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In recent years, knowledge regarding immune regulation has expanded rapidly, and major advancements have been made in immunotherapy for immune-associated disorders, particularly cancer. The programmed cell death 1 (PD-1) pathway is a cornerstone in immune regulation. It comprises PD-1 and its ligands mediating immune tolerance mechanisms and immune homeostasis. Accumulating evidence demonstrates that the PD-1 axis has a crucial immunosuppressive role in the tumor microenvironment and autoimmune diseases. PD-1 receptors and ligands on immune cells and renal parenchymal cells aid in maintaining immunological homeostasis in the kidneys. Here, we present a comprehensive review of PD-1 immunology in various kidney disorders, including renal cell carcinoma, glomerulonephritis, kidney transplantation, renal aging, and renal immune-related adverse events secondary to PD-1 immunotherapy.

Abstract Background Chronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration. Methods A retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children’s Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated. Results Three patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0–23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment. Conclusion Our data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions.

BackgroundAtypical hemolytic uremic syndrome (aHUS) with diacylglycerol kinase epsilon (DGKE) gene variant is a rare variant of thrombotic microangiopathy (TMA). The information on the clinical features, management and long-term outcomes of DGKE-aHUS patients have not yet been fully elucidated. The aim of this study was to report a novel variant of the DGKE gene in a Chinese population with aHUS.Case presentationThe present work reports a 7-month-old boy with aHUS, possibly triggered by gastrointestinal infection, without complement activation, with little response to plasma therapy and nephroprotective measures. The patient died during the 8th week of his hospital stay. The causes of death were intracranial hemorrhage and multiorgan dysfunction. Comprehensive WES of peripheral blood-derived DNA revealed two heterozygous variations in the DGKE exon region: NM_003647.2, c.610dup, p.Thr204Asnfs*4 and deletion of exons 4–6.ConclusionsThis case suggest that atypical HUS with DGKE gene variant has a poor prognosis with a high mortality rate, which typically manifests in the first year of life and presents as a systemic disease with early-onset HUS with rapidly worsening renal function and chronic proteinuria. There is no specific treatment for DGKE-aHUS. There have an uncertain benefit of plasma therapy for DGKE-aHUS patients. The literature demonstrated that anti-complement therapy showed benefits for DGKE-aHUS with complement activation and autoantibodies during the overt TMA presentation but did not prevent TMA relapses. Early diagnosis and treatment may prevent complications and improve prognosis.

Objective: To identify postnatal risk factors for bronchopulmonary dysplasia (BPD) development in preterm infants with gestational age ≤32 weeks.Methods: Seventy-two preterm infants(30 with BPD and 42 non-BPD controls) admitted in the neonatal intensive care unit (NICU) of the Children's Hospital of Soochow University during 2017 were enrolled in this prospective longitudinal study. Perinatal clinical data, a neonatal critical illness score (NCIS), different soluble B7-H3(sB7-H3), and interleukin-18 (IL-18) levels by days after birth were collected. An early predictive model for BPD development was established based on clinical data using multiple logistic regression analysis. And the sensitivity and specificity of the model were assesed by ROC curve.Results: Electrolyte disturbances, hemodynamically significant patent ductus arteriosus (hs-PDA), and the age that infants achieved 120 kcal/kg.d via enteral feeding ≥40 days after birth were found to be associated with the BPD pathogenesis. Serum sB7-H3, IL-18, and NCIS were significantly higher in the BPD group compared to the non-BPD group (p < 0.05). BPD group had significantly lower enteral fluid and caloric intake compared to the non-BPD group at 1, 7, 14, and 28 days after birth. The risk factors were analyzed by multiple logistic regression and a predictive model of a combination of sB7-H3 (day 7), IL-18 (day 14), NCIS, and clinical risk factors was evaluated via ROC curve with an area under the curve (AUC) of 0.960 having sensitivity of 86.7% and a specificity of 97.6%, respectively.Conclusion: The causes of BPD are multifactorial postnatal risk factors. And the combination of sB7-H3 (day 7), IL-18 (day 14), NCIS, and clinical risk factors (electrolyte disturbances, hs-PDA, and the age that infants achieved 120 kcal/kg.d via enteral feeding ≥40 days after birth) might be served as an optimal predictive model for the occurrence of BPD.

Background. Cholestasis is a common but serious clinical condition in preterm neonates. The current management for preterm neonatal cholestasis has limitations. The aim of this study was to determine effects of Bifidobacterium supplementation on the prevention and alleviation of cholestasis in preterm infants with very low birth weight. Methods. Preterm neonates with very low birth weight were enrolled in the Children’s Hospital of Soochow University between December 2012 and December 2017. The patients were randomly assigned into Bifidobacterium and control groups, and effects of Bifidobacterium supplementation on the outcomes were compared between the two groups. Results. There was no significant difference in the baseline characteristics in the two groups. Notably, the proportion of cases with neonatal cholestasis was significantly lower, with fewer neonatal cholestasis-associated complications in the Bifidobacterium group compared with the control group (6% versus 22%, P

Aims. To model the parenteral nutrition-associated liver disease (PNALD) in rat normal hepatocytes BRL and investigate the role of endoplasmic reticulum stress- (ERS-) related IRE1α signal in the process of PNALD. Methods. The BRL cells were treated with different concentrations of soybean oil emulsion (SO) to induce hepatocyte fatty degeneration. The PNALD cell disease model was further confirmed by analysis of Oil Red O staining and biochemical parameters. Next, the IRE1α was silenced by specific shRNAs via lentivirus and the role of IRE1α in anticytotoxicity and the expression level of ERS-related protein IRE1α and p-IRE1α were measured. Results. The results of Oil Red O staining indicated that the PNALD was successfully established in BRL cells and the CCK-8 data indicated which 0.6% that SO was further applied to the experiment owing to its better induction of PNALD and less toxicity to the cells. Besides, the value of biochemical parameters (TBIL, DBIL, ALT, and AST) was also elevated in the SO group compared with the NG group. After knockdown of IRE1α, the PNALD was also induced while the cells were more tolerant to SO. The less positive Oil Red O staining and reduced values of biochemical parameters were observed in the shIRE1α group when compared to the shControl, both of which accepted SO treatment. Conclusion. IRE1α was induced in PNALD cell model and suppression of IRE1α resulted in reduced steatosis in this cell disease model. Taken together, our data suggested that the IRE1α pathway may be involved in the development of PNALD.

Purpose: To explore the lung function of bronchopulmonary dysplasia (BPD) in premature infants to guide clinical prevention, early diagnosis and treatment.Methods: Thirty infants with BPD at 4–36 months of corrected gestational age were enrolled and divided into mild BPD and moderate and severe BPD groups. Thirty full-term healthy infants, and 30 non-BPD infants at 4–36 months of corrected gestational age were included as controls. Clinical information, including respiratory infections and re-hospitalization, was compared among these groups. Furthermore, lung function analysis was performed in the infants.Results: The upper respiratory tract infection rate and re-hospitalization rate were significantly higher in the infants with BPD than in the non-BPD infants. The tidal volume/kg, proportion of time to reach peak tidal expiratory flow/total expiratory time, tidal volume exhaled at peak tidal expiratory flow/total tidal volume in BPD group were significantly lower in the BPD group than those in non-BPD group. These values gradually decreased as the severity of BPD increased. The respiratory rate (RR) in BPD group was significantly higher than that in non-BPD group. As the severity of the BPD increased, slope of the descending branch of expiration of tidal breathing flow capacity ring (TBFVL) increased.Conclusion: There is a correlation between the severity of BPD and a poor prognosis of respiratory system. TBFVL can directly reflect the characteristics of Tidal Pulmonary Function in children with different degrees of BPD.

Parenteral nutrition-associated liver disease (PNALD) is a severe ailment associated with long-term parenteral nutrition. Soybean oil-based lipid emulsions (SOLE) are thought to promote PNALD development, whereas fish oil-based lipid emulsions (FOLE) are thought to protect against PNALD. This study aimed to investigate the effects of SOLE and FOLE on primary rabbit hepatocytes. The results reveal that SOLE caused significant endoplasmic reticulum (ER) and mitochondrial damage, ultimately resulting in lipid droplets accumulation and ER stress. While these deleterious events induce hepatocyte injury, FOLE at high doses cause only minor ER and mitochondrial damage, which has no effect on hepatic function. SOLE also significantly upregulated glucose-regulated protein 94 mRNA and protein expression. These data indicate that SOLE, but not FOLE, damage the ER and mitochondria, resulting in lipid droplets accumulation and ER stress and, finally, hepatocyte injury. This likely contributes to the differential impacts of SOLE and FOLE on PNALD development and progression.