Clinical study of the radiotherapy with EDGE accelerator in the treatment of the moderate and severe thyroid associated ophthalmopathy.

OBJECTIVE: To explore the short-term efficacy, acute complications and response factors after the radiotherapy with EDGE accelerator in patients with moderate and severe thyroid-associated ophthalmopathy (TAO). PATIENTS AND METHODS: A total of 68 patients with moderate and severe TAO who received the radiotherapy with EDGE accelerator between August 1st, 2017 and May 1st, 2011 were enrolled in the present study. The clinical data were collected, and the efficacy and acute complications were followed up, and the response factors were analyzed. RESULTS: Sixty-eight patients (136 eyes) were followed up for 6 months after radiotherapy. The total score after radiotherapy was significantly lower compared to that before the therapy (p<0.05), and the effective rate was 75.74%. After the radiotherapy, the patient's exophthalmia, soft tissue involvement, eye external muscle involvement, corneal involvement, decreased vision and diplopia, tearing and eyelid pain have improved. Acute complications included increased local inflammation, hair loss, pigmentation and xerophthalmias. In addition, multivariate logistic regression analysis demonstrated that thyroid hormone level was the independent factor for the response to the radiotherapy. CONCLUSIONS: For patients with moderate and severe TAO, radiotherapy with EDGE accelerator is a safe and effective treatment option. Maintaining normal thyroid hormone level can improve the effective rate of radiotherapy.

[The morphology and resilience change of upper airway in patients with OSAHS: A MSCT study].

Objective:To analyse the morphology and resilience of upper airway in patients with OSAHS using 128-slice MSCT. Method:CT imaging of the upper airway in 49 patients with OSAHS was acquired in two respiratory status (quiet respiration and Müller maneuver). The two-dimensional measurements of retropalatal and retroglossal regions, airway volume, and airway resilience were measured in patients with severe OSAHS and non-severe OSAHS. And the results were compared between those two groups. Result:① The following measurements during Müller maneuver were smaller than those during quiet respiration: the smallest cross section area of retropalatal and retroglossal region, the anteroposterior diameters(AP) and lateral diameters(L) of retropalatal region, L of retroglossal region, volume and average volume of upper airway and retropalatal area（P<0.01）.②The pharyngeal wall resilience of retropalata region was larger than those of retroglossal region in patients with severe OSAHS. The total resilience of retropalatal was larger than that of retroglossal region in patients with non-severe OSAHS. The pharyngeal wall resilience between severe and non-severe OSAHS had no significant difference. ③ L of retropalatal and retroglossal region, and average area of retropalatal region, were smaller in patients with severe OSAHS than those with non-severe OSAHS during Müller maneuver（P<0.05）.④ The cross-section of upper airway tend to be horizontal oval in retropalatal regions, and vertical oval in retroglossal regions. Conclusion:128-slice MSCT scan can achieve both positioning and quantitative analysis of the morphology and resilience changes of the upper airway in patients with OSAHS.

Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation.

Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction.

Good hydration and cell-biological performances of superparamagnetic calcium phosphate cement with concentration-dependent osteogenesis and angiogenesis induced by ferric iron.

The multifunctionality of calcium phosphate cement (CPC) can be achieved via co-doping with different metallic ions. Magnetism and hyperthermia have been proposed as potential therapeutic methods in bone healing and anti-osteosarcoma treatment. Iron-doping in biomaterials has been confirmed to meet the clinical requirements for these treatments. Herein, superparamagnetic iron-doped CPC (Fe-CPC) showed improved injectability and compressive strength, increased negative surface charge and accelerated hydration with increasing Fe3+ concentration. The superparamagnetism of Fe-CPC was confirmed through vibrating sample magnetometer (VSM) analysis. Mouse bone marrow stromal cells (mBMSCs) cultured on Fe-CPC disks exhibited better attachment morphology and proliferation, and had an enhancement of osteogenic-related gene expression. Moreover, a series of extracts with different concentrations of Fe3+ in cell culture medium were leaching-prepared to simulate the Fe3+-containing liquid environment around the magnetic biomaterials. The performances of mBMSCs and human umbilical vein endothelial cells (HUVECs) cultured in Fe3+-extracts showed increased proliferation rate in a certain amount of Fe3+. Osteogenesis and angiogenesis induced by Fe3+ were observed, but cytotoxicity in mBMSCs appeared when the concentration of Fe3+ was beyond a critical value. Fe-CPC is supposed to have prospective applications in bone remodeling through the combination of self-setting in situ, injectability, superparamagnetism, osteogenesis, angiogenesis, and osteoconductivity.

Specificity redirection by CAR with human VEGFR-1 affinity endows T lymphocytes with tumor-killing ability and anti-angiogenic potency.

Immunotherapy that is based on adoptive transfer of T lymphocytes, which are genetically modified to express chimeric antigen receptors (CARs) that recognize tumor-associated antigens, has been demonstrated to be an efficient cancer therapy. Vascular endothelial growth factor receptor-1 (VEGFR-1), a vital molecule involved in tumor growth and angiogenesis, has not been targeted by CAR-modified T lymphocytes. In this study, we generated CAR-modified T lymphocytes with human VEGFR-1 specificity (V-1 CAR) by electroporation. V-1 CAR-modified T lymphocytes were demonstrated to elicit lytic cytotoxicity to target cells in a VEGFR-1-dependent manner. The adoptive transfer of V-1 CAR T lymphocytes delayed tumor growth and formation and inhibited pulmonary metastasis in xenograft models and such efficacies were enhanced by cotransfer of T lymphocytes that expressed interleukin-15 (IL-15). Moreover, V-1 CAR-modified T lymphocytes lysed primary endothelial cells and impaired tube formation, in vitro. These data demonstrated the antitumor and anti-angiogenesis ability of V-1 CAR-modified T lymphocytes. Our study provides the rationale for the clinical translation of CAR-modified T lymphocytes with VEGFR-1 specificity.

Suppression of ovarian cancer growth via systemic administration with liposome-encapsulated adenovirus-encoding endostatin.

Gene therapy using adenoviral vector containing the endostatin gene is a promising strategy for advanced cancers. However, host immune response to adenovirus and the lack of the requisite coxsackie-adenovirus receptor (CAR) in many primary cells limit the in vivo application. Liposome-complexed adenoviral vectors have proven to be useful for enhancing gene delivery in target cells that lack adenoviral receptors and avoiding a neutralizing antibody response. Here, we investigated antitumor effects of intravenous administration with PEG-PE cationic liposome-encapsulated recombinant human endostatin adenovirus (Ad-hEndo) on CAR-negative ovarian cancer. Electron micrography (EM) showed that these liposomes efficiently encapsulated the vectors, allowing CAR-independent adenovector transduction. The results showed that the complex enhanced transfection efficiency of recombinant adenovirus. Prolonged systemic administration was performed in immunocompetent mice and did not induce significant antibody response. The antitumor effect with PEG-PE cationic liposome encapsulated with Ad-hE (Ad-hE/lipo) was evaluated in the human ovarian cancer model. Systemic administration was well tolerated and resulted in marked suppression of tumor growth in an established ovarian cancer model, which was associated with a decreased number of micro-vessels and increased apoptosis of tumor cells. Our study shows that PEG-PE cationic liposome-encapsulated Ad-hE (Ad-hE/Lipo) can be administrated intravenously and lastingly to inhibit angiogenesis, thus showing promising clinical application.

Management of descending necrotizing mediastinitis.

BACKGROUND: Descending necrotizing mediastinitis (DNM) is uncommon, and may be lethal if not treated adequately and promptly. Delayed diagnosis of the disease is sometimes encountered in clinical practice. METHODS: Eight consecutive patients with acute DNM were identified between 1991 and 1995, including five men and three women. The mean age was 45.8 years (range, 22-71 years). The infectious sources consisted of six esophageal perforations, one cervical cutting injury and one tonsillitis. The clinical presentations were evaluated. Diagnostic procedures including chest radiograph, sonogram and computerized tomography scans of the chest and neck were examined. Diagnosis and treatment, including culture results from drained fluids and debrided tissues, and antibiotic and supportive therapies were reviewed. RESULTS: Six patients who underwent aggressive surgical treatment recovered well. Two patients who received supportive treatment died of sepsis alone. The cultured bacteria included: Klebsiella oxytoca, Staphylococcus aureus, Trichosporum and other mixed oral cavity flora. CONCLUSIONS: Early diagnosis and adequate antibiotic and support therapies are essential to achieve good patient outcomes in acute descending mediastinitis. Adequate drainage and debridement, appropriate antibiotic therapy, and sufficient nutritional and respiratory support are the main treatment elements.