Efficacy and safety of switching from brand-name to domestic generic levetiracetam in children with epilepsy / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of domestic generic levetiracetam in replacement of brand-name levetiracetam in the treatment of children with epilepsy.@*METHODS@#A retrospective analysis was performed on the medical data of 154 children with epilepsy who received domestic generic levetiracetam in the inpatient or outpatient service of Guangdong Provincial People's Hospital from May 2019 to December 2020. Domestic generic levetiracetam and brand-name levetiracetam were compared in terms of efficacy and safety.@*RESULTS@#For these 154 children, the epilepsy control rate was 77.3% (119/154) at baseline. At 6 months after switching to domestic generic levetiracetam, the epilepsy control rate reached 83.8% (129/154), which showed a significant increase (P<0.05). There was no significant change in the frequency of seizures from baseline to 6 months after switching (P>0.05). The incidence of refractory epilepsy in children with no response after switching treatment was significantly higher than that in children with response (P<0.05). Before switching, only 1 child (0.6%) experienced somnolence, while after switching, 3 children (1.9%) experienced mild adverse drug reactions, including dizziness, somnolence, irritability, and bad temper.@*CONCLUSIONS@#Switching from brand-name to generic levetiracetam is safe and effective and holds promise for clinical application, but more prospective randomized controlled trials are required in future.

Long-term follow-up of efficacy of insulin pump in the treatment of children with type 1 diabetes mellitus / 中国当代儿科杂志

OBJECTIVE@#To study the clinical effect of continuous subcutaneous insulin infusion (CSⅡ) versus multiple daily injection (MDI) on blood glucose control in children with type 1 diabetes mellitus (T1DM).@*METHODS@#A retrospective analysis was performed on the medical data of 91 children with T1DM who were treated with CSⅡ for more than 1 year and 75 children with T1DM who were treated with MDI. The two groups were compared in terms of glycosylated hemoglobin (HbA1C) and the recurrence of diabetic ketoacidosis (DKA) to evaluate the difference in the efficacy during the 3-year follow-up. A survey was conducted for the children in the CSⅡ group and their family members to investigate the degree of satisfaction with insulin pump.@*RESULTS@#There was no significant difference in age, sex, and course of diabetes between the CSⅡ and MDI groups at disease onset and in the first year, the second year, and the third year of follow-up (@*CONCLUSIONS@#Children with T1DM treated with CSⅡ have a better control of blood glucose than those treated with MDI, and children and their family members are satisfied with CSⅡ treatment. Therefore, it holds promise for clinical application.

Development of programmed death receptor-1 and programmed death receptor-1 ligand in oral squamous cell carcinoma / 华西口腔医学杂志

Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the oral and maxillofacial region. At present, the treatment of OSCC is mainly based on surgical oriented comprehensive sequence therapy, especially the triple therapy of surgery, radiotherapy, and chemotherapy. However, the overall five-year survival rate is relatively low. Therefore, researching the pathogenesis and treatment methods of OSCC is important. The immune checkpoint of programmed death receptor-1 (PD-1) and programmed death receptor-1 ligand (PD-L1) have been the focus of research in recent years. Several studies have shown that the high expression of PD-1/PD-L1 in most OSCC microenvironments may contribute to the immune escape of tumors. In this study, the research status of immune checkpoint of PD-1/PD-L1 and its relevant inhibitors in OSCC were reviewed.

Ameliorating effects of sericin on retinal oxidative stress and micro-inflammatory status in diabetic rats / 眼科新进展

Objective To investigate the improvement effects of sericin on the retinal oxidative stress and micro-inflammatory state in diabetic rats.Methods A diabetic rat model was established by using high-fat and high-sugar diet and intraperitoneal injection of streptozotocin.Then 24 diabetic rats were randomly divided into sericin treatment group and diabetic model group,with 12 rats for each group,and additional 12 normal rats with the same age were collected as a normal control group.Next,the rats in the sericin treatment group received sericin solution,while the other two groups was given the same amount of normal saline once a day for 35 days.After the agent intervention,the content of malondialdehyde (MDA) and glutathione (GSH) in the retina of all rats were detected by related kits.The expressions of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase 1 (HO-1),nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) protein were detected by Western blot,and finally,the retinal morphology was examined by hematoxylin-eosin staining in the 3 groups.Results The content of MDA,NF-κB and TNF-α protein expression in the sericin treatment group was (4.145 ±0.282) mmol· gprot-1,0.232 ±0.027 and 0.761 ±0.058,respectively,which was significantly lower than that in the diabetic model group [(6.813 ± 0.446) mmol · gprot-1,0.334 ± 0.024 and 0.994 ± 0.084] (all P ＜ 0.05).The content of GSH,Nrf2 and HO-1 protein expression in rat retina in the sericin treatment group was (78.518 ± 4.317) mg · gprot 1,0.591 ± 0.054 and 0.954 ± 0.091,respectively,which was significantly higher than that in the diabetic model group [(59.890 ± 5.932) mg · gprot-1,0.351 ± 0.044 and 0.585 ± 0.054] (all P ＜ 0.05).The diabetic model group presented the disorder arrangement of the neurocyte in different levels in the retina,irregular and swollen inner limiting membrane,vacuoles in the ganglion cells,but in the sericin treatment group,the morphology of retinal layers was more regular and mildly disorderly arranged.The pathological damages in the retina were alleviated significantly.Conclusion Sericin can ameliorate oxidative stress and inflammation in diabetic retina,thereby delaying the development of diabetic retinopathy.

Clinical significance of renal artery ultrasound hemodynamic index and advanced oxidation protein product in evaluating the renal function level in preeclampsia pregnant women / 新乡医学院学报

Objective To explore the clinical significance of renal artery ultrasound hemodynamic index and advanced oxidation protein product(AOPP)in evaluating the renal function level in preeclampsia pregnant women. Methods Seventy two cases of preeclampsia pregnant women in the Central Hospital of Zhumadian City were divided into mild group(39 cases)and se-vere group(33 cases)according to the pathogenetic condition,and 35 healthy pregnant women who were hospitalized and deliv-ered in the same period were selected as the control group. Ratio of systolic to diastolic(S/ D),pulsation index(PI),resistance index(RI)of renal artery were detected by color Doppler ultrasound in all patients. The levels of plasma AOPP and serum creati-nine(Cr),uric acid(UA),cystatin C(Cys C),blood urea nitrogen(BUN)were detected. The results among the three groups were analyzed. Results The S/ D,PI,RI of renal artery,the levels of plasma AOPP and serum Cr,Cys C,BUN in the severe group were significantly higher than those in the mild group and the control group(P <0. 05). The S/ D,PI,RI of renal artery,the levels of plasma AOPP and serum Cys C in the mild group were significantly higher than those in the control group(P < 0. 05). There was no significant difference in the level of serum Cr and BUN between the mild group and the control group(P >0. 05). There was no significant difference in the serum UA level among the three groups(P >0. 05). The results of Pearson correlation analysis showed that the S/ D,PI,RI of renal artery and AOPP were positively correlated with the level of Cys C(r =0. 557,0. 621,0. 597, 0. 608;P <0. 05),but they was not correlated with the level of serum Cr,UA and BUN(r =0. 133,0. 159,0. 215;P >0. 05). The S/ D,PI,RI of renal artery were positively correlated with the level of plasma AOPP(r = 0. 582,0. 639,0. 633;P < 0. 05). Con-clusion Detection of renal artery hemodynamic parameters and AOPP level can help to predict renal function in preeclampsia pregnant women.

Establishment of a Novel Method for Screening Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance Mutations in Lung Cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform.</p><p><b>METHODS</b>A review of the literature revealed 60 mutation hotspots in seven target genes (EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM) that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCarta™ kit in ten lung cancer specimens. EGFR, KRAS, and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility.</p><p><b>RESULTS</b>Our data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCarta™ kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform.</p><p><b>CONCLUSIONS</b>We established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.</p>

Analysis of the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal epilepsy

OBJECTIVE@#To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy (NFLE).@*METHODS@#Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects. Genomic DNA was extracted, and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing.@*RESULTS@#No CHRNA7 gene mutation was detected in all of the NFLE patients. However, five single nucleotide polymorphisms (SNPs) in sporadic cases were found, located in exons 5, 6, and 7 of the CHRNA7 gene. Among them, c.690G>A and c.698A>G are known SNPs, while c.370G>A, c.654C>T, and c.497-498delTG were newly discovered SNPs. These SNPs were also found in some of the healthy controls.@*CONCLUSIONS@#No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE. The CHRNA7 gene is probably not responsible for NFLE in this population.

Analysis of the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal epilepsy

Objective: To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy (NFLE). Methods: Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects. Genomic DNA was extracted, and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing. Results: No CHRNA7 gene mutation was detected in all of the NFLE patients. However, five single nucleotide polymorphisms (SNPs) in sporadic cases were found, located in exons 5, 6, and 7 of the CHRNA7 gene. Among them, c.690G>A and c.698A>G are known SNPs, while c.370G>A, c.654C>T, and c.497-498delTG were newly discovered SNPs. These SNPs were also found in some of the healthy controls. Conclusions: No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE. The CHRNA7 gene is probably not responsible for NFLE in this population.

Detecting the spectrum of multigene mutations in non-small cell lung cancer by Snapshot assay / 癌症

As molecular targets continue to be identified and more targeted inhibitors are developed for personalized treatment of non-small cell lung cancer (NSCLC), multigene mutation determination will be needed for routine oncology practice and for clinical trials. In this study, we evaluated the sensitivity and specificity of multigene mutation testing by using the Snapshot assay in NSCLC. We retrospectively reviewed a cohort of 110 consecutive NSCLC specimens for which epidermal growth factor receptor (EGFR) mutation testing was performed between November 2011 and December 2011 using Sanger sequencing. Using the Snapshot assay, mutation statuses were detected for EGFR, Kirsten rate sarcoma viral oncogene homolog (KRAS), phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), v-ras neuroblastoma viral oncogene homolog (NRAS), dual specificity mitogen activated protein kinase kinase 1 (MEK1), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (HER2) in patient specimens and cell line DNA. Snapshot data were compared to Sanger sequencing data. Of the 110 samples, 51 (46.4%) harbored at least one mutation. The mutation frequency in adenocarcinoma specimens was 55.6%, and the frequencies of EGFR, KRAS, PIK3CA, PTEN, and MEK1 mutations were 35.5%, 9.1%, 3.6%, 0.9%, and 0.9%, respectively. No mutation was found in the HER2, NRAS, or BRAF genes. Three of the 51 mutant samples harbored double mutations: two PIK3CA mutations coexisted with KRAS or EGFR mutations, and another KRAS mutation coexisted with a PTEN mutation. Among the 110 samples, 47 were surgical specimens, 60 were biopsy specimens, and 3 were cytological specimens; the corresponding mutation frequencies were 51.1%, 41.7%, and 66.7%, respectively (P = 0.532). Compared to Sanger sequencing, Snapshot specificity was 98.4% and sensitivity was 100% (positive predictive value, 97.9%; negative predictive value, 100%). The Snapshot assay is a sensitive and easily customized assay for multigene mutation testing in clinical practice.

Bear bile powder (熊胆粉) induces apoptosis of human hepatocellular carcinoma cells via mitochondrion-dependent pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Bear Bile Powder(, BBP) on the growth and apoptosis of HepG2 human hepatocellular carcinoma cells, and investigate the possible molecular mechanisms mediating its anti-cancer activity.</p><p><b>METHODS</b>HepG2 cells were treated with 0.4-1.0 mg/mL of BBP for 24, 48 and 72 h. The viability of HePG2 cells was determined by MTT assay. Cellular morphology was observed via phase-contrast microscopy. Fluorescence-activated cell sorting analysis with Annexin-V/propidium idodide and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazol-carbocyanine iodide (JC-1) staining was performed to determine cell apoptosis and the loss of mitochondrial membrane potential, respectively. Activation of caspase-9 and -3 was evaluated by a colorimetric assay.</p><p><b>RESULTS</b>The treatment with 0.4-1 mg/mL of BBP for 24, 48, or 72 h respectively reduced cell viability significantly by 7%-60%, 20%-90% or 25%-98%, compared with the untreated control cells (P<0.01). In addition, BBP treatment induced morphological changes in HepG2 cells. Furthermore, after treated with 0, 0.4, 0.6, 0.8 and 1.0 mg/mL of BBP, apoptosis cells (including early and late apoptotic cells) were 18.0%±1.3%, 34.9%±2.2%, 33.9%±2.8%, 37.4%±2.8% and 46.0%±2.5%, respectively (P<0.05); and the percentage of cells with reduced JC-1 red fluorescence were 6.6%±0.8%, 8.5%±0.8%, 13.5%±1.6%, 17.6%±2.3% and 46.7%±3.6%, respectively (P<0.01). Finally, BBP treatment significantly and dose-dependently induced activation of both caspase-9 and caspase-3 in HepG2 cells (P<0.05).</p><p><b>CONCLUSIONS</b>BBP could inhibit the growth of HepG2 hepatocellular cancer cells through mitochondrion-mediated apoptosis, which may, in part, explain its anti-cancer activity. BBP may be a potential novel therapeutic agent for the treatment of hepatocellular carcinoma.</p>

Relationship between serum levels of neuron-specific enolase and severity of electroencephalogram in epileptic children / 中华实用儿科临床杂志

Objective To investigate the relationship between the serum levels of neuron-specific enolase (NSE) and the severity of electroencephalogram(EEG) in children with epilepsy.Methods Two hundred and thirty epileptic children and 74 healthy children were enrolled in the study.Serum level of NSE was detected and video EEG was performed before and 1 year after treatment of the epileptic children respectively.Serum level of NSE in healthy control group was also detected.Results The serum level of NSE before treatment of the epileptic children was significantly higher than that of healthy control group(P ＜ 0.001).There was no significant difference in serum level of NSE between generalized seizures and focal seizures (P =0.13).The serum level of NSE 1 year after treatment was significantly decreased compared with that before treatment (P ＜ 0.001),while the degree of severity on EEG was improved significantly.The serum level of NSE of abnormal EEG group was higher than that of the normal range EEG group and bounded EEG group(all P ＜0.05),there was positive correlation between serum level of NSE and the severity of EEG (rs =0.605,P ＜ 0.001).Conclusions The serum levels of NSE are related to the severity of EEG changes.Serum NSE combined with EEG can betterly predict the degree of brain damage in epileptic children.

None mutation in the CHRNA4 gene of 6 families of South China with autosomal dominant noctumal frontal lobe epilepsy was found / 中华实用儿科临床杂志

Objective To investigate the virulence gene and mutation features in the Chinese patients with autosomal dominant noctumal frontal lobe epilepsy(ADNFLE) by using the direct sequencing(DS) PCR products with all the exons of CHRNA4 in 6 ADNFLE families,and to interpret the molecular pathogenesis in Chinese patients affected by ADNFLE.Methods Six ADNFLE families were collected,included 66 people and 24 patients with ADNFLE,and 200 healthy volunteers were selected as control group.The genomic DNA was extracted.The exons 1-6 in CHRNA4 were amplified by the PCR.The amplified products were sequenced and analyzed.All data were analyzed with SPSS 13.0 software.Results There were 4 base substitutions in exon 5,and they were c.909T ＞ G,c.1440G ＞ T,c.1458T ＞ C and c.942C ＞ T.All those base substitutions were synonymous.The first three were homozygosis substitutions,but the last one was heterozygosis substitutions.Conclusions The hot spot mutations of CHRNA4 which have been reported were not detected.Whether or not there is a correlation between ADNFLE and this substitution need to be identified by study with

Rathke cleft cysts in 22 children diagnosed by pituitary magnetic resonance / 中华实用儿科临床杂志

Objective To evaluate the clinical features of Rathke cleft cysts(RCCs) in children diagnosed by pituitary magnetic resonance(MR) and their features on MR.Methods Twenty-two children with RCCs aged 2-18 years old who visited the Affiliated Hospital of Qingdao University Medical College between Jan.2002 and Feb.2012 were enrolled.RCCs was conformed by pituitary MR.The clinical symptoms and imaging features were reviewed retrospectively.Results The clinical presentation of symptomatic children were as follows:endocrinopathy in 13 cases (59.1％),headache in 5 cases(22.7％) and visual disturbance in 1 case(4.5％) and variety of symptoms in 3 cases (13.6％),which including 1 case of short stature and dysgenitalism,1 case of type 1 diabetes with electrolyte disorder and the other of headache associated with visual impairment.Endocrinopathy included short stature 5 cases(22.7％),precocious puberty 4 cases(18.2％)and diabetes insipidus 4 cases(18.2％).Generally,RCCs appeared various on Tl-weighted MR,whereas on T2-weighted sequences the signal intensity was mostly high.High signals in the T1-weighted image on brain MR were related to pituitary hormone deficiency.Hypointensity of the cysts in T1-weighted was appeared when enhanced images.Conclusions The most common clinical manifestation of children with RCCs is endocrinopathy.Pituitary MR shows a certain characteristics and it is favorable in agreement with pathological diagnosis.MR may be of predictive value for the preoperative diagnosis.

Protective effect of Astragalus on insulitis and apoptosis of islet β cells in mice / 中华实用儿科临床杂志

Objective To investigate the protective effect of Astragalus on islet β cell apoptosis in vivo.Methods Fifty-six healthy male mice were divided into control group,diabetic mellitus (DM) group,and Astragalus pretreatment group.After pretreatment with different doses of Astragalus,each group of mice received intraperitoneal injection of Streptozotocin(STZ) in order to induce DM,and then the incidence of DM was observed.Serum nitric oxide (NO)was measured by the nitratase method,the activity of induced nitric oxide synthase(iNOS) was measured by chemical colorimetric method,and insulin level was detected by enzyme linked immunosorbent assay method.Insulitis score was evaluated according to pancreatic histology.Islet β cell apoptosis was measured by using a terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling assay.Results 1.DM attack began 1 week after STZ injection in DM group.Pretreatment with 30 g/(kg · d) of Astragalus,DM appeared 2 weeks after STZ injection.Compared with DM group,the onset of DM was delayed,and the incidence of DM was significantly reduced(P ＜ 0.01).After pretreatment with 15 g/(kg · d) of Astragalus,the DM began 1 week after STZ injection,compared with DM group,the incidence of DM was reduced,but there was no statistical difference(P ＞ 0.05).2.Compared with DM group,after pretreatment with 30 g/(kg · d) of Astragalus,the activity of iNOS was significantly inhibited(all P ＜ 0.01),and then NO level significantly declined(all P ＜ 0.01),and the insulitis score and apoptosis of β cells were also significantly decreased (all P ＜ 0.01) ;after pretreatment with 15 g/(kg · d) of Astragalus,there was no statistical difference in all the indexes (all P ＞ 0.05).Conclusions Astragalus can protect islet β cells of mice in vivo,which is associated with its inhibition on the iNOS activity,reduction on NO generation,and can decrease β cells insulitis and apoptosis.Therefore,improving the body free radicals scavenger ability may prevent and delay the occurrence of DM.

Protective effects of interleukin-10 and insulin-like growth factor-1 gene combination therapy on islet β cells of non-obese diabetic mice / 中华实用儿科临床杂志

Objective To investigate whether IL-10 gene combined with insulin-like growth factor-1 (IGF-1)gene transfer could attenuate pancreatic insulitis,increase the percentage of CD4 + CD25 + Foxp3 + regulatory T cells,and protect β cells from autoimmune destruction.Methods An adenoviral vector containing IL-10 gene (Ad-IL-10) or IGF-1 gene(Ad-IGF-1) was constructed separately.Forty female non-obese diabetic (NOD) mice were injected intraperitoneally with Ad-IL-10 and/or Ad-IGF-1,Ad-green fluorescent protein(GFP) and phosphate buffered saline(PBS)separately,repeated after 3 weeks.Blood glucose concentration was measured weekly.Serum insulin,cytokine production were tested by enzyme-linked immunosorbent assay.CD4 + CD25 + Foxp3 + Treg cells were determined by flow cytometry.Pancreatic histology was measured for determination of insulitis grades.Pancreatic insulin content and β-cell mass,proliferation were measured.Apoptosis was measured by using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay.Results A significantly lower diabetes incidence (P ＜ 0.01) was observed in NOD mice treated with Ad-IL-10 and/or Ad-IGF-1,compared with mice treated with Ad-GFP or PBS alone,especially combined group.Lower insulitis score compared to control mice was found in Ad-IL-10 + Ad-IGF-1 group (all P ＜ 0.01).The serum level of TNF-α and IFN-γwere decreased and the level of IL-10 increased in combination therapy.The CD4 + CD25 +Foxp3 + cells was (7.17 ±0.38)％ in combined group,higher than that in the control groups.There was significantly less β-cell apoptosis(10.29 ±2.20)％ in combined group than that in other groups(all P ＜ 0.05).Conclusions Combination therapy with IL-10 and IGF-1 gene is able to increase the percentage of CD4 + CD25 + Foxp3 + regulatory T cells,reduce autoimmunity and increase pancreatic β-cell mass,indicating promising potential of these therapies as a new treatment strategy for diabetes mellitus.

Clinical features and mutation analysis of CHRNA4 gene for families and sporadic cases affected with autosomal dominant nocturnal frontal lobe epilepsy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate mutations of CHRNA4 gene in Chinese patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).</p><p><b>METHODS</b>Two hundred and fifty-seven patients (including 215 sporadic and 42 familial cases) were analyzed. Mutational screening was performed by sequencing all of the 6 exons of the CHRNA4 gene including the donor and acceptor splice sites.</p><p><b>RESULTS</b>The results have excluded the involvement of any known mutations of the CHRNA4 gene. A novel synonymous mutation c.570C>T(D190D) and 6 single nucleotide polymorphisms (SNPs) of the CHRNA4 gene were detected in 6 sporadic cases, including c.639T/C, c.678T/C, c.1209G/T, c.1227T/C, c.1659G/A, and c.1629C/T. The SNP D190D was hererozygous and absent in 200 healthy controls.</p><p><b>CONCLUSION</b>This results suggested that mutations of the CHRNA4 gene may be rare in southern Chinese population with ADNFLE. The synonymous mutation D190D has not been reported previously. Its impact on the pathogenesis of ADNFLE warrant further study.</p>

Effects of sericine on TGF-beta1/Smad3 signal pathway of diabetic mephropathy rats kidney / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of color silk cocoon extraction-sericine on transforming growth factor-beta1 (TGF-beta1) and Smad3 protein expression in kidney of diabetic nephropathy (DN) rats.</p><p><b>METHODS</b>60 male SD rats were randomly divided into 5 groups (n = 12): normal control group, DN model group, sericine treatment group, metformin group and sericine prevention group. The rats in model group, sericine treatment group, metformin group and sericine prevention group were all established DN rats model by intraperitoneally injected streptozotocin (STZ). Blood glucose > or = 16.7 mmol/L was taken as standard to judge if the rats model were successfully established. After the rats model were successfully established, the rats in sericine treatment group were lavaged with sericine (2.4 g/(kg x d), 35 d). The rats in metformin group were lavaged with metformin (55.33 mg/(kg x d), 35 d). The rats in sericine prevention group were lavaged with the same dose sericine for 35 d before injecting STZ. The blood glucose and kidney weight/body weight of rats in each group were respectively detected. Immunohistochemical staining was used to observe the expression of TGF-beta1 and Western blot to detect the expression of Smad3 in kidney.</p><p><b>RESULTS</b>Compared with normal control rats: the blood glucose, kidney weight/body weight, TGF-beta1 and Smad3 expression in kidney of rats in model group increased obviously (P < 0.01). The blood glucose, TGF-beta1 and Smad3 expression in kidney of rats in sericin treatment group, sericin prevention group and metformin group were significantly lower than that of model group (P < 0.01). Moreover, there were no obvious differences between sericin treatment group, sericin prevention group and metformin group (P > 0.05). The kidney weight/body weight of rats in sericin treatment group, sericin prevention group and metformin group were significantly lower than that of model group (P < 0.01). Moreover, the kidney weight/body weight of rats in sericin treatment group and sericin prevention group were obviously lower than that of metformin group (P < 0.05).</p><p><b>CONCLUSION</b>Sericin can inhibit activation of TGF-beta1/Smad3 signal pathway in kidney of DN rats, lighten glomerulosclerosis and renal interstitial fibrosis, so has protective and preventive effects on kidney injury of DN rats. Moreover, the therapeutical and preventive effects of sericin on DN are similar with metformin.</p>

Mutational analysis of CHRNB2 and CHRNA2 genes in southern Chinese population with autosomal dominant nocturnal frontal lobe epilepsy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the gene mutations of CHRNB2 and CHRNA2 in Chinese population with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).</p><p><b>METHODS</b>One hundred and six Han nationality patients (74 sporadic and 32 familial) were recruited and studied. Mutational screening was performed by sequencing all the 6 coding exons of the CHRNB2 gene and exons 6 and 7 of the CHRNA2 gene including the donor and acceptor splice sites.</p><p><b>RESULTS</b>The results excluded the involvement of all known published mutations of the CHRNB2 and CHRNA2 genes. However, a novel synonymous mutation c.483C>T (H161H) and a single nucleotide polymorphism (c.1407C>G) of CHRNB2 gene were detected in two ADNFLE sporadic patients respectively. The nucleotide variation H161H was heterozygous and absent in 200 healthy control samples. The mutation was also found in the proband's unaffected mother.</p><p><b>CONCLUSION</b>Our study suggests that the mutations of CHRNB2 and CHRNA2 genes may be rare in Chinese ADNFLE population. The novel synonymous mutation of H161H has not been reported previously and its impact on the pathogenesis of ADNFLE needs to be further studied.</p>

Identification of Arg77Cys and Arg174stop double heterozygous mutation in a Chinese family with inherited FXIII deficiency / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify the gene mutation type of an inherited coagulation factor XIII (FXIII) deficiency pedigree.</p><p><b>METHODS</b>PCR and DNA sequencing were used to identify the mutations in the 15 exons and the flank sequence of FXIII gene in the proband. The identified mutations were validated by allele specific PCR, PCR restriction fragment length polymorphism technique or DNA sequencing in the family members and 100 healthy volunteers.</p><p><b>RESULTS</b>Arg77Cys and Argl74stop double heterozygous mutations were discovered in the proband. The pedigree analysis showed that Arg77Cys missense mutation inherited from her father, and Arg174stop from her mother. The Arg77Cys missense mutation in exon 3 was not found in her husband and the other 100 healthy volunteers.</p><p><b>CONCLUSION</b>A novel Arg174stop nonsense mutation was discovered in human FXIII gene. A simple DNA assay based on PCR for detection of this mutation was developed. The congenital FXIII deficiency in the proband might be caused by the coinheritance of the Arg77Cys missense mutation in exon 3 and the Arg174stop nonsense mutation in exon 4.</p>

Expression of antiapoptotic gene aven in de novo acute myeloid leukemia patients and its clinical significance / 中国实验血液学杂志

This study was aimed to investigate the aven mRNA expression level of leukocytes from peripheral blood(PB)of de novo patients with acute myeloid leukemia (AML) and analyze its clinical significance, so as to provide a experimental basis for evaluating prognosis. The aven mRNA expression levels in PB samples from 69 de novo AML patients were detected by using real-time quantitative PCR. The relation of aven mRNA level with clinical and hematological characteristics (age, sex, WBC, Hb, Plt, LDH, Blast% in PB and BM, FAB subtype) and treatment outcome (CR rate and relapse rate) were analyzed. 21 normal individuals served as controls. The results showed that the expression level of aven mRNA was between 11.72% and 178.93% (median 37.2%) in de novo AML and between 10.81% and 50.98% (median 28.81%) in normal individuals. Aven mRNA expression level was higher in the AML group than that in the controls (p = 0.006). As aven mRNA expression level was compared with other clinical and hematological parameters, there were significant correlations between aven mRNA expression level and age (r = 0.25, p = 0.039), and between hemoglobin level (r = 0.29, p = 0.019), FAB subtype(r = 0.253, p = 0.036). The median expression level (50.08%) of aven mRNA in older patients (> or = 44 years) was higher then that (32.41%) in younger patients (< 44 years) (p = 0.018). The complete remission (CR) rate after two cycles of chemotherapy in patients with lower aven mRNA level (25/30, 83.33%) was higher than that in patients with higher aven mRNA level(21/30, 70%), but the difference was not significant(p = 0.22). The difference of aven mRNA expression level between AML patients with relapse and AML patents without relapse was not significant (p = 0.076). It is concluded that the expression level of aven mRNA in de novo AML patients obviously increases, the overexpression of aven mRNA likely involves in genesis of AML. The definite relation of aven mRNA expression level with treatment outcome and relapse was not been found.