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Background. Alopecia has become an exceedingly prevalent dermatological disorder. Etiologically, infection (bacterial and fungal infection), inflammation, and immune dysregulation are the main causes of immune-mediated hair loss. Treating hair loss has remained challenging as the available therapies are limited. Exosomes from adipose-derived stem cells (ADSC-Exos) have been used for treating neurodegenerative diseases and autoimmune diseases and in wound-healing treatments. However, the function and mechanism of ADSC-Exos in alopecia treatment remain unclear. This study is aimed at investigating the effects of ADSC-Exos on hair growth in vitro and in vivo for potentially treating immune-mediated alopecia and further exploring the underlying mechanism. Methods. Cell proliferation, migration, and apoptosis of dermal papilla cells (DPCs) that were treated with ADSC-Exos were detected using the cell counting kit-8 (CCK-8) assay, scratch wound-healing assay, and flow cytometry assay, respectively. A C57BL/6 hair-depilated mouse model was established in vivo; then, ADSC-Exos were subcutaneously injected alone or in combined with minoxidil. The effects of ADSC-Exos on hair growth, pathological changes, and the related mechanism were investigated by HE staining, quantitative real‐time PCR (qRT-PCR), western blotting, and RNA sequencing (RNA-seq). Results. ADSC-Exos significantly promoted DPC proliferation and migration while also reducing apoptosis. In addition, compared with the control group, ADSC-Exos-treated mice had better hair growth, more hair follicles (HFs) and thicker dermis. RNA-seq revealed that the miR-22 and TNF-α signaling pathways were markedly downregulated in DPCs after ADSC-Exos treatment. In addition, according to qRT-PCR and western blotting results, the Wnt/β-catenin signaling pathway was activated in the skin of ADSC-Exos-treated mice. Conclusion. ADSC-Exos therapy positively affected the promotion of hair regrowth by regulating miR-22, the Wnt/β-catenin signaling pathway, and the TNF-α signaling pathway, implying that ADSC-Exos could be a promising cell-free therapeutic strategy for immune-mediated alopecia.

Backgrounds. Infection and inflammation play an important role in prostate cancer (PCa) etiology and pathogenesis. However, the environmental drivers for PCa are not fully understood. Methods. In a cross-sectional study, we analyzed circulating fungal microbiome in plasma samples from age and race-matched healthy control men ( n = 34 ) and preoperative PCa patients ( n = 31 ). Results. The fungal community in the plasma exhibited differences between individuals with PCa and healthy controls according to the beta diversity; there was no difference in the alpha diversity. Moreover, the relative abundance of several fungi differed between the two study groups from the class to species levels. The most significant differences were Filobasidiales family, Pyronemataceae family, and Cryptococcus ater species, which were enriched in PCa patients compared to controls. The increased Bipolaris genus was associated with low prostate-specific antigen (PSA) levels, increased Sordariomycetes class was associated with severe pathological stage, and decreased Phoma herbarum species was associated with disease relapse, compared to corresponding controls. Several fungi from class to species levels were increased in the controls compared to patients. Conclusion. This is the first study to show plasma distinct fungal microbiome and its associations with PSA levels, relapse, and pathology stages in PCa patients.

Background Dysregulation of BZRAP1‐AS1 was associated with immune statuses of cancer or Alzheimer's disease patients, yet little is known about its role in rheumatoid arthritis. Methods RT‐qPCR and western blot were applied to assess the expression of indicated expression. CCK‐8 and BrdU proliferation assays were used to measure the proliferation of RA‐HFLS. Apoptosis in RA‐HFLS was evidenced by the alteration of caspase‐3 activity and apoptosis‐related factors. ELISA was performed to detect IL‐6, IL‐1β, and TNF‐α level. Luciferase reporter, RIP, and pull‐down assays were used to confirm the BZRAP1‐AS1/miR‐1286/COL5A2 cascade predicted by bioinformatics analysis. Results BZRAP1‐AS1 and COL5A2 were downregulated in RA tissues and RA‐HFLS while miR‐1286 was amplified. Overexpression of BZRAP1‐AS1 reduced the RA‐HFLS proliferation, IL‐6, IL‐1β, and TNF‐α level and induced cell apoptosis while BZRAP1‐AS1 silence produced an opposite effect. Overexpression of BZRAP1‐AS1 reduced the miR‐1286 expression which in turn increased the COL5A2 expression, thereby relieving the excessive proliferation and limited apoptosis in RA‐HFLS. Conclusion Our findings suggested that BZRAP1‐AS1 sequestered miR‐1286 and reshaped the COL5A2 expression, thereby suppressed RA‐HFLS proliferation and inflammation, and triggered cell apoptosis, resulting in the attenuation of RA progression.

Background In hospitalized people with HIV (PWH) there is an increased risk of mortality from COVID-19 among hospitalized PWH as compared to HIV-negative individuals. Evidence suggests that tocilizumab—a humanized monoclonal interleukin (IL)-6 receptor inhibitor (IL-6ri) antibody—has a modest mortality benefit when combined with corticosteroids in select hospitalized COVID-19 patients who are severely ill. Data on clinical outcomes after tocilizumab use in PWH with severe COVID-19 are lacking. Case presentation We present a multinational case series of 18 PWH with COVID-19 who were treated with IL-6ri’s during the period from April to June 2020. Four patients received tocilizumab, six sarilumab, and eight received an undocumented IL-6ri. Of the 18 patients in the series, 4 (22%) had CD4 counts 3; 14 (82%) had a suppressed HIV viral load. Eight patients (44%), all admitted to ICU, were treated for secondary infection; 5 had a confirmed organism. Of the four patients with CD4 counts 3, three were treated for secondary infection, with 2 confirmed organisms. Overall outcomes were poor—12 patients (67%) were admitted to the ICU, 11 (61%) required mechanical ventilation, and 7 (39%) died. Conclusions In this case series of hospitalized PWH with COVID-19 and given IL-6ri prior to the common use of corticosteroids, there are reports of secondary or co-infection in severely ill patients. Comprehensive studies in PWH, particularly with CD4 counts

Background Coronavirus disease (COVID‐19) is a global infectious disease with a large burden of illness and high health care costs. This study aimed to compare clinical features among adult COVID‐19 patients in different age groups. Methods Laboratory‐confirmed adult COVID‐19 infection cases between December 31, 2019 to March 8, 2020 obtained from Neighboring Cities. Patients were divided into five age groups. Clinical characteristics were compared among different age groups. Results Of 299 cases, median age was 44 and 158 (53%) were male. A total of 53.3% of 30–40 years, 50% of 40–50 years, 36.6% of, Graphical abstract This study aimed to compare clinical features among adult COVID‐19 patients in different age groups. Among all the observed symptoms, only symptom of dyspnea was significantly different between the elderly group and other groups. Old age, high heart rate on admission, high respiratory rate on admission, and history of chronic heart disease were independently associated with severe or critical.

Introduction Mast cells are regarded as a kind of classical anaphylaxis cells. However autoimmune diseases and allergic reactions have many similarities or overlaps. A large number of papers have proved that mast cells play a significant role in the pathogenesis of systemic lupus erythematosus (SLE). It is speculated that IgE, anti‐IgE antibodies, FcεRI, and anti‐FcεRI antibodies activate mast cells through autoimmune pathways and participate in the disease process of SLE. Naturally occurring protein molecules not only exist in monomer form, but also in polymer of protein molecules. Therefore, whether IgE, FcεRIα, anti‐IgE antibodies, and anti‐FcεRI antibodies also exist in polymeric forms in the natural state is worthy of further investigation. Methods The serum samples and clinical data of 131 patients with SLE were collected from Qilu Hospital (Qingdao). Sixty healthy individuals were collected as the control group. Serum FcεRIα, anti‐IgE, and anti‐FcεRI were detected by enzyme‐linked immunosorbent assay. Serum IgE was detected by rate scatter nephelometry. A Chinese hamster ovarian cancer cell line CHO3D10 transfected with human FcεRIα was cultured and the cell protein extract was prepared. The existence forms of FcεRIα in the cell protein extract were detected by the native‐page method. Results The serum FcεRIα in SLE patients was significantly higher than that in control group (3.52 [2.18, 4.71] µg/ml and 1.87 [1.52, 2.33] µg/ml, respectively; p, First, as autoimmune diseases and allergic reactions have many similarities or overlaps, we compared the differences in serum IgE, FcεRIα, anti‐IgE, and anti‐FcεRI levels of systemic lupus erythematosus group and healthy control group for the first time. The serum FcεRIα in SLE patients is significantly higher than that in the control group and anti‐IgE is significantly lower than that in the control group, which provides a new reference basis for the understanding and further discussion of the inflammatory mechanism of the disease. Second, this study has revealed that the FcεRIα has one kind of monomer and two kinds of polymers in the degeneration conditions, which is worthy of further investigation.

Introduction Hyperinflammatory state has a role in the pathogenesis of COVID‐19. Anakinra could reduce inflammation and help to combat the condition. In this study, we aimed to assess the safety and efficacy of anakinra (PerkinRA®) in severe COVID‐19. Method The study was an open‐label, randomized, controlled trial conducted in Imam Hossein Medical Center from May to July 2020. Patients with a confirmed diagnosis of COVID‐19 were included in this study. We administered anakinra 100 mg daily intravenously. All patients received COVID‐19 pharmacotherapy based on the represented national guideline. The need for invasive mechanical ventilation is considered the primary outcome. Results Thirty patients were included in this study, and 15 of them received Anakinra. Nineteen patients were male (63.3%), and 11 were female (36.7%). The mean age of patients was 55.77 ± 15.89 years. In the intervention group, the need for invasive mechanical ventilation was significantly reduced compared to the control group (20.0% vs. 66.7%, p = .010). Also, these patients had a significantly lower length of hospital stay (p = .043). No significant higher rate of infection was recorded. Conclusion Anakinra as an immunomodulatory agent has been associated with the reduced need for mechanical ventilation in patients admitted to intensive care units because of severe COVID‐19. The medication reduced the hospital length of stay. Furthermore, no increased risk of infection was observed. Further randomized placebo‐controlled trials with a larger sample size are needed to confirm these findings., Anakinra administration significantly reduces the need for mechanical ventilation. No increased risk of infection was observed because of anakinra use. Reduced hospitalization duration observed in patients who received anakinra.

Introduction Coronavirus disease 2019 (COVID‐19) vaccines can cause adverse reactions, mainly from vaccine‐induced immune responses. Some of these may also involve the skin and worry unaware patients. A better understanding of such adverse reactions may reduce concerns and help promote the vaccination of large population groups. Methods All the reports of patients admitted to our Dermatology Primary Care, from March 2021 to June 2021, were retrospectively examined to collect descriptive data on skin reactions arising after COVID‐19 vaccination. Results Out of 200 vaccinated patients admitted to the Dermatology Primary Care, 21 (10.5%) referred cutaneous reactions with onset after vaccination. Only one patient required hospitalization for generalized bullous erythema multiforme, which occurred 48 h after the second vaccine dose. The other patients' cutaneous reactions to vaccination were of mild/moderate degree. Three patients presented exacerbation of their cutaneous diseases. Conclusions Cutaneous reactions observed in our sample were mostly mild or moderate. Awareness must be raised to recognize and treat eventual severe reactions. Future studies are needed to assess the incidence of cutaneous reactions following COVID‐19 vaccination., Graphical abstract After COVID‐19 vaccination, pruritic rashes were frequently reported reactions at the Dermatology Primary care.

Purpose. Bladder cancer is one of the most common urological malignancies worldwide, and approximately 90% of bladder cancer cases are histologically typed as bladder urothelial carcinoma (BLCA). Exosomes are 30 to 200 nm extracellular vesicles that transport microRNAs, long noncoding RNAs (lncRNAs), mRNAs, circular RNAs, and proteins across tissues and through circulation. Urinary exosomes may contain genetic information from tumor cells. Herein, we explored the clinical significance of urinary exosomal lncRNA telomerase RNA component (TERC) levels to provide an urgently needed diagnostic and prognostic biomarker for BLCA. Materials and Methods. In this study, we used RNA-sequencing of samples from four BLCA patients and three healthy controls to identify that TERC was differentially expressed in urinary exosomes. We then used quantitative PCR in different types of clinical samples to validate the biomarker and analyzed results using receiver operating characteristic curves. Results. We found that TERC was significantly upregulated in urinary exosomes from BLCA patients compared with those from healthy controls ( P < 0.0001 ). Urinary exosomal TERC showed higher sensitivity (78.65%) and accuracy (77.78%) than existing indicators including nuclear matrix protein-22 and urine cytometry. Using the cut-off value 4.302, the area under the curve for urinary exosomal TERC was 0.836 (95% confidence interval: 0.768–0.891, P < 0.0001 ). Furthermore, this noninvasive assay could distinguish low-grade and high-grade tumors ( P = 0.0153 ). Conclusions. TERC is enriched in urinary exosomes from BLCA patients. Urinary exosomal TERC could become a diagnostic and prognostic biomarker for BLCA that allows clinicians to realize noninvasive detection of BLCA.

The peptidylarginine deiminases (PADs) and the citrullinated proteins that they generate have key roles in innate immunity and rheumatoid arthritis, an inflammatory arthritis with antibodies that target citrullinated proteins. However, the importance of PADs, particularly PAD2, in the adaptive immune response, both normal and pathogenic, is newly emerging. In this study, we evaluated a requirement for PAD2 in the antibody response in collagen-induced arthritis (CIA), a T and B cell-driven murine model of rheumatoid arthritis, and in the protective antibody response to murine influenza infection. Using PAD2-/- and PAD2+/+ mice on the DBA/1J background, we found that PAD2 is required for maximal anti-collagen antibody levels, but not collagen-specific plasma cell numbers, T cell activation or polarization, or arthritis severity in CIA. Also, we found that PAD2 is required not just for normal levels of persistent hemagglutination inhibiting antibodies but also for full protection from lethal influenza rechallenge. Together, these data provide evidence for a novel modest requirement for PAD2 in a normal antiviral antibody response and in an abnormal autoantibody response in inflammatory arthritis.

Background. Type-2 inflammation commonly marks asthma in childhood. Also, gut and lung dysbiosis is detectable in patients with asthma. Strain-related probiotic supplementation may restore a physiological immune response, dampen airway inflammation, and repair dysbiosis. Therefore, the probiotics in pediatric asthma management (PROPAM) study is aimed at demonstrating that Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) mixture could reduce asthma exacerbations in children, followed in a primary care setting. Methods. The study was randomized, placebo-controlled, and double-blind. It involved 11 Italian primary care pediatricians. The probiotic mixture (containing Ligilactobacillus salivarius LS01 1 × 10 9 live cells and Bifidobacterium breve B632 1 × 10 9 live cells) or placebo was taken twice daily (1 sachet in the morning and 1 in the evening) for eight weeks and subsequently once daily for a further eight weeks. Outcomes included number, severity, and duration of asthma exacerbations, intensity of maintenance and as need treatments, and safety. Results. The per-protocol population included 422 children (mean age seven years, 240 males and 182 females). The probiotic mixture significantly reduced the number of asthmatic exacerbations ( OR = 3.17 ). In addition, the number of children with two exacerbations was less than a third in the active group ( OR = 3.65 ). Conclusions. This PROPAM study demonstrated that probiotic strains Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) were safe and significantly reduced by more than a third the frequency of asthma exacerbations. At present, the first-line treatment of asthma is still drug-based, but specific strains of probiotics may be auxiliary remedies.

Macrophages are an important component of the human immune system and play a key role in the immune response, which can protect the body against infection and regulate the development of tissue inflammation. Some studies found that macrophages can produce extracellular traps (ETs) under various conditions of stimulation. ETs are web-like structures that consist of proteins and DNA. ETs are thought to immobilize and kill microorganisms, as well as play an important role in tissue damage, inflammatory progression, and autoimmune diseases. In this review, the structure, identification, mechanism, and research progress of macrophage extracellular traps (METs) in related diseases are reviewed.

Tumor antigen-specific T cell function is limited by immune tolerance in the tumor microenvironment. In the tumor microenvironment, tumor cells upregulate PD-L1 expression to promote T cell exhaustion by PD-1/PD-L1 interactions and undergo mutations to avoid being targeted by tumor antigen-specific T cells. Thus, tumor cells escape the immune surveillance by causing immune tolerance. We reason that a chimeric molecule made of a PD-L1-specific antibody linked to a cleavable antigenic peptide can target the antigenic peptide to the tumor microenvironment, resulting in the blockade of the PD-1/PD-L1 pathway and killing tumor cells through the coating of antigenic peptide. Here, we have generated a therapeutic chimeric protein containing the PD-L1 single-chain variable fragment (scFv) linked to a cleavable model cytotoxic T lymphocyte (CTL) epitope: E7 CTL peptide. Our study demonstrated that our chimeric protein (named PDL1-scFv-Fc-RE7) can target PD-L1-expressing tumor cells and enable E7 presentation by releasing cleavable E7 CTL peptide to coat tumor cells, resulting in tumor clearance by E7-specific CD8+ T cells. The presentation of the E7 peptide by cancer cells can then render tumor cells susceptible to the killing of preexisting E7-specific CD8+ T cells and contribute to tumor clearance. Our finding suggests a synergistic approach to not only enhance antigen-specific tumor clearance but also bypass immune tolerance.

Introduction. KLRB1 is a gene encoding CD161 expressed in NK cells and some T cell subsets. At present, KLRB1 is believed to affect tumorigenesis and development by regulating the cytotoxicity of NK cells in several cancers. However, there is a lack of systematic reviews of KLRB1 in a variety of malignancies. Objectives. Hence, our research is aimed at providing a relatively comprehensive understanding of the role of KLRB1 in different types of cancer, paving the way for further research on the molecular mechanism and immunotherapy potential of KLRB1. Methods. In this study, we used relevant public databases, including TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus), CCLE (Cancer Cell Line Encyclopedia), GTEx (Genotype Tissue-Expression), and HPA (Human Protein Atlas), to perform a pan-cancer analysis of KLRB1 across 33 types of cancer. We explored the potential molecular mechanism of KLRB1 in clinical prognosis and tumor immunity from the aspects of gene expression, survival status, clinical phenotype, immune infiltration, immunotherapy response, and chemotherapeutic drug sensitivity. Results. KLRB1 was downregulated in 13 cancers while upregulated in kidney cancer. Patients with high expression of KLRB1 have a better prognosis in most types of cancer. Moreover, the KLRB1 expression level is related to TMB and MSI and related to various immune signatures of tumor. The expression of KLRB1 can affect tumor immune cell infiltration. KLRB1 expression level can also affect the sensitivity of chemotherapy drugs. Conclusions. KLRB1 may be a prognostic and immunological biomarker across tumors. At the same time, KLRB1 expression can reflect the sensitivity of cancer patients to chemotherapy drugs. KLRB1 may become a new target for immunotherapy.

Background Although population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related μ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity. Methods We initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response. Results Among 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4+CD4+ effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4+ T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation. Conclusions Without forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN.

Atopic dermatitis (AD) is the most common chronic skin inflammatory disease, with a profound impact on patients' quality of life. AD varies considerably in clinical course, age of onset and degree to which it is accompanied by allergic and non-allergic comorbidities. Skin barrier impairment in both lesional and nonlesional skin is now recognized as a critical and often early feature of AD. This may be explained by a number of abnormalities identified within both the stratum corneum and stratum granulosum layers of the epidermis. The goal of this review is to provide an overview of key barrier defects in AD, starting with a historical perspective. We will also highlight some of the commonly used methods to characterize and quantify skin barrier function. There is ample opportunity for further investigative work which we call out throughout this review. These include: quantifying the relative impact of individual epidermal abnormalities and putting this in a more holistic view with physiological measures of barrier function, as well as determining whether these barrier-specific endotypes predict clinical phenotypes (e.g. age of onset, natural history, comorbidities, response to therapies, etc). Mechanistic studies with new (and in development) AD therapies that specifically target immune pathways, Staphylococcus aureus abundance and/or skin barrier will help us understand the dynamic crosstalk between these compartments and their relative importance in AD.

Background Measurement of allergen-specific IgE antibodies to inhaled allergens is important for the diagnosis and risk evaluation of allergic diseases such as asthma and allergic rhinitis. This study aimed to elucidate the prevalence of allergen sensitization among the healthy population in Japan using serum samples stocked in the Japanese Red Cross for blood donation. Methods Age- and gender-stratified serum samples (n = 800) from residents in Tokyo aged 20–59 years were randomly selected from the stocked serum obtained for blood donation in 2005. Total and specific IgE antibodies to 17 inhaled allergens were measured by the ImmunoCAP method. Individuals with positive (≥0.35 UA/mL) specific IgE antibodies to at least one inhaled allergen were defined as atopic. Stocked serums from donors aged 20–29 years in Sapporo, Osaka, Fukuoka, and Okinawa (n = 200 each) were also obtained for the measurement of IgE to six common inhaled allergens, to evaluate regional differences in the rate of positivity. Results Among residents in Tokyo, the prevalence of atopy was 78.0% and highest in men aged 20–29 years (94.0%), which decreased with age. The prevalence of specific IgE antibodies was highest for Japanese cedar pollen (66.8%), followed by cypress pollen (46.8%), Dermatophagoides pteronyssinus (38.3%), and moths (30.1%). Examination of IgE to Japanese cedar pollen, D. pteronyssinus, and moths identified 97.6% of atopic subjects in Tokyo. There were substantial regional differences in the prevalence of pollen IgE positivity. Conclusions This study demonstrated an extremely high prevalence of positivity in inhaled allergen-specific IgE antibodies among healthy adults in Japan.

Background Allergic rhinitis (AR) is a complex disease involving both mucosal and systemic immune compartments. Greater understanding of the immune networks underpinning AR pathophysiology may assist with further refining disease‐specific biomarkers. Objective To compare immune gene expression profiles in nasal mucosa and peripheral blood samples between adults with AR and controls without AR. Methods This cross‐sectional study included 45 adults with moderate‐severe and persistent AR (37.6 ± 12.8 years; mean ± SD) and 24 adults without AR (36.6 ± 10.2). Gene expression analysis was performed using the NanoString nCounter PanCancer Immune profiling panel (n = 730 immune genes) in combination with the panel plus probe set (n = 30 allergy‐related genes) with purified RNA from peripheral blood and cell lysates prepared from combined nasal lavage and nasal brushing. Results One hundred and thirteen genes were significantly differentially expressed in peripheral blood samples between groups (p, A series of genes were differentially expressed in both peripheral blood and nasal mucosal samples from adults with moderate‐severe persistent allergic rhinitis compared with adults without a history of allergic rhinitis.

Introduction The aim of this study was to investigate the improvements in laboratory testing procedures and the quality and safety management for large‐scale population screening for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Methods Because of epidemic prevention and control needs in Hebei Province, on January 7, 2021, the Health Commission of Zhejiang Province sent a medical team to Hebei Province, to carry out SARS‐CoV‐2 nucleic acid testing. Screening for the SARS‐CoV‐2 nucleic acid test was performed using reverse‐transcription polymerase chain reaction (RT‐PCR). Practical tests and repeated process optimization were adopted to explore the optimal solution for improving laboratory testing procedures and the quality of and safety management for large‐scale population screening for SARS‐CoV‐2. Results The Zhejiang medical team completed 250,000 pooled SARS‐CoV‐2 nucleic acid samples in 24 days in Shijiazhuang, with a peak daily testing capacity of 40,246 samples testing. There were no false‐negative or false‐positive results, and no laboratory personnel was infected with SARS‐CoV‐2. Significant achievements have been made in SARS‐CoV‐2 prevention and control. Conclusions This report summarizes the effort of the medical team regarding their management of the quality and safety of laboratory tests and proposes corresponding empirical recommendations to provide a reference for future large‐scale population screening SARS‐CoV‐2., The Health Commission of Zhejiang Province of china sent a medical team to Hebei Province, to carry out SARS‐CoV‐2 nucleic acid testing. The Zhejiang medical team completed 250,000 pooled more than two million peoples' SARS‐CoV‐2 nucleic acid samples in 24 days in Shijiazhuang, with a peak daily testing volume of 40,246 pooled samples using reverse‐transcription polymerase chain reaction (RT‐PCR). There were no false‐negative or false‐positive results, and no laboratory personnel was infected with SARS‐CoV‐2. Layout recommendations for temporary laboratories for large‐scale nucleic acid screening operation process and experience sharing of each link of nucleic acid detection.

BackgroundDespite high rate of vaccination coverage with 2-doses of measles containing vaccine among Iranian children, outbreaks of measles occurred among different age groups and fully vaccinated subjects. Although the main reason for these outbreaks is unknown, however, vaccine failure was supposed to be an important cause. This study was designed to determine the seroconversion rates to measles- mumps- rubella (MMR) vaccine currently in use among Iranian children.MethodsThis prospective study was conducted among healthy children older than 12 months who were candidates of scheduled MMR vaccination. Blood samples were obtained from each mother- infant pair just before vaccination, and from infants 4–6 weeks after MMR1and MMR2immunization. Collected sera were tested for specific lgG antibodies against MMR agents using ELISA method. The proportion of seroprotected subjects among mother- infant pairs before vaccination as well as the prevalence rates of seroconversion after MMR1and MMR2vaccination were calculated. Collected data were analyzed using descriptive statistical methods.ResultsDuring 22-months study period, 92 mother- infant pairs were participated. Seroimmunity rates against MMR viruses were 85.8%, 84.7% and 86.9% for mothers, and 3.2%, 2.1% and 1.0% for children, respectively. After MMR1vaccination from 52 seronegative children, 80.7%, 78.8% and 75% were seroconverted. These rates increased to 94.8%, 89.7% and 94.8% after the MMR2vaccination. Also, the specific immunity was enhanced among seropositive children.ConclusionMajority of the mothers and few infants were immune to MMR viruses prior to MMR1vaccination. Immune responses detected after MMR1injection, and overall seroconversion rates achieved after 2-doses of MMR vaccination were less than expected and inadequate to preserve long-term protection against MMR agents.

Objective This study was aimed to identify the biomarkers for diagnosis and reveal the immune microenvironment changes in ankylosing spondylitis (AS). Methods GSE73754 was downloaded for the co-expression network construction and immune cell analyses. Flow cytometric analysis was performed to validate the results of bioinformatics analysis. Gene set enrichment analysis (GSEA) was performed to investigate the potential biological characteristic between different phenotypes. Pearson correlation analysis between the hub genes and the xCell score of immune cell types was performed. Results Signal transducer and activator of transcription 3 (STAT3) and Spi-1 proto-oncogene (SPI1) was identified as the hub genes in the datasets GSE73754. And the t-test showed that the expression level of STAT3 and SPI1 in the GSE73754 was significantly higher in AS and human leukocyte antigen (HLA)-B27(+) groups. Flow cytometric analysis showed that natural killer T cells (NKT) cells were upregulated, while Th1 cells were down-regulated in AS, which was consistent with the results obtained from bioinformatics analysis. STAT3 and SPI1 was correlated with the NKT cells and Th1 cells. Conclusion STAT3 and SPI1 may be a key cytokine receptor in disease progression in AS.

Background Natto (fermented soybeans)-induced hypersensitivity is characterized by delayed symptom onset that hampers diagnosis. We aimed to clarify the clinical utility of the basophil activation test (BAT) in the diagnosis of natto-induced hypersensitivity. Methods Five patients with a history of anaphylaxis and chronic urticaria suspected of natto-induced hypersensitivity and seven with chronic spontaneous urticaria clinically unrelated to natto were enrolled in the patient and control groups, respectively. The BAT was performed with two incubation times, 15 min and 1 h, in combination with various concentrations of natto-mucilage extract. Results In controls, CD203c levels in basophils remained low in the 15-min incubation but were significantly increased in the 1-h incubation. In the patient group, in the 15-min condition, basophil CD203c was significantly upregulated by natto mucilage but not by soybean vs controls (P = 0.001). Low concentrations of natto mucilage were sufficient to upregulate basophil CD203c in the anaphylaxis cases, but high concentrations were required to induce the same effect in the urticaria cases. Finally, the dose-dependent pattern of the BAT results differed significantly between the anaphylaxis and urticaria cases (P = 0.006). Thus, a strong background reaction was observed in the BAT with 1 h incubation; 15 min of incubation was sufficient to identify patients with natto-induced hypersensitivity and may distinguish the clinical phenotype of natto-induced hypersensitivity, i.e., anaphylaxis or urticaria. Conclusions The BAT with a 15-min incubation period is useful in diagnosing natto-induced hypersensitivity.

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions. The knowledge on the pathogenesis of AD is driving the development of new drugs. From the research results, it has been revealed that Th2 cell-mediated immunity, skin barrier dysfunction, and pruritus cause a vicious cycle of AD. On the other hand, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway are one of the essential signaling pathways in various inflammatory diseases including AD. In particular, TSLP, IL-4, IL-13 and IL-22 occupy an important position for Th2 cell-mediated immune reaction. Moreover, experimentally pan-JAK inhibitor suppress the STAT3 activation and improved the skin barrier function. Furthermore TSLP, IL-4, IL-13 and IL-31 contribute a lot to chronic pruritus of AD, and transmitted via JAK-STAT pathway. Therefore, JAK inhibitors are promising candidates for the treatment of severe AD. Here we review clinical trials of topical dergocitinib; a pan-JAK inhibitor, ruxolitinib; a JAK1 and JAK2 inhibitor, and tofacitinib; a JAK1, JAK2, and JAK3 inhibitor and oral baricitinib; a JAK1 and JAK2 inhibitor, abrocitinib and upadacitinib; JAK1 inhibitor. Significant improvements in the symptoms were obtained by each drug with low frequency of adverse events. In particular, oral JAK inhibitors have the ability to improve the pruritus and skin symptoms quickly. Therefore, the emergence of these topical and oral JAK inhibitors would be regarded as an innovation in the treatment of atopic dermatitis.

Background Retention in clinical care is important for people living with HIV (PLWH). Evidence suggests that missed clinic visits are associated with interruptions in antiretroviral therapy (ART), lower CD4 counts, virologic failure, and overlooked coinfections. We identified factors associated with missed routine clinic visits in the African Cohort Study (AFRICOS). Methods In 2013, AFRICOS began enrolling people with and without HIV in Uganda, Kenya, Tanzania, and Nigeria. At enrollment and every 6 months thereafter, sociodemographic questionnaires are administered and clinical outcomes assessed. Missed clinic visits were measured as the self-reported number of clinic visits missed in the past 6 months and dichotomized into none or one or more visits missed. Logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between risk factors and missed visits. Results Between January 2013 and March 2020, 2937 PLWH were enrolled, of whom 2807 (95.6%) had initiated ART and 2771 had complete data available for analyses. Compared to PLWH 50+, missed clinic visits were more common among those 18–29 years (aOR 2.33, 95% CI 1.65–3.29), 30–39 years (aOR 1.59, 95% CI 1.19–2.13), and 40–49 years (aOR 1.42, 95% CI 1.07–1.89). As compared to PLWH on ART for Conclusions Inconsistent clinic attendance is associated with worsened HIV-related outcomes. Strategies to improve visit adherence are especially needed for young PLWH and those with depression.

Objective The objective was to evaluate whether initiation of urate-lowering treatment (ULT) during an acute gout flare prolonged the current episode. Methods A comprehensive search of MEDLINE and Web of Science databases was conducted from their inception to 15 March 2021. Five randomized controlled trials (RCTs) with 381 patients met the inclusion criteria. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were used for estimating the clinical efficacy of ULT in acute gout. Results There was no statistical difference in days to resolution (intent-to-treat analysis) (SMD, 0.68; 95% CI − 0.42 to 1.78; I2, 49%; p = 0.22), the pain visual analogue score (VAS) by day 10 (SMD, − 0.07; 95% CI − 0.30 to 0.16; I2, 0%; p = 0.53), C-reactive protein (CRP) from day 7 to 10 (SMD, − 1.14; 95% CI − 5.63 to 3.36; I2, 55%; p = 0.62), erythrocyte sedimentation rate (ESR) from day 7 to 10 (SMD, − 2.51; 95% CI − 5.46 to 0.45; I2, 0%; p = 0.10) and the recurrence of gout flares within 28–30 days (OR 0.78; 95% CI 0.29 to 2.09; I2, 0%; p = 0.62). Conclusion Initiation of ULT during an acute gout flare did not prolong the duration of the flare. However, larger sample size studies are needed to confirm this finding. Trial registration number PROSPERO (CRD42021234581).

Background Autoantibodies (AAbs) against immunoglobulin E (IgE) antibodies (Abs) and their high-affinity receptor alpha subunits (FceRIα) are key factors in the elicitation of type IIb autoimmune chronic spontaneous urticaria (type IIb aiCSU). In this study, we aimed to develop a new method to detect functional anti-FceRIα and anti-IgE AAbs, which can crosslink the plural FceRІα molecules and IgE Abs on the surface of mast cells and basophils, in sera from aiCSU patients using the amplified luminescence proximity homogeneous assay (Alpha). Methods Sera were obtained from 14 aiCSU patients, as diagnosed by recurrent chronic spontaneous urticaria episodes and positive results for the autologous serum skin test and/or histamine release test (HRT). The AAbs to FceRIα and IgE Abs were determined in sera from aiCSU patients using enzyme-linked immunosorbent assay (ELISA) and Alpha by cross-linking (AlphaCL) of IgE Abs and/or FceRІα. Results Serum anti-FceRIα and anti-IgE AAb levels were not significantly different between aiCSU patients and healthy subjects in ELISA. Anti-FceRIα AAbs were detected in 10 of 14 aiCSU patients who displayed positive (5/5) and negative (5/9) results in the HRT for anti-FceRIα AAbs by AlphaCL, whereas no signals were observed in healthy subjects. Additionally, anti-IgE AAbs were detected in two of four aiCSU patients who displayed positive results in the HRT for anti-IgE AAbs. Conclusions A new assay method using AlphaCL can detect anti-FceRIα and anti-IgE AAbs with FceRIα- and IgE-crosslinking abilities in sera from aiCSU patients. This simple and practical assay method may be available as a diagnostic tool for urticaria patients.

Background The effects of bronchial thermoplasty (BT) on smooth muscle (SM) and nerves in small airways are unclear. Methods We recruited 15 patients with severe refractory asthma, who received BT treatment. Endobronchial optical-coherence tomography (EB-OCT) was performed at baseline, 3 weeks' follow-up and 2 years' follow-up to evaluate the effect of BT on airway structure. In addition, we divided 12 healthy beagles into a sham group and a BT group, the latter receiving BT on large airways (inner diameter >3 mm) of the lower lobe. The dogs’ lung lobes were resected to evaluate histological and neuronal changes of the treated large airways and untreated small airways 12 weeks after BT. Results Patients receiving BT treatment had significant improvement in Asthma Control Questionnaire (ACQ) scores and significant reduction in asthma exacerbations. EB-OCT results demonstrated a notable increase in inner-airway area (Ai) and decrease in airway wall area percentage (Aw%) in both large (3rd-to 6th-generation) and small (7th-to 9th-generation) airways. Furthermore, the animal study showed a significant reduction in the amount of SM in BT-treated large airways but not in untreated small airways. Protein gene product 9.5 (PGP9.5)–positive nerves and muscarinic receptor 3 (M3 receptor) expression in large and small airways were both markedly decreased throughout the airway wall 12 weeks after BT treatment. Conclusions BT significantly reduced nerves, but not SM, in small airways, which might shed light on the mechanism of lung denervation by BT.

Introduction: The human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) has long affected millions of individuals across the globe. Historically, the prevalence of this disease is particularly noted within the African continent. Before the coronavirus disease 2019 (COVID‐19) pandemic, many African countries struggled to effectively manage the increasing burden associated with HIV/AIDS. There is now a need to reassess this in a COVID‐19 pandemic context so that the impact of COVID‐19 on HIV/AIDS healthcare within Africa can be adequately evaluated. Methods: Data collection was performed on the PubMed, Ovid MEDLINE and Embase bibliographical databases with a predefined search strategy. Searches were performed in blind duplicate and all articles considering COVID‐19 and HIV/AIDS within African healthcare were considered. Results: The COVID‐19 pandemic has severely exacerbated the many issues surrounding HIV/AIDS care within many African countries. These impacts are noticeable in medical, psychological, and socio‐political contexts. Conclusions: Before efforts are made to improve the provision of HIV/AIDS and COVID‐19 care within Africa, it is important that this issue is brought to the attention of the scientific and clinical community so that the continent can receive the necessary support and aid.

Background Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma. Methods TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control. Results TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment. Conclusions Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.

Background: Allergic rhinitis (AR) is caused by allergic reaction to allergens such as pollen. Galanin (GAL), a neuropeptide that regulates inflammatory processes, is widely expressed in the central and peripheral nervous systems. Although neuropeptides are implicated in arthritis and chemically induced ileitis, their roles in AR remain unclear. Methods: We developed a murine model of AR and generated control, systemic sensitization, mild AR, and severe AR groups. We examined GAL and GAL receptor (GALR) mRNA and protein levels and localization patterns in each group using reverse transcription PCR, western blotting, and immunohistochemical analyses. Additionally, we evaluated the effects of M871, a GALR2 antagonist, on mice with severe AR. Results: Gal and Galr2 are expressed in nasal mucosa and brain (control) samples from control and AR mice. GAL and GALR2 were expressed at similar levels and localized to ciliated epithelial and submucosal gland cells of the nasal mucosa in all four groups. Intranasal M871 administration significantly reduced the incidence of nose rubbing behaviors and sneezing (p

Background Lupus nephritis (LN) is a major source of morbidity and mortality in patients with systemic lupus erythematosus (SLE), with 10–25% of patients progressing to end-stage renal disease (ESRD). Objective This study aims to elucidate the predictive capabilities of 24-h proteinuria (24PTU) and serum creatinine (sCr) after 12 months of treatment with respect to long-term renal outcomes in LN in a single-center cohort of LN patients. Methods A retrospective analysis was performed on 214 patients diagnosed with LN followed in our center. Values of 24PTU and sCr were assessed at baseline and after 3, 6 and 12 months, and after 5 years and/or the last evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) 2 for 3 months or longer. End-stage renal disease (ESRD) was defined as the need for permanent dialysis. Receiver operating characteristics curves (ROC) were used to test the best cut-off value of 24PTU and sCr at 12 months who predict bad long-term renal outcomes. Results The mean follow-up period was 11.2 ± 7.2 years. The best cut-off values for 24PTU and sCr as predictor of CKD were, respectively, 0.9 g/24 h and 0.9 mg/dL. ROC curve for 24PTU had a slightly lower performance than ROC curve for sCr as predictor for CKD (PTU AUC = 0.68; sCr AUC = 0.70), but sensitivity and specificity were better for 24PTU (24PTU: sensitivity = 63.5%, specificity = 71.2%; sCr: sensitivity = 54.8%, specificity = 75.3%). When the outcome was ESRD the best cut-off points were 0.9 g/24hs and 1.3 mg/dL for 24PTU and sCr, respectively, and the curve performance was better for 24PTU (PTU AUC = 0.72; sCr AUC = 0.61). Conclusions In this ethnically diverse population with LN followed for a long time (> 10 years), levels of 24PTU > 0.9/day at 12 months was a good predictor of bad long-term renal outcome. The serum creatinine > 0.9 mg/dL and > 1.3 mg/dL at 12 months were also good predictors of CKD and ESRD, respectively. Patients with 24PTU .

Background Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. Methods We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60–90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. Results This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. Conclusions Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

Atopic dermatitis (AD) is a heterogenous disorder and can be classified into different types. Stratification of subtypes may enable personalized medicine approaches. AD can be categorized into the IgE-high, extrinsic subtype and the IgE-normal, intrinsic subtype. While extrinsic AD is the major subtype possessing skin barrier impairment (high incidence of filaggrin mutations), intrinsic AD occupies about 20% of AD with female dominance and preserved barrier. Extrinsic AD exhibits protein allergy and food allergy, but intrinsic AD shows metal allergy possibly in association with suprabasin deficiency. In particular, accumulated knowledge of food allergy has more clearly characterized extrinsic AD. European American (EA) and Asian AD subtypes have been also proposed. Asian patients with AD are characterized by a unique blended immune dysregulation and barrier feature phenotype between EA patients with AD and those with psoriasis. In another ethnic study, filaggrin loss-of-function mutations are not prevalent in African American patients with AD, and Th1/Th17 attenuation and Th2/Th22 skewing were seen in these patients. Recent endotype classification provides new insights for AD and other allergic disorders. Endotype is defined as the molecular mechanisms underlying the visible features/phenotype. Endotype repertoire harbors activation of type 2 cytokines, type 1 cytokines, and IL-17/IL-22, impairment of epidermal barrier, and abnormalities of intercellular lipids. Classification of endotype has been attempted with serum markers. These lines of evidence indicate a need for personalized or precision medicine appropriate for each subtype of AD.

Background Cystic fibrosis (CF) is a genetic condition that affects multiple organ systems. Allergic bronchopulmonary aspergillosis (ABPA) is a well‐recognised problem but other allergic conditions are less well documented in CF. Objective To characterise the allergic profile of a cohort of children with CF, with a focus on those with ABPA. Methods A cohort of children with CF were interviewed and retrospective data were collected regarding their allergic histories and other relevant clinical features. Results The cohort included 37 children with median age of 9 years (interquartile range: 6‐12). There was a history of ≥1 allergic condition(s) in 28/37 children (76%). The most common allergic condition was allergic rhinitis (AR) in 21/37 (57%) and 16 of these 21 children (76%) had another allergic condition. All children with ABPA (8) had another allergic condition. In some children ABPA exacerbations appeared to be seasonal, suggesting possible cross‐sensitisation between Aspergillus fumigatus and aeroallergens associated with seasonal AR. Allergic conditions were also common in children with Pseudomonas aeruginosa infection., “Example allergic timelines for children with CF”

Background Overactivation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome can lead to severe illness in patients with coronavirus disease‐2019 (COVID‐19). The NLRP3 inhibitor, colchicine, therefore, appears to be promising for the treatment of COVID‐19. Aims We aimed to perform a meta‐analysis of randomized trials investigating the effect of colchicine in patients with COVID‐19. Materials & Methods We systematically searched electronic databases and clinical trial registries (up to October 17, 2021) for eligible studies. The outcomes of interest were all‐cause mortality and duration of hospital stay. Meta‐analysis with the random‐effects model was used to estimate the pooled odds ratio (OR) of mortality and 95% confidence interval (CI). The pooled standardized mean difference of duration of hospital stay with 95% CI between colchicine users and non‐colchicine users was estimated using Cohen's d index. Results The meta‐analyses revealed no significant difference in the odds of mortality (pooled OR = 0.76; 95% CI: 0.53–1.07), but a significant reduction in the duration of hospital stay with the use of colchicine (pooled standardized mean difference = −0.59; 95% CI: −1.06 to −0.13). Discussion and Conclusion The ability of colchicine to reduce the length of stay in hospitalized patients with COVID‐19 is consistent with its potential to prevent clinical deterioration via inhibition of NLRP3 inflammasome. Nevertheless, such beneficial effects of colchicine did not translate into mortality benefits in patients with COVID‐19., Colchicine which is a potent NLRP3 inhibitor had been trialed as a potential treatment of coronavirus disease‐2019 (COVID‐19). This meta‐analysis confirms the ability of colchicine to reduce the length of hospital stay in hospitalized patients with COVID‐19, which is consistent with its potential to prevent clinical deterioration via inhibition of NLRP3 inflammasome. However, this meta‐analysis also revealed no significant difference in the odds of mortality with the use of colchicine in patients with COVID‐19.