The incidence of carpal tunnel syndrome in the population of Rochester, Minnesota, from 1961 through 1980 was determined by use of the medical records-linkage system of the Rochester Epidemiology Program Project at the Mayo Clinic; 1,016 patients (1,600 affected hands) were identified. Incidence (cases per 100,000 person-years) was 99 (crude) overall, whereas the age-adjusted rates were 52 for the men, 149 for the women, and 105 for both sexes combined. Age-adjusted incidence rates increased from 88 during the 1961 to 1965 quinquennium to 125 during the 1976 to 1980 quinquennium; these rates probably reflect better recognition rather than a true increase in incidence rates. Age-specific rates generally increased with age in men, whereas in women a peak was reached in the 45 to 54 age group.

Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XFe24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP+ ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.

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Emergency cesarean sections showed significantly more maternal and fetal complications and mortality than elective cesarean sections in this study. Certain plans should be worked out by obstetric practitioners to avoid the post-operative complications.

PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA () was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy. We first analyzed the STAT3/HOTAIR and PI3K/AKT level in human HNSCC samples. We then activated or suppressed STAT3/HOTAIR and determined the effects on HNSCC cell proliferation and the growth of UM1 xenograft tumor, an orthotopic model of HNSCC. The sensitivity of HNSCC cells toward cisplatin and cetuximab was determined by assays. HNSCC samples showed significantly robust expression/activation of STAT3, HOTAIR, PI3K, and AKT, compared with normal squamous epithelium. STAT3 inhibition with WP1066 decreased HOTAIR level and sensitized HNSCC to cisplatin or cetuximab. STAT3 promoted HOTAIR transcription and its interaction with pEZH2-S21, resulting in enhanced growth of HNSCC cells. In addition, overexpression of HOTAIR promoted the growth of UM1 xenograft tumors Our results suggest that STAT3 signaling promotes HNSCC progression via regulating HOTAIR and pEZH2-S21 in HNSCC with PI3K overexpression/activation. These findings provide a rationale to target the STAT3/HOTAIR/pEZH2-S21 regulatory axis for treating patients with HNSCC..

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BackgroundZinc-finger E-box binding homeobox 1 (ZEB-1), a member of the ZFH family, plays a key role in epithelial–mesenchymal transition during tumor progression in various cancers. However, little information is available on ZEB-1 expression in oral cavity squamous cell carcinoma (OSCC).MethodsThe expression levels of ZEB-1 and E-cadherin were assessed by immunohistochemistry in a cohort of 120 patients with OSCC treated by curative operation, and then the correlations between ZEB-1 and E-cadherin expression and clinical factors were evaluated, including patient prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to assess mRNA levels of ZEB-1 and E-cadherin in 20 matched OSCC specimens.ResultsPatients were followed up for a median period of 66 months (range 8−116 months), and 5-year overall survival was 68.3%. Positive ZEB-1 and E-cadherin immunostaining reactivity was detected in 64 (53.3%) and 53 (44.2%) patients, respectively. There was a negative correlation between ZEB-1 expression and E-cadherin expression. In addition, overexpression of ZEB-1 was significantly associated with recurrence, lymph node metastasis, and pathologic grading of patients, loss of E-cadherin was significantly associated with lymph node metastasis and pathologic grading of patients. Univariate analysis showed that increased ZEB-1 expression, loss of E-cadherin expression, lymph node metastasis, recurrence, and pathology grade were prognostic factors. In multivariate analysis, increased ZEB-1 expression and recurrence remained independent prognostic factors. In particular, patients with both ZEB-1 positivity and loss of E-cadherin expression had a poorer prognosis. qRT-PCR showed that ZEB-1 mRNA expression was higher in OSCC compared to the adjacent nontumorous tissues, while E-cadherin mRNA expression was lower in tumor tissues.ConclusionThis study shows that overexpression of ZEB-1 and loss of E-cadherin expression are significantly correlated with poor survival in OSCC patients, and ZEB-1 expression might serve as an independent prognostic biomarker of OSCC.

BackgroundNeutrophils-linked premetastatic niche plays a key role in tumor metastasis, but not much is known about the heterogeneity and diverse role of neutrophils in niche formation. Our study focuses on the existence and biological function of a rarely delved subset of neutrophils, named as tumor-associated aged neutrophils (Naged, CXCR4+CD62Llow), involved in premetastatic niche formation during breast cancer metastasis.MethodsWe explored the distributions of Naged in 206 patients and mice models (4T1 and MMTV-PyMT) by flow cytometry. The ability of Naged to form neutrophil extracellular traps (NETs) and promote tumor metastasis in patients and mice was determined by polychromatic immunohistochemistry, scanning electron microscopy and real-time video detection. Furthermore, the differences among tumor-associated Naged, Non-Naged and inflammation-associated aged neutrophils were compared by transcriptome, the biological characteristics of Naged were comprehensively analyzed from the perspectives of morphology, the metabolic capacity and mitochondrial function were investigated by Seahorse, co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) and transmission electron microscopy (TEM). Finally, 120 patients’ sample were applied to confirm the acceleration of Naged formation through secreted NAMPT, and the importance of blocking this pathway in mice was evaluated.ResultsWe find that Naged accumulate in the lung premetastatic niche at early stage of breast tumorigenesis in multiple mice models and also exist in peripheral blood and metastatic lung of patients with breast cancer. Naged exhibit distinct cell marker and morphological feature of oversegmented nuclei. Further transcriptome reveals that Naged are completely different from those of Non-Aged or inflammation-associated aged neutrophils and illustrates that the key transcription factor SIRT1 in Naged is the core to maintain their lifespan via mitophagy for their function. The responsible mechanism is that SIRT1 can induce the opening of mitochondrial permeability transition pore channels to release mitochondrial DNA and lead to the mitochondria-dependent vital NETs formation, rather than traditional Cit-Histone H3 dependent fatal-NETs. Further mechanically investigation found tumor derived NAMPT could induce Naged formation. Additionally, therapeutic interventions of Naged and its formation-linked pathways could effectively decrease breast cancer lung metastasis.ConclusionsNaged exerts a vital role in breast cancer lung metastasis, and strategies targeting SIRT1-Naged-NETs axis show promise for translational application.