Progress in researches for perampanel in the treatment of comorbidities of epilepsy / 中国临床药理学与治疗学

Sleep disorder, migraine, cognitive and behavioral disorders, anxiety and depression are common comorbidities of epilepsy. The comorbidity rate of epilepsy patients is eight times that of the general population, which affects the prognosis and quality of life of epilepsy patients. Perampanel (PER), as a third-generation antiseizure medication, has shown promising clinical research and application in the treatment of comorbidities in epilepsy. PER can improve the total sleep time, sleep latency and sleep efficiency of patients with epilepsy comorbid sleep disorder. PER also shows good efficacy in reducing seizure and migraine attacks of patients with epilepsy comorbid migraine. Meanwhile, the impact of PER on overall cognitive characteristics is neutral, with no systematic cognitive deterioration or improvement, but behavioral changes are one of the most common adverse events related to PER. For patients with comorbid anxiety and depression, PER does not exacerbate the anxiety and depression of epilepsy patients, and the severity of anxiety and depression in some patients will improve. This article will review the mechanism of action and clinical treatment research progress of PER on comorbidities of epilepsy.

Study on NAEK-labelled HiD-Hin47 fusion protein as a carrier for pneumococcal polysaccharide conjugate vaccine / 中华微生物学和免疫学杂志

Objective:To develop an unnatural amino acid-labelled HiD-Hin47 fusion protein as a novel carrier.Methods:Twenty versions of the fusion protein were designed, each of which contained a different amino acid site replaced by an azide-bearing amino acid, N6-(2-azidoethoxy) (carbonyl)-L-Lysine (NAEK). These fusion proteins were constructed, expressed and purified, and the yield were evaluated by SDS-PAGE. Based on the highest protein yield, which was approximately 70% of the wild-type yield, the fusion protein with the unnatural amino acid in E677 site was selected. The pneumococcal polysaccharides of serotype 3 (F3) and serotype 6B (F6B) were coupled to the selected fusion protein through a "click" reaction. The conjugates were purified and compared in animal studies with other F3 and F6B conjugates that were coupled to CRM197, tetanus toxoid (TT) and HiD by conventional methods.Results:The immunogenicity of F3 conjugate using HiD-Hin47 as carrier (F3-HiD-Hin47) was slightly better than that of other F3 conjugates. F6B-HiD-Hin47 was significantly better than F6B-TT and F6B-HiD in terms of immunogenicity, but showed no significant difference with F6B-CRM197.Conclusions:NAEK-labelled HiD-Hin47 had the potential as a carrier for pneumococcal polysaccharide conjugate vaccine and was worthy of further study.

Comparison of machine learning method and logistic regression model in prediction of acute kidney injury in severely burned patients / 中华烧伤杂志

Objective@#To build risk prediction models for acute kidney injury (AKI) in severely burned patients, and to compare the prediction performance of machine learning method and logistic regression model.@*Methods@#The clinical data of 157 severely burned patients in August 2nd Kunshan factory aluminum dust explosion accident conforming to the inclusion criteria were collected. Patients suffering AKI within 90 days after admission were enrolled in group AKI, while the others were enrolled in non-AKI group. Single factor analysis was used to choose independent factors associated with AKI, including sex, age, admission time, features of basic injuries, initial score on admission, treatment condition, and mortality on post injury days 30, 60, and 90. Data were processed with Mann-Whitney U test, chi-square test, and Fisher′s exact test. Variables with P<0.1 in single factor analysis and those with possible clinical significance were brought into the establishment of prediction model. Logistic regression and XGBoost machine learning algorithm were used to build the prediction model of AKI. The area under receiver operating characteristic curve (AUC) was calculated, and the sensitivity and specificity for optimal threshold value were also calculated for each model. Nonparametric resampling test was used to compare the significance of difference of AUC of the two models.@*Results@#(1) Eighty-nine (56.7%) patients developed AKI within 90 days from admission. Compared with 68 patients in non-AKI group, 89 patients in group AKI were older (Z=-2.203, P<0.05), with larger total burn area and full-thickness burn area (Z=-5.200, -6.297, P<0.01), worse acute physical and chronic health evaluation (APACHE) Ⅱ score, abbreviated burn severity index score, and sequential organ failure assessment (SOFA) score on admission (Z=-7.485, -4.739, -4.590, P<0.01), higher occurrence rate of sepsis (χ2=33.087, P<0.01), higher rates of accepting tracheotomy, mechanical ventilation, and continuous renal replacement therapy (χ2=12.373, 17.201, 43.763, P<0.01), larger first excision area (Z=-2.191, P<0.05), and higher mortality on post injury days 30, 60, and 90 (χ2=7.483, 37.259, 45.533, P<0.01). There were no statistically significant differences in sex, open decompression, admission time, 24-hour fluid volume after admission, 48-hour fluid volume after admission, the first 24-hour urine volume, the second 24 hour urine volume, the first excision time, and inhalation injury (χ2=0.529, 3.318, Z=-1.746, -0.016, -1.199, -1.824, -0.625, -1.747, P>0.05). The rates of deep vein catheterization of patients in the two groups were both 100%. (2) There were twenty possible prediction variables for preliminary establishment of model according to the difference results of single factor analysis and clinical significance of variables. (3) The logistic regression prediction model had three variables: APACHE Ⅱ score [odds ratio (OR)=1.36, 95% confidence interval (CI)=1.20-1.53, P<0.001], sepsis (OR=2.63, 95% CI=0.90-7.66, P>0.05), and the first 24-hour urine volume (OR=0.71, 95% CI=0.50-1.01, P>0.05). The AUC of the logistic regression prediction model was 0.875 (95% CI=0.821-0.930), with the specificity and sensitivity of optimal threshold value 84.4% and 77.7%, respectively. (4) XGBoost machine learning model had seven main predictive variables: APACHE Ⅱ score, full-thickness burn area, 24-hour fluid volume after admission, sepsis, the first 24-hour urine volume, SOFA score, and 48-hour fluid volume after admission. The AUC of machine learning model was 0.920 (95% CI=0.879-0.962), higher than that of logistic regression model (P<0.001), with the specificity and sensitivity of optimal threshold value 89.7% and 82.0%, respectively.@*Conclusions@#Sepsis and fluid resuscitation are two important predictive variables that can be intervened for AKI in severely burned patients. Machine learning method has a better performance and can provide more accurate prediction for individuals than logistic regression prediction model, and therefore has good clinical application prospect.

Reflection on rescue and treatment of mass burn casualties in 21st century / 中华烧伤杂志

The rescue and treatment of mass burn casualties is a test for both the burn treatment level and the disaster emergency response ability of a country or a region. In recent years, burn disasters happened occasionally around the world despite of the improvement of safety level in production and the awareness of fire prevention. On one hand, mass burn casualty events caused catastrophic damages to human health. On the other hand, they also promoted the development of burn treatment and disaster medicine. This paper may provide some references for further improving the management of mass burn casualties in the future by reviewing several typical cases of burn disaster rescue and treatment in the world since the 21st century.

A retrospective study of antiepileptic drugs, etiology and seizure patterns in hospitalized patients with epilepsy / 中国神经精神疾病杂志

Objective The aim of this study was to investigate and analyze the etiology, seizure type and anti-epileptic drugs (AEDs) utilization of in-patients with epilepsy Methods The study included 5563 cases in-patients with epilepsy. The etiology and seizure type and the date of type, quantity of AEDs in-patient department were collected and their usage frequency were analyzed statistically. Results The most common etiology of epilepsy was traumatic brain injury(13.64%), followed by hippocampal sclerosis (11.52%), stroke (5.24%), nervous system infection (4.98%), perinatal injury ( 5 . 28 % ) and undefined etiology ( 40 . 80 % ) . The most common seizure type was partial seizures (45.43% ). The AEDs of carbamazepine and valproate were the most common used drugs in the clinical and their average usage frequency were 36.88% and 30.80%, respectively. The newer AEDs of Lamotrigine and Levetiracetam were used more frequently. The use of Lamotrigine increased from 16.16% to 28.44% and the Levetiracetam from 0.61% to 20.87% whereas the use of Oxcarbazepine and Topiramate remained a stable level of 15.07% and 9.42%. Conclusion The etiology of epilepsy is complicated and the seizure type of epilepsy was diverse. Among a great variety of anti-epileptic drugs, the newanti-epileptic drugs are being increasingly used.

To analyze the expression of HIF-1 alpha and VEGF in gastric carcinoma and its significance / 中国生化药物杂志

Objective To investigate the expression of hypoxia - inducible factor -1 alpha and vascular endothelial growth factor in gastric carcinoma and its clinical significance. Methods The expression was detected by immunohistochemistry method in 100 cases of gastric carcinoma tissues of patients with carcinoma and HIF-1 alpha, VEGF, VEGF test results comparing the carcinoma tissue and adjacent normal tissues, HIF-1 alpha; different differentiation degree and infiltration depth of tumor tissue of HIF-1 alpha and VEGF detection results of recurrence or metastasis;group, no recurrence or metastasis detection results of HIF-1 alpha and VEGF tumor tissue cancer group. Results The positive rate of HIF-1 expression in gastric tumor tissue of patients with cancer (60.00％), the positive expression rate of VEGF (64.00％) were significantly higher than those in adjacent normal tissues (21.00％, 14.00％), the difference was statistically significant (P<0.05); high ang middle differentiation, invasive depth of tumor tissue before plasma membrane positive in patients with gastric cancer the rate of VEGF, HIF-1 alpha, was low, the data had significant differences (P<0.05); the positive rate of HIF-1 alpha and VEGF expression of gastric carcinoma tumor recurrence or metastasis was found in (70.97％), the positive expression rate of VEGF (77.42％) were significantly higher than those of HIF-1 alpha and VEGF expression in patients with gastric cancer recurrence or tumor tissue the transfer of (55.07％, 57.97％), the difference was statistically significant (P<0.05). Conclusion HIF-1 alpha and VEGF play an important role in the recurrence and metastasis of gastric cancer, is an important basis for the diagnosis and prognosis of gastric cancer patients, clinicians should understand the patients with gastric cancer HIF-1 alpha and VEGF expression, so as to reduce the recurrence and metastasis rate is of important value.

Study of a virus-like particle vaccine containing N-terminal epitopes of human papilloma virus L2 protein / 中国免疫学杂志

Objective:To prepare a virus-like particle (VLP),containing Hepatitis B virus core antigen (HBcAg) and N-terminal peptides of the L2 protein of human papilloma virus (HPV),and investigate the immunogenicity of the VLP in mice and the protection against different strains of HPV .Methods:A fusion gene was synthesized to insert a DNA fragment ,coding for the N-terminal epitopes of the L2 protein of HPV16,into the HBcAg coding sequence;HBc-L2 fusion protein was highly expressed in E.coli using the pET9a and BL21(DE3) expression system;the purified fusion protein was used to immunize BALB/c mice and antibody titers against the L2 epitopes in mouse sera were determined by indirect ELISA;the levels of neutralizing antibodies against both HPV 16 and 18 were also analyzed.Results:HBc-L2 fusion protein was expressed in E.coli and purified,with the purity >80%,by ammonium sulfate pre-cipitation and CL-4B gel filtration;analysis of the purified fusion protein ,using size exclusion chromatography with multi-angle laser light scattering detection ( SEC-MALS) and electron microscope ,revealed that HBc-L2 was assembled into a stable VLP structure auto-matically following its expression;immunization of BALB/c mice with the purified VLPs resulted in high antibody titers in mouse sera against the L2 epitopes;furthermore,it was demonstrated that the sera from the immunized mice had neutralization activities against both HPV16 and HPV18.Conclusion:The immunogenicity of the L2 epitopes was highly enhanced by the construction of HBc-L2 fusion protein and the formation of the VLP structure;the fusion protein was also capable of inducing protections against different serotypes of HPV,therefore,it could be a potential HPV vaccine with a broad coverage and low production cost .

Treatment and prognosis of primary gastric lymphoma / 中华消化外科杂志

Objective To investigate the treatment methods for primary gastric lymphoma (PGL) and analyze the prognostic factors.Methods The clinical data of 55 patients with PGL who were admitted to the First Affiliated Hospital of Dalian Medical University from July 2002 to December 2007 were retrospectively analyzed.Operation,medication or operation combined with medication were applied to patients according to the pathological type,clinical staging,infection of helicobacter pylori and complications.Patients were followed up via phone call till February 2013,and the location,diameter,pathological type,clinical stage of the PGL and the treatment methods were recorded for prognostic analysis.The survival rate was calculated by Kaplan-Meier method,and the univariate analysis of survival was done by Log-rank test.Multivariate analysis was done by COX regression model.Results The PGL located at the gastric antrum in 26 cases,body of the stomach in 17 cases,fundus of the stomach in 5 cases,gastric cardia in 3 cases,body and antrum of the stomach in 4 cases.There were 46 patients with ulcerous PGL,5 with nodular PGL and 4 with diffused and infiltrated PGL.There were 53 B cell lympboma,1 T cell lymphoma and 1 undefined tumor.Of the 53 patients with B cell lymphoma,36 were with mucosa-associated lymphoid tissue lymphoma (MALTL) and 17 with diffuse large B-cell lymphoma (DLBCL).There were 23 patients in stage Ⅰ,23 in stage Ⅱ,4 in stage Ⅲ and 3 in stage Ⅳ.Of the 55 patients,23 received operation,14 received medication,17 received operation + medication,and 1 left untreated.Fifty-three patients had complete follow-up data.The median time of follow-up was 60 months (range,7-132 months).The 1-,3-,5-year cumulative survival rates were 91％,79％ and 72％.The results of univariate analysis showed that tumor diameter,pathological type and clinical staging were risk factors influencing the prognosis of PGL patients (x2 =9.34,6.59,88.01,P ＜ 0.05),while the treatment methods did not influence the prognosis of PGL patients (x2 =3.63,P ＞ 0.05).The results of multivariate analysis showed that DLBCL,clinical stages Ⅲ and Ⅳ were independent risk factors influencing the prognosis of PGL patients (OR =5.758,2.231,95％ confidence interval:2.536-13.073,1.370-3.625,P ＜ 0.05).Conclusion Multi-disciplinary team treatment should be recommended for PGL patients.Pathological type (DLBCL) and clinical stages (stage Ⅲ and Ⅳ) are the independent risk factors influencing the prognosis of PGL patients.

The correlation of notch-1 expression and comprehensive analysis with prognosis in small cell lung cancer / 中国综合临床

Objective To investigate the clinical significance of Notch-1 expression in small cell lung cancer(SCLC) and non-small cell lung cancer(NSCLC),and analyze the role of it in prognosis.Methods SP immunohistochemistry was used to detect the expression of Notch-1 antibody in 43 of SCLC and 40 of NSCLC tissues.Further analysis was carried out to interpret the association of Notch-1 antibody expression with clinicopathological features,lymph node metastasis and prognosis in SCLC.Results The positive rate of Notch-1 expression was 20.93％ ( 9/43 ) in SCLC,while 65.00％ ( 26/40 ) in NSCLC.The expression of Notch-1 antibody was associated with clinical stage and lymph node metastasis ( x2 =5.42,P ＜ 0.05 ; x2 =4.88,P ＜ 0.05respectively),but was not associated with age,sex,tumor location,tumor size ( Ps ＞ 0.05 ).Compared with NSCLC,the expression rates of Notch-1 antibody were significantly higher in SCLC ( x2 =16.50,P ＜ 0.05 ).Kaplan-Meier survival analysis indicated that the survival time of patients with positive Notch-1 expression was significantly longer than that of patients with negative staining( x2 =19.87,P ＜ 0.05 ).Cox regression analysis showed that Notch-1 antibody could significantly reduce the risk of death in patients with SCLC.Conclusion The positive expressions of Notch-1 were significantly different in SCLC and NSCLC,which linked to the clinicalstage,lymph node metastasis and poor prognosis.Accordingly,the expression of Notch-1 may have good value in diagnosis and prognosis.

Hepatitis B surface antigen terminates codon bias selection / 北京大学学报(医学版)

Objective:To investigate the existence condition of hepatitis B surface antigen(HBsAg) termina-tion codon bias.Methods: A total of 174 reference sequences of all kinds of Hepatitis B virus(HBV) genotypes were chosen from GenBank,and compared by BioEdit.Then secondary structure of RNA was constructed and analyzed together.Results:(1) There were two types of HBsAg termination codon: TAA and TGA in 174 reference sequences.TAA was in 124 cases(71.26%);and TGA in 50 cases(28.74%).(2) There was codon bias selection in HBsAg termination codon,and it could affect the secondary structure of RNA and amino acid sequence encoding protein.Conclusion: HBsAg termination codon bias exists and may be related to RNA structure and the conservatiom of protein function in the evolutionary progress.

Pathological study on severe acute respiratory syndrome / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation.</p><p><b>METHODS</b>Tissue specimens from 3 autopsies of probable SARS cases were studied by microscope, and the clinical data was reviewed.</p><p><b>RESULTS</b>The typical pathological changes of lungs were diffuse hemorrhaging on the surface. A combination of serous, fibrinous and hemorrhagic inflammation was seen in most of the pulmonary alveoli with the engorgement of capillaries and detection of micro-thrombosis in some of these capillaries. Pulmonary alveoli thickened with interstitial mononuclear inflammatory infiltrates, suffered diffuse alveolar damage, experienced desquamation of pneumocytes and had hyaline-membrane formation, fibrinoid materials, and erythrocytes in alveolar spaces. There were thromboembolisms in some bronchial arteries. Furthermore, hemorrhagic necrosis was also evident in lymph nodes and spleen with the attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and lesions having existed before hospitalization were observed in the liver, heart, kidney and pancreas.</p><p><b>CONCLUSION</b>Severe damage to the pulmonary and immunological systems is responsible for the clinical features of SARS and may lead to the death of patients.</p>

Studying the Quality of Monitoring System of Teaching Process Quality in Sports Institutes / 中华医学教育探索杂志

Undergraduate education is a basic stage in higher education.Undergraduate physical education is the key to improve physical education in colleges.Monitoring teaching quality is an effective measure to improve the physical teaching quality.

Researching on the relation between lamivudine-resistant mutation and HBV genotypes / 中华检验医学杂志

Objective To analyze the relation between lamivudine-resistant mutation types and HBV genotypes.Methods 95 cases with YMDD mutation were selected from out-patient clinic and sickroom in our hospital.Restriction endonuclease MboⅠand EarⅠwere used to identify HBV genotypes of PCR product, farther a phylogenesis tree was applied to check it.Results We could divide 95 cases into two parts, 75 cases(78.95%) were HBV C genotype and 20 cases(21.05%) were B genotype, these were verified by phylogenesis tree.With regard to the types of YVDD mutation、YIDD mutation and YMDD+YVDD+YIDD mutation, there were 11 cases, 5 cases, 4 cases in genotype B, respectively, but 35 cases, 27 cases, 13 cases in genotype C.We made the cha-test to check genotypes and types of YMDD mutation, ?2= 0.856, P=0.710. There were no significant differences.Conclusions Using MboⅠand EarⅠcan genotype HBV PCR product easily and reliably. It is no statistical significance between HBV B or C genotype and the types of YMDD mutation.

Utilization of Uracil-DNA glycosylase for combining reverse transcription and anti-contamination with polymerase chain reaction in hepatitis C virus / 北京大学学报(医学版)

Objective: To develop a hepatitis C virus(HCV) reverse transcription-polymerase chain reaction (RT-PCR) assay using Uracil-DNA glycosylase (UDG) for amplicon contamination control and evaluate the temperature and UDG concentrations for anti-contamination. Methods: In this new HCV RT-PCR assay, reverse transcription, UDG anti-contamination and the first PCR were carried out at the same time. The layer candles were used to prevent the contamination in the second PCR. dU-DNA was used as quality control for UDG anti-contamination and templates to determine the sensitivity of the new HCV RT-PCR assay. HCV cDNA was detected by DNA enzyme immunoassay (DNA-EIA). Results: Complete degradation of amplicon DNA was observed on the conditions of 0.2 u UDG per reaction volume respectively at 37 ℃ and 42 ℃ for 40 min. The anti-contamination condition also could eliminate all detectible dU-DNA, including the highest concentration of amplicon DNA.The 1∶104 dilution of the HCV RNA sample containing 2.110?105copies/mL copies of RNA could be detected. Conclusion: Our results indicate that this new RT-PCR assay can control the contamination stringently and is sensitive as well.

Analysis and state of HCV genotype 6a infection / 北京大学学报(医学版)

Objective: To investigate the infection state of hepatitis C virus genotype 6a in China.Methods: Three(95,126,150)HCV genotype 6a serum samples were identified by digesting 5′NCR with compound enzyme method.Then,HCV 5′NCR and NS5B fragments were amplified from these samples by RT-PCR assay and sequenced.The phylogenetic trees of the samples were analyzed and compared with 24 HCV complete gene sequences from GenBank.Results: The sequencing reports on 5′NCR showed "CA" bases in 3 serum samples(95,126,150) were inserted into-145 site,and the sequences of 3 serum samples had the highest homology with sequence Y12083(0.934,0.930,and 0.926,respectively).The results of the phylogenetic trees suggested these 3 serum samples belonged to HCV genotype 6a.The sequencing reports on NS5B showed the 3 serum samples also had the highest homology with HC-J4(0.934,0.930,and 0.926,respectively),and the results of the phylogenetic trees suggested these 3 serum samples belonged to HCV genotype 1b.To exclude the influence of amplification efficiency of primers,NS5B fragments were amplified by HCV genotype 6a specific primers and no amplification products appeared.Conclusion: There are different results of HCV genotype by analyzing 5′NCR and NS5B in 3 samples infected with HCV genotype 6a.It may be related with gene recombination.It suggests HCV genotype should be analyzed on more than two regions.