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.

Objective: To evaluate the safety of simultaneous administration of quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and older. Methods: From November 2021 to May 2022, eligible participants aged 60 years and older were recruited in Taizhou City, Jiangsu Province, China, and a total of 2 461 participants were ultimately enrolled in this study. Each participant simultaneously received one dose of quadrivalent influenza split virion vaccine and one dose of 23-valent pneumococcal polysaccharide vaccine. The safety was observed within 28 days after vaccination. Safety information was collected through voluntary reporting and regular follow-ups. Results: All 2 461 participants completed the simultaneous administration of both vaccines and the safety follow-ups for 28 days after vaccination. The mean age of the participants was (70.66±6.18) years, with 54.61% (1 344) being male, and all participants were Han Chinese residents. About 22.51% (554) of the participants had underlying medical conditions. The overall incidence of adverse reactions within 0-28 days after simultaneous vaccination was 2.07% (51/2 461), mainly consisting of Grade 1 adverse reactions [1.83% (45/2 461)], with no reports of Grade 4 or higher adverse reactions or vaccine-related serious adverse events. The incidence of local adverse reactions was 0.98% (24/2 461), primarily presenting as pain at the injection site [0.93% (23/2 461)]. The incidence of systemic adverse reactions was 1.42% (35/2 461), with fever [0.85% (21/2 461)] being the main symptom. In the group with underlying medical conditions and the healthy group, their overall incidence of adverse reactions was 2.53% (14/554) and 1.94% (37/1 907), respectively. The incidence of local adverse reactions in the two groups was 1.62% (9/554) and 0.79% (15/1 907), respectively, and the incidence of systemic adverse reactions was 1.44% (8/554) and 1.42% (27/1 907), respectively, with no statistically significant differences between them (all P>0.05). Conclusion: It is safe for adults aged 60 years and older to receive quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine at the same time.

Objective: To evaluate the safety of simultaneous administration of quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and older. Methods: From November 2021 to May 2022, eligible participants aged 60 years and older were recruited in Taizhou City, Jiangsu Province, China, and a total of 2 461 participants were ultimately enrolled in this study. Each participant simultaneously received one dose of quadrivalent influenza split virion vaccine and one dose of 23-valent pneumococcal polysaccharide vaccine. The safety was observed within 28 days after vaccination. Safety information was collected through voluntary reporting and regular follow-ups. Results: All 2 461 participants completed the simultaneous administration of both vaccines and the safety follow-ups for 28 days after vaccination. The mean age of the participants was (70.66±6.18) years, with 54.61% (1 344) being male, and all participants were Han Chinese residents. About 22.51% (554) of the participants had underlying medical conditions. The overall incidence of adverse reactions within 0-28 days after simultaneous vaccination was 2.07% (51/2 461), mainly consisting of Grade 1 adverse reactions [1.83% (45/2 461)], with no reports of Grade 4 or higher adverse reactions or vaccine-related serious adverse events. The incidence of local adverse reactions was 0.98% (24/2 461), primarily presenting as pain at the injection site [0.93% (23/2 461)]. The incidence of systemic adverse reactions was 1.42% (35/2 461), with fever [0.85% (21/2 461)] being the main symptom. In the group with underlying medical conditions and the healthy group, their overall incidence of adverse reactions was 2.53% (14/554) and 1.94% (37/1 907), respectively. The incidence of local adverse reactions in the two groups was 1.62% (9/554) and 0.79% (15/1 907), respectively, and the incidence of systemic adverse reactions was 1.44% (8/554) and 1.42% (27/1 907), respectively, with no statistically significant differences between them (all P>0.05). Conclusion: It is safe for adults aged 60 years and older to receive quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine at the same time.

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

Objective:To discuss the effect of Sishenwan on phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） signaling pathway related genes and proteins in colon tissue and interleukin-1β（IL-1β） and interleukin-10（IL-10） expression levels in serum of ulcerative colitis （UC） model rats with spleen kidney Yang deficiency. Method:The 120 SPF Wistar rats were randomly divided into normal group and model group after 7 days of adaptive feeding in SPF laboratory. The model group were given dinitrobenzene sulfonate （DNBS）/ethanol solution enema+hydrocortisone subcutaneously injection+senna leaf gavage to establish UC model of spleen kidney yang deficiency. The rats who successfully established the model were randomly divided into five groups：model group， mesalazine （0.36 g·kg^-1） group， and Sishenwan high， medium and low dose （3.2，1.6，0.8 g·kg^-1） groups， the volume of which was 10 mL·kg^-1. The model group and the blank group were given distilled water of the same volume. Once a day for 21 days. Observe the general conditions of the rats daily， and record the weight， fecal traits and occult blood of the mice for disease activity index （DAI） scoring.Take the rat colon tissue to observe the gross morphology and colon injury， and score the colon mucosal injury index （CMDI）. Hematoxylin-eosin （HE） staining was used to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）was used to detect the expression level of PI3K， Akt， mTOR mRNA in colon tissue. The levels of IL-1β and IL-10 in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression level of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， mTOR， p-mTOR protein in colon tissue. Result:Compared with blank group， the general survival status of the rats in model group was relatively poor， the DAI score and the CMDI index were significantly increased （P<0.01）. The intestinal mucosa partially disappears， the glands disappear， and a large number of inflammatory cells infiltrate and gather in the mucosal layer and the base layer in the pathological sections of the model group. The expression levels of PI3K， Akt， and mTOR mRNA were significantly increased （P<0.01）. The IL-1β content was significantly increased and the IL-10 content was significantly decreased （P<0.01）. The expression levels of p-PI3K，p-Akt and p-mTOR protein were significantly increased （P<0.01）. Compared with the model group， the DAI scores of Sishenwan high and medium dose groups and mesalazine group decreased （P<0.05）. The CMDI index of mesalazine group and the high， middle and low dose groups of Sishenwan was significantly reduced （P<0.01）. Pathological sections of rats showed that the inflammatory cells in the drug group decreased， and the mucosal layer structure returned to normal to varying degrees. The mesalazine group and the Sishenwan medium-dose group had the best effects， and the mucosal structure was close to the blank control group. The expression levels of PI3K， Akt， mTOR mRNA in the high and medium dose groups of Sishenwan， mesalazine group and Akt mRNA in low dose group of Sishenwan were significantly reduced （P<0.05，P<0.01）. The expression levels of PI3K and mTOR mRNA in low-dose group of Sishenwan decreased， but the difference was not statistically significant. The IL-1β content was significantly reduced and the IL-10 content was significantly increased in high， medium dose groups of Sishenwan and mesalazine groups （P<0.05，P<0.01）. The level of IL-1β decreased and the level of IL-10 increased in the low-dose group of Sishenwan， but the difference was not statistically significant. The expression levels of p-PI3K， p-Akt and p-mTOR protein in the high， medium， and low dose groups of Sishenwan and mesalazine group decreased to varying degrees， and the differences were statistically significant（P<0.05，P<0.01）. Conclusion:Sishenwan has the effect of improving the general condition and intestinal mucosal damage of ulcerative colitis model rats with spleen and kidney Yang deficiency. The mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway.

Objective To analyze the spatial epidemiological characteristics of measles in Taizhou from 2009 to 2017, so as to provide theoretical basis for measles prevention and control. Methods The spatial autocorrelation analysis and trend surface analysis of measles epidemics data from 2009 to 2017 in Taizhou were performed using ArcGIS 10.0 software. The dynamic characteristics of measles epidemics in Taizhou were analyzed. Results Among 2009-2017 years, the incidences of measles in Taizhou ranged from 0.83/1 million to 65.43/1 million. The results of global autocorrelation analysis showed that there were spatial correlations of the incidence of measles among 2012, 2013, 2015, and 2016 in Taizhou with a high-value clustering distribution. Local autocorrelation analysis indicated that the hot spots of measles incidence in Taizhou from 2009 to 2017 were mainly concentrated in the central towns of Taizhou. Trend surface analysis suggested that the measles incidence in the south towns of Taizhou was higher than that in the north in 2010, and the incidence in the central region was higher than those in other regions in 2013 and 2015. Conclusions According to the spatial analysis, autocorrelation was observed for the spatial distribution of measles incidence in Taizhou from 2009 to 2017, and there are hot spots in the central township. Targeted preventive measures should be taken based on these characteristics.

OBJECTIVETo estimate the size of female sex workers and clients in Taizhou city.

METHODSA household survey using network scale-up method (NSUM) was conducted among the 3000 community residents in Taizhou city from August to October in 2011, which aimed to estimate the social network size (c value) of Taizhou residents, and the c value was adjusted by demographic characteristics, back estimation and outlier elimination. Using the adjusted c value, the number of acquaintance of female sex workers or clients and the respect level toward female sex workers or clients were used to estimate the size of female sex workers and clients.

RESULTSA total of 2783 valid questionnaires were collected, among which 1380 (49.6%) were collected from Taixing city, 1403 (50.4%) were collected from Jingjiang city. 1334 respondents were male (47.9%) and 1449 (47.9%) respondents were female. The mean age was (39.4 ± 10.7) years. The average personal social network size using original data for Taizhou residents was 525, which differed from place, sex, age, educational level and marriage status. Using the remaining known populations through back estimation, the social network size was 419 and became 424 after the elimination of outliers. The estimated population size for female sex worker was 6370 (95%CI: 5886 - 6853), which accounted for 0.52% (6370/1 229 980) of the total number of female aged from 15 to 49. The estimated population size for clients was 15 202 (95%CI: 14 560 - 15 847), which accounted for 1.28% (15 202/1 190 340) of the total number of males aged from 15 to 49 and the ration of clients to female sex worker was 2.39:1.

CONCLUSIONNSUM is an easy and quick way to estimate the size of female sex workers or clients, but the estimated sizes are subject to bias and error due to estimate effect and sample representativeness.

Adolescent ; Adult ; China ; Female ; Humans ; Male ; Middle Aged ; Sex Work ; statistics & numerical data ; Sex Workers ; statistics & numerical data ; Surveys and Questionnaires ; 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

Objective To evaluate the efficacy of 131I treatment for bone metastases from DTC and analyze the survival rates after 131I treatment and prognostic factors. Methods One hundred and six DTC patients with bone metastases treated by 131I during January 1991 and January 2009 were retrospectively analyzed. Treatment efficacy was assessed based on serum Tg change, bone pain palliation and changes on medical imaging. Univariate analysis was performed for defining the factors affecting 131I treatment efficacy. Survival curves were estimated using the life table method. Survival analysis was performed using Kaplan-Meier method. Results Serum Tg decreased dramatically in 37/106 (34.9%) patients treated with131I. Thirty-nine of 61 patients (63.9%) with bone pain had pain relief. Age, tumor subtype and presence of non-osseous distant metastases were significant factors affecting 131I treatment efficacy based on serum Tg change (χ2=6.443, 11.455, 6.756, all P<0.05), but had no significant effects on bone pain palliation (χ2=0, 0, 0.060, all P>0.05). There were no imaging changes of bone metastases in 77.4% of patients after 131I treatment. The overall 5-year and 10-year survival rates from initial diagnosis of bone metastases was 86.47% and 57.90%, respectively. Univariate analysis showed that number of metastases, presence of non-osseous distant metastases and pre-131I treatment surgery were significant factors for survival (Log-rank values were 4.05, 5.98, 4.22, all P<0.05). Conclusions 131I treatment for bone metastases from DTC is effective for lowering serum Tg and palliation of bone pain. Single metastasis, absence of non-osseous distant metastases and pre-131I therapy surgery are favorable predictors of prognosis.

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.