Objective:To screen bile acid-related characteristic genes in IgA nephropathy (IgAN) based on the feature gene selection algorithm in the machine learning method, aiming to exploring the molecular biological mechanisms and biomarkers of IgAN.Methods:The gene expression data and sample grouping information of GSE93798, GSE116626 and GSE35487 were downloaded from the Gene Expression Omnibus (GEO). Bile acid-related gene sequences were obtained from the Molecular Signatures Database (MSigDB). R language was used to identify differentially expressed genes between IgAN samples and healthy control samples. Candidate genes were obtained by intersecting differentially expressed genes and bile acid-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm in machine learning was used to screen the feature genes in the candidate genes as biomarkers, and the feature genes in the training set and validation set were analyzed by the rate of change index. Receiver operating characteristic curve (ROC) method was used to evaluate the diagnostic value of identified bile acid related characteristic genes for IgAN. Gene set enrichment analysis (GSEA) was used to analyze the Spearman correlation between the characteristic genes and all other genes and their related metabolic pathways. The expression of disease-characteristic genes in the kidney tissues of IgAN rats was validated by real-time PCR.Results:Gene expression information from kidney tissue samples of 20 IgAN cases and 22 healthy controls were obtained from GEO database. A total of 204 bile acid-related genes including 24 pathways were obtained from MSigDB. The results of gene differential expression analysis showed that 333 genes in the kidney tissues of IgAN patients were differentially expressed compared with those of healthy controls, including 102 up-regulated genes and 231 down-regulated genes, among which 12 differentially expressed genes were related to bile acid genes, as follows: NR1H4,SLC23A1, ALDH8A1, FABP1, ALB, SLC27A2, DIO1, CYP8B1, BBOX1, PIPOX, AKR1C1 and SLC10A2. Five characteristic genes ( NR1H4, SLC23A1, FABP1, ALB and AKR1C1) were screened by LASSO regression algorithm.ROC analysis results showed that in GSE93798 cohort genes, the AUC of NR1H4, SLC23A1, FABP1 and ALB genes with differential expression was >0.95 respectively in diagnosing IgAN, and that of AKR1C1 genes with differential expression was >0.85 in diagnosing IgAN. The gene expression data of SLC23A1 in GSE35487 cohort was missing. ROC analysis results of other four genes showed that the AUC of differential expression of ALB gene for IgAN was >0.95 respectively, that of NR1H4 gene was >0.70, and that of both FABP1 and AKR1C1 gene was >0.60. In the GSE116626 cohort genes, the AUC of five disease characteristic genes ( NR1H4, SLC23A1, FABP1, ALB, AKR1C1) for diagnosing IgAN was >0.60, respectively. These results suggested that 5 characteristic genes have certain distinguishing ability between IgAN group and control group. GSEA results were displayed that the characteristic genes were related to butyric acid metabolism, propionic acid metabolism, arginine and proline metabolism, valine leucine and isoleucine degradation, fatty acid metabolism, etc. These results suggested that five characteristic genes might be related to IgAN through the above metabolic mechanisms. The verification results of five bile acid characteristic genes in the rat model of IgAN in the kidney tissue showed that the expressions of four genes, NR1H4, SLC23A1, FABP1 and ALB, were higher than those of the control group, and there was no statistical significance in the expression of AKR1C1 gene between the two groups. Conclusions:The expression of bile acid-related characteristic genes is abnormal in the kidney tissue of IgAN patients. Four bile acid-related differentially expressed genes, NR1H4, SLC23A1, FABP1 and ALB, are expected to be biomarkers for non-invasive diagnosis and therapeutic targets .

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) induced by anti-thyroid drugs has been reported occasionally, but methimazole-induced AAV is not as frequently reported. This case report described a 54-year-old male who developed AAV and multiple organ failure after more than 20 days of methimazole treatment. After timely discontinuation of the disease-causing drug methimazole, the patient received methylprednisolone shock, cyclophosphamide immunosuppression, renal replacement therapy, and other supportive treatments, and the disease was alleviated without recurrence.

Objective:To screen bile acid-related characteristic genes in IgA nephropathy (IgAN) based on the feature gene selection algorithm in the machine learning method, aiming to exploring the molecular biological mechanisms and biomarkers of IgAN.Methods:The gene expression data and sample grouping information of GSE93798, GSE116626 and GSE35487 were downloaded from the Gene Expression Omnibus (GEO). Bile acid-related gene sequences were obtained from the Molecular Signatures Database (MSigDB). R language was used to identify differentially expressed genes between IgAN samples and healthy control samples. Candidate genes were obtained by intersecting differentially expressed genes and bile acid-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm in machine learning was used to screen the feature genes in the candidate genes as biomarkers, and the feature genes in the training set and validation set were analyzed by the rate of change index. Receiver operating characteristic curve (ROC) method was used to evaluate the diagnostic value of identified bile acid related characteristic genes for IgAN. Gene set enrichment analysis (GSEA) was used to analyze the Spearman correlation between the characteristic genes and all other genes and their related metabolic pathways. The expression of disease-characteristic genes in the kidney tissues of IgAN rats was validated by real-time PCR.Results:Gene expression information from kidney tissue samples of 20 IgAN cases and 22 healthy controls were obtained from GEO database. A total of 204 bile acid-related genes including 24 pathways were obtained from MSigDB. The results of gene differential expression analysis showed that 333 genes in the kidney tissues of IgAN patients were differentially expressed compared with those of healthy controls, including 102 up-regulated genes and 231 down-regulated genes, among which 12 differentially expressed genes were related to bile acid genes, as follows: NR1H4,SLC23A1, ALDH8A1, FABP1, ALB, SLC27A2, DIO1, CYP8B1, BBOX1, PIPOX, AKR1C1 and SLC10A2. Five characteristic genes ( NR1H4, SLC23A1, FABP1, ALB and AKR1C1) were screened by LASSO regression algorithm.ROC analysis results showed that in GSE93798 cohort genes, the AUC of NR1H4, SLC23A1, FABP1 and ALB genes with differential expression was >0.95 respectively in diagnosing IgAN, and that of AKR1C1 genes with differential expression was >0.85 in diagnosing IgAN. The gene expression data of SLC23A1 in GSE35487 cohort was missing. ROC analysis results of other four genes showed that the AUC of differential expression of ALB gene for IgAN was >0.95 respectively, that of NR1H4 gene was >0.70, and that of both FABP1 and AKR1C1 gene was >0.60. In the GSE116626 cohort genes, the AUC of five disease characteristic genes ( NR1H4, SLC23A1, FABP1, ALB, AKR1C1) for diagnosing IgAN was >0.60, respectively. These results suggested that 5 characteristic genes have certain distinguishing ability between IgAN group and control group. GSEA results were displayed that the characteristic genes were related to butyric acid metabolism, propionic acid metabolism, arginine and proline metabolism, valine leucine and isoleucine degradation, fatty acid metabolism, etc. These results suggested that five characteristic genes might be related to IgAN through the above metabolic mechanisms. The verification results of five bile acid characteristic genes in the rat model of IgAN in the kidney tissue showed that the expressions of four genes, NR1H4, SLC23A1, FABP1 and ALB, were higher than those of the control group, and there was no statistical significance in the expression of AKR1C1 gene between the two groups. Conclusions:The expression of bile acid-related characteristic genes is abnormal in the kidney tissue of IgAN patients. Four bile acid-related differentially expressed genes, NR1H4, SLC23A1, FABP1 and ALB, are expected to be biomarkers for non-invasive diagnosis and therapeutic targets .

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) induced by anti-thyroid drugs has been reported occasionally, but methimazole-induced AAV is not as frequently reported. This case report described a 54-year-old male who developed AAV and multiple organ failure after more than 20 days of methimazole treatment. After timely discontinuation of the disease-causing drug methimazole, the patient received methylprednisolone shock, cyclophosphamide immunosuppression, renal replacement therapy, and other supportive treatments, and the disease was alleviated without recurrence.

Objective To construct a survival prediction model for the patients with extramedullary plasmacytoma (EMP),and to evaluate its application value.Methods The data of the patients diagnosed as EMP from 2000 to 2019 were collected from the National Cancer Institute's Surveillance,Epidemiology,and End Results (SEER) database.Random forest algorithm was used to screen variables,multivariate Cox pro-portional hazards regression model was used to determine the independent risk factors of EMP prognosis,and a nomogram model was constructed based on these factors.The total score of the patients was calculated ac-cording to the nomogram model,and the total samples were divided into the low,medium and high risk groups according to the optimal cutoff value by using X-tile software,and the Kaplan-Meier survival curves of the three groups were analyzed.The predictive performance of the model was evaluated using area under the curve (AUC) of time-dependent receiver operating characteristic (t-ROC) curve,AUC after X years N repeated K-fold cross-validation,calibration curve,and decision curve analysis (DCA).Results A total of 1458 patients with EMP were included,including 796 cases of deletions and 662 cases of death.In the deletion and deaths groups,the majority were aged 60-<75 years old (35.4％,41.2％),male (63.1％,66.3％),white race peo-ple (81.3％,80.4％),and married (68.2％,59.4％).Finally,age (45-<60 years old/60-<75 years old/≥ 75 years old),marital status (single/others),non-primary malignant tumor,and without surgery and radio-therapy were determined to be the independent risk factors for the survival of EPM patients (P<0.05).Based on the above independent risk factors,a survival prediction model was constructed,and a nomogram was drawn.According to the optimal cutoff value,the total sample was divided into the score of 0-96 group (low risk group),score of 98-135 group (medium risk group) and score of 139-191 group (high risk group).The Kaplan-Meier survival analysis revealed that there was statistically significant difference in the survival time a-mong the three groups (P<0.0001).AUC of t-ROC curves for 1,3,5 years and AUC after cross-validation all were>0.7,indicating that the model had a good degree of differentiation.The calibration curves suggested a good consistency between the prediction and practical over survival rate,and DCA indicated that the model could improve the clinical benefits.Conclusion The constructed survival prediction model for EMP patients based on the SEER database could help the clinicians to identify the prognostic risk factors and predict the o-verall survival rate of the patients.

【Objective】 To retrospectively analyze the clinical manifestations, related laboratory examinations and gene mutation of 20 patients with congenital Fibrinogen disorders (CFD) admitted to our hospital from February 2017 to December 2021, so as to improve the understanding of CFD diagnosis. 【Methods】 Clinical characteristics and laboratory examination of 20 CFD patients were collected, and common secondary hypoFibrinemia factors were excluded. Gene sequencing was performed on all exons and flanks of FGA, FGB and FGG genes of 20 patients to find gene mutation sites. The peripheral blood genomic DNA was collected from the family members of two CFD patients, and the genes of the corresponding mutation sites of the proband were detected. 【Results】 The 20 CFD patients had no history of bleeding; 11 female patients had no history of spontaneous abortion; all 20 patients had reduced Fib and prolonged thrombin time (TT). There were 13 gene mutations of different types in 20 patients, among which 90% (18/20) were missense mutations, 5% (1/20) was deletion mutation, and 5% (1/20) was frameshift mutation. Seven patients (35%) had Arg35His mutation at site 104 of the FGA chain, among which 3 new gene mutations have not been reported in China. 【Conclusion】 Most CFD patients with mild or asymptomatic symptoms can be diagnosed by genetic testing and screening. FGA chain Arg35His is a mutation hotspot in this region, and all of them are Uyghur. Whether the mutation of this site is related to ethnicity needs to be confirmed by further studies.

Objective:To observe the reliability and validity of using a head-neck relocation test (HRT) in assessing cervical position sense.Methods:A total of 62 subjects were recruited, including 32 with neck pain and 30 healthy subjects. All received two HRTs conducted by two independent assessors at a first session, and then they received another HRT 24 hours later administered by one of them. The joint position error (JPE) was measured in the four directions of cervical motion: flexion, extension, levorotation and dextrorotation. The intra- and inter-rater reliability was quantified in terms of intra-class correlation coefficients (ICCs) and the difference in JPE between the two groups was also determined for validity.Results:The intra- and inter-rater reliability for the HRT in the four directions had ICC values of 0.603-0.830 and 0.597-0.837 respectively. The corresponding standard error of measurement (SEM) values were 1.52-2.15cm and 1.69-2.09cm, while the minimal detectable change (MDC) values were 4.20-5.97cm and 4.69-5.79cm, respectively. The patients with neck pain had significantly larger JPE in cervical extension and right rotation compared to healthy individuals, on average. And their JPE for cervical extension had an area under the curve (AUC) of the receiver′s operating curve of 0.755.Conclusions:The HRT showed good intra- and inter-rater reliability in assessing cervical joint position sense. The JPE for cervical extension can be used to discriminate those with neck pain from healthy subjects.

OBJECTIVE：To investigate the correlation between CYP2C19 gene polymorphisms and antiplatelet reactivity of clopidogrel in Xinjiang Uygur patients with acute coronary syndrome （ACS）. METHODS ：Totally 90 Uygur patients with ACS who were admitted to the cardiovascular department of Xinjiang Kashi Second People ’s Hospital from Jan. 2018 to Jan. 2019 were selected as the study subjects. They were given anti-platelet therapy of asprin+clopidogrel ，and received the treatment continuously for one year after discharge. The platelet aggregation inhibition （DPAI）rate of the patients were determined ，and the response to clopidogrel was evaluated. PCR-fluorescence probe method was used to detect genotype of CYP2C19*2 and * 3，and PCR-direct sequencing method was used to detect genotype of * 17. Multivariate Logistic regression analysis was adopted to investigate the correlation of gene and non-gene factors with DPAI of patients. RESULTS ：Among 90 patients，there were 10 patients with clopidogrel resistance （CR）and 80 patients with non-CR. There were 58，28 and 4 patients with CYP2C19*2 G/G，G/A，A/A genotype，respectively；there were 88 and 2 patients with CYP2C19*3 G/G，G/A genotype ，respectively；there were 64 and 26 patients with CYP2C19*17 C/C，C/T genotype ，respectively；the genotype frequency of each genotype was consistent with Hardy-Weinberg equilibrium （P＞0.05）. After treatment ，DAPIs of patients with CYP2C19*2 G/A，A/A genotype were decreased significantly，while those of the patients with A/A genotype were significantly lower than patients with G/A genotype patients （P＜ 0.05）. DAPIs of patients with CYP2C19*17 C/T genotype were increased significantly ，compared with C/C genotype 2016D01C087） patients （P＜0.05）. There was no statistical significance in @fudan.edu.cn DAPIs between CYP2C19*3 G/A and A/A genotype patients （P＞0.05）. Multivariate Logistic regression analysis showed 85775264@qq.com that CYP2C19 gene pol ymorphism was independently related to DPAI in Xinjiang Uygur patients with ACS [OR ＝2.314，95％CI（1.569，3.144），P＝0.009]，while age ，gender，smoking and other non-gene factors were not related to DPAI （P＞0.05）. CONCLUSIONS ：CYP2C19 gene polymorphism is associated with antiplatelet reactivity of clopidogrel in Xinjiang Uygur patients with ACS. * 2 wild type patients may have higher DPAI ，while * 17 wild type patients may have lower DPAI.

Objective:To investigate the correlation of multiple single nucleotide polymorphisms(SNPs)of thyroid peroxidase(TPO)and thyroglobulin(Tg)genes with Hashimoto′s thyroiditis(HT).Methods:Based on the gene mutation sites obtained from the second-generation sequencing of the target region of the previous autoimmune thyroid disease cases in our research group, the representative sites were selected for confirming in the expanded samples. A total of 301 Uyghur patients with HT and 383 controls were selected to determine the genotypes of representative SNPs(rs4927631, rs2071400, rs2071403, rs2403883, rs4236899, rs4736434, rs180195)using MassArry Sequenom platform. Correlation analysis and linkage analysis were performed with SPSS 21.0 software.Results:(1)The SNP rs4927631 gene frequency and genotype of TPO gene were significantly different between the case and control groups. The SNP rs2071403 gene frequency of TPO gene revealed statistically different between the case and control groups.(2)With analysis under different genetic models, the rs4927631 and rs2071403 of TPO gene were associated with HT under the additive model(AA/GG)and dominant model( P<0.05). The rs180195 of Tg gene was associated with HT in a recessive model( P<0.05). (3)All subjects were grouped according to the dominant genotype(AA+ GA)and recessive genotype(GG)of the TPO gene rs2071403, and mean age, gender distribution, proportion of those with higher TSH, and lower FT 4 were compared between two groups. Only thyroid peroxidase antibody(TPOAb) level displayed a statistical difference( P<0.05). This was the case for the patients with HT after grouped according to the above method( P<0.05). Conclusion:The rs4927631 and rs2071403 loci of TPO gene are associated with the pathogenesis of HT in Xinjiang Uygur.

Objective To establish a reference range for specific thyroid function during pregnancy and to explore the influencing factors of hypothyroxinemia during pregnancy.Methods A retrospective analysis of 2 996 cases of thyroid function in the pregnant women who were with single pregnancy and without thyroid diseases and family history of those diseases.Results (1) Establish a unified reference range for specific thyroid function during pregnancy;the early,middle,and late trimesters thyrotropin (TSH) ranges were 0.02-6.39,0.16-6.23,0.64-6.59 mU/L,respectively,while free thyroxine (FT4) ranges were 11.32-23.00,9.39-18.92,8.54-16.73 pmol/L respectively.The specific reference ranges of Han and Uygur pregnant women were established separately.There was no difference in the detection rates of various thyroid diseases when using their respective reference ranges and the unified reference range of the hospital (P ＞ 0.05).(2) The detection rate of various thyroid diseases (except subclinical hyperthyroidism) of our subjects with China guideline reference range was significantly higher than the reference range with the hospital (P＜0.05).(3) The detection rates of hypothyroxinemia in all pregnant women with FT4 cut points of P2.5 and P5 were 4.3％ and 7.4％,respectively,of which the Han population was 4.3％ and 7.1％,respectively,and the Uygur population was 4.3％ and 7.9％,respectively.(4) Comparing the mean age,gestational age,median urine iodine,and thyroid antibody positive rate between the hypothyroxinemia group and the control group,only the mean age and gestational age were different (P＜0.05);Logistic binary regression analysis showed that age was the risk factor for hypothyroxinemia during pregnancy (OR =1.035,95％ CI 1.006-1.066,P ＜ 0.05).Conclusions The Han and Uygur pregnant women in this area both can use the thyroid reference range of our hospital during pregnancy.The establishment of thyroid reference range may avoid over-diagnosis of thyroid disease during pregnancy.Age is a possible influencing factor of hypothyroxinemia during pregnancy.