Search

Background: Patients with hematological malignancies face an increased risk of developing second primary neoplasms due to various factors, including immune system compromise and chemotherapy-related effects. However, the incidence and associated risk factors in older patients remain poorly understood. This study aimed to assess the incidence, identify risk factors, and evaluate their impact on survival outcomes among older patients with hematological malignancies. Methods: This retrospective single-center study analyzed data from 163 patients, focusing on the occurrence of second primary neoplasms. Cumulative incidence rates were calculated, and risk factor analysis was conducted using a competing risk model. Results: Among 124 eligible patients with a total follow-up duration of 572.57 person-years, the incidence rate of second primary neoplasms was 15.72/1000 person-years. The standardized incidence ratio (SIR) was 0.81 (95% confidence interval [CI] [0.39–1.48], P = 0.518). History of radiotherapy emerged as a significant risk factor (sub-distribution hazard ratio [SHR] = 21.61 [2.81–166.14], P = 0.003), whereas regular natural killer (NK) cell infusion was associated with reduced risk (SHR = 3.25 e−8 [9.81 e−9–1.08 e−7], P ＜ 0.001). Conclusions: These findings underscore the importance of informing older patients with hematological malignancies about the long-term risks of second primary neoplasms. Healthcare providers should carefully weigh risk factors when formulating treatment strategies. The results are valuable for investigating the fundamental principles underlying the occurrence and progression of second primary neoplasms.

Abstract Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ’s effects on MM are unclear. We investigated CTZ’s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ’s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Abstract The application of ChatGPTin the medical field has sparked debate regarding its accuracy. To address this issue, we present a Multi-Role ChatGPT Framework (MRCF), designed to improve ChatGPT's performance in medical data analysis by optimizing prompt words, integrating real-world data, and implementing quality control protocols. Compared to the singular ChatGPT model, MRCF significantly outperforms traditional manual analysis in interpreting medical data, exhibiting fewer random errors, higher accuracy, and better identification of incorrect information. Notably, MRCF is over 600 times more time-efficient than conventional manual annotation methods and costs only one-tenth as much. Leveraging MRCF, we have established two user-friendly databases for efficient and straightforward drug repositioning analysis. This research not only enhances the accuracy and efficiency of ChatGPT in medical data science applications but also offers valuable insights for data analysis models across various professional domains.

Abstract Background Anhui Province is currently facing an increase in imported malaria cases as a result of globalization and international travel. In response, Anhui Province has implemented a comprehensive adaptive framework to effectively address this threat. Methods This study collected surveillance data from 2012 to 2022 in Anhui Province. Descriptive statistics were used to analyze the epidemiological characteristics of imported malaria cases. Additionally, multivariate logistic regression was employed to identify factors associated with severe malaria. Documents were reviewed to document the evolution of the adaptive framework designed to combat imported malaria. The effectiveness of the adaptive framework was evaluated based on the rates of timely medical visits, timely diagnosis, and species identification. Results During the study period, a total of 1008 imported malaria cases were reported across 77 out of 105 counties in Anhui Province, representing a coverage of 73.33%. It was found that 10.52% of imported cases went undiagnosed for more than seven days after onset. The multivariate analysis revealed several potential risk factors for severe malaria, including increasing age (OR = 1.049, 95%CI:1.015–1.083), occupation (waitperson vs. worker, OR = 2.698, 95%CI:1.054–6.906), a longer time interval between onset and the initial medical visit (OR = 1.061, 95%CI:1.011–1.114), and misdiagnosis during the first medical visit (OR = 5.167, 95%CI:2.535–10.533). Following the implementation of the adaptive framework, the rates of timely medical visits, timely diagnosis, and species identification reached 100.00%, 78.57%, and 100.00%, respectively. Conclusions Anhui Province has successfully developed and implemented an adaptive framework for addressing imported malaria, focusing on robust surveillance, prompt diagnosis, and standardized treatment. The experiences gained from this initiative can serve as a valuable reference for other non-endemic areas.

Introduction: An increasing number of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been reported during clinical treatment. We aimed to explore the clinical characteristics of patients with ICIs-induced ITP under different therapeutic strategies based on the FAERS database and explore the potential biological mechanisms in combination with TCGA pan-cancer data.Methods: Data from FAERS were collected for ICIs adverse reactions between January 2012 and December 2022. Disproportionality analysis identified ICIs-induced ITP in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PRP), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker algorithms (MGPS). The potential biological mechanisms underlying ITP induced by ICIs were examined using TCGA transcriptome data on cancers.Results: In the FAERS, 345 ICIs-induced ITP reports were retrieved, wherein 290 (84.06%) and 55 (15.94%) were reported as monotherapy and combination therapy, respectively. The median age of the reported patients with ICIs-induced ITP was 69 years (IQR 60-76), of which 62 (18%) died and 47 (13.6%) had a life-threatening outcome. The majority of reported indications were lung, skin, and bladder cancers, and the median time to ITP after dosing was 42 days (IQR 17-135), with 64 patients (43.5%) experiencing ITP within 30 days of dosing and 88 patients experiencing ITP in less than 2 months (59.9%). The occurrence of ICIs-induced ITP may be associated with ICIs-induced dysregulation of the mTORC1 signaling pathway and megakaryocyte dysfunction.Conclusion: There were significant reporting signals for ITP with nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab/ipilimumab, and pembrolizumab/ipilimumab. Patients treated with anti-PD-1 in combination with anti-CTLA-4 are more likely to have an increased risk of ICIs-induced ITP. Patients with melanoma are at a higher risk of developing ITP when treated with ICI and should be closely monitored for this risk within 60 days of treatment. The potential biological mechanism of ICIs-induced ITP may be related to the dysfunction of megakaryocyte autophagy through the overactivation of the mTOR-related signaling pathway. This study provides a comprehensive understanding of ICIs-induced ITP. Clinicians should pay attention to this potentially fatal adverse reaction.

Immune checkpoint inhibitors (ICIs) are employed in immunotherapeutic applications for patients with weakened immune systems and can improve the ability of T cells to kill cancer cells. Although ICIs can potentially treat different types of cancers in various groups of patients, their effectiveness may differ among older individuals. The reason ICIs are less effective in older adults is not yet clearly understood, but age-related changes in the immune system, such as immunosenescence and inflammation, may play a role. Therefore, this review focuses on recent advances in understanding the effects of immunosenescence and inflammation on the efficacy of ICIs.

Purpose Patients with multiple myeloma (MM) are prone to developing persistent renal insufficiency. Novel therapeutic medications have improved long-term survival, making kidney transplantation (KT) a viable treatment option for MM survivors with end-stage renal disease. This study aimed to investigate the clinical outcomes in patients with MM who have received KT. Methods Data from hospitalized patients ≥ 40 years of age with MM in the Nationwide Inpatient Sample 2016–2018 of the United States were queried. Patients were classified as having or not having undergone KT, as well as the stage of chronic kidney disease (CKD) for those who had not received KT. Propensity-score matching (PSM) was applied to balance the characteristics between the groups. Binary logistic regression was utilized to determine the associations between study variables and inhospital mortality, unfavorable discharges, prolonged length of stay (LOS), and major complications. Results In total, 50,654 hospitalized patients with MM were identified, of whom 165 (0.3%) had received KT and 50,489 had not (5,905 at stage 5 CKD [CKD5D], 11,559 at stage 1–4 CKD [CKD1-4D], and 33,025 who were CKD-free). After PSM, between-group demographic and hospital-related characteristics were balanced. Binary regression analysis revealed that, compared to patients who were CKD-free, patients at CKD5D were significantly more likely to experience a prolonged LOS (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01–1.70) after adjusting for relevant confounders. Furthermore, compared to CKD-free patients, those who underwent KT were significantly more likely to have sepsis (OR, 1.48; 95% CI, 1.02–2.14). However, KT showed no association with the other adverse inpatient outcomes. Conclusions Although KT is not common in MM patients, those who had undergone KT had comparable hospital outcomes to CKD-free patients. These data will help clinicians deliver better consultations to MM patients attempting to receive KT.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving “full coverage” treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Abstract. Background. Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods. This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants’ epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results. Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; P < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; P = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (β Value 0.081; 95% CI, −1.012 to 3.657; P = 0.265) or discharge (β Value 0.114; 95% CI, −0.723 to 6.408; P = 0.117). d-dimer (β Value, 0.144; 95% CI, 0.012 to 0.817; P = 0.044), LDH (β Value 0.260; 95% CI, 0.010 to 0.034; P < 0.001), and antiviral therapy (β Value 0.220; 95% CI, 1.373 to 6.263; P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (β Value −0.206; 95% CI, −6.248 to −1.197; P = 0.004), LDH (β Value 0.231; 95% CI, 0.012 to 0.048; P = 0.001), antiviral therapy (β Value 0.143; 95% CI, 0.058 to 7.497; P = 0.047), and antibacterial therapy (β Value 0.152; 95% CI, 0.133 to 8.154; P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=−2.362, P = 0.018; Z=−2.010, P = 0.044) and a shorter hospital stay (Z=−2.735, P = 0.006; Z=−3.858, P < 0.001). Conclusions. In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

Background: The benefits and harms of methylprednisolone treatment in patients with moderate coronavirus disease 2019 (COVID-19) remain controversial. In this study, we investigated the effect of methylprednisolone on mortality rate, viral clearance, and hospitalization stay in patients with moderate COVID-19. Methods: This retrospective study included 4827 patients admitted to Wuhan Huoshenshan and Wuhan Guanggu hospitals from February to March 2020 diagnosed with COVID-19 pneumonia. The participants’ epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death; secondary outcomes were time from admission to viral clearance and hospital stay. Univariate and multivariate logistic or linear regression analysis were used to assess the roles of methylprednisolone in different outcomes. The propensity score matching (PSM) method was used to control for confounding factors. Results: A total of 1320 patients were included in this study, of whom 100 received methylprednisolone. Overall, in-hospital mortality was 0.91% (12/1320); the 12 patients who died were all in the methylprednisolone group, though multivariate logistic regression analysis showed methylprednisolone treatment was not a risk factor for in-hospital death in moderate patients before or after adjustment for confounders by PSM. Methylprednisolone treatment was correlated with longer length from admission to viral clearance time and hospital stay before and after adjustment for confounders. Conclusions: Methylprednisolone therapy was not associated with increased in-hospital mortality but with delayed viral clearance and extended hospital stay in moderate COVID-19 patients.

Immune thrombocytopenia (ITP) is common in the elderly. Because of the coexistence of multiple diseases, there are many reservations regarding corticosteroid use in the elderly. Thrombopoietin (TPO) and its analogs can promote platelet production, but it is often difficult to correct TP in a short period. Recombinant human TPO (rh-TPO) acting on the cell membrane and the small-molecule TPO-receptor (MPL) agonist acting on the transmembrane receptor may have synergistic effects and accelerate platelet production because of different sites of action in the signaling pathway. In this study, two elderly patients with refractory ITP were successfully treated with two TPO-MPL signaling pathway agonists: recombinant human thrombopoietin (rh-TPO) and eltrombopag. This combination is safe with rapid and lasting effects. However, in elderly patients with refractory, recurrent, and glucocorticoid contraindications, the combination of different TPO agonists' clinical efficacy and adverse reactions needs to be further evaluated.

Objective: Using bioinformatics analyses, this study aimed to identify lncRNAs related to the immune status of acute myeloid leukemia (AML) patients and ascertain the potential impact in immunity-related competing endogenous RNA (ceRNA) networks on AML prognosis.Methods: AML-related RNA-seq FPKM data, AML-related miRNA expression microarray data, and gene sets associated with immunity-related pathways were, respectively, obtained from the TCGA, GEO, and ImmReg databases. An immunity-related ceRNA network was then constructed according to the predicted interactions between AML-related mRNAs, lncRNAs, and miRNAs. After performing LASSO and multivariate Cox regression analyses, lncRNAs in the ceRNA network were used to establish an AML prognostic model. According to mutual regulatory relationships and consistent trends of expression among candidate ceRNAs, two ceRNA subnetworks related to the AML prognostic model were determined. Finally, the correlation between the expression levels of mRNAs, lncRNAs, and miRNAs in each ceRNA subnetwork and immune cell infiltration (assessed by combining the ESTIMATE and CIBERSORT methods and ssGSEA) was analyzed.Results: A total of 424 immunity-related differentially expressed (IR-DE) mRNAs (IR-DEmRNAs), 191 IR-DElncRNAs, and 69 IR-DEmiRNAs were obtained, and a ceRNA network of 20 IR-DElncRNAs, 6 IR-DEmRNAs, and 3 IR-DEmiRNAs was established. Univariate Cox regression analysis was conducted on 20 IR-DElncRNAs, and 7 of these were identified to be significantly correlated with the overall survival (OS) time in AML patients. Then, two IR-DElncRNAs (MEG3 and HCP5) were screened as independent OS-related factors by LASSO and multivariable Cox regression analyses, and a prognostic model was constructed to evaluate the survival risk in AML patients. Survival analyses indicated that the OS of patients was often poor in the high-risk group. Additionally, from this model, two ceRNA regulatory pathways, namely, MEG3/miR-125a-5p/SEMA4C and HCP5/miR-125b-5p/IL6R, which were potentially involved in the immune regulation of AML prognosis were identified.Conclusion: lncRNAs HCP5 and MEG3 may act as key ceRNAs in the pathogenesis in AML by regulating immune cell representation as part of the regulatory lncRNA-miRNA-mRNA axes. The candidate mRNAs, lncRNAs, and miRNAs included in the ceRNA network identified here may serve as useful prognostic biomarkers and immunotherapeutic targets for AML.

Ferulic acid is a beneficial human health phenolic acid that reduces the risk of serious diseases such as diabetes, cholesterol, heart disease and cancer. Ferulic acid is the highest content phenolic acid in wheat, mainly concentrated in wheat bran. With the improvement of people’s awareness of health care, the preparation and function of ferulic acid in wheat bran have been paid more and more attention. The methods of preparing ferulic acid from wheat bran generally include alkaline hydrolysis, biological enzyme and biological fermentation, and many studies have assisted the above preparation methods by physical means, such as ultrasonic and high temperature steam, etc. In this paper, the distribution and form of ferulic acid in wheat and the method of preparing ferulic acid from wheat bran are summarized, and the advantages and disadvantages of the method of preparing ferulic acid from wheat bran are analyzed, so as to provide some references and ideas for the development, research and industrial production of ferulic acid in wheat bran.

Background: In view of the increasing human life and the aging of the population, the search for safe anti-aging drugs has become a hot topic. Agaricus blazei Murrill is a rare edible fungus, with a variety of biological activities. The purpose of this study was to clarify the anti-aging effect and mechanism of ABM-A on the aging induced by D-Galactose in mice. Results: The result showed that ABM-A contained 87.2% of glucose, 3.3% of galactose, 3.8% mannose and 5.7% gluconic acid. The behavior of mice in the treatment group was significantly improved after administration of ABM-A. And the activity of SOD and CAT and the level of T-AOC were increased (p

The development of premature coronary artery disease (PCAD) is dependent on both genetic predisposition and traditional risk factors. Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies. Genome-wide association studies (GWASs) have identified a considerable number of common genetic variants that are associated with PCAD. Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms (SNPs). The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity. Some characteristic genetic variants have been identified in Chinese populations. Although translating this genetic knowledge into clinical applications is still challenging, these genetic variants can be used for CAD phenotype identification, genetic prediction and therapy. In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD. We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.

Abstract Cardiac ischemia, hypoxia, arrhythmias, and heart failure share the common electrophysiological changes featured by the elevation of intracellular Ca2+ (Ca2+ overload) and inhibition of the inward rectifier potassium (IK1) channel. IK1 channel agonists have been considered a new type of anti‐arrhythmia and cardioprotective agents. We predicted using a drug repurposing strategy that tetramisole (Tet), a known anthelminthic agent, was a new IK1 channel agonist. The present study aimed to experimentally identify the above prediction and further demonstrate that Tet has cardioprotective effects. Results of the whole‐cell patch clamp technique showed that Tet at 1–100 μmol/L enhanced IK1 current, hyperpolarized resting potential (RP), and shortened action potential duration (APD) in isolated rat cardiomyocytes, while without effects on other ion channels or transporters. In adult Sprague–Dawley (SD) rats in vivo, Tet showed anti‐arrhythmia and anticardiac remodeling effects, respectively, in the coronary ligation‐induced myocardial infarction model and isoproterenol (Iso, i.p., 3 mg/kg/day, 10 days) infusion‐induced cardiac remodeling model. Tet also showed anticardiomyocyte remodeling effect in Iso (1 μmol/L) infused adult rat ventricular myocytes or cultured H9c2 (2‐1) cardiomyocytes. Tet at 0.54 mg/kg in vivo or 30 μmol/L in vitro showed promising protections on acute ischemic arrhythmias, myocardial hypertrophy, and fibrosis. Molecular docking was performed and identified the selective binding of Tet with Kir2.1. The cardioprotection of Tet was associated with the facilitation of IK1 channel forward trafficking, deactivation of PKA signaling, and inhibition of intracellular calcium overload. Enhancing IK1 may play dual roles in anti‐arrhythmia and antiventricular remodeling mediated by restoration of Ca2+ homeostasis.

BackgroundCoronary heart disease (CHD) is the most common progressive disease that is difficult to diagnose and predict in the young asymptomatic period. Our study explored a mechanistic understanding of the genetic effects of premature CHD (PCHD) and provided potential biomarkers and treatment targets for further research through high throughput sequencing and integrated bioinformatics analysis.MethodsHigh throughput sequencing was performed among recruited patients with PCHD and young healthy individuals, and CHD-related microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using R software. Enrichment analysis and CIBERSORT were performed to explore the enriched pathways of DEGs and the characteristics of infiltrating immune cells. Hub genes identified by protein–protein interaction (PPI) networks were used to construct the competitive endogenous RNA (ceRNA) networks. Potential drugs were predicted by using the Drug Gene Interaction Database (DGIdb).ResultsA total of 35 DEGs were identified from the sequencing dataset and GEO database by the Venn Diagram. Enrichment analysis indicated that DEGs are mostly enriched in excessive immune activation pathways and signal transduction. CIBERSORT exhibited that resting memory CD4 T cells and neutrophils were more abundant, and M2 macrophages, CD8 T cells, and naïve CD4 T cells were relatively scarce in patients with PCHD. After the identification of 10 hub gens, three ceRNA networks of CD83, CXCL8, and NR4A2 were constructed by data retrieval and validation. In addition, CXCL8 might interact most with multiple chemical compounds mainly consisting of anti-inflammatory drugs.ConclusionsThe immune dysfunction mainly contributes to the pathogenesis of PCHD, and three ceRNA networks of CD83, CXCL8, and NR4A2 may be potential candidate biomarkers for early diagnosis and treatment targets of PCHD.

Abstract Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was −13.31%, 95% CI −29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: −15.45%; 95% CI −30.82%, −0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

This study aims to determine hub genes related to the incidence and prognosis of EGFR-mutant (MT) lung adenocarcinoma (LUAD) with weighted gene coexpression network analysis (WGCNA). From The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we used 253 EGFR-MT LUAD samples and 38 normal lung tissue samples. At the same time, GSE19188 was additionally included to verify the accuracy of the predicted gene. To discover differentially expressed genes (DEGs), the R package “limma” was used. The R packages “WGCNA” and “survival” were used to perform WGCNA and survival analyses, respectively. The functional analysis was carried out with the R package “clusterProfiler.” In total, 1450 EGFR-MT–specific DEGs were found, and 7 tumor-related modules were marked with WGCNA. We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (p < 0.05). Functional analysis of the hub genes showed the metabolism and protein synthesis–related terms added value. In conclusion, we used WGCNA to identify hub genes in the development of EGFR-MT LUAD. The established prognostic factors could be used as clinical biomarkers. To confirm the mechanism of those genes in EGFR-MT LUAD, further molecular research is required.

Background: Anti-inflammatory therapy has been proposed as a promising treatment for coronary heart disease (CHD) that could reduce residual inflammation risk (RIR) and therefore major adverse cardiovascular events. We implemented a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the clinical benefits of anti-inflammatory agents in patients with CHD based on secondary cardiovascular prevention.Methods: We systemically searched the PubMed, Embase, and Cochrane Library databases for RCTs (published between Jan 1, 1950, and June 1, 2021; no language restrictions) that focused on anti-inflammatory therapy for coronary heart disease. Our primary end points of interest were a composite of all-cause death, recurrent myocardial infarction and stroke. We processed pooled data using a random-effects model.Results: Of 1497 selected studies, 18 studies with 67,449 participants met our inclusion criteria and were included in the present meta-analysis. Comparing anti-inflammatory agents with placebo, there was no significant decrease in risk of primary end points, secondary end points, all-cause mortality, cardiac mortality, recurrent myocardial infarction, stroke or revascularization. Further subgroup analysis indicated that anti-inflammatory agents led to a significant reduction in secondary end points (OR 0.87, CI 0.77–0.99; P = 0.03), recurrent myocardial infarction (OR 0.86, CI 0.78–0.95; P = 0.003) and revascularization (OR 0.81, CI 0.70–0.92; P = 0.001) in patients with stable CHD compared with placebo. Moreover, stable CHD patients had a lower propensity for recurrent myocardial infarction than acute coronary syndrome (ACS) patients when using anti-inflammatory agents (P = 0.03). The colchicine subgroup analysis showed that colchicine yielded a promising reduction in the primary end points (OR 0.81, CI 0.70–0.95; P = 0.009) compared with placebo. Anti-inflammatory agents were associated with a higher risk of infection (OR 1.13, CI 1.03–1.23; P = 0.007) and negligible effects on cancers (OR 0.98, CI 0.90–1.06; P = 0.61).Conclusion: Anti-inflammatory agents appear to have beneficial effects in reducing the risk of recurrent myocardial infarction in patients with stable CHD, albeit at the cost of increased infection. Notably, colchicine demonstrates a promising cardioprotective effect with a lower incidence of major cardiovascular events and thus is a potential therapeutic strategy for stable CHD patients.Systematic Review Registration: PROSPERO, identifier CRD42021245514.

Agaricus blazei is a kind of fungus plant with an edible as well as a medicinal use. Previous experiments have shown its crude peptide to possess an obvious anti-aging effect. In the present study three active components viz. ABp-RRQ, ABp-RQR and ABp-TRAR were obtained from the Agaricus blazei polypeptide. ABp-RQR was the main active component with a molecular weight of 458 Dalton, and HPLC confirmed it’s a purity > 98%. When the D-galactose(D-gal)-induced NIH/3T3 cells were treated with ABp-RQR, changes were observed in the oxidative stress activities and the contents of inflammatory factors. Cell morphology and the percentage of positive cells were observed using the β-galactosidase staining. Western blot was used to detect the expression levels of the proteins modulated in the inflammatory and antioxidant signaling pathways. Our study suggests that ABp-RQR may play an anti-aging role by alleviating the oxidative inflammatory reactions in D-gal-induced NIH/3T3 cells.

Objective This study was performed to examine the treatment regimen used for an elderly patient with diffuse large B-cell lymphoma (DLBCL) complicated with renal dysfunction. Case report An 85-year-old man presented with nasal and sinus disorders in May 2018. He was also found to have renal insufficiency caused by long-term consumption of compound aminopyrine phenacetin tablets. Physical examination revealed irritation of the nasal mucous membrane on the right side and dark red nasal passages with a smooth surface. The right side of the neck contained several small peanut-sized lymph nodes. A biopsy of the right nasal neoplasm revealed germinal center type DLBCL. The mini–rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen (mini-R-CHOP) was administered as the main chemotherapy regimen. Additionally, the use of thrombopoietin prevented further deterioration in renal function. This individualized treatment program helped the patient to achieve complete remission. The creatinine level decreased and was well maintained. Conclusion The mini-R-CHOP and rituximab cross-use regimen was found to be safe in an elderly patient with chronic renal insufficiency. Thrombopoietin exerted a protective effect on renal function.

Acute coronary syndrome (ACS) is a major cause of acute death worldwide. Both innate and adaptive immunity regulate atherosclerosis progression, plaque stability, and thrombus formation. Immune and inflammation dysfunction have been indicated in the pathogenesis of ACS. The imbalance in the proatherogenic and antiatherogenic immune networks promotes the transition of plaques from a stable to unstable state and results in the occurrence of acute coronary events. The residual inflammatory risk (RIR) has received increasing attention in recent years, and lowering RIR has been expected to improve the outcomes of ACS patients. The CANTOS, COLCOT, and LoDoCo trials verified the benefits of reducing cardiovascular events using anti-inflammation therapies; however, most of the other studies focusing on lowering RIR produced negative or contradicting results. Therefore, restoring the balance in autoimmune regulation is essential because proatherogenic and antiatherogenic immunomodulatory effects are equally important in the complex human immune network. In this review, we summarized the recent evidence of the roles of proatherogenic and antiatherogenic immune networks in the pathogenesis of ACS and discussed how immune and inflammation contribute to atherosclerosis progression, plaque instability, and adverse cardiovascular events. We also provide a “from bench to bedside” perspective of a novel and promising personalized strategy in RIR intervention and therapeutic approaches for the treatment of ACS.

Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083).

BACKGROUND: Some cardiovascular risk factors have been confirmed to be positively correlated with arterial stiffness. However, it is unclear whether HDL-C, a well-established anti-risk factor, has an independent association with arterial stiffness. The aim of this study was to evaluate the relationship between HDL-C levels and arterial stiffness and the possible role of high-sensitivity C-reactive protein (hs-CRP) in this potential correlation in apparently healthy adults undergoing a general health examination in China. MATERIALS AND METHODS: This was a cross-sectional survey. In total, 15,302 participants (age range, 18-82 years; mean, 43.88±8.44 years) were recruited during routine health status examinations. A questionnaire was used and we measured the body mass index, systolic and diastolic blood pressure, and fasting glucose, and serum lipid, uric acid, hs-CRP, and serum creatinine levels of each participant. Central arterial stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV). RESULTS: HDL-C levels decreased as cf-PWV increased. Pearson's correlation analysis revealed that HDL-C levels were associated with cf-PWV (r=-0.18, P

Abstract Objective To understand the awareness and practice of diabetic kidney disease (DKD) or nephropathy screening among community-based patients with type 2 diabetes in six provinces and cities in China, and to analyse the related factors affecting screening practices. Methods From December 2021 to March 2022, a cross-sectional survey was conducted using a structured questionnaire in 6230 patients with type 2 diabetes aged 18 years and older. The content of the questionnaire includes three parts: the general situation of diabetic patients (gender, age, ethnicity, marriage, education, occupation, etc.), DKD screening practices, and the evaluation of DKD screening services. Results 89.70% of the patients had their fasting blood glucose measured every six months, 21.12% of the patients had their glycosylated hemoglobin measured every six months, and only 13.11% and 9.34% of the patients had a urine protein-creatinine ratio test and estimated glomerular filtration rate test every 12 months. The proportions of glycosylated hemoglobin, urine protein-creatinine ratio, and estimated glomerular filtration rate were relatively high in young, northern, highly educated, and long-duration type 2 diabetic patients. Conclusion The results of this survey found that the proportion of urine protein-creatinine ratio testing, estimated glomerular filtration rate testing, and glycosylated hemoglobin testing in Chinese patients with type 2 diabetes was very low. Patients with type 2 diabetes in rural areas, southern areas, with low education level, and short course of disease have lower detection rates for DKD, and hence lower rates of prevention and treatment.

ObjectiveTo examine the prevalence and influencing factors of multimorbidity among community diabetic patients in six provincial-level administrative divisions (PLADs) of China for providing evidence to disease management and multimorbidity prevention in the patients. MethodsUsing stratified multistage random sampling, we selected 6 713 adult patients ( ≥ 18 years) with type 2 diabetics registered in local basic public health service systems in urban communities and rural villages in Tianjin and Chongqing municipality and Guangdong, Hubei, Heilongjiang, Gansu province. Relevant information of the participants were collected via face-to-face surveys with a self-designed questionnaire from December 2021 to March 2022 and analyzed using descriptive statistics and logistic regression. ResultsMultimorbidity was reported by 3235 (51.93%) of the 6230 patients with eligible responses. The top three most reported multimorbidities were hypertension (reported by 44.77% of the patients), coronary heart disease (12.34%) and stroke (4.65%) and the number (proportion) of the patients with one, two, and three or more multimorbidities were 2190 (35.15%), 754 (12.10%), and 291 (4.67%), respectively, with the most prevalent multimorbidity of diabetes and hyperten-sion reported by 29.15% of the patients. Multivariate unconditional logistic regression analysis indicated that aged 45 years and older, living in northern regions, having alcohol consumption and a diabetes duration of 10 years and more were significant risk factors for multimorbidity; whereas, being married was a significant protective factor. ConclusionThe prevalence of chronic disease comorbidity is relatively high and mainly influenced by age, marital status, living region, alcohol consumption and diabetes duration among community diabetic patients in urban and rural areas of six PLADs in China.

Based on the research and development (R&D) state of prefabricated buildings, this paper establishes an evolutionary game model involving such three parties as latecomer prefabricated building firm (LPBF), related firm, and university-research institute, and simulates the evolutionary results of the game to determine the evolutionarily stable strategy (ESS) of the game. The results show that: In the tripartite system evolution, the evolution and trend of each party are closely related with the strategies chosen by the other two parties; eventually, the LPBF strategy always converges to R&D, while the strategies of related firm, and university-research institute always converge to cooperation in R&D. Whether the game system converges to the desired equilibrium state hinges on the R&D profit and cost of, and opportunistic profit from subsequent cooperation with the LPBF. During the development of prefabricated buildings, the game parties should promote the high-quality development of the industry by stepping up technological R&D, forging a complete industrial chain, and implementing industry-university-research cooperation.