Heart failure (HF) represents a major global health challenge. This condition is closely linked to the dysregulation of a key signaling mechanism known as the Wnt/β-catenin pathway. Using an isoproterenol (ISO)-induced mice model of HF and H9c2 cells injury, we examined the effects of Icariside II (ICS II) on ventricular remodeling and apoptosis, focusing on the Wnt/β-catenin and mitochondrial apoptotic pathways. ICS II significantly improved cardiac function, reduced left ventricular hypertrophy, and decreased expression of the HF markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). In HF mice treated with ICS II, Western blot analysis revealed reduced levels of both Wnt/β-catenin pathway proteins and apoptotic markers in cardiac tissue. Consistent with these in vivo findings, ICS II also protected H9c2 cells from ISO-induced injury in vitro. This protection was accompanied by a decrease in cell area and apoptosis, as well as a similar suppression of Wnt/β-catenin pathway proteins. GSK-3β inhibitor SB216763 reversed ICS II's protective effects, increasing H9c2 cells apoptosis and restoring Wnt/β-catenin pathway activity (except Wnt3A). These findings demonstrate that ICS II alleviates HF by modulating the Wnt/β-catenin-mitochondrial apoptotic pathway. Given that this compound improves cardiac function while simultaneously addressing pathological remodeling and apoptosis, it holds promise as a new therapeutic approach for HF.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare immunodeficiency characterized by increased vulnerability to weakly virulent mycobacteria. However, its clinical and molecular spectrum, as well as its susceptibility to infections beyond mycobacteria, remains incompletely understood. To evaluate the clinical and genetic characteristics of MSMD patients, focusing on their susceptibility to mycobacteria, SARS-CoV-2 and endemic fungal infections. Thirteen MSMD patients underwent genetic analyses, immunological assays, and clinical evaluations. COVID-19 outcomes were documented. Pathological findings and mNGS confirmed Talaromyces marneffei infections. Following BCG vaccination, 92.3

ObjectiveJuvenile systemic sclerosis (jSSc) is a rare but serious rheumatic disease in children that significantly impacts growth and development. This study aimed to summarize the clinical characteristics and disease patterns of jSSc and to evaluate the treatment response over an 11-year period at our center.MethodsTwenty-one pediatric jSSc patients treated at our center from January 2015 to December 2025 were retrospectively analyzed. Classification was based on the 2013 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) systemic sclerosis classification criteria. Overall disease severity and multiorgan activity were assessed using the Juvenile Systemic Sclerosis Severity Score (J4s; range 0–40), while skin involvement was specifically evaluated using the modified Rodnan skin score (mRSS; range 0–51). The median follow-up duration was 2.3 years (range 0.5–7.2 years). Paired t-tests and Wilcoxon signed-rank tests were used to compare pre- and posttreatment parameters, with p < 0.05 considered statistically significant.ResultsTwenty-one patients were enrolled. Skin sclerosis was the most common symptom (100.0%). Antinuclear antibody (ANA) was positive in 16 cases (76.2%), with anti-single-stranded DNA (anti-ssDNA) antibody being the most common specific antibody (23.8%), followed by anti-PM-Scl antibody (19.0%). Glucocorticoids and methotrexate were commonly used as initial therapies. After a median treatment duration of 24 months, overall disease severity (J4s) significantly decreased (5.94 ± 1.66 vs 2.67 ± 2.22, p = 0.003), and skin involvement (mRSS) also improved significantly (10.0 ± 9.21 vs 7.42 ± 8.26, p = 0.008). Fourteen patients received biologic agents, with 11 using tocilizumab. During the follow-up, no deaths or serious adverse events occurred.ConclusionsjSSc is a rare and severe multiorgan disease with unique autoantibody profiles in Chinese children. The J4s and mRSS serve as objective assessment tools for evaluating overall disease severity and skin involvement, respectively, and are effective in monitoring treatment response. Early diagnosis and individualized therapy, including the adjunctive use of tocilizumab, may improve clinical outcomes.

BACKGROUND:Compound heterozygous mutations in the MRTFA gene have not been reported; the complete clinical phenotypic spectrum associated with MRTFA deficiency remains undefined. Whether such mutations can result in autoinflammatory manifestations is also yet to be determined. METHODS:Comprehensive analyses were conducted on a patient with novel compound heterozygous MRTFA variants, encompassing clinical data collection, genetic validation, and functional studies. Functional assays included protein stability assessment, SRF transcriptional activity measurement, and neutrophil functional evaluation. Lymphocyte profiling was performed using flow cytometry. Transcriptomic alterations in neutrophils and PBMCs were examined through bulk RNA-sequencing. RESULTS:The patient presented with early-onset infections, rashes, and bloody stools, accompanied by neutropenia and thrombocytopenia. Whole-exome sequencing identified two novel heterozygous nonsense mutations in MRTFA (Q377X/C684X), which caused the absence of MKL1 protein expression and reduced cytoskeletal protein levels. Both mutants presented protein instability and impaired SRF transcriptional activation. F-actin content was reduced in various cell types from the patient. Neutrophils from the patient showed impaired F-actin polymerization, decreased migration ability, reduced ROS production, increased apoptosis, diminished NETs formation, and decreased MPO levels. Transcriptome profiling revealed neutrophil-specific downregulation of cytoskeletal genes with concomitant upregulation of antimicrobial peptide/inflammatory pathways, while PBMCs presented upregulated adhesion/migration-related genes. CONCLUSION:This study identifies the first reported case with compound heterozygous mutations in the MRTFA gene. The patient demonstrated a milder infectious phenotype but with marked neutrophil dysfunction and prominent autoinflammatory features. This study expands the disease spectrum of MKL1 deficiency and highlights the broader impacts of MKL1 deficiency on neutrophil function and immune regulation.

The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igβ respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.

BACKGROUND:Individuals with obesity have higher level of circulating succinate, which acts as a signaling factor that initiates inflammation. It is obscure whether succinate and succinate receptor 1 (SUCNR1) are involved in the process of obesity aggravating acute lung injury (ALI). METHODS:The lung tissue and blood samples from patients with obesity who underwent lung wedgectomy or segmental resection were collected. Six-week-old male C57BL/6J mice were fed a high-fat diet for 12 weeks to induce obesity and lipopolysaccharides (LPS) were injected intratracheally (100 μg, 1 mg/ml) for 24 h to establish an ALI model. The pulmonary SUCNR1 expression and succinate level were measured. Exogenous succinate was supplemented to assess whether succinate exacerbated the LPS-induced lung injury. We next examined the cellular localization of pulmonary SUCNR1. Furthermore, the role of the succinate-SUCNR1 pathway in LPS-induced inflammatory responses in MH-s macrophages and obese mice was investigated. RESULT:The pulmonary SUCNR1 expression and serum succinate level were significantly increased in patients with obesity and in HFD mice. Exogenous succinate supplementation significantly increased the severity of ALI and inflammatory response. SUCNR1 was mainly expressed on lung macrophages. In LPS-stimulated MH-s cells, knockdown of SUCNR1 expression significantly inhibited pro-inflammatory cytokines' expression, the increase of hypoxia-inducible factor-1α (HIF-1α) expression, inhibitory κB-α (IκB-α) phosphorylation, p65 phosphorylation and p65 translocation to nucleus. In obese mice, SUCNR1 inhibition significantly alleviated LPS-induced lung injury and decreased the HIF-1α expression and IκB-α phosphorylation. CONCLUSION:The high expression of pulmonary SUCNR1 and serum succinate accumulation at least partly participate in the process of obesity aggravating LPS-induced lung injury.

AIMS:The inflammatory response in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is heightened in obesity. The aim of this study was to investigate whether lncRNAs are involved in the effects of obesity on acute lung injury and to find possible effector lncRNAs. MAIN METHODS:Microarray analysis was used to assess the transcriptional profiles of lncRNAs and mRNAs in lung tissues from normal (CON), high-fat diet induced obese (DIO), and obese ALI mice (DIO-ALI). GO and KEGG analyses were employed to explore the biological functions of differentially expressed genes. A lncRNA-mRNA co-expression network was constructed to identify specific lncRNA. Lung tissues and peripheral blood samples from patients with obesity and healthy lean donors were utilized to confirm the expression characteristics of lncFirre through qRT-PCR. lncFirre was knocked down in MH-S macrophages to explore its function. ELISA and Griess reagent kit were used to detect PGE2 and NO. Flow cytometry was used to detect macrophages polarization. KEY FINDINGS:There were 475 lncRNAs and 404 mRNAs differentially expressed between DIO and CON, while 1348 lncRNAs and 1349 mRNAs between DIO-ALI and DIO. Obesity increased lncFirre expression in both mice and patients, and PA elevated lncFirre in MH-S. PA exacerbated the inflammation and proinflammatory polarization of MH-S induced by LPS. LncFirre knockdown inhibited the secretion of PGE2 and NO, M1 differentiation while promoted the M2 differentiation in PA and LPS co-challenged MH-S. SIGNIFICANCE:Interfering with lncFirre effectively inhibit inflammation in MH-S, lncFirre can serve as a promising target for treating obesity-related ALI.

Background Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity. Methods Human lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m 2 ) and control patients (BMI 18.5–24.9 kg/m 2 ). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192. Results In obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge. Conclusions Our study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI. Graphical Abstract

Purpose Good sleep is one of the necessary conditions to ensure the normal performance of the physiological and psychological functions of college students. This study aimed to explore the relationship between mobile phone addiction and bedtime procrastination among Chinese college students and the mediating mechanisms of physical exercise and anxiety between the two, with a view to seek ways to prevent and intervene in college students' sleep procrastination and improve their sleep quality. Methods Using SPSS 29.0 analysis with Bootstrap's method, 3,800 first-year students, sophomores, and juniors were given the Mobile Phone Addiction Tendency Scale, Bedtime Procrastination Scale, Physical Activity Scale, and Anxiety Scale. The results of the analyses included mediation tests and effect analyses of anxiety and physical activity. Results The correlation analysis revealed significant positive correlations between mobile phone addiction and bedtime procrastination (r = 0.149, p < 0.01) as well as anxiety (r = 0.497, p < 0.01). Additionally, there was a significant negative correlation between mobile phone addiction and physical activity (r = -0.447, p < 0.01). Physical activity was also found to have significant negative correlations with anxiety (r = -0.506, p < 0.01) and bedtime procrastination (r = -0.424, p < 0.01). Furthermore, anxiety showed a significant positive correlation with bedtime procrastination (r = 0.334, p < 0.01). Physical activity and anxiety acted as substantial mediators between mobile phone addiction and nighttime procrastination. Both mediators had considerable masking effects, with the mediating effect amounting to 50.3% and 25.1%, respectively. Physical exercise and anxiety played a chain mediating role between mobile phone addiction and bedtime procrastination, and the masking effect was also significant, with a mediating effect size of 13.4%. Conclusions This study reveals the special characteristics of the influencing factors and pathways of bedtime procrastination in this group of college students, providing targeted evidence for the prevention and intervention of bedtime procrastination in college students. It also has an important reference value for the effects of exercise and comprehensive intervention to improve bedtime procrastination and enhance the quality of sleep in college students.

Objectives We sought to investigate the sex distribution, clinical presentations, disease outcomes and genetic background of early-onset paediatric SLE (eo-pSLE) in a single centre in China to help enable early diagnosis and timely treatment. Methods The clinical data of children aged less than 5 years old with SLE (n = 19) from January 2012 to December 2021 were reviewed and analysed. We performed DNA sequencing in 11 out of 19 patients to survey the genetic aetiologies. Results Our study included 6 males and 13 females. The mean age at onset was 3.73 years. The median diagnostic delay was 9 months and was longer in male patients (P = 0.02). Four patients had an SLE-relevant family history. The most common clinical manifestations at diagnosis were fever, rash and hepatosplenomegaly. ANA positivity and low C3 were identified in all children. The renal (94.74%), mucocutaneous (94.74%), haematological (89.47%), respiratory (89.47%), digestive (84.21%), cardiovascular (57.89%) and neuropsychiatric (52.63%) systems were involved to varying degrees. We identified 13 SLE-associated gene mutations in 9 out of 11 patients: TREX1, PIK3CD, LRBA, KRAS, STAT4, C3, ITGAM, CYBB, TLR5, RIPK1, BACH2, CFHR5 and SYK. One male patient showed a 47, XXY chromosomal abnormality. Conclusion Early-onset (<5 years) pSLE is characterized by an insidious onset, typical immunological patterns, and the involvement of multiple organs. Immunological screening and genetic testing should be performed as soon as feasible in patients with an early onset of multisystemic autoimmune diseases to confirm the diagnosis.

Objective To analyze the clinical phenotype and immunological characteristics of a patient with heterozygous mutation of PTEN and enrich the clinical phenotypes related to PTEN mutation. Methods A retrospective analysis of the clinical data of a patient with PTEN heterozygous mutation admitted to the Children's Hospital of Chongqing Medical University was conducted. Peripheral venous blood was extracted for medical whole-exome comprehensive detection, and the PTEN mutation was confirmed by Sanger sequencing. Flow cytometry was applied to detect the lymphocyte subsets and immunophenotype of the patient. The expression level of PTEN protein in peripheral blood mononuclear cells was detected by Western blot, and the healthy control was the patient's father. Results The patient was a boy of 1 year and 4 months, with macrocephaly (head circumference > P99), verrucous epidermal nevus, delayed psychomotor development and delayed language learning as the main manifestations. Gene sequencing revealed a de novo heterozygous mutation of PTEN c.388C > T(p.R130X). Reduced expression of PTEN protein was observed in peripheral blood mononuclear cells of the patient. For immunological characteristics, the IgA level mildly decreased(0.177 g/L), with increased counts of terminally differentiated memory CD4+ T cells, terminally differentiated memory CD8+ T cells, transitional B cells, but phosphorylation of PI3K/Akt/mTOR pathway in T cells was normal. The patient mainly manifested as PTEN hamartoma tumor syndrome related phenotype, without any classic activated phosphatidylinositol 3-kinase δ syndrome-like phenotype. Conclusions This patient has a de novo heterozygous mutation of PTEN c.388C > T(p.R130X), which has not been previously reported in China. This article could enrich clinicians' understanding of the disease and assist clinical diagnosis and treatment.

BACH2-related immunodeficiency and autoimmunity (BRIDA) is an inborn error of immunity, newly reported in 2017, presenting with symptoms of immunoglobulin deficiency and ongoing colitis. Studies using a mouse model have demonstrated that BACH2 deficiency predisposes individuals to systemic lupus erythematosus (SLE); however, no BACH2 deficiency has been reported in SLE patients. Here we describe a patient with BRIDA presenting with early-onset SLE, juvenile dermatomyositis, and IgA deficiency. Whole exome sequencing analysis of the patient and her parents revealed a novel heterozygous point mutation in BACH2, c.G1727T, resulting in substitution of a highly conserved arginine with leucine (R576L), which is predicted to be deleterious, in the patient and her father. Reduced BACH2 expression and deficient transcriptional repression of the BACH2 target, BLIMP1, were detected in PBMCs or lymphoblastoid cell lines of our patient. Notably, extreme reduction of memory B cells was detected in the patient's father, although he had no obvious symptoms. SLE symptoms and recurrent fever were relieved by treatment with prednisone combined with tofacitinib. Thus, we present the second report of BRIDA and demonstrate that BACH2 may be a monogenic cause of SLE.

Patients with DEX (deficiency in ELF4, X-linked) were recently reported by our team and others, and cases are very limited worldwide. Our knowledge of this new disease is currently preliminary. In this study, we described 5 more cases presenting mainly with oral ulcer, inflammatory bowel disease-like symptoms, fever of unknown origin, anemia, or systemic lupus erythematosus. Whole exome sequencing identified potential pathogenic ELF4 variants in all cases. The pathogenicity of these variants was confirmed by the detection of ELF4 expression in peripheral blood mononuclear cells from patients and utilizing a simple IFN-b luciferase reporter assay, as previously reported. Our findings significantly contribute to the current understanding of DEX.

Purpose Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. Methods A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. Results Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. Conclusion To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Objective Obesity-induced endoplasmic reticulum (ER) stress plays a role in increased susceptibility to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The activation of peroxisome proliferator-activated receptor-γ (PPARγ) is associated with lung protection and is effective in ameliorating ER stress and mitochondrial dysfunction. The aim of this study was to investigate the expression of PPARγ in the lung tissues of obese mice and explore whether the PPARγ-dependent pathway could mediate decreased ALI/ARDS by regulating ER stress and mitochondrial biogenesis. Methods We determined PPARγ expression in the lung tissues of normal and obese mice. ALI models of alveolar epithelial cells and of obese mice were used and treated with either PPARγ activator rosiglitazone (RSG) or PPARγ inhibitor GW9662. Lung tissue and cell samples were collected to assess lung inflammation and apoptosis, and ER stress and mitochondrial biogenesis were detected. Results PPARγ expression was significantly decreased in the lung tissue of obese mice compared with that in normal mice. Both in vivo and in vitro studies have shown that activation of PPARγ leads to reduced expression of the ER stress marker proteins 78-kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and Caspase12. Conversely, expression of the mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1α), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) increased. Furthermore, activation of PPARγ is associated with decreased levels of lung inflammation and epithelial apoptosis and increased expression of adiponectin (APN) and mitofusin2 (MFN2). GW9662 bound to PPARγ and blocked its transcriptional activity and then diminished the protective effect of PPARγ on lung tissues. Conclusions PPARγ activation exerts anti-inflammation effects in alveolar epithelia by alleviating ER stress and promoting mitochondrial biogenesis. Therefore, lower levels of PPARγ in the lung tissues of obese mice may lead to an increased susceptibility to ALI.

This study aimed to investigate the alterations of myocardial succinate and fumarate levels with or without succinate dehydrogenase (SDH) inhibitor dimethyl malonate during 24 h of lipopolysaccharides (LPS) challenge, as well as the effects of dimethyl malonate on the impaired cardiac tissue. Myocardial succinate and fumarate levels were increased in the initial 9 h of LPS challenge. During this time, dimethyl malonate increased the succinate level, decreased the fumarate level, aggravated the cardiac dysfunction, reduced the oxidative stress, had little effect on interleukin-1 beta production, promoted interleukin-10 production and bothered the ATP pro-duction. Co-treatment with exogenous succinate significantly increased interleukin-1 beta production in this period. After 12 h of LPS challenge, myocardial the succinate level increased sharply, while the fumarate level gradually decreased. During 12-24 h of LPS challenge, dimethyl malonate effectively reduced the succinate level, increased the fumarate level, improved cardiac dysfunction, inhibited interleukin-1 beta production, and had little effect on oxidative stress, interleukin-10 production, and ATP production. LPS challenge also significantly increased the myocardial succinate receptor 1 expression and circulating succinate level. Inhibition of succinate receptor 1 significantly reduced the mRNA expression of interleukin-1 beta. In conclusion, the current study suggests that myocardial succinate accumulates during LPS challenge, and that SDH activity may be transformed (from for-ward to reversed) and involved in a line of stress response. Dimethyl malonate inhibits SDH and, depending on the time of treatment, reduces LPS-induced cardiac impairment. Furthermore, accumulated succinate exerts pro-inflammatory effects partly via succinate receptor 1 signaling.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a primary immunodeficiency first described in 2013, which is caused by gain-of-function mutations in PIK3CD or PIK3R1, and characterized by recurrent respiratory tract infections, lymphoproliferation, herpesvirus infection, autoimmunity, and enteropathy. We sought to review the clinical phenotypes, immunological characteristics, treatment, and prognosis of APDS in a large genetically defined Chinese pediatric cohort. Clinical records, radiology examinations, and laboratory investigations of 40 APDS patients were reviewed. Patients were contacted via phone call to follow up their current situation. Sinopulmonary infections and lymphoproliferation were the most common complications in this cohort. Three (10.3%) and five (12.5%) patients suffered localized BCG-induced granulomatous inflammation and tuberculosis infection, respectively. Twenty-seven patients (67.5%) were affected by autoimmunity, while malignancy (7.5%) was relatively rare to be seen. Most patients in our cohort took a combined treatment of anti-infection prophylaxis, immunoglobulin replacement, and immunosuppressive therapy such as glucocorticoid or rapamycin administration. Twelve patients underwent hematopoietic stem cell transplantation (HSCT) and had a satisfying prognosis. Clinical spectrum of APDS is heterogeneous. This cohort’s high incidence of localized BCG-induced granulomatous inflammation and tuberculosis indicates Mycobacterial susceptibility in APDS patients. Rapamycin is effective in improving lymphoproliferation and cytopenia. HSCT is an option for those who have severe complications and poor response to other treatments.

Background: Resveratrol (RES) has a protective effect on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Our purpose was to conduct a meta−analysis to investigate the efficacy of RES for ALI/ARDS in animal models.Methods: PubMed, EMBASE and Web of Science were searched to screen relevant preclinical trials. The standardized mean difference (SMD) was used to compare the lung injury score, lung wet−dry weight ratio (W/D ratio), tumor necrosis factor−α (TNF−α), interleukin−1β (IL−1β), IL−6, IL−10, the number of neutrophils in bronchoalveolar lavage fluid (BALF) and the total protein in BALF between the treatment and control groups. SYRCLE’s risk of bias tool was used for quality assessment.Results: A total of 17 studies published from 2005 to 2021 were included in our study to calculate the SMD with corresponding confidence interval (CI). As compared with controls, RES significantly decreased the lung injury score (SMD −2.06; 95% CI −2.77, −1.35; p < 0.00001) and W/D ratio (SMD −1.92; 95% CI −2.62, −1.22; p < 0.00001). RES also reduced the number of neutrophils in BALF (SMD −3.03; 95% CI −3.83, −2.24; p < 0.00001) and the total protein in BALF (SMD −5.59; 95% CI −10.10, −1.08; p = 0.02). Furthermore, RES was found to downregulate proinflammatory mediators such as TNF−α (SMD −2.02; 95% CI −3.09, −0.95; p = 0.0002), IL−1β (SMD −2.51; 95% CI −4.00, −1.02; p = 0.001) and IL−6 (SMD −2.26; 95% CI −3.49, −1.04; p = 0.0003). But RES had little effect on the anti−inflammatory mediators such as IL−10 (SMD 2.80; 95% CI −0.04, 5.63; p = 0.05). Sensitivity analysis and stratified analysis were performed for the outcome indicators with heterogeneity.Conclusion: RES treatment is effective on reducing the severity of ALI. However, more animal studies and human trials are needed for further investigation. Our study may provide a reference for preclinical and clinical studies in the future to some extent.