Cerebral small vessel disease refers to a type of disease that damages the small blood vessels of the brain and causes parenchymal lesions due to various reasons,which is a common health hazard in the elderly population.It has a slow onset and progressive progression,gradually affecting the whole brain,which can cause stroke,cognitive impairment and other diseases,and seriously affect people's life quality.This article reviewed the correlation between the serological marker β2 microglobulin and cerebral small vessel disease in recent years,aiming to provide guidance for the early diagnosis and prevention of cerebral small vessel disease,and to provide new ideas for the clinical treatment of diagnosed patients.

Objective:To investigate the effects of long non-coding RNA (lncRNA) FBXL19-AS1 on the proliferation, migration and invasion of pancreatic cancer cells, and to determine the targeting relationship of lncRNA FBXL19-AS1 and microRNA-339-3p (miR-339-3p).Methods:From January 2017 to August 2019, 73 cancer tissues and matched normal pancreatic tissues adjacent to cancer from patients pathologically diagnosed as pancreatic cancer who underwent surgical resection in Yantai Hospital of Yantai were collected. Normal pancreatic epithelial cells (hTERT-HPNE) and 3 pancreatic cancer cell lines (Capan-1, SW1990, PaTu8988) were cultured in vitro. The real-time fluorescent quantitative PCR was used to detect the expression of lncRNA FBXL19-AS1 and miR-339-3p in pancreatic cancer tissues and cell lines. The Capan-1 cells were divided into the NC group (normal control group), si-NC group (transfected with meaningless negative sequence), si-FBXL19-AS1 group (transfected with FBXL19-AS1 small interfering RNA), miR-NC group (transfected with empty plasmid control), miR-339-3p group (transfected with miR-339-3p overexpression lentiviral vector), si-FBXL19-AS1+ anti-miR-339-3p NC group (cotransfected with FBXL19-AS1siRNA and miR-339-3p inhibitor negative control sequence) and si-FBXL19-AS1+ anti-miR-339-3p group (cotransfected with FBXL19-AS1siRNA and miR-339-3p inhibitor). CCK-8 method was used to detect cell proliferation activity. Transwell chamber was used to detect cell migration and invasion ability, and western blotting method was used to detect cell cyclinD1, matrix metalloproteinase 2 (MMP2) and MMP9 protein expression. Bioinformatics and dual luciferase reporter gene experiments were used to analyze the targeting relationship between lncRNA FBXL19-AS1 and miR-339-3p.Results:The expression of lncRNA FBXL19-AS1 in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue adjacent to cancer (2.96±0.21 vs 1.00±0.13, P<0.05), and the expression of miR-339-3p was significantly lower than that in normal pancreatic tissue adjacent to cancer (0.37±0.05 vs 1.00±0.11, P<0.05). The expression of lncRNA FBXL19-AS1 in Capan-1, SW1990 and PaTu8988 cells were 2.43±0.18, 1.97±0.13 and 1.73±0.14, respectively, which were significantly higher than that of hTERT-HPNE cells 1.00±0.07. The expression of miR-339-3p were 0.42±0.03, 0.54±0.03 and 0.57±0.04, respectively, which were all significantly lower than 1.00±0.05 of hTERT-HPNE cells. Among them, the expression of lncRNA FBXL 19-AS1 in Capan-1 cells was the highest, and the miR-339-3p was the lowest. Compared with the si-NC group, the absorbance value ( A450) of Capan-1 cells in the si-FBXL19-AS1 group, the number of migrating cells, and the number of transmembrane cells were significantly decreased (0.47±0.03 vs 0.94±0.06, 81.00±7.41 vs 187.00±16.13, 67.00±5.41 vs 141.00±9.24), the protein expression of cyclinD1, MMP2 and MMP9 was significantly reduced (0.44±0.03 vs 0.83±0.05, 0.48±0.03 vs 0.92±0.07, 0.38±0.02 vs 0.73±0.05). Compared with the miR-NC group, the A450, the number of migrating cells, and the number of transmembrane cells of Capan-1 cells in the miR-339-3p group were significantly decreased (0.54±0.04 vs 0.94±0.05, 98.00±6.53 vs 193.00±10.02, 83.00±6.58 vs 146.00±7.11, the protein expression of cyclinD1, MMP2 and MMP9 was significantly reduced (0.47±0.03 vs 0.81±0.07, 0.43±0.03 vs 0.94±0.06, 0.32±0.02 vs 0.71±0.06). Compared with the si-FBXL19-AS1+ anti-miR-NC group, the A450, the number of migrating cells and the number of transmembrane cells in the si-FBXL19-AS1+ anti-miR-339-3p group increased significantly (0.96±0.07 vs 0.48±0.03, 204.00±11.25 vs 83.00±5.11, 157.00±8.76 vs 64.00±4.12, P all <0.05), the protein expression of cyclinD1, MMP2 and MMP9 increased significantly (0.84±0.06 vs 0.42±0.03, 0.96±0.08 vs 0.47±0.08, 0.74±0.06 vs 0.37±0.02, P all <0.05). The luciferase activity of Capan-1 cells cotransfected with WT-FBXL19-AS1 and miR-339-3p mimics was significantly lower than that of the cotransfected with WT-FBXL19-AS1 and miR-NC (0.47±0.04 vs 1.00±0.10, P all <0.05). The difference of the luciferase of Capan-1 cells in the cotransfected MUT-FBXL19-AS1 and miR-339-3p mimics group and the cotransfected MUT-FBXL19-AS1 and miR-NC group was not statistically significant. Conclusions:LncRNA FBXL19-AS1 was highly expressed in pancreatic cancer tissues and Capan-1 pancreatic cancer cell lines. Knockdown of lncRNA FBXL19-AS1 can target miR-339-3p to regulate the proliferation, migration and invasion of pancreatic cancer cells, and promote the occurrence and development of pancreatic cancer.

Objective To review and analyze the clinical and pathological data of children with autoimmune hepatitis (AIH).Methods Medical records of 46 patients hospitalized in Pediatric Liver Diseases Treatment and Research Center,Fifth Medical Center,General Hospital of People's Liberation Army(PLA) from April 2012 to April 2018 were extracted.Medical data included type of AIH,clinical manifestations,biochemical parameters,liver biopsy results,and outcomes of treatment were analyzed retrospectively.Among 46 children,19 were males and 27 were females.The age of onset was 10.1 (1.4-18.0) years old.Chi-Square test,Rank sum test or t test were used for inter-group comparison.Results There were 32 (70％)AIH-Ⅰ cases and 14 (30％)AIH-Ⅱ cases (x2=12.565,P=0.000).Among the 46 patients,there were 5 modes of onest:17 cases (37％) had acute viral hepatitis-like presentation,2 cases (4％)had fulminant hepatic failure,9 cases (20％) had insidious onset,5 cases (11％) showed cirrhosis and portal hypertension,and 13 cases (28％) were incidentally found to be due to elevated hepatic aminotransferases.Comorbidities including primary sclerotic cholangitis (n=3),primary biliary cholangitis (n=1),systemic lupus erythematosus (n=1) and inflammatory bowel disease (n=2),were all seen in AIH-Ⅰ cases.The elevated biochemical parameters of these patients were as follows:alanine aminotransferase (n=46),aspartate transminase (n=46),total bilirubin (n=35) γ-glutamyl transpeptadase (n=39),γ-globulin (n=32) and IgG (n=33).The γ-globulin and IgG levels were significantly higher in AIH-Ⅰ patients than those with AIH-Ⅱ ((32±9)％ vs.(23±8)％,t=3.217,P=0.002,(27± 10) vs.(18±8)g/L,t=3.193,P=0.003,respectively).Thirty-nine patients received liver biopsy,among whom 22 (56％) with inflammation grade (G)≥3,26(67％) with fibrosis stage (S) ≥3,and 7 with hepatic cirrhosis (S4) according to pathological analysis.Typical histopathological changes of AIH included:36 cases of interfacial hepatitis (92％),23 cases of lymphocyte/plasma cell infiltration (59％),3 cases of rosette (8％).Forty patients received prednisolone monotherapy or combined with azathioprine after diagnosis.Complete remission was seen in 29 (72％) patients,partial remission in 10 (25％) patients and no response in 1 (3％) patient.Among complete remission patients,15 (52％) had relapse in the process of prednisolone reduction.Repeated liver biopsy performed in 8 patients after treatment showed that hepatic inflammation and fibrosis were both improved in 6 patients,only inflammation was alleviated without fibrosis improvement in 1 patient,and neither inflammation nor fibrosis was improved in 1 case.The length of follow-up was 3.3 (0.3-10.5) years,and none of the 39 prednisolone-responded cases discontinued treatment successfully.Adverse effect of long-term prednisolone therapy included bilateral cataract (n=6),spinal fracture accompanied with delayed bone age development (n=1).Conclusions AIH-Ⅰ is more common than AIH-Ⅱ in children,with diverse clinical characteristics.Most cases have progressive liver inflammation and fibrosis when diagnosed.Prednisolone monotherapy or combined with azathioprine could achieve both biochemical and pathological improvement,but relapse is inevitable during drug tapering,hence long-term treatment is essential.

OBJECTIVETo analyze the clinical phenotype of a Chinese pedigree affected with hereditary dentinogenesis imperfecta and mutation of dentin sialophosphoprotein (DSPP) gene.

METHODSAffected members underwent intraoral photography, dental film and panoramic radiography. Genomic DNA was extracted from peripheral venous blood samples. Coding regions of the DSPP gene were subjected to PCR amplification and Sanger sequencing. Functional effect of the mutation was predicted with SIFT and PolyPhen-2. The tertiary structure of wild type and mutant proteins were predicted by Swiss-Port.

RESULTSA heterozygous c.50C to T (p.P17L) mutation was identified in exon 2 of the DSPP gene in the proband and her father. The same mutation was not found among 200 unrelated healthy controls. The Pro-17 residues and its surrounding positions in DSPP are highly conserved across various species. The mutation was predicted to be damaging to the structure of DSPP protein.

CONCLUSIONThe c.50C to T (p.P17L) mutation of the DSPP gene probably underlies the disease in this pedigree. Above finding has expanded the spectrum of DSPP gene mutations and provided a basis for genetic counseling and prenatal diagnosis for this family.

Objective Cancer-related fatigue (CRF) is a key in the management of cancer patients' clinic syptoms.This article investigated the status quo of nurses' knowledge and attitude towards CFR.Methods THe method of cross-sectional survey and questionnaire was used to investigate the knowledge and attitude towards CRF among nurses from related departments of three Grade III hospitals in Nanjing.Results 142 nurses answered the questionnaire.The average correct rate was 76.25%, among which nurses from the oncology department had better congition rate than nurses from other medical and surgical departments (84.3%, 75.98%, 79.57%) , representing significant difference (P<0.05).64.79% of the nurses found the relatives of cancer patients and nurses often fail to understand cancer patients;complaint of fatigue, 76.76% of nurses assumed there is lack of communication in fatigue between patients and medical staff.94.36% of nurses agreed medical institutions should strengthen the management of CRF.Conclusion At present, the clinical nurses have inadequate knowledge about CRF, which should be enhanced in future work.

Objective To investigate correlation between seizures and uric acid level in the hippocampus in a mouse model with acute limbic seizures by pharmacological and genetic method. Methods Normal male C57BL/6 and mutant mice were used in this study,including urate oxidase overexpression (UOx-OE) and urate oxidase knock-out (UOx-KO) ;These mice were divided into the following groups,including the control,KA, All ,OE ,KO group respectively;during the experiment ,behaviors ,latency and duration time were recorded;dialysates were collected by microdialysis technique and uric acid level was detected by FPLC;Uric acid in the hippocampus,seizures status,latency and duration were compared. Results Twenty-four mice in total were enrolled and only 1 death occurred until the end of the study. Seizures state appeared after KA treatment. Compared to the KA group,uric acid and generalized seizures declined by the treatment of KA and All (P< 0.05) . Compared to the KA group,uric acid,latency and generalized seizures elevated in the KO group (P < 0.05). Compared to the KA group,there was no difference of latency,duration,partial and generalized seizures occurring in the OE group (P> 0.05). Conclusions Uric acid level in the hippocampus of mice may have effects on seizures ,in which it suggests that uric acid and its relevant signal pathway could be a potential therapy target in seizures clinically.

Background and purpose:For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activatingEGFR gene mutation.Methods:This study included 61 patients with lung adenocarcinoma harboring an acti-vatingEGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then re-ceived pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/peme-trexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events.Results:Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9-7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C).Conclusion:Among patients withEGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.

Background and objectivehTe prognosis for patients with lung cancer and brain metastases remains poor, with approximately 6 months of survival, despite active measures atfer treatment. In this study, we determined and ana-lyzed clinical parameters that affect the survival of patients with lung cancer and brain metastases to provide clinical guidance. MethodsLung cancer cases with brain metastases were retrospectively collected during 2002 and 2008 from Shanghai Chest Hospital, Shanghai Jiao Tong University.Kaplan-Meier method andCox regression were performed for univariate and multi-variate analyses, respectively, to explore independent predictors inlfuencing the survival of patients with lung cancer and brain metastases.Results Age, Eastern Cooperative Oncology Group performance status (ECOG PS), metastasis interval, number of metastasis, treatment method, treatment period, symptoms of brain metastases, extracranial metastasis, and brain metastasis order were factors that affect the survival of patients with brain metastases as conifrmed through theKaplan-Meiermethod. Treatment periods and extracranial metastasis were independent survival predictors in patients with lung cancer and brain me-tastasis as indicated byCox proportional hazard model.ConclusionTreatment periods and extracranial metastasis were inde-pendent predictors of survival of patients with lung cancer and brain metastasis. Treatment periods and extracranial metastasis were independent predictors of survival of patients with lung cancer and brain metastasis.

10.3969/j.issn.1007-3969.2013.05.002

ObjectiveTo investigate the characteristic and the function of the eye movements system of the patients with vertebral-basilar insufficiency (VBI).Methods83 patients with VBI and 57 healthy controls were tested with electronystagmogram instrument,include saccade test, Eye Tracking Test (ETT) and optokinetic test(OKN).Results and ConclusionDelay lower accuracy of saccade test, decreased gain of OKN, asymmetry of horizontal ETT were showed in the patients with VBI.