Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Abstract: Objective　To analyze the epidemiological characteristics of public health emergencies in Xishuangbanna Dai Autonomous Prefecture from 2012 to 2021, and to provide reference for formulating relevant prevention and control measures. Methods　The data of public health emergencies reported in Xishuangbanna from 2012 to 2021 were collected and analyzed through the China Disease Prevention and Control Information System. Results A total of 78 public health emergencies (including "Unrated" events) were reported in Xishuangbanna from 2012 to 2021. The highest 21 cases and the lowest 3 cases were reported every year. A total of 1 0374 cases were reported in 78 public health emergencies, involving a population of 1 703 049, with a morbidity of 609.14/100 000, 24 deaths, mortality of 1.41/100 000 and fatality rate of 231.35/100 000. The event level was mainly "general (level Ⅳ)" with 52 incidents, accounting for 66.67%, and 17 incidents of "major (level Ⅲ)", accounting for 21.79%. 51 cases were mainly infectious diseases, accounting for 65.39%. The peak periods for incidents were May-July and November-February of the next year; there were 39 incidents in schools, accounting for 50%, followed by 20 incidents in families, accounting for 25.64%. The top three reported cases were food poisoning (32.05%), chicken pox 17 (21.79%) and dengue fever 10 (12.82%). Among the 24 deaths in public health emergencies, 22 were caused by food poisoning. Wild bacteria poisoning and alcohol poisoning were the main causes of food poisoning, accounting for 45.83% and 37.5% of the total deaths, respectively. Conclusion Infectious diseases, especially respiratory diseases and food poisoning are the focus of the prevention and control of public health emergencies in Xishuangbanna Dai Autonomous Prefecture, of which Schools and families should be pay close attention. Plague, a Class A infectious disease, caused by the bacterium Yersinia pestis has occurred in two inter-animal outbreaks in 10 years and spread to the population, which should be of great concern.

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis

Humans ; Infant ; Male ; Phenotype ; Wiskott-Aldrich Syndrome ; diagnosis ; genetics ; immunology

Fragments encoding amino acids 76-130 in the linear conserved region (LCR) of A/Hubei/1/2010 (H5N1) HA2 was fused to hepatitis B core antigen (HBc) to generate a LCR-HBe virus-like particle (VLP). Results showed that the fusion protein of LCR-HBc was highly expressed in this prokaryotic expression system. The purified LCR-HBc particle stimulated high levels of IgG production in mice with a titer of > 1:12 800, and provided 50% cross-protection against lethal challenge by H1N1 viruses.
Amino Acid Sequence ; Animals ; Female ; Hemagglutinin Glycoproteins, Influenza Virus ; immunology ; Influenza A Virus, H5N1 Subtype ; immunology ; Influenza Vaccines ; immunology ; Interferon-gamma ; biosynthesis ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data

Objective To quantitatively analyze the effects of high background radiation area (HBRA) on the frequencies of translocation and unstable chromosome aberrations in human peripheral blood lymphocytes.Methods Based on the data from 9 published articles retrieved from 7 electronic databases,the Meta-analysis was performed to evaluate the effects of high natural background radiation (HNBR) on the frequencies of chromosome aberrations in the peripheral blood lymphocytes in 17 777 persons from HBRA and 10 386 from the control area (CA).Cochrane's Q and I2 statistics were used to evaluate heterogeneity among studies and pooling odds ratio (OR) with 95％ confidence intervals (95％ CI) were calculated using random-effect models.Publication bias was also calculated by funnel plot,Egger linear regression test and Begg rank correlation test.Results The pooling OR of translocation [OR(95％ CI) =1.57(1.10-2.24)] and unstable chromosome aberration [OR(95％ CI) =2.04(1.32-3.14)] of long-term exposed inhabitants living in HBRA were higher than control.The subgroup analysis showed that,fortranslocation,the OR (95％ CI) were 1.24 (1.09-1.42,I2 =0.00) for male,1.37 (1.17-1.60,I2 =0.00) for female,1.17 (1.05-1.30,I2 =69.50％) for adults,and 1.38 (1.25-1.51,I2 =0.00) for Chinese.For unstable chromosome aberration,the OR (95％ CI) were 3.78 (2.40-5.97,I2 =0.00) for female,2.60 (2.25-3.00,I2 =69.60％) for adults,1.03(0.85-1.24,I2 =0.00) for children,3.19 (2.46-4.13,I2 =21.60％) for Iranian,and 1.64 (1.33-2.02,I2 =0.00) for Chinese.HBRA,age and sex differences were the reasons of above heterogeneity.Conclusions To the inhabitants living in HBRA,the frequencies of translocation and unstable chromosome aberration of peripheral blood lymphocytes are higher than those in control area.More comprehensive analysis should be performed to assess the health risk in HBRA inhabitants,which may arise new stragety in radiation protection.

Nucleoprotein (NP) of influenza virus is highly conserved and type-specific. NP can trigger strong cell-mediated immune responses in host and is involved in the protection against the challenges with different subtype influenza viruses. Here, NP of an avian H5N1 (A/Hubei/1/2010, HB) was expressed by baculovirus surface-display technology and its immunogenicity as well as protective mechanism was investigated in mice infection model. Western blot and immunolabeled electron microscopy assay showed NP was displayed on baculovirus surface. ELISA results showed NP could induce high level of anti-NP IgG in the sera from NP-Bac-inoculated mice. Two cellular immune peptides (NP57-74 IQNSITIERMVLSAFDER and NP441-458 RTEIIKMMESARPEDLSF) were identified by IFN-gamma ELISPOT assay. NP57-66 and NP441-450 and NP protein could be able to trigger the activation of CD4+ and CD8+ T cells, and the response of CD8+ T was more predominant. The challenge study of mice-adapted virus A/PR/8/34 (H1N1) showed that NP-Bac could reduce viral load and attenuate the damage to lung tissue. 50% protection ratio against the virus could be detected.
Animals ; Antibodies, Viral ; immunology ; Baculoviridae ; genetics ; metabolism ; Cross Protection ; Enzyme-Linked Immunospot Assay ; Female ; Humans ; Immunity, Cellular ; Influenza A Virus, H1N1 Subtype ; genetics ; immunology ; Influenza A Virus, H5N1 Subtype ; genetics ; immunology ; Influenza, Human ; immunology ; virology ; Mice ; Mice, Inbred BALB C ; RNA-Binding Proteins ; genetics ; immunology ; T-Lymphocytes ; immunology ; Viral Core Proteins ; genetics ; immunology

BACKGROUNDAndrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers. The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.

METHODSCell proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay, and morphologic structure with transmission electron microscopy. Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2, Bax, and caspase-3 expressions.

RESULTSAndrographolide showed a time- and concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to controls, the number of cells in the G0-G1-phase increased significantly, S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and both early and late apoptotic rates increased significantly compared to the controls, all in a concentration-dependent manner. Bax and caspase-3 expressions were markedly increased, and Bcl-2 expression was decreased.

CONCLUSIONSAndrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression. Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.

Apoptosis ; drug effects ; Caspase 3 ; analysis ; genetics ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Stomach Neoplasms ; drug therapy ; pathology ; bcl-2-Associated X Protein ; analysis ; genetics

OBJECTIVECystic fibrosis (CF) is rare in Chinese mainland. We present two cases of CF patients diagnosed by gene analysis. Their clinical manifestations and genetic mutation features are analyzed in this article. It will be of special interest to pediatricians in recognition of CF.

METHODThe clinical material of two CF patients who were diagnosed by gene analysis was retrospectively analyzed.

RESULTThe first patient is a 13-year-old girl. She had a complaint of recurrent fever and cough for 6 months, expectoration for 2 months and hemoptysis for 20 days. After 3 months of her birth, she was operated on for bullae of lung. She was susceptible to upper respiratory tract infection. There was no family history of recurrent wheeze and other special diseases. Aspergillus fumigatus specific IgE was at grade 3 and aspergillus fumigatus IgG was high. Pseudomonas aeruginosa was positive in sputum culture. Sweat testing was performed and Na+ was higher. Pulmonary CT indicated bronchiectasis. Nasal sinus CT showed optical density of soft tissue within maxillary sinus and chronic bilateral sinusitis. The electron microscopy of cilia suggested immobile cilia syndrome. A heterozygotic mutation (263T > G, 2909G > A) was found after CFTR genetic mutation analysis. Both her parents were carriers. She was treated with inhalation of nebulized hypertonic saline and postural drainage for a long time. And she got better during a follow up period of 1 year. The second patient was a 10-year-old girl who complained of recurrent expectoration for 3 years and shortness of breath for half a year. She had a history of sinusitis and steatorrhea. The family history was normal. Both the lipase and insulin level in blood serum was lower.Pseudomonas aerugino and Aspergillus fumigatus were both positive in sputum culture. Aspergillus fumigatus IgE was normal. Pulmonary CT indicated bronchiolitis and bronchiectasis. Nasal sinus CT showed bilateral maxillary sinusitis. CFTR genetic mutation analysis revealed a homozygous mutation (3196C > T). Her parents and relatives did not participate in this study. Unfortunately, this child died of respiratory failure 3 months after discharge.

CONCLUSIONCFTR gene mutation was a main cause of CF. Common symptoms are those of bronchiectasis, pancreatitis and sinusitis. The two Chinese patients were diagnosed by gene analysis. One had a heterozygous mutation (263T > G, 2909G > A) and the other had a homozygous mutation (3196C > T), not ΔF508 which is common in western countries.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Bronchiectasis ; etiology ; genetics ; Child ; Cystic Fibrosis ; complications ; diagnosis ; genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; genetics ; DNA Mutational Analysis ; Female ; Heterozygote ; Homozygote ; Humans ; Mutation ; Retrospective Studies ; Sinusitis ; etiology ; genetics

ObjectiveTo investigate the effect of drinking brick tea with low-fluoride level on prevention of tea type fluorosis.MethodsHandahangacha,Hadayinggegacha,Dalainuoyi town,in Keshiketengqi Inner Mongolia endemic fluorosis area were selected as test points,and brick tea with fluoride [(204.5 ± 10.2),(308.2 ±15.4)mg/kg] was given for 12 months.Dental fluorosis,clinical skeletal fluorosis,and X-ray diagnosis of skeletalfluorosis [according to “Endemic Skeletal Fluorosis Diagnostic Criteria” (WS 192-2008)] of adults 20 to 70 years of age were examined and level of fluoride before and after the prevention trial,in brick tea,drinking water,milk tea and urine were tested (fluoride ion selective electrode method),and fluoride intake through tea was calculated.ResultsDetection rate of adult dental fluorosis in Handahangacha was 68.89％ (62/90),clinical detection of skeletal fluorosis was 55.32％ (52/94),and X-ray detection of skeletal fluorosis was 65.17％ (58/89); adult dental fluorosis detection rate in Hadayinggegacha was 54.84％(51/93),clinical detection of skeletal fluorosis was 65.69％(67/102),and X-ray detection rate of skeletal fluorosis was 61.36％ (54/88).Brick tea fluoride was (831.4 ±138.9),(864.3 ± 134.6)mg/kg before the prevention trial in Handahangacha and Hadayinggegacha,respectively,drinking water fluoride content was (0.27 ± 0.05),(0.54 ± 0.24)mg/L,fluoride content of milk tea was (216 ± 1.12),(2.82 ± 1.38)mg/L,adult urine fluoride content was (2.78 ± 1.57),(2.96 ± 1.80)mg/L,and fluoride intake through milk tea was (8.12 ± 5.84),(6.42 ± 5.04)mg/d,respectively; after the prevention trial the fluoride content of brick tea was (204.5 ± 10.2),(308.2 ± 15.4)mg/kg,fluoride content of drinking water (0.34 ± 0.11),(0.62 ± 0.30)mg/L,fluoride content of milk tea(0.97 ± 0.33),(1.83 ± 0.66)mg/L,fluoride content in urine(1.29 ± 0.55),( 1.47 ±0.62)mg/L,fluoride intake through milk tea (3.45 ± 2.05),(3.71 ± 2.07)mg/d,respectively; in Handahan and Hadayinggegacha after the prevention trial the fluoride in brick tea,milk tea,urine fluoride,and fluoride intake through milk tea was significantly lower than that before the trial (t =14.30,12.97 ;6.46,3.95;6.69,5.72;6.27,3.57,all P ＜ 0.01 ).Fluoride intake in Handahangacha through milk tea was within the state heath standard limits( ＜ 3.5mg/d).ConclusionDrinking low-fluoride brick tea can prevent drinking brick tea type fluorosis,the preventive effect is especially more reliable with low fluoride brick tea (204.5 ± 10.2)mg/kg.