Expression of Serum Cytokines Profile in Neonatal Sepsis.

Objective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection. Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System. Results: Our results showed that serum IL-6, IL-8, TNF-α, IL-1ß, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p<0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (all p<0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p<0.05). Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.

A novel humanized MUC1 antibody-drug conjugate for the treatment of trastuzumab-resistant breast cancer.

Mucin 1 (MUC1) has been regarded as an ideal target for cancer treatment, since it is overexpressed in a variety of different cancers including the majority of breast cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1. In this study, we generated a humanized MUC1 (HzMUC1) antibody from our previously developed MUC1 mouse monoclonal antibody that only recognizes MUC1 on the surface of tumor cells. Furthermore, an antibody-drug conjugate (ADC) was generated by conjugating HzMUC1 with monomethyl auristatin (MMAE), and the efficacy of HzMUC1-MMAE on the MUC1-positive HER2+ breast cancer in vitro and in 'Xenograft' model was tested. Results from western blot analysis and immunoprecipitation revealed that the HzMUC1 antibody did not recognize cell-free MUC1-N in sera from breast cancer patients. Confocal microscopy analysis showed that HzMUC1 antibody bound to MUC1 on the surface of breast cancer cells. Results from mapping experiments suggested that HzMUC1 may recognize an epitope present in the interaction region between MUC1-N and MUC1-C. Results from colony formation assay and flow cytometry demonstrated that HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in trastuzumab-resistant HER2-positive breast cancer cells. Meanwhile, HzMUC1-MMAE significantly reduced the growth of HCC1954 xenograft tumors by inhibiting cell proliferation and enhancing cell death. In conclusion, our results indicate that HzMUC1-ADC is a novel therapeutic drug that can overcome trastuzumab resistance of breast cancer. HzMUC1-ADC should also be an effective therapeutic drug for the treatment of different MUC1-positive cancers in clinic.

Associations of sirtuins with clinicopathological parameters and prognosis in non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide and it is critical to discover specific biomarkers to provide better individualized treatment and subsequently better prognosis. The sirtuins (SIRT1-7) have been reported to be involved in cancers including non-small cell lung cancer (NCSLC), however, the results are not consistent and not all the seven sirtuins are explored and compared. METHODS: TCGA data was downloaded and used to investigate and compare the associations of sirtuins mRNA levels with clinicopathological parameters and prognosis in NSCLC. RESULTS: Our results suggested SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adeno-carcinoma (ADC) patients and female patients while SIRT5 were highly expressed in squamous cell carcinoma (SCC) patients and male patients. Associations of high SIRT7 with younger onset age, high SIRT1 with distant metastasis and low T stage, and high SIRT4 with high T stage and TNM stage were also found. Kaplan-Meier plot curves and univariate Cox proportional regression analyses indicated that high SIRT2, SIRT4, and SIRT6 expressions were associated with longer overall survival (OS) time. Multivariate analyses indicated that SIRT2 and SIRT6 were still associated with OS. For recurrence-free survival (RFS), high SIRT1 expression was significantly associated with shorter RFS time while high SIRT2-3 and SIRT5-7 expressions were associated with longer RFS time in univariate analyses. After adjusting the confounding factors, significant associations were still found in SIRT1-2 and SIRT5-7 but not in SIRT3. We also stratified the patients by combining SIRT1 and SIRT2 and revealed that the combination of SIRT1 and SIRT2 was a better prediction model for RFS in NSCLC. To preliminarily understand the potential mechanisms of sirtuins in NSCLC carcinogenesis, the genes co-expressed with sirtuins were analyzed and annotated. CONCLUSION: sirtuins might be the potential therapy targets and prognostic biomarkers in NSCLC.

Identification of Long Non-Coding RNAs for Predicting Prognosis Among Patients with Thymoma.

BACKGROUND: Thymoma is the most common primary anterior mediastinal neoplasm with a high recurrence rate. Long noncoding RNAs (lncRNAs) have recently been indicated to be used as diagnostic and prognostic indicators for different cancers. The aim of this study was to identify new tumor-specific prognostic lncRNA markers that can improve the treatment and follow-up of patients with thymomas. METHODS: One hundred seventeen thymoma patients with clinical information and level 3 RNAseqv2 data were downloaded from The Cancer Genome Atlas. Prognostic lncRNAs were identified using Kaplan-Meier survival analyses and univariate Cox proportional hazards regression analyses. A predictive risk scoring model was subsequently created using independently significant lncRNAs from a multivariate Cox regression analysis. RESULTS: Masaoka stage and 13 lncRNAs were significantly associated with RFS among 117 thymoma patients, while 59 lncRNAs were significantly associated with OS (all p < 0.05). Multivariate analyses revealed that OS was only independently associated with one lncRNA (JPX) and that RFS was only independently associated with three lncRNAs (AFAP1-AS1, LINC00324, and VLDLR-AS1). A risk score model constructed by the three lncRNA expressions showed that the high-risk group was more likely to experience recurrence. CONCLUSIONS: The expression profile for three lncRNAs (AFAP1-AS1, LINC00324, and VLDLR-AS1) could be used to independently predict RFS among thymoma patients, which may be as prognostic biomarkers for thymoma.

Vitamin D status among infants, children, and adolescents in southeastern China.

OBJECTIVE: Vitamin D deficiency and insufficiency are global public health problems, which must first be identified before they can be appropriately addressed, and yet information is strikingly lacking in most parts of the Asia and Pacific region. The study aimed to document and account for the actual situation in Wenzhou on the southeastern coast of China. SUBJECTS AND METHODS: Serum 25-hydroxyvitamin D levels among a total of 5845 infants, preschool children, school children, and adolescents aged 1-18 years were examined between March 2014 and February 2015. RESULTS: Their mean levels were (110.2±26.8), (77.5±25.7), (55.6±15.4), and (47.2±13.9) nmol/L, respectively. Older age groups were involved in increasing risk of vitamin D deficiency and insufficiency. There were significant seasonal differences in its median level and prevalence of deficiency and insufficiency among school children and adolescents, but there was no significant sex difference in mean level and prevalence in any age group. CONCLUSIONS: Vitamin D deficiency and insufficiency were prevalent among infants, preschool children, school children, and adolescents in Wenzhou. A vitamin D-rich diet and outdoor activities for 1-2 h per day under the natural conditions favorable to its endogeous synthesis do not suffice. The vitamin D status in Wenzhounese infants excelling over that in the US was the result of its supplementation thanks to the Chinese Medical Association recommendations, which should be consequently extended to more age groups. Life style shaped by socio-economic environments affects vitamin D status. Knowledge on the importance of vitamin D for healthy growth should be popularized.

Relationship between HOMA-IR and serum vitamin D in Chinese children and adolescents.

BACKGROUND: The objective of this study was to examine the cross-sectional relationship between homeostasis model assessment for insulin resistance (HOMA-IR) and serum 25-hydroxyvitamin D (25-OHD) level in Chinese children and adolescents. METHODS: Anthropometric indices, lipid metabolic profile, and serum levels of glucose, insulin and 25-OHD were determined among 278 healthy prepubertal and pubertal, normal and overweight/obese children and adolescents aged 8-18 years between March 2014 and February 2015. RESULTS: HOMA-IR was significantly different across vitamin D statuses (p<0.001), even after adjusting for body mass index (BMI) (p=0.035) and waist-to-height ratio (p=0.044); the difference was not significant between the vitamin D deficient and insufficient groups (p=0.120). HOMA-IR negatively correlated with serum 25-OHD level for all subjects (R2=0.148, p<0.001). Furthermore, they negatively correlated in the normal (R2=0.160, p<0.001) and overweight/obese (R2=0.086, p<0.001) groups, respectively. The regression lines of the two groups were parallel (p=0.669) but had a significantly different intercept (p<0.001). An association between HOMA-IR and BMI and serum 25-OHD level (R2=0.654, p<0.001) was demonstrated based on the stepwise multiple linear regression analysis of age, sex, pubertal maturation, BMI, waist-to-height ratio, triglyceride, cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), 25-OHD and HOMA-IR. CONCLUSIONS: Our findings supported that lower vitamin D status is strongly associated with worse HOMA-IR.

[Relationship between hepatitis B virus DNA and hepatitis B virus large envelope protein].

OBJECTIVE: To investigate the relationship between HBV DNA and hepatitis B virus large envelope protein (HBV-LP) in patients with chronic hepatitis B. METHODS: Serum HBV DNA was detected by RT-PCR and the HBV-LP was detected by enzyme linked immunosorbent assay in 320 serum samples collected from patients with chronic hepatitis B. RESULTS: There were no significant difference between positive rate of HBV-LP and that of HBV DNA in different HBeAg patterns (P>0.05). Serum HBV-LP levels were closely correlated with HBV DNA copies (r=0.949). CONCLUSION: Serum HBV-LP is a reliable serological marker that can reflect the replication of HBV.