Combined Use of Emapalumab With Ruxolitinib and Dexamethasone as an Effective Treatment for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis Complicated With Multiorgan Damage and Severe Infection.

Anti-interferon-γ monoclonal antibody emapalumab and JAK1/2 inhibitors ruxolitinib have been widely reported for the treatment of hemophagocytic lymphohistiocytosis (HLH) recently. These targeted drugs have fewer side effects and may provide new options for patients with HLH who are refractory to previous treatment or intolerant to chemotherapy. Herein, we reported a case of Epstein-Barr virus-related HLH, which did not respond well to HLH-94 plus ruxolitinib and developed severe fungal infection. The disease was successfully controlled after a combination therapy of emapalumab, ruxolitinib, and dexamethasone.

Genome-Wide Identification and Characterization of the CCT Gene Family in Rapeseed (Brassica napus L.).

The CCT gene family is present in plants and is involved in biological processes such as flowering, circadian rhythm regulation, plant growth and development, and stress resistance. We identified 87, 62, 46, and 40 CCTs at the whole-genome level in B. napus, B. rapa, B. oleracea, and A. thaliana, respectively. The CCTs can be classified into five groups based on evolutionary relationships, and each of these groups can be further subdivided into three subfamilies (COL, CMF, and PRR) based on function. Our analysis of chromosome localization, gene structure, collinearity, cis-acting elements, and expression patterns in B. napus revealed that the distribution of the 87 BnaCCTs on the chromosomes of B. napus was uneven. Analysis of gene structure and conserved motifs revealed that, with the exception of a few genes that may have lost structural domains, the majority of genes within the same group exhibited similar structures and conserved domains. The gene collinearity analysis identified 72 orthologous genes, indicating gene duplication and expansion during the evolution of BnaCCTs. Analysis of cis-acting elements identified several elements related to abiotic and biotic stress, plant hormone response, and plant growth and development in the promoter regions of BnaCCTs. Expression pattern and protein interaction network analysis showed that BnaCCTs are differentially expressed in various tissues and under stress conditions. The PRR subfamily genes have the highest number of interacting proteins, indicating their significant role in the growth, development, and response to abiotic stress of B. napus.

Disseminated Cunninghamella elegans Infection Diagnosed by mNGS During Induction Therapy in a Child With Intermediate-risk Acute Lymphoblastic Leukemia: A Case Report and Review of Literature.

We described a 14-year-old girl with acute lymphoblastic leukemia who developed disseminated mucormycosis during induction therapy. Disseminated Cunninghamella elegans infection was confirmed by histopathology, microbiological culture, and metagenomic next-generation sequencing analysis of skin tissue, blood, and cerebrospinal fluid. Subsequently, the patient received a combination of liposomal amphotericin B, posaconazole, and caspofungin for antifungal treatment, but eventually died because of severe fungal pneumonia, respiratory failure, and septic shock. Moreover, case reports of pulmonary mucormycosis in children published since 1959 were reviewed. In summary, metagenomic next-generation sequencing is an effective diagnostic method for Cunninghamella with high speed and sensitivity.

Enhanced photocatalytic degradation of 4-chlorophenol under visible light over carbon nitride nanosheets with carbon vacancies.

Two-dimensional graphitic carbon nitride (g-C3N4, GCN) is considered as one of the promising visible light-responsive photocatalysts for energy storage and environmental remediation. However, the photocatalytic performance of pristine GCN is restricted by the inherent shortcomings of rapid charge carrier recombination and limited absorption of visible light. Vacancy engineering is widely accepted as the auspicious approach for boosting the photocatalytic activity of GCN-based photocatalysts. Herein, a magnesium thermal calcination method has been developed to reconstruct GCN, in which magnesium serves as a carbon etcher for introducing carbon vacancies and pores into GCN (Vc-GCN). The fabricated Vc-GCN demonstrates excellent photocatalytic performances of degrading hazardous 4-chlorophenol under visible light irradiation benefiting from the improved carrier separating and light absorption ability as well as rich reactive sites. The optimal Vc-GCN sample delivers 2.3-fold enhancement from the pristine GCN. The work provides a tactic to prepare GCN photocatalysts with controllable carbon vacancies and for a candidate for the degradation of organic pollutants from the environment.

Statins can benefit patients with primary membranous nephropathy on venous thromboembolism.

OBJECTIVE: The aim of this study was to investigate the role of prophylactic use of statin in venous thromboembolism (VTE) in patients with primary membranous nephropathy (PMN). METHODS: A total of 734 patients with PMN were consecutively enrolled in this retrospective study. 564 patients had received statins prescription, while 170 patients did not. Kaplan-Meier methods were used for cumulative incidence plots of thromboembolic events and Cox proportional hazards regression models were used to assess risk factors. Finally, the effects of different potency of statins were evaluated. RESULTS: In the cohort, 37 patients (5.0%) experienced VTE. In a univariate Cox proportional hazard model, the hazard ratio (HR) for VTE in statin users versus statin non-users was 0.5 (95% CI 0.3-0.8, p = .03). Multivariable model proportional-hazards analysis corrected for co-medications and risk factors revealed that adjusted HR was 0.4 (95% CI 0.1-0.7, p = .03). According to the type and dose, statin users were assigned into 3 groups: high-intensity group (n = 278), moderate-intensity group (n = 186), and low-intensity group (n = 49). In comparison, incidences of VTEs in the three groups were similar (2.9% vs 4.8% vs 2.0%, p = .45). CONCLUSIONS: The prophylactic use of statins could effectively decrease the occurrence of VTE in patients with PMN, and the benefits have no difference in different potency of statins.

The role of prophylactic use of low molecular weight heparin or aspirin in thromboembolic events in primary membranous nephropathy.

Objective: The aim of this study is to investigate the role of prophylactic anticoagulation regimens based on low molecular weight heparin (LMWH) or aspirin in thromboembolic events in patients with primary membranous nephropathy (PMN). Methods: A total of 717 patients with PMN were consecutively enrolled in this retrospective study. The propensity score matching method was utilized to adjust for the selection bias inherent in an analysis of outcomes, which was stratified by the anticoagulation prophylaxis regimen. Results: According to the anticoagulation prophylaxis regimen, patients were assigned into three groups: only LMWH therapy (L + A-, n = 53), only aspirin therapy (L - A+, n = 97), and no therapy of LMWH or aspirin (L - A-, n = 567). After performing 1:1 match, 37 patients were selected in the L + A - group and the L - A- group, respectively, and 94 patients were selected in the L - A+ group and the L - A- group, respectively. It showed that the prophylactic use of LMWH had no protective effects on arterial thromboembolic events (ATEs) (10.8% vs. 21.6%, p = .21) or venous thromboembolic events (VTEs) (8.1% vs. 10.8%, p = .69). The incidence of VTEs in the L - A+ group was lower than the L - A- group (2.1% vs. 10.6%, p = .02), while there were no significant differences in the incidences of ATEs between the L - A+ group and the L - A- group (5.3% vs. 7.4%, p = .55). Conclusions: The prophylactic use of LMWH showed no benefits on the incidence of ATEs or VTEs in patients with PMN. Aspirin effectively decreased the incidence of VTEs, without effects on the occurrence of ATEs.

Extending the SLEUTH model to integrate habitat quality into urban growth simulation.

This study aims to support sustainable urban and environmental planning by using urban growth simulation models, in which environmental quality is employed as one of the inputs. We proposed an extended SLEUTH urban growth model (UGM) for the regions threatened by environmental quality degradation caused by uncontrolled urban expansion. In this model, habitat quality is assessed by the InVEST model and is used to represent environmental quality, which is utilized in urban growth simulation. The habitat quality map is used to replace the slope layer as input for the SLEUTH model's urban growth simulation for cities where relatively flat topography makes this layer of minimal explanatory value. The extended SLEUTH UGM was calibrated using data for Changzhou city, China in 1990, 2000, 2010, and 2014. The best value of the Optimal SLEUTH Metric (OSM) was calculated for both the standard SLEUTH UGM and the extended SLEUTH UGM independently. The OSM value for the latter model was much higher than that of the former model, which indicated that the extended model provided a better explanation of urban growth in the study area. The calibrated extended SLEUTH UGM was applied to predict growth in Changzhou city from 2014 to 2030. The result showed that the urban area is expected to expand about 626 km2 by 2030. Comparison with the prediction result by using standard SLEUTH UGM showed that the area with high habitat quality could be reserved and the urban expansion could be limited by using our model. The findings demonstrate that the extended SLEUTH UGM could be a valuable tool for sustainable urban and environmental planning and management in developing regions where environmental protection should be considered as one of the major land-use objectives in their rapid urbanization process.

Therapy of Rituximab in Idiopathic Membranous Nephropathy with Nephrotic Syndrome: A Systematic Review and Meta-analysis.

Objective To investigate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN) with nephrotic syndrome with a systematic review and meta-analysis. Methods PubMed, Embase, Cochrane Library and Clinical Trials (December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission (CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated. Result Seven studies involved 120 patients (73% were men) were included in our systematic review and meta-analysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric (four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m2) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44 (36.7%) had immunosuppressive treatment]. In 12- and 24-month, 56% (95%CI, 0.47-0.65) and 68% (95%CI, 0.41-0.87) patients could reach remission, while 15% (95%CI, 0.09-0.23) and 20% (95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions. Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.

A Cohort Study of Incidences and Risk Factors for Thromboembolic Events in Patients with Idiopathic Membranous Nephropathy.

Objective The aims of this study were to assess incidences and characteristics of arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) in Chinese patients with idiopathic membranous nephropathy (IMN), and to identify the predisposing risk factors of them.Methods A total of 766 consecutive Chinese patients with IMN were enrolled in this retrospective cohort study. The cumulative incidences of newly diagnosed ATEs and VTEs were calculated using Kaplan-Meier methods. Univariable risk prediction model analysis followed by multivariable survival analysis was used to evaluate the potential risk factors of ATE and VTE.Results At 0.5, 1, 2, 3, and 5 years after biopsy diagnosis of IMN, the cumulative incidence of newly diagnosed ATEs were 4.3%, 5.7%, 6.3%, 7.1%, and 8.0%, and of newly diagnosed VTEs were 5.9%, 6.8%, 6.9%, 7.0%, and 7.2%, respectively. In 78 ATEs events (71 patients), cardiovascular diseases, thrombotic ischemic stroke (IS) and peripheral artery disease accounted for 50%, 45% and 5% respectively; in 60 VTEs events(53 patients), the deep vein thrombosis, renal vein thrombosis and pulmonary embolism accounted for 60%, 13% and 27% respectively. At the time of event, 42.1% patients with ATEs and 81.5% patients with VTEs were at nephrotic syndrome(NS) status (χ 2=18.1, P<0.001). Severe proteinuria, aging, smoking, hypertension and prior ATE history were associated with ATEs. Aging was demonstrated as the independent risk factor for ATEs (P=0.001), and hypoalbuminemia was the dominant independent risk factor for VTEs (P=0.03). Conclusions Patients with IMN have increased incidences of ATEs and VTEs, and most of events occurred within the first 6 months of the disease. IS was very common in ATEs in our cohort. Severe proteinuria and classic risk factors for atherosclerosis were associated with onset of ATEs. Hypoalbuminemia independently predicted VTEs. Risks of both ATEs and VTEs were particularly high in the status of NS, particularly VTEs.

[Pathogenic Mechanisms of the Focal Segmental Glomerulosclerosis and Its Role in the Progression of IgA Nephropathy].

Focal segmental glomerulosclerosis (FSGS),a common pathological change in kidney diseases,may be caused by primary factors or multiple secondary factors. Its pathogenic mechanism remains a hot topic in kidney disease research. FSGS-like pathologic changes are highly in IgA nephropathy. It has been speculated that FSGS in IgA nephropathy might be caused by hemodynamics changes,and podocyte injury,which,however,have not been well documented. Our current review focuses on the pathogenesis of secondary FSGS and its role in the progression of IgA nephropathy,with an attempt to provide more insights in the treatment of IgA nephropathy.

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy△.

Objective To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria < 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 (AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm2) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 (six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 m2 vs. -8.1±21.4 ml/min per 1.73 m2, P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

A two-photon off-on fluorescence probe for imaging thiols in live cells and tissues.

A two-photon (TP) fluorescence imaging probe (Z1) was designed to detect biothiols through a photoinduced electron transfer pathway utilizing N-butyl-naphthalimide as the fluorophore and 2,4-dinitrobenzene-sulfonyl as the responsive group, which were linked together by piperazine. The synthesized Z1 displayed high selectivity to biothiols, significant fluorescence off-on properties, and a marked two-photon absorption cross section (δ = 110 GM). Moreover, Z1 showed good biocompatibility and insensitivity toward changes in the biologically relevant pH range (7.2-8.4), which enabled the utilization of Z1 to monitor biothiol levels not only in live cells but also in tissues at depths of 50-250 µm.

Imaging of fluoride ion in living cells and tissues with a two-photon ratiometric fluorescence probe.

A reaction-based two-photon (TP) ratiometric fluorescence probe Z2 has been developed and successfully applied to detect and image fluoride ion in living cells and tissues. The Z2 probe was designed designed to utilize an ICT mechanism between n-butylnaphthalimide as a fluorophore and tert-butyldiphenylsilane (TBDPS) as a response group. Upon addition of fluoride ion, the Si-O bond in the Z2 would be cleaved, and then a stronger electron-donating group was released. The fluorescent changes at 450 and 540 nm, respectively, made it possible to achieve ratiometric fluorescence detection. The results indicated that the Z2 could ratiometrically detect and image fluoride ion in living cells and tissues in a depth of 250 µm by two-photon microscopy (TPM).

Role of mitochondrial dysfunction in kidney disease: Insights from the cGAS-STING signaling pathway.

ABSTRACT: Over the past decade, mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney disease. However, the precise molecular mechanisms linking mitochondrial damage to kidney disease remain elusive. The recent insights into the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthetase (cGAS)-stimulator of interferon gene (STING) signaling pathway have revealed its involvement in many renal diseases. One of these findings is that mitochondrial DNA (mtDNA) induces inflammatory responses via the cGAS-STING pathway. Herein, we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage, focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney diseases. Furthermore, we summarize the latest findings of cGAS-STING signaling pathway in cell, with a particular emphasis on its downstream signaling related to kidney diseases. This review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway, kidney diseases, and mitochondrial dysfunction.

Analysis of ultrasound coronary parameters and blood red cell distribution width and N-terminal pro-brain natriuretic peptide concentrations following coronary lesions in children with Kawasaki disease.

Aims/Background Kawasaki disease is an acute inflammatory condition primarily affecting the young children. It can lead to coronary artery abnormalities, which can worsen the prognosis. Early diagnosis of coronary disease is crucial for the effective treatment and the prognosis evaluation. To explore the clinical significance of ultrasound examination characteristics, peripheral blood red cell distribution width, and changes in N-terminal pro-brain natriuretic peptide levels for the early detect coronary artery abnormality in children with Kawasaki disease. Methods The case-control study was conducted. 85 Kawasaki disease patients diagnosed in our hospital from January 2020 to December 2023 were selected as the Kawasaki disease group. 100 healthy children who received physical examination in the Department of Child Healthcare during the same period were selected as control group. The cardiac ultrasound indicators, erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, N-terminal pro-brain natriuretic peptide of two groups were compared. The Kawasaki disease group was further divided into the coronary artery lesion group and the non-coronary artery lesion group based on whether coronary artery lesions occurred in the Kawasaki disease patients. The differences of above indicators were compared. Results The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of the Kawasaki disease group were all higher than those of the control group (p < 0.05). There was no significant difference in left ventricular ejection fraction between Kawasaki disease group and control group (p > 0.05). The erythrocyte sedimentation rate, C-reactive protein, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease group were all higher than those of control group (p < 0.05). The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions (p < 0.05). The left ventricular ejection fraction of Kawasaki disease patients with coronary artery lesions was lower than that of Kawasaki disease patients without coronary artery lesions (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions, and the differences were statistically significant (p < 0.05). After treatment, the left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions significantly decreased (p < 0.05), and the left ventricular ejection fraction significantly increased (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with or without coronary artery lesions significantly decreased after treatment compared with before treatment in the same group (p < 0.05). Conclusion Kawasaki disease patients with coronary artery lesions exhibit significantly increased coronary artery vessel diameter, as well as elevated red cell distribution width and N-terminal pro-brain natriuretic peptide concentration. The combined use of ultrasound combined with red cell distribution width and N-terminal pro-brain natriuretic peptide examination can assist in determining whether Kawasaki disease patients have coronary artery lesions and assessing the clinical treatment effect.

Clinical presentations and diagnostic approaches of pediatric necrotizing tracheobronchitis with influenza A virus and Staphylococcus aureus co-infections.

In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.

Inducing preferential growth of the Zn (002) plane by using a multifunctional chelator for achieving highly reversible Zn anodes.

Aqueous zinc-ion batteries (AZIBs) have demonstrated great potential for large-scale energy storage. However, their practical applications have been restricted by fast Zn dendrite growth and severe side reactions at the Zn/electrolyte interface. Herein, sodium gluconate is incorporated into a mild acidic electrolyte as a multifunctional additive to stabilize the Zn anode. Experiments and theoretical calculations reveal that the SG additive can induce planar growth of Zn along its (002) direction, thereby inhibiting Zn dendrite growth. This dendrite inhibition effect is attributed to the preferential adsorption of Zn2+ on the Zn (002) plane, while the Zn (100) and (101) planes are shielded by gluconate ions. Consequently, Zn||Zn symmetric cells with the electrolyte additive exhibit significantly prolonged cycle lives of 2000 h at 1 mA cm-2, 1 mA h cm-2 and 900 h at 5 mA cm-2, 2.5 mA h cm-2. Futhermore, the Zn||NH4V4O10 full cell retains 95% of its initial capacity after 2000 cycles at a current density of 5 A g-1 with an average CE of nearly 100%. This work offers a cost-effective strategy to enhance the electrochemical performance of AZIBs.

Guiding uniform Zn deposition with a multifunctional additive for highly utilized Zn anodes.

The practical applications of aqueous zinc-ion batteries (AZIBs) have been restricted by the fast growth of Zn dendrites and severe side reactions at the Zn/electrolyte interface. Herein, a multifunctional additive, L-leucine (Leu), is incorporated into a mild acidic electrolyte to stabilize the Zn anode. The Leu molecule, featuring both carboxyl and amino groups, exhibits strong interactions with Zn2+, which can reshape the solvation structure of Zn2+ and facilitate the uniform electrodeposition of Zn. Simultaneously, the Leu molecule exhibits preferential adsorption onto the Zn surface, effectively isolating it from direct contact with water, thus suppressing unwanted side reactions. Consequently, the Zn∥Cu asymmetric cell exhibits a high and stable coulombic efficiency of 99.5% at a current density of 5 mA cm-2 for 1100 h. Importantly, the capacity retention of the Zn∥NH4V4O10 full cell based on the Leu electrolyte reaches 80% after 1200 cycles at a current density of 2 A g-1. The successful application of the low-cost Leu effectively enhances the cycling stability of the AZIBs and accelerates their applications.