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Objective The coronavirus disease 2019 (COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge. Currently, some COVID-19 vaccines are being developed and applied on general population; however, whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China. Methods A cross-sectional study was conducted in Eastern China from June 17th to September 3rd, 2021. Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine; following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance. Results A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05% (519/2158); further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine (35.54%), and 872 were willing to get vaccinated (40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants, patients’ knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the “vaccine hesitancy” population and “vaccine acceptance” population. Multivariate logistic regression analysis indicated that parameters including alcohol consumption (odds ratio [OR] = 1.849; 95% confidence interval [CI]: 1.375–2.488; P -reference [ P -Ref] < 0.001 vs non-drinkers), income impacted by COVID-19 pandemic (OR = 1.930, 2.037 and 2.688 for mild, moderate, and severe impact, respectively; all P -Ref < 0.01 vs no impact), knowledge of how the vaccine was developed (OR = 1.616; 95% CI: 1.126–2.318; P -Ref = 0.009 vs unknown), believing in the safety of the vaccine (OR = 1.502; 95% CI: 1.024–2.203; P -Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine (OR = 3.042; 95% CI: 2.376–3.894; P -Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated (OR = 2.744; 95% CI: 1.759–4.280; P -Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired (OR = 0.586; 95% CI: 0.438–0.784; P -Ref < 0.001 vs...

Background: Emerging scientific evidence has disclosed a correlation between iron metabolism and type 2 diabetes (T2D). Objective: The objective of this study was to test the hypothesis that body iron stores are higher in a Chinese population with altered glucose homeostasis. Design: Serum iron, ferritin, and soluble transferrin receptor concentrations were measured in 298 subjects, including 70 subjects with normal glucose tolerance (NGT group), 60 subjects with prediabetes (prediabetes group), and 168 subjects with T2D (T2D group). Hepatic iron stores in 88 subjects were assessed by using a magnetic resonance imaging (MRI) T2* gradient-recalled-echo technique. A general linear model ANOVA was performed for comparisons between groups after adjustment for age and BMI.Stepwise multiple linear regression analysis was used to identify factors associated with the MRI-estimated hepatic iron concentration (M-HIC). Results: Mean (6SD) M-HIC and R2* values in the prediabetes and T2D groups were significantly higher than in the NGT group (M-HIC: 40.6 6 8.6 and 39.3 6 10.7 lmol/g compared with 27.8 6 9.1 lmol/g; R2* values: 47.9 6 11.9 and 47.3 6 11.5 s 21 compared with 34.9 6 7.0 s 21; all P , 0.01). No significant difference was shown in M-HIC and R2* values between prediabetes and T2D groups. The M-HIC independently contributed to 43.3% of the glycated hemoglobin variance after adjustment for main clinical indexes (P , 0.001). The proportions of subjects with mild hepatic iron overload in the NGT, prediabetes, and T2D groups were 12.5%, 70.6%, and 63.6%, respectively. Conclusions: To our knowledge, our findings provide novel evidence to support the hypothesis of a mild iron overload in patients with prediabetes and T2D. A cohort study concerned with the effect of the attenuation of excess iron on glucose metabolism in a prediabetic population is warranted.Am J Clin Nutr 2011;94:1012-9.

Current challenges for recombinant adeno-associated virus (rAAV) vector-based cancer treatment include the low efficiency and the lack of specificity in vivo. rAAV serotype 3 (rAAV3) vectors have previously been shown to be ineffective in normal mouse tissues following systemic administration. In the present study, we report that rAAV3 vectors can efficiently target and transduce various human liver cancer cells in vivo. Elimination of specific surface-exposed serine and threonine residues on rAAV3 capsids results in further augmentation in the transduction efficiency of these vectors, without any change in the viral tropism and cellular receptor interactions. In addition, we have identified a potential chemotherapy drug, shikonin, as a multifunctional compound to inhibit liver tumor growth as well as to significantly enhance the efficacy of rAAV vector-based gene therapy in vivo. Furthermore, we also document that suppression of tumorigenesis in a human liver cancer xenograft model can be achieved through systemic administration of the optimized rAAV3 vectors carrying a therapeutic gene, and shikonin at a dose that does not lead to liver damage. Our research provides a novel means to achieve not only targeted delivery but also the potential for gene therapy of human liver cancer.

We have observed that of the 10 AAV serotypes, AAV6 is the most efficient in transducing primary human hematopoietic stem cells (HSCs), and that the transduction efficiency can be further increased by specifically mutating single surface-exposed tyrosine (Y) residues on AAV6 capsids. In the present studies, we combined the two mutations to generate a tyrosine double-mutant (Y705+731F) AAV6 vector, with which >70% of CD34+ cells could be transduced. With the long-term objective of developing recombinant AAV vectors for the potential gene therapy of human hemoglobinopathies, we generated the wild-type (WT) and tyrosine-mutant AAV6 vectors containing the following erythroid cell-specific promoters: β-globin promoter (βp) with the upstream hyper-sensitive site 2 (HS2) enhancer from the β-globin locus control region (HS2-βbp), and the human parvovirus B19 promoter at map unit 6 (B19p6). Transgene expression from the B19p6 was significantly higher than that from the HS2-βp, and increased up to 30-fold and up to 20-fold, respectively, following erythropoietin (Epo)-induced differentiation of CD34+ cells in vitro. Transgene expression from the B19p6 or the HS2-βp was also evaluated in an immuno-deficient xenograft mouse model in vivo. Whereas low levels of expression were detected from the B19p6 in the WT AAV6 capsid, and that from the HS2-βp in the Y705+731F AAV6 capsid, transgene expression from the B19p6 promoter in the Y705+731F AAV6 capsid was significantly higher than that from the HS2-βp, and was detectable up to 12 weeks post-transplantation in primary recipients, and up to 6 additional weeks in secondary transplanted animals. These data demonstrate the feasibility of the use of the novel Y705+731F AAV6-B19p6 vectors for high-efficiency transduction of HSCs as well as expression of the b-globin gene in erythroid progenitor cells for the potential gene therapy of human hemoglobinopathies such as β-thalassemia and sickle cell disease.

Postsurgical recurrence within 2 years is the major cause of poor survival of hepatocellular carcinoma (HCC) patients. However, the molecular mechanism underlying HCC recurrence remains unclear. Here, we distinguish the function and mechanism of Sec62 in promoting HCC recurrence. The correlation between Sec62 and early recurrence was demonstrated in 60 HCC samples from a prospective study. HCC cells with Sec62 knockdown (Sec62KD) or overexpression (Sec62OE) were used to determine the potential of Sec62 in cell migration in vitro. Microarray analysis comparing Sec62KD or Sec62OE to their control counterparts was used to explore the mechanisms of Sec62-induced recurrence. A luciferase-labelled orthotopic nude mouse model of HCC with Sec62KD or Sec62OE was used to validate the potential of Sec62 in early HCC recurrence in vivo. We found that high expression of Sec62 was positively correlated with surgical recurrence in clinical HCC samples. Multivariate analysis revealed that Sec62 was an independent prognostic factor for early recurrence in postoperative HCC patients. Moreover, Sec62 promoted migration and invasion of HCC cells in vitro and postsurgical recurrence in vivo. Mechanically, integrinα/CAV1 signalling was identified as one of the targets of Sec62 in cell movement. Overexpression of integrin α partially rescued the Sec62 knockdown-induced inhibition of cell migration. Sec62 is a potentially prognostic factor for early recurrence in postoperative HCC patients and promotes HCC metastasis through integrinα/CAV1 signalling. Sec62 might be an attractive drug target for combating HCC postsurgical recurrence.

Cell adhesion molecules (CAM) expressed by vascular endothelium in response to cytokine stimulation play a key role in leukocyte adhesion to endothelium during the inflammatory response. Tripterine, a chemical compound of the Chinese plant Tripterygium wilfordii Hook f, displays anti-inflammatory properties in several animal models. However, mechanisms of its action are poorly understood. In the present study, we show that in inflammatory conditions, mimicked by tumor necrosis factor alpha (TNF-alpha) stimulation, pretreatment for 6 h with tripterine at nontoxic concentrations of 20-200 nM inhibits the expression of E-selectin, vascular cell adhesion molecule (CAM)-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner. Tripterine (200 nM) almost completely inhibits expression of VCAM-1 [50% inhibitory concentration (IC50) = 52 nM] and ICAM-1 (IC50 = 51 nM) and 73% of E-selectin (IC50 = 94 nM). This inhibition effect is prominent, compared with that of dexamethasone, ibuprofen, methotrexate, or probucol, which revealed a much weaker inhibition at doses as high as 1 mM. Effects on endothelial CAM of other proinflammatory cytokines, such as interleukin-1beta and interferon-gamma, were also inhibited significantly by tripterine. Moreover, significant inhibition was equally observable in postincubation experiments. In addition, tripterine inhibited adhesion of human monocytes and T lymphocytes to TNF-alpha-stimulated HUVEC. Finally, tripterine inhibited TNF-alpha-driven CAM mRNA transcription and nuclear factor-kappaB nuclear (NF-kappaB) translocation. Hence, we describe a new mechanism of tripterine's anti-inflammatory action obtained at nanomolar concentrations, owing to the negative regulation of cytokine-induced adhesion molecule expression and adhesiveness in human endothelium.