with STIs perceive high social exclusion. Therefore, health providers should consider the psychological status of these patients and implement strategies to support their integration into society.

Neoantigen-reactive T cell: An emerging role in adoptive cellular immunotherapy.

Adoptive cellular immunotherapy harnessing the intrinsic immune system for precise treatment has exhibited preliminary success against malignant tumors. As one of the emerging roles in adoptive cellular immunotherapy, neoantigen-reactive T cell (NRT) focuses on the antigens expressed only by tumor cells. It exclusively obliterates tumor and spares normal tissues, achieving more satisfying effects. However, the development of NRT immunotherapy remains in a relatively primitive stage. Current challenges include identification of NRTs and maintenance of adoptive cell efficacy in vivo. The possible side effects and other limitations of this treatment also hinder its application. Here, we present an overview of NRT immunotherapy and discuss the progress and challenges as well as the prospects in this promising field.

Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy.

OBJECTIVE: Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. METHODS: Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. RESULTS: 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree = 24), GNB3 (degree = 23), QSOX1 (degree = 21), and APOB (degree = 17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. CONCLUSION: Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.

Correlation between coronary stenosis and Toll-like receptors 2 and 4 levels in Chinese Zhuang patients with coronary heart disease.

The present study attempted to determine the correlation of the degree of coronary artery stenosis and Tolllike receptor 2/4 (TLR2/4) levels in Chinese Zhuang patients with coronary heart disease (CHD). A total of 466 Chinese patients from the Zhuang Ethnic population diagnosed with CHD at the Department of Cardiology the Affiliated Hospital of Youjiang Medical University between January 2016 and August 2017, together with 102 control patients, were recruited for the present study. The patients with CHD were divided into three groups depending on the number of diseased arteries. The patients with CHD were also classified according to their Gensini scores. Blood liver and renal function parameters, as well as blood sugar and lipid levels were measured. ELISA was used for TLR2/4 measurements. There were no significant differences with gender, age and body mass index between the CHD and control groups. The levels of TLR2/4 in the peripheral blood of the control and CHD groups were 2.34±0.85/5.08±2.41 and 5.22±3.16/9.33±4.92 ng/ml, respectively, and the differences were significant (P<0.001). Analysis of the three subgroups of vessel disease indicated that the expression of TLR2/4 was progressively higher with the increase in the number of affected vessels (P<0.01). There were also significant differences between the mild, moderate and severe stenosis groups (P<0.01). A positive linear correlation between TLR2/4 and the Gensini coronary artery score was identified (r=0.508 and 0.346, respectively; P<0.0001). In conclusion, the present study determined a positive correlation between the degree of coronary artery stenosis and the expression level of TLR2/4 in the serum of Chinese Zhuang patients with CHD. Serum TLR2/4 may be used to predict the severity of CHD.

Association of Toll-like receptor 4 polymorphisms with the risk of coronary artery disease in the ethnic Zhuang population of the Guangxi Province of China.

OBJECTIVES: Toll-like receptor 4 (TLR4) is known to be involved in the innate immunity and inflammatory responses that plays a crucial role in the pathogenesis of coronary artery disease (CAD). This study aimed to examine the potential relationship of TLR4 polymorphisms and serum TLR4 protein levels and the risk of CAD in the ethnic Zhuang population of China. METHODS: 1171 serum samples were collected from Zhuang patients, including 556 CAD cases (≥50% luminal stenosis of any coronary vessel) and 615 normal healthy controls (subjects with no luminal stenosis in coronary arteries). Detection of TLR4 polymorphisms was by single base extension polymerase chain reaction (Snapshot PCR) and DNA sequencing (rs11536879A/G and rs11536889G/C) gene sequence in all subjects. Serum TLR4 protein concentrations was measured by ELISA. RESULTS: There are significant differences in the allele and genotype frequencies of TLR4 gene rs11536889 between Chinese Zhuang CAD patients and controls, especially in the males. Male carriers of rs11536879 andrs11536889 variant alleles show an increased risk of CAD compared to non-carriers. Serum TLR4 protein levels of CAD patients are higher than controls and the levels tended to increase with the number of coronary artery lesions. Serum TLR4 protein levels of CAD patients showed no correlation with rs11536879 and rs11536889 polymorphisms. CONCLUSIONS: The rs11536879 and rs11536889 polymorphisms of TLR4 gene and serum TLR4 protein levels may contribute to the occurrence and development of CAD. However, the rs11536879 and rs11536889 polymorphisms have no significant effects on the expression of serum TLR4 protein in Zhuang patients with CAD.