Abstract Objectives: To evaluate patient activation in Rheumatoid Arthritis (RA) patients using the patient activation measure 13 (PAM-13) on a national level in Saudi Arabia. Method: A national survey was administered across multiple centres in Saudi Arabia. The survey assessed patient activation using the PAM-13. The Compliance Questionnaire for Rheumatology (CQR) and the RA Impact of Disease (RAID) tool, were assessed. The data from the survey were analysed, and the results were stratified based on activation level. All factors affecting patient activation were explored and reported. Results: A total of 1241 participants were included. Most of the patients were females (85%), the mean age was 47 (±14), and most patients lived in the central region (47%). The mean (±SD) patient activation score was 578.7 (±13.0). Patient activation was affected by multiple factors: demographic characteristics, such as education, with a beta value of 1.11 (95% CI 0.64 ̵̶ 1.58, p<0.001). Higher CQR scores were associated with higher activation level, with a beta value of 2.61 (95% CI 0.80 ̵̶ 4.44, p=0.005); and higher RAID scores were associated with lower activation levels, with a beta value of 3.13 (95% CI 1.36 ̵̶ 4.91, p=0.001). Conclusions: Patient activation was affected by several demographic characteristics and impact of RA. A higher activation may improve compliance. Future longitudinal studies are required to confirm these findings and should explore the underlying mechanism of these effects.

Background: As a polyphenolic compound originated from the food spice turmeric, curcumin (CUR) has various pharmacological effects, such as anti-inflammatory, anti-oxidation, anti-proliferative and anti-angiogenic activities. Psoriasis is centered on the overproduction of Th1- and Th2-related cytokines (e. g. IL-23, IL-17, TNF-α, IL-22), which is involved in the occurrence and development of its pathogenesis. However, whether CUR is involved in the treatment of psoriasis and its specific mechanisms are not fully understood. Methods: In this study, we detected the therapeutic effect of CUR (100mg/kg· d) on IMQ-induced dermatitis in mice, analyzed by PASI scores, ELISA, HE staining, immunofluorescence. Moreover, we further confirmed the alteration in the relative abundance of the gut microbiota through 16sRNA to explore whether CUR could regulate the gut microbiota of IMQ-induced mice. Result: Through intragastric administration, CUR can alleviate psoriasis-like lesions of mice by decreasing PASI scores, reducing the level of IL-6, IL-17A, IL-22, IL-23, TNF-α and TGF-β1, promoting the expression of IL-10. Moreover, 16 sRNA sequencing revealed that CUR could regulate the alteration in the abundance alteration of gut microbiota related to inflammation, such as Alistipes, Mucispirillum and Rikenella at genus level. The correlation analysis further confirmed the close association between important microflora and psoriasis-like inflammation indicators. Conclusions: CUR exerts the effect of alleviating dermatitis of psoriatic mice by regulating Th-17 related inflammatory factors. Moreover, the changes in gut microbiota via CUR may be another factor of relieving IMQ-induced lesions in mice. Therefore, CUR may be a highly promising candidate for the treatment of psoriasis.

The Marburg virus, which is a member of the same virus family as the Ebola virus called Filoviridae, causes the severe infectious disease known as Marburg Virus Disease (MVD). Previously, different outbreaks of MVD have appeared in different African countries, including Ghana, Guinea, Uganda, Angola, the Democratic Republic of the Congo, Kenya, and South Africa. For the first time, Equatorial Guinea and Tanzania are experiencing MVD outbreaks. A total of 15 laboratory-confirmed cases of MVD and 23 probable cases have been reported in Equatorial Guinea since the confirmation of the outbreak on 13 February 2023. The first MVD outbreak in the United Republic of Tanzania was formally confirmed by the Ministry of Health on March 21, 2023. As of 22 March, there were eight cases and five fatalities (case fatality ratio [CFR]: 62.5%). Due to the facts that Ebebiyin and Nsock Nsomo districts, the affected regions of Equatorial Guinea, borders Cameroon and Gabon, and Kagera region, the affected region of Tanzania, borders Uganda, Rwanda and Burundi, there is fear of cross-border spread of MVD due to cross-border migrations, and this can be a great crisis in West and East Africa. Although there are currently outbreaks of MVD in Equatorial Guinea and Tanzania, there is currently no proof of an epidemiological connection between the two outbreaks. The aim of this paper is to describe Marburg Virus Disease (MVD), describe its first outbreak in Equatorial Guinea and Tanzania, explain the efforts being used and the challenges being faced in MVD mitigation, and recommend different measures to be taken to cope with the outbreak of MVD in Equatorial Guinea and Tanzania.

Background: Kawasaki disease (KD) is a kind of vasculitis with an unidentified etiology. Cathelicidin (LL-37) may be involved in the development of the KD process; therefore, further research to investigate the molecular mechanism of LL-37 involvement in KD is warranted. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α, IL-1β, NLRP3, and LL-37 in the sera of healthy subjects, children with KD, and children with pneumonia. Subsequently, human recombinant LL-37 or/and TLR4-specific inhibitor TAK-242 stimulated HCAECs cells, CCK-8 was used to detect cell proliferation, flow cytometry to detect apoptosis, transmission electron microscopy to observe cytoskeletal changes, Transwell to measure cell migration ability, ELISA to detect inflammatory factor levels, Western blotting to analyze protein levels of TLR4 and NF-κB p-65, and qRT-PCR to determine LL-37, NLRP3 mRNA levels. Results: In this study, we found that the level of LL-37 was highly expressed in the serum of children with KD, and after LL-37 stimulation, apoptosis was significantly increased in HCAECs, and the expression levels of TLR4, NLRP3 and inflammatory factors in cells were significantly enhanced. Intervention with the TLR4-specific inhibitor TAK-242 significantly alleviated the LL-37 effects on cellular inflammation, TLR4, NLRP3 promotion effect. Conclusions: Our data suggest that LL-37 induces an inflammatory response in endothelial cells via TLR4-NF-κB, leading to coronary artery injury in KD, providing a potential target to treat KD.

Objective: Acute-on-chronic liver failure (ACLF) causes organ system failures and the high mortality, and there is currently a lack of effective means of prevention. The purpose of the study was to explore the therapeutic effects of Resolvin D1 (RvD1) on ACLF rats and its underlying mechanism. Methods: ACLF rat model was constructed by intraperitoneally injecting CCl4 and porcine serum for 6 weeks and then induced acute liver injury by treating with both LPS and D-Galn. The ACLF rats were pretreated with different doses of RvD1 (0.3 or 1 ug/kg) before the acute liver injury. Biochemical analysis, H&E and sirius red staining, flow cytometry assay and real-time PCR were used to assess rat liver histopathological injury, determine the Treg cell frequencies in spleen and the mRNA levels of transcription factors and immunologic cytokines in liver. Results: The necro-inflammatory scores and the serum levels of transaminase significantly increased in ACLF model rats compared to those in normal control rats, with the peak at 8 h. Low-dose of RvD1 could limit necrosis and inflammation and decrease the ALT level of ACLF rats. The degree of damage in ACLF rats was related to the increased mRNA levels of IL-17 and IL-6 in the ACLF rats’ liver and Treg cells reduction in the spleen. Low-dose of RvD1 could protect against liver injury in ACLF rats, as indicated by increasing Treg cell frequency in rats’ spleen and the mRNA levels of Foxp3/RORγ and decreasing the expression of both IL-6 and IL-17. Conclusion: Low-dose of RvD1 plays a protective role in ACLF rats by increasing the proportion of Treg cells. It is the first time to reveal the function of RvD1 in the treatment of ACLF. This work may help us clarify the pathogenesis of ACLF and find effective therapeutic drugs for ACLF.

Considering the efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS-CoV-2 patients. Type I interferon (IFN-I) signature and cytokines genes were evaluated by real time RT-PCR. The vaccinated patients had increased negative rate of SARS-CoV-2 RT/real-time PCR tests as compared to unvaccinated ones after mAbs treatment. Unvaccinated patients but also those that resulted negative for serum anti-S antibodies despite vaccination had lower IFN-I and higher IFN-I related genes and cytokines mRNAs levels as compared to vaccinated individuals before mAbs. In addition, patients with low anti-S antibody titer showed immune genes expression levels between those found in negative and patients with high titer of anti-S antibodies. Changes in IFN-I pathway and cytokines levels were observed in unvaccinated patients after mAbs treatment, while the expression of most of the type I IFN genes and cytokines analysed, except for ISGs and IL-10 mRNAs, remained unchanged vaccinated patients. These data suggest that mAbs treatment is associated to a different virological and immunological response in SARS-CoV-2 infected patients according to their vaccination status and related anti-S antibodies titers.

Background: As people in China travel less and consume less imported frozen food during the COVID-19 pandemic, the composition ratio of allergens may have changed. Objective: To investigate the changes of composition ratio of 20 types of specific allergens from January 2020 to June 2021 of 618 patients in China. Methods: The 20 items of allergen-specific IgE (sIgE) detection includes dermatophagoides pteronyssinus, dermatophagoides farina, ambrosia artemisiifolia, salix babylonica, dander of dog, alternaria, cockroach, artemisia argyi, dander of cat, house dust, milk, hen’s egg, mutton, cod, peanut, beef, soybean, shrimp, crab and wheat. The results of detection were collected from patients of dermatology, pediatrics or allergy department. They are from 17 hospitals in China from January 2020 to June 2021, and participants were required to have at least one positive result of sIgE detection (≥0.35 IU/mL). The age ranges from 0 to 89 years old. Serum detection was performed by enzyme allegro-sorbent test (REAST). Results: The proportion of inhaled allergens in 618 patients was significantly lower than that of ingested allergens. Most of the inhaled allergens were indoor allergens. In the first half of 2020, the second half of 2020 and the first half of 2021, the positive proportions of wheat, shrimp and crab were changed. Compared with the same period in 2020, the positive proportion of wheat and shrimp in the spring of 2021 significantly decreased, while that of crab was significantly increased. The ratio fluctuation of dermatophagoides pteronyssinus and dermatophagoides farina was related to seasonal factors. There was no significant difference in the proportion of other allergens. Conclusion: The special historical background of the epidemic may have a certain influence on the change of the proportion of allergens, but it is not the only factor.

Background/aim: To investigate the frequency and clinical relevance of an extended autoantibody (ab) profile in patients with SSc. Materials and Methods: In this cross-sectional study, serum from 100 consecutive patients was subjected to indirect immunofluorescence (HEp-20-10/primate liver mosaic) and Systemic Sclerosis Profile by EUROIMMUN (Lübeck, Germany) to evaluate ANA and autoantibodies against 13 different autoantibodies in patients with SSc less than three years. Results: 93 of 100 patients were positive for ANA by indirect immunofluorescence (IIF). The prevalence of Anti-Scl70 ab was 41%, anti-centromere (ACA) 27%, and anti-RNA polymerase (RNAPIII) 15%. Scl70 was more associated with diffuse subtype (p<0.001), ILD (p<0.001), and high mRSS (p=0.002); ACA with limited disease (p<0.001), less ILD (p<0.001), overlap (p=0.017) and low mRSS (p=0.024); RNAPIII with diffuse disease (p=0.027), ILD (p=0.016) and high mRSS (p=0.001). Fifty-three patients showed single positivity (26 anti-Scl70, 16 ACA, 6 anti-RNAPIII, 1 anti-Ku ab, 1 anti-PM/Scl100, 2 anti-PM/Scl75, 1 anti-Ro52), whereas 32 patients had multiple auto-antibody positivities. Among common SSc-specific autoantibodies, Scl70 and RNAPIII showed the highest co-occurrence (n=4). One patient was simultaneously positive for anti-RNAPIII ab and ACA, and one was positive for ACA and Scl70. The clinical features were not statistically different between single and multiple autoantibody-positivity for common SSc-specific autoantibodies (ACA, Scl70, and RNAP III), except for digital ulcer in multi-antibody positive ACA group (p=0.019). Conclusion: Based on our results, co-expression of auto-antibodies is not uncommon in SSc patients. Although SSc-specific auto-antibodies generally show known clinical features, the clinical presentation of the co-expression in specific and non-specific auto-antibody positivity continues to be important.

Objective: To assess the effectiveness and safety of the total glucosides of paeony (TGP) combined with Hydroxychloroquine (HCQ) on the treatment of primary Sjögren’s syndrome (pSS) by conducting a meta-analysis. Methods: Eight databases were searched for randomized controlled trials reporting the use of TGP combined with HCQ for pSS, which are before May 10,2022. Meta analyses were performed on disappeared clinical symptoms (dry mouth, dry eyes),schirmer’s test, saliva flow test, erythrocyte sedimentation rate (ESR), index of immunoglobulin G(IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and adverse events (AEs). The Revman 5.4 software was used for this Meta-analysis.Results: Seven RCTs which included 632 participants were identified.The pooled results showed significant differences in clinical symptoms disappear(dry mouth, dry eyes)(P=0.0004), IgM(P < 0.00001) , IgA(P < 0.00001) , salivary flow rate(P < 0.00001) and schirmer’s test(p=0.02) in the comparison of TGP combined with HCQ and HCQ alone. For the IgG and ESR, both pooled and subgroup analyses showed that TGP+HCQ was superior to HCQ alone. For the safety analysis, no significant differences in AEs(P=0.39) was revealed. The more frequently seen adverse reactions were diarrhea, vomit and there was no severe adverse events were reported in TGP+HCQ group. Conclusion: Therefore, TGP+HCQ can be considered to be a potentially valid and safe combination for the treatment of pSS in the clinic.

Background: Ulcerative colitis (UC) is a chronic inflammatory disease caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, known for its various bioactivities, including anti-inflammatory, anti-obesity, and antipyretic activities. However, the potential anti-inflammatory effects of PHI on UC and its underlying mechanisms are still poorly understood. Methods: In this study, we investigated the therapeutic effects of PHI on acute UC induced by DSS and TNBS. We evaluated the effects of PHI on disease activity index, body weight, mortality, intestinal mucosal barrier, cytokine secretion, and macrophage infiltration into colon tissue using various techniques such as flow cytometry, immunofluorescence, ELISA, RT-qPCR, and Western blotting. Results: Our findings revealed that PHI has therapeutic properties in UC treatment. PHI was able to maintain body weight, reduce disease activity index and mortality, restore the intestinal mucosal barrier, and inhibit cytokine secretion. Flow cytometry assay and immunofluorescence indicated that PHI reduces macrophage infiltration into colon tissue. Additionally, both in vivo and in vitro results suggested that PHI may exert anti-inflammatory effects by downregulating the TLR4/MyD88/NF-κB pathway, inhibiting NLRP3 inflammasome activation. Conclusion: In conclusion, PHI possesses anti-inflammatory properties and has the potential as a therapeutic agent for the treatment of UC. Our study provides insights into the underlying mechanisms of PHI’s therapeutic effects and highlights the potential for further research in developing PHI-based treatments for UC.

Autoimmune diseases (AD) are severe pathophysiological ailments that are stimulated by an exaggerated immunogenic response towards self-antigens, which can cause systemic or site-specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression of AD, thus providing significant insight into the regulatory mechanism of microRNA (miRNA). miRNAs are short, non-coding RNAs that have been identified as essential contributors to the post-transcriptional regulation of host genome expression and as crucial regulators of a myriad of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development. Pertaining to the differential expression of miRNA attributed in target tissues and cellular bodies of innate and adaptive immunity, a paradigm of scientific expeditions suggests an optimistic correlation between immunogenic dysfunction and miRNA alterations. Therefore, it is not astonishing that dysregulations in miRNA expression patterns are now recognized in a wide spectrum of disorders, establishing themselves as potential biomarkers and therapeutic targets. Owing to its theranostic potencies, miRNA targets have been widely utilized in the development of biosensors and other therapeutic molecules originating from the same. This article tends to deliberate and conceptualize the brief pathogenesis and pertinent epigenetic regulatory mechanism as well as miRNA networks majorly affecting five different ADs namely Rheumatoid Arthritis (RA), Diabetes, Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE) and Inflammatory Bowel Disorder (IBD) thereby providing novel theranostic interventions.

The DC-T cell axis is a bridge connecting innate immunity and adaptive immunity. The initial immune response against tumors is mainly induced by mature antigen-presenting dendritic cells (DC). Enhancing the crosstalk between DC and T cells could improve the immune response to non-small cell lung cancer. This article reviews the interaction between DC-T cells in the treatment of non-small cell lung cancer and how this interaction impacts the treatment outcome.

Autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) are the most prevalent rheumatic autoimmune disorders affecting autologous connective tissues caused by the breakdown of the self-tolerance mechanisms of the immune system. During the last two decades, stem cell therapy has been increasingly considered as a therapeutic option in various diseases, including parkinson’s disease, alzheimer, stroke, spinal cord injury, multiple sclerosis, inflammatory bowel disease, liver disease, diabete, heart disease, bone disease, renal disease, respiratory diseases, and hematological abnormalities such as anemia. This is due to the unique properties of stem cells that divide and differentiate to the specialized cells in the damaged tissue. Moreover, they impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as rheumatic autoimmune disorders. In the present review, efficacy of stem cell therapy with two main types of stem cells, including mesenchymal stem cells, and hematopoietic stem cells in animal models or human patients of one common rheumatic autoimmune diseases, including, RA, will be reviewed. Moreover, other related issues, including safety, changes in immunological parameters, suitable choice of stem cell origin, conditioning regimen, limitations, and complications of stem cell treatment will be discussed.

Immunocompromised individuals have been shown to mount a reduced response to vaccination, resulting in reduced vaccine effectiveness in this cohort. Therefore, in the post vaccination era, immunocompromised individuals remain at high risk of breakthrough infection and COVID-19 related hospitalisation and death. There has been a marked paucity of systematic review evaluating existing data describing the clinical measures of efficacy of COVID-19 vaccination in protecting immunocompromised individuals, specifically against, breakthrough infections and severe COVID-19. Therefore, we conducted a systematic review which aimed to provide a summary of current clinical evidence of the effectiveness of COVID-19 vaccination in the immunocompromised population. Our findings demonstrated that immunocompromised patients remained at high risk of breakthrough infection and severe COVID-19 outcomes compared to the general population. These groups included those with: cancer, organ transplants, chronic kidney disease, HIV and immunodeficiencies, amongst others. This demonstrated that vaccination does not offer an adequate level of protection in these groups, necessitating further measures such as Evusheld and further boosters.

Anti-MDA5 antibody-positive dermatomyositis (DM) is a rare clinical autoimmune disease, and anti-MDA5-positive DM with interstitial lung disease (ILD) is the most important cause of death in DM patients. We reported the efficacy of the JAK1/3 inhibitor tofacitinib as an anti-MDT5-negative treatment option for patients with anti-MDA5-positive DM-ILD. Here we report a 51-year-old female patient with cough, sputum, shortness of breath for 5 months, rash for 3 months, and muscle pain in the extremities for 1 month. After conventional immunosuppressive therapy plus hormone therapy, the remission was slow. Methylprednisolone was successfully reduced after we administered tofacitinib and tacrolimus. After 132 weeks of follow-up, anti-MDA5 antibody turned negative, clinical symptoms were relieved, and lung Imaging tests were successfully reversed. There is currently no report of tofacitinib supplement therapy for anti-MDA5 positive to negtive DM. With this case report, tofacitinib is an option for the treatment of anti-MDA5-positive DM-ILD, which deserves attention.

Background: Pulmonary thromboembolism (PTE) is a common complication of SARS-CoV-2, which raises the COVID-19 disease’s fatality rate from 3% to 45%. Nevertheless, due to fairly indistinguishable clinical symptoms and a lack of validated clinical prediction models, PTE diagnosis in COVID-19 patients is challenging. This study aims to investigate the applicability of hematological indices to predict PTE incidence and its severity in SARS-CoV-2 patients. Methods: A retrospective cohort study was conducted on hospitalized patients with a confirmed diagnosis of SARS-CoV-2 infection who underwent CT angiography to assess probable PTE in them. The correlation between CBC parameters one day prior to CT angiography and CT angiography outcomes, and simplified Pulmonary Embolism Severity Index (s-PESI) was investigated. Results: We discovered that among individuals with a probable PTE, males and those with higher platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte (NLR) ratios had a greater likelihood of PTE incidence. PLR was a significant and independent predictor of PTE. Moreover, a higher neutrophil count was associated with a higher s-PESI score in COVID-19 patients developing PTE. Conclusions: Among haematological indices, NLR and more precisely PLR are cost-effective and simply calculable markers that can assist physicians in determining whether or not COVID-19 patients with clinically probable PTE require CT angiography and the higher neutrophil count can be employed as an indicator of PTE severity in COVID-19 patients. Further large multicenter and prospective studies are warranted to corroborate these observations.

Background: To investigate the distribution of bacterial pathogens of lower respiratory tract infection (LRTI) in hospitalized elderly patients during the COVID-19 epidemic and to explore the influence of COVID-19 on the distribution of bacterial pathogens, in order to provide guidance for clinical diagnosis. Methods: Specimens of sputum from elderly LRTIs patients at Fuding Hospital of China were collected from October 2022 to January 2023. Cultures and identification were done, and RT-PCR was employed to detect SARS-Cov-2 nucleic acid. Results: A total of 195 isolates were characterized in 163 sputum samples of consecutive hospitalized elderly patients, of which 11.3% were Gram-positive bacteria and 88.7% Gram-negative. The top of frequently isolated pathogens were Klebsiella pneumonia (30.3%), Pseudomonas aeruginosa (19.0%), Acinetobacter baumannii (12.8%), Stenotrophomonas maltophili, (7.7%), Escherichia coli (7.2%). According to the results of novel coronavirus nucleic acid detection, the 163 patients were divided into COVID-19 group and non-COVID control (CNT) group. The comparison of bacterial distribution between the groups revealed that Stenotrophomonas maltophilia was lower in the COVID-19 than in the CNT group, while Acinetobacter baumannii was higher in the COVID-19 group, and the difference was statistically significant (P < 0.05). Conclusion: The major bacteria identified in sputum culture of hospitalized elderly patients were Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Escherichia coli. Furthermore, the distribution of Stenotrophomonas maltophilia and Acinetobacter baumannii between the COVID-19 and CNT groups was found to be significantly different (P< 0.05), while there were no significant differences in the distribution of other bacteria.

Meningitis, a disease that commonly manifests in African meningitis belt, continues to be a public health problem as it is a fatal disease that leave survivors with long-term effects. Most cases of meningitis are due to bacterial and viral infection, although parasites, fungus, cancer, drugs, and immune disorders can rarely cause meningitis. Stiff neck, high temperature, light sensitivity, disorientation, headaches, and vomiting are the most typical symptoms of meningitis. Niger being in African meningitis belt, has been impacted by many meningitis outbreaks. Since 2015, a total of 20 789 cases and 1369 fatalities (CFR 6.6%) have been documented in Niger. In contrast to earlier seasons, the current outbreak of meningitis in Niger exhibits both an increase in the number of cases and a rise in the growth rate. A total of 559 instances of meningitis, including 18 fatalities (overall CFR 3.2%), were reported in the Zinder Region, southeast of Niger, from 1 November 2022 to 27 January 2023, compared to 231 cases reported from 1 November 2021 to 31 January 2022. In the current outbreak, the Neisseria meningitidis serogroup C (NmC) is responsible for the majority of laboratory confirmed cases (104/111; 93.7%). To organize the response to the pandemic, a global team from the WHO and other partners, including MSF and UNICEF, has been sent out in Niger. Even though there are many challenges in battle against meningitis in Niger, immunization, antibiotics administration and strong disease surveillance are recommended techniques to cope with the current meningitis outbreak in Niger.