Objective To explore the value of serum stearoyl sphingosine(C18∶1-Cer)and 1-stearoyl-sn-glycero-3-phospho-choline(LPC 18∶0)levels in pregnant women's serum samples during pregnancy in predicting gestational diabetes mellitus(GDM).Methods The clinical data and laboratory indicators of 126 pregnant women were retrospectively analyzed.The sub-jects were divided into GDM group(n=66)and control group(n=60)according to the GDM diagnosis results.Mass spec-trometry was used to detect the serum C18∶1-Cer and LPC18∶0 levels of the subjects in early and mid pregnancy.Logistic re-gression analysis was used to screen out the risk factors for GDM.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of C18∶1-Cer,LPC18∶0 and their combination for GDM.Results Compared with the control group,the serum C18∶1-Cer and LPC18∶0 levels of the subjects in the GDM group were significantly increased in early(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)and mid pregnancy(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml),and the differences were statistically significant(t=7.127,15.637;-5.984,2.174,all P＜0.05)C18∶1-Cer was positively correlated with fasting plasma glucose(FPG),fasting plasma insulin(FPI),homeostasis model assessment of insulin resistance(HOMA-IR),glycated hemoglobin(HbA1c)and triglyceride(TG)(r=0.458,0.209,0.317,0.223,0.219,all P<0.05).LPC18.0 was positively correlated with FPG,FPI,HOMA-IR,HbA1c,total cholesterol(TC)and TG(r= 0.715,0.426,0.580,0.465,0.232,0.372,all P<0.05).Logistic regression analysis results showed that C18∶1-Cer[OR(95%CI):1.522(1.136～2.039),P<0.05]and LPC18:0[OR(95%CI):1.198(1.102～1.302),P<0.001]were independent risk factors for GDM.ROC curve analysis results showed that the area under the curve(AUC)of serum C18∶1-Cer,LPC18∶0 and the combination of the two indicators were 0.819,0.971 and 0.986,respectively.The predictive performance of the combination of the two indicators was better than that of the single detection.Conclusion Serum C18∶1-Cer and LPC18∶0 in early pregnancy were closely related to the occurrence of GDM.C18∶1-Cer combined with LPC 18∶0 has a certain predictive value for the early diagnosis of GDM.

Objective:To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation, and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease. Methods:The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected, video electroencephalogram, craniocerebral magnetic resonance imaging and family whole exon sequencing were improved, and the suspected mutation sites were verified by Sanger sequencing. Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene. Results:It was found that there was a heterozygous missense mutation at the locus c.866G>A (p.A289H) of NR4A2 gene in the child, which was a de novo mutation, and both parents were wild type. According to the American Society of Medical Genetics and Genomics variation classification, it was assessed as a suspected pathogenic variation. Through literature review, there were 16 related cases reported internationally, with clinical phenotypes including mental retardation/mental retardation, language disorders, seizures, muscle tone changes and different psychological and behavioral problems. Conclusions:The NR4A2 gene is not only associated with dopa responsive disorders, but also with neurological development, intellectual impairment, language development delay, and epilepsy. The mutation of NR42A gene c.866G>A (p.A289H) is the genetic cause of the patient, and the detection of this locus expands the NR4A2 gene spectrum. NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members. RESULTS: The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%. CONCLUSION The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.
Epilepsy/genetics* ; Humans ; NAV1.1 Voltage-Gated Sodium Channel/genetics* ; Pedigree ; Phenotype ; Seizures, Febrile/genetics*

Objective:To explore the diagnostic value of synthetic magnetic resonance imaging (syMRI) quantitative parameters for benign and malignant breast lesions.Methods:From September 2018 to March 2019, a total of 43 cases of breast lesions which were confirmed by surgery and pathology in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled in this study. All patients underwent syMRI sequence scans before and after enhancement except for conventional T2WI, DWI, and enhancement scans. GE AW4.7 workstation was used to generate syMRI parameter maps (T1, T2, proton density mappings), and ITK-SNAP software was used to delineate the volume of interest. The T1, T2, PD values before and after dynamic contrast enhanced (DCE) were obtained, and the change values of each parameter were calculated. Meanwhile, the apparent diffusion coefficient (ADC) and time intensity curve (TIC) of the lesions were measured. The differences of each parameter value were compared between benign and malignant breast lesions, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of each parameter.Results:Among the 43 enrolled cases, 13 were benign and 30 were malignant. Among the syMRI parameters, the pre-enhancement parameters including T1pre (median 1 663.07 ms), T2pre (median 103.33 ms), post-enhancement parameters ΔT1 (median 1 022.68 ms) and ΔT2 (median 27.67 ms) of benign group, significantly higher than those of the malignant group (the medians were 1 141.74, 92.53, 664.95, and 16.19 ms, respectively, P<0.05). The ADC value of the benign group (median 1.66×10 -3mm 2/s) was significantly higher than that of the malignant group (median 1.00×10 -3mm 2/s, P<0.05). The benign group included 6 cases of TIC curve type Ⅰ, 5 cases of type Ⅱ, and 2 cases of type Ⅲ. The malignant group included 2 cases of TIC curve type Ⅰ, 17 cases of type Ⅱ, and 11 cases of type Ⅲ. The difference between the two groups was statistically significant ( P<0.05). The area under the ROC curve (AUC) of T1pre before DCE was 0.869, higher than 0.806 of ADC and 0.697 of TIC. When the best cut-off value of 1 282.94 ms was chosen, the sensitivity and specificity of diagnosis were 76.9% and 93.3%, respectively. The combination of T1pre and T2pre can further improve the diagnostic performance (AUC=0.908). Conclusions:Among the syMRI quantitative parameters, T1pre, T2pre, ΔT1 and ΔT2 have good value for the differential diagnosis of benign and malignant breast lesions. T1pre has the best diagnostic performance, and the combination of T1pre and T2pre can further improve the diagnostic performance.

Objective:To explore the diagnostic value of synthetic magnetic resonance imaging (syMRI) quantitative parameters for benign and malignant breast lesions.Methods:From September 2018 to March 2019, a total of 43 cases of breast lesions which were confirmed by surgery and pathology in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled in this study. All patients underwent syMRI sequence scans before and after enhancement except for conventional T2WI, DWI, and enhancement scans. GE AW4.7 workstation was used to generate syMRI parameter maps (T1, T2, proton density mappings), and ITK-SNAP software was used to delineate the volume of interest. The T1, T2, PD values before and after dynamic contrast enhanced (DCE) were obtained, and the change values of each parameter were calculated. Meanwhile, the apparent diffusion coefficient (ADC) and time intensity curve (TIC) of the lesions were measured. The differences of each parameter value were compared between benign and malignant breast lesions, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of each parameter.Results:Among the 43 enrolled cases, 13 were benign and 30 were malignant. Among the syMRI parameters, the pre-enhancement parameters including T1pre (median 1 663.07 ms), T2pre (median 103.33 ms), post-enhancement parameters ΔT1 (median 1 022.68 ms) and ΔT2 (median 27.67 ms) of benign group, significantly higher than those of the malignant group (the medians were 1 141.74, 92.53, 664.95, and 16.19 ms, respectively, P<0.05). The ADC value of the benign group (median 1.66×10 -3mm 2/s) was significantly higher than that of the malignant group (median 1.00×10 -3mm 2/s, P<0.05). The benign group included 6 cases of TIC curve type Ⅰ, 5 cases of type Ⅱ, and 2 cases of type Ⅲ. The malignant group included 2 cases of TIC curve type Ⅰ, 17 cases of type Ⅱ, and 11 cases of type Ⅲ. The difference between the two groups was statistically significant ( P<0.05). The area under the ROC curve (AUC) of T1pre before DCE was 0.869, higher than 0.806 of ADC and 0.697 of TIC. When the best cut-off value of 1 282.94 ms was chosen, the sensitivity and specificity of diagnosis were 76.9% and 93.3%, respectively. The combination of T1pre and T2pre can further improve the diagnostic performance (AUC=0.908). Conclusions:Among the syMRI quantitative parameters, T1pre, T2pre, ΔT1 and ΔT2 have good value for the differential diagnosis of benign and malignant breast lesions. T1pre has the best diagnostic performance, and the combination of T1pre and T2pre can further improve the diagnostic performance.

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the diagnosis of fetal chromosomal aneuploidies among women with advanced gestational age. METHODS: 14 047 pregnant women have voluntarily accepted the NIPT test. The results of NIPT and amniocytic karyotyping analysis were compared, and the outcome of pregnancy was followed up. RESULTS: NIPT has identified 104 cases with a high risk for trisomies 21, 18 and 13, and 44 cases with a high risk for sex chromosome abnormalities. After genetic consultation, 87 of 104 cases have accepted amniocyte chromosomal karyotyping. 63 cases of fetal chromosome abnormality were confirmed, including 46 cases of 21 trisomy, 11 cases of 18 trisomy and 6 cases of 13 trisomy. The positive predictive value was 83.64% (46/55), 61.11% (11/18), and 42.86% (6/14), the specificity was 99.93%, 99.95%, 99.94%, and the sensitivity was 100%. Among the 44 cases, 34 received amniocytic chromosomal karyotyping analysis, 11 cases were confirmed, the positive predictive value was only 32.35%. No aneuploidy was found in the low-risk cases. The negative predictive value was 100%. CONCLUSION As a prenatal screening method for women with advanced gestational age, NIPT has the highest positive predictive value for trisomy 21 and trisomy 18, but a lower positive predictive value for sex chromosome abnormalities. NIPT has a very low rate of missed diagnosis of trisomies 21, 18 and 13, which can significantly reduce the number of women undergoing invasive prenatal diagnosis.

Objective:To study the expression of ubiquilin2 (UBQLN2) in non-small cell lung cancer (NSCLC) and its effect on the proliferation, invasion and metastasis ability of NSCLC cells.Methods:Immunohistochemistry was used to detect the expression of UBQLN2 in NSCLC cancer (24 cases) and adjacent normal tissues (24 cases), and to analyze the relationship between the expression of UBQLN2 and lymph node metastasis of NSCLC cancer. The expression of UBQLN2 in human normal bronchopulmonary epithelial cells and NSCLC cells was detected by real-time quantitative polymerase chain reaction (qRT-PCR)and Western blot; the effect of UBQLN2 on the proliferation of NSCLC cells was detected by lentivirus overexpression technology combined with MTS and EDU experiments in vitro; the effect of UBQLN2 on the invasion and metastasis of NSCLC cells was detected by scratch experiments in vitro and transwell experiments; a dual-fluorescence autophagy flow detection system was constructed by GFP-LC3-RFP-mLC3 plasmid packaging virus and Western blot was used to detect the change of autophagy after overexpression of UBQLN2; TCGA online data was uesd to analyze the expression level of UBQLN2 and lung cancer patients relevance of prognosis. Results:The expression of UBQLN2 in normal lung tissues was significantly higher than that in NSCLC tissues ( P<0.01), and the expression in patients with negative lymph node metastasis was significantly higher than that in patients with positive lymph node metastasis ( P<0.01); the expression of UBQLN2 in NSCLC cells was significantly lower than that in normal lung epithelial cells, and the overexpression of UBQLN2 could inhibit the proliferation and invasion and metastasis of tumor cells. The expression of UBQLN2 was positively correlated with the prognosis of NSCLC. Conclusions:The expression of UBQLN2 is significantly lower in lung cancer tissues and cells, and is negatively correlated with the lymph node metastasis of NSCLC; UBQLN2 can inhibit the proliferation and invasion of NSCLC cells; the expression of UBQLN2 is positively correlated with the prognosis of patients.

OBJECTIVE: To analyze the prevalence and influencing factors of multisite work-related musculoskeletal disorders(WMSDs) of workers in a railway vehicle manufacturing enterprise. METHODS: A total of 366 male workers in the assembly and riveting workshop of a railway vehicle manufacturing enterprise were selected as the research subjects using the cluster sampling method. The Chinese Musculoskeletal Questionnaire was used to investigate the prevalence of multiple sites of WMSDs. Multiple logistic regression analysis was used to analyze the influencing factors. RESULTS: The total prevalence of WMSDs was 56.3%(206/366). The prevalence of WMSDs in all parts from high to low was as follows: lower back(35.5%), hand and wrist(27.6%), neck(23.2%), shoulder(21.0%), knee(19.9%), upper back(18.6%), hip and leg(18.0%), ankle/foot(15.8%) and elbow(12.3%)(P<0.01). The total prevalence of multisite WMSDs was 38.0%(139/366). The prevalence of WMSDs in different numbers of parts from high to low was as follows: 6 or more parts(12.0%), 2 parts(10.7%), 3 parts(6.6%), 5 parts(5.5%) and 4 parts(3.3%)(P<0.01). Multiple logistic regression analysis results showed that the overweight and obese workers had higher risk of multi site WMSDs than those with normal body mass index(P<0.05).Those with long-term low heads, frequent bending, long bending of the elbows, and higher frequency of work requirements, and less frequently communicated with the leader had higher risk of multi site WMSDs(P<0.05). CONCLUSION: The prevalence of multisite WMSDs in railway vehicle manufacturing enterprise is relatively high. The influencing factors include individual factors, adverse ergonomic factors and psychosocial factors.

OBJECTIVE: To investigate the correlation of mental workload and prevalence of work-related musculoskeletal disorders musculoskeletal disorders( WMSDs) in railway vehicle manufacturing workers.METHODS: A total of 362 male workers in assembling and welding workshop from a railway vehicle manufacturing enterprise were selected as study subjects by cluster sampling method.The level of mental workload and prevalence of WMSDs were investigated using a revised Subjective Workload Assessment Technique and China Musculoskeletal Questionnaire.RESULTS: The median score of mental workload was 67 and the prevalence rate of WMSDs was 56.9%.The multivariate logistic regression analysis results indicated that the higher the mental workload of railway vehicle manufacturers,the higher their risk for WMSDs after excluding the influence of confounding factors( P < 0.05).Workers in welding work showed a higher risk than those in assembling work( P < 0.01).Workers with fast work rhythm showed higher risk of WMSDs than those with regular working rhythm( P < 0.01).Workers with comfortable working environment and temperature showed lower risk of WMSDs than those with uncomfortable working environment and temperature( P < 0.01).CONCLUSION: The mental workload can increase the risk of WMSDs,with a dose-effect relationship in railway vehicle manufacturing workers.The type of work,work frequency and the temperature in working environment are also influencing factors of WMSDs.

Objective To evaluate the use of WeChat platform in extended care for discharged patients with diabetic retinopathy. Methods WeChat public account was applied,and the "health education forum of diabetic retinopathy" was established. Totally 120 patients who could use WeChat independently were selected and were randomly divided into the observation group (n=60) and the control group (n=60). Patients in the control group were given extended care by duty nurses according to routine discharge education,while patients in the observation group and their family members were given extended care by WeChat group members through WeChat platform. Results There were significant differences in the understanding of disease related knowledge,treatment compliance,quality of life and patient's satisfaction between two groups (P < 0.01). Conclusions The use of WeChat platform can effectively resolve problems related disease that discharged patients with diabetic retinopathy,and improve the quality of life of patients.