Objective:To explore the clinical effect of simultaneous whole-course hyperfractionated intensity-modulated radiation therapy combined with chemotherapy and nimotuzumab in the treatment of advanced nasopharyngeal carcinoma.Methods:A total of 64 patients with advanced nasopharyngeal carcinoma who were admitted to Kaiping Central Hospital of Guangdong Province from June 2017 to January 2019 were selected and divided into the observation group and control group according to the random number table method, with 32 cases in each group. Both groups were given chemotherapy and nimotuzumab on the basis of radiotherapy. The observation group received simultaneous whole-course hyperfractionated intensity-modulated radiation therapy, and the control group received conventional fractionated intensity-modulated radiation therapy. The short-term efficacy, Karnofsky score, overall survival rate, progression-free survival rate, acute radiation reaction, and late radiation injury in the two groups were observed.Results:Six months after radiotherapy, the efficient rate of the observation group was higher than that of the control group [96.9% (31/32) vs. 75.0% (24/32), χ2 = 6.335, P < 0.05]. At the end of radiotherapy and 3 months after the end of radiotherapy, the Karnofsky scores of the observation group were higher than those of the control group, and the differences were statistically significant [(75±3) points vs. (71±3) points, t = 5.891, P < 0.05; (80±4) points vs.(77±4) points, t = 3.201, P = 0.002]. All patients were well tolerated, no grade 4 acute radiation reaction was observed, and radiotherapy was completed as planned. The incidence rate of oral mucosal reaction in the observation group was lower than that in the control group [21.9% (7/32) vs. 50.0% (16/32), χ2 = 5.497, P < 0.05]. The incidence rates of severe dry mouth and neck soft tissue fibrosis in the observation group were lower than those in the control group [6.2% (2/32) vs. 28.1% (9/32), χ2 = 5.379, P = 0.043; 3.1% (1/32) vs. 21.9% (7/32), χ2 = 5.143, P < 0.05]. The follow-up time was 14-20 months, and the median follow-up time was 17 months. There was no statistical difference in overall survival time between the two groups ( χ2 = 0.553, P = 0.557). The progression-free survival time of the observation group was better than that of the control group ( χ2 = 3.954, P = 0.044). Conclusion:The simultaneous whole-course hyperfractionated intensity-modulated radiation therapy combined with chemotherapy and nimotuzumab are effective in the treatment of advanced nasopharyngeal carcinoma, and the adverse reactions can be tolerated.

Male guinea pigs were exposed to 750ppm or l000ppm or 1 500ppm toluene (8h/d, for 14d), and their hearing thresholds were tested by means of Madsen ERA 2250 system 3d and 14d after exposure. Hearing impairment was observed in all groups. The degree of impairment was related to the exposure concentration and had a tendency to further damage in two weeks. The results indicate that toluene can cause acute hearing impairment even if its concentration is as low as 750ppm and the impairment develops from bad to worse at least in two weeks.

Objective To investigate the malnutrition status among the elderly in age care institutions in Shanghai suburb and analyze its potential influential factors.Methods The MiniNutritional Assessment (MNA) was adopted to evaluate the nutritional status of the 190 elderly people in age care institutions.The dietary supply by the institution canteen and the quantity of residual food left by the malnourished elderly people were weighted.Results In the age care institutions,the malnutrition rate reached 23.7％,47.9％ of the elderly people were at the risk of malnutrition,and only 28.4％ of the elderly people were well nourished.Logistic regression analysis showed that the major influential factors for malnutrition in the elderly people were food intake ability,mobile capability,chewing and swallowing ability,ageing and mental Illness.The malnourished elderly people had the most residual meat and vegetables,and insufficiency of nutrient intake was the main cause for the malnutrition in the elderly people.Conclusions The elderly people in age care institutions in Shanghai suburb have the higher risk of malnutrition.The malnutrition occurs under influence of many factors,of which some are unavoidable,however,some factors like dietary factors can be changed to improve the nutritional status of the elderly people in age care institutions.

Objective To study the expression and the role of interferon-gamma (IFN-?)in murine systemic infection of Scedosporum apiospermum. Methods The murine models of systemic Scedosporum apiospermum infection was established by inoculation of the pathogenic fungi. ELISA and RT-PCR were applied to detect the expression level of IFN-? protein and mRNA in spleens, respectively. Colony formingunit (cfu) of infected kidneys was determined with the plating dilution method. The mean survival time (MST) of the mice was also recorded. Results IFN-? levels in lethal infection group were lower than those of the normal controls (P 0.05 on day 7). IFN-? levels of sublethal infection group were higher than those of normal controls (P 0.05 on day 7). But the IFN-? levels were significantly lower in the immunosuppressed group than those in the sublethal infection group (P

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. Epigallocatechin-3-gallate (EGCG) is a polyphenolic constituent of green tea. In this study, inhibitory effect of combined use of EGCG and TRAIL on human melanoma A375 cells was examined and the possible mechanism investigated. The cells were divided into 4 groups: control group, EGCG group (EGCG: 10, 20 mug/mL), TRAIL group (TRAIL: 25 ng/mL) and EGCG+TRAIL group (combined group). The growth inhibition was measured in the A375 cells treated with different concentrations of TRAIL ((25, 50, 75, 100, 125, 150 ng/mL) by MTT assay. The apoptosis was assessed by flow cytometry. The expressions of DR4 and DR5 were detected by flow cytometry and western blotting. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that TRAIL could dose-dependently inhibit the growth of A375 cells and the IC(50) of TRAIL was 150 ng/mL. The apoptosis rate was 11.8% in the TRAIL group, 5%-7% in the EGCG group and 48.9%-59.1% in the combined group. Significant difference was found in the apoptosis rate between the combined group and the EGCG or TRAIL group (P<0.05 for each). The expression of DR4 instead of DR5 was significantly increased in the EGCG group. The activity of caspase-3 rather than caspase-8 was substantially enhanced in the EGCG group. These results suggest that EGCG is useful for the TRAIL-based treatment for melanoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. However, emergence of drug resistance limits its potential use. Plumbagin is a natural quinonoid compound isolated from plant. In this study, induced apoptosis effect of the combined treatment with plumbagin and TRAIL on human melanoma A375 cell line was examined and possible mechanism was investigated. The cells were divided into four groups: control group, plumbagin group (plumbagin, 5 or 10 mumol/L), TRAIL group (TRAIL, 30 ng/mL) and plumbagin+TRAIL group (combined treatment group). The apoptosis, and the expression of DR4 and DR5 were detected by flow cytometry. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that the apoptosis rate was 8.3% in TRAIL group, 10.35%-16.94% in plumbagin group and 52.39%-65.39% in combined treatment group, respectively, with the difference being significant between combined treatment group and plumbagin or TRAIL group (P<0.05 for each). Moreover, plumbagin alone could markedly up-regulate DR5 mRNA and protein expression, and slightly increase DR4 mRNA and protein expression. Treatment of human melanoma A375 cells with plumbagin resulted in the activation of Caspase-3, but not Caspase-8. These results suggest that plumbagin might be useful for TRAIL-based treatment for melanoma.

Objective: To explore the trichloroethylene-induced alteration of methylation on the promoter region of SET and related mechanisms in hepatic L-02 cells. Methods: L-02 cells were treated with different concentrations of TCE(0 mmol/L, 1 mmol/L, 2 mmol/L, 4 mmol/L, 8 mmol/L) for 24 h. The genomic DNA were then extracted and modified by bisulfite sodium. The DNA methylation was then analyzed using bisulfite sequencing PCR (BSP). Results: The overall methylation on promoter region of SET was decreased along with the increased concentrations of TCE in hepatic L-02 cells. Moreover, 73 CpG islands were found abnormally altered, among which 9 were predicted in transcriptional factor binding regions. Conclusion The decreased levels of CpG islands in the transcriptional factor binding region may contribute to the elevation of SET in TCE-induced hepatotoxicity.

Objective: To further explore TCE-induced hepatotoxicity and its mechanisms by identification of trichloroethylene (TCE) induced abnormal histone methylation in human liver cells. Methods: L-02 cells were treated with 0 and 8 mmol/L TCE for 24 h. Histones were extracted by acid. Liquid chromatography electrospray ionization tandem mass spectrometry (ESI-LC-MS/MS) were used to identify and quantify TCE related histone methylations. TCE induced abnormal methylation of H3K79 me2 and H3K79 me3 were validated by Western blot analysis. The further analysis of the function of histone abnormal methylation modifications were done by single cell gel electrophoresis (SCGE) and Western blot analysis of p53 and ɤH2AX. Results: After treatment with TCE for 24 h in L-02 cells, the 36 TCE related histone methylation sites in 28 peptide segments were identified by MS. After treatment with TCE in concentrations of 0 and 8.0 mmol/L in L-02 cells for 24 h, the relative expression level of histone H3K79 me3 were 1.00±0.06, 0.70±0.09 (t=15.01, P=0.015); the relative expression level of histone H3K79 me2 were 1.00±0.05, 0.74±0.07 (t=16.69, P=0.018); the Olive Tail Moment about DNA damage were 1.46±0.28, 3.12± 0.68 (t=15.22, P=0.018); the relative expression levels of p53 were 1.00±0.04, 1.24±0.04 (t=18.71, P= 0.012); and the relative expression levels of ɤH2AX were 1.00 ± 0.03, 1.56 ± 0.11 (t=8.32, P=0 045). Conclusion TCE can induce changes in the relative expression level of H3K79 me2 and H3K79 me3 in L-02 cell, and induce DNA damage, suggesting that TCE may induce changes in the relative expression level of H3K79 me2 and H3K79 me3 by DNA damage.

Objective:To explore the causal relationship between thyroid dysfunction and sepsis based on the bidirectional two-sample Mendelian randomization (MR) method.Methods:The genome-wide association study (GWAS) dataset were selected to screen single nucleotide polymorphisms (SNP) associated with thyroid dysfunction as instrumental variable (IV) for genetic variation, using hypothyroidism and hyperthyroidism as exposure factor and sepsis as outcome factor. Potential causal relationship between thyroid dysfunction and sepsis was analyzed using a bidirectional two-sample MR method primary analysis method of inverse-variance weighted (IVW). Potential pleiotropic analysis of SNP was performed using the MR Egger regression intercept test. Sensitivity analysis was performed using the "leave one out" test. Reverse MR method was used to prove the causal relationship.Results:The GWAS data were screened based on the three main assumptions of MR, resulting in 101 SNP strongly associated with hypothyroidism and 10 SNP strongly associated with hyperthyroidism entering the MR analysis. The results of the MR using the IVW method showed that the risk of sepsis in individuals with hypothyroidism was 2.293 times higher than those without hypothyroidism [odds ratio ( OR) = 2.293, 95% confidence interval (95% CI) was 1.199-4.382, P = 0.012]. There was no significant difference in the risk of sepsis between hyperthyroid and non-hyperthyroid populations ( OR = 1.049, 95% CI was 0.999-1.100, P = 0.560). MR Egger regression intercept test showed that the included SNP did not have pleiotropy, and the MR-PRESSO test did not find outliers. Sensitivity analysis suggested that the results of MR were stable. The results of the reverse MR analysis showed that the reverse causal relationship between hyperthyroidism and sepsis was not proved ( OR = 0.996, 95% CI was 0.988-1.004, P = 0.338), which further confirmed the robust MR analysis result. Conclusion:The results of the bidirectional two-sample MR analysis show that hypothyroidism can increase the risk of sepsis onset, while there is no causal relationship between hyperthyroidism and sepsis.

Purpose: The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM). Methods: This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients’ initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)–free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups. Results: PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040). Conclusion For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.