Objective:To assess the safety and efficacy of induction chemotherapy with cisplatin and docetaxel followed by radia-tion concurrent with weekly cisplatin for unresectable, locally advanced esophageal cancer. Methods: Thirty-three patients with T3N0M0 to T4N2M0 thoracic esophageal squamous cell carcinoma without celiac lymph node metastasis were included in the study. They were treated with cisplatin (75 mg/m2 d1, d22) and docetaxel (75 mg/m2 d1, d22) neoadjuvant chemotherapy followed by three-dimensional conformal radiotherapy (60Gy/30F/6w) concurrent with cisplatin (30 mg/m2 d1, 8, 15, 22, 29, 36 from the beginning of radiation). Results:Grade 4 hematological toxicities were observed in 13.33%(4/33) of the patients after the neoadjuvant chemother-apy. No grade 3 or above hepatic or renal toxicities were found. During concurrent chemoradiation, the highest grade 3 hematological toxicities were observed in the erythrocyte, granulocyte, and macrophage at 21.21%(7/33), 15.15%(5/33), and 3.01%(1/33), respec-tively. No grade 2 or above hepatic or renal toxicities were observed. Grade 3 radiation esophagitis was observed in 9.1%(3/33) of the patients, whereas grade 3 and above radiation esophagitis or grade 1 and above acute radiation pneumonitis did not occur. The evalua-tion results after treatment completion were 84.85%(28/33), 12.12%(4/33), and 3.03%(1/33) for CR+PR, SD, and PD , respectively. Two months after treatment completion, the results changed to 75.76%(25/33), 9.10%(3/33), and 15.15%(5/33), respectively. Overall, 15 patients died. The one-year survival rate was 66.4%. Local failure was approximately 46.67%(7/15), whereas the local+distant fail-ure was approximately 26.67%(4/15). Therefore, local failure is the main pattern of failure in esophageal cancer. Conclusion:The re-sults indicate that neoadjuvant chemotherapy with cisplatin and docetaxel followed by radiotherapy concurrent with weekly cisplatin for locally advanced esophageal cancer is safe. Local failure remains the main pattern of failure in esophageal cancer.

Objective To investigate the clinical value of serum metabonomic profile of pancreatic cancer using nuclear magnetic resonance (NMR)-based metabonomics.Methods The retrospective case-control study was adopted.The clinical data of 23 patients with pancreatic cancer (PC group) and 16 healthy volunteers (control group) who were admitted to the Fujian Medical University Union Hospital between December 2013 and December 2014 were collected.The serum of the 2 groups was measured by 1H NMR spectroscopy.Multivariate statistical analyses were performed to identify the characteristic metabolites in the 2 groups,including principal component analysis (PCA),partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA).Observation indicators included:(1) multivariate statistical analysis of serum metabonomic profile,results of PCA,PLS-DA and OPLS-DA,(2) screening of metabolites.Measurement data with normal distribution were presented as x ± s.The comparison between groups was evaluated with the t test.The count data were analyzed using the chi-square test.Results (1) The multivariate statistical analysis of serum metabonomic profile:results of PCA showed that expression rates of principal component 1 (PC1) and principal component 2 (PC2) to original data were 54.9％ and 23.5％,with both cumulative contribution rate of 78.4％.Results of PLS-DA showed that the separative trend between PC group and control group was appeared,and variance of X and Y matrixes and predictive value were 0.254,0.816 and 0.385.Results of OPLS-DA showed that the differences of samples between the 2 groups were further increased,and differential metabolites were screened according to the distinction of scores between the 2 groups,value of R2X,R2Y and Q2 was 0.254,0.816 and 0.433.(2) Screening of metabolites:35 serum metabolites were detected in the 2 groups.Compared with the control group,levels of 3-hydroxybuyarate,citrate,formate,glutamate,isoleucine,methionine and phenylalanine in the PC group were elevated (r =0.524,0.511,0.656,0.566,0.503,0.498,0.648,P ＜0.05),and levels of 3-methylhistidine,alanine,glutamine,LDL and VLDL in the PC group were decreased (r =-0.607,-0.508,-0.560,-0.568,-0.559,P ＜ 0.05).Conclusions Compared with healthy controls,several amino acids,citrate and lipoproteins demonstrate the metabolic differences in the serum of patients with pancreatic cancer.NMR based metabonomic profile technology can distinguish the difference of serum metabolites between patients with pancreatic cancer and healthy controls.NMR based metabonomic technology may be a promising method for the diagnosis of pancreatic cancer.

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

OBJECTIVE: To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer. METHODS: TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed. RESULTS: The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05). CONCLUSION Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.
Animals ; Humans ; Mice ; Apoptosis ; Dendritic Cells/immunology* ; Glycyrrhizic Acid/pharmacology* ; HMGB1 Protein ; Lung Neoplasms/immunology*

Objective:To screen the HIV standard strains with typical biological characteristics of HIV strains circulating in China through the isolation, culture, genotype and phenotype identification of HIV from the whole blood samples of HIV-infected persons, confirm genetic characteristics, traceability, and in line with the Standard Strains of Pathogenic Microorganism-technical Specifications for Establishment of HIV Strains (T/CPMA 027—2023).Methods:Whole blood samples were collected from 48 HIV infected patients. Peripheral blood mononuclear cells (PBMCs) were isolated from the samples and co-cultured with PBMCs isolated from healthy persons′ whole blood samples to isolate and culture HIV from infected persons. We determined concentration of p24 antigen and the virus titer in the culture supernatant. The viral RNA was extracted from the successfully isolated strains, and the gag, pol genes and env C2V3 fragments of the viral genome were amplified and sequenced. The genotype, gene recombination and drug resistance sites were determined according to the viral gene sequences. Virus infection and replication were monitored by inoculating the virus culture supernatant into Ghost cells expressing CCR5 or CXCR4 to determine the viral tropism.The formation of syncytium was observed by inoculating the virus culture supernatant into MT-2 cells to determine whether was a syncytium-induced phenotype. Results:Fourteen strains with p24 antigen concentration > 1 ng/ml in culture supernatant were isolated and cultured from 48 fresh EDTA anticoagulated whole blood samples of HIV infected persons. Of the 14 strains, only one strain with a titer≥10 5 TCID 50/ml, 8 strains with titers ≥10 4 TCID 50/ml, and the other 5 strains with titers≥10 3 TCID 50/ml. Phylogenetic analysis showed that the genotypes of the strains were 9 strains of subtype B, 3 strains of CRF01_AE and 2 strains of CRF07_BC recombinant. Genotypic resistance analysis showed that 11 strains contained drug resistance sites. Ghost cells were used to verify the tropism of the strains, and it was found that 8 strains were CCR5 tropism, 6 strains were CXCR4 & CCR5 dual tropism. Only 2 of the 14 strains could induce MT-2 cytopathic effect, which was syncytium-inducing phenotype. Conclusions:Fourteen HIV strains with typical biological and genetic characteristics were isolated to screen the standard HIV strains. Among which, 1 strain was evaluated as a standard HIV strain that meets the Standard Strains of Pathogenic Microorganism-technical Specifications for Establishment of HIV Strains (T/CPMA 027—2023). This study can also provide technical guidance for the screening of the HIV standard strains. Next step is to complete the application and reserve database construction according to the sharing mechanism of the HIV standard strains, to provide resources for the researches of HIV vaccines and drugs.

Objective:To construct a prognostic nomogram based on epithelial-stromal interaction protein 1(EPSTI1)and predict the pro-gnosis of clear cell renal cell carcinoma(ccRCC).Methods:A retrospective analysis was performed from January 2012 to December 2015 at The First Affiliated Hospital of Fujian Medical University,on 221 patients with ccRCC who underwent surgical treatment in our center and 533 patients with ccRCC in The Cancer Genome Atlas(TCGA)database.Immunohistochemical(IHC)staining was performed on adjacent nor-mal and cancerous tissues to analyze the expression level of EPSTI1 and its correlation with clinicopathological characteristics.Kaplan-Meier survival analysis was performed for the overall survival(OS)and disease-free survival(DFS)of patients with high and low EPSTI1 expression levels.Univariate and multivariate Cox proportional hazards models were used to analyze the prognostic factors for OS,and a nomogram model was constructed and verified.Results:The IHC scores and mRNA expression levels of EPSTI1 were significantly higher in ccRCC tissues than in normal tissues(all P<0.001).EPSTI1 was expressed at higher levels in cancer tissues at higher T stages(P=0.036,P=0.006).The EPSTI1 protein expression level was related to the maximum tumor diameter and TNM stage(P=0.002,P=0.032,respectively).The OS and DFS were higher in the low-EPSTI1-expression group than the high-EPSTI1-expression group(P=0.046,P=0.003,P=0.001).Univariate and multivariate Cox regression analyses showed that a high EPSTI1 protein expression level,WHO/ISUP grade,and AJCC/TNM stage were independent risk factors for poor prognosis(P=0.009,P=0.039,P<0.001).The prognostic nomogram model constructed based on the above variables was su-perior to the AJCC/TNM stage in predicting the 5-year OS,and the calibration curve showed that the predicted value of the model was con-sistent with the actual value.Conclusions:The nomographic model based on EPSTI1,AJCC/TNM staging and WHO/ISUP staging has a strong predictive ability for the prognosis of renal clear cell carcinoma.