AIM: To investigate the genetic association and potential causal relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR), and to elucidate their shared molecular mechanisms through differential gene expression analysis and Mendelian randomization(MR).METHODS: Transcriptomic data of DN and DR were obtained from the Gene Expression Omnibus(GEO)database and analyzed for differentially expressed genes(DEGs). Genes meeting the significance threshold(log2FC>1, P<0.05)were identified, followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to explore shared biological pathways. Using genome-wide association study(GWAS)summary statistics for DN and DR, two-sample MR analysis was performed, with DN as the exposure and DR as the outcome. The causal effect was primarily estimated with the inverse-variance weighted(IVW)method, and sensitivity analyses were conducted to assess robustness.RESULTS: MR analysis revealed that DN significantly increased the risk of DR. IVW estimates indicated that the odds ratio(OR)for non-proliferative DR(NPDR)was 3.23(95% CI: 2.12-4.95, P<0.001), and the OR for proliferative DR(PDR)was 1.10(95% CI: 1.06-1.15, P<0.001). DEG analysis identified several key genes, including FN1, COL1A2, and THBS2. FN1 and COL1A2 are involved in extracellular matrix remodeling and fibrosis, contributing to vascular permeability alterations and microvascular damage in diabetic complications. THBS2 is closely associated with angiogenesis and vascular homeostasis, suggesting its potential role in DR. KEGG enrichment analysis showed that these DEGs were mainly enriched in advanced glycation end products(AGEs)-RAGE signaling, extracellular matrix degradation, and oxidative stress pathways, all of which are highly relevant to the pathogenesis of DN and DR.CONCLUSION: This study demonstrates the genetic association between DN and DR using MR and DEGs analyses. The shared mechanisms, particularly involving extracellular matrix remodeling, inflammatory response, and angiogenesis, may serve as novel therapeutic targets and provide a theoretical basis for the early diagnosis and targeted treatment of diabetic complications.

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity

Objective To investigate and evaluate the nutrition status in serum 25-hydroxy vitamin D[25(OH)D]levels of 0～12 years old children in Xi'an.Methods A total of 2 670 patients aged 0～12 years old who underwent routine physical examinations in Children's Health Department of the Second Hospital of Air Force Medical University were selected from March 2020 to July 2023,and the 25(OH)D data of these patients were conducted in retrospective analysis.The nutritional status of vitamin D in these children of different genders,ages and seasons were also analyzed.Results ①This study included 2 670 children aged 0～12 years old in Xi'an,with the average level of serum 25(OH)D was 40.80±18.00 ng/ml.Among them,38 cases(1.42%)had serum 25(OH)D deficiency,333 cases(12.47%)had serum 25(OH)D insufficience,and 2 299 cases(86.11%)had sufficient serum 25(OH)D.②There was a statistically significant difference in serum 25(OH)D levels among different age groups(H=1 524.23,P=0.000).The group aged 1～<4 has the highest value of 52.51±13.57 ng/ml,while the group aged 8～12 has the lowest value of 21.65±6.75 ng/ml.③The levels of serum 25(OH)D in summer(39.44±17.46 ng/ml)were lower than those in spring(41.96±17.76 ng/ml)and autumn(42.71±18.15 ng/ml),with statistical significant differences(Z=101.57,-134.06,all P<0.01).However,the deficiency and inadequate rate of serum 25(OH)D in winter(18.95%)was higher than those in spring,summer and autumn(13.52%,12.75%,12.36%),with statistical significant differences(χ2=14.32,P=0.026).④There was no statistically significant difference in serum 25(OH)D levels between genders(H=0.933,P=0.351).However,the deficiency and inadequate rate of serum 25(OH)D in boys(12.51%)was lower than that in girls(15.46%),and the difference was statistically significant(χ2=9.257,P=0.010).Conclusion The nutritional status of serum 25(OH)D in children aged 0～12 years in Xi'an area is comparatively fine,and it is necessary to strengthen the intake and supplementation of vitamin D in over 3 years old children.

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*

Objective: To comprehensively understand the disinfection quality of secondary and primary schools and kindergartens in Wuxi, so as to find out problems and to provide advice for improvement. Methods: Stratified random sampling method was applied in the investigation to select 73 schools and classes. The qualities of room air, surface of object, hand hygiene of staff, tableware, ultraviolet lamp and disinfectant in use (including bacterial contamination and concentration of chlorine-containing) were all tested. Results: A total of 2 563 samples were collected with the total disinfection qualified rate 88.02%. The qualified rates of kindergarten, primary and secondary schools were 87.89%, 90.67% and 85.83% respectively. The rates of Xishan and Jiangyin districts were 75.24% and 75.89% respectively. The quality of urban schools was better than the rural(χ 2=16.57, P<0.01). There was no statistical significance between public and private schools (χ 2=0.01, P=0.92). The rank of qualified rates of different objects was: bacterial contamination (100.00%) > room air (93.13%) > tableware (91.87%) > surface of object (89.40%) > ultraviolet lamp (84.00%) > concentration of chlorine-containing (73.68%) > hand hygiene of staff (73.53%). The quality of secondary schools was lower than kindergartens and primary schools in the aspects of room air and surface of object. Conclusion The disinfection quality of secondary and primary schools and kindergartens in Wuxi is good in general. More attention should be paid on hand hygiene, concentration of chlorine-containing and ultraviolet lamp. The qualities of room air and surface of object of secondary schools need to be improved.

Objective:To evaluate the protective immunity by vaccination of BALB/c mice with rLV-HA-GCN4,a recombinant lentivirus expressing the trimeric HA of swine H1N1 influenza virus. Methods:The female mice were randomly divided into rLV-HA-GCN4,rLV-HA,LV and PBS groups. Mice were primed with plasmid and boosted with lentivirus by the administration of intramuscular thigh injections at an interval of two weeks. At day 28 post-prime immunization,mice were inoculated intranasally with 100TCID50 of swine H1N1 influenza virus in a 50 μl volume. The immune levels were assessed by the T lymphocyte transformation test, flow cytometry,indirect ELISA and the indexes of spleen and lung. Results:The spleen lymphocyte transformation rate was 0. 3±0. 11 in the rLV-HA-GCN4 group at day 14 post-boost immunization, showing a statistical significance ( P<0. 01 ) compared to the PBS group. Meanwhile,rLV-HA-GCN4 could cause T lymphocyte response mainly based on the Th1-type CD4+ T cells. The IgG antibody titer reached to 1:8 000 at day 14 post-boost immunization and approximately 1:7 000 at day 14 post challenge. After challenge,the spleen and lung indexes of rLV-HA-GCN4 group were significantly lower than those of PBS group (P<0. 05). The body weight of rLV-HA-GCN4 group demonstrated a slight decrease before 3 days post challenge and then a gradual increase compared to the LV and PBS groups (P<0. 05). Conclusion:rLV-HA-GCN4 can effectively induce cellular and humoral immune response in BALB/c mice against swine H1N1 influenza virus.

BACKGROUND:Ti6Al4V is a titanium aloy that is widely used in human joint replacement, but its modulus of elasticity is greater than human bone, resulting in the bad stability of the prosthesis. Ti35Nb3Zr2Ta, a new βtitanium aloy, has a lower modulus of elasticity, and maybe becomes a new-generation human joint prosthesis material that has a better biocompatibility. OBJECTIVE:To study the biocompatibility of Ti35Nb3Zr2Ta in prosthesis. METHODS:Wanfang, CNKI and PubMed databases were retrieved using a computer with “new β titanium;prosthesis; biocompatible” as keywords, and the retrieval time ranged from 2010 to 2015. Articles focusing on current application status for medical prosthesis materials and the biocompatibility of Ti35Nb3Zr2Ta in prosthesis were selected. RESULTS AND CONCLUSION:Compared with Ti6Al4V, Ti35Nb3Zr2Ta has higher surface roughness and smaler surface contact angle; the alkaline phosphatase activity and amount of calcium deposits in osteoblasts cultured at Ti35Nb3Zr2Ta is significantly higher than that at Ti6Al4V. Ti35Nb3Zr2Ta has good biocompatibility, and can be considered to be widely used as joint prosthesis material further.

AIM:To investigate the effect of Notch-1 knockdown on the growth of dihydroartemisinin-inhibited human osteosarcoma cell line U-2OS.METHODS:U-2OS cells treated with different concentrations of dihydroartemisinin (5, 10, 15 and 20μmol/L) were collected.The expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels was measured by real-time PCR and Western blotting, respectively.U-2OS cells were transfected with Notch-1 siRNA for 24 h and incubated with dihydroartemisinin for another 24 h.The cell apoptotic rate , protein expression of MMP-2, MMP-9 and Hes-1, and the migration ability were measured by MTT assay , Western blotting and Transwell experiment , respectively.RESULTS:Dihydroartemisinin (5, 10, 15 and 20 μmol/L) decreased the expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels in a dose-dependent manner .Down-regulation of Notch-1 significantly en-hanced the effect of dihydroartemisinin on the cell apoptosis , the protein expression of MMP-2, MMP-9 and Hes-1, and mi-gration ability ( P<0.05 ) .CONCLUSION: Notch-1 pathway is involved in the process of dihydroartemisinin-inhibited U-2OS cell growth.Knockdown of Notch-1 augments the inhibitory effect of dihydroartemisinin on U-2OS cell viability.

Objective To study the imaging features and possible aetiology of osteonecrosis in adults with acute leukemia.Methods Ten adult patients with acute leukemia for osteonecrosis were reviewed retrospectively.All the lesions were confirmed with MRI.Results Four patients with ALL had accepted chemotherapy contained corticosteroids,two of them were performed HSCT,and one patient suffered GVHD.Six patients with AML had accepted chemotherapy without steroids,five of them were performed HSCT,and four patients suffered GVHD.One patient with AML-M3 had accepted chemotherapy including four courses of ATRA.The mean time between diagnosis of osteonecrosis and leukemia was 25.1 months.Nine cases had multiple lesions,one case had single lesion.The lesions involved femurs,tibias,patellas,iliums,and lumbars.Plain radiographs in six patients can not detect any lesion.Circinal reaction ossification could be detected in CT images of four cases.All the cases had typical feature in MRI.Conclusions In adult leukemia patients,osteonecrosis is a complication after chemotherapy or HSCT.Steroids in chemotherapy protocols or treatment for GVHD,ATRA for APML,chemotherapy-induced direct cytotoxic effect or leukemia itself can be the possible risk factor.For the diagnosis,MRI is the most effective way,and CT features of osteonecrosis in leukemia patients are different from those in non-leukemia patients.

Objective To evaluate the clinical application of CT perfusion in predicting the status of axillary lymph nodes in patients with breast cancer.Methods Fony-five patients with infiltrating breast cancers and 46 clinically palpable axillary lymph nodes underwent dynamic mtdti-slice spiral CT(MSCT).Semi-automatic calculation of perfusion parameters including blood flow(BF),blood volume(BV),mean transit time(MTT)and permeability surface(PS)of "target" lymph nodes and muscles in the same scan level were respectively meagured and analyzed.Nonparametric Mann-Whitney U test was used for the statistics.Results Forty-six "target" lymph nodes examined by CTP were metastasis in 32 cases and reactive hyperplastic lymph node inflammation in 14 cases at pathology.22 of 32 metastatic "target" nodes (68%)were sentinel lymph nodes(SLN).BF of CIP for inflammation and metastatic "target" nodes were (76.18±31.53)and(161.60±40.94)ml·100 mg-1·min-1,BV were(5.81±2.50)and(9.15±3.02)ml／100 mg.MTT were(6.80±1.55)and(5.50±1.84)s,PS were(25.82±4.62)and (25.96±7.47)ml·100 mg-1·min-1.There were significant correlations between the BF value of inflammation and metastatic "target" nodes(r=0.14,P<0.05)and there were no significant correlations among the BV,MTT and PS values of inflammation and metastatic "target" nodes(r=-0.03,0.05,0.07.P>0.05).Conelusion CTP can provide useful informafion for evaluating lymph node status.