Objective:To analyze the Risk factors for rapid progression of inpatients with anti-melanoma differentiation associated gene5 (MDA5) antibody-positive dermamyositis (DM) complicated with interstitial lung disease (ILD), and construct a clinical predictive model.Methods:A total of 63 hospitalized patients with anti MDA5 positive DM combined with ILD (MDA5+ DM-ILD) from January 1, 2016 to May 30, 2022 at the Second Affiliated Hospital of the Air Force Military Medical University were included in the study. They were divided into a control group (DM-ILD) and an observation group (DM-RPPILD) based on whether they had rapidly progressing interstitial lung disease (RPILD). Retrospective collection and organization of clinical case data from patients were conducted, and binary logistic regression was used to summarize the risk factors of DM-RPILD. R software was used to construct a clinical prediction model for RPILD occurrence using training set data, and validation set data was used to verify the predictive ability of the model.Results:The proportion of patients with SpO 2<90% at the initial diagnosis of ILD, the titers of anti MDA5 antibodies, immunoglobulin M (IgM), serum ferritin (FER) levels, and positive rates of anti Ro52 antibodies in the observation group were higher than those in the control group, the lymphocyte (LYM) count level was lower than that of the control group (all P<0.05). Binary logistic regression analysis showed SpO 2<90% at the initial diagnosis of ILD, FER level, LYM count, and anti Ro52 antibody were the influencing factors for the occurrence of RPILD (all P<0.05). The area under the curve (AUC) of the training set prediction model for predicting resistance to MDA5+ DM-RPILD was 0.922(95% CI: 0.887-0.957), with a sensitivity of 95.7% and a specificity of 72.5%; In the validation set, the prediction model predicted an AUC of 0.939(95% CI: 0.904-0.974) for resistance to MDA5+ DM-RPILD, with a sensitivity of 90.0% and a specificity of 88.9%; The calibration curves of the training and validation sets indicated that the predictive model had good calibration ability. Conclusions:SpO 2<90% at the initial diagnosis of ILD, FER levels increase, LYM count levels decrease, and anti Ro52 antibody positivity are risk factors for RPILD. The constructed clinical model has good predictive ability and has certain guiding significance for clinical work.

Objective:To analyze the clinical and genotype features of infants with epilepsy caused by RYR2 gene mutations, and explore the correlation between RYR2 gene mutations and epilepsy. Methods:The clinical characteristics and genetic test results of 2 infants with epilepsy caused by RYR2 gene mutations, admitted to Department of Pediatrics, First Affiliated Hospital of Zhengzhou University in December 2020 or May 2022, were retrospectively analyzed. The related literature was reviewed. Results:These 2 infants had onset at the infancy (4 and 9 months after birth), characterized by repeated unprovoked seizures; 1 patient had abnormal dynamic electrocardiogram results without malignant ventricular arrhythmia; 1 patient showed abnormal discharge in interictal electroencephalogram, which was effectively controlled after treatment with levetiracetam oral solution. Whole exon sequencing revealed heterozygous missense mutation of the RYR2 gene c.14767A>G(p.Met4923Val) in 1 child, heterozygous missense mutation of the RYR2 gene c.14014A>G(p.Met4672Val) in 1 child, and no other known epilepsy pathogenic gene mutation was found in 2 children. American Society for Medical Genetics and Genomics guidelines evaluated 2 mutations as pathogenic mutations (PS2+PM1+PM2+PP2+PP3). Conclusion:RYR2 gene is potentially a novel epilepsy gene.

Primary biliary cholangitis is a chronic autoimmune cholestatic disease with a progressive course. This disease is not rare in China, but standardized diagnosis and treatment for primary biliary cholangitis are insufficient. Based on the evidence and guidelines from China and other countries, Rheumatology Branch of Chinese Medical Association developed the recommendations of diagnosis and treatment for primary biliary cholangitis in China. The aim is to help clinicians recognize clinical characters, therapeutic selection and prognosis judgement of primary biliary cholangitis, which will contribute to make diagnosis in time, to select treatment properly and to manage follow-up scientifically.

Endoscopic teaching has always been a difficult point in clinical medical skill teaching.A standardized teaching plan was set up for the beginners to learn gastroscopy skills,which took 16 weeks.This training program included teaching the basic structure of a gastroscopy,the theory of operation skills,cleaning and disinfection of gastroscopy,and the operation of the virtual digestion endoscopy simulation training system.Only by passing the examinations of what mentioned above,could a beginner do gastroscopy of clinical subjects and write reports.According to a questionnaire survey of 15 trainees,100％ of trainees believed that virtual digestive endoscopy was necessary for the teaching of endoscopic skills.It was believed that the teaching plan were very strict and strict with 63.3％ and 33.3％ respectively.Therefore,this teaching plan with higher recognition and acceptance is suitable for the clinicians specializing in liver diseases and infectious diseases in infectious diseases specialist hospitals,who want to learn gastroscopy skills.

Objective To investigate the effects of low dose of gamma knife irradiation on the expression of N-methyl-D-aspartate (NMDA) receptor subunits in cortex and hippocampus of epileptic rats. Methods The rats were randomly divided into 4 groups: control group, GK group, pentylenetetrazole (PTZ) group and GK+ PTZ group. The rats were injected intraperitoneally with PTZ to establish the epileptic models. Gamma knife irradiation was performed on bilateral frontal cortex of rats at a peripheral dose of 15Gy. After irradiation, the changes of the seizure and behaviors were observed and recorded. The rats were killed on the 12th week after irradiation, Immunohistochemstry and western blotting were used to detect the relative expression levels of NMDAR subunits (NR1, NR2A, and NR2B) in the cortex and hippocampus. Results There were no epileptic seizures in the control group and the GK group. Compared with the PTZ group, the epileptic seizures of rats in the GK+PTZ group were significantly reduced after low dose gamma knife irradiation (P<0.05). Compared with control group, the protein expression levels of NR1, NR2A and NR2B in the PTZ group increased significantly in the cortex and hippocampus, and so were the positive neurons and their average absorbance value (P<0.05). Compared with PTZ group, the protein expression levels of NR1, NR2A and NR2B of the GK+PTZ group decreased remarkably in the cortex and hippocampus (P<0.05). Protein expression levels of NR1, NR2A and NR2B were not significantly different between control group and GK group (P＞0.05). Conclusion Epileptic rats exhibited an increase in the protein expression levels of NR1, NR2A and NR2B in the cortex and hippocampus while low dose of gamma knife irradiation can decrease expression levels of NMDA receptor subunits in the cortex and hippocampus of epileptic rats, which might represent a possible mechanism underlying the therapeutic effects of gamma knife irradiation on epileptic seizure.

Objective: To explore the relation between platelet-to-lymphocyte ratio (PLR) or neutrophil-to-lymphocyte ratio (NLR) with disease activity in Takayasu arteritis (TA) patients. Methods: Present retrospective study involved 289 patients with TA, who were hospitalized in our department between January 2010 and October 2017, and 280 age and gender matched healthy controls,who underwent thealth examination in our health examination center during the same period (control group). TA patients were further divided into active and inactive groups (180 and 109 cases respectively) according to Kerr scores. The clinical data were compared between groups. Pearson correlation analysis was used to evaluate the relationship between PLR or NLR and disease activity (Kerr score or C-reactive protein or erythrocyte sedimentation rate). Receiver operating characteristic (ROC) curve was employed to judge the cut-off value of disease activity for TA patients. Results: PLR and NLR were significantly higher in TA group than in control group(137.33 (97.38, 193.37) vs. 120.55 (96.86, 144.60) and 2.38 (1.76, 3.57) vs. 1.66 (1.35, 2.08) , respectively, all P<0.001). PLR and NLR were significantly higher in active TA group than in inactive TA group (163.43 (123.64, 224.15) vs. 110.53 (84.22, 147.24) and 2.59 (1.96, 3.94) vs. 1.95 (1.53, 2.86) respectively, all P<0.001). PLR and NLR of active group were significantly decreased after 6 months treatment (164.05 (123.29, 226.29) vs. 104.67 (77.22, 138.43) and 2.58 (1.96, 3.91) vs. 2.15 (1.67, 2.60) respectively, all P<0.001). PLR was positively correlated with Kerr score (r=0.439, P<0.001), C-reactive protein (r=0.328, P<0.001) and erythrocyte sedimentation rate (r=0.410, P<0.001). NLR also exhibited a positive relationship with Kerr score (r=0.235, P<0.001), C-reactive protein (r=0.169, P=0.005) and erythrocyte sedimentation rate (r=0.123, P=0.037). A PLR level of 176.709 was shown to be the best predictive cut-off value for TA disease activity (sensitivity 44.6%, specificity 93.0%, and area under the curve=0.766).A NLR level of 2.128 was shown to be the best predictive cut-off value for TA disease activity (sensitivity 70.9%, specificity 47.7%, and area under the curve=0.691). Conclusion PLR and NLR are useful markers for predicting disease activity of TA patients.

Objective To assess pregnancy outcome and pregnancy related concerns in Takayasu arteritis (TA) patients.Methods We analyzed 68 female patients with TA retrospectively from Xijing hospital.Data on the number of pregnancies,births and pregnancy outcomes before and after disease onset were retrieved from medical charts,patient questionnaires and the department of Obstetrics in Xijing Hospital.Data on pregnancy related concerns were gathered from patient questionnaires.Results Altogether,68 women in the TA study cohort had 106 pregnancies,73 (in 41 patients) before disease onset and 33 (in 28 patients) after disease onset.There were no difference in the frequencies of miscarriages,induced abortions and maternal complications before and after TA onset.Pregnancy related hypertension was seen in 4.7％ of the TA patients compared to 2.0％ (x2=1.238,P＞0.05) of the reference cohort from the department of Obstetrics in Xijing Hospital and preeclampsia/eclampsia in 4.7％ of the TA patients compared to 2.8％ of the reference cohort (x2=1.835,P＞0.05).The mean gestational age at delivery in pregnancies after TA onset was (37±6) weeks compared to (39±4) weeks in the reference cohort (x2=14.665,P＜0.01).Caesarian sections were more frequent in deliveries after TA onset (36％) than in the reference cohort (15％) (x2=13.322,P＜0.01).86％ of the TA patients had pregnancy related concerns.Of these concerns,72％ was about passing the disease to offsprings.Conclusion In this population based TA cohort,the maternal and fetal outcomes are favorable.Pregnancy related concerns are very popular in TAK patients.

Objective To evaluate the frequency of mutations that occur in PHEX,FGF - 23 and DMP - I genes associated with familial hypophosphatemic vitamin D resistant rickets among 6 patients from 4 families in China. Methods The peripheral blood samples from 4 families were collected and other 10 persons from different families were selected as normal controls,and then the total gene DNA was extracted from the whole blood. Using polymerase chain reaction(PCR)amplication,sequences of the exons and flanking zones in PHEX,FGF - 23 and DMP - I genes were sequenced by direct DNA sequencing and TA cloning,and then the mutations found were analyzed. Results In exon 6 of DMP - I gene,c1218 C ﹥ T and c1230 G ﹥ A mutations were detected in lineage 1,as same sense mutation (propositus and its sister:homozygous mutation;mother:heterozygous mutation);c1333 - 1334 GC ﹥ TT mutation,as missense mutation,was found in exon 12 of PHEX gene on the propositus of lineage 2,determined as heterozygous muta-tion,but the same mutation was not found from their parents. In exon 3 of FGF - 23 gene,c716 C ﹥ T,p. T239M hetero-zygous mutation was found on the propositus and its mother. In exon 6 of the DMP - I gene,c205 A ﹥ T homozygous mutation was detected in lineage 3. In lineage 3,c716 C ﹥ T mutation of the FGF - 23 gene was detected,and the pro-positus and their father had the same mutation. No disease causing mutations of the PHEX,FGF - 23 and DMP - I genes were detected in the family members of lineage 1,3 and 4. Conclusions The mutation c1333 - 1334 GC ﹥ TT detected in exon 12 of PHEX gene might be the cause of disease for the propositus of lineage 2,as missense mutation, which needs further verification;c716 C ﹥ T,p. T239M mutation of the FGF - 23 gene detected in lineage 2 and 3 might not be the causes of the hypophosphatemic rickets and abnormal phenotype.

Objectives To study the molecular genetics of Niemann-Pick's disease (NPD), and its implication in the diagnosis of NPD. Methods The clinical data and blood samples of three unrelated families were collected. The genomic DNA was extracted from peripheral blood. The six coding exons and their lfanking intronic sequences of SMPD1 gene in all members of three pedigrees were ampliifed by polymerase chain reaction (PCR). The SMPD1 gene sequencing results were compared with the normal sequence from Genbank to identify possible causative mutations. The ampliifcation products of exons where mutations were located were cloned into TA vector for further conifrmation. Results Family 1 proband had homozygous T107C mutation and the parents had heterozygous T107C mutation. The homozygous delete mutation (c.108-113delGCTGGC) was detected and conifrmed by TA cloning in all members of family 2 and 3. The 20 normal control members did not have this delete mutation. Conclusions The genetic basis of NPD in the proband of family 1 is the homozygous T107C mutation in SMPD1 gene, while parents in family 1 are carriers of recessive T107C mutation. The homozygous mutation c.108-113delGCTGGC exists in SMPD1 gene in all members of the family 2 and 3. This delete mutation is considered to be genetic polymorphism.

Objective To study the variation characteristics of peripheral blood β-catenin and DKK1 levels in patients with rheumatoid arthritis (RA) and the correlation with bone and joint damage.Methods One hundred and eight patients with RA (observation group) and 110 healthy individuals (control group) were selected.The bone mineral density(B MD) in the femur (femur neck,Ward area,greater trochanter,total femur area) and lumbar spine (L2,3,4) were measured by dual-energy X-ray absorptiometry instrument.X-ray for two hands were evaluated according to the Sharp score.The peripheral blood β-catenin and DKK1 levels were detected by enzyme-linked immunosorbent assay (ELISA).Multiple analysis was completed by multiple linear regression and Logistic regression.Results The peripheral blood DKK1 level in observation group was significantly higher than that in control group [(8.2 ±5.0) mg/L vs.(6.1 ±4.2)mg/L],there was statistical difference (t =2.452,P =0.025),but there was no statistical difference in β-catenin level between the 2 groups (t =15.947,P =0.142).Compared to control group,patients with RA had lower BMD at femur and lumbar spine (P ＜ 0.01).The incidence of osteoporosis in observation group was significantly higher than that in control group [31.5％ (34/108) vs.15.5％ (17/110)],there was statistical difference (x2 =9.289,P =0.005).The correlation analysis results showed that the peripheral blood DKK1 was positive correlation with erythrocyte sedimentation rate (ESR),28-jonit disease activity score (DAS28),alkaline phosphatase (AKP) and two hands X-ray joint narrowing space score in patient with RA (P ＜ 0.01 or ＜ 0.05) ;the peripheral blood β-catenin level was positively correlated with ESR and AKP (P ＜ 0.01 or ＜ 0.05).The multiple linear regression results showed that the disease duration,health assessment questionnaires (HAQ),DKK1 influenced two hands X-ray joint narrowing space score; but the age,disease duration,HAQ influenced two hands X-ray bony erosion score.The multiple Logistic regression results showed that the two hands X-ray Sharp score was the risk factor of osteoporosis at femur in patients with RA; but the age was the risk factor of osteoporosis at lumbar in patients with RA.Conclusions Peripheral blood DKK1 level in patients with RA increases significantly,while there is no apparent alteration in β-catenin level.Peripheral blood DKK1 level is correlated with disease activity and joint space narrow score.