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Abstract Background As a rare mitochondrial disorder, the pyruvate dehydrogenase complex (PDC) deficiency is a rare inborn disease characterized with glucose metabolism defects, which leads to neurological dysfunction, serum lactic acid buildup and a resultant trend of metabolic acidosis. Although the ketogenic diet (KD) is the first-line treatment for PDC deficiency, there is currently no widely accepted consensus on specific implementation of KD for this condition. Due to the combined effect of pre-existing hyperlactacidemia and KD-induced ketoacidosis that can further exacerbate metabolic disturbances, maintaining metabolic homeostasis should be prioritized during the implementation of KD. Case presentation Herein, the authors present a 6-year-old boy with lactic acidosis, ataxia, hypotonia and neuromotor development retardation. The KD was started after the patient was diagnosed with PDC deficiency based on genetic testing. The initiation with classic KD resulted in severe non-diabetic ketoacidosis with elevated anion gap, which was promptly alleviated by dextrose supplementation and dietary modification to a less-restrictive KD. Long-term supervision demonstrated the efficacy of a modified KD in improving both clinical course and metabolic acidosis of the patient. Conclusions This rare case adds to the limited evidence of KD application in PDC deficiency, and provides valuable insights into the importance of reasonably lowering the ketogenic ratio of KD at the start of treatment to reduce the risk of metabolic acidosis.

Invasion and migration are the primary factors for mortality in lung adenocarcinoma (LUAD) patients. The precise role of RNA-binding motif protein15 (RBM15)-mediated m6A modification in LUAD is not yet fully clarified. This research aims to elucidate the mechanism of RBM15 in the invasion and migration of LUAD.Western blot and dot blot assay results showed that RBM15 and methylation levels of m6A were highly expressed in LUAD tissues. Overexpression of RBM15 by lentivirus transfection increased m6A levels and promoted the invasion, migration, and proliferation of A549 and H1734 cells. Knockdown of RBM15 by lentivirus transfection had opposite effects on m6A levels, invasion, migration, and proliferation of A549 and H1734 cells. The results of nude mouse proliferation models confirmed that RBM15 knockdown inhibited in vivo tumor proliferation . Sequencing and immunoprecipitation identified RASSF8 as an interacting protein of RBM15 involved in cell invasion and migration. RBM15-mediated m6A modification inhibited RASSF8 protein levels and increased LUAD cell invasion and migration. The rescue assays demonstrated that the regulation of RBM15 on LUAD cell invasion and migration was partially rescued by RASSF8.In conclusion, RBM15-mediated m6A modification inhibits the RASSF8 protein levels and increases cell invasion and migration. Thus, targeting the RBM15-m6A-RASSF8 axis may be a promising strategy for repressing LUAD cell invasion and migration.

IntroductionImproving photosynthetic use efficiency in dryland agroecosystems to sustain high agricultural yields is a key responsibility for ensuring food security.MethodsThis study was conducted in the regions on the semiarid Loess Plateau of China during 2018–2020. Dryland maize of Xianyu 335 comprised four modes: basic yield input (CK, plastic film mulching, 37500 plant.ha-1 of plant density and unfertilized), farmer input (FP, plastic film mulching, 45000 plant.ha-1 of plant density and inorganic nitrogen(N) and phosphate(P) fertilizer were 150kg.ha-1 and 90kg.ha-1), high yield and high-efficiency input (HH, full plastic-film mulching on double furrow, 67500 plant.ha-1 of plant density and N, P and organic manure(M) fertilizer were 230kg.ha-1, 140kg.ha-1 and 1500kg.ha-1), and super high yield input (SH, full plastic-film mulching on double furrow, 9000 plant.ha-1 of plant density and N, P and organic M fertilizer were 300kg.ha-1, 180kg.ha-1 and 7500kg.ha-1). The effects of different cultivation modes on yield, WUE, net photosynthetic rate(Pn), leaf area index(LAI), chlorophyll index(SPAD value) and root index were studied.ResultsThe results showed that the value average of yield and WUE for CK were 7790kg and 17480kg.ha-1 in three years. SH, HH and FP cultivation modes of yield and WUE was significant higher compared with CK cultivation mode (P

Abstract Purpose Based on the quantitative and qualitative features of CT imaging, a model for predicting the invasiveness of ground-glass nodules (GGNs) was constructed, which could provide a reference value for preoperative planning of GGN patients. Materials and methods Altogether, 702 patients with GGNs (including 748 GGNs) were included in this study. The GGNs operated between September 2020 and July 2022 were classified into the training group (n = 555), and those operated between August 2022 and November 2022 were classified into the validation group (n = 193). Clinical data and the quantitative and qualitative features of CT imaging were harvested from these patients. In the training group, the quantitative and qualitative characteristics in CT imaging of GGNs were analyzed by using performing univariate and multivariate logistic regression analyses, followed by constructing a nomogram prediction model. The differentiation, calibration, and clinical practicability in both the training and validation groups were assessed by the nomogram models. Results In the training group, multivariate logistic regression analysis disclosed that the maximum diameter (OR = 4.707, 95%CI: 2.06–10.758), consolidation/tumor ratio (CTR) (OR = 1.027, 95%CI: 1.011–1.043), maximum CT value (OR = 1.025, 95%CI: 1.004–1.047), mean CT value (OR = 1.035, 95%CI: 1.008–1.063; P = 0.012), spiculation sign (OR = 2.055, 95%CI: 1.148–3.679), and vascular convergence sign (OR = 2.508, 95%CI: 1.345–4.676) were independent risk parameters for invasive adenocarcinoma. Based on these findings, we established a nomogram model for predicting the invasiveness of GGN, and the AUC was 0.910 (95%CI: 0.885–0.934) and 0.902 (95%CI: 0.859–0.944) in the training group and the validation group, respectively. The internal validation of the Bootstrap method showed an AUC value of 0.905, indicating a good differentiation of the model. Hosmer–Lemeshow goodness of fit test for the training and validation groups indicated that the model had a good fitting effect (P > 0.05). Furthermore, the calibration curve and decision analysis curve of the training and validation groups reflected that the model had a good calibration degree and clinical practicability. Conclusion Combined with the quantitative and qualitative features of CT imaging, a nomogram prediction model can be created to forecast the invasiveness of GGNs. This model has good prediction efficacy for the invasiveness of GGNs and can provide help for the clinical management and decision-making of GGNs.

Abstract Background Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs. Methods This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses. Results A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions. Conclusion The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.

Abstract Permittivity at microwave frequencies determines the practical applications of microwave dielectric ceramics. The accuracy and universality of the permittivity prediction by Clausius–Mossotti equation depends on the dielectric polarizability (αD) database. The most influential αD database put forward by Shannon is facing three challenges in the 5 G era: (1) Few data, (2) Simplistic relation and (3) Low frequency (kHz–MHz) oriented. Here, we optimized and extended the Shannon’s database for microwave frequencies by the four-stage multiple linear regression and support vector machine model. In comparison with the conventional database, the optimized and extended databases achieved higher accuracy and expanded the amount of data from 60 to more than 900. Besides, we analyzed the relationships between αD and ion characteristics, including ionic radius (IR), atomic number (N), valence state (V) and coordination number (CN). We found that the positive cubic law of “αD ~ IR3” discussed in Shannon’s work was valid for the IR changed by the N, but invalid for the change caused by the CN.

Microwave dielectric ceramics (MWDCs) with a high Q×f value can improve the performance of radio frequency components like resonators, filters, antennas and so on. However, the quantitative structure-property relationship (QSPR) for the Q×f value is complicated and unclear. In this study, machine learning methods were used to explore the QSPR and build up Q×f value prediction model based on a dataset of 164 ABO4-type MWDCs. We employed five commonly-used algorithms for modeling, and 35 structural features having correlations with Q×f value were used as input. In order to describe structure from both global and local perspectives, three different feature construction methods were compared. The optimal model based on support vector regression with radial basis function kernel shows good performances and generalization capability. The features contained in the optimal model are primitive cell volume, molecular dielectric polarizability and electronegativity with A- and B-site mean method. The relationships between property and structure were discussed. The model used for the Q×f value prediction of tetragonal scheelite shows excellent performances (R2 = 0.8115 and RMSE = 8362.73 GHz), but it needs auxiliary features of average bond length, theoretical density and polarizability per unit volume for monoclinic wolframite ceramics to improve model prediction ability.

Abstract Background Cytomegalovirus (CMV) plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, it is not clear whether the anti-CMV treatment has an impact on the prognosis of SLE patients with CMV infection. We aimed to analyze the clinical characteristics and prognosis of CMV infection in pediatric SLE (pSLE) and to evaluate the effect of anti-CMV treatment on pSLE outcome. Methods A retrospective study including 146 pSLE from 2012 to 2021 was conducted. CMV-positive and CMV-negative groups were compared by univariate analysis and stepwise logistic multiple regression to analyze the clinical characteristics of CMV infection in pSLE. Generalized estimating equations (GEE) were used to model the longitudinal dynamics of pSLE disease activity with or without CMV infection and anti-CMV treatment. Results The CMV infection rate was 74.7% (109/146) in this pSLE cohort. CMV-positive pSLE patients were more likely to present positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement (P < 0.05). Survival analysis showed that CMV-positive pSLE patients were more prone to disease flare and poorer outcomes. GEE modeling indicated that CMV phosphoprotein 65 (pp65) titers were positively correlated with SLEDAI-2K, and anti-CMV treatment could better reduce pSLE activity than non-treatment (P < 0.05). Conclusions CMV infection is highly prevalent among pSLE patients. Positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement were significant clinical clues indicating CMV infections in pSLE. CMV infection is correlated with higher disease activity and poorer outcome. Anti-CMV treatment can reduce disease activity and flares.

In this work, ordered macropore arrays in n-type silicon wafers were fabricated by anodic etching using a double-tank electrochemical cell. The effects of the wafer thickness, etching time and voltage on the quality of macropore arrays were investigated. Homogeneous macropore arrays could be achieved in 200 μm thick silicon wafers, but could not be obtained from 300 and 400 μm thick silicon wafers. Highly ordered macropore arrays with an aspect ratio of 19 were fabricated in 200 μm thick n-type silicon at 4.5 V. The etching current decreases in 200 μm thick silicon but increases in thicker silicon with an increase in time. It demonstrates that the minority carrier transportation capability from the illuminated surface to the reactive surface is different for silicon wafers with different thicknesses. The minority carrier concentration at the illuminated surface for stable macropore formation and the current under different etching voltages were calculated based on a hole transport model. The results show that appropriately decreasing wafer thickness and increasing voltage can help stable macropore array fabrication in the illumination-limited double-tank cell.

Abstract Background NLRP3-associated autoinflammatory disease (NLRP3-AID), caused by mutations of NLRP3, is one of the autoinflammatory diseases affecting inflammasomes. Since there are little cases of Chinese NLRP3-AID, we reported 14 Chinese NLRP3-AID patients in our center and summarized the clinical features of all Chinese patients by reviewing the literature. Results Fourteen patients had been diagnosed as NLRP3-AID in our center. 12 different NLRP3 variants were identified, among which one is novel: p.Leu361Trp. Rash, recurrent fever, arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS), and increased inflammatory markers (including CRP, ESR, except Ferritin) were the common findings in Chinese patients. The frequencies of fever, neurological symptoms, musculoskeletal manifestations and ocular manifestations in Chinese patients might differ from that of patients from other regions. Besides, we also found clubbing fingers and optic neuritis in some NLRP3-AID patients, which were not commonly mentioned in previous reports. Conclusion In our study, we expanded the clinical spectrum as well as the genetic pathogenic variants of NLRP3-AID. We also found that there were some differences between Chinese patients and patients from other regions, and that Chinese patients were more likely to develop severe symptoms.

Co and Co9S8 nanoparticles uniformly embedded in S, N-doped porous carbons (Co/Co9S8@SNC) were fabricated by pyrolytic treatments of [Co(tdc)(bpy)]n2 (Co2+ is taken as the central ion, 2,5-thiophenedicarboxylic acid (tdc) and 4,4-bipyridine (bpy) are taken as the organic ligands) at 3 temperatures: 800 °C, 900 °C and 1000 °C. Among samples obtained, Co/Co9S8@SNC-900 from pyrolysis at 900 °C shows the highest proportion of Co and N atoms in form of Co nanoparticles and Pyridine-N. Due to the coordination between Pyridine-N and Co atoms, Co/Co9S8@SNC-900 has the best ORR/OER bifunctional electrocatalytic activity, conductivity and stability with the aid of the synergy of Co9S8 nanoparticles and C-S-C. Electrochemical test results show that the ORR limit current density of Co9S8@SNC-900 is 5.2 mA cm−2, which is close to commercial Pt/C (20 wt.%). In the OER tests, the overpotential of Co/Co9S8@SNC-900 at 10 mA cm−2 is 0.31 V, which is lower than that of RuO2. Co/Co9S8@SNC-900 also shows the best conductivity and pore volume. In application of Zn-air batteries (ZABs), Co/Co9S8@SNC-900 shows better maximum power density (106.6 mW cm−2) and stability than Pt/C + RuO2 catalyst.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1)-related multiple arterial stenoses is a rare clinical syndrome in which global arterial calcification begins in infancy, with a high probability of early mortality, and hypophosphatemic rickets develops later in childhood. The vascular status of an ENPP1-mutated patient when they enter the rickets phase has not been thoroughly explored. In this study, we presented a case of an adolescent with an ENPP1 mutation who complained of uncontrolled hypertension. Systematic radiography showed renal, carotid, cranial, and aortic stenoses as well as random calcification foci on arterial walls. The patient was incorrectly diagnosed with Takayasu’s arteritis, and cortisol therapy had little effect on reducing the vascular stenosis. As a result, phosphate replacement, calcitriol substitution, and antihypertensive medication were prescribed, and the patient was discharged for further examination. This research presented the vascular alterations of an ENPP1-mutanted patient, and while there is less calcification, intimal thickening may be the primary cause of arterial stenosis.

Abstract Background Transient antenatal Bartter’s syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation. Case presentation We encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter’s syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter’s syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal. Conclusions We reported the first Chinese case of transient antenatal Bartter’s syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.

Low permittivity microwave dielectric ceramics (MWDCs) are attracting great interest because of their promising applications in the new era of 5G and IoT. Although theoretical rules and computational methods are of practical use for permittivity prediction, unsatisfactory predictability and universality impede rational design of new high-performance materials. In this work, based on a dataset of 254 single-phase microwave dielectric ceramics (MWDCs), machine learning (ML) methods established a high accuracy model for permittivity prediction and gave insights of quantitative chemistry/structure-property relationships. We employed five commonly-used algorithms, and introduced 32 intrinsic chemical, structural and thermodynamic features which have correlations with permittivity for modeling. Machine learning results help identify the permittivity decisive factors, including polarizability per unit volume, average bond length, and average cell volume per atom. The feature-property relationships were discussed. The optimal model constructed by support vector regression with radial basis function kernel was validated its superior predictability and generalization by verification dataset. Low permittivity material systems were screened from a dataset of ∼3300 materials without reported microwave permittivity by high-throughput prediction using optimal model. Several predicted low permittivity ceramics were synthesized, and the experimental results agree well with ML prediction, which confirmed the reliability of the prediction model.

Background: Mucopolysaccharidosis Type II (MPS II) is a rare, progressive and ultimately fatal X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. This report conducted a retrospective analysis to investigate the clinical characteristics, genotypes and management strategies in a large cohort of Chinese patients with MPS II.Methods: In this study, we explored 130 Chinese patients with MPS II between September 2008 and April 2022. Clinical manifestations, auxiliary examination, IDS pathogenic gene variants and IDS enzyme activity, surgical history were analysed in the study.Results: A total of 130 patients were enrolled and the mean age at diagnosis was 5 years old. This study found the most common symptoms in our patients were claw-like hands, followed by coarse facial features, birthmarks (Mongolian spot), delayed development, inguinal or umbilical hernia. The most commonly cardiac manifestations were valve abnormalities, which were mitral/tricuspid valve regurgitation (71.9%) and aortic/pulmonary valve regurgitation (36.8%). We had found 43 different IDS pathogenic gene variants in 55 patients, included 16 novel variants. The variants were concentrated in exon 9 (20% = 11/55), exon 3 (20% = 11/55) and exon 8 (15% = 8/55). A total of 50 patients (38.5%) underwent surgical treatment, receiving a total of 63 surgeries. The average age of first surgery was 2.6 years, and the majority of surgery (85.7%, 54/63) was operated before 4 years old. The most common and earliest surgery was hernia repair. Three patients were died of respiratory failure.Conclusion: This study provided additional information on the clinical, cardiac ultrasound and surgical procedure in MPS II patients. Our study expanded the genotype spectrum of MPS II. Based on these data, characterization of MPS II patients group could be used to early diagnosis and treatment of the disease.

Distant metastasis is the main cause of death in non-small cell lung cancer (NSCLC) patients. The mechanism of metastasis-associated protein 1(MTA1) in NSCLC has not been fully elucidated. This study aimed to reveal the mechanism of MTA1 in the invasion and metastasis of NSCLC.Bioinformatics analysis and our previous results showed that MTA1 was highly expressed in NSCLC tissues and correlated with tumor progression. Knockout of MTA1 by CRISPR/Cas9 significantly inhibited the migration and invasion of H1299 cells, but enhanced cell adhesion. Stable overexpression of MTA1 by lentivirus transfection had opposite effects on migration, invasion and adhesion of A549 cells. The results of in vivo experiments in nude mouse lung metastases model confirmed the promotion of MTA1 on invasion and migration. Tight junction protein 1 (TJP1) was identified by immunoprecipitation and mass spectrometry as an interacting protein of MTA1 involved in cell adhesion. MTA1 inhibited the expression level of TJP1 protein and weakened the tight junctions between cells. More importantly, the rescue assays confirmed that the regulation of MTA1 on cell adhesion, migration and invasion was partially attenuated by TJP1.In Conclusion, MTA1 inhibits the expression level of TJP1 protein co-localized in the cytoplasm and membrane of NSCLC cells, weakens the tight junctions between cells, and changes the adhesion, migration and invasion capabilities of cells, which may be the mechanism of MTA1 promoting the invasion and metastasis of NSCLC. Thus, targeting the MTA1-TJP1 axis may be a promising strategy for inhibiting NSCLC metastasis.

Abstract Objective Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity. Materials and methods MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan–Meier survival curves. The publication bias was examined by Egger’s test. Results Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542–1.969, P

Abstract Background Systematic lymph node dissection is an important part of radical resection for lung cancer. Insufficient incision of the mediastinal pleura results in a tapered or tunnel-like operation surface, which increases the difficulty of uniportal video-assisted thoracoscopic mediastinal lymph node dissection. The objective of this study was to report our concept of broad exposure and investigate the efficacy and safety of this concept in uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection. Methods We retrospectively analyzed the clinical data of the 204 non-small cell lung cancer patients who underwent uniportal video-assisted thoracoscopic surgery for anatomical lobectomy and systematic lymph node dissection following the concept of broad exposure. SPSS 23.0 software was used for statistical analysis. Results All operations were completed under uniportal video-assisted thoracoscopic surgery following the concept of broad exposure. The median surgery time was 102 (range, 76–285) minutes and the median blood loss was 50 (range, 20–900) milliliters. The median chest tube duration time was 2 (range, 1–6) days, the median postoperative hospital duration time was 5 (range, 4–10) days. The median number of dissected lymph node stations and dissected lymph nodes were 8 (range,6–9) and 15(range,12–19), respectively. The median number of dissected mediastinal lymph nodes stations and dissected mediastinal lymph nodes were 5(range,3–6) and 11(range,10–15), respectively. The up-staging rate of N staging was 6.86%. The postoperative complication rate was 10.29% and there was no perioperative death. Conclusions According to our results, it’s effective and safe to perform uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection following the concept of broad exposure. This new concept not only emphasizes sufficient exposure, but also focuses on protection of important tissues.

Abstract Background Systemic juvenile idiopathic arthritis (sJIA) has many clinical features overlapping with familial Mediterranean fever (FMF), which is caused by mutations in MEFV gene. And FMF patients were easily misdiagnosed as sJIA in China. So we speculate that MEFV is critical genetic background for sJIA and influences patients’ severity. In this study, we aim to figure out whether MEFV mutations are risk factor for the occurrence of sJIA and to study the association of MEFV mutations with disease severity of sJIA patients. Methods The present study includes 57 sJIA children and 2573 healthy controls. Odd ratio with 95% confidence interval based on allelic frequency of MEFV mutations or variants was used to evaluate their contribution to sJIA susceptibility. Meta-analysis was then performed to reach comprehensive conclusion. All included sJIA patients were grouped by presence and number of MEFV mutations. Clinical data and indicators of disease severity were compared among different groups. Multiple linear regression method was used to find out whether the number of MEFV variants is associated with the severity of sJIA. Kaplan-Meier curves and log rank test were used to estimate the probability of the first relapse. Results The MEFV mutations of our subjects predominantly existed in exons 2 and 3. No significant difference was found in allelic frequency between sJIA children and healthy controls. Meta-analysis demonstrated that p.M694V/I was a risk factor for sJIA (pooled OR: 7.13, 95% CI: 3.01–16.89). The relative period of activity was significantly lower in the one mutation group than those with more than one mutation (p = 0.0194). However, no relevance was found in multiple linear regression models. Conclusions The mutation p.M694V/I in MEFV might be a risk factor for sJIA. SJIA patients carrying more than one heterozygous mutation in MEFV tend to be more severe than those containing only one, but studies in other cohort of patients need to be performed to validate it.

ObjectiveThis study aimed to assess the efficacy and safety of 2 Janus kinase (JAK) inhibitors (jakinibs) tofacitinib and ruxolitinib in the treatment of type I interferonopathies patients including STING-associated vasculopathy with onset in infancy (SAVI), Aicardi-Goutières syndrome (AGS), and spondyloenchondrodysplasia with immune dysregulation (SPENCD).MethodsA total of 6 patients were considered in this study: 2 patients with SAVI, 1 patient with AGS1, 1 patient with AGS7, and 2 patients with SPENCD. Clinical manifestations, laboratory investigations, radiology examinations, treatment, and outcomes were collected between November 2017 and November 2021 in Peking Union Medical College Hospital. The disease score for patients with SAVI and AGS scale for patients with AGS were documented. The expression of 6 interferon-stimulated genes (ISGs) was assessed by real-time PCR.ResultsThree patients (1 patient with SAVI, 2 patients with AGS) were treated with ruxolitinib and 3 patients (1 patient with SAVI, 2 patients with SPENCD) were treated with tofacitinib. The mean duration of the treatment was 2.5 years (1.25–4 years). Upon treatment, cutaneous lesions and febrile attacks subsided in all affected patients. Two patients discontinued the corticoid treatment. Two patients with SAVI showed an improvement in the disease scores (p

Abstract Background Primary immunodeficiency diseases (PIDs) patients may show systemic lupus erythematosus (SLE)-like autoimmunity disorders, such as cytopenias, as well as polyarthritis, which leads to concerns of misdiagnosis. We diagnosed three RALD cases between 2015 and 2018, who were suspected as SLE and summarized clinical characteristics. Methods We collected and analyzed the clinical data of the 3 cases. DNA was extracted from the patients’ and their parents’ peripheral blood as well as oral mucosa cells, hair follicles, and nails. Genes were detected with the application of gene trapping high-throughput sequencing using PIDs panel and suspicious gene or mutation was further verified by Sanger sequencing. Results 1. Clinical features: On the one hand, the patients presented with severe thrombocytopenia, facial erythema, arthritis, positive autoantibodies and other manifestations, supporting the diagnosis of SLE. On the other hand, symptoms including early onset ages, recurrent infections, lymphadenopathy, hepatosplenomegaly, monocytosis and hypergammaglobulinemia, were common observed in PIDs. 2. Gene analysis: NRAS mutations (c.38G > A, p.G13D or c.37G > T, p.G13C) were found in the blood of the patients. Besides, the same set of mutations was detected in buccal mucosa of patient 1 and nails of patient 3 while the frequency was much lower. However, no mutation was found in other tissues or in their parents’ blood. Consequently, they were NRAS somatic mutated RALD. Conclusions For those early-onset SLE-like patients with predominant hematologic disorders, monocytosis, recurrent infectious history, accompanied with hepatosplenomegaly and lymphadenopathy, a genetic screening of PIDs might be required.

Hypersonic vehicles are drawing more and more attention now and for the near future, especially in the low-altitudes near space, from 20 km to 45 km. The reliable separation of the protecting shroud from the hypersonic vehicle is a prerequisite and critical issue for the success of the entire flight mission. The unsteady multi-body separation characteristics and flow characteristics of hypersonic shroud separation at Mach 7.0 are investigated based on numerical simulation in this paper. The improved delayed detached eddy simulation (IDDES) method, dynamic hybrid overset mesh method, and HLLE++ numerical scheme are used to ensure numerical accuracy. Numerical results show that there are four types of vortexes and three types of shock waves inside the shrouds during the separation process, which generate complex shock wave/vortex/boundary layer interactions. Further, an unsteady process of the expansion-transfer-dissipation of an A-type vortex is found, which is the result of strong shock/vortex/boundary layer interactions. The adverse pressure gradient is the root cause driving the generation and transfer of the A-type vortex during the shroud separation. Furthermore, the transfer process of the A-type vortex only lasts for 5.52 ms but causes a large disturbance to the aerodynamic force of the shroud. The results of this paper could provide a reference for the design of near-space hypersonic vehicles.

The internal weapon bay is widely used in modern aircraft; however, because the unsteady flows of the cavity would cause dangerous store separation and intense aerodynamic noise, the leading-edge spoiler is an easy and efficient passive flow-control method. The flow control of the leading-edge flat spoiler before the cavity of a low-aspect-ratio flying-wing aircraft is investigated based on numerical simulation. Numerical results show that the leading-edge flat spoiler completely changes the cavity flow; it obviously lifts up the shear layer and reduces the pressure inside the cavity. For the store separation from the weapon bay, the leading-edge flat spoiler is a very good passive flow-control method that curbs the nose-up trend of the store and produces a safe and stable store separation. Besides, the leading-edge spoiler reduces the noise in the rear of the cavity (max 8.2 dB), but increases the noise in the middle of the cavity (max 11.3 dB). In addition, the leading-edge spoiler brings in a large drag increase to the aircraft (39.41% when the height of spoiler is 0.2 m), which would affect the operational stability of the aircraft. The results of this paper could provide a reference for the flow control of weapon bays and the design of aircraft.

Objective: Monogenic autoinflammatory diseases (AIDs) are inborn disorders caused by innate immunity dysregulation and characterized by robust autoinflammation. We aimed to present the phenotypes and genotypes of Chinese pediatric monogenic AID patients.Methods: A total of 288 pediatric patients clinically suspected to have monogenic AIDs at the Department of Pediatrics of Peking Union Medical College Hospital between November 2008 and May 2019 were genotyped by Sanger sequencing, and/or gene panel sequencing and/or whole exome sequencing. Final definite diagnoses were made when the phenotypes and genotypes were mutually verified.Results: Of the 288 patients, 79 (27.4%) were diagnosed with 18 kinds of monogenic AIDs, including 33 patients with inflammasomopathies, 38 patients with non-inflammasome related conditions, and eight patients with type 1 interferonopathies. Main clinical features were skin disorders (76%), musculoskeletal problems (66%), fever (62%), growth retardation (33%), gastrointestinal tract abnormalities (25%), central nervous system abnormalities (15%), eye disorders (16%), ear problems (9%), and cardiopulmonary disorders (8%). The causative genes were ACP5, ADA2, ADAR1, IFIH1, LPIN2, MEFV, MVK, NLRC4, NLRP3, NLRP12, NOD2, PLCG2, PSMB8, PSTPIP1, TMEM173, TNFAIP3, TNFRSF1A, and TREX1.Conclusions: The present study summarized both clinical and genetic characteristics of 18 kinds of monogenic AIDs found in the largest pediatric AID center over the past decade, with fever, skin problems, and musculoskeletal system disorders being the most prevalent clinical features. Many of the mutations were newly discovered. This is by far the first and largest monogenic AID report in Chinese pediatric population and also a catalog of the phenotypic and genotypic features among these patients.

Background: Familial Mediterranean fever (FMF) is an inherited auto-inflammatory disorder and is extremely rare in Chinese. This study aimed to investigate the demographic, clinical, and genetic features of FMF in a series of Chinese pediatric patients.Methods: This was a retrospective case series of children with recurrent febrile or inflammatory episodes and referred to the Peking Union Medical College Hospital between 06/2013 and 06/2018. All suspected patients were genetically diagnosed and met the Tel-Hashomer criteria for FMF. Demographic, clinical, genetic, and treatment characteristics were collected. Descriptive statistics were used.Results: Eleven patients were included (seven boys and four girls). The median age at the time of disease onset was 7.1 (range, 3–12) years, while the median age at diagnosis was 10.9 (range, 6–15) years. The median delay in diagnosis was 2.1 years (range, 6 months to 6.7 years). Fever (100%, 11/11) was the most common symptom, followed by joint pain (63.6%, 7/11), rash (54.5%, 6/11), abdominal pain (36.4%, 4/11), and oral ulcers (18.2%, 2/11), without evidence of amyloidosis. C-reactive protein (81.8%, 9/11) and erythrocyte sedimentation (90.9%, 10/11) were increased during attacks. All patients harbored one to five different MEFV mutations, with E148Q and L110P being the most frequent. A novel non-synonymous mutation F636Y in exon 10 was discovered. Favorable responses to colchicine was observed in all six treated patients.Conclusion: The most common variants in our study were E148Q and L110P. F636Y may found for the first time. Colchicine led to favorable responses in all treated patients.

Tin(II) monosulfide (SnS) nanosheets were synthesized using SnCl4•5H2O and S powders as raw materials in the presence of H2O via a facile chemical bath method. Orthorhombic phase SnS nanosheets with a thickness of ~100 nm and lateral dimensions of 2~10 μm were obtained by controlling the synthesis parameters. The formation of a SnO2 intermediate is key to the valence reduction of Sn ions (from IV to II) and the formation of SnS. The gas sensors fabricated from SnS nanosheets exhibited an excellent response of 14.86 to 100 ppm ethanol vapor when operating at 160 °C, as well as fast response and recovery times of 23 s and 26 s, respectively. The sensors showed excellent selectivity for the detection of ethanol over acetone, methanol, and ammonia gases, which indicates the SnS nanosheets are promising for high-performance ethanol gas sensing applications.

In this work, we report a passive wireless eddy current proximity sensor based on inductive-capacitive (LC) resonance using a low temperature co-fired ceramic (LTCC) technology. The operation principle of the LC proximity sensor to the metal targets was comprehensively discussed through electromagnetic simulation and circuit model. Copper and aluminum were selected as the metal target materials for the measurements. Circular copper plates with different diameters and thickness were used to investigate the influence of the surface area and thickness of the target on the sensitivity. The decreases of the sensitivity with the decrease of the surface area and thickness were observed. The LC proximity sensor showed a high sensitivity of 11.2 MHz/mm for the proximity distance of 1–3 mm, and large detection range up to 10 mm. The developed LC proximity sensor is promising for passive wireless metal detections and proximity measurements under harsh environments.

This work reports a novel wireless microfluidic biosensor based on low temperature co-fired ceramic (LTCC) technology. The wireless biosensor consists of a planar spiral inductor and parallel plate capacitor (LC) resonant antenna, which integrates with microchannel bends in the LTCC substrate. The wireless response of the biosensor was associated to the changes of its resonant frequency due to the alteration in the permittivity of the liquid flow in the microchannel. The wireless sensing performance to different organic liquids with permittivity from 3 to 78.5 was presented. The measured results are in good agreement with the theoretical calculation. The wireless detection for the concentration of glucose in water solution was investigated, and an excellent linear response and repeatability were obtained. This kind of LC wireless microfluidic sensor is very promising in establishing wireless lab-on-a-chip for biomedical and chemical applications.

OBJECTIVE:The aim of the current study was to determine the contributions of several common mutations in the Mediterranean fever (MEFV) gene, namely, E148Q, M680I, M694V and V726A, to ankylosing spondylitis (AS) susceptibility. METHODS:Two investigators independently searched the literature regarding the association of MEFV with AS in the PubMed, EMBASE, Web of Science, and Scopus databases. They independently selected eligible articles and then extracted data from the included studies. The associations between MEFV mutations and AS risk were assessed with odds ratios (ORs) and 95% confidence intervals (95% CI). Further analyses were conducted with STATA 12.0 software (Stata Corp.; College Station, Texas, USA). RESULTS:Four mutations (E148Q, M680I, M694V and V726A) were genotyped in 869 AS cases and 879 controls from the 8 eligible studies. Of the four mutations, M694V (pooled OR: 3.330, 95% CI: 2.129-5.208) was found to be associated with AS through overall analysis. However, the other mutations demonstrated no relation with AS (pooled ORs: 1.295, 1.258, 1.778; 95% CI: 0.886-1.891, 0.688-2.298 and 0.938-3.371). No significant publication bias was discovered in the meta-analysis. CONCLUSIONS:The present study indicates that the MEFV M694V mutation may contribute to the pathogenesis of AS. The associations between the other mutations and AS need to be validated with more relevant and well-designed studies.

This paper presents a kind of passive wireless pressure sensor comprised of a planar spiral inductor and a cavity parallel plate capacitor fabricated through low-temperature co-fired ceramic (LTCC) technology. The LTCC material with a low Young’s modulus of ~65 GPa prepared by our laboratory was used to obtain high sensitivity. A three-step lamination process was applied to construct a high quality cavity structure without using any sacrificial materials. The effects of the thickness of the sensing membranes on the sensitivity and detection range of the pressure sensors were investigated. The sensor with a 148 μm sensing membrane showed the highest sensitivity of 3.76 kHz/kPa, and the sensor with a 432 μm sensing membrane presented a high detection limit of 2660 kPa. The tunable sensitivity and detection limit of the wireless pressure sensors can meet the requirements of different scenes.