Fatigue is one of the most common and distressing symptoms, leading to markedly decreased quality of life among a large subset of patients with a variety of disorders. Susceptibility to fatigue may be influenced by genetic factors including single nucleotide polymorphisms (SNPs), especially in the regulatory regions, of relevant genes. To further investigate the association of SNPs with fatigue in various patient populations, a systematic search was conducted on Pubmed, CINAHL, PsycINFO, and Sociological Abstracts Database for fatigue related-terms in combination with polymorphisms or genetic variation-related terms. Fifty papers in total met the inclusion and exclusion criteria for this analysis. These 50 papers were further classified into three subgroups for evaluation: chronic fatigue syndrome (CFS), cancer-related fatigue (CRF) and other disease-related fatigue. SNPs in regulatory pathways of immune and neurotransmitter systems were found to play important roles in the etiologies of CFS, CRF and other disease-related fatigue. Evidence for associations between elevated fatigue and specific polymorphisms in TNFα, IL1b, IL4 and IL6 genes was revealed for all three subgroups of fatigue. We also found CFS shared a series of polymorphisms in HLA, IFN-γ, 5-HT and NR3C1 genes with other disease-related fatigue, however these SNPs (excluding IFN-γ) were not found to be adequately investigated in CRF. Gaps in knowledge related to fatigue etiology and recommendations for future research are further discussed.

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Astragalin, as a bioactive flavonoid with anti-inflammatory, antioxidant, and protective properties, provides a potential agent for rheumatoid arthritis (RA). In this study, its therapeutic efficacy and the underlying mechanisms were explored using DBA/1J mice with collagen-induced arthritis (CIA). It was demonstrated that astragalin could significantly attenuate inflammation of CIA mice. The effects were associated with decreased severity of arthritis (based on the arthritis index), joint swelling and reduced bone erosion and destruction. Furthermore, astragalin treatment suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), and inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) in chondrocytes and synovial cells of CIA mice. Fibroblast-like synoviocytes derived from RA patients (MH7A cells) were applied to verify these effects. In vitro , astragalin inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) dose-dependently in TNF-α-induced MH7A cells, with no apparent cytotoxicity. Furthermore, astragalin suppressed the phosphorylation of p38, JNK, and the activation of c-Jun/AP-1 in TNF-α-induced MH7A cells. In conclusion, it has proven that astragalin could attenuate synovial inflammation and joint destruction in RA at least partially by restraining the phosphorylation of MAPKs and the activating of c-Jun/AP-1. Therefore, astragalin can be a potential therapeutic agent for RA.

P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the link of their activity to the extrinsic apoptosis pathway and showed that their autophagy modification has a critical stand point in tumorigenesis. These findings explain their vital role in controlling the process of cell death and survival. It has been shown recently that p62 and ubiquitin overexpression in different types of cancers, such as triple negative breast and ovarian cancers, have directly correlated with incidence of distant metastases. We aim to evaluate p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic, and pancreatic origin, and correlate with annotated clinicopathologic data. In gastric carcinoma (61), positive p62 nuclear expression was noted in 57% and cytoplasmic in 61%, while positive ubiquitin was nuclear expressed in 68.8%, and cytoplasmic in 29.5%. In colon carcinoma (45), positive p62 nuclear expression was noted in 29% and cytoplasmic in 71%, while positive ubiquitin was nuclear in 58% and cytoplasmic in 44%. In pancreatic cancer (18), positive p62 nuclear expression was noted in 78% and cytoplasmic in 56%, while positive ubiquitin was nuclear in 83% and cytoplasmic in 72%. Normal gastric (6), colon (4), and pancreatic (4) tissues were negative for both P62 and ubiquitin (nuclear and cytoplasmic staining <20%). Ubiquitin high expression was associated with more lymph node metastases in colon (4.14 vs 1.70, P = 0.04), and pancreatic adenocarcinomas (3.07 vs 0.33, P = 0.03). Also, ubiquitin high expression was associated with worse pancreatic adenocarcinoma overall survival (1.37 vs 2.26 mos, P = 0.04). In addition, gastric cancer patients with high p62 expression tend to have more poorly differentiated grade when compared to those with low expression (21 vs 17, P = 0.04) but less lymph node metastases (2.77 vs 5.73, P = 0.01). P62 and ubiquitin expression did not correlate with other clinicopathologic parameters in gastric, colon or pancreatic denocarcinomas. The results suggest that p62 and ubiquitin are highly expressed in gastric, colonic, and pancreatic carcinomas. High ubiquitin expression was noted to have an impact on number of lymph node metastases in patients with colon and pancreatic adenocarcinomas, but on overall survival only in patients with pancreatic adenocarcinoma. Also, P62 high expression is correlated with poor differentiation, but less lymph node metastases, in gastric carcinoma.

Background and Aim Baidu, currently the top online search tool in China, has developed an internet search trends gathering and analysis tool called the Baidu Index. The aim of this study was to explore the value of the Baidu Index for monitoring online kidney stones-related information-seeking behavior and understanding of population features and priorities in China. Materials and Methods The Baidu Index was queried using the term “kidney stones” for the period 2014–2018. The search volume was recorded as well as a demand graph, with a geographic and demographic distribution. For surgical treatment modalities, the medical term “extracorporeal shock wave lithotripsy (ESWL)” was analyzed and then compared to the term “kidney stone surgery” to assess changes. Results The search trend for the term “kidney stones” remained sustained growth over time. Searches were mostly presented by the age 20–49, in males in the south of China. The demand graph indicated that the diagnosis, followed by the treatment, and dietary control of kidney stones had received the most attention. The search volume related to ESWL showed a similar increasing trend, but was searched with a greater volume than the term “kidney stone surgery” for most of the last 5 years. Conclusion The Baidu Index is a useful tool to track online health information-seeking behavior of internet users in China. The geographic and demographic characteristics in kidney stones seem to be reflected in online search trend data to some extent.

Associations of individual base excision repair (BER) genotypes with colorectal adenoma risk are unclear, but likely modest. However, genetic risk scores (GRS) that aggregate information from multiple genetic variants might be useful for assessing genetic predisposition to colorectal adenoma. We analyzed data pooled from three colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 488 cases, 604 controls) that collected blood for genotyping and extensive dietary and other data. We randomly split our population sample into training samples (half of the participants) and validation samples (the remaining participants) 10 times. Associations of 65 individual single nucleotide polymorphisms (SNPs) in 15 BER genes were assessed in the training samples and used to combine information from multiple risk variants into a BER GRS among the validation samples using unweighted and weighted methods. We also combined 15 extrinsic exposures with known pro- or antioxidant properties into an oxidative balance score (OBS). Associations of the BER GRS with colorectal adenoma, overall and jointly with the OBS, were assessed using multivariable logistic regression. The odds ratio for those in the highest relative to the lowest tertile of the weighted BER GRS was 2.07 (95% confidence interval, 1.26-3.40; p = 0.01). Relative to those with both a low GRS and a high (more antioxidant) OBS, the estimated direct association for those with both a high BER GRS and a low OBS was stronger than for those in other GRS/OBS categories. Our findings suggest that BER genotypes collectively may be associated with incident sporadic colorectal adenomas.

Type II diabetes is associated with poor breast cancer prognosis. To study the association between a diabetes risk reduction diet (DRRD) and survival following breast cancer, we followed 8,482 women with breast cancer from two large cohort studies. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. The DRRD includes 9 components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated/saturated fat ratio; and lower glycemic index, trans fat, sugar-sweetened beverages, and red meat. Cumulative average DRRD score was calculated using repeated measures of postdiagnostic diet. Deaths were assessed by family members or via National Death Index. Multivariable-adjusted HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. During a median of 14 years of follow-up since diagnosis, 2,600 deaths occurred among participants, 1,042 of which were due to breast cancer. Women with higher postdiagnostic DRRD score had a 20% lower risk of breast cancer–specific mortality (top vs. bottom quintile HR = 0.80; 95% CI = 0.65–0.97; Ptrend = 0.02) and 34% lower risk of all-cause mortality (HR = 0.66; 95% CI = 0.58–0.76; Ptrend &lt; 0.0001). Compared with women who consistently had lower score (≤median) before and after diagnosis, those whose score improved from low to high had a lower risk of breast cancer–specific mortality (HR = 0.77; 95% CI = 0.62–0.95) and overall mortality (HR = 0.85; 95% CI = 0.74–0.97). These findings demonstrate that greater adherence to DRRD was associated with better survival, suggesting postdiagnosis dietary modification consistent with type II diabetes prevention may be important for breast cancer survivors. Significance: This study suggests that greater adherence to the diabetes risk reduction diet after diagnosis associates with improved survival outcomes among a large number of breast cancer survivors.

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