Objective To analyze the efficacy and safety of hypofractionated stereotactic radiotherapy ( FSRT ) combined with temozolomide ( TMZ ) for large brain metastases ( BMs ) in a prospective phaseⅡclinical trial.Methods From 2010 to 2015, a total of 33 patients were enrolled as subjects.The median Karnofsky Performance Status scores before and after treatment were 70 and 80, respectively.The major primary tumor was non-small cell lung cancer (57.6%).The brain metastasis had a diameter of≥3 cm or a volume of ≥6 cm3 .The radiation dose was 52 Gy in 13 fractions or 52.2 Gy in 15 fractions.Patients received TMZ at a dose of 75 mg/m2 per day concurrently.The radiotherapy was followed by 6 cycles of adjuvant treatment with TMZ (150 mg/m2, days 1-5, 28 days per cycle).Patients were reexamined by magnetic resonance imaging ( MRI) during the treatment.The radiation field would be shrunk if the gross target volume ( GTV) was reduced by≥20%.The treatment outcomes were evaluated by MRI at 2-3 months after treatment.Results The total numbers of tumors and GTVs were 95 and 38, respectively. Twenty-four (63%) out of the 38 GTVs had a volume larger than 10 cm3 and the median GTV was 15.3 cm3 (5.7-142.8 cm3).Twenty-two (67%) out of the 33 patients achieved field shrinking during the treatment, and the median reduction rate of GTV was 44%( 21%-88%) .The median total dose was 59.5 Gy, and 100%and 21.2%of patients completed the concurrent and adjuvant treatment with TMZ, respectively.In all patients, the overall response rate was 97.0%;the 1-year local control, intracranial progression-free
survival, and overall survival rates were 97%, 70%, and 62%, respectively;the median survival time was 15.3 months.The main adverse reactions were grade 1-2 nausea and vomiting.One patient got grade 3 liver function impairment.Conclusions FSRT combined with TMZ is a safe and effective approach for treating large BMs.More than 50%of patients can achieve field shrinking to shorten treatment duration and reduce toxicity.Clinical Trial Registry ClinicalTrials.gov,registration number:NCT02654106.

OBJECTIVETo investigate the effect of losartan (an angiotensin II type I receptor antagonist) on endothelial cells exposed to high glucose in vitro and related mechanism.

METHODSVascular endothelial cells of human umbilical vein were cultured in media with high glucose levels. The activities of SOD and CAT, the level of MDA were measured by spectrophotometry in the conditioned media of endothelial cells, the VEGF mRNA expression was performed using semi-quantitative reverse transcription PCR (RT-PCR) in the cell lysates, and the protein expression of VEGF was examined by enzyme-linked immunosorbent assay (ELISA) in the supernatants of cultured cells.

RESULTWhen endothelial cells were cultured in high glucose, the activities of SOD and CAT were significantly decreased, but the level of MDA was markedly increased. However, the high glucose-induced effects were inhibited by losartan. The application of high glucose upregulated the mRNA and protein expression of VEGF in endothelial cells, which was also attenuated by losartan.

CONCLUSIONHigh glucose disrupts the oxidative equilibrium and increases the expression of VEGF in endothelial cells, which can be inhibited by losartan.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Cells, Cultured ; Endothelium, Vascular ; cytology ; metabolism ; Glucose ; pharmacology ; Humans ; Losartan ; pharmacology ; Peroxidase ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Superoxide Dismutase ; metabolism ; Umbilical Veins ; cytology ; Vascular Endothelial Growth Factors ; biosynthesis ; genetics

OBJECTIVETo analyze prognostic factors of and to develop a prognostic model for patients with chronic severe hepatitis (CSH).

METHODSFrom December 1998 to October 2003, 385 in-patients being treated for chronic severe hepatitis were evaluated. The main clinical and laboratory variables were analyzed as predictive factors of survival with Cox univariate and multivariate regression models.

RESULTSThe median survival time of this study group was 47 days. The survival rates at 1, 3, 6 months, 1-year, and 3 years were 66.2%, 32.9%, 26.9%, 22.9% and 17.7% respectively. Four prognostic factors were extracted using Cox's proportional hazard model; the prognostic index (PI) was calculated using the following formula consisting of these factors. PI = 0.016loge + 1.148 hepatic encephalopathy + 0.294loge (bilirubin micromol/L) - 0.826loge (prothrombin time activity). The model accurately predicted 3 months survival in an independent series of 84 patients with chronic severe hepatitis.

CONCLUSIONThe developed model is valuable in prognostic evaluation of chronic severe hepatitis and it may be useful to guide clinicians in selecting treatment methods for CSH.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Chronic Disease ; Female ; Hepatitis, Viral, Human ; diagnosis ; mortality ; Humans ; Male ; Middle Aged ; Models, Biological ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Severity of Illness Index

OBJECTIVEAdenovirus (ADV) is one of the most common causes of acute respiratory infections in infants and children. The objective of this study was to investigate the prevalence of adenovirus infection among pediatric patients with acute respiratory infections in Beijing and the types of the adenoviruses circulating in Beijing on the molecular bases.

METHODClinical specimens including throat swabs from outpatients and nasopharyngeal aspirates from hospitalized patients were collected from patients with acute respiratory infections in a consecutive period of 6 years from Jan 2003 to Dec 2008. Adenoviruses were identified from the collected clinical specimens by tissue culture and/or immunofluorescence assay and typed by nested-PCR based on the sequence of the encoding gene of hexon. Primers were designed for PCR amplification using hexon gene of adenovirus as target. One primer pair was designed as universal primers for amplifying a 1278 bp gene fragment located at the hexon gene of adenovirus types 3, 7, 11 and 21. Four primer pairs with the sequences located within the region of this 1278 bp fragment were designed specifically for amplifying adenoviruses types 3, 7, 11 or 21, respectively, which were used for a multiplex nest-PCR in a single tube. The products from this multiplex nest-PCR were 502 bp (for type 3), 311 bp (for type 7), 880 bp (for type 11) and 237 bp (for type 21), respectively, and the type of the adenovirus tested can be determined after agarose electrophoresis analysis of the PCR products. For those strains which could not be typed by the multiplex nest-PCR, the gene fragment was amplified by a universal primer pair for all adenovirus types from group A to F and the PCR products were sequenced directly.

RESULTOut of 17 941 clinical specimens collected, including 4378 throat swabs from outpatients and 13 563 nasopharyngeal aspirates from hospitalized patients, 304 were adenovirus positive by tissue culture and/or immunofluorescence assay, the overall positive rate was 1.69% (304/179 41). Among these 304 adenovirus positive specimens, 184 were by virus isolation and 184 by immunofluorescence assay, among which 64 were positive by both methods. The types of the adenoviruses were tested for 285 patients including 174 viral isolates and 111 clinical specimens. By using the multiplex nest-PCR, 272 were typable, including 174 (61.1%, 174/285) for ADV3, 92 (32.3%, 92/285) for ADV7, 6 for ADV11 (2.1%, 6/285) and no adenovirus type 21 was detected. Sequence analysis for those 13 nontypable specimens by the multiplex nest-PCR showed that 9 were ADV2 (3.2%, 9/285), 2 were ADV6 (0.7%, 2/285), 1 was ADV1 (0.4%, 1/285) and 1 was ADV5 (0.4%, 1/285). Most of the patients positive for adenovirus were under 5 years of age and 64.4% were from patients with lower respiratory infections, such as bronchiolitis and pneumonia. All the 5 cases of severe pneumonia with pulmonary failure were caused by ADV7 infection.

CONCLUSIONAdenovirus is still an important pathogen for acute respiratory infection in infants and young children and most of the adenoviruses associated with acute respiratory infections in children in Beijing from 2003 to 2008 were ADV3 and ADV7. ADV7 could cause severe lower respiratory infections.

Acute Disease ; Adenoviridae ; classification ; isolation & purification ; Adenoviridae Infections ; epidemiology ; prevention & control ; Adolescent ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Prevalence ; Respiratory Tract Infections ; epidemiology ; prevention & control ; virology

OBJECTIVETo analyze the clinical characteristics of hospitalized pediatric patients infected with 2009 H1N1 influenza.

METHODSTotally 159 children (83 male and 76 female) with influenza A (H1N1) confirmed by the real-time reverse-transcriptase-polymerase-chain-reaction assay were admitted to a special ward of Capital Institute of Pediatrics from November 2009 to January 2010. Clinical manifestations, laboratory and therapy data from the hospitalized children were collected by designed case report form and analyzed.

RESULTSOut of 159 hospitalized patients, 139 (87.4%) were under the age of 5 years and 34.0% of them had at least one underlying medical conditions. Proportions of the severe cases, pneumonia and underlying medical diseases were similar between the 78 infants and 81 older children. All of these 159 cases had influenza-like symptoms at onset and the most common presentations were fever (115 cases, 72.3%) and cough (154 cases, 96.8%). Five severe cases presented dyspnea, cyanosis and hypoxemia. The virus easily invaded into the lower respiratory tract as indicated by that 61% of the cases had findings consistent with pneumonia by X-ray and/or CT and 21.6% had bacterial co-infection. Part of them had mycoplasma pneumonia (20 cases, 27.0%) or other respiratory viruses (5 cases, 3.1%) co-infection simultaneously. The duration of fever was similar between the H1N1 virus sole infection group and the co-infection group (t = 0.975, P > 0.05), but the average course of the disease and hospitalized days of the latter group were longer than the former (t = 3.182 and 3.190, P < 0.01). The proportion of children with pneumonia in the co-infection group was significantly higher than that in the H1N1 sole-infection group (χ(2) = 4.082, P < 0.05).

CONCLUSIONSMost of the H1N1 infected pediatric patients had mild respiratory symptoms, a few of them developed severe manifestations. Dyspnea and hypoxemia were the early signals for the developing severe cases. Rational and experienced treatment with antibiotics was important addition to the antiviral therapy for those co-infected with bacteria.

Child ; Child, Hospitalized ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; diagnosis ; epidemiology ; pathology ; therapy ; Male

OBJECTIVEThe fact that the acute lower respiratory infections (ALRI) are associated with a newly discovered virus, human metapneumovirus (hMPV), has been shown in several studies. The authors conducted this study to understand the etiological and clinical characteristics of bronchiolitis, one of the most common ALRI in infants, caused by hMPV.

METHODSNasopharyngeal aspirate specimens from 54 out of 126 infants with bronchiolitis admitted to the Children's Hospital Affiliated to Capital Institute of Pediatrics, Beijing from November 2002 to February 2003 were examined for hMPV gene fragments by reverse transcription-polymerase chain reaction (RT-PCR). Prior to the detection, the specimens were confirmed as negative for the common respiratory pathogens including RSV, influenza A and B, parainfluenza I, II, III, adenovirus, Mycoplasma pneumoniae by indirect immunofluorescence test, virus isolation and ELISA test. The clinical data of the patients diagnosed etiologically as hMPV infection analyzed included the infants' age, sex, the degree of fever, the severity of wheezing and clinical Lowell score, the findings of chest examination and chest X-ray, the white blood cell count and blood gas analysis, the course of the disease, the major treatments and the outcome of the disease.

RESULTSTwenty-one specimens showed the predicted 213 bp PCR products in agarose gel and the positive rate was 16.7% of all patients (21/126) and 39% of the patients with negative results for common respiratory pathogens detections (21/54). The range of patients' age was 2 - 15 months and the young infants with hMPV bronchiolitis (1 - 6 month of age) accounted for 62% and the male:female ratio was 3.2:1. The patients presented a low-medium grade fever (T < 39 degrees C) accounted for 86%; 81.0% of patients had a white blood cell count lower than 10.0 x 10(9)/L. The radiological findings were patchey opacity in both lungs (68%) and(or) hyperinflation (62%). Assessed by the Lowell score system, 5 out of 21 cases were considered as severe cases. The major clinical findings of hMPV bronchiolitis had no significant difference compared with that of subgroup A hRSV bronchiolitis, and showed longer course of disease than that of subgroup B hRSV bronchiolitis (P < 0.01).

CONCLUSIONSOf the infants with bronchiolitis hospitalized in our hospital from November of 2002 through February of 2003, 16.7% were caused by hMPV infection. These data showed that the major clinical characteristics and the outcome of treatment of hMPV bronchiolitis had no statistically significant difference compared to the cases with either subgroup A or subgroup B hRSV infection.

Bronchiolitis ; therapy ; virology ; China ; Female ; Humans ; Infant ; Male ; Metapneumovirus ; genetics ; Mucus ; virology ; Paramyxoviridae Infections ; therapy ; virology ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction

Adult ; Carcinoma, Neuroendocrine ; Female ; Genetic Testing ; Humans ; Multiple Endocrine Neoplasia Type 2a ; genetics ; Proto-Oncogene Proteins c-ret ; genetics ; Thyroid Neoplasms ; genetics

OBJECTIVETo explore the effects of humanized interleukin 21 (IL-21) on anti-leukemic activity of cytokine induced killer(CIK) cells derived from peripheral blood(PB) and the mechanism.

METHODSMononuclear cells were separated from peripheral blood and cultured with cytokines to induce CIK cells. Proliferation of CIK cells with or without IL-21 stimulation and their cytotoxic activity against K562 cells was measured by MTT method. IL-21 receptor (IL-21R) and immunophenotypes of CIK cells were measured by flow cytometry. The expression of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), tumor necrosis factor-β (TNF-β), perforin, granzyme A, granzyme B, FasL and NKG2D mRNA were measured by semi-quantitative RT-PCR. FasL on the surface of CIK cells and intra-cellular perforin and granzyme B of CIK cells were measured by flow cytometry. The concentration of IFN-γ and TNF-α in the cultured supernatant were measured by enzyme immunoassay. JAK-STAT signalling pathway of CIK cells were measured by Western-blot.

RESULTSAfter IL-21 stimulation, the proportion of CIK cells increased from (17.5 ± 4.7)% to (26.5 ± 2.1)%. Cytotoxic activity against K562 cells by CIK cells increased from (22.8 ± 2.8)% to(44.6 ± 8.3)%. The expression of IL-21R increased about 2 folds. The mRNA expression of IFN-γ increased almost 2 folds from (0.3760 ± 0.2358) to (0.7786 ± 0.2493), TNF-α increased almost 2 folds from (0.6557 ± 0.1598) to (1.3145 ± 0.2136), perforin increased almost 1.5 folds from (0.6361 ± 0.1457) to (0.9831 ± 0.1265), granzyme B increased almost 2 folds from (0.4084 ± 0.1589) to (0.7319 ± 0.1639), FasL increased almost 2 folds from (0.4015 ± 0.2842) to (0.7381 ± 0.2568), the expression of granzyme A, TNF-β and NKG2D were similar with control. Flow cytometry analysis showed that the expression of FasL of CIK cells was higher than that of control (0.19% vs 0.04%), the expression of perforin increased from 35.28% to 53.16%, and the expression of granzyme B increased from 43.16% to 78.82%. The concentration of IFN-γ in the culture supernatant increased almost 2 folds from (25.8 ± 6.1) ng/L to (56.0 ± 2.3) ng/L, and TNF-α increased almost 3 folds from (5.64 ± 0.61) µg/L to (15.14 ± 0.93) µg/L. Western blot showed that the expression of STAT1 and STAT5a had no significant differences, but the expression of STAT3 and STAT5b were higher than that of control.

CONCLUSIONHumanized IL-21 could enhance the anti-leukemic activity of CIK cells via increasing IL-21R, perforin, granzyme B, FasL, IFN-γ and TNF-α, as well as activating JAK-STAT signaling pathway. These data indicate that IL-21 has a potential clinical value in the enhancement of anti-leukemic immunotherapy.

Cells, Cultured ; Cytokine-Induced Killer Cells ; cytology ; drug effects ; Fas Ligand Protein ; metabolism ; Granzymes ; metabolism ; Humans ; Interferon-gamma ; metabolism ; Interleukins ; pharmacology ; K562 Cells ; Perforin ; metabolism ; Receptors, Interleukin-21 ; metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism

Background:We investigated the prognostic value of preoperative fibrinogen levels in hepatocellular carcinoma patients receiving liver transplantation by building a scoring model for predicting tumor recurrence. Methods:Cox regression analysis was used to identify factors that predicted tumor recurrence,and a scoring model was generated by assigning a value of 0 or 1 to each independent risk factor.The cut-off value for fibrinogen was determined by receiver operating characteristic curve analysis. Results:Preoperative fibrinogen concentration was significantly higher in patients with vs.without tu-mor recurrence(3.27 g/L vs.2.34 g/L,P＜0.001),with vs.without macrovascular invasion(3.54 g/L vs.2.82 g/L,P=0.007),and with＞400 vs.≤400 ng/mL plasma alpha-fetoprotein concentration(3.43 g/L vs.2.76 g/L,P=0.007).The 5-year disease-free survival rate was significantly lower for patients with elevated(≥2.68 g/L)vs.normal(＜2.68 g/L)fibrinogen concentration(37.2％vs.78.4％,P=0.001).Mac-rovascular invasion,＞3 tumor nodules,and elevated fibrinogen concentration were independent risk factors for tumor recurrence.A scoring model based on these risk factors predicted recurrence with a sensitivity of 68.3％and a specificity of 87.5％. Conclusions:Elevated preoperative plasma fibrinogen concentration is associated with tumor recurrence in HCC patients after liver transplantation.A new scoring model predicted recurrence with good sensitivity and specificity.

Pulmonary sparganosis mansoni is rare in humans and bronchial sparganosis mansoni has not been reported. We reported a patient with a soft-tissue mass in the right hilum area on a chest computed tomography (CT) scan that was suspected of being lung cancer. Bronchoscopy identified sparganum larvae. Bronchial sparganosis mansoni accompanied by abnormal hyperplasia was diagnosed by histopathology. We introduced our experience and reviewed the clinical characteristics of three pulmonary sparganosis mansoni cases and three pleural cavity sparganosis mansoni cases that have been reported.
Aged ; Bronchi ; pathology ; Bronchial Diseases ; pathology ; Bronchoscopy ; Humans ; Hyperplasia ; Male ; Schistosomiasis mansoni ; pathology ; Sparganosis ; pathology