Cytotoxicity and osteogenic effects of aluminum ions.

In this study, we monitored the effect of Al3+ ions on mesenchymal cells (KUSA-A1) and human fibroblasts (NHDF) by means of in vitro experiments by culturing the cells with addition of small concentrations of aluminum ions (i.e., 0.1, 1, 10, and 100 ppm). Bone formation test was then conducted using KUSA-A1. Small concentrations of aluminum ions delayed but did not completely inhibit cell proliferation. The amount of bone tissue decreased as the concentration of Al3+ increased and crystallinity changes were also detected by Raman spectroscopic experiments. Moreover, Al3+ ions greatly affected both structure and chemistry of bone tissues with mineral nodules becoming larger and atomic substitution of Ca with Al in bone tissue being more preponderant with increasing Al3+ concentration. Such effects in turn impaired the balance between mineral and collagen in the formed bone tissue.

Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride

IntroductionViral disease spread by contaminated commonly touched surfaces is a global concern. Silicon nitride, an industrial ceramic that is also used as an implant in spine surgery, has known antibacterial activity. The mechanism of antibacterial action relates to the hydrolytic release of surface disinfectants. It is hypothesized that silicon nitride can also inactivate the coronavirus SARS-CoV-2. MethodsSARS-CoV-2 virions were exposed to 15 wt.% aqueous suspensions of silicon nitride, aluminum nitride, and copper particles. The virus was titrated by the TCD50 method using VeroE6/TMPRSS2 cells, while viral RNA was evaluated by real-time RT-PCR. Immunostaining and Raman spectroscopy were used as additional probes to investigate the cellular responses to virions exposed to the respective materials. ResultsAll three tested materials showed >99% viral inactivation at one and ten minutes of exposure. Degradation of viral RNA was also observed with all materials. Immunofluorescence testing showed that silicon nitride-treated virus failed to infect VeroE6/TMPRSS2 cells without damaging them. In contrast, the copper-treated virus suspension severely damaged the cells due to copper ion toxicity. Raman spectroscopy indicated differential biochemical cellular changes due to infection and metal toxicity for two of the three materials tested. ConclusionsSilicon nitride successfully inactivated the SARS-CoV-2 in this study. The mechanism of action was the hydrolysis-mediated surface release of nitrogen-containing disinfectants. Both aluminum nitride and copper were also effective in the inactivation of the virus. However, while the former compound affected the cells, the latter compound had a cytopathic effect. Further studies are needed to validate these findings and investigate whether silicon nitride can be incorporated into personal protective equipment and commonly touched surfaces, as a strategy to discourage viral persistence and disease spread.

Comparison of food allergy prevalence of food allergy in children with or without bronchial asthma in cite of China / 中华实用儿科临床杂志

Objective To explore the prevalence and clinical characteristics of food allergy in bronchial asth-matic children less than 14 years old in China. Methods A case - controlled study was designed. The questionnaires were given to children,who were diagnosed to be asthmatic during the national epidemiological survey of asthma in chil-dren in 31 cities from September 2009 to August 2010. Non - asthmatic children,matched with the cases in age and gender,were selected during the same survey as control subjects if they were matched with the cases in age and sex. In-formation regarding the food allergen and symptom of food - induced anaphylaxis was analyzed. The difference in food allergy was compared between children with or without bronchial asthma. Results As a result,9235 asthmatic children and 11391 control subjects were enrolled in the case - control study. There were 14. 66％(1354 / 9235 cases)of the asthmatic children who had food allergy,compared to 3. 99％(455 / 11391 cases)of the non - asthmatics children, and the findings showed a significant difference (χ2 = 725. 25,P < 0. 001). The most common food allergens were fish and shrimp in both groups,and the difference was not significant [44. 09％ (597 / 1354 cases)vs. 42. 20％ (192 / 455 cases),χ2 = 0. 50,P > 0. 05]. The rate of peanut allergy was 4. 58％ (62 / 1354 cases)and 1. 54％ (7 / 455 cases) (χ2 = 8. 58,P < 0. 05),respectively. And the rates of fruit allergy in the asthmatic group and the non - asthmatic group were 14. 03％(190 / 1354 cases)and 27. 69％(126 / 455 cases)(χ2 = 44. 01,P < 0. 05),respectively. Cutaneous and nasal symptoms were common clinical manifestations. The rates of rash,pruritus,and swelling sympions were 47. 27％(640 / 1354 cases)and 61. 32％(279 / 455 cases)(χ2 = 26. 90,P < 0. 001),respectively for asthmatic group and non -asthmatic group. Rates of nasal symptoms were 17. 13％(232 / 1354 cases)and 10. 55％(48 / 455 cases)(χ2 = 11. 29, P = 0. 001),respectively in the asthmatic group and the non - asthmatic groups. Respiratory symptoms,such as cough and wheezing,were 25. 33％(343 / 1354 cases)and 5. 49％(25 / 455 cases)(χ2 = 80. 72,P < 0. 001)in 2 groups. Twenty cases of 1354 asthmatic children had severe food allergy,while such severe conditions occurred only 1 child without asthma (455 cases)occurred severe condition (1. 48％ vs. 0. 22％,χ2 = 4. 96,P < 0. 05). Conclusion The-rate of food allergen sensitization is highly prevalent in the children with asthma. Compared to those without asthma, and their types of food allergen and clinical symptoms are different from the latter.

The association between plasma TGF-α levels and EGFR-TKI treatment sensitivity and prognosis in NSCLC patients with EGFR mutation / 中国癌症杂志

Background and purpose: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is of advantage in treating non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, their clinical effects vary individually. This study aimed to evaluate whether the EGFR ligand, plasma transforming growth factor α (TGF-α), could act as a predictor for the EGFR-TKI treatment e?ciency in NSCLC patients with EGFR mutations and the association between TGF-α and prognosis in these patients. Methods: Seventy-five NSCLC patients with EGFR gene positive mutation were included in the current study from May 2012 to Jul. 2014 in Ruikang Hospital A?liated to Guangxi University of Chinese Medicine. Plasma TGF-α was measured using enzyme-linked immunosorbent assay (ELISA) in all of the patients before EGFR-TKI treatment. The radiographic evaluation was performed 2 months after the therapy. The association between TGF-α and clinical outcome and its prediction e?ciency were determined, followed by the further analysis of the association between TGF-α and overall survival (OS) as well as progression-free survival (PFS). Results: After EGFR-TKI treatment, there were 20 patients with partial response (PR), 25 with stable disease (SD) and 30 with progression disease (PD) in all 75 NSCLC patients harboring EGFR positive mutation. The disease control (DC) rate reached 60%. Patients in PD group presented statistically significant higher plasma TGF-αthan patients in the DC group (P<0.01). Multivariate COX model indicated that smoking status, lymph node metastasis and plasma TGF-α levels were independent risk factors for prognosis in these patients. The ROC analysis revealed that baseline plasma TGF-α showed good prediction e?ciency [area under the curve (AUC)=0.926] and the cut-off point of TGF-α was 16.75 pg/mL. Higher level of TGF-α (≥16.75 pg/mL) was associated with smoking history, clinical stage, lymph node metastasis and clinical outcome of the patients (P<0.05). In comparison to patients with low TGF-α, the patients with high TGF-α concentration presented significantly reduced median OS and PFS (log-rank P<0.05). Conclusion: Higher plasma TGF-α (≥16.75 pg/mL) had a predictive role in EGFR-TKI resistance and poor prognosis.

Prognostic factors and model of primary liver cancer treated with transcatheter arterial chemoembolization combined with radiofrequency ablation / 中华肿瘤杂志

Objective@#To investigate the prognostic factors of primary liver cancer treated with transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA), and then to establish a prognostic model.@*Methods@#Clinicopathological and follow-up data of 145 patients who underwent TACE combined with RFA from January 2010 to December 2012 were retrospectively analyzed. Univariate and multivariate survival analyses were performed using the Cox proportional hazards model, and the prognostic model was established.@*Results@#The 1, 2, and 3-year survival rates were 92.6%, 81.4% and 66.2%, respectively. The 3-year recurrence and metastasis rate was 64.8%.Multivariate analysis showed that female cases and higher serum albumin levels were the protective factors for the 3-year overall and relapse-free survival of patients(P<0.05 for all). High levels of alpha-fetoprotein (AFP), alanine aminotransferase (ALT), total bilirubin (TBIL), portal vein thrombosis and higher Child Pugh stages were the independent risk factors for the 3-year overall survival(P<0.05 for all). High levels of AFP, TBIL, portal vein thrombosis and advanced stages of BCLC staging (B and C) were the independent risk factors for tumor recurrence and metastasis(P<0.05 for all). The predictive model established based on the multivariate analysis showed good sensitivity and specificity. The area under ROC curve were higher than 0.90.@*Conclusions@#The prognosis of liver cancer patients treated with TACE combined with RFA is affected by various clinicopathological factors. The systematic evaluation of the relevant factors before treatment may help to select proper patients and improve prognosis.

Influence of simvastatin treatment on Toll-like receptor 4 in monocytes of peripheral blood in patients with sepsis and severe sepsis / 中华危重病急救医学

Objective To investigate the influence of simvastatin treatment on Toll-like receptor 4 (TLR4) in monocytes of peripheral blood in patients with sepsis and severe sepsis and its significance. Methods A prospective randomized controlled trial was conducted. 106 patients with sepsis and 92 patients with severe sepsis admitted to Department of Critical Care Medicine of Henan Provincial People's Hospital from August 2013 to June 2015 were enrolled. These two groups of patients were randomized into conventional treatment group and simvastatin group. All patients received treatment according to the 2012 International Sepsis Treatment Guidelines, including anti-infection drugs, nutritional support, and palliative treatment, and the patients with severe sepsis were given early goal-directed therapy (EGDT). The patients in simvastatin group received simvastatin 40 mg daily orally for at least 15 days. The peripheral blood was collected and the monocytes were isolated at 1, 5, 10, 15 days after intensive care unit (ICU) admission. TLR4 expression on the surface of TLR4/CD14+ double positive monocytes was determined by flow cytometry, and adverse reaction was observed during treatment. Results TLR4 expression on the surface of monocytes showed a tendency of decreasing with prolongation of simvastatin treatment in the simvastatin group in patients with sepsis (n = 59) or severe sepsis (n = 54). However, in patients with sepsis, TLR4 level was significantly decreased from 10 days in simvastatin group as compared with that of conventional therapy group (n = 47), and it was decreased up to 15 days [mean fluorescence intensity (MFI): 21 (19, 28) vs. 27 (25, 33) at 10 days, Z = 2.198, P = 0.021; 16 (15, 21) vs. 26 (23, 34) at 15 days, Z = 4.611, P = 0.002]. In patients with severe sepsis, there was no significant difference in TLR4 level at different time points between simvastatin group and conventional treatment group (n = 38) [MFI: 55 (52, 63) vs. 56 (48, 65) at 1 day, Z = 0.313, P = 0.692; 47 (42, 56) vs. 49 (41, 58) at 5 days, Z = 0.827, P = 0.533; 40 (35, 42) vs. 42 (37, 45) at 10 days, Z = 1.012, P = 0.301; 33 (30, 38) vs. 38 (35, 41) at 15 days, Z = 0.539, P = 0.571]. No adverse reaction related with simvastatin was found during treatment in patients with sepsis or severe sepsis. Conclusions Statins could significantly down-regulate the TLR4 expression on peripheral blood monocytes in septic patients, while it showed no significant influence on TLR4 expression in patients with severe sepsis. A different effect of statins on TLR4 expression and the downstream inflammation process in sepsis and severe sepsis patients might partially explain the discrepancy in previous reports about the therapeutic effect of statins therapy in sepsis and severe sepsis patients.

Clinical observation on oxaliplatin reintroduction combined with raltitrexed as second-line chemotherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients / 中国肿瘤临床

Objective:To investigate the efficacy and toxicity of oxaliplatin reintroduction combined with raltitrexed as second-line che-motherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients. Methods:The 48 evaluable pa-tients with advanced colorectal cancer following disease progression prior to the first-line chemotherapy were treated with oxaliplatin and raltitrexed (raltitrexed 3 mg/m2 ivgtt d1, oxaliplatin 100-130 mg/m2 ivgtt d1, q21d). All 48 patients were divided into two groups:Group A, non-oxaliplatin-based regimens as the first-line chemotherapy, 20 cases;Group B, oxaliplatin-based regimens as the first-line chemotherapy, 28 cases. Each group was evaluated every two cycles. Results:The response rates (RR) of Groups A and B were 30.0%(6/20) and 32.1%(9/28), the disease control rates (DCR) were 80.0%(16/20) and 75.0%(21/28), the median progression free survival time (mPFS) was 6.5 and 7.0 months, and the median overall survival time (mOS) was 10 and 13 months, respectively. No statistical sig-nificance was observed between the two groups in their RR, CR, mPFS, and mOS (P=0.264, 0.514, 0.713, 0.788), respectively. The most common adverse effects observed wereⅠ-Ⅱgrades of bone marrow suppression, aminotransferase abnormality, and digestive toxici-ties. The incidence of neurotoxicity (Ⅰ-Ⅱgrades) between the two groups was similar. Conclusion:Instead of irinotecan combined with raltitrexed, oxaliplatin reintroduction combined with raltitrexed for second-line chemotherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients is feasible.

Innovative tribometer for in situ spectroscopic analyses of wear mechanisms and phase transformation in ceramic femoral heads.

The literature on tribological assessments of artificial hip joints usually focuses on correlations between joint composition, size, and specific wear rates, but conspicuously ignores the physical aspects behind the occurrence of degradation mechanisms of friction and wear. Surface degradation in artificial joints occurs because of increases in temperature and local exacerbation of contact stresses inside the moving contact as a consequence of physical and chemical modifications of the sliding surfaces. This article reports about the development of a new pin-on-ball spectroscopy-assisted tribometer device that enables investigating also physical rather than merely engineering aspects of wear processes using in situ Raman and fluorescence techniques. This innovative tribometer is designed to bring about, in addition to conventional tribological parameters, also information of temperature, stress and phase transformations in the femoral heads as received from the manufacturer. Raman and fluorescence spectra at the point of sliding contact are recorded durilng reciprocating hard-on-hard dry-sliding tests. Preliminary results were collected on two different commercially available ceramic-on-ceramic hip joint bearing couples, made of monolithic alumina and alumina-zirconia composites. Although the composite couple showed direct evidence of tetragonal-to-monoclinic phase transformation, which enhanced the coefficient of friction, the specific wear rate was significantly lower than that of the monolithic one (i.e., by a factor 2.63 and 4.48 on the pin and head side, respectively). In situ collected data compared to ex situ analyses elucidated the surface degradation processes and clarified the origin for the higher wear resistance of the composite as compared to the monolithic couple.