Revealing the changes in signaling pathways caused by tofacitinib in patients with rheumatoid arthritis through RNA sequencing and the correlation with clinical parameters.

OBJECTIVES: The current study is to accelerate the understanding of how tofacitinib works in patients with rheumatoid arthritis (RA) due to the lack of relevant information. METHOD: We selected ten patients with active RA and obtained the expression profile for their peripheral blood mononuclear cells before and after the tofacitinib treatment by RNA sequencing. The gene set enrichment analysis was conducted, and the significantly enriched gene sets were identified. The hub gene highly correlated with clinical parameters in the gene set was selected. We constructed the weighted gene co-expression network, linked modules with clinical indicators, and screened hub genes. The expression of representative hub genes was validated by real-time quantitative PCR (qPCR). RESULTS: Gene set interferon (IFN) α and IFN ß signaling was the most significantly down-regulated after tofacitinib treatment. In this gene set, genes Oas2 and Oasl showed a significant positive correlation with morning stiffness. In co-expression network, gene Vgll3 from the violet module with the highest correlation coefficient, was positively correlated with morning stiffness. Among them, Oasl and Vgll3 have shown significant down-regulation in qPCR validation. CONCLUSIONS: Our results highlighted the role of type I IFN, mainly including IFN α and IFN ß, in the pathogenesis of RA and action for tofacitinib, and provided a new entry point for further elucidating the mechanism of morning stiffness. Key Points • Gene set IFN α and IFN ß signaling was the most significantly down-regulated after tofacitinib treatment in RA patients. • Gene Oasl and Vgll3 were correlated with morning stiffness and significantly down-regulated due to the action of tofacitinib. • Type I IFN system was highlighted in the action of tofacitinib.

Therapeutic potential of Angelica sinensis in addressing organ fibrosis: A comprehensive review.

Fibrosis-related diseases (FRD) include conditions like myocardial fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and others. The impact of fibrosis can be severe, causing organ dysfunction, reduced functionality, and even organ failure, leading to significant health issues. Currently, there is a lack of effective modern anti-fibrosis drugs in clinical practice. However, Chinese medicine has a certain beneficial effect on the treatment of such diseases. Angelica sinensis, with its considerable medicinal value, has garnered attention for its anti-fibrosis properties in recent investigations. In the past few years, there has been a growing number of experimental inquiries into the impact of angelica polysaccharide (ASP), angelica water extract, angelica injection, and angelica compound preparation on fibrosis-associated ailments, piquing the interest of researchers. This paper aims to consolidate recent advances in the study of Angelica sinensis for the treatment of fibrosis-related disorders, offering insights for prospective investigations. Literature retrieval included core electronic databases, including Baidu Literature, CNKI, Google-Scholar, PubMed, and Web of Science. The applied search utilized specified keywords to extract relevant information on the pharmacological and phytochemical attributes of plants. The investigation revealed that Angelica sinensis has the potential to impede the advancement of fibrotic diseases by modulating inflammation, oxidative stress, immune responses, and metabolism. ASP, Angelica sinensis extract, Angelica sinensis injection, and Angelica sinensis compound preparation were extensively examined and discussed. These constituents demonstrated significant anti-fibrosis activity. In essence, this review seeks to gain a profound understanding of the role of Angelica sinensis in treating fiber-related diseases. Organ fibrosis manifests in nearly all tissues and organs, posing a critical challenge to global public health due to its widespread occurrence, challenging early diagnosis, and unfavorable prognosis. Despite its prevalence, therapeutic options are limited, and their efficacy is constrained. Over the past few years, numerous studies have explored the protective effects of traditional Chinese medicine on organ fibrosis, with Angelica sinensis standing out as a multifunctional natural remedy. This paper provides a review of organ fibrosis pathogenesis and summarizes the recent two decades' progress in treating fibrosis in various organs such as the liver, lung, kidney, and heart. The review highlights the modulation of relevant signaling pathways through multiple targets and channels by the effective components of Angelica sinensis, whether used as a single medicine or in compound prescriptions.

Molecular characteristics of circulating B cells and kidney cells at the single-cell level in special types of primary membranous nephropathy.

Background: Although primary membranous nephropathy (pMN) associated with podocyte autoantibodies (POS) is becoming well-known, the molecular characteristics of the specific type of pMN that is negative for podocyte autoantibodies (NEG) is still unclear. Methods: We performed single-cell transcriptome sequencing and single-cell B cell receptor sequencing on circulating CD19+ cells and kidney cells of a NEG paediatric patient with pMN. The single-cell datasets of POS patients and healthy control individuals were included for integrative analysis. Results: The gene expression characteristics and clonal expansion of naïve and memory B cells in the NEG patient changed significantly. We found that a group of CD38+ naïve B cells expanded in the NEG patient, which had the functional characteristics of cell activation. In addition, the conversion between immunoglobulin M (IgM)/IgD and IgG1 in the NEG patient was increased. Parietal epithelial cells (PECs) and podocytes shared similar signature genes (WT1, CLIC5), and new candidate marker genes for PECs, such as NID2, CAV1 and THY1, might contribute to the definition of cell subsets. PECs might have undergone significant changes in the disease, mainly manifested by changes in the expression of CCN2, PLAAT4 and SEPTIN2. The scores of gene sets related to extracellular matrix, cell adhesion and calcium channel in podocytes of the NEG patient was significantly increased. The gene expression of sodium transporter in a group of proximal tubule cells in the disease was significantly increased, especially SLC5A12, which might be related to the oedema of patients. Conclusions: Our research demonstrated the cell type-specific molecular features in the circulation and kidney of the NEG pMN patient.

Global research trends of diabetes remission: a bibliometric study.

Background: Research on diabetes remission has garnered prominence in recent years. However, to date, no pertinent bibliometric study has been published. This study sought to elucidate the current landscape and pinpoint potential new research directions through a bibliometric analysis of diabetes remission. Methods: We perused relevant articles on diabetes remission from January 1, 2000, to April 16, 2023, in the Web of Science. We utilized CiteSpace software and VOSviewer software to construct knowledge maps and undertake analysis of countries, institutional affiliations, author contributions, journals, and keywords. This analysis facilitated the identification of current research foci and forecasting future trends. Results: A total of 970 English articles were procured, and the annual publication volume manifested a steady growth trend. Most of the articles originated from America (n=342, 35.26%), succeeded by China and England. Pertaining to institutions, the University of Newcastle in England proliferated the most articles (n=36, 3.71%). Taylor R authored the most articles (n=35, 3.61%), and his articles were also the most co-cited (n=1756 times). Obesity Surgery dominated in terms of published articles (n=81, 8.35%). "Bariatric surgery" was the most prevalently used keyword. The keyword-clustering map revealed that the research predominantly centered on diabetes remission, type 1 diabetes, bariatric surgery, and lifestyle interventions. The keyword emergence and keyword time-zone maps depicted hotspots and shifts in the domain of diabetes remission. Initially, the hotspots were primarily fundamental experiments probing the feasibilities and mechanisms of diabetes remission, such as transplantation. Over the course, the research trajectory transitioned from basic to clinical concerning diabetes remission through bariatric surgery, lifestyle interventions, and alternative strategies. Conclusion: Over the preceding 20 years, the domain of diabetes remission has flourished globally. Bariatric surgery and lifestyle interventions bestow unique advantages for diabetes remission. Via the maps, the developmental milieu, research foci, and avant-garde trends in this domain are cogently portrayed, offering guidance for scholars.

Development and validation of a nomogram to predict cardiac death after radiotherapy for esophageal cancer.

Background: Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision-making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer. Methods: A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5- and 10-year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C-index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan-Meier (K-M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five- and ten-year survival rates for the two groups were shown using K-M curves. Results: The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C-indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5- and 10-year risk of cardiac death. The model exhibited moderate predictive power for 5- and 10-year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively). Conclusions: Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.

Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome.

Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7 high, TCF7 high, and HLA-DR low) and Treg2 (CCR7 low, TCF7 low, and HLA-DR high). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.

Development and Validation of a Nomogram Model for the Risk of Cardiac Death in Patients Treated with Chemotherapy for Esophageal Cancer.

The primary cause of mortality in esophageal cancer survivors is cardiac death. Early identification of cardiac mortality risk during chemotherapy for esophageal cancer is crucial for improving the prognosis. We developed and validated a nomogram model to identify patients with high cardiac mortality risk after chemotherapy for esophageal cancer for early screening and clinical decision-making. We randomly allocated 37,994 patients with chemotherapy-treated esophageal cancer into two groups using a 7:3 split ratio: model training (n = 26,598) and validation (n = 11,396). 5- and 10-year survival rates were used as endpoints for model training and validation. Decision curve analysis and the consistency index (C-index) were used to evaluate the model's net clinical advantage. Model performance was evaluated using receiver operating characteristic curves and computing the area under the curve (AUC). Kaplan-Meier survival analysis based on the prognostic index was performed. Patient risk was stratified according to the death probability. Age, surgery, sex, and year were most closely related to cardiac death and used to plot the nomograms. The C-index for the training and validation datasets were 0.669 and 0.698, respectively, indicating the nomogram's net clinical advantage in predicting cardiac death risk at 5 and 10 years. The 5- and 10-year AUCs were 0.753 and 0.772 for the training dataset and 0.778 and 0.789 for the validation dataset, respectively. The accuracy of the model in predicting cardiac death risk was moderate. This nomogram can identify patients at risk of cardiac death after chemotherapy for esophageal cancer at an early stage.

Pharmacological action of Hedysarum polysaccharides: a review.

Hedysarum, a traditional Chinese herbal medicine and food with a long history of clinical application, is used to improve health conditions and treat various diseases. Hedysarum polysaccharides (HPS), flavonoids, saponins, and alkaloids, are the primary components of Hedysarum. HPS is the most important natural active ingredient of Hedysarum, which has many pharmacological effects. Currently, HPS exhibits significant promise in drug development for various ailments such as tumors, diabetes, cardiovascular diseases, Alzheimer's disease, and fibrosis. This review paper discusses the extraction, separation, and content determination techniques of HPS, along with the investigation of its chemical constituents. More importantly, we reviewed the anti-inflammatory pharmacological effects of HPS, such as inhibition of inflammatory factors and NF-κB signaling pathway; antitumor activity through apoptosis induction in tumor cells and blocking tumor cell proliferation and metastasis; antioxidant effects; regulation of various cytokines and immune cells; regulation of blood sugar levels, such as in type I and type II diabetes and in diabetic complications; improvement in symptoms of Alzheimer disease; anti-aging and anti-fibrosis properties; and improvement in cerebral ischemia-reperfusion injury. This review paper establishes the theoretical foundation for future studies on the structure, mechanism, and clinical use of HPS.

Early diagnostic value of high-sensitivity cardiac troponin T for cancer treatment-related cardiac dysfunction: a meta-analysis.

Early diagnosis of cancer treatment-related cardiac dysfunction (CTRCD) is important as cancer therapy increases the risk of cardiac dysfunction. High-sensitivity cardiac troponin T (hs-cTnT) is a highly specific marker of myocardial injury. However, its diagnostic value for CTRCD has not been systematically evaluated. This meta-analysis aimed to evaluate whether hs-cTnT could be used as an early diagnostic biomarker for CTRCD. We systematically surveyed PubMed, Embase, Cochrane Library, and Web of Science databases for studies of hs-cTnT for the diagnosis of CTRCD before 1 April 2022. Patients of all ages and all cancer types who underwent echocardiographic left ventricular ejection fraction assessment and blood hs-cTnT and received anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, immune checkpoint inhibitors, and other treatments) were included in this study, resulting in a total of eight studies with 1294 patients. The occurrence of CTRCD was associated with elevated hs-cTnT [sensitivity: 0.78, 95% confidence interval (CI): 0.64-0.88; specificity: 0.75, 95% CI: 0.59-0.86; area under the curve (AUC): 0.83, 95% CI: 0.80-0.86]. We further performed subgroup analysis and found that the AUC of hs-cTnT elevation for the diagnosis of CTRCD increased from 0.83 to 0.90 (95% CI: 0.87-0.92) at 3-6 months, suggesting a higher early diagnostic value of hs-cTnT compared with echocardiography for CTRCD. In terms of clinical applicability, the Fagan plot showed pre-test and post-test probabilities of 51% and 9%, respectively, indicating that hs-cTnT testing can improve the accuracy of clinical diagnosis of CTRCD. However, it was not possible to determine the optimal cut-off value for early diagnosis of CTRCD with hs-cTnT. The Deeks funnel plot was largely symmetrical (P = 0.74); hence, publication bias was not observed. Hs-cTnT allowed early CTRCD diagnosis at 3-6 months. However, further high-quality research is needed to determine the optimal cut-off value for early CTRCD diagnosis with this biomarker.

Corrigendum: Global research trends in catheter ablation and surgical treatment of atrial fibrillation: A bibliometric analysis and science mapping.

[This corrects the article DOI: 10.3389/fsurg.2022.1048454.].

High-throughput RNA-sequencing reveals novel targets of tofacitinib in the treatment of rheumatoid arthritis.

OBJECTIVES: Although tofacitinib has been confirmed to have good efficacy and safety in the treatment of rheumatoid arthritis (RA), the relevant mechanism at the whole transcriptome level has not yet been revealed. In this study, peripheral blood mononuclear cells (PBMCs) from patients with active RA before and after tofacitinib treatment were analysed using whole transcriptome sequencing technology. METHODS: Fourteen patients with active RA were selected to detect the alterations of mRNAs, lncRNAs, circRNAs, and miRNAs in PBMCs before and after tofacitinib treatment using whole transcriptome sequencing. Through bioinformatics analysis, differentially expressed RNAs and their functions were identified. Then the competitive endogenous RNA (ceRNA) network and the protein interaction network were constructed. And qRT-PCR validation was performed for RNAs in the ceRNA network. RESULTS: Based on 69 DEmRNAs, 1743 DElncRNAs, 41 DEcircRNAs, and 4 DEmiRNAs obtained from whole transcriptome sequencing, an RNA interaction network including mRNA DEPDC1, lncRNA ENSG00000272574, circRNA hsa_circ_0034415, miR-190a-5p, and miR-1298-5p was constructed according to ceRNA theory. The qRT-PCR validation results of DEPDC1, hsa_circ_0034415 and miR-1298-5p involved in the network were consistent with the sequencing results, which provided important research evidence for further study of these RNAs. CONCLUSIONS: The new discovered circRNA/lncRNA-miRNA-mRNA network in RA patients relevant to tofacitinib therapy will provide new enlightenment for the role of tofacitinib in the treatment of RA and shed light on a new direction for further exploring the deep-seated mechanism of this drug.

Ultrasensitive and Self-Powered Multiparameter Pressure-Temperature-Humidity Sensor Based on Ultra-Flexible Conductive Silica Aerogel.

The application of silica aerogel has been limited because of its poor mechanical properties. In order to expand the application scope of silica aerogel, this study fabricated an ultra-flexible conductive silica aerogel as a multiparameter sensor. The sample is fabricated by introducing poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) on a base of ultra-flexible silica aerogel, which was prepared by a diene synthesis reaction at atmospheric pressure. The pressure, temperature, and humidity can be converted into electrical signals. The pressure sensitivity can reach up to 54.88 kPa-1, and the detection limit is as low as 5 Pa. The temperature resolution is up to 0.1 K, and the response time of humidity is within 4 s. More importantly, the developed multiparameter sensor can be self-powered to realize multiparameter sensing of pressure, temperature, and humidity. The ultra-flexible conductive silica aerogel is a promising candidate for monitoring human activities and fire-affected areas.

Research progress of natural medicine Astragalus mongholicus Bunge in treatment of myocardial fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis (MF) is a common pathological manifestation of many cardiovascular diseases at a certain stage, with excessive accumulation of collagen fibers, excessive increase in collagen content, and a significant increase in collagen volume as the main pathological changes. There are currently no effective drugs for the treatment of myocardial fibrosis. Traditional Chinese medicine (TCM), the main component of the medical practice used for more than 5000 years, especially in China, often exerts a wider action spectrum than previously attempted options in treating human diseases. In recent times, the great potential of TCM in the treatment of MF has received much attention. Especially many experimental studies on the treatment of MF by Astragalus mongholicus Bunge have been conducted, and the effect is remarkable, which may provide more comprehensive database and theoretical support for the application of Astragalus mongholicus Bunge in the treatment of MF and could be considered a promising candidate drug for preventing MF. AIM OF THE REVIEW: This review summarizes the chemical components of Astragalus mongholicus Bunge, Astragalus mongholicus Bunge extract, Astragalus mongholicus Bunge single prescription, and Astragalus mongholicus Bunge compound preparation in the treatment of MF, and provides comprehensive information and a reliable basis for the exploration of new treatment strategies of botanical drugs in the therapy of MF. METHODS: The literature information was obtained from the scientific databases on ethnobotany and ethnomedicines (up to August 2022), mainly from the PubMed, Web of Science, and CNKI databases. The experimental studies on the anti-myocardial fibrosis role of the effective active components of Astragalus mongholicus Bunge and the utility of its compound preparation and the involved mechanisms were identified. The search keywords for such work included: "myocardial fibrosis" or "Cardiac fibrosis ", and "Astragalus mongholicus Bunge", "extract," or "herb". RESULTS: Several studies have shown that the effective active components of Astragalus mongholicus Bunge and its formulas, particularly Astragaloside IV, Astragalus polysaccharide, total saponins of Astragalus mongholicus Bunge, triterpenoid saponins of Astragalus mongholicus Bunge, and cycloastragenol, exhibit potential benefits against MF, the mechanisms of which appear to involve the regulation of inflammation, oxidant stress, and pro-fibrotic signaling pathways, etc. Conclusion: These research works have shown the therapeutic benefits of Astragalus mongholicus Bunge in the treatment of MF. However, further research should be undertaken to clarify the unconfirmed chemical composition and regulatory mechanisms, conduct standard clinical trials, and evaluate the possible side effects. The insights in the present review provided rich ideas for developing new anti-MF drugs. THESIS: Myocardial fibrosis (MF) with excessive accumulation of collagen fibers, excessive increase in collagen content, and a significant increase in collagen volume as the main pathological changes is a common pathological manifestation of many cardiovascular diseases at a certain stage, which seriously affects cardiac function. At present, there is still a lack of effective drugs for the treatment of MF. Traditional Chinese medicine (TCM), the main component of the medical practice used for more than 5000 years especially in China, often exerts wider action spectrum than previously attempted options in treating human diseases. In recent times, the great potential of TCM in the treatment of MF has received much attention. Especially many experimental studies on the treatment of MF by Astragalus mongholicus Bunge have been conducted, and the effect is remarkable, which may provide more comprehensive data base and theoretical support for the application of Astragalus mongholicus Bunge in the treatment of MF and could be considered a promising candidate drug for preventing MF.

PVA-assisted CNCs/SiO2 composite aerogel for efficient sorption of ciprofloxacin.

Efforts to develop a green, inexpensive and effective adsorbent are crucial for eliminating antibiotics in polluted water. The sorption capacity of the as-prepared polyvinyl alcohol (PVA)-assisted cellulose nanocrystals/SiO2 (CNCs/SiO2) composite aerogel to ciprofloxacin (CIP) rises with the increase of temperature and initial concentration. Reverse trend of sorption capacity can be found when increasing the adsorbent dosage of adsorbent. The optimal pH value for the sorption is proved to be 4. It's found in the uniaxial compression test that the maximum load that PVA-assisted aerogels can withstand is nearly 100 times than that of non-PVA aerogels. Sorption results confirm that the Pseudo-second order (R2 = 0.9885) and Langmuir models (R2 = 0.9959) fit well to sorption kinetics and equilibrium data, respectively. The rate constant differs from the initial concentration of CIP according to the Pseudo-second order model. The composite aerogel sorption capacity of Langmuir (qmax) for CIP was 163.34 mg·g-1. The thermodynamic studies showed that the sorption process is endothermic with the value of enthalpy change of 41.032 kJ/mol. Hydrogen bonding, π-π interaction, hydrophobic and electrostatic interactions are the dominant mechanisms of CIP sorption by the PVA-assisted CNCs/SiO2 composite aerogel.

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy.

Cardiotoxicity is a serious complication of cancer therapy. It is the second leading cause of morbidity and mortality in cancer survivors and is associated with a variety of factors, including oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and abnormal myocardial energy metabolism. A number of studies have shown that traditional Chinese medicine (TCM) can mitigate chemoradiotherapy-associated cardiotoxicity via these pathways. Therefore, this study reviews the effects and molecular mechanisms of TCM on chemoradiotherapy-related cardiotoxicity. In this study, we searched PubMed for basic studies on the anti-cardiotoxicity of TCM in the past 5 years and summarized their results. Angelica Sinensis, Astragalus membranaceus Bunge, Danshinone IIA sulfonate sodium (STS), Astragaloside (AS), Resveratrol, Ginsenoside, Quercetin, Danggui Buxue Decoction (DBD), Shengxian decoction (SXT), Compound Danshen Dripping Pill (CDDP), Qishen Huanwu Capsule (QSHWC), Angelica Sinensis and Astragalus membranaceus Bunge Ultrafiltration Extract (AS-AM),Shenmai injection (SMI), Xinmailong (XML), and nearly 60 other herbs, herbal monomers, herbal soups and herbal compound preparations were found to be effective as complementary or alternative treatments. These preparations reduced chemoradiotherapy-induced cardiotoxicity through various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism. However, few clinical trials have been conducted on these therapies, and these trials can provide stronger evidence-based support for TCM.

Correlation Between the MTHFR C677T Genotype and Coronary Heart Disease in Populations from Gansu, China.

This study was designed to evaluate the relationship between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and coronary heart disease (CHD) in populations from the Gansu region of China. The MTHFR C677T polymorphism genotypes from 209 patients with CHD, as confirmed by coronary angiography, and 212 non-CHD control patients were identified using PCR gold magnetic particle chromatography. We simultaneously evaluated homocysteine (Hcy) and folate levels in these samples using biochemical methods. The TT genotype of the MTHFR C677T locus was significantly more frequent in the CHD group than in the control, while the CC genotype was significantly less frequent in CHD patients than in non-CHD patients (p < 0.05). In addition, biochemical analysis revealed that the serum Hcy levels increased, and folate levels decreased in the TT genotype. Logistic regression analysis showed that this correlation was independent of nationality, sex, age, body mass index, medical history, and blood lipid level (p < 0.05). The occurrence of the TT genotype at the MTHFR C677T locus was closely associated with CHD in the Gansu population and may serve as a biomarker of increased risk for this disease.

Research Progress of Traditional Chinese Medicine in Treatment of Myocardial fibrosis.

Effective drugs for the treatment of myocardial fibrosis (MF) are lacking. Traditional Chinese medicine (TCM) has garnered increasing attention in recent years for the prevention and treatment of myocardial fibrosis. This Article describes the pathogenesis of myocardial fibrosis from the modern medicine, along with the research progress. Reports suggest that Chinese medicine may play a role in ameliorating myocardial fibrosis through different regulatory mechanisms such as reduction of inflammatory reaction and oxidative stress, inhibition of cardiac fibroblast activation, reduction in extracellular matrix, renin-angiotensin-aldosterone system regulation, transforming growth Factor-ß1 (TGF-ß1) expression downregulation, TGF-ß1/Smad signalling pathway regulation, and microRNA expression regulation. Therefore, traditional Chinese medicine serves as a valuable source of candidate drugs for exploration of the mechanism of occurrence and development, along with clinical prevention and treatment of MF.

TGFß-Associated Signature Predicts Prognosis and Tumor Microenvironment Infiltration Characterization in Gastric Carcinoma.

Background: Gastric carcinoma (GC) is a carcinoma with a high incidence rate, and it is a deadly carcinoma globally. An effective tool, that is, able to predict different survival outcomes for GC patients receiving individualized treatments is deeply needed. Methods: In total, data from 975 GC patients were collected from TCGA-STAD, GSE15459, and GSE84437. Then, we performed a comprehensive unsupervised clustering analysis based on 54 TGFß-pathway-related genes and correlated these patterns with tumor microenvironment (TME) cell-infiltrating characteristics. WGCNA was then applied to find the module that had the closest relation with these patterns. The least absolute shrinkage and selection operator (LASSO) algorithm was combined with cross validation to narrow down variables and random survival forest (RSF) was used to create a risk score. Results: We identified two different TGFß regulation patterns and named them as TGFß Cluster 1 and Cluster 2. TGFß Cluster 1 was linked to significantly poorer survival outcomes and represented an inflamed TME subtype of GC. Using WGCNA, a module (magenta) with the closest association with the TGFß clusters was identified. After narrowing down the gene list by univariate Cox regression analysis, the LASSO algorithm and cross validation, four of the 243 genes in the magenta module were applied to build a risk score. The group with a higher risk score exhibited a considerably poorer survival outcome with high predictive accuracy. The risk score remained an independent risk factor in multivariate Cox analysis. Moreover, we validated this risk score using GSE15459 and GSE84437. Furthermore, we found that the group with a higher risk score represented an inflamed TME according to the evidence that the risk score was remarkably correlated with several steps of cancer immunity cycles and a majority of the infiltrating immune cells. Consistently, the risk score was significantly related to immune checkpoint genes and T cell-inflamed gene expression profiles (GEPs), indicating the value of predicting immunotherapy. Conclusions: We have developed and validated a TGFß-associated signature, that is, capable of predicting the survival outcome as well as depicting the TME immune characteristics of GC. In summary, this signature may contribute to precision medicine for GC.

Identification of two immune-related risk score signatures through integrated analysis of multi-omics data in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Immunotherapy has become a major treatment for advanced HCC, but the therapeutic effects remain unsatisfactory. In this study, we constructed an immune cell risk score (ICS) and an immune cell-related gene risk score (ICRGS) for the prognosis prediction of HCC through integrated analysis of bulk and single-cell RNA (scRNA) sequencing data. These two risk score signatures both showed good predictive values in the training and validation cohorts. The potential interactions among these prognostic immune cell types were elucidated by cell-cell communication analysis. The results of enrichment analysis and gene set enrichment analysis (GSEA) of the prognostic genes showed that metabolic-related processes were involved in the immune response of HCC. Furthermore, the results of correlation analyses further confirmed the hub genes that were strongly correlated with immune cells. Finally, potential therapeutic drugs targeting these hub genes were screened by CellMiner based on NCI-60 cell line set. Taken together, two useful models for the prognosis prediction of HCC patients were constructed in this study. The functional differences between the two groups of HCC patients separated by ICS or ICRGS provide fundamental knowledge for finding synergistic therapeutic targets for HCC immunotherapy.

Single-cell RNA sequencing reveals the molecular features of peripheral blood immune cells in children, adults and centenarians.

Peripheral blood immune cells have different molecular characteristics at different stages of the whole lifespan. Knowledge of circulating immune cell types and states from children to centenarians remains incomplete. We profiled peripheral blood mononuclear cells (PBMCs) of multiple age groups with single-cell RNA sequencing (scRNA-seq), involving the age ranges of 1-12 (G1), 20-30(G2), 30-60(G3), 60-80(G4), and >110 years (G5). The proportion and states of myeloid cells change significantly from G1 to G2. We identified a novel CD8+CCR7+GZMB+ cytotoxic T cell subtype specific in G1, expressing naive and cytotoxic genes, and validated by flow cytometry. CD8+ T cells showed significant changes in the early stage (G1 to G2), while CD4+ T cells changed in the late stage (G4 to G5). Moreover, the intercellular crosstalk among PBMCs in G1 is very dynamic. Susceptibility genes for a variety of autoimmune diseases (AIDs) have different cell-specific expression localization, and the expression of susceptibility genes for AIDs changes with age. Notably, the CD3+ undefined T cells clearly expressed susceptibility genes for multiple AIDs, especially in G3. ETS1 and FLI1, susceptibility genes associated with systemic lupus erythematosus, were differentially expressed in CD4+ and CD8+ effector cells in G1 and G3. These results provided a valuable basis for future research on the unique immune system of the whole lifespan and AIDs.