[Primary laryngeal Non-Hodgkin' s lymphoma: a case report].

Non-Hodgkin' s lymphoma is a kind of disease which might manifest in varied form. Unlike squamous cell carcinoma, the majority of laryngeal tumors, non-Hodgkin' s lymphoma in larynx is extremely rare. Here we present a primary laryngeal non-Hodgkin' s lymphoma, a 66-year-old female, with a history of recurrent sore throat and hoarseness for over 1 year. Laryngoscope and computed tomography result were presented, and surgical resection was performed under the suspension laryngoscope using CO2 laser. According to the pathological immunohistochemistry result, the final diagnosis was laryngeal non-Hodgkin' s lymphoma. Postoperative adjuvant chemotherapy was applied. There was no recurrence.

[Crouzon syndrome coupled with OSAHS and congenital heart disease: a case report].

A case of Crouzon syndrome coupled with OSAHS and congenital heart disease in our hospital was reported. The patient who was a 2 years and 7 months old boy, was admitted in our hospital for repetitive sore throat, snoring with mouth breathing during sleep for more than 2 years and been found with some typical defect of Crouzon syndrome during physical examination. Half a year ago the boy underwent ventricular septal defect closure surgery. PSG shows severe apnea hypopnea and low ventilation existed. Under general anesthesia, the patient accepted bilateral tonsillectomy and adenoidectomy but dyspnea occurred after post-operative extubation till 2 days later the boy can breathe by himself. The follow-up at 6 months and 1 year revealed that the patient did not have snoring or mouth breathing during sleep. For this kind of case, we should assess detailed pre-operation and observe carefully post-operation so as to reduce the perioperative period risks.

[Incidence of postoperative venous thromboembolism after thoracic surgery and its characteristic: a single center, prospective cohort study].

Objective: To evaluate the incidence of postoperative venous thromboembolism (VTE) after thoracic surgery and its characteristic. Methods: This was a single-center, prospective cohort study. Patients undergoing major thoracic surgeries between July 2016 and March 2017 at Department of Thoracic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University were enrolled in this study. Besides the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower-extremity ultrasonography after surgery. CT pulmonary angiography (CTPA) was carried out if patients had one of the following conditions including typical symptoms of PE, high Caprini score (>9 points) or new diagnosed postoperative DVT. Caprini risk assessment model was used to detect high risk patients. No patients received any prophylaxis of VTE before surgery. Further data was analyzed for identifying the incidence of postoperative VTE. The t-test, χ2 test or Wilcoxon rank-sum test was used to analyze the quantitative data and classification data, respectively. Results: Totally 345 patients who undergoing major thoracic surgery were enrolled in this study including 145 benign diseases and 200 malignant diseases.There were 207 male and 138 female, aging from 15 to 85 years. Surgery procedures included 285 lung surgeries, 27 esophagectomies, 22 mediastinal surgeries and 11 other procedures. The overall incidence of VTE was 13.9% (48 of 345) after major thoracic surgery including 39 patients with newly diagnosed DVT (81.2%), 1 patient with PE (2.1%) and 8 patients with DVT+ PE (16.7%). The median time of VTE detected was 4.5 days postoperative. There were 89.6% (43/48) VTE cases diagnosed in 1 week. The incidence of VTE was 9.0% in patients with benign diseases, while 17.5% in malignant diseases (χ2=5.112, P<0.05). The incidence of VTE in patients with pulmonary diseases was 12.6%, among that, in patients with lung cancer and benign lung diseases was 16.4% and 7.5 % (χ2=4.946, P<0.05), respectively. Regarding to Caprini risk assessment model, the incidence of VTE in low risk patients, moderate risk patients (Caprini score 5 to 8 points)and high risk patients(≥9 points)were 0(0/77), 15.2%(33/217) and 29.4%(15/51), respectively(Z=-12.166, P<0.05). In patients with lung cancer, 98.2% of patients were moderate risk or high risk; only 3 cases scored low risk. The incidence of VTE in moderate risk and high risk patients was 13.4%(18/134) and 32.1%(9/28), respectively, while it was 0(0/3) in low risk patients. Conclusions: The overall incidence of VTE after major thoracic surgeries is 13.9%, and the incidence of VTE after lung cancer surgeries was 16.4%. Most of the VTE cases occurr within one week after the surgery. Caprini risk assessment model can identify high risk patients effectively.

[The early changes of respiratory system resistance and γδT lymphocytes infiltrated in graft after lung transplantation of mouse].

Objectives: To generate an orthotopic left lung transplantation model in mice, and to observe the early changes of respiratory system resistance and γδT lymphocytes infiltrated in grafts. Methods: The research time was from March 2014 to May 2015. The male C57BL/6 mice (n=35) and BALB/c mice (syngenic group, n=10) were randomly divided into five groups. Control group (n=5): wild C57BL/6 mice; syngenic transplant group (n=10): C57BL/6→C57BL/6; allogenic transplant group(allogenic group, n=10): BALB/c→C57BL/6; each transplant group was randomly divided into 3-day and 7-day subgroups (n=5). Respiratory system resistance and histological features of grafts were assessed, and differences in graft infiltrating γδT lymphocytes and mRNA expression of interleukin (IL)-17A were quantified on 3 and 7 days after transplantation. Multiple comparisons were performed using one-way analysis of variance and least significant difference analysis. Results: (1) The respiratory system resistance of syngenic group and allogenic group were (2.61±0.59) cmH2O·s/ml and (2.84±0.31) cmH2O·s/ml 3 days post-operation, both of them increased compared to control group (1.39±0.17) cmH2O·s/ml (1 cmH2O=0.098 kPa) (P=0.001, 0.000). The respiratory system resistance of allogenic group were (4.33±0.67) cmH2O·s/ml 7 days post-operation, which was significantly higher than that of syngenic 7-day subgroup (1.87±0.27) cmH2O·s/ml and control group (1.39±0.17) cmH2O·s/ml (P=0.000, 0.000). (2) The isografts of syngenic group showed a relatively normal histological appearance with minimal infiltration of inflammatory cells, and the allografts of allogenic group infiltrated apparently by inflammatory cells, especially 7-day subgroup showed acute cellular rejection. (3) The percentage of γδT lymphocytes infiltrated in isografts and allografts were 3.90%±0.86% and 4.40%±0.57%, respectively, which were significantly increased compared to that of control lungs 2.00%±0.23% 3 days post-operation(P=0.000, 0.000); The percentage of γδT lymphocytes infiltrated in 7 days allografts was 5.40%±0.98% , which was higher compared to that of 7 days isografts 2.60%±0.54% and control lungs 2.00%±0.23% (P=0.000, 0.000). (4) IL-17A mRNA expression levels were 3.37±0.55 and 5.23±1.50 in isografts and 6.77±0.93 and 27.32±4.20 in allografts, on postoperative day 3 and 7 respectively. All of them were significantly upregulated compared to that of control lungs 0.99±0.08 (P=0.000, 0.000), and allografts exhibited significantly greater IL-17A transcript levels compared to isografts on postoperative day 3 and 7 (P=0.000, 0.000). Conclusion: The rise of respiratory system resistance of lung grafts after transplantation may relate to the increased IL-17A-producing γδT lymphocytes infiltrated in the grafts.

[Modified radical mastoidectomy on"drum sinus" type chronic suppurative otitis media:our experience].

Objective:To our experience of modified radical mastoidectomy on "drum sinus" type chronic suppurative otitis media.Method:We measured the size of tympanic sinus,the extent of meningeal plate lowering and the extent of sigmoid ante-displacement in 54 patients of chronic suppurative otitis media,and determined the criterion of "drum sinus".The patients who comply with the criterion received modified radical mastoidectomy and tympanoplasty via epitympanum approach.The patients were followed up for at least 3 months,The time of dry ear,growth of repaired tympanic membrane,and any complications such as dizziness,facial paralysis,cerebrospinal fluid leakage were recorded.Result:Twenty-nine out of the 54 CSOM patients complied with the criterion of drum sinus.Two cases were lost to follow-up.Therefore,27 cases were included in the study.Three months after the operation,the rate of dry ear was 81.5% Tympanic membrane was successfully repaired in 77.8% of the patients.Three cases had dizziness after operation.No facial paralysis or cerebrospinal fluid leakage was observed.Conclusion:For"drum sinus" type chronic suppurative otitis media,the modified radical mastoidectomy and tympanoplasty via epitympanum approach can be taken.

[Clinical analysis of plasma cell granuloma in nasal cavity and nasal sinus].

The plasma cell granuloma occurred in nasal cavity and sinus, which is rarely seen in clinical practice,the common clinical features included nasal congestion,nose bleeding,eye protrusion and olfactory impairment.Its clinical manifestations are similar to the clinical manifestations of malignant tumors, the correct diagnosis depends on histopathology and immunohistochemistry, and surgical treatment is the main method, can be supplemented by hormone therapy, radiotherapy,the prognosis could be better.

The dynamic expression of allograft inflammatory factor-1 in hepatic tissues and splenic cells of BALB/c mice with Schistosoma japonicum infection.

Allograft inflammatory factor-1 (AIF-1) was originally cloned from a rat heart allograft under chronic rejection. Data from many studies suggested an important role of AIF-1 in several inflammatory processes. The aim of this study was to examine the dynamic expression of AIF-1 and its association with the pathogenesis of hepatic schistosomiasis in BALB/c mice infected with S. japonicum. The expression of AIF-1 and tumour necrosis factor-alpha (TNF-α) was determined by enzyme-linked immunosorbent assay, western blot and immunohistochemistry. AIF-1 and TNF-α were overexpressed in hepatic tissues at the early stage of infection, and then diminished with the length of infection. On culturing splenocytes stimulated by soluble egg antigen for 72 h, the expression of AIF-1 in infected mice was suppressed, but TNF-α increased gradually. Our results showed that AIF-1 was overexpressed in the liver of BALB/c mice infected with S. japonicum, and the interaction between AIF-1 and TNF-α or other cytokines played an important role in the pathogenesis and progression of hepatic schistosomiasis.

Differential diagnosis of pandemic (H1N1) 2009 infection by detection of haemagglutinin with an enzyme-linked immunoassay.

A sensitive and convenient immunoassay that can directly differentiate pandemic (H1N1) 2009 (pH1N1) virus from seasonal influenza virus can play an important role in the clinic. In the presented study, a double-sandwich ELISA (pH1N1 ELISA), based on two monoclonal antibodies against haemagglutinin (HA) of the pH1N1 virus, was developed. After laboratory determination of the sensitivity and specificity characteristics, the performance of this assay was evaluated in a cohort of 904 patients with influenza-like illness. All seven strains of pH1N1 virus tested were positive by pH1N1 ELISA, with an average lower detection limit of 10(3.0 ± 0.4) tissue culture infective dose (TCID)(50) /mL (or 0.009 ± 0.005 HA titre). Cross-reaction of the assay with seasonal influenza virus and other common respiratory pathogens was rare. In pH1N1-infected patients, the sensitivity of the pH1N1 ELISA was 92.3% (84/91, 95% CI 84.8-96.9%), which is significantly higher than that of the BD Directigen EZ Flu A + B test (70.3%, p <0.01). The specificity of pH1N1 ELISA in seasonal influenza A patients was 100.0% (171/171, 95% CI 97.9-100.0%), similar to that in non-influenza A patients (640/642, 99.7%, 95% CI 98.9-100.0%). The positive predictive value for pH1N1 ELISA was 97.7% and the negative predictive value was 99.1% in this study population with a pH1N1 prevalence of 10.1%. In conclusion, detection of HA of pH1N1 virus by immunoassay appears to be a convenient and reliable method for the differential diagnosis of pH1N1 from other respiratory pathogens, including seasonal influenza virus.

Sequence based high resolution chromosomal CGH.

We aimed to directly align a chromosomal CGH (cCGH) pattern with the gene mapping data by taking advantage of the clustering of the GGCC motif at certain positions in the human genome. The alignment of chromosomal with sequence data was achieved by superimposition of (i) the fluorescence intensity of the sequence specific fluorochrome, Chromomycin A3 (CMA3), (ii) the cCGH fluorescence intensity profile of individual chromosomes and (iii) the GGCC density profile extracted from the Ensembl genome sequence database. The superimposition of these three pieces of information allowed us to precisely localize regions of amplification in the neuroblastoma cell line STA-NB-15. Two prominent cCGH peaks were noted, one at 2p24.3, the position 15.4 mega base (Mb), and the other at 2p23.2, 29.51 Mb. FISH and high resolution array CGH (aCGH) experiments disclosed an amplification of MYCN (16 Mb) and ALK (29.2-29.9 Mb), thus confirming the cCGH data. The combined visualization of sequence information and cCGH data drastically improves the resolution of the method to less than 2 Mb.

The MYCN oncogene is a direct target of miR-34a.

Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype. Database searches identified five microRNAs that map to the commonly deleted region of 1p36 and we hypothesized that the loss of one or more of these microRNAs contributes to the malignant phenotype of MYCN-amplified tumors. By bioinformatic analysis, we identified that three out of the five microRNAs target MYCN and of these miR-34a caused the most significant suppression of cell growth through increased apoptosis and decreased DNA synthesis in neuroblastoma cell lines with MYCN amplification. Quantitative RT-PCR showed that neuroblastoma tumors with 1p36 loss expressed lower level of miR-34a than those with normal copies of 1p36. Furthermore, we demonstrated that MYCN is a direct target of miR-34a. Finally, using a series of mRNA expression profiling experiments, we identified other potential direct targets of miR-34a, and pathway analysis demonstrated that miR-34a suppresses cell-cycle genes and induces several neural-related genes. This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma.

Targeting tumor angiogenesis with gene therapy.

A recent target of cancer gene therapy is tumor angiogenesis. An appealing feature of gene therapy targeting the tumor vasculature is that it is readily accessible, particularly when the carrier and its gene are administered systemically. Several gene-based viral and nonviral therapies that target tumor angiogenesis have demonstrated the "proof of principle" of antiangiogenic therapy in preclinical models. The utility of antiangiogenic gene therapy in a clinical setting will depend in large part on developing vectors with minimal toxicity and with increased in vivo transfection efficiency. In this review, we discuss the current status and future directions of antiangiogenic gene therapy.

Branched co-polymers of histidine and lysine are efficient carriers of plasmids.

We previously determined that a linear co-polymer of histidine and lysine (HK) in combination with liposomes enhanced the transfection efficiency of cationic liposomes. In the current study, we designed a series of HK polymers with increased branching and/or histidine/lysine ratio to determine if either variable affects transfection efficiency. In the presence of liposomes, the branched polymer with the highest number of histidines, HHK4b, was the most effective at enhancing gene expression. Furthermore, when serum was added to the medium during transfection, the combination of HHK4b and liposomes as a gene-delivery vehicle increased luciferase expression 400-fold compared to liposomes alone. In contrast to linear HK polymers, the higher branched HHK polymers were effective carriers of plasmids in the absence of liposomes. Without liposomes, the HHK4b carrier enhanced luciferase expression 15-fold in comparison with the lesser branched HHK2b carrier and increased expression by 5-logs in comparison with the HHK or HK carrier. The interplay of several parameters including increased condensation of DNA, buffering of acidic endosomes and differential binding affinities of polymer with DNA have a role in the enhancement of transfection by the HK polymers. In addition to suggesting that branched HK polymers are promising gene-delivery vehicles, this study provides a framework for the development of more efficient peptide-bond-based polymers of histidine and lysine.

Co-polymer of histidine and lysine markedly enhances transfection efficiency of liposomes.

Development of nonviral delivery systems is progressing toward a transfection efficiency sufficient to affect metabolic and neoplastic diseases in humans. Nevertheless, inadequate transfection efficiency of target cells with current nonviral systems still limits the utility of this therapy. In the current study, we have determined that a co-polymer of histidine and lysine (H-K) enhances the transfection efficiency of liposomes, a leading nonviral system. We found that in the absence of serum, the addition of this polymer increased transfection as much as 10-fold in comparison with the liposome:DNA complex alone. More impressively, the co-polymer in the presence of serum increased transfection efficiency up to 100-fold. Furthermore, in vivo expression of luciferase in a tumor increased 15-fold with the addition of H-K polymer to the liposome:plasmid DNA complexes. Without liposomes, the H-K polymer had little to no effect on transfection efficiency. We anticipate that further modifications of this co-polymer will yield molecules with both increased complexity and transfection efficiency.

Antiangiogenic Gene Therapy in Cancer.

One of the most recent and exciting approaches in cancer gene therapy is the ability to target the developing blood supply of the tumor. An appealing feature of antiangiogenic gene therapy is that the tumor vasculature is a readily accessible target, particularly when the carrier and its gene are administered systemically. This is in contrast to several other gene therapy approaches in which the tumor vasculature represents a major obstacle to achieving high levels of transfection of the tumor cells. Several gene-based viral or non-viral therapies that target tumor angiogenesis have shown efficacy in pre-clinical models. Genes that encode antiangiogenic polypeptides such as angiostatin and endostatin have significantly inhibited tumor growth, inducing a microscopic dormant state. The products of these genes are thought to act extracellularly to inhibit angiogenesis. An alternative approach that investigators have used successfully in tumor-bearing mice is to target angiogenic growth factors or their receptors that are essential for tumor growth. Levels of angiogenic factors such as vascular endothelial growth factor (VEGF) have been reduced by either antisense methods or the use of genes encoding truncated angiogenic decoy receptors. Despite these promising findings of tumor reduction with antiangiogenic gene therapy, advances in the viral and/or non-viral delivery systems are essential for this therapy to have clinical utility. In this review, we will discuss the mechanisms of angiogenesis/antiangiogenesis, and the current status and future directions of antiangiogenic gene therapy.

Liposomes complexed to plasmids encoding angiostatin and endostatin inhibit breast cancer in nude mice.

Gene therapy transfer of angiostatin and endostatin represents an alternative method of delivering angiogenic polypeptide inhibitors. We examined whether liposomes complexed to plasmids encoding angiostatin or endostatin inhibited angiogenesis and the growth of MDA-MB-435 tumors implanted in the mammary fat pads of nude mice. We determined that plasmids expressing angiostatin (PCI-Angio) or endostatin (PCI-Endo) effectively reduced angiogenesis using an in vivo Matrigel assay. We then investigated the efficacy of these plasmids in reducing the size of tumors implanted in the mammary fat pad of nude mice. Both PCI-Angio and PCI-Endo significantly reduced tumor size when injected intratumorally (P < 0.05). Compared to the untreated control group, the mice treated with PCI-Angio and PCI-Endo exhibited a reduction in tumor size of 36% and 49%, respectively. In addition, we found that i.v. injections of liposomes complexed to PCI-Endo reduced tumor growth in the nude mice by nearly 40% when compared to either empty vector (PCI) or untreated controls (P < 0.05). These findings provide a basis for the further development of nonviral delivery of antiangiogenic genes.

Systemic gene therapy with p53 inhibits breast cancer: recent advances and therapeutic implications.

Development of gene therapy technologies is approaching clinical realization for the treatment of neoplastic diseases. The use of tumor suppressor genes has been one useful strategy in gene therapy. Modifications and development of vectors as well as increased knowledge of the anti-tumor mechanisms of the p53 will play a significant role in the further advancement of this therapy. Currently, several laboratories have demonstrated that intratumoral injection of a virus carrying the p53 gene decreases tumor size in pre-clinical and clinical studies. Our lab has focused on a tumor-bearing mouse model in which intravenous delivery of liposome: p53 complexes decreases tumor growth. Although a high transfection efficiency of the tumor was thought to be necessary for gene therapy to exhibit anti-tumor activity with tumor suppressor genes, marked inhibition of the tumor occurs even with a low transfection efficiency. p53 may exhibit its bystander anti-tumor effect, at least in part, through an antiangiogenic effect. We believe that understanding the mechanism by which the p53 tumor suppressor gene inhibits tumor growth will lead to improvement in cancer therapy.