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Purpose Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. Methods A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. Results Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. Conclusion To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

In this paper, a novel mask electrochemical additive and subtractive combined manufacturing technique was proposed. This is a machining method at the atomic level, and it can be used to produce metal microstructures with high profile accuracy and low surface roughness. Due to the accumulation of electric field lines during mask electrochemical deposition, the height of the edges of the microcolumns is usually twice or more the height of the central position in the deposition plane. A combined machining method based on the electric-field constraint of the mask is thus proposed to improve the accuracy of the profile and its surface roughness. The feasibility of the proposed method was verified by both simulations and experiment. The height difference between the column center and the surrounding layer on the surface of nickel microcolumns was reduced from 13 to 2 µm, and the roughness of the tops of the microcolumns was also improved. Experiments to examine electrolysis leveling were carried out to verify the correctness of the results of the simulations and theoretical calculations. Finally, the parameters were optimized using orthogonal experiments, and an array of nickel microcolumns with a diameter of 200 µm and a height of nearly 50 µm was obtained using these optimal parameters. The profile accuracy and surface roughness of the high-precision microcolumn array were improved by using the mask electrochemical additive and subtractive combined machining technique, and a high-precision microcolumn array structure was manufactured.

Accurate identification of priority areas for ecological restoration is an important prerequisite for ecological protection and restoration, but it is a current challenge in landscape planning. Northern Shaanxi, which is located in the middle of the Loess Plateau in China, was selected as a study area in this paper. A three-dimensional framework including natural potential, human disturbance, and landscape pattern factors was used to construct an ecological security evaluation index system, and spatial principal component analysis (SPCA) was used to quantitatively evaluate the ecological security levels of the study area. The ecological security assessment result was used as a resistance surface, and landscape elements were identified by morphological spatial pattern analysis (MSPA), minimum cumulative resistance (MCR) model and the gravity model. On this basis, priority areas for ecological restoration were identified by considering ecosystem security and the matching degree of landscape elements. The resulting area with low and moderately low security levels was 27,574.87 km

Whether peripheral immune cell subsets can predict pathological complete response (pCR) in breast cancer patients remains to be elucidated. We aimed to dissect the relationship between peripheral immune cell subsets and pCR.Two hundred and twenty-six eligible patients from two prospective clinical trials (SHPD001 and SHPD002) in China were randomly divided into a training cohort and a validation cohort. The breast cancer subtypes in this study included hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 95), HER2-positive (n = 100), and triple negative (n = 31) breast cancer. We defined the "Neo-Peripheral Adaptive Immune Score" for neoadjuvant chemotherapy (neoPAI Score) based on the percentages of CD4 + T cells, CD8 + T cells, B cells, and the CD4 + /CD8 + ratio in peripheral blood. We also evaluated the ability of the neoPAI Score derived from tumor-infiltrating immune cells (TIICs) to predict survival by employing The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database.In the training cohort, multivariate analysis showed that HR status [odds ratio (OR) 0.325; 95% confidence interval (CI) 0.135-0.761; P = 0.010], HER2 status (OR 2.657; 95% CI 1.266-5.730; P = 0.011), Ki67 index (OR 3.191; 95% CI 1.509-6.956; P = 0.003), histological grade (OR 2.297; 95% CI 1.031-5.290; P = 0.045) and neoPAI Score (OR 4.451; 95% CI 1.608-13.068; P = 0.005) were independent predictors of pCR. In the validation cohort, histological grade (OR 3.779; 95% CI 3.793-1.136 × 10The neoPAI Score defined by the percentages of peripheral immune cell subsets could be used as a potential biomarker for neoadjuvant chemotherapy efficacy.

Preeclampsia (PE) is characterized by placenta-mediated pregnancy complication. The only effective treatment for PE is the delivery of the placenta. However, this treatment may cause preterm birth and neonatal death. Therefore, preventing PE is needed. The mechanism of PE involves abnormal placentation, which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation. These mediators contribute to systemic vascular dysfunction, inflammatory responses, and excessive thrombin generation. Microparticles (MPs) are reportedly involved in PE by promoting the thromboinflammatory response. This study describes a strategy to prevent PE by reducing MP release using the recombinant protein, diannexin. Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation. Additionally, diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells. Moreover, in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice. Furthermore, diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro. These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.