BACKGROUND:Rheumatoid arthritis is a chronic autoimmune disease.Early diagnosis is crucial for preventing disease progression and for effective treatment.Therefore,it is of significance to investigate the diagnostic characteristics and immune cell infiltration of rheumatoid arthritis. OBJECTIVE:Based on the Gene Expression Omnibus(GEO)database,to screen potential diagnostic markers of rheumatoid arthritis using machine learning algorithms and to investigate the relationship between the diagnostic characteristics of rheumatoid arthritis and immune cell infiltration in this pathology. METHODS:The gene expression datasets of synovial tissues related to rheumatoid arthritis were obtained from the GEO database.The data sets were merged using a batch effect removal method.Differential expression analysis and functional correlation analysis of genes were performed using R software.Bioinformatics analysis and three machine learning algorithms were used for the extraction of disease signature genes,and key genes related to rheumatoid arthritis were screened.Furthermore,we analyzed immune cell infiltration on all differentially expressed genes to examine the inflammatory state of rheumatoid arthritis and investigate the correlation between their diagnostic characteristics and infiltrating immune cells. RESULTS AND CONCLUSION:In both rheumatoid arthritis and normal synovial tissues,we identified 179 differentially expressed genes,with 124 genes up-regulated and 55 genes down-regulated.Enrichment analysis revealed a significant correlation between rheumatoid arthritis and immune response.Three machine learning algorithms identified LRRC15 and MICB as potential biomarkers of rheumatoid arthritis.LRRC15(area under the curve=0.964,95%confidence interval:0.924-0.992)and MICB(area under the curve=0.961,95%confidence interval:0.923-0.990)demonstrated strong diagnostic performance on the validation dataset.The infiltration of 13 types of immune cells was altered,with macrophages being the most affected.In rheumatoid arthritis,the majority of proinflammatory pathways in immune cell function were activated.Immunocorrelation analysis revealed that LRRC15 and MICB had the strongest correlation with M1 macrophages.To conclude,this study identified LRRC15 and MICB as potential diagnostic markers for rheumatoid arthritis,with strong diagnostic performance and significant correlation with immune cell infiltration.Machine learning and bioinformatics analysis deepened the understanding of immune infiltration in rheumatoid arthritis and provided new ideas for the diagnosis and treatment of rheumatoid arthritis.

Objective To investigate the serological and molecular characteristics of twenty blood samples carrying ABO?AW.37 allele and to analyze ABO allelic enhancement.Methods The ABO phenotype of the twenty samples was de-termined by serological methods and the genotype of 1-7 ABO exons was analyzed by Sanger sequencing.Results Sequen-cing analysis showed that all twenty samples contained a c.940A>G(p.Lys314Glu)mutation of A allele,which was defined as ABO?AW.37.When ABO?AW.37 and B alleles were inherited simultaneously in 9 cases,in forward typing anti-A anti-bodies all agglutinated and the serological phenotype was Aw B.Among the 11 cases with ABO?AW.37 and O alleles inherited simultaneously,there was no agglutination of anti-A in forward typing.For absorption and elution tests,5 cases were weakly positive and the serological phenotype was Ael,while 6 cases were negative for absorption and elution tests and the serologi-cal phenotype was O type.Conclusion Allelic enhancement occured when both ABO?AW.37 allele and B allele were in-herited simultaneously.When ABO? AW.37 was inherited simultaneously with O allele,the serological phenotype was Aelor O type and attention should be paid to blood type identification.

【Objective】 To investigate the reasonable serological detection method by analyzing the characteristics of anti-K and anti-Wr^a from a patient who received treatment with daratumumab. 【Methods】 Unexpected antibody screening and identification were performed by saline method, polybrene, cardioagglutinin, dithiothreitol (DTT) treatment, trypsin treatment and papain treatment in the patient's plasma and acid elution solution. Heat elution test was detected after absorbing patient serum with K antigen negative red blood cells. The characteristics of antibodies were analyzed and their titer was continuously detected. Cross matching was performed after excluding interference of daratumumab. 【Results】 Anti-K and anti-Wr^a were detected in saline and polybrene in the patient's plasma. The patient's elution solution contained daratumumab. DTT or trypsin treatment excluded interference of daratumumab but papain treatment did not. DTT treatment destroyed K antigen and missed the detection of IgG antibodies in the Kell system. Trypsin treatment did not affect K antigen and can detect IgG antibodies of Kell system(anti-k)in the serum of the patient treated with daratumumab. Anti K was IgM and the titer was 4 by saline method and it decreased to no agglutination in room temperature after 39 days. Anti-Wr^a was IgG and the titer by polybrene method was 4, and it decreased to 1 after 39 days. After 76 days, neither anti-K nor anti-Wr^a could be detected. Transfusions of K and Wr^a antigen negative red blood cells were safe and effective. 【Conclusion】 DTT treatment can exclude interference of daratumumab, but attention should be paid to missed detection of anti-K. To avoid interference of daratumumab and identify unexpected antibody, multiple methods such as DTT treatment, polybrene and trypsin treatment in combination are recommended.

Objective:To comprehensively evaluate the tricuspid valve, right heart anatomical characteristics and related dynamic parameters in patients with different degrees of functional tricuspid regurgitation (FTR) using four-dimensional auto tricuspid valve quantitative(4D Auto TVQ), four-dimensional auto right ventricle quantitative(4D Auto RVQ), and four-dimensional auto left atrium quantitative(4D Auto LAQ), and to investigate the structural and functional changes of the tricuspid valve and right heart in them.Methods:Sixty-three patients with FTR diagnosed by echocardiography at the First Affiliated Hospital of Guangxi Medical University from February to July 2022 were prospectively selected as the case group, including 30 patients with mild FTR and 33 patients with moderate or above FTR, and 30 healthy subjects were selected as the control group. Transthoracic echocardiography was used for two-dimensional and three-dimensional image acquisition of the heart. The tricuspid regurgitation volume, left ventricular ejection fraction (LVEF), right ventricular global strain (RVGS) were measured by 2D images, and pulmonary artery systolic pressure (PASP) were measured from the tricuspid regurgitation pressure difference. The 3D images were imported into EchoPAC 204 to obtain the tricuspid valve, right heart structure and related dynamic parameters. The annulus area (AA), annulus perimeter(AP), spherical index (SI), annulus area change fraction (AC), coaptation point height (CPH), and tenting volume (TV) were measured by 4D Auto TVQ. The right atrial maximum volume (RAVmax) and right atrial minimum volume (RAVmin) were measured by 4D Auto LAQ. Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), right ventricular fractional area change (RVFAC) and tricuspid annular plane systolic excursion (TAPSE) were measured by 4D Auto RVQ. After standardizing the dimension parameters with body surface area (BSA), the differences in the above parameters were compared between the three groups, the correlation between regurgitant volume and each parameter was compared by correlation analysis, and the independent factors of increased tricuspid regurgitant volume were investigated by univariate and multivariate linear regression analysis.Results:There were statistically significant differences in PASP, AA/BSA, AP/BSA, AC, TV, RAVmax/BSA, RAVmin/BSA, RVFAC, RVGS, and TAPSE between the three groups (all P<0.05). There were statistically significant differences in LVEF, CPH, RVEDV/BSA, and RVESV/BSA in the moderate and above FTR group compared with the control and mild FTR groups (all P<0.05). Correlation analysis showed that RAVmin was the most highly correlated with tricuspid regurgitant volume ( r=0.875, P<0.001) and TV and end-systolic annulus area(ESAA) were highly correlated with tricuspid regurgitant volume ( r=0.747, 0.683; both P<0.001) in patients with FTR. Multifactorial linear regression showed that RAVmin, TV and regurgitant volume were independently positively correlated (β=0.721, 0.205; both P<0.05). Conclusions:The four quantification technique can provide valid structural and functional information by quantifying the tricuspid valve as well as the right heart in patients with FTR, and RAVmin and TV are independent correlates of increased tricuspid regurgitant volume.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with autism spectrum disorder (ASD) in conjunct with congenital heart disease (CHD). METHODS: A child who was hospitalized at the Third People's Hospital of Chengdu on April 13, 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). A GTX genetic analysis system was used to analyze the WES data and screen candidate variants for ASD. Candidate variant was verified by Sanger sequencing and bioinformatics analysis. Real-time fluorescent quantitative PCR (qPCR) was carried out to compare the expression of mRNA of the NSD1 gene between this child and 3 healthy controls and 5 other children with ASD. RESULTS: The patient, an 8-year-old male, has manifested with ASD, mental retardation and CHD. WES analysis revealed that he has harbored a heterozygous c.3385+2T>C variant in the NSD1 gene, which may affect the function of its protein product. Sanger sequencing showed that neither of his parent has carried the same variant. By bioinformatic analysis, the variant has not been recorded in the ESP, 1000 Genomes and ExAC databases. Analysis with Mutation Taster online software indicated it to be disease causing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. By qPCR analysis, the expression level of mRNA of the NSD1 gene in this child and 5 other children with ASD was significantly lower than that of the healthy controls (P < 0.001). CONCLUSION The c.3385+2T>C variant of the NSD1 gene can significantly reduce its expression, which may predispose to ASD. Above finding has enriched the mutational spectrum the NSD1 gene.
Male ; Child ; Humans ; Autism Spectrum Disorder/genetics* ; Heart Defects, Congenital/genetics* ; Computational Biology ; Genomics ; Mutation ; RNA, Messenger/genetics* ; Histone-Lysine N-Methyltransferase/genetics*

OBJECTIVE: To explore the molecular reasons of weak expression of B antigen on the red cell. METHODS: Serological test for blood group was carried out, including red cell and plasma grouping, and anti-A1 and anti-H testing, and confirming weak A or B antigens by adsorption and elution. Exons 1-7 were sequenced directly, and one of them was cloned and sequenced. RESULTS: All of the 23 samples showed the weak B antigen by serological method. The alleles of the subgroups were identified by DNA sequencing, including 2 Bel subgroup, 4 B3 subgroup, 14 Bw subgroup, 2 CisAB subgroup and a novel allele. The novel allele showed a nucleotide substitution 662G>A in the exon 7, and the sequence was submitted to Blood Group Antigen Gene Mutation Database, and the novel allele was named Bel10. CONCLUSION Nucleotide substitution in exon results in blood subgroup, which showed that the antigens were weakened, and Bw phenotype was the most frequently subgroup.
ABO Blood-Group System/genetics* ; Alleles ; Exons ; Genotype ; Humans ; Nucleotides ; Phenotype

Talents constitute core resource in the development of healthcare sector. Based on the situation of the talent team in the Affiliated Hospital of Qingdao University, the authors systematically constructed the hierarchical and classified system for talent cultivation, centering on three key areas of talent cultivation, evaluation and assessment. The authors analyzed the achievements since the implementation in 2016, namely the innovation of talent evaluation, the construction of discipline echelon, and the communication and inter-departmental cooperation. At the same time, the authors further put forward targeted suggestions to promote the development of talent teams in terms of transforming the human resource management model, increasing policy support and funding, implementing refined management, and improving talent evaluation indicators by the levels and types.

Talents constitute key resources for the development of healthcare sector, and studying abroad is an important and effective means for their training. Based on the analysis of the current status of China′s international talents training project of hospitals, this study summarized existing problems in such training. The authors covered such six aspects as lawful standardization of project management methods, selection of trainees by levels and by types, innovation of the process tracking management mechanisms and strengthened full-process assessment, all dimensional institutional support, consolidation of the responsibilities by individual disciplines in talent team building, and measures to cope with the impact of COVID-19. In accordance with the research results, the study analyzed the exploration and practice of the international training project under the " Elite Talents Cultivation Project" of the Affiliated Hospital of Qingdao University, and raised targeted recommendations on attention to the strategic and forward-looking planning, precise setup of training goal categories, classified evaluation of study results, and lawful management among others.

Background The pollution of agricultural products and the health risks caused by metals have become a hot spot of social concern. As China's main economic agricultural products, peppers are essential for health risk assessment. Objective By exploring the enrichment of common metals in different varieties of peppers in major growing areas of China, a bioavailability-based approach is used to assess dietary health risks of common metals in groups with different characteristics. Methods Through random sampling method, dried pepper samples from major pepper growing areas of China were purchased from the market, and were divided into Hippophae, Capsicum annuum, Magnoliopsida, Capsicum frutescens var, and Capsicum by morphological taxonomy, and a total of 667 batches of peppers were collected. Six common metals arsenic (As), cadmium (Cd), lead (Pb), nickel (Ni), copper (Cu), and zinc (Zn) were evaluated; physiologically based extraction test was designed to estimate the bioavailability of the metals in peppers and their associated dietary health risks were assessed. Results The concentrations of metals Cd and Ni in pepper exceeded the limits of China, and the disqualification rates were 6.1% and 22.7% respectively. The other metals were within the safe range; there were differences in the concentrations of As, Cd, Pb, Cu, and Zn among different pepper varieties (P<0.05). The order of bioavailability of the six metals in pepper from high to low was As (57.9%)>Cd (43.07%)>Zn (42.74%)>Pb (38.04%)>Ni (31.97%)>Cu (31.4%). Based on bioavailability, when the metal concentration in pepper was at the median level, the order of hazard quotient of metals in pepper was Cu>Cd>As>Ni>Zn>Pb, and at the 90th quantile level, the order was Cd>As>Cu>Ni>Zn>Pb; the hazard quotient of single metal element and the total target hazard quotient of combined metal elements were both less than 1, and these indicators of adults were higher than those of children. Conclusion In the collected pepper samples, the non-carcinogenic health risks of single metal elements and multiple metal elements are in the safe range. Based on gastrointestinal bioavailability, the dietary health risk of pepper is further reduced.

Objective:To investigate the effects of anemoside B4 on apoptosis of retinal cells in diabetic rats.Methods:Sixty Sprague-Dawley rats were randomized into three groups: the normal control(control), diabetic rats(DM)and diabetic rats treated with Anemoside B4(B4)groups(n=20, each group). Rats in the DM and B4 groups were rendered diabetic with an intraperitoneal injection of streptozotocin(STZ, 60 mg/kg). After 3 days of successful modeling, rats in the B4 group were intraperitoneally injected with anemoside B4(5 mg/kg), twice/day, for 8 weeks, while rats in the control and DM groups were injected with an equivalent volume of normal saline.After 8 weeks of anemoside B4 and normal saline injection, rats were sacrificed and retinas were harvested for examination.Paraffin sections of retina were stained with the hematoxylin-eosin(H-E)method for morphological evaluation.Protein levels of Bax and Bcl-2 were detected by using Western blot.The expression of caspase-3 mRNA was detected with quantitative PCR.Results:H-E staining results showed the control group had intact retinal structure and clear morphological features, whereas disordered retinal structure, thinner layers, and sparse and disorganized cells were seen in the DM group.However, retinal structure and morphology were improved after treatment with anemoside B4.Compared with the control group, the protein expression of Bcl-2 was lower( t=57.81, P<0.01), the protein expression of Bax was higher( t=10.47, P<0.01), and the Bcl-2/Bax ratio was lower( t=23.98, P<0.01)in the DM group.Compared with the DM group, the protein expression of Bcl-2 was higher( t=41.07, P<0.01), the protein expression of Bax was lower( t=6.811, P<0.01), and the Bcl-2/Bax ratio was higher( t=14.70, P<0.01)in the B4 group.Caspase-3 mRNA expression was higher in the DM group than in the control group( t=7.916, P<0.01), but was lower in the B4 group compared with the DM group( t=6.221, P<0.01). Conclusions:Anemoside B4 can inhibit the apoptosis of retinal cells by up-regulating Bcl-2 expression and down-regulating Bax and caspase-3 expression in diabetic rats.