Abstract: A systemic and local inflammatory immune imbalance is thought to be the cause of traumatic tracheal stenosis (TS). However, with CD4+ T lymphocytes being the predominant immune cells in TS, the mechanism of action and recruitment has not been described. In our research, using flow cytometry, ELISA, immunofluorescence, and Transwell chamber assays, the expression, distribution, and potential chemotactic function of CD4+ T cells in TS patients were examined before and after treatment. The results showed that the untreated group had significantly more CD4+ T cells and their secreted TGF-β1 than the treated group. Additionally, the untreated group’s CD4+ T cells showed a significant rise in CCL22 and CCL1, as well as a larger proportion of CCR4 and CCR8. CD4+ T cells and CD68+ macrophages located in TS also expressed CCL1 and CCL22. In vitro, anti-CCL1 and anti-CCL22 can partially block the chemoattractant effect of TS bronchoalveolar lavage (BAL) on purified CD4+ T cells. The findings of this study indicated that TS contained unbalanced CD4 immune cells that were actively recruited locally by CCR4/CCL22 and CCR8/CCL1. As a result, it is anticipated that CD4 immune rebalancing can serve as a novel treatment for TS.

Recent studies have shown that exosomes are involved in pathogenesis and in the treatment of various tumors and inflammatory diseases. We examined the impacts of exosomes released from Talaromyces marneffei (T. marneffei)-infected macrophages on human macrophages to determine whether they play a role in the pathogenesis of T. marneffei infection. Exosomes derived from macrophages were extracted using commercial kits and characterized by transmission electron microscopy and western blot. Further, we examine exosomes that regulate IL-10 and TNF-α production and activation of p42 and p44 extracellular signal-regulated kinase 1 and 2 (ERK1/2) and activation of autophagy. We found that exosomes induced activation of ERK1/2 and autophagy, IL-10 and TNF-α production in human macrophages. Furthermore, exosomes decreased the replication of T. marneffei in T. marneffei-infected human macrophages. Interestingly, exosomes isolated from T. marneffei-infected but not from uninfected macrophages can stimulate a proinflammtory response in resting macrophages. Our studies are the first to demonstrate that exosomes isolated from T. marneffei-infected macrophages can induce a proinflammatory response, and we hypothesize that exosomes play significant roles in activation of ERK1/2 and autophagy, the replication of T. marneffei and cytokine release during T. marneffei infection.

From January 2021 to June 2022, CDC required pre-departure SARS-CoV-2 testing for all air passengers arriving into the United States. Using data collected during a pilot surveillance program, this manuscript describes pre-departure testing behavior among a convenience sample of international air passengers entering the United States from July to September 2021 at six US ports of entry. We analyzed pairwise relationships between self-reported test type, test timing, demographic and travel characteristics, and COVID-19 vaccination status. We found that test type was significantly associated with departure region, likely reflecting the regional disparities in the availability of tests at the time of the activity.

Background: Rhinitis, allergic rhinitis in particular, and urticaria are both common atopic problems globally. However, there is controversy regarding the correlation between rhinits and urticaria. Objectives: To examine the accurate association between rhinitis and urticaria. Methods: Three medical databases (PubMed, Embase, and Web of Science) were searched from database inception until January 11, 2022. The prevalence and association between rhinitis and urticaria were estimated by meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed, and quality assessment was performed using the Newcastle–Ottawa Scale. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) and pooled prevalence were calculated using random-effects models. Results: Urticaria prevalence in patients with rhinitis was 17.6% (95% CI, 13.2%–21.9%). The pooled prevalence of rhinitis was 31.3% (95% CI, 24.2%–38.4%) in patients with urticaria, and rhinitis prevalence in patients with acute urticaria and chronic urticaria was 31.6% (95% CI, 7.4%–55.8%) and 28.7% (95% CI, 20.4%–36.9%), respectively. Rhinitis occurence was significantly associated with urticaria (OR, 2.67; 95% CI, 2.625–2.715). Limitations: Urticaria and rhinitis were diagnosed based on different criteria possibly resulting in a potential misclassification of these two diseases. Conclusion: Rhinitis and urticaria were significantly correlated. Physicians should be cognizant regarding this relationship and address nasal or skin symptoms in patients.

Heat stroke is a life-threatening disease with high mortality rate and unexpected complications. Vascular endothelial glycocalyx is essential for maintaining endothelial cell structure and function as well as preventing adhesion of inflammatory cells. Potential relationship that underlays the imbalance in inflammation and coagulation remains elusive. Moreover, the role of endothelial glycocalyx in heat stroke-induced organ injury remained unclear. Heat stress and lipopolysaccharide (LPS) are employed to construct in vitro models to study the change of glycocalyx structure and function in human pulmonary microvascular endothelial cells (HPMEC), as well as levels of heparansulfate proteoglycan (HSPG), syndecans-1, heparansulfate, TNF-α, IL-6, vWF, ET-1, Occludin, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and reactive oxygen species (ROS). Here, we showed that heat stress and LPS devastated endothelial glycocalyx structure, activated endothelial glycocalyx degradation, and triggered oxidative damage in addition to apoptosis in HPMEC. Stimulation of heat stress and LPS increased HSPG, syndecans-1 (SDC-1), and heparansulfate levels, and promoted the ability to produce and release pro-inflammation cytokines (TNF-α, IL-6,) and coagulative factor (vWF, ET-1) in HPMEC. Furthermore, E-selectin, VCAM-1, and ROS expression were upregulated in contrast to Occludin downregulation. These changes could be deteriorated by Heparanase, whereas could be ameliorated by unfractionated heparin. This study highlights that heat stroke-induced endothelial glycocalyx degradation can trigger oxidative and apoptosis in HPMEC, in addition to dysfunction of inhibition of inflammatory response and protection in vascular permeability.

Introduction: Vaccination plays a fundamental role in mastering the COVID-19 pandemic and protecting vulnerable groups. Persons with autoimmune inflammatory rheumatic diseases (AIIRD), on immunosuppressive therapies, are prioritized for vaccination. However, data concerning immunogenicity and safety of the BBIBP-CorV vaccine in immunosuppressed patients are not found. This study presents data on the efficacy and safety of the BBIBP-CorV vaccine in immunosuppressed patients compared to healthy controls. Methods: Study population consisted of 100 healthy controls and 100 patients with AIIRD. Vaccination was performed according to national guidelines with the BBIBP-CorV vaccine. SARS-CoV2 neutralizing antibody titers were quantified by ELISA before initial vaccination and 1–3 months after secondary vaccination. Adverse events were assessed before study initiation and 7 days after the second dose. Disease activity was studied before entering the study and 3-8 weeks after the second dose. Results: Vaccination-induced positive immunogenic response rates and SARS-CoV2 neutralizing antibody titers were significantly lower in the AIIRD patients than healthy subjects (P<0.05). There are significant differences in neutralizing antibody titers among patients suffering from RA, SLE, SSc, and AS (P<0.01-0.05). The rates of seropositive vaccine responses were similarly distributed across all diseases. Healthy and AIIRD individuals had a similar profile in adverse events. No significant difference was observed in SARSCoV2 antibody titers between subjects suffering from side effects and those who did not have. SARS-CoV2 neutralizing antibody levels were significantly higher in SARS-CoV2-infected persons than noninfected subjects (P<0.01-0.05). Seropositive subjects had a significant increase in the percentage of vaccine-related adverse events compared to seronegative persons (P<0.05). Despite a minor change in the disease activity of patients with RA and SLE, disease activity indices were overall stable in the AIIRD patients. Conclusion: The BBIBP-CorV vaccine is effective in the development of neutralizing antibody in immunosuppressed patients without considerable reactogenicity or induction of disease flares.

Behçet syndrome (BS) is a chronic, multisystemic inflammatory condition with unanswered questions regarding its pathogenesis and rational therapeutics. A microarray-based comparative transcriptomic analysis was performed to elucidate the molecular mechanisms of BS and identify any potential therapeutic targets. Twenty-nine BS patients (B) and 15 age and sex-matched control subjects (C) were recruited. Patients were grouped as mucocutaneous (M), ocular (O), and vascular (V) according to their clinical phenotypes. GeneChip Human Genome U133 Plus 2.0 arrays were used for expression profiling on peripheral blood samples of the patients and the control subjects. Following documentation of the differentially expressed gene (DEG) sets, the data were further evaluated with bioinformatics analysis, visualization, and enrichment tools. Validation of the microarray data was performed using qRT-PCR. When P ≤0.05 and fold change ≥2.0 were chosen, the following numbers of DEGs were obtained; B vs. C: 28, M vs. C: 20, O vs. C: 8, V vs. C: 555, M vs. O: 6, M vs. V: 324, O vs. V: 142. Venn diagram analysis indicated only two genes, CLEC12A and IFI27, in the intersection of M vs. C and O vs. C and V vs. C. Another noteworthy gene appeared as CLC in the DEG sets. Cluster analyses successfully clustered distinct clinical phenotypes of BS. While innate immunity-related processes were enriched in the M group, adaptive immunity-specific processes were significantly enriched in the O and V groups. Distinct clinical phenotypes of BS patients displayed distinct expression profiles. In Turkish BS patients, expression differences regarding the genes CLEC12A, IFI27, and CLC seemed to be operative in the disease pathogenesis. Based on these findings, future research should consider the immunogenetic heterogeneity of BS clinical phenotypes. Two anti-inflammatory genes, namely CLEC12A and CLC, may be valuable as therapeutic targets and may also help design an experimental model in BS.

Introduction: Probiotics are live microorganisms that, when administered in appropriate colonies, can delay the destruction of the immune system and contribute to the maintenance of immunity in HIV patients. Probiotics play an important role in stimulating natural killer T cells, strengthening the functional gut barrier, and reducing systemic inflammation. Methods: This study was a randomized double blind clinical trial involving 30 patients treated with ART who had experienced immunological failure despite HIV viral suppression. Patients were divided into two equal groups of 15, the first group received 2 probiotic capsules daily with a colony count of 10⁹CFU per capsule containing seven strains ,after three months they were examined for CD4+ counts by flow cytometry, after a one month washout period the participants who had received probiotics were switched to placebo, and the participants who had received placebo were given probiotics for three months, and they were examined for CD4+ counts seven months after the start of the study. Results: In the first group, administration of the placebo resulted in a decrease in CD4 count in the first three months (from 202.21 to 181.79, p-value < 0.001),which may be due to the natural history of the disease. After probiotics administration, CD4 count increased significantly (from 181.79 to 243.86, p-value < 0.001). Overall, after 7 months of study, there was a significant increase in the mean CD count from 202.21 to 243.86 (p-value < 0.001). In the second group, administration of probiotics in the first three months of the study resulted in a significant increase in the mean CD4 count (from 126.45 to 175.73, p-value < 0.001).Termination of treatment with probiotics resulted in a significant decrease (from 175.73 to 138.9, p-value < 0.001)but overall the CD4 count at the end of the study was significantly higher than at baseline (p-value < 0.001).

Background: Patients with human immunodeficiency virus (HIV) are at a significantly higher risk of cardiovascular disease (CVD) compared to HIV-negative people. Left heart dysfunction is the most common cardiac complication in people living with HIV/AIDS (PLWHA), and diastolic dysfunction is an important predictor of cardiovascular events. The aims of this study were 1) to detect changes in left cardiac structure and function in antiretroviral therapy (ART)-naive PLWHA using echocardiography; and 2) to investigate the risk factors for the development of left ventricular diastolic dysfunction (LVDD) in ART-naive PLWHA. Methods: We retrospectively included 105 ART-naïve PLWHA and included 90 healthy subjects as controls to compare the differences in left heart structure and function between the two groups. Univariate and multifactorial logistic regression were employed to explore the risk factors of the development of LVDD in ART-naive PLWHA. Results: The left ventricular end-diastolic internal diameter (LVEDD), left ventricular mass index (LVMI), and left atrial volume index (LAVI) were significantly greater in PLWHA than in controls (p＜0.05). The E/A ratio, lateral e’ velocity, and mitral deceleration time (DT) were significantly lower in PLWHA than in controls (p < 0.05). Average E/e’ ratio was significantly higher in PLWHA than in controls (p < 0.05). Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were not significantly different between PLWHA and controls (p＞0.05). Multifactorial logistic regression analysis showed that age, body mass index (BMI), and CD4+ count < 200 cells/μL were independent influencing factors for LVDD in ART-naive PLWHA (OR=1.781, 1.228, 3.683, p＜0.05). Conclusions: Left ventricular systolic function did not differ between PLWHA and controls, and left ventricular diastolic function was lower in PLWHA than in controls. Age, BMI, and CD4+ count were independent factors affecting LVDD in ART-naive PLWHA.