Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
Humans ; Adenosine Deaminase/deficiency* ; Monocytes/cytology* ; Cell Differentiation ; Intercellular Signaling Peptides and Proteins/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Biomarkers/metabolism* ; Macrophages/metabolism* ; Pneumonia/metabolism*

Objective To noninvasively predict isocitrate dehydrogenase(IDH)status of glioma via combining imaging and clini-cal features before surgery,so as to provide basis for individualized clinical treatment decision.Methods A total of 47 patients with glioma confirmed by pathological and molecular genetic tests were included,including 20 with IDH mutant type and 27 with IDH wild type.After diffusion tensor imaging(DTI)scanning,fractional anisotropy(FA)and mean diffusivity(MD)values of tumor paren-chyma were calculated.Combining DTI parameters with MRI morphological features of tumor,blood neutrophil/lymphocyte ratio(NLR)and patient's age,binary logistic regression model was established to effectively predict IDH status of glioma patients before surgery.Results There were significant differences in FAmean/FANAWM,MDmin,NLR,tumor location and age between IDH mutant type and IDH wild type groups(P<0.05).The binary logistic regression model concluding,FAmean/FANAWM,MDmin,cystic degeneration,NLR and age,predicted IDH status of glioma with area under the curve(AUC)of 0.961 and 95%confidence interval(CI)of 0.914-1.00.Conclusion The regression model established via combining DTI,MRI morphological features and blood NLR has great performance in classifying IDH status of glioma,and can help predict IDH status noninvasively before surgery,so as to assist clinical individualized treatment.

Alzheimer's disease(AD), the most common neurodegenerative disease, has shown an increasing incidence among younger people. With the onset of disease, most patients' cognitive function will show a progressive decline, bringing a heavy burden to the society and the family. Studies have shown that fibroblast growth factor (FGF) may be involved in the pathogenesis of AD through multiple mechanisms. This article reviews the mechanism of FGF in AD, with the hope of providing new ideas for elucidating the pathogenesis and early diagnosis of AD.

Objective To evaluate the short-term clinical effect of arthroscopic repair of rotator cuff injury with all-suture anchor using a prospective and single-cohort clinical trial.Methods Twenty-five patients with rotator cuff injuries(1.5 cm0.05).Conclusion Arthroscopic rotator cuff repair with all-suture anchor is feasible and safe,and has good short-term clinical effect.

Cleft lip and palate is a common congenital developmental defect,which is mainly manifested as congenital oral and maxil-lofacial malformations.In patients with cleft lip and palate,jaw deformity often involves three-dimensional orientation,among which the correction of sagittal dysmorphism is the key point and difficulty in its diagnosis and treatment.In this article,we will elaborate on the indications and corrective methods for the treatment of maxillary retraction of cleft lip and palate,and introduce our experience in the sequential treatment of cleft lip and palate maxillary retraction in order to promote the standardization of its diagnosis and treatment.

Objective To explore the utility of CT for the evaluation of abdominal aortic calcification(AAC)in chronic kidney disease(CKD).Methods Laboratory examination indexes and abdominal plain CT imaging of 132 CKD stage 3-5 patients were analyzed retrospectively.The ACC score was evaluated according to quantitative method,the risk factors related to AAC were analyzed.Results In correlation analyses,AAC score was positively correlated with creatinine(Cr)level,CO2 combining power(P＜0.05),and negatively corrected with albumin(ALB).Logistic regression analysis showed that Cr level were risk factors for AAC,and ALB were protective factors.Conclusion Based on abdominal plain CT images,Cr level,CO2 combining power and ALB level are related to AAC.Quantitative method based on CT has a high application value in evaluating AAC.

In recent years, the relationship between non-alcoholic fatty liver disease (NAFLD) and vascular cognitive impairment (VCI) has received increasing attention. The mechanism underlying the relationship between the two diseases remains unclear, which may be associated with neuroinflamation, oxidative stress, cerebrovascular disease, gut microbiota imbalance, and insulin resistance. This article reviews the correlation and potential mechanisms between NAFLD and VCI, with the aim of providing reference for further exploration of their correlation.

Objective:To explore a fast and accurate method to diagnose children's pneumonia according to respiratory signals, so as to avoid the cancer induction caused by traditional X-ray examination.Methods:A Mach Zehnder optical fiber sensor was used to build a respiratory signals(RSPs) detection system, and the RSPs of the monitored children were extracted according to the vibration signal generated by the children's lung rales. Preprocessing methods such as the discrete cosine transform(DCT) were used to compress and denoise the RSPs. Multi-feature extraction of RSPs was conducted through signal processing methods such as the Hilbert transform and autoregressive (AR) model spectrum estimation. A support vector machine (SVM) classification model was constructed to classify the collected RSPs.Results:The accuracy rate of the proposed RSP classification of children with or without pneumonia was 94.41%, which was higher than the previous methods.Conclusions:The children's pneumonia diagnosis system based on an optical fiber sensor has a higher detection accuracy, and is expected to be widely used in clinical practice.

AIM: To study the pharmacokinetic characteristics of single-dose oral moxifloxacin hydrochloride tablets under fasting and fed conditions, and use moxifloxacin hydrochloride tablets produced by Bayer Pharma AG as a reference to compare the pharmacokinetic parameters of the two preparations, and evaluate the human bioequivalence of the two preparations. METHODS: A single-center, randomized, open, two-period, and self-crossover design was adopted to conduct a fasting and fed bioequivalence study of 23 healthy subjects each. The 0.4 g dose preparations were taken orally per cycle on fasting or fed administration. The plasma concentrations of moxifloxacin at different times after administration were determined by HPLC-MS/MS. The main pharmacokinetic parameters were calculated, and the bioavailability of the test preparation relative to the reference preparation was evaluated. RESULTS: After subjects in the fasting group took the test preparation T and the reference preparation R, the main pharmacokinetic parameters of moxifloxacin hydrochloride were: C

OBJECTIVE：To stud y the effects of Zhitong shunqi capsule on JAK/STAT signaling pathway of chronic atrophic gastritis（CAG）model rats ，and to provide reference for clarifying its mechanism of improving CAG. METHODS ：Totally 60 SD rats were randomly divided into blank group ，model group ，positive control group [vitacoenzyme ，0.09 g/（kg·d）]，Zhitong shunqi capsule low-dose ，medium-dose and high-dose groups [ 0.75，1.5，3 g/（kg·d）]，with 10 rats in each group. Except for blank group，other groups were given N-methyl-N′-nitro-N-nitrosoguanidine freely drinking combined with abnormal ingestion method to induce CAG model. After end of modeling ，administration groups were given relevant medicine intragastrically ，blank group and model group were given constant volume of water intragastrically ，for consecutive 28 d. After end of medication ，ELISA method was used to determine the serum levels of IL- 1β and IL-6；the gastric mucosa tissue pathologic change was observed by HE staining；mRNA and protein expressions of JAK 1，STAT3，SOCS-3 and c-Myc in gastric mucosa tissue were detected by real-time PCR and Western blotting assay. RESULTS ：Compared with blank group ，the sparse and irregular glands with deep staining cell nucleus could be seen in the gastric mucosa of rats in model group ；serum levels of IL- 1 β and IL-6，mRNA and protein expressions of JAK 1，STAT3 and c-Myc in gastric mucosa tissue were increased significantly （P＜0.05），while mRNA and protein expression of SOCS- 3 in gastric mucosa tissue were decreased significantly （P＜0.05）. Compared with model group ， glandular arrangement of gastric mucosa was more orderly and the number of heavy stained cells was less in administration groups；serum level of IL- 6 and mRNA expression of c-Myc in gastric mucosa of rats was decreased significantly in Zhitong shunqi capsule low-dose group （P＜0.05），while the protein expression of SOCS- 3 was increased significantly （P＜0.05）； serum levels of IL- 1β and IL-6，mRNA expressions of JAK 1，STAT3 and c-Myc in gastric mucosa tissue ，protein expression of JAK1 were decreased significantly in Zhitong shunqi capsule medium-dose group （P＜0.05），while mRNA and protein expression of SOCS- 3 was increased significantly in gastric mucosa tissue （P＜0.05）；above indexes were improved significantly in positive control group and Zhitong shunqi capsule high-dose group （P＜0.05）. Compared with positive control group ，mRNA and protein expression of STAT 3 in gastric mucosa tissue were decreased significantly in Zhitong shunqi capsule high-dose group （P＜0.05）. CONCLUSIONS：Zhitong shunqi capsule can improve CAG model rat to certain extent ，the mechanism of which may be associated with the down-regulation of mRNA and protein of JAK 1，STAT3 and c-Myc ，and up-regulation of mRNA and protein of SOCS-3.