Objective: To explore the causal association between micronutrients and irritable bowel syndrome (IBS) using a Mendelian randomization (MR) method, so as to provide the evidence for formulating prevention and treatment measures for IBS. Methods: Genome-wide association studies (GWAS) summary data for 14 micronutrients (copper, selenium, zinc, iron, magnesium, calcium, potassium, folate, vitamin C, vitamin D, vitamin E, vitamin B6, vitamin B12, and carotene) were collected from the MRC Integrative Epidemiology Unit at the University of Bristol GWAS data and the UK Biobank data. GWAS data for IBS were obtained from the FinnGen R10 database. A bidirectional two-sample MR analysis was conducted to assess the causal relationships between micronutrients and IBS, with the inverse-variance weighted method as the primary analytical approach. Heterogeneity among instrumental variables was evaluated using Cochran's Q test. Horizontal pleiotropy was assessed via MR-Egger regression and the MR-PRESSO test. The robustness of the results was examined using leave-one-out and funnel plot. Results: Forward MR analysis revealed a statistically significant association between vitamin B12 and IBS (OR=1.523, 95%CI: 1.093-2.213), while no significant associations were observed for the other 13 micronutrients (all P>0.05). Reverse MR analysis showed no significant association between IBS and any of the 14 micronutrients (all P>0.05). Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among the instrumental variables (all P>0.05). The robustness of the findings was supported by leave-one-out and funnel plot. Conclusion Higher vitamin B12 level is associated with an increased risk of IBS, but no reverse causal relationship between vitamin B12 and IBS has been found.

Objective:To analyze the clinical, genetic mutation characteristics, and treatment prognosis of type 2A hereditary hemochromatosis (HH) in China.Methods:Peripheral blood samples and clinical data of patients with primary iron overload were collected through the China Registry of Genetic/Metabolic Liver Disease from June 2015 to November 2023. HH-related genes were detected by Sanger sequencing. Clinical characteristics and gene mutation characteristics of HH patients carrying HJV gene mutations were analyzed.Results:Among the 37 cases with primary iron overload, ten cases (27.0%, 10/37) had detectable HJV gene mutations, which included four homozygous mutations, five compound heterozygous mutations, and one monoheterozygous mutation. p.Q6H and p.C321X (80.0%, 8/10) were the most common mutated sites. The average age of onset was 30.7±14.7 years. The age of diagnosis was 35.7±16.2 years, with male-to-female ratio of 7:3. Ferritin and transferrin saturation were (5 267±905) ng/ml, and 94.3%±1.2%, respectively. Magnetic resonance imaging showed iron overload in the liver, pancreas, and myocardium. Liver biopsy showed diffuse iron deposition within hepatocytes. All ten cases had elevated transaminases; one case (1/10, 10.0%) had liver cirrhosis; four cases (4/10, 40.0%) had heart failure and arrhythmia; five cases (5/10, 50.0%) had diabetes; six cases (6/10, 60.0%) had hypogonadism; six cases (6/10, 60.0%) had skin pigmentation; and six cases (6/10, 60.0%) had fatigue symptoms. All six cases underwent bloodletting therapy, and ferritin levels dropped to about 100 ng/ml. Two cases of oral administration of the iron chelator deferasirox did not meet the ferritin level standard, and one case died from acute heart failure following a confirmed diagnosis during hospitalization.Conclusion:The HJV gene may be one of the main pathogenic genes of HH in China. The p.Q6H and p.C321X mutations were one of the hotspot mutations. The onset age of HJV gene-related HH was between 20 and 30 years old, and their condition was severe. Therefore, early bloodletting treatment can have a favorable outcome.

Objective To establish a novel real-time quality control method for rapidly identifying the random error of sodium ion con-centration in serum using an artificial intelligence voting algorithm,and evaluate the relevant effectiveness of the model established on this basis.Methods A total of 144 754 test results of serum sodium ion rom the inpatients measured by Beckman AU5400 biochemis-try analyzer from January to May 2021 were obtained retrospectively from laboratory information system of the Department of Clinical La-boratory,Nanjing Drum Tower Hospital,and all the data were used as unbiased data for the current study.The random errors were arti-ficially introduced to generate the corresponding biased data set.Subsequently,the voting algorithm-based internal quality control model(ViQC)was established using the principles of the voting algorithm.The ViQC model and five classical PBRTQC(patient-based real-time quality control)algorithms were performed direct to each biased data.The analytical performance of the ViQC model was evaluated by using classification model criteria.The trimmed average number of patient samples until error detection(tANPed)was used to com-pare the clinical detection efficacy of the ViQC model with those of the five classical algorithms,and the error detection curves were plotted.Results Compare with all the classical algorithms,the ViQC model showed a false positive rate below 0.002 and achieved ac-curacy above 0.951 in detecting all the deviations.When the error factors were 1.5,2.5,and 3.0,the false positive rate of the ViQC model was zero.When the error factor was 2.5,its accuracy reached 0.979.Compared to the five classical PBRTQC algorithms,the ViQC model reduced the overall average tANPed by up to 34％and showed higher sensitivity for error detection.In addition,the ViQC model demonstrated the area under the ROC curve was as high as 0.989 at TEa on the test set,but the value of tANPed wasonly five.Conclusion We successfully established a real-time quality control model for the data of patients based on artificial intelligence algo-rithms,and its efficacy of clinical detection was superior to the traditional PBRTQC algorithms.

This experiment was divided into two parts:in vivo and in vitro.In the in vivo experi-ment,10 healthy and 10 ketotic cows were selected,and adipose tissues were collected.ELISA re-sults showed that malonaldehyde(MDA)content and reactive oxygen species(ROS)activity were higher in adipose tissues of cows with clinical ketotic compared with healthy cows,and glutathione peroxidase(GPP)activity was higher than that of cows with clinical ketotic.Western blot results showed that compared with the healthy group,adipose tissue of the ketotic group showed a signifi-cant increase in the expression level of TP53 induces glycolysis and apoptosis factors(TIGAR)protein,a significant up-regulation in the expression level of Nrf2-HMOX1 signaling pathway pro-tein,and a significant increase in the expression level of oxidative stress protein in adipose tissue of the ketotic group.The expression level of TIGAR protein was significantly up-regulated,the pro-tein level of Nrf2-HMOX1 signaling pathway was significantly up-regulated,and the protein levels of oxidative stress-related indexes SOD1,catalase(CAT)and glutathione S-transferase(GST)were significantly increased.It indicated that oxidative stress occurred in the adipose tissue of ketotic cows in vivo.In vitro experiments were carried out to detect the effect of TIGAR on oxida-tive stress in bovine adipocytes by adenoviral silencing or overexpression of TIGAR in isolated and cultured bovine primary adipocytes as well as by the addition of hydrogen peroxide in vitro for 2 h.The Western blot results showed that the hydrogen peroxide group showed enhanced oxidative stress compared with the control group,and the nuclear correlation factor 2 was significantly in-creased.correlation factor 2(Nrf2)pathway,decreased expression of Nrf2 and hemeoxygenase-1(HMOX1),and decreased expression of related oxidative stress proteins in the hydrogen peroxide group;compared with the hydrogen peroxide group,the protein expression levels of Nrf2-HMOX1 and related oxidative stress proteins were up-regulated in the group with overexpression of TIGAR and hydrogen peroxide,and the expression levels of related oxidative stress proteins were up-regu-lated in the group with overexpression of TIGAR and hydrogen peroxide.Expression level was up-regulated,and the expression of related oxidative stress proteins SOD1,CAT and GST increased.This indicates that overexpression of TIGAR alleviated hydrogen peroxide-induced oxidative stress in adipocytes.Protein expression of Nrf2-HMOX1 signaling pathway and oxidative stress-related proteins SOD1,CAT and GST were down-regulated in the silencing TIGAR plus hydrogen perox-ide group compared to the hydrogen peroxide group.It indicates that silencing TIGAR exacerbated the oxidative stress caused by hydrogen peroxide to adipocytes.

Objective:To investigate the relapse risk factors of anti-aquaporin 4 (AQP4)-IgG positive neuromyelitis optica spectrum disorders (NMOSD) patients treated with immunosuppressant.Methods:Data (from January 2011 to June 2021) of AQP4-IgG positive NMOSD patients treated with immunosuppressant for longer than 5 years from MSNMObase, a hospital-based electronic registry for multiple sclerosis and related disorders in Peking Union Medical College Hospital, were collected. Clinical features and risk factor differences between patients with and without relapse under the immunosuppressive therapy were analyzed.Results:One hundred and twelve patients with AQP4-IgG positive NMOSD were included, 105 (93.8%) of which were female. The disease onset age was (34.9±11.3) years, 13(11.6%) had an older disease onset age than 50 years (late onset), and the disease duration was 8.1 (6.6, 11.4) years. Sixty-four (57.1%) patients had relapse, and the proportion of late onset patients was significantly lower in relapse group than in non-relapse group [4/64(6.3%) vs 9/48(18.8%), χ2=4.18, P=0.041]. Compared with those without relapse, both the annualized relapse rate (ARR) before treatment [1.07 (0.36, 2.25) vs 0.34 (0, 1.11), Z=2.92, P=0.003] and the proportion of patients with relapse before treatment [54/64(84.4%) vs 33/48(68.8%), χ2=3.86, P=0.049] were significantly higher for patients in relapse group. Multivariate Logistic regression analysis revealed the relapse risk of late-onset patients was lower than that of early-onset patients ( HR=0.26, 95% CI 0.10-0.73, P=0.010) and patients with higher ARR before treatment showed a higher risk of relapse under the immunosuppressive therapy ( HR=1.55,95% CI 1.26-1.91, P<0.001). Conclusion:AQP4-IgG positive NMOSD patients with younger disease onset age than 50 years or with frequent relapses before treatment had a higher relapse risk under the immunosuppressive therapy, and they may need highly effective treatments.

Objective:Longitudinally extensive transverse myelitis (LETM) could be seen in patients with connective tissue disease (CTD), especially systemic lupus erythematosus (SLE) or primary Sj?gren′s syndrome (pSS). Some patients are combined with neuromyelitis optica spectrum disorders (NMOSD)(termed CTD-LETM-NMOSD) while others without (termed CTD-LETM-non-NMOSD). The aim of this study is to compare the clinical characteristics of CTD-LETM-NMOSD patients to CTD-LETM-non-NMOSD patients.Methods:We retrospectively collected data from 40 CTD patients with LETM who were admitted to the Department of Neurology or Rheumatology at Peking Union Medical College Hospital from Jan, 2006 to Dec, 2016. They were divided into CTD-LETM-NMOSD and CTD-LETM-non-NMOSD two groups. Demographic characteristics, clinical and laboratory features were obtained from the database. Relapse rates and clinical outcome were analyzed by Kaplan-Meier method.Results:Among 40 patients with CTD, 28 (70.0%) were NMOSD while 12 (30.0%) were not. The positivity rates of anti-SSA, antibodies to aquaporin-4 (anti-AQP4) were significantly higher in patients with NMOSD than those in patients with non-NMOSD ( P<0.05). Age, gender, clinical features, disease duration, anti-double-stranded DNA antibody, anti-ribosomal P antibody, antiphospholipid antibodies, expanded disability status scale (EDSS) scores, and magnetic resonance imaging (MRI) features were all comparable between two groups. CTD-NMOSD patients had significantly higher disease relapse rate (75.0% vs. 3/12, P<0.01). Conclusion:Anti-SSA and anti-AQP4 positivity is associated with NMOSD and higher relapse rates, which suggests that NMOSD in CTD-LETM patients may represent distinct characteristics and pathogenesis from patients with CTD-LETM-non NMOSD.

Objective:To explore the clinical value of sarcopenia and vitamin D deficiency on gluco-corticoid induced osteoporosis (GIOP) in patients with rheumatoid arthritis (RA).Methods:Three hundred and eleven patients with RA from January 2017 to December 2018 were enrolled in the study. One hundred and fifty-eight sex, age-matched normal subjects were recruited as control group. Clinical and laboratory features, daily dosage and treatment duration of glucocorticoid (GC) were recorded in detail. Skeletal muscle mass was measured by biological electrical impedance. Serum levels of 25-hydroxy vitamin D [25(OH)D] were examined using electro-chemiluminescence. Bone mineral density (BMD) at total hip and lumbar vertebra were detected by dual energy X-ray absorptiometry (DEXA). Numerical data and categorical data comparisons were analyzed using χ2 test, non-parametric test, Logistic regression analysis test. Results:① The prevalence of osteoporosis (OP) in RA patients was 33.4%(104/311), which was higher than that in the control group 12.7%(20/158)( χ2=23.267, P<0.01). Percentage of GC taking in 311 RA patients was 56.6%(176/311), and the prevalence of GIOP was 40.9%(72/176). The prevalence of sarcopenia in RA patients was 61.7%(192/311), which was higher than that in the control group [9.0%(14/156), χ2=117.310, P<0.01]. The prevalence of vitamin D deficiency in RA patients was 81.7%(254/311), which was higher than that in control group [38.0%(60/158), χ2=90.415, P<0.01]. ② The prevalence of OP in RA without sarcopenia was 17.6% (21/119), which was lower than that in patients with sarcopenia [43.2%(83/192), χ2=21.601, P<0.01]. In condition without GC, the prevalence of OP in RA without sarcopenia was 9.8%(6/61), which was significantly lower than that in patients with sarcopenia [35.1%(26/74), χ2=11.834, P<0.01]. Under circumstances with GC, the prevalence of OP in RA without sarcopenia (25.9%, 15/58), which was significantly lower than that in patients with sarcopenia (48.3%, 57/118, χ2=8.103, P<0.01). ③ No matter whether existing vitamin D deficiency or not, the prevalence of OP in RA without GC was 23.7%(32/135), which was significantly lower than that in patients with GC [40.9%(72/176), χ2=10.161, P<0.01]. In patients without vitamin D deficiency, the prevalence of OP in RA without GC was 21.4%(6/28), which was similar to that in patients with GC [31.0%(9/29), χ2=0.678, P>0.05]. In the case of vitamin D deficiency, the prevalence of OP in RA without GC was 24.3%(24/107), which was significantly lower than that in patients with GC [42.9% (63/147), χ2=9.370 2, P<0.01]. ④ In RA patients with GC, age( t=5.313, P<0.01), Sharp score ( Z=2.999, P<0.01), disease duration ( Z=2.141, P<0.05) and treatment duration of GC ( Z=2.460, P<0.05) were higher in group with GIOP than that in group without GIOP, while erythrocyte sedimentation rate (ESR)( Z=2.262, P<0.05), C-reactive protein levels (CRP) ( Z=2.551, P<0.05) and body mass index (BMI) ( t=2.425, P<0.05) were lower and the composition ratio of X-ray staging was worse ( χ2=12.484, P<0.01).⑤ Logistic regression analysis (LR Backward) showed that female gender [ OR(95% CI)=14.240(3.878, 52.288), P<0.01], age [ OR(95% CI)=1.079(1.042, 1.118), P<0.01] and sarcopenia [ OR(95% CI)=2.470(1.192, 5.120), P<0.05] were the risk factors for GIOP in RA patients. Conclusion:The proportion of treatment with GC in RA patients is very high (about 60%), and the prevalence of GIOP is 40.9%, which is closely related to sarcopenia and vitamin D deficiency.

Objective: To investigate factors affecting X-ray structure of the spine in patients with ankylosing spondylitis (AS). Methods: A total of 206 AS patients were recruited. Clinical and laboratory parameters in AS patients were recorded in detail. Disease activity index [Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAScrp)], X-ray structural damage index-modified stoke ankylosing spondylitis spine score (mSASSS) and grading results of radiographic examination of sacroiliac joint were calculated. Statistical analysis using Statistical Package form Soci-science(SPSS) 17.0 Chi-square test, rank test, Logistics regression analysis and other statistical methods were used. Differences of mSASSS levels, spine involvement (mSASSS>0) and rates of bone bridge formation were compared between different groups. Results: Incidences of spine involvement (100%) and bone bridge formation(65.2%) in AS patients ≥40 years old were significantly higher than those in AS patients <40 years old (90.6%、31.9%)(χ²=4.651, P=0.031; χ²=16.647, P<0.01), and the level of mSASSS was also higher (Z=5.575, P<0.01). In AS patients with BMI ≥24 kg/m², disease duration ≥5 years (49.2%, 50.4%), rates of bone bridge formation was significantly higher than those in AS with BMI <24 kg/m², but the disease duration (34.5%, 19.7%)(χ²=4.014, P=0.045; χ²=18.173, P=0.03), and mSASSS values were significantly higher (Z=2.281, P=0.023, Z=4.828, P<0.01). Bone bridge formation rate in smoking patients (50.6%) was significantly higher than that in non-smoking patients (31.0%) (χ²=7.346, P=0.007) and mSASSS value was significantly higher (Z=2.045, P=0.041). Bone bridge formation rates in AS with high-ESR and high-CRP(48.6%, 49.0%) were significantly higher than those in patients with normal-ESR and normal-CRP(25.6%, 28.9%)(χ²=10.784, P=0.001; χ²=8.102, P=0.004) and mSASSS value was clearly higher(Z=2.379, P<0.01; Z=3.112, P<0.01). Bone bridge formation rate in AS with BASDAI≥4 or ASDAScrp≥2.1 groups (52.8%, 46.4%) were significantly higher than that in AS with BASDAI<4 or ASDAScrp<2.1 groups (34.2%, 30.7%) (χ²=5.681, P=0.017; χ²=4.646, P=0.031) and mSASSS values were significantly higher (Z=3.887, P<0.01; Z=3.895, P=0.004). Rates of bone bridge formation among different X-ray grading of sacroiliac joint (10.8%, 35.6%, 60.3%) and MRI findings (33.3%, 50.0%, 15.4%) differed with each other (χ²=25.714, P<0.01; χ²=6.855, P=0.032). Logistics regression analysis showed that BMI [OR(95%CI)=1.145(1.037, 1.265), P<0.01], disease duration [OR(95%CI)=1.144(1.055, 1.239), P<0.01], smoking [OR(95%CI)=2.832(1.343, 5.969), P<0.01] and sacroiliac joint X-ray staging [OR(95%CI)=2.584(1.337, 4.997), P<0.01] were risk factors for the bone bridge formation in spine of AS. Conclusion Spinal involvement in AS is related to disease activity. Bone bridge formation correlateswith disease duration, BMI and disease-status, especially with smoking.

Objective To explore the prevalence and reference value of disease features of patients with spondyloarthritis. Methods Spondyioarthritis features and laboratory indexes and radiographic indexes of 505 patients with spondyloarthritis (SpA) including 353 patients with ankylosing spondylitis (AS), 62 patients with non-radiographic axial spondyloarthritis (nr-axSpA) and 90 patients with peripheral spondyloarthritis (pSpA) were recorded. One-way analysis of variance, Kruskal-Wallis test, x2-test, Logistic regression were used for statistical analysis. Results Sex ratio ( x2=20.673, P<0.01), age ( x2=22.258, P<0.01), disease duration ( x2=76.052, P<0.01) were different among AS, nr-axSpA and pSpA. Besides, Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAScrp), erythrocyte sedimentation rate (ESR), C-reactionprotein (CRP) and Bath ankylosing spondylitis functional index (BASFI)were different among SpA subgroups ( x2/F=13.196-40.028, P<0.01). Prevalence of inflammatory back pain, peripheral arthritis, preceding infection, positive human lymphocyte antigen (HLA)-B27 and elevated CRP were different among SpA subgroups ( x2=11.416, 32.657, P<0.01). Prevalence of dactylitis in SpA with positive HLA-B27 was lower than that in SpA with negative HLA-B27 ( x2=5.414, P=0.02). Prevalence of enthesitis and dactylitis in SpA patients with peripheral arthritis was higher than that in SpA without peripheral arthritis involvement ( x2=7.177, 14.428, P<0.01). Prevalence of good response to Non-steroid anti-inflammatory drugs. (NSAIDs) in patients with anterior uveitis involvement was higher than SpA without anterior uveitis involvement ( x2=4.578, P=0.032). SpA patients were stratified by total number of SpA features into 4 subgroups (n≤1, n=2, n=3, n≥4). Prevalence of inflammatory back pain, positive HLA-B27, good response to NSAIDs were the top three in all subgroups. Inflammatory back pain and HLA-B27 (+) were risk factors for axSpA (OR=3.254, 3.323, P<0.01). Peripheral arthritis, dactylitis, and preceding infection were risk factors for pSpA (OR=3.759, 4.134, 17.044, P<0.01). Conclusion Inflammatory back pain, HLA-B27 (+) and good response to NSAIDs should be emphasized for the diagnosis of SpA. Inflammatory back pain and HLA-B27(+) always means axSpA. Peripheral arthritis, dactylitis and preceding infection always indicates pSpA.