LASSO-derived nomogram for early identification of pediatric monogenic lupus.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

Interference of holon strings in 2D Hubbard model.

The 2D Hubbard model with large repulsion is an important problem in condensed matter physics. At half filling, its ground state is an antiferromagnet (AMF). The dope AMF below half filling is believed to capture the physics of highTcsuperconductors. And the fermion excitation of this dope AMF is theorized as splitting up into holons and spinons that carry charge and spin separately. It is believed that these exotic holons and spinons are the origins of the unusual properties of highTcsuperconductors. Despite the interests in holons and spinons, the direct observations of these excitations remain difficult in solid state experiments. Here, we show that with the rapid advances in the experimental techniques in cold atoms, the direct observation of holons is possible in quantum quench dynamic processes in cold atom settings. We show that the well-known holon-strings generated by the motion of a holon as well as their interferences can be detected by the measurements spin-spin correlations and demonstrate the presence of the Marshall phase associated with a holon string reflecting an underlying AMF background. Moreover, we show that the interferences of the holon strings make a holon propagate anisotropically, with a diffusion pattern clearly distinct from that of spinless fermions. At the same time, we show that these interferences lead to a large suppression in magnetic order in the region swept through by the strings (even to about 95% for some bond). We further demonstrate the Marshall phase of the holon-strings by comparing the dynamics of holon in thetJmodel with that of the so-calledσtJ-model, which is thetJmodel with the Marshall phase removed. The holons in these models propagate entirely differently.

Phenotype of Takayasu-like vasculitis and cardiopathy in patients with Blau syndrome.

OBJECTIVES: We aimed to determine the prevalence of cardiovascular involvement in our Blau syndrome (BS) cohort and provide detailed analysis of their cardiovascular manifestations and outcome. We also tried to find out the risk factors for developing cardiovascular involvement. METHODS: Clinical manifestations, laboratory findings, and treatments were reviewed. Clinical features were compared between children with cardiovascular involvement and those without angiocardiopathy. RESULTS: A total of 38 BS children were eligible for final analysis. Among them, 13 (34.2%) developed Takayasu-like vasculitis and/or cardiopathy. Compared with those without angiocardiopathy, recurrent fever was more frequent in BS patients with cardiovascular involvement (p < 0.001). What is more, tumor necrosis factor alpha antagonists (anti-TNF) were more urgently needed in children with cardiovascular involvement (p = 0.015). BS patients with cardiovascular involvement include 4 with Takayasu-like vasculitis and 9 with cardiopathy. The onset of cardiovascular manifestations ranged from 0.75 to 18.5 years of age, with most cases occurring before school period. Symptoms were elusive and lacked specificity, such as dizziness, short of breath, and edema. Some patients were even identified because of the unexpected hypertension during follow-up. Cardiopathy and vasculitis occurred in patients with different genotypes. Imaging changes were discovered before the presentation of the typical triad in 3/4 patients with Takayasu-like vasculitis. Three children developed left ventricular dysfunction with decreased left ventricular ejection fraction. Combination of glucocorticoids and methotrexate with anti-TNF agents is a common treatment option for these BS patients. In the cohort, BS-related cardiovascular involvement was controlled well, with cardiac structural and functional abnormalities completely recovered and slower progression of vasculitis lesions. CONCLUSION: Cardiovascular manifestations is not rare in BS patients. Because of its insidious onset, a systematic and comprehensive assessment of cardiovascular involvement should be performed in newly diagnosed patients with BS. Aggressive initiation of anti-TNF agents may be beneficial to improve the prognosis. Key Points • About 34.2% patients with Blau syndrome developed Takayasu-like vasculitis and/or cardiopathy. • Compared with those without angiocardiopathy, recurrent fever and application of anti-TNF agents were more frequent in BS patients with cardiovascular involvement (p < 0.001, p = 0.015) • Regular assessment of cardiovascular involvement is extremely necessary because of its insidious onset.

Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression. CASE PRESENTATION: We describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6. CONCLUSIONS: Ruxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS.

Efficacy and safety of thalidomide in children with monogenic autoinflammatory diseases: a single-center, real-world-evidence study.

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.

Prediction of acrylamide content in potato chips using near-infrared spectroscopy.

Acrylamide (ACR), a neurotoxin with carcinogenic properties that can affect fertility, is commonly found in fried and baked foods such as potato chips. This study was carried out to predict the ACR content in fried and baked potato chips using near-infrared (NIR) spectroscopy. Effective wavenumbers were identified using competitive adaptive reweighted sampling (CARS) and the successive projections algorithm (SPA). Six wavenumbers (12799 cm-1, 12007 cm-1, 10944 cm-1, 10943 cm-1, 5801 cm-1, and 4332 cm-1) were selected using the ratio (λi/λj) and difference (λi-λj) of any two wavenumbers from the CARS and SPA results. First, partial least squares (PLS) models were established based on full spectral wavebands (12799-4000 cm-1), and the prediction models were subsequently redeveloped based on effective wavenumbers to predict ACR content. Results showed that the full and selected wavenumbers-based PLS models obtained the coefficient of determination (R2) of 0.7707 and 0.6670, respectively, and the root mean square errors of prediction (RMSEP) of 53.0442 µg/kg and 64.3810 µg/kg, respectively, in the prediction sets. The results of this work demonstrate the suitability of NIR spectroscopy as a non-destructive method for predicting ACR content in potato chips.

Deep learning radiomics model based on breast ultrasound video to predict HER2 expression status.

Purpose: The detection of human epidermal growth factor receptor 2 (HER2) expression status is essential to determining the chemotherapy regimen for breast cancer patients and to improving their prognosis. We developed a deep learning radiomics (DLR) model combining time-frequency domain features of ultrasound (US) video of breast lesions with clinical parameters for predicting HER2 expression status. Patients and Methods: Data for this research was obtained from 807 breast cancer patients who visited from February 2019 to July 2020. Ultimately, 445 patients were included in the study. Pre-operative breast ultrasound examination videos were collected and split into a training set and a test set. Building a training set of DLR models combining time-frequency domain features and clinical features of ultrasound video of breast lesions based on the training set data to predict HER2 expression status. Test the performance of the model using test set data. The final models integrated with different classifiers are compared, and the best performing model is finally selected. Results: The best diagnostic performance in predicting HER2 expression status is provided by an Extreme Gradient Boosting (XGBoost)-based time-frequency domain feature classifier combined with a logistic regression (LR)-based clinical parameter classifier of clinical parameters combined DLR, particularly with a high specificity of 0.917. The area under the receiver operating characteristic curve (AUC) for the test cohort was 0.810. Conclusion: Our study provides a non-invasive imaging biomarker to predict HER2 expression status in breast cancer patients.

Detection of the 5-hydroxymethylfurfural content in roasted coffee using machine learning based on near-infrared spectroscopy.

Since 5-hydroxymethylfurfural (5-HMF) is carcinogenic to humans, its detection in foods is essential. This study performed near-infrared (NIR) spectroscopy (11998-4000 cm-1) to determine the 5-HMF content in roasted coffee. The random forest (RF) was used to extract important wavenumbers, after which three machine learning models (ordinary least square (OLS), support vector machine (SVM), and RF) were established for the prediction. RF obtained the best prediction results (Rc2 = 0.98 and Rp2 = 0.92) compared with OLS and SVM and effectively extracted the important wavenumbers (11667 cm-1, 11666 cm-1, 10905 cm-1, 7096 cm-1, 7095 cm-1, 7094 cm-1, 7093 cm-1, 7092 cm-1, 5054 cm-1, 5026 cm-1, 5025 cm-1, and 5024 cm-1). The results demonstrated that machine learning models based on NIR spectroscopy could provide a non-destructive approach for determining 5-HMF content in roasted coffee.

The effect of antinuclear antibody titre and its variation on outcomes in children with primary immune thrombocytopenia.

Antinuclear antibody (ANA) can be positive in children with primary immune thrombocytopenia (ITP), but the effect of ANA titre and its variation on outcomes of children with primary ITP remains unclear. Here, we conducted a single-centre retrospective cohort study of children with primary ITP at the Peking Union Medical College Hospital in China. A total of 324 children with primary ITP included in this study were followed for a median time of 25 months. In this cohort, 39.2% had an ANA titre of 1:160 or higher. Results from a generalized estimating equation model revealed that patients with higher ANA titres had lower platelet counts at onset but a higher recovery rate of subsequent platelet counts. Results from Cox regression models adjusted for potential confounders revealed that patients with ANA titres of 1:160 or more were more likely to develop to autoimmune disease (AID) than those without, and the risk of AID development increased with the rise of ANA titres (p value for trend less than 0.001). These data highlight the predictive value of ANA titre for platelet counts and the risk of AID development in children with primary ITP.

Clinical phenotypes and prognosis of cytomegalovirus infection in the pediatric systemic lupus erythematosus: a longitudinal analysis.

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.

Differential diagnosis of gallbladder neoplastic polyps and cholesterol polyps with radiomics of dual modal ultrasound: a pilot study.

PURPOSE: To verify whether radiomics techniques based on dual-modality ultrasound consisting of B-mode and superb microvascular imaging (SMI) can improve the accuracy of the differentiation between gallbladder neoplastic polyps and cholesterol polyps. METHODS: A total of 100 patients with 100 pathologically proven gallbladder polypoid lesions were enrolled in this retrospective study. Radiomics features on B-mode ultrasound and SMI of each lesion were extracted. Support vector machine was used to classify adenomas and cholesterol polyps of gallbladder for B-mode, SMI and dual-modality ultrasound, respectively, and the classification results were compared among the three groups. RESULTS: Six, eight and nine features were extracted for each lesion at B-mode ultrasound, SMI and dual-modality ultrasound, respectively. In dual-modality ultrasound model, the area under the receiver operating characteristic curve (AUC), classification accuracy, sensitivity, specificity, and Youden's index were 0.850 ± 0.090, 0.828 ± 0.097, 0.892 ± 0.144, 0.803 ± 0.149 and 0.695 ± 0.157, respectively. The AUC and Youden's index of the dual-modality model were higher than those of the B-mode model (p < 0.05). The AUC, accuracy, specificity and Youden's index of the dual-modality model were higher than those of the SMI model (p < 0.05). CONCLUSIONS: Radiomics analysis of the dual-modality ultrasound composed of B-mode and SMI can improve the accuracy of classification between gallbladder neoplastic polyps and cholesterol polyps.

Early recombinant human growth hormone treatment improves mental development and alleviates deterioration of motor function in infants and young children with Prader-Willi syndrome.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader-Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS. METHODS: A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m2/day for first four weeks, and 1 mg/m2/day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed. RESULTS: Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in < 9-month group were significantly higher than ≥ 9-month group. Mild to moderate severity adverse drug reactions were reported in six patients. CONCLUSION: Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients < 9 months old.

Early indicators of neonatal-onset hereditary thrombotic thrombocytopenia purpura.

Background: Neonatal-onset hereditary thrombotic thrombocytopenia purpura (hTTP) is often misdiagnosed due to its rarity. It begins with jaundice, similar to infants with ABO incompatibility. Objective: To explore early indicators of neonatal-onset hTTP. Methods: This study was a retrospective case series of newborns with hTTP and ABO incompatibility. We compared the clinical characteristics and laboratory test results in these two groups. Results: This study included four hTTP patients and 20 ABO-incompatible newborns. All patients manifested disease during the neonatal period. There were equal numbers of males and females in each group. hTTP newborns showed earlier (median difference, 57.0 h; 95% confidence interval [CI], 24.0-65.0) and more severe hyperbilirubinemia (mean difference, 8.0 mg/dl; 95% CI, 3.8-12.1) than ABO-incompatible newborns. In hTTP newborns, anemia was more common within 7 days after birth than in ABO-incompatible newborns (odds ratio, 25.4; 95% CI, 1.2-551.6), and platelet counts were lower than in ABO-incompatible newborns (17 ± 12 × 109/L vs. 291 ± 76 × 109/L). The levels of serum creatinine (median difference, 51.8 µmol/L; 95% CI, 16.0-109.4) and blood urea nitrogen (median difference, 5.7 mmol/L; 95% CI, 2.8-38.7) were higher in hTTP newborns than in ABO-incompatible newborns. There were no significant differences in white blood cell counts, C-reactive protein, alanine aminotransferase, or albumin levels. Conclusions: Severe jaundice soon after birth, early anemia, and severe thrombocytopenia were more common in newborns with hTTP than ABO incompatibility. These are distinguishing early features of hTTP.

The quantum dynamics of two-component Bose-Einstein condensate: anSp(4,R)symmetry approach.

The compact groups such asSU(n) andSO(n) groups have been heavily studied and applied in the study of quantum many body systems. However, the non-compact groups such as the real symplectic groups are less touched. In this paper, it is revealed that the quantum dynamics of two-component Bose-Einstein condensate can be described by a non-compact real symplectic groupSp(4,R). With this group, an explicit form of the wavefunction in any time of the evolution can be given, meanwhile, this whole time evolution can be shown to correspond to a trajectory in a six-dimensional manifold. By introducing a polar coordinate, we can visualize this six-dimensional manifold in 2d unit disk and reveal the relation between the behavior of the trajectory in this manifold and the eigenenergies of the Hamiltonian. Furthermore, the time evolution of expectation value of a physical observable such as number operator is proven closely related to the behavior of the trajectory in this manifold.

Expression of Serum Omentin, CTRP9, and Vaspin in Patients with Polycystic Ovary Syndrome.

Objective: To explore the relationship between serum omentin, C1q/tumor necrosis factor-related protein-9 (CTRP9), and visceral fat-specific serine protease inhibitor (vaspin) levels in different phenotypes in patients with polycystic ovary syndrome (PCOS). Methods: One hundred PCOS patients treated at our hospital's clinic of reproductive medicine were chosen and included into the research group, and 100 healthy women who came for physical examination during the same time period were included into the control group. According to the definition of obesity by the WHO (body mass index (BMI) ≥25 kg/m2), 100 patients with PCOS were equally divided into obese (study group A) and nonobese (study group B) groups. 100 healthy women were also divided into obese (control group A) and nonobese (control group B) groups with 50 patients each. Comparison among the 4 groups was performed in factors/indicators including the serum omentin, CTRP9, and vaspin levels and biochemical indexes (triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), total testosterone, and homeostasis model assessment of insulin resistance (HOMA-IR) levels), and the correlation analysis was conducted with omentin, CTRP9, and vaspin. Results: There was no significant difference in age, TG, TC, and LDL-C among the 4 groups (P > 0.05). The BMI, WHR, HDL-C, and omentin of the obese phenotype were significantly different from those of the nonobese phenotype (P < 0.05). Among the four groups, FINS, HOMA-IR, and vaspin in group A (obesity) was the highest, and the control group B (nonobese) was the lowest. There was no significant difference in the levels of study group B (nonobese) and control group A (obesity). The level of CTRP9 in the study group was significantly lower than that in the control group (P < 0.05). Taking serum omentin, CTRP9, and vaspin levels of patients in the study group as dependent variables, Pearson correlation analysis showed that the omentin level was negatively correlated with BMI, WHR, FINS, TG, TC, LDL-C, HOMA-IR, and TT levels (P < 0.05) and was positively correlated with the HDL-C level (P < 0.05); CTRP9 level was negatively correlated with BMI, TC, and HOMA-IR (P < 0.05) and was not correlated with age, WHR, FINS, TG, HDL-C, LDL-C, HOMA-IR, and TT levels. The vaspin level was positively correlated with BMI, WHR, FINS, TG, TC, LDL-C, HOMA-IR, and TT levels (P < 0.05) and negatively correlated with HDL-C levels (P < 0.05) and was not correlated with age. Conclusion: When compared with healthy people, PCOS patients have higher serum vaspin levels and lower CTRP9 levels; BMI, TC, LDL-C, FINS, TG, total testosterone, HDL-C levels, waist-to-hip ratio, and HOMA-IR are all closely related to serum vaspin and CTRP9 levels; increasing serum CTRP9 levels and decreasing vaspin levels help to slow progress and promote prognosis of the disease. Serum omentin level is connected with the obesity index but not with PCOS.

Clinical and genetic spectrum of 14 cases of NLRP3-associated autoinflammatory disease (NLRP3-AID) in China and a review of the literature.

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.

Janus Kinase Inhibitors in the Treatment of Type I Interferonopathies: A Case Series From a Single Center in China.

Objective: This 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). Methods: A 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. Results: Three 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 < 0.05). The erythrocyte sedimentation rate normalized in 2 patients with AGS. The interferon score (IS) was remarkably decreased in 2 patients with SPENCD (p < 0.01). Catch-ups with growth and weight gain were observed in 3 and 2 patients, respectively. Lung lesions improved in 1 patient with SAVI and remained stable in 3 patients. Lymphopenia was found in 3 patients during the treatment without severe infections. Conclusion: The JAK inhibitors baricitinib and tofacitinib are promising therapeutic agents for patients with SAVI, AGS, and SPENCD, especially for the improvement of cutaneous lesions and febrile attacks. However, further cohort studies are needed to assess the efficacy and safety.

Hypoxic ucMSC-secreted exosomal miR-125b promotes endothelial cell survival and migration during wound healing by targeting TP53INP1.

A hypoxic microenvironment is a common feature of skin wounds. Our previous study demonstrated that three-dimensional coculture of umbilical cord-derived mesenchymal stem cells (ucMSCs) and endothelial cells facilitates cell communication and host integration in skin tissue engineering. Here, we aimed to identify the mechanism by which ucMSCs affect endothelial cells under hypoxic conditions after skin injury. We demonstrate that hypoxia enhances the exosome-mediated paracrine function of ucMSCs, which increases endothelial cell proliferation and migration. In a mouse full-thickness skin injury model, ucMSC-derived exosomes can be taken up by endothelial cells and accelerate wound healing. Hypoxic exosomes lead to a better outcome than normoxic exosomes by promoting proliferation and inhibiting apoptosis. Mechanistically, microRNA-125b (miR-125b) transcription is induced by hypoxia in ucMSCs. After being packaged into hypoxic exosomes and transported to endothelial cells, miR-125b targets and suppresses the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1) and alleviates hypoxia-induced cell apoptosis. Inhibition of miR-125b-TP53INP1 interaction attenuates the protective effect of hypoxic exosomes. Moreover, artificial agomiR-125b can accelerate wound healing in vivo. Our findings reveal communication between ucMSCs and endothelial cells via exosomal miR-125b/TP53INP1 signaling in the hypoxic microenvironment and present hypoxic exosomes as a promising therapeutic strategy to enhance cutaneous repair.

Management of Follow-Up With Preterm Infants During the Outbreak in China.

Introduction: Coronavirus disease 2019 (COVID-19) swept Wuhan in January 2020. Other cities in China also suffered during the pandemic. Routine medical services were conducted in the Neonatal Intensive Unit (NICU) as usual, but the follow-up after discharge was seriously affected. Objective: To investigate the feasibility and effectiveness of a combination of online and face-to-face follow-up for preterm infants during the COVID-19 epidemic and to explore a follow-up pattern that can provide follow-up services while maximizing the protection of preterm infants and soothing the fear of their parents. Methods: Preterm infants (n = 35) whose first follow-up appointment was scheduled from February 1 to April 30, 2020, and preterm infants (n = 43) in the NICU follow-up group who were discharged from January 1, 2018, to January 31, 2020, who had a second or later routine follow-up appointment scheduled from February 1 to April 30, 2020, were enrolled. We provided a combination of online and face-to-face follow-up for preterm infants surveyed with the Wenjuanxing platform before and after the online follow-up and compared the first-time follow-up rate between the outbreak and the same period of the previous year. Results: Feeding and oral medicine and supplements were the most concerning problems of the parents of preterm infants. The anxiety level of the family was significantly decreased after online follow-up (P < 0.05). A total of 96.8% of parents were satisfied or very satisfied with online follow-up, and 95.2% of parents thought that online follow-up had answered all their questions. Only 35.5% of parents thought online follow-up could replace face-to-face follow-up. Conclusion: The combination of online and face-to-face follow-up alleviated the anxiety of the parents during the outbreak and achieved a similar first-time follow-up rate as the same period in 2019.

[Effect of breastfeeding on the development of infection-related diseases during hospitalization in late preterm infants in 25 hospitals in Beijing, China].

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, P=0.033). The multivariate logistic regression analysis showed that breastfeeding was an independent protective factor against infectious diseases (OR=0.534, P=0.004), while male sex, premature rupture of membranes, gestational diabetes mellitus, and asphyxia were risk factors for infectious diseases (OR=1.328, 5.386, 1.535, and 2.353 respectively, P < 0.05). CONCLUSIONS: Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.