Objective To evaluate the short- and long-term efficacy of microwave hyperthermia combined with chemoradiotherapy in treating metastatic nasopharyngeal carcinoma to the cervical lymph nodes. Methods A total of 154 cases of stage N2-N3 nasopharyngeal carcinoma (1992 stage system) were randomized into two groups: group A (76 cases, treated with microwave hyperthermia combined with chemoradiotherapy) and group B (78 ca-ses, treated with chemoradiotherapy alone). Both groups received 1 to 2 cycles of chemotherappy with cisplatin and 5-fluorouracil and then received regular radiotherapy. The total doses of radiotherapy were 70-78 Gy/35-39 f, 47-51 d for the primary loci of nasopharynx and 68-72 Gy/34-36 f,46-50 d for the metastatic loci in the neck. Group A received microwave hyperthermia on the metastatic cervical node at the beginning of radiotherapy, with the micro-wave hyperthermia administered for 45 min every time,two times a week, totaling 8 to 14 times. Results The complete extinction rates of neck metastatic carcinoma were 80.3% and 61.5% , respectively, in groups A and B (P<0.05). The overall response rates of neck metastasis in the two groups were 100% and 96.2% , respective-ly. When the cervical lymph node metastasis disappeared, the radiotherapy doses in group A and B were (45.8 ± 5.46 ) Gy and (58.8±5.03 ) Gy, respectively (P<0.01). The 5-year local control rates of cervical lymph node in group A and B were 97.4% and 76.9%(P<0.05 ), respectively. The one-, three- and five- year survival rates were 97.4% , 76.3% and 59.2% respectively, in group A, versus 93.6% (P>0.05) ; and 52.6% (P< 0.01) and 41.0% (P<0.05), respectively, in group B. Conclusions Microwave hyperthermia combined with chemoradiotherapy can elevate the complete extinction rate of cervical lymph node metastasis of nasopharyngeal carcinoma and reduce the radiotherapy dose needed of effective control. The 5-year local control rate of cervical lymph node metastasis in combined therapy group is superior to that in the chemoradiotherapy alone group,and can elevate the long-term survival rate of patients.

Objective:To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by syntaxin-binding protein 1 (STXBP1) gene mutation.Methods:The clinical data, gene variation and treatment outcome of 15 children with STXBP1 encephalopathy admitted to Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2014 to June 2019 were analyzed retrospectively.Results:Among 15 patients, 11 were male and 4 were female, age ranged from 2 months to 69 months. The clinical manifestations of 14 children were epilepsy and developmental delay (DD) and the remaining one showed developmental delay without seizure. The onset age of epilepsy ranged from two days to 19 months and 11 of them experienced the first attack before 1 year of age. The common seizure types were epileptic spasms and tonic seizures. Seven patients were diagnosed with Ohtahara syndrome or West syndrome. Epileptic form discharges were observed in the interictal electroencephalograms (EEG) of 11 patients, including multifocal discharges, suppression-burst and hypsarrhythmia. The brain magnetic resonance imaging of 7 children were abnormal, including myelin dysplasia, less white matter, lack of corpus callosum or hypoplasia. The follow-up time ranged from 2 months to 57 months, after the last follow-up, 3 cases were seizure free, 6 children showed partial response and the other 5 patients had no response on multitherapy. Six of 8 patients showed good responses to levetiracetam (LEV) monotherapy or in combination with other antiepileptic drugs (AEDs). Vigabatrin (VGB) was applied to 5 patients with epileptic spasms and 4 of them showed response. All patients showed different degrees of developmental delay while four of them showed autistic features. STXBP1 gene mutations were identified in all cases and there were 15 types of gene variations, including 8 missense mutations, 1 nonsense mutation, 5 frame shift mutations and 1 complex mutation. Five novel mutations were unreported before, including c.1193A>G, c.172delG, c.1769C>T, c.1038_1039delCC, c.348_351dupTGAA.Conclusions:Development delay and epilepsy are the major and independent clinical phenotypes in children with STXBP1 encephalopathy. The variation of STXBP1 gene is mainly de novo. Levetiracetam and vigabatrin may be more effective in epilepsy control than other AEDs.

Objective To investigate the clinical application of three-dimensional intracavitary/free-hand interstitial brachytherapy technique in radical radiotherapy for cervical cancer. Methods A retrospective study was conducted on the clinical data of patients with cervical cancer who underwent radical radiotherapy using CT-guided three-dimensional intracavitary/free-hand interstitial brachytherapy technique in The Affiliated Cancer Hospital of Nanjing Medical University from April 2019 to September 2021. The short-term efficacy and adverse reactions were analyzed, and the independent predictors affecting short-term efficacy were evaluated by logistic risk regression model. Results A total of 182 patients were included, and all patients successfully completed the treatment. Clinical efficacy assessment performed 3 months after treatment revealed an overall response rate of 90.65%; the incidence of grade 3 and 4 adverse reactions in the lower gastrointestinal tract was 4.4% during treatment. After reclassifying stage IIIC patients according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system and including factors affecting the stage, it was found that the tumor volume before brachytherapy was the main factor affecting the clinical efficacy of patients at this stage (P = 0.004). Conclusion As a key method in radical radiotherapy for cervical cancer, three-dimensional intracavitary/free-hand interstitial brachytherapy technique is safe and effective and can be quickly popularized in primary hospitals beyond regional cancer centers for cervical cancer brachytherapy.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*