American journal of clinical and experimental immunology最新文献

Recent studies have shown that ultrashort plasma cell-free DNA (uscfDNA), a novel type of cfDNA fragment approximately 50 nucleotides long, differs from conventional monocyte-derived cfDNA in several aspects, including specific extraction requirements and a higher incidence of tumor-specific genetic alterations. uscfDNA shows promise in enhancing liquid biopsy sensitivity for cancer detection, with distinct methylation profiles observed in cancer patients. These findings suggest uscfDNA analysis could significantly improve non-invasive cancer diagnostics, offering new avenues for early detection and personalized medicine strategies.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, mortality rates of coronavirus disease 2019 (COVID-19) have significantly decreased. However, a variable proportion of patients exhibit persistent prolonged symptoms of COVID-19 infection (long COVID). This virus primarily attacks respiratory system, but numerous individuals complain persistent skeletal muscle pain or worsening pre-existing muscle pain post COVID-19, which severely affects the quality of life and recovery. Currently, there is limited research on the skeletal muscle pain in long COVID. In this brief review, we review potential pathological mechanisms of skeletal muscle pain in long COVID, and summarize the various auxiliary examinations and treatments for skeletal muscle pain in long COVID. We consider abnormal activation of inflammatory response, myopathy, and neurological damages as pivotal pathological mechanisms of skeletal muscle pain in long COVID. A comprehensive examination is significantly important in order to work out effective treatment plans and relieve skeletal muscle pain. So far, rehabilitation interventions for myalgia in long COVID contain but are not limited to drug, nutraceutical therapy, gut microbiome-targeted therapy, interventional therapy and strength training. Our study provides a potential mechanism reference for clinical researches, highlighting the importance of comprehensive approach and management of skeletal muscle pain in long COVID. The relief of skeletal muscle pain will accelerate rehabilitation process, improve activities of daily living and enhance the quality of life, promoting individuals return to society with profound significance.

Background: Gout is closely tied to metabolism, yet there is limited evidence on how metabolites may cause or prevent the condition.

Methods: This study utilized a two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between 1,400 serum metabolites and gout. We primarily employed the inverse variance-weighted (IVW) method to estimate causal effects, supplemented by MR-Egger regression, weighted median, simple mode, and weighted mode for comprehensive evaluations. Additionally, we conducted tests for pleiotropy and heterogeneity.

Results: After a rigorous selection process, we identified eight known metabolites and four unknown metabolites associated with gout. Among the eight known metabolites, Glucuronide of piperine metabolite C17H21NO3 and the Phosphate to mannose ratio were positively associated with an increased risk of gout. Conversely, levels of 5 alpha-androstan-3 beta, 17 alpha-diol disulfate, Pantoate, N-carbamoylalanine, Sphingomyelin (d18:0/20:0, d16:0/22:0), Hydroxypalmitoyl sphingomyelin (d18:1/16:0(OH)), and Mannose were linked to a decreased risk of gout.

Conclusion: This study identified eight metabolites from 1,400 blood samples significantly linked to gout risk. Integrating genomics and metabolomics offers valuable insights for gout screening and prevention, indicating that specific blood metabolites can help identify individuals at higher risk.

Mutations in oncogenes and tumor suppressor genes can significantly impact cellular function during cancer development. A comprehensive analysis of their mutation patterns and significant gene ontology terms can provide insights into cancer emergence and suggest potential targets for drug development. This study analyzes twelve cancer subtypes by focusing on significant genetic and molecular factors. Two common genetic mutations associated with cancer are single nucleotide variants (SNVs) and copy number alterations (CNAs). Oncogenes, derived from mutated proto-oncogenes, disrupt normal cell functions and promote cancer, while tumor suppressor genes, often inactivated by mutations, regulate cell processes like proliferation and DNA damage response. This study analyzed datasets from The Cancer Genome Atlas (TCGA), which provides extensive genomic data across various cancers. In our analysis results, many genes with significant p-values based on Kaplan Meier gene expression data were identified in eight cancers (BRCA, BLCA, HNSC, KIRC, LUAD, KIRP, LUSC, STAD). Moreover, STAD is the only cancer for genes with both significant p-values and functional terms reported. Interestingly, we found that LIHC was the cancer reported with only one CNA mutated gene and its survival plot p-value being significant. Additionally, KICH has no reported significant genes at all. Our study proposed the relationship between tumor suppressor and oncogenes and shed light on cancer tumorigenesis due to genetic mutations.

Background: Whole-body vibration (WBV) is a commonly used physical exercise for disease prevention and rehabilitation. Recent studies indicated the beneficial mechanism of WBV may be associated with its anti-inflammatory potential, however, its regulatory roles on different inflammatory mediators remained controversial. The aim of this study was to perform a meta-analysis to re-confirm the effects of WBV exercise on various inflammatory factors.

Methods: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 to collect all articles comparing WBV with control (or post-pre trials). The effect size was expressed as the standardized mean difference (SMD) and 95% confidence intervals (CI).

Results: A total of 31 eligible studies were included, including 14 pre-clinical and 17 clinical studies. The meta-analysis of pre-clinical studies showed that compared with the control group, WBV exercise could significantly reduce the level of IL-6 (SMD: -1.03, 95% CI: -1.93, -0.13), TNF-α (SMD: -1.36, 95% CI: -2.54, -0.17) (for disease subgroup), IL-1β (SMD: -2.20, 95% CI: -3.24, -1.15), IFN-γ (SMD: -1.91, 95% CI: -2.71, -1.12), IL-4 (SMD: -0.71, 95% CI: -1.39, -0.03) and IL-17 (SMD: -1.32, 95% CI: -2.05, -0.59) overall. Pooling of clinical studies revealed WBV exercise significantly reduced the level of TNF-α (WBV vs control: SMD: -1.11, 95% CI: -2.16, -0.06; post vs pre: SMD: -1.29, 95% CI: -1.91, -0.67), CRP (SMD: -3.59, 95% CI: -6.36, -0.82, P = 0.011) and enhanced the level of IL-10 (WBV vs control: SMD: 2.90, 95% CI: 1.10, 4.71; post vs pre: SMD: 1.75, 95% CI: 0.64, 2.87) and IL-6 (SMD: 0.91, 95% CI: 0.31, 1.52) (healthy subgroup).

Conclusion: WBV may be an effective prevention and rehabilitation tool for inflammatory diseases.

Background: Coronavirus disease 2019 (COVID-19) affects different organ systems, including the skin. A retrospective analysis of skin manifestations in Chinese outpatient and inpatient settings is lacking. The study aims to analyze cutaneous manifestations in COVID-19 patients and the recurrence or aggravation of previous skin diseases.

Materials and methods: A retrospective cross-sectional study was conducted from November 2022 to July 2023 in a university hospital in eastern China. It involved reverse transcriptase polymerase chain reaction (RT-PCR)-positive COVID-19 patients, documenting various skin manifestations and the recurrence or aggravation of pre-existing skin conditions. The pattern of skin lesions and other variables were assessed.

Results: The study included 303 patients, with 127 males and 176 females. Maculopapular rash was the predominant new cutaneous manifestation (54.92%), mainly in middle-aged individuals. Other findings included urticaria (16.39%), herpes zoster (11.89%), and herpes simplex (4.10%), vesicular rashes (2.46%), purpura (2.05%), erythema multiforme (1.64%), livedo reticularis (0.41%) and so on. Severe disease was associated with herpes zoster and livedo reticularis. Critical COVID-19 cases were linked to vesicular rashes, purpura, and erythema multiforme. The mean time for skin lesion emergence post-infection varied from 3 days for seborrheic dermatitis to 17.48 days for herpes zoster. Vasculitic manifestations correlated with elevated D-dimer levels. A total of 59 cases (19.47%) of recurrent or aggravated skin diseases were reported following infection with COVID-19, with dermatitis being the most common, followed by acne and folliculitis, psoriasis, urticaria, bullous pemphigoid, pemphigus, tinea corporis and androgenetic alopecia.

Conclusion: The cutaneous phenotypes delineated in this study expand the dermatologic spectrum associated with COVID-19. Cutaneous manifestations may result from overactive immune responses, complement activation, and microvascular damage. Herpes zoster typically occurs in elderly COVID-19 patients with weaker immune systems or more severe diseases. Purpura and livedo reticularis, although rare, may indicate disease severity. It is possible to predict the course of COVID-19 with different severity through cutaneous manifestations. Recognizing these skin manifestations could aid in predicting COVID-19 severity and guide dermatologists in managing the pandemic response.

To explore the characteristics of hematologic indicators and related risk factors of lower extremity deep vein thrombosis (LDVT) in patients with cerebral infarction.

Methods: This study retrospectively analyzed data from 174 patients with cerebral infarction admitted to The Rehabilitation Department of Shanghai Fifth Rehabilitation Hospital and Shanghai First People's Hospital from June 2022 to June 2023. Based on the results of lower limb venous color Doppler ultrasound examinations, patients were divided into two groups: the LDVT group (35 cases) and the non-LDVT group (139 cases). We compared the clinical data and hematologic indicators (D-dimer value, fibrinogen, white blood cells, platelets, uric acid, creatinine, etc.) of the two groups to identify the risk factors of cerebral infarction complicated with LDVT.

Results: Statistical analysis revealed that the D-dimer values of the LDVT group were significantly (P<0.05) higher than those of the non-LDVT group. The uric acid value of the LDVT group was significantly lower than that of the non-LDVT group, with statistical significance (P<0.05). The Brunnstrom staging in the LDVT group was significantly different from that in the non-LDVT group (P<0.05). Meanwhile, binary logistic regression analysis showed that LDVT complicated with cerebral infarction was associated with D-dimer level [OR=1.302, 95% CI (1.077, 1.575)], uric acid level [OR=0.995, 95% CI (0.990, 1.000)], and Brunnstrom staging [OR=3.005, 95% CI (1.312, 6.880)].

Conclusion: D-dimer value, uric acid value, and Brunnstrom stage I to II are closely related to the occurrence of LDVT in patients with cerebral infarction. High D-dimer value, low uric acid value, and Brunnstrom stage I to II are independent risk factors for LDVT in cerebral infarction. Early assessment of D-dimer value, uric acid value, and Brunnstrom stage of cerebral infarction should be considered in clinical practice.

Background: Leucine rich pentatricopeptide repeat containing (LRPPRC) protein is a multifunctional protein involved in cell cycle progression and tumor development. However, its prognostic significance and association with immune infiltration in Liver hepatocellular carcinoma (LIHC) remain unclear.

Methods: We utilized transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases of LIHC patients to investigate the potential pro-cancer role of LRPPRC, including differential expression of LRPPRC in LIHC, prognostic value, clinicopathological features, immune cell infiltration relevance and function enrichment analysis.

Results: Our findings suggest that LRPPRC is upregulated in LIHC and exhibits correlations with survival, clinical stage, and tumor grade in LIHC patients. Additionally, immune infiltration analysis revealed significant negative correlations between LRPPRC expression and multiple tumor-infiltrating immune cells, including CTLs, DCs, pDCs, B cells, Th17 cells, neutrophils, T cells, Mast cells, Th1 cells, Tregs, and NK cells, whereas a significant positive correlation was observed with infiltration of Th2 cells, T helper cells and Tcms. Furthermore, functional enrichment analysis indicated that LRPPRC may be involved in G2m checkpoint, mitotic spindle, E2f targets, Wnt Beta catenin signaling, spermatogenesis and other processes.

Single-cell sequencing is an emerging technology that can effectively identify cell types in tumors. In the tumor microenvironment of bladder cancer, macrophages play a crucial role in invasion and immune escape. This study aimed to assess the expression of macrophage-related genes (MRGs) in the tumor microenvironment of bladder cancer patients and construct a prognostic model based on MRGs using bioinformatics methods.

Methods: Single-cell sequencing data from bladder cancer patients was downloaded from the GEO. After quality control and cell type identification, macrophages in the samples were extracted for re-clustering. Feature genes were then identified, and MRGs were assessed. Genetic data from TCGA database bladder cancer patients was also downloaded and organized. The intersection of MRGs and the TCGA gene set was determined. Clinical information was connected with this intersection, and the data was divided into training and validation sets. The training set was used for model construction and the validation set for model verification. A prognostic model based on MRGs was built using the LASSO algorithm and Cox regression. Patients were divided into high-risk and low-risk groups based on their prognostic features, and survival information in the training and validation sets was observed. The predictive ability of the model was assessed using a ROC curve, followed by a calibration plot to predict 1-, 3-, and 5-year survival rates.

Results: Four cell types were identified, and after extracting macrophages, three cell subgroups were clustered, resulting in 1,078 feature genes. The top 100 feature genes from each macrophage subgroup were extracted and intersected with TCGA expressed genes to construct the model. A risk prediction model composed of CD74, METRN, PTPRR, and CDC42EP5 was obtained. The survival and ROC curves showed that this model had good predictive ability. A calibration curve also demonstrated good prognostic ability for patients.

Conclusion: This study, based on single-cell data, TCGA data, and clinical information, constructed an MRG-based prognostic model for bladder cancer using multi-omics methods. This model has good accuracy and reliability in predicting the survival and prognosis of patients with bladder cancer, providing a reference for understanding the interaction between MRGs and bladder cancer.