Several studies have linked metal exposure to preterm birth (PTB), but the underlying mechanisms remain poorly understood. This study investigated the mediating role of inflammatory blood cell counts in the relationship between metal exposure at 10-12 weeks of gestation and PTB. The combined effects of metals were assessed using quantile g-computation (Q-gcomp) and Bayesian kernel machine regression (BKMR) models. Linear and logistic regression models evaluated the associations between individual metal levels and blood cell counts, as well as their impact on PTB risk. Mediation analysis was conducted to explore the potential role of blood cell counts in mediating the metal exposure-PTB relationship. Metal exposure was significantly associated with PTB, with serum levels of barium (Ba), lead (Pb), and cadmium (Cd) showing positive correlations with PTB risk. Mediation analysis revealed that white blood cell (WBC) and neutrophilic granulocyte (NE) counts mediated the association between serum Ba exposure and PTB. Additionally, mixed-exposure analysis demonstrated that higher overall metal exposure was linked to an increased risk of PTB. This study highlights the association between early pregnancy serum Ba exposure and PTB, with WBC and NE counts mediating this relationship. These findings offer valuable insights into the mechanisms underlying PTB.

Immunoglobulin A nephropathy is a predominant cause of chronic kidney disease in the pediatric population. Despite standard-of-care treatments, a significant subset of children remains refractory to conventional immunosuppressive therapies, necessitating exploration of novel targeted interventions. Telitacicept, a recombinant fusion protein targeting both B lymphocyte stimulator and a proliferation-inducing ligand, has demonstrated efficacy in adult immunoglobulin A nephropathy; however, real-world evidence in pediatric cases remains limited. This exploratory retrospective case series evaluated the efficacy and safety of telitacicept in seven pediatric patients with refractory immunoglobulin A nephropathy. Telitacicept was administered subcutaneously once weekly using a weight-stratified dosing regimen (80 mg for patients weighing <40 kg and 160 mg for patients weighing ≥40 kg) over a 24-week period. At the end of follow-up, clinical remission (defined as urine protein-to-creatinine ratio <0.2 g/g) was achieved in five of the seven patients (71.4%). Notably, a rapid therapeutic response was observed, with 85.7% of patients achieving at least partial remission by month 3. Although estimated glomerular filtration rate remained stable throughout the study, significant reductions were observed in serum immunoglobulin A, immunoglobulin G, and immunoglobulin M levels (all p < 0.05), correlating with clinical improvement. However, two patients with specific pathological features, including minimal change disease or advanced chronic lesions, showed limited response to treatment. The treatment was well tolerated, with only one instance of mild upper respiratory tract infection and no serious adverse events reported. These preliminary findings suggest that weight-stratified telitacicept is a promising and safe adjuvant therapy for pediatric patients with refractory immunoglobulin A nephropathy, although its efficacy may be influenced by individual clinicopathological characteristics.

BACKGROUND:Chronic kidney disease (CKD) in children and adolescents elevates lifelong cardiovascular and kidney failure risk, yet global epidemiological studies remain limited. METHODS:Data from the Global Burden of Disease (GBD) Study 2021 were extracted to analyse the incidence, prevalence, mortality and disability-adjusted life years (DALYs) of CKD in children and adolescents ages 0-19 years. Age-standardized rates (ASRs) and estimated annual percentage change (EAPC) were calculated. The study further examines differences across regions, age groups, sex, risk factors and aetiologies. Health inequality analysis was performed not only to investigate the distribution of CKD, but also to assess the impact of kidney replacement therapy (KRT, including dialysis and transplantation) accessibility on CKD-related DALYs. The Bayesian Age-Period-Cohort model was applied to predict trends in disease burden from 2022 to 2050. RESULTS:In 2021, the global incidence of CKD among individuals ages 0-19 years was estimated at ≈7.54 million, with an age-standardized incidence rate (ASIR) of 28.62 (95% uncertainty interval 20.88-38.08). Central Asia had the highest ASIR. The low-middle Socio-Demographic Index (SDI) region experienced the fastest increase in ASIR, with an EAPC of 0.403 (95% confidence interval 0.332-0.475). Incidence rates in adolescents ages 14-19 years increased by 44.29%. A strong negative correlation was observed between the SDI and age-standardized mortality rate (ρ = -0.822, P < .001). The concentration index for DALYs shifted from -0.240 in 1990 to -0.293 in 2021. Areas with higher accessibility to KRT consistently bore a lower burden of CKD. By 2050, the ASIR is projected to decrease to 25.54. CONCLUSIONS:The increase in the health inequality concentration index underscores the importance of enhancing early CKD screening in low SDI areas. Targeted policies, including health education and early CKD screening, should be prioritized.

Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-kappa B signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1R, IL-6, tumor necrosis factor-alpha (TNF-alpha) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-kappa B P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF kappa B. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.

OBJECTIVE:To explore whether streptococcal infection may aggravate renal damage in children with Henoch-Schönlein purpura nephritis and its possible mechanism. METHODS:In the study, 485 children diagnosed with Henoch-Schönlein purpura nephritis from July 2015 to December 2019 were selected to analyze their clinical data retrospectively. According to the diagnosis of discharge, whether it was combined with streptococcal infection, the children were divided into two groups. The experimental group contained 91 children with Henoch-Schönlein purpura nephritis combined with streptococcal infection, and there were 394 children who were not infected with Streptococcus in the control group. Suitable test items were preliminarily selected through artificial neural network, and then data analysis was performed through SPSS 23.0. RESULTS:The children with Henoch-Schönlein purpura nephritis infected with streptococcus had statistically significant differences compared with the uninfected children in the test items of urine protein, liver and kidney function, immunoglobulin and complement. Anti-streptolysin O had mild correlation with IgG (Spearman r=-0.328), fibrin degradation products (Spearman r=-0.207), total protein (Spearman r=-0.202) and globulin (Spearman r=-0.223). Compared with the children who were not infected with streptococcus, the differences of the average levels of age (P=0.001), IgG (P < 0.001), fibrin degradation products (P=0.019), total protein (P < 0.001), globulin (P < 0.001), IgA (P < 0.001), IgM (P=0.003), complement 3 (P=0.016), complement 4 (P=0.002), albumin/globulin ratio (P=0.007), alkaline phosphatase (P=0.036), and estimated glomerular filtration rate (P=0.039) in the infected children were statistically significant. In order to explore the risk factors of kidney damage in the children with Henoch-Schönlein purpura nephritis, Logistic regression was performed using anti-streptolysin O, age, immunoglobulin and complement as independent variables, urine protein detection parameters, liver and kidney functions as dependent variables. Age ≤10 years old and hypocomplementemia might be risk factors for aggravating renal damage in the children with Henoch-Schönlein purpura nephritis. CONCLUSION:Streptococcal infections may aggravate renal damage in children with Henoch-Schönlein purpura nephritis, in which hypocomplementemia, inflammation, fibrinolysis and disorders of coagulation perhaps play an important role. Children with streptococcal infection should be treated with anti-infective treatment in time and necessarily, and followed up after discharge regularly.

Background: To investigate the diagnostic value of angiotensin (Ang), gamma-glutamyltransferase (g-GT), blood lactic acid and renal resistive index (RRI) for acute kidney injury (AKI) after neonatal asphyxia. Methods: A total of 120 asphyxiated neonates admitted to the hospital from May 2021 to April 2024 were retrospectively selected. According to whether AKI occurred after asphyxia, the neonates were divided into AKI group and non-AKI group. The occurrence of AKI in neonates with different degrees of asphyxia was analyzed. Plasma Ang-I and Ang-II levels and urine g-GT level were compared between the AKI group and the non-AKI group. The blood gas analyzer was used to determine blood lactic acid levels and color Doppler ultrasound was used to evaluate RRI. The correlation between blood Ang, urine g-GT, blood lactic acid, RRI and serum creatinine (Scr) and blood urea nitrogen (BUN) was discussed. Multivariate logistic regression model was used to identify factors influencing the occurrence of AKI after neonatal asphyxia. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of relevant indicators for AKI after neonatal asphyxia.

Acute lung injury (ALI) is driven by dysregulated inflammation, but how mitochondrial damage engages necroptosis in alveolar macrophages remains unclear. We aimed to define the mechanistic link between mitochondrial impairment and Zinc finger protein 1 (Zbp1)–mediated necroptosis in the murine alveolar macrophage–like cell line (MH-S). MH-S cells were stimulated with lipopolysaccharide (LPS) and profiled by RNA sequencing; necroptotic death was quantified by Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) release, Zbp1 localization was examined by immunofluorescence microscopy, and Zbp1, receptor-interacting protein kinase 3 (RIPK3)/phospho-RIPK3 (p-RIPK3) and mixed lineage kinase domain-like protein (MLKL)/phospho-MLKL (p-MLKL) were measured by Western blotting. Mitochondrial status was assessed by mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potential (ΔΨm; JC-1), mitochondrial permeability transition pore (MPTP) opening, adenosine triphosphate (ATP) content, and the markers ATP synthase F1 subunit alpha (ATP5a1), mitochondrial transcription factor A (TFAM), and translocase of outer mitochondrial membrane 20 (TOMM20); inflammatory responses were quantified by flow cytometry and qPCR. The mitochondria-targeted antioxidant Mito-TEMPO was used to interrogate the role of oxidative stress. LPS markedly increased Zbp1 transcription, coincident with upregulation of pro-inflammatory genes and activation of necroptosis; mitochondrial damage and elevated mtROS were critical upstream events for Zbp1 induction, driving RIPK3 and MLKL phosphorylation, necroptosis, and cytokine release. Mito-TEMPO restored mitochondrial function, lowered mtROS, downregulated Zbp1 and its necroptotic effectors (p-RIPK3, p-MLKL), and significantly reduced both necroptotic injury and inflammatory output. Collectively, mitochondrial dysfunction–driven mtROS initiates the Zbp1/RIPK3/MLKL necroptotic axis in alveolar macrophages, thereby amplifying pulmonary inflammation in ALI; targeting mtROS may mitigate necroptosis and protect against lung injury.

IntroductionTo explore how MP and RTX impact TRPC6's expression and localization, and assess MP's and RTX's effects on podocyte injury and recovery.MethodsMPC5 cells were simultaneously grown alongside a control group and under various conditions: exposure to puromycin aminonucleoside (PAN) stimulation, treatment with methylprednisolone (MP), and treatment with rituximab (RTX), and a combined treatment with both MP and RTX.ResultsAt 8, 24, and 48 h, CCK-8 assay showed that PAN (50 μg/mL) had a decrease in cell viability and an increase in cell death, and it could be used as the optimum concentration to induce podocyte injury; MP (100 ng/mL) and RTX (100 μg/mL) maintained cell viability and had minimal impact on cell morphology, and they were the best concentrations. Following 24 and 48-h exposure to MP or RTX, there was a decrease of 30%–50% in apoptosis rates by flow cytometry in comparison to the group stimulated with PAN, accompanied by a substantial reduction in nearly 10%–60% of TRPC6 mRNA and 5%–20% of protein levels which were measured using qRT-PCR and western blot analyses, akin to the observed decrease in levels of IL-1β and IL-18. Additionally, calcium entry showed considerable reductions after 8, 24, and 48 h of MP treatment relative to the PAN-stimulation group, paralleling the effect seen with 24-h RTX treatment.DiscussionTherefore, MP and RTX safeguarded podocytes, and averted proteinuria by decreasing podocyte apoptosis, diminishing TRPC6 mRNA and protein levels, and suppressing inflammatory markers and calcium entry.

Purpose to investigate the role of red cell distribution width (RDW), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in the pathogenesis of Immunoglobulin A vasculitis (IgAV) in Tibetan children at high altitude. A total of 360 children were enrolled: 103 in the IgAV group, 138 in the NIgAV group, and 119 in the control group. There were no significant differences in race, gender, and age among the three groups (P > 0.05). Yet, RDW, TNF-α, and IL-6 were higher in the NIgAV and IgAV groups than in the control group (P < 0.05). In addition, RDW, TNF-α, and IL-6 were higher in the IgAV group than in the NIgAV group (P < 0.05). The increased RDW, TNF-α, and IL-6 were associated with renal injury in children with IgAV. Spearman correlation analysis showed that RDW, TNF-α, and IL-6 were positively correlated (r = 0.157, p = 0.003; R = 0.357, P < 0.001). The receiver operating characteristic curve showed that RDW, IL-6, and all combinations had high predictive values for IgAV (P < 0.05) compared with TNF-α, with RDW having the highest predictive value (Youden’s index: 0.355). TNF-α, IL-6, and particularly RDW were identified as risk factors for IgAV in Tibetan children, and there was no regional difference between Tibetan and Han children at high altitudes .

ObjectiveThe risk factors for Henoch–Schönlein purpura nephritis (HSPN) remain largely unclear, particularly in family environment and vaccination. This study aimed to develop a predictive framework to quantify the risk of HSPN by examining family environmental factors and COVID-19 vaccination outcomes in children with Henoch–Schönlein purpura (HSP) in Anhui, China.MethodsThis study retrospectively analyzed 362 children diagnosed with HSP at Anhui Children’s Hospital between January 2020 and February 2024. A questionnaire was designed to collect information from enrolled children. For patients with incomplete medical records, parents were contacted via phone or the questionnaire was sent to them to complete the survey. After data collection, the patients were split randomly into a training group and a validation group at a 7:3 ratio, univariate and multivariate logistic regression analyses were performed to identify risk factors for nephritis, and a nomogram was constructed from these factors to provide a visual prediction of the likelihood of nephritis in HSP. The nomogram’s performance was evaluated in both the training and validation groups using the area under the receiver operating characteristic (AUC) curve, calibration plots, and decision curve analysis (DCA).ResultsThe study identified family income/month, age of onset, BMI, number of recurrences, and COVID-19 vaccination status as independent risk factors for HSPN. A nomogram was subsequently developed afterward using these factors. In the training group, the nomogram achieved an area under the curve (AUC) of 0.83 (95% CI: 0.78–0.88), while in the validation group, the AUC was 0.90 (95% CI: 0.84–0.96), demonstrating strong predictive performance. The calibration curve showed that the nomogram’s predictions were well-aligned with the actual outcomes. Additionally, DCA indicated that the nomogram provided considerable clinical net benefit.ConclusionThe nomogram offers accurate risk prediction for nephritis in children with HSP, helping healthcare professionals identify high-risk patients early and make informed clinical decisions.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant disorder characterized by midlife-onset cerebrovascular disease and dementia. It is caused by mutations in the NOTCH3 gene, which affects the amount of cysteine in the extracellular domain (ECD) of the receptor, leading to protein misfolding and receptor aggregation. Emerging evidence indicates that beyond classical missense mutations, other variants including cysteine-sparing missense mutations, homozygous mutations, small deletions, duplications, splice site mutations, a deletion/insertion and loss-of-function mutations may lead to distinct phenotypes with variable severity and disease penetrance. The marked heterogeneity in genotypes and phenotypes poses significant challenges for CADASIL diagnosis and clinical management. The aim of this review is to summarize the mutational spectrum of CADASIL, explore the possible genotype–phenotype correlations and discuss the phenotypic heterogeneity of NOTCH3 mutations. More studies are needed in the future to demonstrate whether CADASIL can be expanded from classical cerebral small vessel disease to a new spectrum of diseases that share the same pathogenesis as mutations in the NOTCH3 gene.

Maternal exposure to heavy metals is linked to adverse birth outcomes, but combined effects remain understudied. Examine associations between mid-pregnancy serum metals (Iron [Fe], Selenium [Se], Rubidium [Rb], Thallium [Tl], Antimony [Sb], and Iodine [I]) and preterm birth (PTB), congenital anomalies, low birth weight (LBW), macrosomia, SGA, and LGA. Prospective cohort (n = 429 mother-infant pairs). Serum metals quantified via ICP-MS. Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression assessed mixture effects. Both BKMR and WQS analyses indicated that combined metal exposure correlated positively with PTB risk, but inversely with congenital anomalies and LGA. Thallium (Tl) and iron (Fe) demonstrated negative associations with PTB (Tl exhibiting highest weight), whereas selenium (Se), antimony (Sb), and iodine (I) showed positive associations (Se as primary contributor). WQS regression confirmed: Positive association with PTB (β = 1.366, 95 % CI: 0.041-2.692; p = 0.043), Negative association with LGA (β = -2.224, 95 % CI: -3.783--0.666; p = 0.005). Our findings advance understanding of prenatal multi-metal exposure risks, revealing complex relationships between elemental mixtures and birth outcomes. This evidence supports targeted preventive strategies for maternal-fetal health protection.

A 44-year-old woman presented with acute dysarthria and left-sided hemiparesis without young vascular risk factors. Her medical history includes two prior episodes of cerebral infarction, each characterized by similar neurological deficits. Laboratory evaluations for young stroke-associated risk factors were negative, and serial carotid Doppler ultrasonographies (US) revealed no abnormalities. She was maintained on dual antiplatelet therapy consistently. Magnetic resonance imaging (MRI) performed during the current episode identified an acute ischemic stroke in the right cerebral hemisphere, with lesion distribution corresponding to the cerebrovascular territories involved in a previous cerebral infarction (Fig 1A). Carotid Doppler ultrasonography (US) showed a hyperechoic membrane-like structure in the proximal segment of the right internal carotid artery (ICA) (Fig 1B, C), consistent with a carotid web (CW), with a thrombus above it that moved with the cardiac cycle (Video S1). Furthermore, Computed tomography angiography (CTA), referenced from the North American Symptomatic Carotid Endarterectomy Trial (NASCET), revealed a membrane filling defect in the initial segment of the right ICA, aligning with CW and significant luminal stenosis (Fig 1D, E). Finally, post-carotid endarterectomy validated that was a CW with huge thrombosis (Fig 1F). CW, a subtype of intimal fibromuscular dysplasia,1 is an underestimated etiology of cryptogenic stroke. The atypical morphology of CW results in elevated shear stress within the recirculation zones and along the vessel walls, fostering turbulent flow and hemodynamic stasis (Video S2). These hemodynamic disturbances facilitate distal thrombus formation,1 thereby increasing the risk of recurrent ischemic events.1, 2 Carotid endarterectomy effectively diminishes the potential for thromboembolic complications associated with CW.3 The authors acknowledge the patient for her participation in this study. Y.J. and F.D. contributed to the conception and design of the study and drafting the text. F.D. contributed to the acquisition and analysis of data. Y.J. contributed to preparing the figures. On behalf of all authors, the corresponding author states that there are no conflicts of interests. Data sharing is not applicable to this article as no new data were created or analyzed in this study. Video S1. Floating thrombosis on carotid web. Doppler Ultrasongraphy showed a hyperechoic membrane-like structure in the proximal segment of the right internal carotid artery, consistent with a carotid web, with a thrombus above it that moved with the cardiac cycle. Video S2. The pathogenesis of ischemic stroke caused by carotid web. The atypical morphology of a carotid web results in increased shear stress in the recirculation zone and along the vessel wall, causing turbulence and hemodynamic arrest, which promotes the formation of distal thrombosis. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Objective Here, we explored the phenotype and function of MAIT cells in the peripheral blood of patients with HSP. Methods Blood samples from HSP patients and HDs were assessed by flow cytometry and single-cell RNA sequencing to analyze the proportion, phenotype, and function of MAIT cells. Th-cytokines in the serum of HSP patients were analyzed by CBA. IgA in cocultured supernatant was detected by CBA to analyze antibody production by B cells. Results The percentage of MAIT cells in HSP patients was significantly reduced compared with that in HDs. Genes related to T cell activation and effector were up-regulated in HSP MAIT cells, indicating a more activated phenotype. In addition, HSP MAIT cells displayed a Th2-like profile with the capacity to produce more IL-4 and IL-5, and IL-4 was correlated with IgA levels in the serum of HSP patients. Furthermore, CD40L was up-regulated in HSP MAIT cells, and CD40L + MAIT cells showed an increased ability to produce IL-4 and to enhance IgA production by B cells. Conclusion Our data demonstrate that MAIT cells in HSP patients exhibit an activated phenotype. The enhanced IL-4 production and CD40L expression of MAIT cells in HSP patients could take part in the pathogenesis of HSP.

OBJECTIVE:To explore the clinical significance of detecting mycoplasma pneumoniae (MP)-DNA, C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, and IL-10 in children with mycoplasma pneumoniae pneumonia (MPP).METHODS:The data from 106 children who received treatment or underwent health examination in the Children's Medical Center of Anhui Medical University from January 2021 to October 2022 were collected and analyzed retrospectively. The observation group (OG) consisted of 64 children with MPP, while the control group (CG) consisted of 42 healthy children. The levels of IL-6, IL-8, IL-10, CRP, and MP-DNA were compared between the two groups. The diagnostic value of MP-DNA in patients with MPP and its correlation with the levels of IL-6, IL-8, IL-10 and CRP were analyzed.RESULTS:The level of MP-DNA in the OG was notably higher than that in the CG (P<0.05). Additionally, the levels of IL-6, IL-8, IL-10, and CRP in the OG were significantly higher than those in the CG (P<0.05). MP-DNA was positively correlated with the levels of IL-6, IL-8, IL-10, and CRP (P<0.05). The area under the curve of MP-DNA in diagnosing MPP was 0.979, with a specificity of 92.19% and a sensitivity of 97.62%.CONCLUSION:Indicators such as MP-DAN, IL-6, IL-8 are crucial in the development and progression of MPP, playing an important role in diagnosing and treating patients with MPP.

Previous studies have found the effect of ShuganJieyu capsule and St. John’s wort on the treatment of depression and explored their potential benefits for somatic symptoms, while the evidence of comparison of them for depression with somatic complaints is lacking. In this multicenter randomized controlled trial, 198 major depressive disorder (MDD) patients with somatic complaints were randomly allocated, 92 in the ShuganJieyu capsule group, and 91 in the St. John’s wort group completed 8 weeks treatment. Primary outcome was the change score of the 17-item Hamilton Depression Rating Scale (HDRS-17) at week 8. Secondary outcomes included other indices of depression, somatic symptoms, anxiety, insomnia, quality of life, and adverse events. The change scores of HDRS-17 were not significantly difference between the two groups, but the reduction in HDRS-17 was significantly improved in both the ShuganJieyu capsule (HDRS-17Δ = − 11.35 ± 5.38, p < 0.001) and St. John’s wort (HDRS-17Δ = − 11.20 ± 5.71, p < 0.001) groups. The other outcomes showed similar results. Compared with St. John’s wort, the ShuganJieyu capsule induced significantly greater HDRS-17 reductions in male (SMD, − 0.55; 95% CI, − 1.08 to − 0.02) but not in female. Overall, The ShuganJieyu capsule was comparable to St. John’s wort as a complementary and alternative intervention for MDD patients with somatic complaints in the acute treatment, especially for male patients.

Sepsis is a systemic inflammatory response caused by an infection, which can easily lead to acute lung injury. Quiescin Q6 sulfhydryl oxidase 1 (QSOX1) is a sulfhydryl oxidase involved in oxidative stress and the inflammatory response. However, there are few reports on the role of QSOX1 in sepsis-induced acute lung injury (SALI). In this study, mice model of SALI was constructed by intraperitoneal injection with lipopolysaccharide (LPS). The increased inflammatory response and lactate dehydrogenase activity in bronchoalveolar lavage fluid (BALF) indicated successful modeling. Increased QSOX1 expression was both observed in lung tissues and lung macrophages of sepsis mice accompanied by increased polarization of M1-type macrophages. To explore the role of QSOX1 in the SALI, lentivirus containing QSOX1-specific overexpression or knockdown vectors were used to change QSOX1 expression in LPS-treated RAW264.7 cells. QSOX1 suppressed LPS-induced M1 polarization and further inhibited inflammatory response in RAW264.7 cells. Interestingly, the phosphorylation of epidermal growth factor receptor (EGFR), the promoter of M1 polarization in macrophages, was found to be downregulated upon QSOX1 overexpression in RAW264.7 cells. Mechanically, the binding of QSOX1 to EGFR protein promoted EGFR ubiquitination and degradation, thereby down-regulating EGFR phosphorylation. Moreover, inhibiting EGFR expression or its phosphorylation restored the impact of QSOX1 silencing on M1 polarization and inflammation in the LPS-treated RAW264.7 cells. In summary, QSOX1 may exert anti-inflammatory effects in SALI by inhibiting EGFR phosphorylation-mediated M1 macrophage polarization. This presented a potential target for the treatment and prevention of SALI.

Background: pRIFLE (Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease), KDIGO (Kidney Disease Improving Global Outcomes) and pROCK (Pediatric Reference Change Value Optimized for AKI) are diagnostic criteria used for acute kidney injury (AKI) incidence evaluation. The aim of this study was to explore the diagnostic consistency, incidence and mortality rate, clinical signs, and influencing factors of renal injury related to sepsis in children diagnosed by three different AKI diagnostic criteria, and then evaluate which one was more valuable. Methods: A retrospective analysis was performed on the clinical data of children with severe sepsis. The patients were diagnosed and staged according to the 2007 pRIFLE standard, the 2012 KDIGO standard, and the 2018 pROCK standard. The clinical characteristics and prognosis of children with different stages of sepsis were compared between the three diagnostic standards. Results: A total of 62 patients with sepsis were included. Blood stream infection is common (11 cases, 17.74%). According to pRIFLE, KDIGO, and pROCK standards, the incidence of sepsis -associated AKI (SA-AKI) was 74.2%, 67.7%, and 56.5%, respectively. The pRIFLE had the highest diagnostic rate of early detection of SA-AKI. There was no statistical difference in SA-AKI incidence or staging consistency between the pRIFLE and KDIGO groups (kappa=0.0671; kappa>0.60); the consistency of SA-AKI diagnoses across the three standards was good (all P values <0.05), and pROCK demonstrated a higher specificity. A high Pediatric Risk of Mortality (PRISM) score and high procalcitonin level were independent risk factors. Shock and renal replacement therapy were independent risk factors for SA-AKI death. Death from admission to 28 days after admission was used as an endpoint to draw a survival graph, which revealed that the AKI group had a significantly higher risk of death than did the non-AKI group. Conclusions: The consistency of diagnosing SA-AKI across the three classification criteria was similar, and mortality rate increased with increased SA-AKI staging. The pRIFLE criteria were more sensitive in the early detection of SA-AKI, while the pROCK had higher specificity. There was no significant difference between the pRIFLE and KDIGO in terms of incidence, diagnosis, or staging of SA-AKI.

Objective: To evaluate the efficacy and safety of early Rituximab (RTX) treatment in reducing relapses within two years for newly diagnosed steroid-sensitive nephrotic syndrome (SSNS). Methods: A randomized controlled trial was conducted in the Anhui Children's Hospital from June 2021 to February 2022. This prospective study included 30 children diagnosed with initial SSNS who were randomly divided into RTX and steroid control groups. The RTX group received 375 mg/m2 RTX within one week, while the control group underwent standard treatment according to current evidence-based guidelines. Kaplan-Meier analysis was used to assess relapse-free survival rates and the incidence of frequent relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS). Analysis of variance was employed to evaluate IL-8 levels before and after treatment. Results: The two-year survival curves, with relapse as the endpoint event, showed significant differences between the RTX and steroid control groups (log-rank test c2=5.49, P<0.05). The two-year relapse-free survival rates were 57.14% and 21.42% for the RTX and control groups, respectively. In the RTX group, IL-18 decreased significantly from 55.90±12.36 pre-treatment to 24.98±1.96 one month post-treatment (P<0.05). Conclusion: Early RTX treatment can improve relapse-free survival rates in pediatric SSNS patients. IL-18 levels decrease one month after RTX treatment. This therapy is relatively safe, and no severe adverse reactions were observed.

BackgroundPrevious researches have clarified that miR-155 is increased in methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and modulates Th9 differentiation. Like Th9 cells, Th17 cells were also a subset of CD4+ T cells and involved in MRSA pneumonia progression. This work aimed to investigate the role and mechanism of miR-155 in Th17 differentiation.MethodsBronchoalveolar lavage fluid (BALF) was collected from children with MRSA pneumonia and bronchial foreign bodies. MRSA-infected murine model was established followed by collecting BALF and lung tissues. qRT-PCR, ELISA and flow cytometry were performed to examine the mRNA expression and concentration of IL-17 and the number of Th17 cells in above samples. HE and ELISA were used to evaluate inflammatory responses in lung. Furthermore, CD4+ T cells were isolated from BALF of children for in vitro experiments. After treatments with miR-155 mimic/inhibitor, the roles of miR-155 in Th17/IL-17 regulation were determined. The downstream of miR-155 was explored by qRT-PCR, western blotting, dual luciferase reporter analysis and RIP assay.ResultsThe levels of IL-17 and the proportion of Th17 cells were increased in children with MRSA pneumonia. A similar pattern was observed in MRSA-infected mice. On the contrary, IL-17 neutralization abolished the activation of Th17/IL-17 induced by MRSA infection. Furthermore, IL-17 blockade diminished the inflammation caused by MRSA. In vitro experiments demonstrated miR-155 positively regulated IL-17 expression and Th17 differentiation. Mechanistically, FOXP3 was a direct target of miR-155. miR-155 inhibited FOXP3 level via binding between FOXP3 and Argonaute 2 (AGO2), the key component of RNA-induced silencing complex (RISC). FOXP3 overexpression reversed elevated IL-17 levels and Th17 differentiation induced by miR-155.ConclusionsmiR-155 facilitates Th17 differentiation by reducing FOXP3 through interaction of AGO2 and FOXP3 to promote the pathogenesis of MRSA pneumonia. IL-17 blockade weakens the inflammation due to MRSA, which provides a nonantibiotic treatment strategy for MRSA pneumonia.