IntroductionSystemic sclerosis (SSc) (scleroderma) is a complex autoimmune disease that clinically manifests as progressive fibrosis of the skin and internal organs. Anti-centromere antibodies (ACAs), anti-topoisomerase antibodies (ATAs), and anti-RNA polymerase III antibodies (ARAs) are three mutually exclusive SSc-associated autoantibodies that correlate with distinct clinical subsets characterized by extent of cutaneous involvement and pattern of organ involvement. The current report sought to determine whether plasma cytokine profiles differ in SSc patients grouped according to these SSc-associated autoantibody subsets.MethodsPlasma from 444 SSc patients and 216 healthy controls was obtained from the Scleroderma Family Registry and University of Texas Rheumatology Division. Patients were classified according to the presence of ACAs, ATAs, ARAs, or none of the above (antibody-negative). Levels of 13 cytokines were determined using multiplex assays.ResultsCompared with females, healthy control males had higher plasma levels of IL-2 (P = 0.008), IL-5 (P = 0.01) and IL-8 (P = 0.01). In addition, in controls, IL-6 (P = 0.02) and IL-17 (P = 0.01) levels increased with advancing age. After adjusting for age and gender, SSc patients had higher circulating levels of TNFα (P < 0.0001), IL-6 (P < 0.0001), and IFNγ (P = 0.05) and lower IL-17 (P = 0.0005) and IL-23 (P = 0.014). Additional analyses demonstrated that disease duration also influenced these cytokine profiles. IL-6 was elevated in ATA-positive and ARA-positive patients, but not in ACA-positive patients. IL-8 was uniquely increased in the ATA-positive subset while both ATA-positive and ACA-positive subsets had elevated IFNγ and IL-10. IL-5 was only significantly increased in the ACA-positive subset. Lastly, patients with interstitial lung disease had elevated IL-6 and patients with pulmonary hypertension had elevated IL-6 and IL-13.ConclusionsPlasma cytokine profiles differ in SSc patients based on the presence of SSc-associated autoantibodies. Plasma cytokine profiles in SSc patients may also be affected by disease duration and the pattern of internal organ involvement.

No abstract

No abstract

Oral squamous cell carcinoma (OSCC) is predominantly a disease of middle-aged men with long-term exposure to tobacco and alcohol. An increasing trend has been reported at a younger age worldwide. Clinical records of 100 patients under the age of 45 years treated specifically for oral cavity SCC in our hospital during a 10-year period were retrospectively analyzed to calculate the survival rates. An obvious male predominance coincided with smoking trend among Chinese young individuals and female patients were more likely to have no traditional risk factors such as smoking or drinking. The 5-year overall survival rate and disease-free survival rate were 61.0% and 75.5%, respectively, consistent with other published series over the decade showing a relatively better survival among the young. No significant differences clearly correlated with outcome when comparing non-smokers non-drinkers to ever-smokers and ever drinkers (P>0.05). Overall survival rate and disease free survival rate was found to be significantly higher in patients with early-stage disease than with advanced stage disease (P=0.001, P=0.009 respectively). The strong influence of clinical stage on prognosis emphasizes the importance of early diagnosis and treatment of oral malignancies for this unique clinical subgroup.

Background Cohort studies have shown that neoadjuvant chemotherapy (NAC) is not associated with increased risk of postoperative complications and mortality as compared to upfront surgery (SURG). Objective The aim of this study was to compare postoperative morbidity and mortality after NAC with SURG. Patients and methods Patients who underwent gastrectomy with D2 lymphadenectomy for advanced gastric cancer (GC) between 2010 and 2017 were selected. The impact of neoadjuvant chemotherapy on surgical safety was investigated by using propensity score matching. Results Three hundred and seventy-seven patients were included. After propensity score matching, 86 patients in each group were matched. The percentage of patients with one or more complications was 10.5% in NAC group and 15.1% in SURG group ( P =0.361), there was no mortality developed in either group. The total blood loss was significantly more in the NAC group than that in the SURG group (320.79 vs 243.37 ml, P <0.04). In univariate and multivariate of the matched cohort, sex, age (<70), BMI (<24), ASA grade, surgical procedure (open vs laparoscopy), gastrectomy extent, cTNM and Charlson index comorbidity were not associated with postoperative complications (all P >0.05). Conclusion This study showed that postoperative morbidity and mortality were similar for NAC group and SURG group.

Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases.

K E Y W O R D S:

The link between lipoprotein metabolism and Alzheimer's disease (AD) has been established. Apolipoprotein A-IV (apoA-IV), a component of lipoprotein particles similar to apolipoprotein E, has been suggested to play an important role in brain metabolism. Although there are clinical debates on the function of its polymorphism in AD, the pathologic role of apoA-IV in AD is still unknown. Here, we report that genetic ablation of apoA-IV is able to accelerate AD pathogenesis in mice. In a mouse model that overexpresses human amyloid precursor protein (APP) and presenilin 1, genetic reduction of apoA-IV augments extracellular amyloid-β peptide (Aβ) burden and aggravates neuron loss in the brain. In addition, genetic ablation of apoA-IV also accelerates spatial learning deficits and increases the mortality of mice. We have found that apoA-IV colocalizes within Aβ plaques in APP/presenilin 1 transgenic mice and binds to Aβ in vitro. Subsequent studies show that apoA-IV in this model facilitates Aβ uptake in the Aβ clearance pathway mediated by astrocytes rather than the amyloidogenic pathway of APP processing. Taken together, we conclude that apoA-IV deficiency increases Aβ deposition and results in cognitive damage in the mouse model. Enhancing levels of apoA-IV may have therapeutic potential in AD treatment.