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.

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.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with the main clinical characteristics of multi-system and multi-organ involvement of the whole body. It is commonly seen in skin mucosa, skeletal muscle, and respiratory system while rarely involved the spleen. The etiology of SLE is complex and related to many factors such as genetics, sex hormones, and environment. In this case, we present a young female patient with SLE with the symptom of progressing splenic calcification.

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.

ABSTRACT: Backgr ound : Vaccination is an important method for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. There is currently a lack of real-world clinical data regarding the safety and efficacy of coronavirus disease 2019 (COVID- 19) vaccines with respect to plaque psoriasis treatment involving tumor necrosis factor (TNF)-α and interleukin (IL)- 17A inhibitors. Method s: We longitudinally analyzed 152 patients with plaque psoriasis, 86 of whom received two doses of inactivated COVID- 19 vaccine (either BBIBP-CorV or CoronaVac). Comparisons were made between patients undergoing treatment with biologics (TNF- α inhibitors or IL- 17A inhibitors) or acitretin. Routine blood tests were used to assess safety; the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI) were used to assess efficacy. Results: After inactivated COVID- 19 vaccination, biologics retained considerable advantages in terms of improving skin lesions (measured by PASI) and quality of life (measured by DLQI), compared with conventional treatment (p<0.05 and p<0.01, respectively). Routine blood tests and hepatorenal function analyses suggested that inactivated SARS-CoV-2 vaccines did not alter the safety of biologics treatment (p>0.05). Conclusions: Inactivated SARS-CoV-2 vaccines do not have significant impacts on the safety and efficacy of biologics (TNF-α inhibitors or IL- 17A inhibitors) in patients with moderate to severe plaque psoriasis.

Background: Maintenance doses for AIT have been recommended for at least 3 years, little data on long-term efficacy is available depending on AIT duration. To show sustained efficacy 10 years after completion of treatment with depigmented-polymerized house dust mite (dpg-pol HDM) allergen extract in adults with asthma and/or rhinoconjunctivitis. Methods: Patients included in a double-blind placebo-controlled AIT study with dpg-pol HDM allergen extract were reviewed at completion of the perennial treatment and 10 years later (10y-FU). Change in symptom and rescue medication score was the primary objective. Visual analogue scale, asthma control test (ACT) and degree of disease control were secondary objectives. A comparative analysis between patients who underwent treatment for < 3 years and ≥ 3 years was performed. Results: Data from 31 patients (mean age 38 years) were available at 10y-FU. All had asthma and 29 had rhinoconjunctivitis at baseline. Twenty-three patients were treated ≥ 3y and 8 for < 3y. Seventeen (55%) patients were asymptomatic at completion AIT completion, with significant differences for nasal, conjunctival and bronchial symptoms (p<0.0001) compared to baseline only in patients treated ≥3y. Nine (52.9%) patients remained completely asymptomatic at 10yFU , all were treated for ≥ 3 years. Moreover, significant reduction in the number of patients with rhinitis (p=0.0117), conjunctivitis (p<0.0001) and bronchial (p=0.0005) symptoms was observed at 10y-FU compared to baseline only in the ≥3y treated. Ten (32.3%) patients didn´t require any rescue medication at 10y-FU, all had been treated for ≥ 3y. ACT at 10y-FU showed a good control of asthma (median 23.5; 95% IC[22.0, 25.0]). No significant differences were observed between VAS at end of treatment compared to VAS at 10y-FU. Conclusions: Sustained clinical efficacy is achieved 10 years after completion of depigmented-polymerized HDM, however these findings were observed only if patients are treated for at least 3 years.

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.

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.

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.

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.

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.

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.

Toll-like receptors (TLRs) are a family of pattern-recognition receptors (PRRs) triggered by pathogen-derived and tissue-damage-related ligands. TLRs were previously believed to only be expressed in immune cells. However, it is now confirmed that they are ubiquitously expressed in cells within the body including neurons, astrocytes, and microglia of the central nervous system (CNS). Activation of TLRs is capable of inducing immunologic and inflammatory responses to injury or infection of CNS. This response is self-limiting that usually resolves once the infection has been eradicated or the tissue damage has been repaired. However, the persistence of inflammation-inducing insults or a failure in normal resolution mechanisms may result in overwhelming inflammation which may induce neurodegeneration. This implies that TLRs may play a role in mediating the link between inflammation and neurodegenerative diseases namely Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). So, new therapeutic approaches that specifically target TLRs may be developed by better understanding TLR expression mechanisms in the CNS and their connections to particular neurodegenerative disorders. Therefore, this review paper discussed the role of TLRs in neurodegenerative diseases.

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.

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.

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.

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.

Tumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer-testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response. The expression of CTA affects the occurrence, development, and prognosis of ovarian cancer and is closely related to tumor immunity. This review outlines a comprehensive of overview the regulatory mechanism, immunogenicity, clinical expression significance, tumorigenesis, and application prospects of CTA in ovarian cancer, all of which can provide novel insights in the improvement of diagnosis and treatment for ovarian cancer.