BACKGROUND:Fibroblast-like synoviocytes (FLS) in the synovial lining layer are related to the cell proliferation, invasion, migration and apoptosis as well as bone resorption in rheumatoid arthritis. OBJECTIVE:To compare the migration and invasion abilities of FLS (MH7A) in rheumatoid arthritis and normal FLS (HFLS). METHODS:The capacities of cell migration and invasion were evaluated by Transwell cell migration and invasion assays. The primers of the indicated microRNAs were designed and synthesized, and the expression levels of miRNAs were determined by real-time PCR according to the SYBR?PrimeScript?miRNA RT-PCR Kit instruction. RESULTS AND CONCLUSION:MH7A possessed stronger migration and invasion abilities than HFLS. Compared with HFLS, obviously upregulated miR-132, -155, -203, -223 and -124, and significantly downregulated miR-15a, -16, 18a, -19a, -26a and -146a were found in MH7A. These findings suggest that the differentially expressed 11 kinds of rheumatoid arthritis-associated miRNAs participate in the pathogenesis of rheumatoid arthritis probably by enhancing the migration and invasion capacities of MH7A.

AIM:To study the effect of roscovitine on the inflammatory hyperplasia of carotid artery intima in rats and the related mechanisms .METHODS: SD rats ( n=60 ) were randomly divided into 3 groups including control group, model group and treatment group .The rat model was established by trypsin digestion injury .The rats in control group were given sham operation .The rats in treatment group were administered with 0.5 mL roscovitine (2 g/L) slow-re-leasing gelatin.The rats in each group were fed normally for 4 weeks, then killed to take out carotid arteries for further ob-servations .The effects of roscovitine on the inflammatory hyperplasia of carotid artery intima and the related mechanism via nuclear factor-κB ( NF-κB) in the rats were detected by Western blot .RESUITS:Roscovitine inhibited the activation of NF-κB and the expression of inflammatory factors cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1),TNF-αand IL-6 via blocking the phosphorylation activation of NF-κB and inhibiting the degradation of IκB-α.CON-CLUSION:Roscovitine inhibits inflammatory hyperplasia of carotid artery intima in the rats via suppressing NF-κB activa-tion.

Purpose To explore whether potassium perchlorate shall be taken orally to occlude gastric mucosa before taking 99Tcm-3PRGD2 SPECT/CT gastric image,and to provide theoretical evidence for clinical application.Material and Methods Eighteen adult male Wistar rats were divided into three groups randomly:low dose group of potassium perchlorate (36 mg/kg),high dose group (72 mg/kg) and normal saline control group,with six rats in each group.All rats were conducted with gavage of 1 ml/100 g respectively and,one hour later,injected with 99Tcm-3PRGD2 intravenously to rat tail.Then 99Tcm-3PRGD2 gastric image was taken two hours later.The same film reader carried out audio analysis of the image and then gastric and radioactivity ratio (T/N) on the lung of the same side were analyzed.Results Preparation of 99Tcm-3PRGD2 was simple and radiochemical purity of final products was (98.90±0.70)％.Rat weights in high dose group of potassium perchlorate,low dose group and control group were (479.7t21.5) g,(481.0± 17.6) g and (478.5± 16.5) g,respectively.The differences were of no statistical significance (F=0.027,P＞0.05).T/N values in rat stomach area were 1.2219±0.0165,1.2204±0.0167 and 1.2186±0.0175,respectively.The differences were of no statistical significance (F=0.055,P＞0.05).Conclusion Preparation of 99Tcm-3PRGD2 is simple and radiochemical purity is high.There is great possibility of no need to take potassium perchlorate orally to occlude gastric mucosa when taking 99Tcm-3PRGD2 SPECT/CT image (especially when the radiochemical purity of final products is over 98％),making it convenient in clinical promotion and utilization.

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree affected with pseudohypoparathyroidism. METHODS: Peripheral blood samples of the proband and his parents were collected and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified among the pedigree and 50 randomly selected healthy individuals through analysis of restriction fragment length polymorphism. Short tandem repeat (STR) linkage analysis was used to verify the parental origin of the pathogenic variants. RESULTS: Trio-WES and Sanger sequencing showed that the proband and his mother had both harbored a c.121C>G (p.His41Asp) variant of the GNAS gene, which was not found in other family members and the 50 healthy controls. The variant was not found in international databases. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic. CONCLUSION The novel c.121C>G variant of the GNAS gene probably underlay the disease in this pedigree. Above finding has enriched the spectrum of GNAS gene variants.
Female ; Humans ; Pedigree ; East Asian People ; Mothers ; Exome Sequencing ; Pseudohypoparathyroidism/genetics* ; Mutation ; China ; Chromogranins/genetics* ; GTP-Binding Protein alpha Subunits, Gs/genetics*

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate (NSCLP). METHODS: With informed consent obtained, members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate. One affected member was subjected to whole-exome sequencing and bioinformatics analysis. Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals. RESULTS: Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G (p.Cys85Arg) variant in exon 4 of the IRF6 gene, which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals. CONCLUSION The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.
Brain/abnormalities* ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Female ; Humans ; Interferon Regulatory Factors/genetics* ; Mutation, Missense ; Pedigree ; Whole Exome Sequencing

Objective:To investigate the effect of electroacupuncture (EA) on synaptic plasticity and the expression of autophagy-related proteins in the hippocampus in Alzheimer′s disease (AD). To explore how EA might improve cognition in AD.Methods:Healthy male Sprague-Dawley rats were randomly divided into a sham operation group, a model group and an EA group. The rat model of AD was established by injecting Aβ1-42 into the bilateral CA1 area of the hippocampus. The sham operation group was injected with an equal amount of normal saline at the same site. Starting the day after the successful modelling, the EA group received 20 minutes of EA treatment at the Baihui (DU20) and bilateral Shenshu (BL23) acupoints once a day, 6 times a week for 2 weeks. The rats′ learning and memory were then tested using a Morris water maze. The long-term potentiation (LEP) in the hippocampus was assessed using a MED64 microelectrode array and any ultrastructural changes of autophagosomes were detected using an electron microscope. The expression of the autophagy-related proteins Beclin-1 and microtubule associated protein light chain 3 (LC3) in the hippocampus were determined using western blotting.Results:The escape latency was significantly shorter and the times crossing the platform increased significantly in the EA group compared with the model group. The average amplitude of the postsynaptic excitatory field potentials in the EA group was significantly higher than among the model group. There were many autophagosomes in the hippocampal neurons of the model group, significantly more than in the EA group. The LC3II/LC3I ratio and Beclin-1 protein expression decreased significantly in the EA group compared to the model group.Conclusions:EA can improve learning and memory and restore LEP in the hippocampus of rats modeling AD. The mechanism may be related to its regulation of autophagy in hippocampal neurons.

Objective　This study aims to explore the correlation between white blood cell count (WBC),absolute neutrophil count (ANC),relative neutrophil count (RNC) and neurological impairment,poor prognosis at discharge and 90 days after onset.Methods　This study was a retrospective study,including patients aged 18 to 45 years old with first ischemic stroke within 72 hours.NIHSS score at discharge,mRS score at discharge and 90 days were used as outcome.Multivariate logistic regression was used to analyze the relationship between WBC quartile,ANC,RNC and neurological deficit (NIHSS score>4) and poor prognosis (mRS score 2~5).Results　WBC>7.82×10 9/L was independently associated with moderate and severe neurological deficit at discharge and poor prognosis at 90 days.The ANC was only associated with poor prognosis at 90 days,independently.The RNC was an independent risk factor for moderate and severe neurological impairment at discharge,poor prognosis at discharge and 90 days.Conclusion　WBC>7.82×10-9/L is an independent risk factor for moderate and severe neurological impairment at discharge and poor prognosis at 90 days in young patients with stroke.The increase of RNC,which is independently related to moderate and severe neurological impairment and poor prognosis,is more indicative than ANC for poor prognosis in young patients with stroke.

Objective:To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE 3) levels and XLI. Methods:A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE 3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results:Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE 3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant ( Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions:The decrease levels of uE 3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE 3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.

OBJECTIVE: To analyze the genomic variation characteristics of fetal with abnormal serological screening, and to further explore the value of copy number variation (CNV) detection technology in prenatal diagnosis of fetal with abnormal serological screening. METHODS: 7617 singleton pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal Down's serological screening were selected. According to the results of serological screening, the patients were divided into high risk group, borderline risk group and single abnormal multiple of median (MOM) group. CMA and CNV-Seq were used to detect the copy number variation of amniotic fluid cell genomic DNA and combined with amniotic fluid cell karyotype analysis for prenatal diagnosis. Outpatient revisit combined with telephone inquiry was used for postnatal follow-up. RESULTS: Among 7617 amniotic fluid samples, aneuploidy was detected in 138cases (1.81%) by CMA and CNV-Seq, 9 cases of aneuploid chimerism were detected by amniotic fluid cell karyotype analysis, and 203 cases of fetus carrying pathogenic and likely pathogenic CNV (P/LP CNV) were detected, the variant of uncertain significance (VUS) was detected in 437 cases (5.7%), the overall abnormal detection rate was 10.33%. The detection rate of aneuploidy by CMA and CNV-Seq in three group were 123 cases (2.9%), 13 cases (1.3%) and 2 cases (0.4%), respectively,and showing no significant difference (χ ²=7.469, P=0.024). The detection rate of pathogenic and likely pathogenic CNV in three group were 163cases (2.6%); 24 cases (2.6%) and 16 cases (3.3%), respectively, and showing no significant difference (χ ²=0.764, P=0.682). The CMA reported 2.9% (108/3729)P/LP CNV, and CNV-seq reported 2.4% (95/3888)P/LP CNV, both tests showed similar detective capabilities (χ ²=1.504, P=0.22).The most popular P/LP CNV in this cohort were Xp22.31 microdeletion, 16p13.11 microduplication /microdeletion, 22q11.21 microduplication /microdeletion. In fetuses with P/LP CNV CNV, 59 fetuses were terminated pregnancy, and 32 of 112 fetuses born had abnormal clinical manifestations. Non-medically necessary termination of pregnancy occurred in 11 fetuses carrying VUS CNV, 322 fetuses carrying VUS CNV were born, 4 of them presented abnormal clinical manifestations. CONCLUSION Compared with the traditional chromosome karyotype, CMA and CNV-Seq can improve the detection rate of pathogenic and likely pathogenic CNV. CMA and CNV-seq can be used for first tier diagnosis of pregnant women in the general population with abnormal Down's serological screening.
Amniotic Fluid ; Aneuploidy ; Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Genomics ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Pregnant Women ; Prenatal Diagnosis/methods* ; Technology

Objective: To examine the relative importance of four emotion regulation strategies (i.e. cognitive reappraisal, expressive suppression, rumination and mindfulness) in explaining job burnout and depression of nurses. Methods: We conducted a cross-sectional study with questionnaires for 1 037 nurses from two general hospitals. Maslach Burnout Inventory-Human Service Survey (MBI-HSS), the Patient Health Questionnaire-9 (PHQ-9), Emotion Regulation Questionnaire (ERQ), Ruminative Responses Scale (RRS) and Short Inventory of Mindfulness Capability (SIM-C) were assessed. Results: Dominance analysis revealed that in terms of job burnout, rumination, cognitive reappraisal and mindfulness could explain 41.38% (0.132/0.319), 30.09% (0.096/0.319) and 28.53% (0.091/0.319). In terms of depression, rumination and mindfulness could explain 68.6% (0.362/0.528)and 24.43% (0.129/0.528). Conclusions Rumination and mindfulness were important predictors of job burnout and depression of nurses. This study indicates that reducing ruminative responses and enhancement of mindfulness are the important approach to reduce nurses′ job burnout and depression.