Objective To explore the effect of LIMK1 on the progression of cervical cancer(CC).Methods HeLa and C-33A human cervical cancer cells overexpressing LIMK1 were established and injected subcutaneously into nude mice.The tumor volume was measured and expression of NOX2,NOX4,p-Src,p-RUNX3,RUNX3,and MMP-9 proteins in tumor cells was detected by Western blot assays.LIMK1-overexpressing HeLa and C-33A cells were cultured in 5％O2 with antioxidants.The protein expression of LIMK1,NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 in the cells was detected by Western blot assays.Cell migration was assessed by a scratch assay.Transwell assays were used to assess cell migration and invasion.A monoclonal proliferation assay was used to assess cell proliferation.Results The tumor volume in nude mice injected with LIMK1-overexpressing HeLa cells was increased significantly,and NOX2,NOX4,p-Src,p-RUNX3 and MMP-9 protein levels were increased,while RUNX3 protein expression was decreased.In LIMK1-overexpressing HeLa and C-33A cells,the protein expression of LIMK1,NOX4,p-Src,p-RUNX3,and MMP-9 was increased,RUNX3 protein expression was decreased,and cell migration,invasion,and proliferation were increased.However,after adding antioxidants,the expression levels of NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 proteins,and cell migration,invasion,and proliferation were not different from those of control cells.Conclusions LIMK1 promotes the progression of cervical cancer by enhancing the ROS/Src pathway,thereby promoting the migration,invasion,and proliferation of cervical cancer cells.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Schaaf-Yang syndrome (SYS). METHODS: Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Sanger sequencing was used for family constellation verification, and bioinformatic analysis was performed for the candidate variant. RESULTS: The child, a 1-year-and-9-month-old boy, had clinical manifestations of retarded growth, small penis, and unusual facies. Genetic testing revealed that the child has harbored a novel heterozygous variant of c.3078dupG (p.Leu1027Valfs*28) of the MAGEL2 gene. Sanger sequencing showed that neither parent of the child carried the same variant. The c.3078dupG(p.Leu1027Valfs*28) variant of the MAGEL2 gene has not been included in the databases of ESP, 1000 Genomes and ExAC. According to the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was judged to be pathogenic. CONCLUSION The c.3078dupG (p.Leu1027Valfs*28) variant of the MAGEL2 gene probably underlay the SYS in this child, which has further expanded the spectrum of the MAGEL2 gene variants.
Child ; Humans ; Infant ; Male ; Exome Sequencing ; Genetic Testing ; Heterozygote ; Mutation ; Proteins/genetics* ; Developmental Disabilities/genetics*

Objective:To improve clinicians′ understanding of developmental and epileptic encephalopathy (DEE) caused by PPP3CA gene mutation. Methods:Clinical data of a patient with DEE diagnosed in the First Department of Neurology, Hebei Children′s Hospital in September 2018 were collected. The whole-exome sequencing of the proband′s family was performed, and the characteristics of gene mutation were analyzed. Literature review was carried out based on the reported cases related to PPP3CA gene. Results:The proband, a 3 months and 20 days old girl, was admitted to the hospital with a history of paroxysmal confusion with extremities shaking for 2 days. The clinical manifestations included frequent epilepsy seizures and hypoevolutism. Brain magnetic resonance imaging showed that the bilateral frontotemporal extracerebral space was slightly wider. The video electroencephalography showed hyperarrhythmia and a cluster of spastic seizures. Whole exome sequencing of the family revealed that the proband had a heterozygous de novo frameshift truncating mutation in the PPP3CA gene: c.1255-1256delAG (p.Ser419Cysfs*31). From the establishment of the database to May 2022, 8 foreign literatures and 1 Chinese literature were retrieved, and a total of 21 children with PPP3CA gene mutation were reported, with clinical developmental delay, cognitive dysfunction and abnormal electroencephalography activity. Conclusions:The frameshift truncating mutation of the PPP3CA gene (c.1255-1256delAG) is the hereditary etiology of this patient. For cases of frequent seizures with poor efficacy of antiepileptic drugs, and developmental delay, genetic testing should be performed to confirm diagnosis and treatment.

Objective:To summarize the clinical features and treatment of voltage-gated sodium channel α2-subunit (SCN2A) gene-related epilepsy.Methods:The clinical manifestion, video electroencephalography, head magnetic resonance imaging of a child diagnosed with epilepsy in Hebei Children′s Hospital were analyzed. Additionally, blood samples of the family were tested for the whole exome sequencing.Results:The boy aged 20 months,had been developed backward since childhood and accompanied by autism spectrum disorder manifestations. Seizures occurred at 19 months, manifested as isolated and clusters of spasms or generalized tonic seizures. The whole exome sequencing of the family revealed that the proband had c.4543C>T heterozygous mutation in the SCN2A gene, and both parents showed wild type. The effect of multiple anti-epileptic drugs on the children was not good, but the epilepsy was controlled after the final addition of perampane.Conclusions:The c.4543C>T heterozygous variant of SCN2A gene is the cause of disease in this child. This variant can cause epilepsy with autism spectrum disorder. The location and type of SCN2A mutations are strongly related with phenotypes, and a clear genetic etiology contributes to accurate treatment of children.

Objective:To investigate the expression level and significance of peripheral lymphocyte immunity and humoral immunity in children with autoimmune encephalitis and children with mycoplasma encephalitis.Methods:From July 2018 to July 2019, 52 children with autoimmune encephalitis (autoimmune encephalitis group) and 68 children with mycoplasma encephalitis (mycoplasma encephalitis group) in Hebei Children′s Hospital were enrolled, and 43 children with mycoplasma infection who were treated at the same time were selected as control group. Serum immunoglobulin (IgA, IgG, IgM) levels were detected using a fully automated biochemical analyzer, and peripheral T-lymphocyte subsets (CD 3+, CD 4+, CD 8+, CD 4+/CD 8+) levels were measured using flow cytometry. The receiver operating characteristic (ROC) curve was used to analyze the clinical differential diagnostic value of serum immunoglobulin and T lymphocyte subsets indicators for autoimmune encephalitis and mycoplasma encephalitis. Results:The levels of serum IgA, IgM in three groups had significant differences ( P<0.05); the levels of serum IgA, IgM in mycoplasma encephalitis group were significantly higher than those in autoimmune encephalitis group and control group [(1.64 ± 0.56) g/L vs. (1.23 ± 0.48),(0.82 ± 0.25) g/L; (1.81 ± 0.45) g/L vs. (1.56 ± 0.48), (1.12 ± 0.34) g/L]( P<0.05); the level of IgG in three groups has no significant difference ( P>0.05). The levels of CD 4+,CD 8+ in mycoplasma encephalitis group were significantly higher than those in autoimmune encephalitis group and control group [(31.21 ± 3.86)% vs. (28.76 ± 3.57)%, (26.58 ± 3.49)%; (26.86 ± 1.89)% vs. (25.90 ± 2.16)%, (24.71 ± 2.46)%]( P<0.05); the level of CD 4+/CD 8+ in three groups has no significant difference ( P>0.05). The areas under the curve of serum IgA, IgM, CD 3+, CD 8+, CD 4+ and five combined diagnosis were 0.971, 0.835, 0.833, 0.631, 0.706 and 1.000. The optimal critical values were 1.255 g/L, 1.465 g/L, 57.435%, 26.456%, 29.750% and 1.858. The sensitivity was 100.0%, 64.7%, 95.6%, 92.6%, 69.1% and 100.0%, and the specificity was 95.6%, 57.0%, 57.1%, 23.4%, 36.4% and 100.0%. Conclusions:The expression levels of serum IgA, IgM and peripheral serum CD 3+, CD 4+ and CD 8+ in children with autoimmune encephalitis are significantly lower than those in children with mycoplasma encephalitis, and IgA, IgM, CD 3+, CD 8+ and CD 4+ has high differential diagnosis value.

Objective To analyze the clinical characteristics of Brucellar spondylitis and evaluate its surgical treatment effect.Methods From 2002 to 2015,the clinical data of diagnosed patients with Brucellar spondylitis aged ≥65 years old were collected retrospectively in the First Affiliated Hospital of Hebei North University,patients' clinical manifestations and characteristics,laboratory diagnosis,imaging changes and surgical treatment effects were analyzed.Pain and imaging scores and clinical efficacy were evaluated according to follow-up data within 12 months after surgery.Results A total of 38 cases of senile patients with Brucellar spondylitis were studied.The main clinical symptoms during the visit were persistent severe lumbar back pain,local tenderness,obvious percussion pain,muscle spasm,and constrained movements of spine.Rose bengal plate test (RBPT) was positive in 11 cases,serum tube agglutination test (SAT) titer was higher than 1:100 in 28 cases.During the operation,28 cases of patients with inflammatory granuloma or abscess were cultured positive for Brucella.Before surgery,manifestations of X-ray:of which 29 cases showed intervertebral space narrowing,the density increased,and the margins of the verbebral bodies destructed;of which 9 cases showed vertebral body bone sclerosing hyperplasia in the shape of a bird's beak,forming a bone bridge with the adjacent vertebral body margin.Manifestations of CT:of which 29 cases showed different sizes and multiple lesions of the vertebral body margin,and hyperplasia and sclerosis around the lesion,and destruction of the lesion in the new bone tissue to form "lacy vertebra";in 9 cases,the destruction of intervertebral discs showed isodensity shadow,and the hyperplasia and sclerosis of articular surface resulted in the formation of "labial" osteophytes;of which 10 cases showed vertebral body destroyed the plane in which the bilateral psoas were widened and abscess formed.Manifestations of MRI:of which 38 cases showed that the vertebral bodies,intervertebral discs,accompaniment and the intra of vertebral canal were uneven high signal and dural sac or cauda equina compression.The pain scores [(2.1 ± 0.2),(0.7 ± 0.4),(0.2 ± 0.1),(0.0 ± 0.0),(0.0 ± 0.0) scores] at 2 weeks and 1,3,6,12 months after surgery were significantly lower than that before surgery [(9.2 ± 0.3) scores,P ＜ 0.05].The blind imaging evaluation scores [(4.68 ± 0.04),(4.92 ± 0.08),(5.00 ±0.00) scores] at 3,6 and 12 months after surgery were significantly higher than that before surgery [(0.37 ± 0.03) scores,P ＜ 0.05].The cure rates of clinical efficacy [92.11％ (35/38),100.00％ (38/38)] at 6 and 12 months after surgery were significantly higher than that of 3 months after surgery [78.95％ (30/38),P ＜ 0.05)].Conclusions Senile Brucellar spondylitis has the typical imaging features,laboratory examination is helpful to early diagnosis.Surgery is much better to relieve the pain and stable spine function and accelerate rehabilitation.

Objective To investigate the effect and the mechanism of epithelial-mesenchymal transition (EMT) in renal tubular cells induced by uric acid.Methods Normal rat kidney tubular cell line (NRK-52E) were exposed to different concentrations of uric acid (100,200,400,600,800 μmol/L UA) for 48 hours to induce EMT.Morphological changes of the NRK-52E cells were examined under an inverted phase contrast microscope.The protein expression of E-cadherin,α-SMA,p-Akt and Akt were detected by Western blotting.The distribution of E-cadherin and α-SMA were detected by immunofluorescence.NRK-52E cells were pretreated by different concentrations of LY294002(0,2.5,5,10,15 μmol/L),the inhibitor of PI3K/p-Akt signaling pathway,and then processed by uric acid (400 μmol/L) for 48 hours.Western blotting was used to detect the protein expression of p-Akt and Akt.NRK-52E cells were then divided into four groups:normal group (N),uric acid group (UA),LY294002 group (LY),uric acid with LY294002 group (UA + LY).The protein expression of E-cadherin and α-SMA were detected by Western blotting,the distribution of E-cadherin,α-SMA and p-Akt were detected by immunofluorescence.Results There was abundant cellular expression of E-cadherin in unstimulated renal tubular cells whereas its expression was significantly decreased in uric acidstimulated cells (P ＜ 0.05).In addition,uric acid induced de novo expression of α-SMA in contrast to almost negative staining in untreated cells (P ＜ 0.05).p-Akt were obviously increased in high uric acid group (P ＜ 0.05) and Akt changed not significantly (P ＞ 0.05).NRK-52E cells transformed into elongated fibroblast-like cells from cuboidal clustered epithelial cells.These indicated that uric acid has induced EMT and activated PI3K/p-Akt signaling pathway in NRK-52E cells.However,the above effects of uric acid were abolished when p-Akt was blocked by the PI3K inhibitor (10,15 μmol/L LY294002),indicated that LY294002 has reversed the trend of EMT.Conclusions High uric acid induces phenotypic transition of renal tubular cells probably via activating PI3K/Akt signaling pathway.

Objective To assess the impact of physical training on physiological function of adult renal transplant recipients by meta-analysis and to provide theoretical guidance for clinical practice.Methods Randomized controlled trials of physical training for the treatment of renal transplant recipients until October 2017 were searched in the database of Cochrane library,PubMed,Embase,Web of Science,Wanfang Data and CNKI.Data extracted from the literatures were analyzed with RevMan software (version 5.3).Results A total of 10 studies in 10 manuscripts met the inclusion criteria,and 557 cases were included.Meta-analysis results were as follows.Compared with the control group (routine drug therapy),the level of peak exercise oxygen uptake (peak VO2) was significantly increased in physical training group (routine drug therapy and physical training) (MD=2.40,95％ CI 0.15-4.64,P=0.04).However,there was no statistically significant difference in the change of blood lipid,blood pressure,hemoglobin and serum creatinine between the two groups (all P ＞0.05).Conclusions Physical training can improve cardio respiratory fitness of renal transplant recipients in the early stage,but it has no obvious effect on blood pressure,blood lipid,hemoglobin and blood creatinine.

Objective To study the EEG discharge index, intelligence test and event-related potential P300 in BECT, and to analyze the change of EEG discharge index and cognitive function before and after the treatment.Methods Sixty patients with BECT were enrolled in this study, they were treated with EEG, intelligence tests and P300 before and after the treatment.Results (1) The EEG discharge index were reduced remarkly after treatment in BECT with levetiracetam and lamotrigine, the difference was statistically significant (P ＜ 0.05).(2) Comparing before and after 3 or 6 months treatment, the latency of P300 had reduced with significant difference (P ＜ 0.05).(3) After 3 months treatment, VIQ and FIQ has no obvious improvement, but PIQ has improved.After 6 months treatment, VIQ、 PIQ and FIQ were improved.The difference was statistically significant (P ＜ 0.05).(4) There was a negative correlation of EEG P300 latency (r =0.175), as well as there was a negative correlation between EEG discharge index and intelligence test (r =0.044).Conclusion There is impaired cognitive function in BECT, especially the more frequently the EEG discharge, the more extended of P300 latency, as well as the more serious damage of intelligence and cognition after treatment.The intelligence were improved after treatment with Levetiracetam and lamotrigine, the longer the treatment time, the more obvious of intelligence levels improve.

Decoction is one of the most commonly used dosage forms of traditional Chinese medicine. The stability of chemical constituents in decoction is closely related to the clinical efficacy and safety. There were few reports about the influence of metal ions in the stability of chemical constituents in traditional Chinese medicine. However, there is no evidence that metal ions in decoction water need to be controlled. In this study, 2,3,5,4'-tetrahydroxy stilbene-2-O-β-D-glucoside (THSG), one of the main constituents in Polygoni Multiflori Radix was studied. Ordinary tap water, deionized water, and water containing different metal ions were used to investigate and compare the influence on THSG. The results showed that after storage in a dark place at the room temperature for 10 days, the degradation of THSG was 7% in deionized water, while undetectable in tap water. The content of THSG could be decreased by different kinds of metal ions, and the effect was concentration-dependent. Moreover, Fe3+ and Fe2+ showed the greatest influence at the same concentration; and our study has shown that THSG decreased more than 98% in Fe and Fe2+ solutions at 500 ppm concentration. In the same time we found out p-hydroxybenzaldehyde (molecular weight: 122.036 7) and 2,3,5-trihydroxybenzaldehyde-2-O-glycoside (molecular weight: 316.079 4) were the main degradation products of THSG in tap water and water containing Cu2+, Ca2+, Zn2+, Mg2+ and Al3+. The product of THSG dimer with a water molecule was found in water containing Fe3+ and Fe2+. The above results showed that the metal ions in water could significantly influence the stability of THSG in water, indicating that the clinical efficacy and safety of decoction would be affected if the metal ions in water were not under control. It's suggested that deionized water should be used in the preparation of decoction containing Polygoni Multiflori Radix in the clinic to avoid degradation of THSG. Meanwhile, decoction prepared by tap water should be taken by patients in a short time. Our investigation provides important information and reference about the influence of metal ions on the stability of decoctions in other traditional Chinese medicine that have unstable groups such as hydroxyls and unsaturated bonds, etc.