Objective To investigate the relationship betw een the serum bilirubin level and the severity of disease and short-term outcome in patient w ith acute ischemic stroke. Methods A total of 120 consecutive inpatients w ith acute ischemic stroke w ere enroled and 105 healthy subjects at the same time w ere used as a control group. The biochemical indicators, such as serum total bilirubin, direct bilirubin, indirect bilirubin, blood lipid, and blood glucose w ere measured w ithin 24 h after admission. The National Institutes of Health Stroke Scale ( NIHSS ) w as used to assess the neurological deficits on the day of admission. The NIHSS score <8 w as defined as mild stroke and ≥8 w as defined as moderate to severe stroke. At discharge or 14 d after onset, the modified Rankin Scale (mRS) w as used to evaluate the clinical outcomes, 0-2 w as defined as good outcome and > 2 w as defined as poor outcome. The levels of serum total bilirubin, direct bilirubin, and indirect bilirubin w ere measured again. Results The levels of serum total bilirubin, direct bilirubin, and indirect bilirubin in the moderate to severe stroke group w ere significantly higher than those in the mild stroke group ( P <0.01) and the control group ( P <0.01). Multivariate logistic regression analysis show ed that the increased levels of serum total bilirubin (odds ratio [OR] 1.855,95%confidence interval [CI] 1.390-2.475; P <0.01), indirect bilirubin ( OR 3.380, 95%CI 1.271-11.901; P <0.05), and direct bilirubin ( OR 3.51, 95%CI 1.062-11.473; P <0.01) had significantly independent correlation w ith baseline disease severity. Univariate analysis show ed that the increased serum total bilirubin level on admission w as associated w ith the short-term poor outcome ( P <0.05), but after adjustment for other confounding factors, there w as no statistical significance ( OR 2.411, 95%CI 0.803-7.243, P >0.05). Conclusions The serum bilirubin level show ed stress increase in patients w ith cerebral infarction in acute phase; and it w as significantly associated w ith the degree of neurological deficit, but it w as not associated w ith short-term outcome. It might be a defense response to the body for stroke events.

OBJECTIVETo study the metastasis-associated molecules differentially expressed in highly and poorly metastatic sublines and the mechanism of metastasis in lung giant cell carcinoma.

METHODSHighly and poorly metastatic sublines (PLA801D and PLA801C)were used as metastasis model. Cell motility and invasion assay in vitro were first compared between the two sublines. Then, gelatin zymography analysis was used to determine the MMP-2 and MMP-9 activity. The protein expression level of secreted MMP-2, MMP-9, TIMP-1, TIMP-2 and intracellular expression level of p53, p16, PCNA, CD44(V6) isomeride, E-cadherin, CK18, nm23-H1 as well as the mRNA expression level of MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF were compared through Western blot. Semi-quantitative RT-PCR analysis was used to determine the intracellular mRNA expression of MMP-2, MMP-9, TIMP-1, TIMP-2 and VEGF.

RESULTSThe in vitro cell invasion potential of highly metastatic subline PLA801D was significantly higher than that of poorly metastatic subline PLA801C by about 4 folds, while the cell motility potential was similar. The secreted MMP-2 activity was notably higher in PLA801D, which was initiated by the higher expression of MMP-2 at protein and mRNA level. In addition, the expression level of p53, PCNA, CK18 protein and VEGF mRNA were significantly higher, while the expression level of p16, E-cadherin and nm23-H1 protein were significantly lower in PLA801D. Some molecules such as MMP-9, TIMP-1, TIMP-2, CD44(V6) isomeride, which had been reported to be associated with tumor metastasis, were not observed to change significantly between the two sublines.

CONCLUSIONThere are significant differences in metastatic potential and phenotypes between highly and poorly metastatic sublines of lung giant cell carcinoma. Some differentially expressed molecules might be playing roles in promoting or inhibiting metastasis of lung giant cell carcinoma, which may be useful to elucidate the mechanism of metastasis.

Carcinoma, Giant Cell ; metabolism ; pathology ; Cell Line, Tumor ; Humans ; Interleukin-8 ; genetics ; Lung Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; RNA, Messenger ; analysis ; Tissue Inhibitor of Metalloproteinase-1 ; analysis ; Vascular Endothelial Growth Factor A ; genetics

OBJECTIVETo study the function of IL-18 in promoting metastasis of lung cancer.

METHODSThe differential expression of IL-18 protein or mRNA level between highly and poorly metastatic sublines of human lung giant cell carcinoma metastatic model was detected by Western blot, semi-quantitative RT-PCR and northern blot analysis. The poorly metastatic PLA801C subline or highly metastatic PLA801D subline was transfected with constructed IL-18 sense or IL-18 antisense expressed plasmid by lipofectamine stable transfection technique. The metastasis-related effect mediated by IL-18, the metastatic phenotype differences, cell motility and cell invasion potential in vitro determined by MICS system and the expression level of metastasis-associated biomarkers detected by Western blot analysis, were compared between IL-18 stably transfectants and mock control, i.e. between PLA801C/IL-18(S) and PLA801C/pcDNA3.1, or between PLA801D/IL-18(As) and PLA801D/pcDNA3.

RESULTSIL-18 was only present in highly metastatic PLA801D subline at either protein or mRNA level, which implied that IL-18 might play a role in promoting metastasis of lung cancer. After IL-18 sense expressed plasmid was transfected into poorly metastatic PLA801C subline, IL-18 fused protein with myc tag detected by Western blot analysis using either IL-18 or myc tag monoclonal antibody. In addition, cell motility ability in vitro was significantly increased about 3 times and E-cadherin protein was significantly down-regulated at about 50% in PLA801C/IL-18(S) transfectants compared with mock control. While IL-18 expressed plasmid was transfected into highly metastatic PLA801D subline, IL-18 protein and mRNA were simultaneously decreased by 30%. In addition, cell invasion ability in vitro was significantly decreased at about 75% and E-cadherin protein was significantly up-regulated in PLA801D/IL-18(As) transfectants compared with mock control.

CONCLUSIONIL-18 might play a role in enhancing tumor metastasis of lung cancer by down-regulating E-cadherin protein expression.

Cadherins ; metabolism ; Carcinoma, Giant Cell ; metabolism ; secondary ; Cell Line, Tumor ; Cell Movement ; DNA, Antisense ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-18 ; biosynthesis ; genetics ; Lung Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; genetics ; Plasmids ; RNA, Messenger ; biosynthesis ; genetics ; Transfection

Objective:To discuss the topical action characteristics of the biological transmission of moxibustion heat via temperature collection and numerical modeling.Methods:Temperature of moxibustion was measured at multiple points at a distance of 3 cm to obtain the moxibustion temperature field nephograms by the high-accuracy temperature measure array.Finite element analysis was used to imitate the three-dimensional dynamic distribution of temperature in acupoint tissues.Results:Through numerical analysis,the one-dimensional,two-dimensional and three-dimensional distributions of temperature in human acupoint tissues at 5 min of moxibustion were established.The result showed that moxibustion heat mainly transmitted from the surface of the tissue to the internal,and the influence of moxibustion heat decreased with the depth of the tissue.The analysis of the nephograms of acupoint tissue temperature at 5,10,15 and 20 min of moxibustion showed that with the increase of the moxibustion time,the temperature in acupoint tissues constantly rose,and the transmission depth of moxibustion heat also further expanded inside acupoint.Conclusion:By establishing the three-dimensional dynamic model of heat transmission inside acupoint tissues with the biological parameters of human tissues and the temperature values obtained,this study used finite element analysis software ANSYS 14.0 and discovered the rules in the transmission of heat in body tissues during moxibustion,and the features in moxibustion heat transmission (from the proximal to the distant) and heat penetration (from the surface to the internal).This study provides theoretical and experimental support for the application of moxibustion in clinical practice.

OBJECTIVETo investigate the antigen clearance time, time to symptom disappearance, and the association between them using immunofluorescence assay for dynamic monitoring of influenza virus antigen in children with influenza.

METHODSA total of 1 063 children suspected of influenza who visited the Hunan People's Hospital from March to April, 2016 were enrolled. The influenza A/B virus antigen detection kit (immunofluorescence assay) was used for influenza virus antigen detection. The children with positive results were given oseltamivir as the antiviral therapy and were asked to re-examine influenza virus antigen at 5, 5-7, and 7 days after onset.

RESULTSOf all children suspected of influenza, 560 (52.68%) had an influenza virus infection. A total of 215 children with influenza virus infection were followed up. The clearance rate of influenza virus antigen was 9.8% (21 cases) within 5 days after onset. The cumulative clearance rate of influenza virus antigen was 32.1% (69 cases) within 5-7 days, and 98.1% (211 cases) within 7-10 days after onset. Among these children, 6 children (2.8%) achieved the improvement in clinical symptoms within 3 days after onset. The cumulative rate of symptom improvement was 84.7% (182 cases) within 3-5 days after onset, and 100% achieved the improvement after 5 days of onset.

CONCLUSIONSThe time to improvement in symptoms after treatment is earlier than antigen clearance time. Almost all of the children achieve influenza virus antigen clearance 7-10 days after onset. Therefore, it is relatively safe for children to go back to school within 7-10 days after onset when symptoms disappear.

Antigens, Viral ; blood ; Child ; Child, Preschool ; Female ; Fluorescent Antibody Technique ; Humans ; Infant ; Influenza A virus ; immunology ; Influenza B virus ; immunology ; Male ; Time Factors

Objective To investigate the pathogen infections of Mongolian gerbils raised in a conventional facility,and to provide a basis for the establishment of local standards for pathogen detection in Mongolian gerbils. Methods A total of 16 species of bacteria,11 species of viruses and 8 species of parasites were detected in 30 gerbils raised in a conventional facility, according to the national standards of microorganism and parasite detection in mice and rats. Results Gerbils raised in this conventional facility were infected with lymphocytic choriomeningitis virus(a positive rate of 6. 7%), sendai virus(3. 3%), pneumonia virus of mice(100. 0%), reovirus type III(6. 7%), mouse encephalomyelitis virus(10. 0%), mycoplasma spp.(6. 7%), Tyzzer's organism(6. 7%)and Helicobacter spp. (56.7%),according to our antibody detection results. Meanwhile,the detected positive rate of Pasteurella pneumotropica was 3.3%,Staphylococcus aureus 10.0%,Escherichia coli O115 a,C,K(B)6.7%,Tritrichomonas muris 100.0% and flagellates 100.0%. Conclusions The results of our study provide a reference for the establishment of classification standards for gerbils according to their pathogen and parasite infections.

Objective To investigate the correlations of serum cystatin C level with severity of stroke and short-term outcome in patients with acute ischemic stroke.Methods Patients with first-ever acute ischemic stroke aged ≥50 years who did not receive thrombolysis and took a visit within 3 d after onset were selected prospectively.The serum cystatin C level was detected within 24 h after admission and various clinical data were collected.The National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological deficits on the day of admission.The NIHSS score ＜8 was defined as mild stroke and ≥8 was defined as moderate to severe stroke.The modified Rankin Scale (mRS) was used to evaluate the short-term outcome at discharge or 14 d after onset,0-2 was defined as good outcome and ＞2 was defined as poor outcome.Results A total of 188 patients were enrolled,including 93 (49.5％) females and 95 (50.5％) males,their mean age was 65.4 ±9.2 years old (range 50-87).There were 120 patients with mild stroke (63.8％),68 with moderate to severe stroke (36.2％);106 patients (56.4％) had good outcome and 82 (43.6％) had poor outcome.Univariate analysis showed that serum cystatin C level in the moderate to severe stroke group was significantly higher than that in the mild stroke group (1.36 ± 0.29 mg/L vs.1.21 ±0.23 mg/L;t =3.902,P ＜ 0.001),the serum cystatin C level in the poor outcome group was significantly higher than that in the good outcome group (1.38 ± 0.25 mg/L vs.1.22 ± 0.25 mg/L;t =4.101,P =0.001).Multivariate logistic regression analysis showed that the serum cystatin C level was an independent risk factor for stroke severity (odds ratio 12.182,95％ confidence interval 11.163-13.202;P ＜ 0.001) and short-term poor outcome (odds ratio 9.025,95 ％ confidence interval 8.202-9.848;P ＜ 0.001).Conclusion The serum cystatin C level is significantly correlated with the severity of stroke and the short-term outcome in patients with acute ischemic stroke.

OBJECTIVETo evaluate the safety of recombinant human interferon alpha-2b for nasal spray for the prevention of SARS and other upper respiratory viral infections.

METHODSField epidemiologic evaluation was conducted, the design was randomized and had a synchronously parallel control group. In the study, the drugs were given for five days and all subjects were followed up for ten days.

RESULTSDuring the period of using interferon, body temperature of the experimental group was normal compared to the control group. Experimental group had more influenza-like symptoms than the control group (P < 0.05), such as headache (4.83%-7.09%), dizziness (7.17%-11.63%), lassitude (8.55%-15.06%), muscular soreness (4.43%-7.09%), pharynx dryness (12.10%-17.85%), angina (6.25%-8.72%), abdominal pain (2.30%-5.50%) and diarrhea (2.45%-5.66%). Most of side effects reached their peak with in the first 3 days. Except for pharynx dryness, the incidences of all other side effects declined after completion of the use of the trial drug, and incidences of some symptoms in experimental group were lower than those of the control group. There were no significant differences in the symptoms of cough and expectoration between the experimental group and the control group. The incidence of exanthem in the control group was significantly higher than that in the experimental group. The side effect of bloody nasal mucus was not observed in experimental group, which had been reported by other authors in several volunteer studies.

CONCLUSIONUsing recombinant human interferon alpha-2b for nasal spray could lead to some influenza-like symptoms, however, all those symptoms were mild , reversible, and relieved after completion of the use of the trial drug. No serious side effects were found during the period of following up. The authors conclude that the drug is safe.

Abdominal Pain ; chemically induced ; Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Dizziness ; chemically induced ; Female ; Follow-Up Studies ; Headache ; chemically induced ; Humans ; Interferon-alpha ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Recombinant Proteins ; SARS Virus ; drug effects ; Severe Acute Respiratory Syndrome ; prevention & control ; virology ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the correlation of contrast-enhanced pattern with expression of hypoxia inducible factor-1α (HIF-1α) and microvessel density (MVD) in mice breast cancer.

METHODSA total of 22 mice were implanted with breast cancer cells (Ca761) subcutanously in the thigh. The tumors were examined with conventional ultrasound and contrast-enhanced ultrasound (CEUS) on days 4,6,7,8,9,10,and 11 after implantation and then sacrificed. Three or four mice were included each time. Expressions of HIF-1α and MVD in cancer tissues were detected immunohistochemically. Correlation of contrast-enhanced patterns with expression of HIF-1α and MVD in breast cancer was analyzed.

RESULTSMice were divided into 3 groups according to the tumor volume:group 1 (volume<0.05 cm(3),n=5),group 2 (volume 0.05-0.75 cm(3),n=9),and group 3 (volume>0.75 cm(3),n=8). The CEUS pattern was different in different groups:four mice in group 1 presented as type 1 (peripheral ring enhancement with no enhancement within the tumor) and 1 case presented as type 2 (peripheral ring enhancement with deep penetration). Most mice in group 2 presented as type 3 (homogeneous or heterogeneous enhancement in the whole tumor,n=5). In group 3,most mice presented as type 4 (peripheral ring enhancement with focal nodular enhancement within the tumor,n=7). Contrast-enhanced pattern was significantly different in different volume groups (P<0.01). Enhanced pattern (type 1-4) was closely correlated with tumor volume (r=0.841,P<0.05). The expression of HIF-1α was negatively correlated with enhanced patterns (type 1-4) (r=-0.596,P＝0.003),but not with tumor volume (P>0.05). There was no significant difference in MVD values between different enhanced patterns (type 1-4),and there was no correlation between the MVD and tumor volumes (P>0.05).

CONCLUSIONCEUS can be used as a noninvasive tool to monitor tumor angiogenesis in tumor and the enhanced patterns may reflect the expression of HIF-1α inside the tumor.

Animals ; Breast Neoplasms ; Cell Line, Tumor ; Contrast Media ; Hypoxia-Inducible Factor 1, alpha Subunit ; Mice

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.