Diabetic kidney disease （DKD） is one of the common microvascular complications of diabetes mellitus （DM） and a primary cause of chronic kidney disease （CKD） and end-stage renal disease （ESRD）. Inflammation is currently a hot topic in exploring the pathogenesis of DKD. Macrophages， T cells， interleukins， tumor necrosis factor， NOD-like receptor protein 3 （NLRP3） inflammasome， Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway， and nuclear factor-kappa B （NF-κB）-related signaling pathway all play a role in regulating the inflammation of DKD and accelerating its progression. Astragali Radix， a Chinese herbal medicine， is widely used in the treatment of DKD and possesses strong anti-inflammatory effects. Studies have revealed that active ingredients of Astragali Radix， including polysaccharides， astragaloside Ⅳ， total flavonoids， calycosin， and quercetin， can regulate multiple signaling pathways to ameliorate the microinflammatory state and alleviate kidney damage， thereby slowing down the progression of DKD. This article systematically reviews the factors influencing the inflammation in DKD and analyzes recent research findings and mechanisms concerning active ingredients of Astragali Radix in the management of DKD inflammation， aiming to offer novel insights and directions for the prevention， treatment， and research of DKD.

Objective:To explore the clinical features and genetic variants in three children suspected for β-ketothiolase deficiency (BKTD).Methods:Clinical manifestations, laboratory examination and genetic testing of three children suspected for BKTD at Henan Children′s Hospital between January 2018 and October 2022 were collected, and their clinical and genetic variants were retrospectively analyzed.Results:The children were all males with a age from 7 to 11 months. Their clinical manifestations have included poor spirit, shortness of breath, vomiting, convulsions after traumatic stress and/or infection. All of them had severe metabolic acidosis, elevated ketone bodies in blood and urine, hypoglycemia, with increased isoprenyl-carnitine and 3-hydroxyisovalyl-carnitine in the blood, and 2-methyl-3-hydroxybutyrate and methylprotaroyl glycine in the urine. All of them were found to harbor compound heterozygous variants of the ACAT1 gene, including c. 1183G>T and a large fragment deletion (11q22.3-11q23.1) in child 1, c. 121-3C>G and c. 826+ 5_826+ 9delGTGTT in child 2, and c. 928G>C and c. 1142T>C in child 3. The variants harbored by children 2 and 3 were known to be pathogenic or likely pathogenic. The heterozygous c. 1183G>T variant in child 1 was unreported previously and rated as a variant of unknown significance (PM2_Supporting+ PP3+ PP4) based on guidelines from the American College of Medical Genetics and Genomics. The large segment deletion in 11q22.3-11q23.1 has not been included in the DGV Database and was rated as a pathogenic copy number variation. Conclusion:The variants of the ACAT1 gene probably underlay the pathogenesis of BKTD in these three children.

objectiveTo investigate the differences in clinical indices and lipid metabolism between the patients with nonalcoholic fatty liver disease （NAFLD） and healthy individuals in the overweight population. MethodsIn this study， body mass index （BMI）>23 kg/m² was defined as overweight. A total of 62 overweight patients with NAFLD who were admitted to Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2020 to April 2021 were enrolled as overweight NAFLD group， and 50 overweight individuals who underwent physical examination during the same period of time were enrolled as control group. Clinical information and blood biochemical parameters were recorded for all subjects. Ultra-performance liquid chromatography-tandem mass spectrometry was used to analyze serum lipidomic profile， and principal component analysis and orthogonal partial least squares-discriminant analysis were used to perform the multivariate statistical analysis of lipidomic data. The chi-square test was used for comparison of categorical data between two groups， and the independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups. ResultsThe overweight NAFLD group had a significantly higher BMI than the overweight control group （Z=-2.365， P=0.018）. As for serological markers， compared with the overweight control group， the overweight NAFLD group had significantly higher levels of red blood cells， hemoglobin， hematocrit， uric acid， total protein， globulin， alkaline phosphatase， gamma-glutamyl transpeptidase， alanine aminotransferase， aspartate aminotransferase， cholinesterase， low-density lipoprotein， total cholesterol， triglyceride， apolipoprotein B， and blood glucose （all P<0.05）. The lipidomic analysis showed that there was a significant difference in lipid metabolism between the two groups， and a total of 493 differentially expressed lipids were identified （VIP value>1， P<0.05）， among which 143 lipids were significantly upregulated and 350 lipids were significantly downregulated in the overweight NAFLD group. The mean total fatty acid content in the overweight NAFLD group was 3.6 times that in the overweight control group. Compared with the overweight control group， the overweight NAFLD group had a significant reduction in the content of triglyceride with>3 unsaturated bonds （P<0.001） and a significant increase in the content of triglyceride with ≤3 unsaturated bonds （P<0.001）. ConclusionCompared with healthy overweight individuals， overweight NAFLD patients tend to have significant abnormalities in some biochemical parameters and lipid metabolites， with significant increases in the content of fatty acid in blood and the types of saturated fat chains in triglycerides.

Objective:To investigate the distribution of potential suitable habitats for Ixodes persulcatus in Heilongjiang Province during different climatic periods. Methods:The geographical location data of Ixodes persulcatus in Heilongjiang Province from 1980 to 2023 were collected through literature search and field ecological investigation. The environmental factor variables were downloaded from the WorldClim website and the Resource and Environmental Science and Data Platform. A combination of SDMtune, ENMTools packages, and the maximum entropy (MaxEnt) model were used to predict the potential habitats of Ixodes persulcatus in Heilongjiang Province during different climatic periods and determine its dominant environmental factors. Among them, the time range of historical climatic period data was 1970 - 2000. The future climatic period data (2021 - 2040, 2041 - 2060) were selected as the low forcing scenario (SSP126 scenario) of the shared socioeconomic pathways (SSP) in the Beijing Climate Center - Climate System Model version 2-Medium Resolution, to simulate the impact of global warming on the distribution of potential habitats for Ixodes persulcatus in Heilongjiang Province. Results:A total of 83 geographical distribution sites of Ixodes persulcatus in Heilongjiang Province were obtained. After screening, 10 environmental factors were included in the MaxEnt model. Among them, the cumulative contribution percentage of annual precipitation, average annual temperature, and vegetation type was 67.3%. Compared with historical climatic period, the total potential habitats of Ixodes persulcatus in Heilongjiang Province increased from 29.81 × 10 4 km 2 to 32.24 × 10 4 km 2 in 2041 - 2060. The center of potential habitats moved to 47.75° N, and 128.66° E, with a northwest offset of 126.07° and a migration distance of 45.83 km. Conclusion:With global climate warming, the total potential habitats of Ixodes persulcatus in Heilongjiang Province has increased, showing an overall trend of migration to the northwest.

Objective:To investigate the relationship between microsatellite instability (MSI) , and clinicopathological features ,prognosis in patients with stage Ⅱ and Ⅲ colon cancer.Methods:Patients undergoing surgical resection for stage Ⅱ and Ⅲ colonic tumor in the Affiliated Hospital of Qingdao University from Dec 2016 to Nov 2018 were enrolled. All the 292 patients were with stage Ⅱ and Ⅲ colon cancer and MSI status. Propensity score matching method was used to match the two groups of patients according to 1:1. χ 2 analysis, Logistic Regression and COX regression was used to analyse the relationship between MSI status, the clinicopathological features and prognosis. Results:The risk of MSI-H in young patients ( OR=0.340, 95% CI: 0.126~0.921, P=0.034), right-sided colon cancer ( OR=7.985, 95% CI: 3.040-20.973, P<0.001), mucinous adenocarcinoma ( OR=4.285, 95% CI: 1.495-12.284, P=0.007), poorer differentiation ( OR=4.848, 95% CI: 1.597-14.716, P=0.005), N0 staging ( OR=0.235 , 95% CI: 0.077-0.719, P=0.011) increased . The total OS of colon cancer patients in the MSS group (66.7%) and the MSI-H group (86.9%) were statistically different( P=0.003). The MSI status ( HR=0.367, 95% CI: 0.151-0.891, P=0.027) is an independent factor affecting the prognosis of patients. Conclusions:In stage Ⅱ and Ⅲ colon cancer, patients with MSI-H have a better prognosis. MSI status is prognosis relevant factor for colon cancer patients.

Cell membrane affinity chromatography has been widely applied in membrane protein (MP)-targeted drug screening and interaction analysis. However, in current methods, the MP sources are derived from cell lines or recombinant protein expression, which are time-consuming for cell culture or purification, and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase. In this study, a novel in situ synthesis membrane protein affinity chromatography (iSMAC) method was developed utilizing cell-free protein expression (CFE) and covalent immobilized affinity chromatography, which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase. The advantages of iSMAC are: 1) There is no need to culture cells or prepare recombinant proteins; 2) Specific and purified MPs with stable and controllable content can be obtained within 2 h; 3) MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase; 4) The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites. iSMAC was successfully applied to screen PDGFRβ inhibitors from Salvia miltiorrhiza and Schisandra chinensis. Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h. Two new PDGFRβ inhibitors, salvianolic acid B and gomisin D, were screened out with K _D values of 13.44 and 7.39 μmol/L, respectively. In vitro experiments confirmed that the two compounds decreased α-SMA and collagen Ӏ mRNA levels raised by TGF-β in HSC-T6 cells through regulating the phosphorylation of p38, AKT and ERK. In vivo, Sal B could also attenuate CCl₄-induced liver fibrosis by downregulating PDGFRβ downstream related protein levels. The iSMAC method can be applied to other general MPs, and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.

OBJECTIVE：To discuss the inhibitory effect of lanthanum chloride on the calcification of vascular smooth muscle cells（VSMCs）induced by high phosphorus and its mechanism. METHODS ：On the basis of screening the action concentration and time of lanthanum chloride by MTT method ，human VSMCs were divided into control group （1 mmol/L phosphorus solution ）， lanthanum chloride high concentration control group （1 mmol/L phosphorus solution+ 60 μmol/L lanthanum chloride），model group （3 mmol/L phosphorus solution ），sodium chloride group （3 mmol/L phosphorus solution+ 180 μmol/L sodium chloride），nuclear factor κB（NF-κB）signaling pathway agonist+lanthanum chloride group （3 mmol/L phosphorus solution+ 1 μg/mL lipopolysaccharide+ 60 μmol/L lanthanum chloride），positive control group （3 mmol/L phosphorus solution+ 100 μmol/L sodium pyrophosphate），and lanthanum chloride low ，medium，and high concentration groups （3 mmol/L phosphorus solution+ 15，30，60 μmol/L lanthanum chloride）. Alizarin red S staining and Von Kossa staining were used to detect cell calcification in each group after treated with phosphorus solution for 6 d and relevant medicine for 2 d. Western blot assay was used to detect the protein expression of TNF-α receptor associated protein 6（TRAF6），nuclear factor κB inhibitor protein α（IκBα），NF-κB p65，bone morphogenetic protein 2 （BMP-2），smooth muscle 22 α（SM22α）and Runt related transcription factor 2（Runx2）. Real-time fluorescence quantitative polymerase chain reaction was used to detect mRNA expression of TRAF 6，IκBα，BMP-2，SM22α and Runx2. RESULTS ： Compared with control group ，no cell calcification was observed in the lanthanum chloride high concentration control group ，while obvious cell calcification and significant increase of OD value were observed in model group and sodium chloride group （P＜ 0.01）；protein and mRNA expression of TRAF 6 and BMP- 2 in cytoplasm as well as mRNA expression of Runx 2，protein expression of NF-κB p65 and Runx 2 in nucleus were significantly increased （P＜0.01）；protein and mRNA expression of IκBα and SM22α as well as protein expression of NF-κB p65 in cytoplasm were significantly decreased （P＜0.01）. Compared with model group，cell calcification was significantly improved in lanthanum chloride groups and positive control group ，while OD values were significantly reduced ；the expression levels of the above-mentioned protein and mRNA were reversed to varying degrees （P＜0.05 or P＜0.01）. Compared with lanthanum chloride high concentration group ，obvious cell calcification was observed in NF-κB signaling pathway agonist + lanthanum chloride group ，and OD value was significantly increased ；the above indexes were significantly reversed in cytoplasm and nucleus （P＜0.05 or P＜0.01）. CONCLUSIONS ：Lanthanum chloride can inhibit the calcification of VSMCs induced by high phosphorus ，and its mechanism may be related to the inhibition of NF-κB signaling pathway activation.

Objective:To investigate the clinical pathological features of primary pulmonary and tracheal glomus tumors.Methods:The clinical and pathological features of 11 cases (4 cases from Shanghai Pulmonary Hospital, Tongji University School of Medicine, China and 7 cases from Fudan University Shanghai Cancer Center, China) of respiratory glomus tumor diagnosed from 2010 to 2019 were analyzed, and reviewed in light of the relevant literature.Results:In the 11 cases, there were 5 males and 6 females, with the onset ages of 29?66 years (median age of 43). Six tumors were located in the lung, and 5 in the trachea. The tumor diameters ranged 1.0?7.5 cm, with the average diameter of 2.6 cm. At low magnification, the tumors were diffuse or lobulated in shape. The tumor cells composed of sheets of oval to short spindle cells, with sharply defined cell border and prominent branching thin-walled vessels. Among the 4 benign glomus tumors, one was classified as benign symplastic glomus tumor owing to the hyperchromatic or degeneration nuclei. Two cases were classified as glomus tumors of uncertain malignant potential, on the account of cellular atypia and rare atypical mitotic figures. Five cases were classified as malignant glomus tumors, owing to the tumor necrosis, vascular invasion, marked nuclear atypia, prominent nucleoli and brisk mitoses (2-20/10HPF) including pathological mitotic figures. The tumor cells showed strong immunostaining for SMA, vimentin, type Ⅳ collagen and caldesmon to different extents, while CD34, cytokeratin and S-100 stains were negative. One of the cases was positive for desmin, and one case positive for synaptophysin. Follow-up information was available in 8 patients with the duration ranging from 6 to 95 months. At the end of the follow-up, 6 patients were alive without recurrence or metastasis, and two of the patients with malignant glomus tumors died.Conclusions:Primary pulmonary and tracheal glomus tumors is rare. Among the reported cases, malignant glomus tumor is the most frequent, followed by benign glomus tumors and uncertain malignant potential glomus tumors. Glomus tumors show sheet-like growth pattern and clusters of round epithelioid cells with numerous vascular spaces. They can be easily misdiagnosed as carcinoid tumor. The final diagnosis should be combined with immunohistochemical staining, such as SMA, caldesmon and vimentin.

Objective: To investigate the early typing diagnostic and predictive value of anti-keratin antibodies(AKA), anti-perinuclear factor(APF) and anti-citrullinated protein antibodies(ACPA) in patients of juvenile idiopathic arthritis (JIA). Methods: A retrospective study was conducted to collect 144 cases of JIA who were hospitalized in Capital Institute of Pediatrics from December 2013 to June 2016 and followed up for at least one year.Among them,66 were males (46%) and 78 were females (54%).The age at diagnosis was between 1 year 5 months to 15 years 9 months.144 patients were tested for AKA,ACPA,APF and TNFα upon admission. Chi-square test or Fisher exact test were used to compare the positive rates of three antibodies among different subtypes. Mann-Whitney nonparametric test and Chi-square test or Fisher exact test were used to analyze the data of prognosis between antibody-positive group and antibody-negative group in the course of disease. Results: In 144 patients, 49(34%) were classified as systemic arthritis, 28 (19.4%) as polyarthritis, 61(42.3%) as oligoarthritis, and 6(4.2%) as enthesitis-associated arthritis. 52 cases (36.1%) were positive for one antibody or more antibodies of AKA/APF/ACPA at the early stage, 14(9.7%) were AKA positive, 44(30.6%) were ACPA positive and 12(8.3%) were APF positive. The positive rates of ACPA/AKA/APF antibodies were significantly different among different subtypes(χ²=33.863,26.860,14.395; P<0.01,<0.01,<0.05).The rates in polyarthritis were higher than those in systemic arthritis and oligoarthritis; In 95 children with non-systemic form, the level of TNFα in antibody-positive group (43 cases) was higher than that in antibody-negative group (52 cases) at the early stage(Z=4.785, P<0.01);144 patients were followed up for at least one year,the rates of patients who accepted biologic therapies were significantly different between antibody-positive group and antibody-negative group (50% vs 25%). So do the rates of patients with joint deformities (17.3% vs 2.2%) and with important joints involvement (hip and axis joints) (59.6% vs 14.1%) (χ²=9.249,10.875,32.392; P<0.01,<0.01,<0.01). Further more, the number of joints involved in the antibody-positive group (7.07±3.85) was significantly more than that in the antibody-negative group (2.31±1.64) (F=63.822, P<0.01). Conclusions AKA,APF and ACPA are important in the early typing diagnosis of JIA,and may be closely related to the prognosis of patients with JIA.

Members of the proto-oncogene superfamily are indispensable molecular switches that play critical roles in cell proliferation, differentiation, and cell survival. Recent studies have attempted to prevent the interaction of RAS/GTP with RAS guanine nucleotide exchange factors (GEFs), impair RAS-effector interactions, and suppress RAS localization to prevent oncogenic signalling. The present study aimed to investigate the effect of the natural triterpenoic acid inhibitor glycyrrhetinic acid, which is isolated from the roots of plant species, on RAS stability. We found that glycyrrhetinic acid may bind to the P-loop of RAS and alter its stability. Based on our biochemical tests and structural analysis results, glycyrrhetinic acid induced a conformational change in RAS. Meanwhile, glycyrrhetinic acid abolishes the function of RAS by interfering with the effector protein RAF kinase activation and RAS/MAPK signalling.