Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

We aimed to assess the risks of
China ; Cryptosporidiosis/microbiology* ; Cryptosporidium/isolation & purification* ; Giardia/isolation & purification* ; Giardiasis/microbiology* ; Humans ; Risk Assessment ; Water Microbiology ; Water Supply/statistics & numerical data*

AIM:To investigate whether rebamipide repairs the small intestinal epithelial barrier in aspirin-induced small intestinal injury (SII) in mice and its mechanism.METHODS:Small intestinal injury was induced by aspirin (200 mg · kg-1 · d-1 for 5 d) in BALB/c mice.Based on the treatment with aspirin and/or rebamipide (320 mg ·kg-1 · d-1),the mice were divided into 4 groups (n =18 in each group).The living mice in each group (n =6) were sacrificed via cervical dislocation method at day 0,day 5,and day 10.The structure and function of intestinal barrier and the levels of the signaling pathway factors were measured by transmission electron microscopy,immunohistochemistry,qPCR,and Western blot.RESULTS:Tight junctions between intestinal epithelial cells improved significantly after rebamipide treatment.The expression of ZO-1 and occludin in the injured small intestine showed a gradually increasing trend after rebamipide administration (P ＜ 0.05).There was a decreased trend of D-lactate level in rebamipide-treated SII mice (P ＜ 0.05).The expression of cyolooxygenase-2 (COX-2),β-catenin,and c-Myc,and prostaglandin E2 concentration in small intestinal tissues were significantly increased in rebamipide treatment group (P ＜ 0.05).However,down-regulated COX-1 expression in the SII mice was sustained at a low level after rebamipide administration.CONCLUSION:Rebamipide repairs the injury of small intestinal mucosa and improves the structure and function of small intestinal barrier in aspirininduced SII mice by up-regulating the expression of COX-2.

Objective To evaluate the feasibility and effectiveness of secundum atrial septal defect(ASD)occlusion with the septal occluder through right-chest small incision. Methods The clinical data of 140 secundum ASD patients (47 males and 93 females) aged 3-63 years who were treated in our center from August 2004 to July 2014 were retrospectively analyzed. The diameter of ASD was 6 to 36 mm. Under general anesthesia, all patients underwent intraoperative transtsophageal echocardiography (TEE), during which no associated cardiac deformity was found. All patients received ASD occlusion via a small incision (3-4 cm) at the right anterior chest. The occluders were released with the help of TEE. Results The atrial septal defect closure was successfully completed in 134 cases. Six cases received surgical closure of ASD after the failure of occlusion. The reasons of conversion included postoperative dislodgement of occlusion device (n=2, both were central type with large size) and technically unsuitable for occlusion (n=4, in whom residual shunt was found in 2 case, sieve pore type in 1 case, and intraoperative dislodgement in 1 case). All of these 6 patients were treated surgically under cardiopulmonary bypass. No dislocation of the device or atrial shunt was found within 3 to 48 months after the operation. Conclusion Occlusion via small chest incision of ASD under TEE guidance without cardiopulmonary bypass is a safe, minimally invasive, effective, and convenient treatment and worth clinical application.
Adolescent ; Adult ; Anesthesia, General ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Echocardiography ; Female ; Heart Septal Defects, Atrial ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Septal Occluder Device ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the effects of modified vacuum sealing drainage (VSD) technique in treating refractory sinus in the lower leg.

METHODSFrom January 2010 to December 2011, 11 patients with refractory sinus in the lower leg, including 7 males and 4 females, with an average age of 34.5 years (ranged,23 to 56). These patients were treated with modified VSD technique after thorough cleaning sinus and continuous washing. After 14 to 21 days of treatment, removed VSD and re-debrided the sinus and sutured wound.

RESULTSInfections got control after operation, sinus in the lower leg healed. All patients were followed up from 6 to 14 months with an average of 10 months, no recidivations were found.

CONCLUSIONModified VSD technique is an effective method in the treatment of stubborn sinus in the lower leg.

Adult ; Drainage ; methods ; Female ; Fracture Fixation, Internal ; adverse effects ; Humans ; Leg Bones ; injuries ; surgery ; Male ; Middle Aged ; Postoperative Complications ; therapy ; Vacuum

BACKGROUNDThree randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.

METHODSIn the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.

RESULTSOf 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.

CONCLUSIONSWe found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Bevacizumab ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; Bridged-Ring Compounds ; adverse effects ; therapeutic use ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; genetics ; metabolism ; Taxoids ; adverse effects ; therapeutic use ; Young Adult

BACKGROUNDChromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.

METHODSAll 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.

RESULTSThe analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.

CONCLUSIONSChinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

Adult ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology

Objectives To explore the clinical significance of preoperative abdominal multislice spiral CT angiography (MSCTA) in radical resection of gastric cancer. Methods One hundred and three patients with gastric cancer were divided into two groups according to their desires. Group Ⅰ included 57 patients who underwent preoperative MSCTA and group Ⅱ included 46 patients who underwent surgery without preoperative MSCTA. All these patients were operated by the same surgical team. Results Six patients (10.5%) with abnormal gastric artery in group Ⅰ were discovered. The diagnostic concordance rate between MSCTA and intraoperative findings was 100% in group Ⅰ in the locations and alignments of main perigastric vessels and their relationship with cancer lesions.Operative time in group Ⅰ was shorter than that in group Ⅱ [(206±23)min vs. (257±32)min, P=0.044]. Operative time [(190±50) min] of patients with abnormal gastric artery of group Ⅰ was shorter than that [(255±62) min] of patients with abnormal gastric artery discovered during operation of group Ⅱ (P=0.048). However there were no differences in blood loss, extent of lymph node dissection,complication rate, length of hospital stay, and hospitalization cost between the two groups (P＞0.05).Conclusion Preoperative MSCTA is beneficial to the evaluation of vascular structure of the cancer and the adjacent tissues, which may reduce postoperative complications.

Objectives To explore the clinical significance of preoperative abdominal multislice spiral CT angiography (MSCTA) in radical resection of gastric cancer. Methods One hundred and three patients with gastric cancer were divided into two groups according to their desires. Group Ⅰ included 57 patients who underwent preoperative MSCTA and group Ⅱ included 46 patients who underwent surgery without preoperative MSCTA. All these patients were operated by the same surgical team. Results Six patients (10.5%) with abnormal gastric artery in group Ⅰ were discovered. The diagnostic concordance rate between MSCTA and intraoperative findings was 100% in group Ⅰ in the locations and alignments of main perigastric vessels and their relationship with cancer lesions.Operative time in group Ⅰ was shorter than that in group Ⅱ [(206±23)min vs. (257±32)min, P=0.044]. Operative time [(190±50) min] of patients with abnormal gastric artery of group Ⅰ was shorter than that [(255±62) min] of patients with abnormal gastric artery discovered during operation of group Ⅱ (P=0.048). However there were no differences in blood loss, extent of lymph node dissection,complication rate, length of hospital stay, and hospitalization cost between the two groups (P＞0.05).Conclusion Preoperative MSCTA is beneficial to the evaluation of vascular structure of the cancer and the adjacent tissues, which may reduce postoperative complications.

Objective To analyse the prognostic factors and the neck treatment strategy of early tongue squamous cell carcinoma (SCC). Methods Total of 152 cases of early tongue SCC underwent surgery between January 1994 December 2003 were reviewed. The patients, according to their neck managements, were divided into two groups, or wait-whach group (n = 32) and neck dissection group (n =120) ,and the neck dissection group was subdivided into supraomohyoid neck dissection (SND) group and comprehensive neck dissection(CND) group (including radical neck dissection and modified radical neck disssection). Results All patients were followed up over 5 years or until death and the 5-year follow-up rate was 94. 7%. The regional recurrence rates of wait-whach group and neck dissection group were 34. 4% and 14. 2% respectively (χ2 = 6. 865, P < 0. 01) and 5-year overall survival rates of the two groups were 68% and 79% respectively (χ2 = 1. 699, P > 0. 05). There were no significant difference in the regional recurrence rate or 5-year survival rate between SND group and CND group (P > 0. 05). The patients with pathologically node positive had a low 5-year survival rate compared to those with node negative. The patients with regional recurrence had a significant low 5-year survival rate compared to patients without regional recurrence (P<0.01). Conclusions Occult lymph node metastasis and regional recurrence were important prognostic factors for early tongue cancer. Supraomohyoid neck dissection can not improve the 5-year survival rate, but significantly reduce the rate of neck recurrence. The results suggest that the selective neck dissection for ipsilateral level Ⅰ - Ⅲ should be applied to the patients with early tongue carcinoma which does not cross the midline.