Efficacy of relative dose intensity of nab-paclitaxel for the short-term outcomes, survival, and quality of life in patients with advanced pancreatic cancer: a retrospective study.

Background: To optimize treatment, choosing the appropriate relative dose intensity (RDI) of nab-paclitaxel is an important way to improve patient tolerance, therapeutic efficacy, and survival. However, few studies have focused on the efficacy of the RDI of nab-paclitaxel in patients with advanced pancreatic cancer, and whether the RDI of nab-paclitaxel could be employed as an index for treatment remains unknown. To explore the relationship between RDI of nab-paclitaxel and chemotherapy efficacy, survival, quality of life (QoL), and adverse effects in patients with advanced pancreatic cancer. Methods: In this retrospective study, a total of 32 patients with advanced pancreatic cancer, ECOG score of 0 to 2 were included from January 2017 to March 2020. The patients were treated with nab-paclitaxel combined with gemcitabine as a first-line treatment and divided into high and low RDI groups. Chemotherapy efficacy, survival, QoL, and adverse effects between two groups were compared. Results: The disease control rate (DCR) was 20.0% in the low RDI group, compared with 81.8% in the high RDI group (P=0.002). A good correlation between nab-paclitaxel RDI and short-term efficacy was observed in all 32 patients (r=0.728, P<0.01). Furthermore, the high RDI group had significantly better median overall survival (mOS: 12 vs. 8 months, P=0.034) and median progression-free survival (mPFS: 5.5 vs. 3 months, P=0.052) compared to that of low RDI patients. Univariate regression analysis showed that longer overall survival was associated with lower ECOG score [hazard ratio (HR): 10.88; 95% confidence interval (CI): 2.54-46.5, P=0.001], tumors located in the body or tail of pancreases (HR: 3.82; 95% CI: 1.4-10.3, P=0.0081), and higher RDI (HR: 0.21; 95% CI: 0.071-0.6, P=0.004). The high RDI group had a significantly better physical function and emotional function improvement compared to the low RDI group (P<0.05). Moreover, high RDI did not increasing the severity and frequency of the adverse events. Conclusions: It is recommended to maintain a sufficient RDI of nab-paclitaxel to ensure that the balance between lerability, therapeutic efficacy, and survival benefits is satisfied in patients with advanced pancreatic cancer.

Development and verification of a hypoxia- and immune-associated prognosis signature for esophageal squamous cell carcinoma.

Background: Esophageal cancer is one of the most common gastrointestinal malignancies worldwide, with high morbidity and mortality in China. The clinical importance of the interaction between hypoxia and immune status in the tumor microenvironment has been established in esophageal squamous cell carcinoma (ESCC). This study aims to develop a new hypoxia- and immune-based gene signature to predict the survival of ESCC patients. Methods: The RNA-sequencing and clinical data of 173 cases of ESCC and 271 normal tissues were obtained from The Cancer Genome Atlas (TCGA) data portal and the Genotype-Tissue Expression (GTEx) database. Hypoxia-related genes (HRGs) and immune-related genes (IRGs) were retrieved from publicly shared data. Differentially expressed gene (DEG) analyses were carried out by the DESeq2 method using the edgeR package in R. Based on the intersection of the DEGs and HRGs/IRGs, differentially expressed HRGs (DEHRGs) and differentially expressed IRGs (DEIRGs) were obtained. DEHRGs and DEIRGs associated with prognosis were evaluated using univariate Cox proportional hazards analysis. A prognostic risk score model was constructed according to the genes acquired through Cox regression. Univariate analysis and Cox proportional hazards analysis were used to determine the independent prognostic factors related to prognosis. A nomogram was developed to predict the 1-, 2-, and 3-year overall survival (OS) probability. Results: A total of 73 intersecting genes were obtained as DEHRGs and a total of 548 intersecting genes were obtained as DEIRGs. The risk score was established using 8 genes (FABP7, TLR1, SYTL1, APLN, OSM, EGFR, IL17RD, MYH9) acquired from univariate Cox analysis. Based on this 8-gene-based risk score, a risk prognosis classifier was constructed to classify the samples into high- and low-risk groups according to the median risk score. The nomogram model was constructed to predict the OS of ESCC patients. Conclusions: The hypoxia- and immune-based gene signature might serve as a prognostic classifier for clinical decision-making regarding individualized management, follow-up plans, and treatment strategies for ESCC patients.

Pattern of distant metastases and predictive nomograms in colorectal mucinous adenocarcinoma: a SEER analysis.

BACKGROUND: We evaluated the metastatic patterns and explored the prognostic value of distant metastasis pattern in patients with metastatic colorectal mucinous adenocarcinoma (MC) using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Between 2010 and 2015, newly diagnosed colorectal MC patients were selected using the SEER database. Patient prognosis was compared based on the clinicopathological parameters, treatment method, and the site and number of metastatic organs. Cox analyses were used to identify factors associated with overall survival (OS). A nomogram was built to predict the patient's survival. Harrell's concordance index (c-index) and calibration curves were used to analyze the discriminative ability of the prognostic factors. RESULTS: Of 3,088 patients diagnosed with colorectal MC, the liver was the only metastatic organ in 78.4% (997/1,271) of all liver metastasis cases, the lung was the only metastatic organ in 41.0% (164/400) of all lung metastasis cases, bone was the only metastatic organ in 26.6% (29/109) of all bone metastasis cases, and the brain was the only metastatic organ in 23.5% (4/17) of all brain metastasis cases. Compared with the untreated cases, those treated with chemotherapy, surgery, and radiotherapy had better OS (P<0.001). There were marked OS differences (P<0.001) between patients with and without liver and bone metastases. Patients with bone metastasis had the best survival, while those with brain metastasis had the worst survival (P<0.001). Patients with one metastatic site had better prognosis compared to those with two or three (P<0.001). Patients with liver metastasis had the best survival, while those with bone and brain metastasis had the worst survival (P<0.001). Multivariate analysis showed that age <65 years, non-black race, grade I, N0 stage, chemotherapy, radiation, surgery, liver metastasis, and bone metastasis were independent prognostic factors. A nomogram was constructed to predict survival probability. The c-index value was up to 0.745. The calibration plot showed that the nomogram was clinically useful. CONCLUSIONS: Metastatic MC (mMC) patients had a characteristic distant metastasis pattern. This study constructed a new and sufficiently accurate prognostic model of mMC based on population-based data. These findings can be utilized to predict prognosis and guide mMC patient management.

[Preliminary development and cytotoxicity of Eucommia ulmoides gum composite soft denture liner].

PURPOSE: To prepare a soft lining material with high elastic on the basis of excellent characteristics of Eucommia ulmoides gum, and explore its basic physical performance and cytotoxity. METHODS: Basic formula was used based on the existing formula of elastic Eucommia ulmoides gum and medical rubber, then hardness, tensile strength and elongation at break were investigated to determine the final formula of the material, named Eucommia ulmoides gum composite soft denture liner. L929 mouse fibroblasts cultured in vitro were used to detect the toxic effects of 50% of leaching solution released from three kinds of denture soft lining materials by MTT assay. Statistical analysis was performed using SPSS16.0 software package. RESULTS: The kinds and blending proportion of rubber matrix had significant impact on mechanical properties of Eucommia ulmoides gum composite soft denture liner, the addition of Eucommia ulmoides gum significantly increased the hardness, tensile strength and elongation at break of the butadiene rubber. MTT assay showed Eucommia ulmoides gum composite soft denture liner did not have cytotoxicity on L929 mouse fibroblasts. The toxicity levels of 5 groups of Eucommia ulmoides gum composite soft denture liner in the 2nd, 4th, 7th day were maintained in the first stage, only 70:30 group reached the second stage on the 7th day. The cell relative appreciation rate of Silagum and 5 groups of Eucommia ulmoides gum composite soft denture liner in 2nd, 4th, 7th day were significantly higher than that in the self-curing acrylic soft lining material (P<0.05). CONCLUSIONS: Eucommia ulmoides gum and butadiene rubber blend ratio of 70:30, adding appropriate amount of zinc oxide, magnesium, stearic acid, sublimed sulfur, CZ, antioxidants, can get optimum mechanical properties. Eucommia ulmoides gum composite soft denture liner has no effect on L929 fibroblasts proliferation, indicating good biocompatibility.

The inhibition of hepatic bile acids transporters Ntcp and Bsep is involved in the pathogenesis of isoniazid/rifampicin-induced hepatotoxicity.

Co-treatment of isoniazid (INH) and rifampicin (RFP) is well known for clinically apparent liver injury. However, the mechanism of INH/RFP-induced liver injury is controversial. Emerging evidence shows links between inhibition of bile acids transporters and drug-induced liver injury (DILI). The present study investigates whether sodium taurocholate cotransporting polypeptide (NTCP/Ntcp; SLC10A1) and bile salt export pump (BSEP/Bsep; ABCB11) are involved in the anti-tuberculosis medicines induced liver injury. ICR female mice were intragastrically treated with INH (50 or 100 mg/kg), RFP (100 or 200 mg/kg), or the combination of INH/RFP (50 + 100 mg/kg or 100 + 200 mg/kg) for 14 consecutive days. Liver histopathological examination, serum biochemical and liver malondialdehyde tests were evaluated. Apparent histopathological alterations and hepatic oxidative stress showed in INH (100 mg/kg), RFP (200 mg/kg) and their combination group. The hepatoxic effect was also indicated by increased serum biomarkers, such as aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBil), total bilirubin (TBil) and total bile acids (TBA). Both doses of INH/RFP administration significantly down-regulated the expression of Ntcp and Bsep in liver. Furthermore, the combination of INH and RFP displayed stronger effect on the expression of Ntcp compared with the corresponding dose of INH or RFP alone. In conclusion, down-regulated expression of hepatic Ntcp and Bsep might play an important role in the development of INH and RFP induced liver injury.

[Correlation between anxiety, depression and pefectionistic tendencies in patients before orthodontic treatment].

PURPOSE: To discuss the relationships between the level of anxiety, depression and perfectionism in dental patients before orthodontic treatment. METHODS: A modified Corah Dental Anxiety Scale (MDAS), Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS) and Chinese Frost Multidimensional Perfectionism Scale (CFMPS) were used in 170 patients before orthodontic treatment. The data was analyzed by independent sample t test, correlation and multiple regression analysis using SPSS16.0 software package. RESULTS: 24.71% of the patients had obvious dental anxiety with MDAS scores≥11, there was significant difference in the scores of SAS, SDS between dental anxiety group and non-dental anxiety group (P<0.01), the scores of concern over mistakes (CM), personal standards (PS), doubts about actions (DA) and organization (OR) of dental anxiety patients were of significant difference compared with that in the non-dental anxiety group (P<0.05). Concern over mistakes (CM), personal standards (PS) and doubts about actions (DA) had significant positive correlations with the scores of SAS and SDS (P<0.01); while organization (OR) had negative correlation with the scores of SDS (P<0.05); Regression analysis showed that the scores of concern over mistakes (CM), organization (OR) and age seemed to be a strong predictor of the scores of SAS and SDS. CONCLUSIONS: The level of anxiety and depression of dental anxiety patients before orthodontic treatment is higher than non-dental anxiety group, and it has significant correlation with perfectionistic tendencies, for dental anxiety of patients with early intervention should be combined with different age and perfectionism personality characteristics.

Methanol triggered ligand flip isomerization in a binuclear copper(I) complex and the luminescence response.

Methanol drives the blue emissive complex, [Cu(2)(dppy)(3)(MeCN)](BF(4))(2) (dppy = diphenylphosphino-pyridine), with a head-to-tail arrangement of the three bridging phosphine ligands to convert to its linkage isomer (head-to-head, green emissive) in the solid state, and the transformation could be reversibly realized through recrystallization in different solvents.

Ligand- and anion-controlled formation of silver alkynyl oligomers from soluble precursors.

Novel silver(I) alkynyl cluster complexes ([Ag5(bpy)4(C [triple bond] CBu(t))2](3+), [Ag8(bpy)6(C [triple bond] CBu(t))4](4+), and [Ag 12(bpy)4(C [triple bond] CBu(t))6(CF3CO2)6]) have been synthesized by reacting soluble polymeric precursors with bipyridine ligands, and control of the nuclearity can be achieved by varying the molar ratio of the reactants and using different types of anions.