Objective To develop a rat model of type 2 diabetes, and to investigate the effect of AT1 receptor antagonist-irbesartan on activation of renal NF-?B in type 2 diabetic rat. Methods The rats of model groups were intraperitoneally given low-dose streptozotocin (STZ, 30 mg/kg) after having the sucrose-and fat-enriched diets(20% sucrose, 10% pig fat, 2. 5% cholesterol) for one month. Immuohistochemistry and computer image-pattern analysis system were used to analyze activation of NF-?B and expression of monocyte/macrophage (ED-1) in renal tissues. Results (1) Insulin resistance was induced by feeding diets enriched in sucrose and fat, and hyperglycemia was induced with a dose of STZ that did not cause diabetes in chow-fed rats. After 6 weeks, rats of model group presented itself early changes of diabetic nephropathy (DN). (2) Compared to normal group, the activation of NF-?B and expression of ED-1 increased in glomeruli of experimental type 2 diabetic rat. Irbesartan inhibited significantly the activation of NF-?B, ameliorated monocyte/macrophage infiltration, partly improved the renal function and matrix accumulation. Conclusions (1) A rat model of type 2 diabetes mellitus is developed successfully by combination of dietary-induced insulin resistance and low-dose STZ-induced hyperglycemia. (2) Renal NF-?B activation is greatly increased in experimental type 2 diabetic rat. The protection of irbesartan against kidney is associated, at least in part, with down-regulating NF-?B activation and monocyte/macrophage recruitment in renal tissue.

A method was developed for the determination of four sulfa antibiotics in groundwater, soil and excreta using solid phase micro extraction disks coupled with high performance liquid chromatography. The influence of eluent, different solid phase micro extraction membranes on the recovery of sulfa antibiotics in groundwater was investigated and it was found that when using the mixture of methyl alcohol and 1 . 0% formic acid as eluent, HLB ( divinyl benzene-N-vinyl pyrrolidone polymer ) as extraction membranes, an optimal enrichment effect was obtained. Different pretreatment methods for the 3 kinds of samples abovementioned were also examined. It was found that the signal response values obtained by using mixture of methyl alcohol and 1 . 0% formic acid as base solution of standard or sample solution was higher 8-10 times than that by using methyl alcohol only. Under the optimal conditions, good linear relationships were obtained in the sulfa antibiotics concentrations of 0 . 005-10 . 0 mg/L with the correlation coefficients>0 . 9999;The detection limits of sulfathiazole ( ST ) , sulfadiazine ( SM ) , sulfamethazine ( SM2 ) , sulfamethoxazole ( SMX ) were 1 . 08 , 3. 56, 4. 63 and 1. 84 ng/L(S/N=3), respectively. The enrichment factors for four sulfa antibiotics were 4000 times with solid phase micro extraction disks. The RSD of matrix spiked samples were 0. 1%-0. 4%(n=7). The proposed method was applied to the determination of the four sulfa antibiotics in groundwater, soil and excreta with spiked recoveries of the four sulfa antibiotics in the range of 69 . 80%-117 . 60%.

Objective To analyze the clinical and imaging characteristics of pediatric neuromyelitis optica spectrum disorders(NMOSD)in children. Methods The clinical data,imaging manifestations and follow - up data of 16 NMOSD patients at Department of Pediatric Neurology,Shandong Provincial Hospital Affiliated to Shandong Univer-sity between July 2013 and September 2017 were respectively analyzed. Results In 16 patients,initial presentations included optica neuritis(ON)in 5 cases,longitudinally extensive transverse myelitis(LETM)in 6 cases,and among them there were 2 cases with acute disseminated encephalomyelitis and 3 cases with both ON and LETM. Eleven cases received aquaporin - 4(AQP4)antibody examination and 4 cases were found seropositive. One case out of 7 detected cases was found AQP4 antibody positive in cerebrospinal fluid. Eleven cases received optica magnetic resonance imaging (MRI),and 8 cases were found abnormal signals in optic nerve and optica chiasma. The spinal cord MRI showed 13 ca-ses with LETM manifestations,and abnormal signals were found in vertebral segments(5 - 13),and among them 1 case had cervical cord,3 cases were thoracic cord and 9 cases were both of the above. Lesions in the cervical cord in 2 cases were extended upward to the medulla. Fifteen cases received brain MRI and all of them had brain lesions,which were mainly involved in the central and subcortical white matter,thalamus,corpus callosum,brainstem,the junction of spinal cord and medulla,cerebellum,and so on. All patients received treatment for acute attacks with high - dose Methylpred-nisolone and/ or gamma globulin and got obvious relief. Two cases with recurrent ON received treatment of Rituximab and their vision became improved. Fifteen patients were followed up,and 2 cases had limb disorders and 4 cases had visual impairment,other patients had no clinical symptoms. Conclusions Pediatric NMOSD has a diverse clinical pre-sentation at the onset disease. Those who are initial diagnosed acute myelitis,ON and acute disseminated encephalomye-litis should be considered the possibility of NMOSD. Antibody to AQP4 testing can assist the diagnosis. The typical ima-ging characters of NMOSD children are abnormal signals in the high expression area of AQP4. Intracranial lesions are more common in children. The acute treatment includes the high - dose Methylprednisolone and gamma globulin. Rituximab can be used for the recurrent patients.

Objective:To summarize initial experience of applying nanopore third-generation sequencing detection method (nanopore sequencing) for genetic diagnosis of non-classical 21 hydroxylase deficiency (NC 21-OHD), and to explore its performance and application prospects.Methods:Clinical data of the two NC 21-OHD patients, who were hospitalized at the First Affiliated Hospital of Zhengzhou University in May 2019, were collected. Peripheral venous blood was collected and genome DNA extracted. Genetic variants was detected by nanopore sequencing and underwent bioinformatic analysis. Pathogenetic mutations in CYP21A2 gene were validated with PCR-sanger sequencing in the two patients and their parents.Results:The average reads length and sequence depth in the patient one was 12, 792 bp and 27.19×. The average reads length and sequence depth in the patient two was 13, 123 bp and 21.34×. Compound variants of c.293-13C>G/c.844G>T (p.Val282Leu) and c.332_339delGAGACTAC (p.Gly111Valfs)/c.844G>T (p.Val282Leu) were detected in these two patients, which were consistent with clinical phenotype of NC 21-OHD. Further analysis showed that c.293-13C>G mutation was inherited from her father and c.844G>T (p.Val282Leu) mutation was inherited from her mother for the patient one. The c.844G>T (p.Val282Leu) mutation was inherited from her father and c.332_339delGAGACTAC (p.Gly111Valfs) mutation from her mother.Conclusions:The heterozygous mutations in CYP21A2 gene are the cause of NC 21-OHD in these two patients. Nanopore sequencing technique is a reliable new detection method for patients with NC 21-OHD.

BACKGROUND:Metal ions play an important role in the human body.With the progress of material synthesis and processing technology,a variety of metal ions that can be used in bone tissue engineering have been developed,such as magnesium(Mg2+),zinc(Zn2+),manganese(Mn2+),strontium(Sr2+),and copper(Cu2+). OBJECTIVE:To summarize the research progress and development direction of metal ions in bone tissue engineering. METHODS:The literature collected by CNKI,PubMed and WanFang databases from 2014 to 2022 was retrieved.The Chinese and English key words were"metal ions,bone tissue engineering,osteogenic activity,magnesium ions,zinc ions,manganese ions,strontium ions,copper ions,calcium ions,lithium ions,cobalt ions". RESULTS AND CONCLUSION:Different metal ions will be released to varying degrees after the materials are implanted into the body,which can change the tissue microenvironment,thus improving the ability of materials to form blood vessels and bones.Compared with growth factors,metal ions are easier to control the release rate,have lower cost,and can also improve the mechanical properties of implant materials.The application of metal ions in bone tissue engineering is full of prospects.Although some metal ions can already be used to treat bone defects,the mechanism of action of many metal ions in the human body is not completely clear,and the application effect is a lack of clinical experiment verification.Further exploration is needed before clinical application.

【Objective】 To investigate the viability of rapamycin-treated rapamycin-treated dendritic cells (DCs) in intervening transfusion-related acute lung injury (TRALI) after infection. 【Methods】 1)The TRALI mouse model was induced by lipopolysaccharide (LPS) combined with anti-H2Kd antibody. The mice anal temperature and the wet/dry ratio of lung, kidney, spleen and brain tissues were measured. 2) Mouse bone marrow-derived DC cells were induced in vitro and treated with rapamycin (10nM) for 24h. 3) Mice were injected with or without rapamycin or rapamycin-treated DC, then injected with LPS intraperitoneally one hour later, finally injected with anti-H2Kd antibody 24 hours later to induce the onset of TRALI. The death situation of the mice was observed and recorded. The condition of mice after the onset of TRALI was analyzed by mouse body temperature, lung wet-dry ratio, and pleural effusion weight and lung histopathological sections. 【Results】 By comparing the induction effects of anti-H2Kd antibody solutions with different concentrations and volumes, the mouse model induced by 0.1mg/kg LPS combined with 4.5 mg/kg anti-H2Kd antibody (infusion volume of 100μL) was selected as the TRALI mouse model for this study. After the onset of TRALI, the wet/dry ratio of the lungs could be significantly increased and the body temperature could be significantly reduced in the model mice. After the intervention of TRALI mice with DCs treated with rapamycin, the mortality rate was significantly reduced, and the lung tissue lesions of the mice were significantly improved, whose protection effect was better than that of the rapamycin-treated group. Compared with the TRALI incidence group, the weight of pleural effusion in the intervention group was significantly reduced (P<0.05), but there was no significant difference in lung wet/dry ratio and body temperature. 【Conclusion】 The combination of LPS and antibodies can effectively induce a stable and typical TRALI mouse model, suggesting that the presence of infectious inflammation and blood transfusion-related inflammatory substances are the decisive factor for the pathogenesis of TRALI. Meanwhile, DCs treated with rapamycin have a protective effect on post-infection transfusion-related acute lung injury, which is expected to be a potential cell therapy strategy to intervene in the exacerbation of TRALI.

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC