Clinical Diagnostic Value of circ-ARHGER28 for Breast Cancer and its Effect on MCF 7 Cell Proliferation and Apoptosis.

BACKGROUND/AIM: Clinical diagnostic value of circ-ARHGER28 in breast cancer (BC), and the biological functions of circ-ARHGER28 on the proliferation and apoptosis of MCF-7 cells were investigated. MATERIALS AND METHODS: Human circRNA microarray was performed to analyze the expression of circRNAs in BC patients. RT-qPCR combined with bioinformatics analysis was applied to verify the candidate circRNAs in BC tissues and peripheral blood samples. Circ-ARHGER28 was chosen as the candidate gene for further research. The clinical diagnostic value and biological functions of circ-ARHGER28 were analyzed. The overexpression and negative control vector of circ-ARHGER28 were constructed and transfected to MCF-7 cells. The CCK 8 assay and clone formation experiments were applied to detect the cell proliferative and migratory abilities. Flow cytometry was used to analyze cell apoptosis and cell cycle distribution. RT-qPCR and Western blot were performed to detect apoptosis and expression of PI3K/AKT/mTOR-associated genes and proteins. RESULTS: Overexpression of circ-ARHGER28 inhibited the proliferation, colony formation and migration of MCF-7 cells, while increasing the population of the cells in the G2/M phase and the apoptotic rate. Apoptosis associated genes and proteins were significantly increased, whereas gene and protein expression of PI3K, AKT and mTOR were decreased in the cells. CONCLUSION: Circular RNA ARHGER28 exhibits promising diagnostic value for BC. Circ-ARHGER28 inhibited MCF-7 cell proliferation and increased the apoptotic rate. The function of circ-ARHGER28 was associated with the PI3K/AKT/mTOR signaling pathway. Circ-ARHGER28 could be an ideal biomarker for BC diagnosis and a novel target for BC therapy.

Postmastectomy Intensity Modulated Proton Therapy: 5-Year Oncologic and Patient-Reported Outcomes.

PURPOSE: To report oncologic, physician-assessed, and patient-reported outcomes (PROs) for a group of women homogeneously treated with modern, skin-sparing multifield optimized pencil-beam scanning proton (intensity modulated proton therapy [IMPT]) postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: We reviewed consecutive patients who received unilateral, curative-intent, conventionally fractionated IMPT PMRT between 2015 and 2019. Strict constraints were applied to limit the dose to the skin and other organs at risk. Five-year oncologic outcomes were analyzed. Patient-reported outcomes were evaluated as part of a prospective registry at baseline, completion of PMRT, and 3 and 12 months after PMRT. RESULTS: A total of 127 patients were included. One hundred nine (86%) received chemotherapy, among whom 82 (65%) received neoadjuvant chemotherapy. The median follow-up was 4.1 years. Five-year locoregional control was 98.4% (95% CI, 93.6-99.6), and overall survival was 87.9% (95% CI, 78.7-96.5). Acute grade 2 and 3 dermatitis was seen in 45% and 4% of patients, respectively. Three patients (2%) experienced acute grade 3 infection, all of whom had breast reconstruction. Three late grade 3 adverse events occurred: morphea (n = 1), infection (n = 1), and seroma (n = 1). There were no cardiac or pulmonary adverse events. Among the 73 patients at risk for PMRT-associated reconstruction complications, 7 (10%) experienced reconstruction failure. Ninety-five patients (75%) enrolled in the prospective PRO registry. The only metrics to increase by >1 point were skin color (mean change: 5) and itchiness (2) at treatment completion and tightness/pulling/stretching (2) and skin color (2) at 12 months. There was no significant change in the following PROs: bleeding/leaking fluid, blistering, telangiectasia, lifting, arm extension, or bending/straightening the arm. CONCLUSIONS: With strict dose constraints to skin and organs at risk, postmastectomy IMPT was associated with excellent oncologic outcomes and PROs. Rates of skin, chest wall, and reconstruction complications compared favorably to previous proton and photon series. Postmastectomy IMPT warrants further investigation in a multi-institutional setting with careful attention to planning techniques.

Akkermansia muciniphila ameliorates depressive disorders in a murine alcohol-LPS (mALPS) model.

Depression is the most common mental disorder in the world. Recently, an increasing number of studies have reported alcohol-related depression. However, there is no simple, efficient, and time-saving alcohol-related depression animal model yet. Based on the fact that people with alcohol addiction often have impaired gastrointestinal (GI) tract health like dysbiosis, which serves as a primary factor to augment lipopolysaccharides (LPS), we first developed a murine alcohol-LPS model (mALPS), with oral gavage of LPS in acute alcohol treated mice, and successfully observed depression-like symptoms. We found that acute alcohol treatment damaged the intestinal barrier and caused dysbiosis, which further increased the translocation of LPS and neuroinflammatory responses (TNF-α and IL-1ß) and led to abnormal expression of the depression-related genes, i.e. BDND and IDO, reduced the levels of 5-HT and caused depressive behaviors in mice. Probiotic intervention could improve depressive symptoms without notable adverse effects. Akkermansia muciniphila (AKK), one of the next-generation probiotics, has been widely used for the restoration of the intestinal barrier and reduction of inflammation. Here, we found that AKK significantly ameliorated alcohol-related depressive behaviors in a mALPS model, through enhancing the intestinal barrier and maintaining the homeostasis of the gut microbiota. Furthermore, AKK reduced serum LPS, ameliorated neuroinflammation (TNF-α and IL-1ß), normalized the expression of depression-related genes and increased the 5-HT levels in the hippocampus. Our study suggests that AKK supplements will be a promising therapeutic regime for alcohol-associated depression in the future.

Effect of electroacupuncture on inflammatory signal expression in local tissues of rats with chronic pelvic pain syndrome based on purinergic 2X7 receptor/NOD-like receptor pyrin domain-containing 3 signal pathway.

OBJECTIVES: To study the expression of inflammatory signal in local prostate tissue of chronic pelvic pain syndrome (CPPS) rats by electroacupuncture (EA) of Guanyuan (CV4), Zhongji (CV3), Huiyang (BL35) and Sanyinjiao (SP6), and to explore the possible mechanism of anti-inflammatory and analgesic effects of EA. METHODS：A total of 36 Sprague-Dawley male rats were randomly divided into three groups: control, model and EA (n=12 rats/group). The CPPS model was made by injection of CFA into ventral lobes of the prostate (0.1 mL). Electric acupuncture apparatus was applied to stimulate Guanyuan (CV4), Zhongji (CV3), bilateral Huiyang (BL35) and Sanyinjiao (SP6) acupoints in EA group. The general condition of rats was observed and the prostate index (PI) was calculated. The thermal pain threshold was collected after each therapeutic course. Histopathological changes of the prostate tissue were examined by hematoxylin-eosin staining method. The expression levels of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and prostaglandin E2 (PGE2) in prostatic homogenates were measured by enzyme linked immunosorbent assay (ELISA). Moreover, the expression levels of purinergic 2X7 receptor (P2X7R), NOD-like receptor pyrin domain-containing 3 (NLRP3), caspase-1 and interleukin-18 (IL-18) mRNA were quantified by quantitative real-time polymerase chain reaction. RESULTS: Compared with control group, the PI of rats increased, and the thermal pain threshold decreased significantly in model group. The morphological structure of prostate tissues of rats in model group was severely damaged with a large number of inflammatory cells infiltration. Additionally, the levels of TNF-α, IL-1ß and PGE2 were higher, and the expressions of P2X7R, NLRP3, caspase-1 and IL-18 mRNA were higher than those in control group. After EA treatment, the PI was significantly decreased, the thermal pain threshold was significantly increased, and the tissue damage was significantly improved. The expressions of inflammatory cytokines were lower in EA group, and expression of P2X7R/NLRP3 pathway was down-regulated. CONCLUSION: The effect of EA at Guanyuan (CV4), Zhongji (CV3), Huiyang (BL35) and Sanyinjiao (SP6) can improve inflammation and pain symptoms of CPPS rats induced by Complete Freund's adjuvant (CFA). This suggests that EA at Guanyuan (CV4), Zhongji (CV3), Huiyang (BL35) and Sanyinjiao (SP6) can produce anti-inflammatory analgesia effect by preventing the activation of P2X7R/NLRP3 signal pathway, inhibit the release of inflammatory cytokines in CPPS rats, which may provide a putative novel target for the treatment of CPPS.

Proton therapy for the treatment of inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) poses a radiotherapeutic challenge due to dermal lymphatic involvement, which often necessitates larger target volumes and chest wall boosts, making advanced planning techniques attractive to reduce exposure to nearby organs. We report our experience with intensity modulated proton therapy (IMPT) for the treatment of IBC. METHODS: Between 2016 and 2020, all IBC patients treated with adjuvant IMPT at our institution were identified. Overall survival (OS) and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were assessed using CTCAE version 5.0. RESULTS: Nineteen patients were identified with median 24-month follow-up. CTVs included skin, chest wall, and regional lymph nodes. Median dose was 50 Gy in 25 fractions, with fifteen receiving chest wall boost (median 56.25 Gy in 25 fractions). During treatment, plan re-optimization was required in 9 (47%). Acute grade 3 dermatitis occurred in 2 (11%). Rib facture occurred in 4 (21%). One patient with pre-existing surgical seroma experienced a grade 3 fistula. Mean heart, left anterior descending artery, and right coronary artery doses were 0.7 Gy, 2.3 Gy, and 0.1 Gy, respectively. Mean ipsilateral lung V20Gy was 14.9%. At 2 years, there were no locoregional recurrences, and OS and DMFS were 89% and 82%, respectively. CONCLUSION: IMPT for IBC is well-tolerated with excellent dosimetry, low rates of AEs, and favorable early locoregional control outcomes. Follow-up for long-term outcomes is ongoing. Our findings suggest that IMPT is feasible and an attractive modality worthy of further investigation in patients with IBC.

Alterations of the Human Lung and Gut Microbiomes in Non-Small Cell Lung Carcinomas and Distant Metastasis.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of the lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive. We recruited in total 121 participants, including 87 newly diagnosed treatment-naive NSCLC patients of various stages and 34 healthy volunteers, and surveyed their fecal and sputum microbiota. We compared the microbial profiles between groups, identified microbial biomarkers, and generated machine learning models for distinguishing healthy individuals from patients with NSCLC and patients of various stages. We found significant perturbations of gut and sputum microbiota in patients with NSCLC and DM. A machine learning model combining both microbiota (combined model) performed better than an individual data set in patient stratification, with the highest area under the curve (AUC) value of 0.896. Sputum and gut microbiota both contributed to the combined model; in most cases, sputum-only models performed similar to the combined models. Several microbial biomarkers were shared by both microbiotas, indicating their similar roles at distinct body sites. Microbial biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for DM could be acquired early. Furthermore, Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating that distinct types of DMs could have different microbes. Our results indicate that alterations of the sputum microbiota have stronger relationships with NSCLC and DM than the gut and strongly support the feasibility of metagenome-based noninvasive disease diagnosis and risk evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT03454685). IMPORTANCE Our survey on gut and sputum microbiota revealed that both were significantly disturbed in non-small cell lung cancer (NSCLC) and associated with distant metastasis (DM) while only the sputum microbiota was associated with non-DM NSCLC. The lung microbiota could therefore have a stronger association with (and thus may contribute more to) disease development than the gut microbiota. Mathematic models using both microbiotas performed better in patient stratification than using individual microbiota. Sputum models, however, performed similar to the combined models, suggesting a convenient, noninvasive diagnostic for NSCLC. Microbial biomarkers of distinct disease stages were mostly shared, suggesting that the same set of microbes were underlying disease progression, and the signals for distant metastasis could be acquired at early stages of the disease. Our results strongly support the feasibility of noninvasive diagnosis of NSCLC, including distant metastasis, are of clinical importance, and should warrant further research on the underlying molecular mechanisms.

[Research progress on chemical constituents, pharmacological action and quality control of Scutellaria barbata].

Scutellaria barbata is a recognized anti-cancer traditional Chinese medicine, with the effects of clearing heat and detoxi-fication, dispelling blood stasis and stopping bleeding, diuresis and detumescence. At present, terpenoids, flavonoids, polysaccharides and volatile oils have been isolated from S. barbata, which have many pharmacological effects, such as resisting tumor, virus, bacteria and oxidation, and immunomodulation. This paper reviews the studies on the chemical constituents, pharmacological action and quality control of S. barbata, in the expectation of providing ideas and references for the further development and studies of S. barbata.

Evaluating the impact of dose reductions and delays on progression-free survival in women with ovarian cancer treated with either three-weekly or dose-dense carboplatin and paclitaxel regimens in the national prospective OPAL cohort study.

OBJECTIVES: To determine the impact of chemotherapy dose reductions and dose delays on progression-free survival (PFS) in women with ovarian cancer receiving first line chemotherapy in a real world prospective cohort study. METHODS: Patients with newly diagnosed epithelial ovarian (or peritoneal, fallopian tube) cancer enrolled in a national Australian prospective study, OPAL, who commenced three-weekly carboplatin (AUC 5 or 6) and paclitaxel 175 mg/m2 (CP) or carboplatin (AUC 5 or 6) and dose-dense weekly paclitaxel 80 mg/m2 (DD-CP) were eligible. Primary endpoint was PFS. RESULTS: 634 evaluable patients, 309 commenced CP and 325 DD-CP. Patient's age was similar in the two groups (median 62 years, range 21-79). All planned chemotherapy doses were completed by 66% vs 40% (p < 0.001) in the CP and DD-CP groups respectively. There was at least one treatment delay in 28% vs 58% (p < 0.001) in the CP and DD-CP groups, respectively, and 29% vs 49% (p < 0.001), respectively, required at least a 15% dose reduction for either carboplatin or paclitaxel. Median PFS was 29.2 [22.9, 43.8] and 21.5 [19.4, 23.1] months in the CP and DD-CP groups respectively. Adjusting for age, histology and FIGO stage PFS did not differ between treatment groups. Median PFS was similar in patients irrespective of dose reduction or dose delay. CONCLUSION: Patients receiving DD-CP required more dose reductions and delays due to haematological toxicities and lower completion rates than CP without significant difference in median PFS between CP and DD-CP. Median PFS was similar in patients irrespective of dose reduction or dose delay.

GMrepo: a database of curated and consistently annotated human gut metagenomes.

GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purpose is to facilitate the reusability and accessibility of the rapidly growing human metagenomic data. This is achieved by consistently annotating the microbial contents of collected samples using state-of-art toolsets and by manual curation of the meta-data of the corresponding human hosts. GMrepo organizes the collected samples according to their associated phenotypes and includes all possible related meta-data such as age, sex, country, body-mass-index (BMI) and recent antibiotics usage. To make relevant information easier to access, GMrepo is equipped with a graphical query builder, enabling users to make customized, complex and biologically relevant queries. For example, to find (1) samples from healthy individuals of 18 to 25 years old with BMIs between 18.5 and 24.9, or (2) projects that are related to colorectal neoplasms, with each containing >100 samples and both patients and healthy controls. Precomputed species/genus relative abundances, prevalence within and across phenotypes, and pairwise co-occurrence information are all available at the website and accessible through programmable interfaces. So far, GMrepo contains 58 903 human gut samples/runs (including 17 618 metagenomes and 41 285 amplicons) from 253 projects concerning 92 phenotypes. GMrepo is freely available at: https://gmrepo.humangut.info.

Treatment of lumbar vertebra epithelioid hemangioma with radiation therapy: a case report.

BACKGROUND: Although epithelioid hemangiomas involving bone have been described in previous case reports and case series, the effects of radiation therapy on vertebral epithelioid hemangioma has not been fully reported. Here we provide a case report of tumor response to radiation therapy in a young adult with a large epithelioid hemangioma involving the fourth lumbar vertebrae. CASE PRESENTATION: A 27-year-old Latino man with a past medical history of type 1 diabetes and a 3-year history of low back pain presented to a hospital emergency department following acute worsening of back pain. On transfer to our tertiary medical center, he described the pain as "shock-like" which originated at the lateral aspect of his right hip and radiated down to his right knee. Paresthesia was also reported along the medial aspect of his lower right leg. Imaging included a computed tomography scan and magnetic resonance imaging which revealed fourth lumbar and right iliac lytic bone lesions. Image-guided biopsies of the lytic lesions were consistent with a diagnosis of epithelioid hemangioma and radiation therapy was recommended as the primary treatment. Our patient's low back and leg pain were initially managed with acetaminophen, oxycodone, pregabalin, and lidocaine patch 5%. He noted improvement in pain after his third fraction of radiation. Pain intensity continued to decline and oxycodone was discontinued. CONCLUSIONS: This case report demonstrates an unusual etiology of back and leg pain in a young man and elucidates the palliative effects of radiation therapy for epithelioid hemangioma involving the lumbar spine.

Metabolic Dependencies Underlie Interaction Patterns of Gut Microbiota During Enteropathogenesis.

In recent decades, increasing evidence has strongly suggested that gut microbiota play an important role in many intestinal diseases including inflammatory bowel disease (IBD) and colorectal cancer (CRC). The composition of gut microbiota is thought to be largely shaped by interspecies competition for available resources and also by cooperative interactions. However, to what extent the changes could be attributed to external factors such as diet of choice and internal factors including mutual relationships among gut microbiota, respectively, are yet to be elucidated. Due to the advances of high-throughput sequencing technologies, flood of (meta)-genome sequence information and high-throughput biological data are available for gut microbiota and their association with intestinal diseases, making it easier to gain understanding of microbial physiology at the systems level. In addition, the newly developed genome-scale metabolic models that cover significant proportion of known gut microbes enable researchers to analyze and simulate the system-level metabolic response in response to different stimuli in the gut, providing deeper biological insights. Using metabolic interaction network based on pair-wise metabolic dependencies, we found the same interaction pattern in two IBD datasets and one CRC datasets. We report here for the first time that the growth of significantly enriched bacteria in IBD and CRC patients could be boosted by other bacteria including other significantly increased ones. Conversely, the growth of probiotics could be strongly inhibited from other species, including other probiotics. Therefore, it is very important to take the mutual interaction of probiotics into consideration when developing probiotics or "microbial based therapies." Together, our metabolic interaction network analysis can predict majority of the changes in terms of the changed directions in the gut microbiota during enteropathogenesis. Our results thus revealed unappreciated interaction patterns between species could underlie alterations in gut microbiota during enteropathogenesis, and between probiotics and other microbes. Our methods provided a new framework for studying interactions in gut microbiome and their roles in health and disease.

Post-mastectomy intensity modulated proton therapy after immediate breast reconstruction: Initial report of reconstruction outcomes and predictors of complications.

PURPOSE: To report reconstructive outcomes of patients treated with post-mastectomy intensity modulated proton therapy (IMPT) following immediate breast reconstruction (IBR). MATERIALS AND METHODS: Consecutive women with breast cancer who underwent implant-based IBR and post-mastectomy IMPT were included. Clinical characteristics, dosimetry, and acute toxicity were collected prospectively and reconstruction complications retrospectively. RESULTS: Fifty-one women were treated between 2015 and 2017. Forty-two had bilateral reconstruction with unilateral IMPT. The non-irradiated contralateral breasts served as controls. Conventional fractionation (median 50 Gy/25 fractions) was administered in 37 (73%) and hypofractionation (median 40.5 Gy/15 fractions) in 14 (27%) patients. Median mean heart, ipsilateral lung V20Gy, and CTV-IMN V95% were 0.6 Gy, 13.9%, and 97.4%. Maximal acute dermatitis grade was 1 in 32 (63%), 2 in 17 (33%), and 3 in 2 (4%) patients. Surgical site infection (hazard ratio [HR] 13.19, 95% confidence interval [CI] 1.67-104.03, p = 0.0012), and unplanned surgical intervention (HR 9.86, 95% CI 1.24-78.67, p = 0.0068) were more common in irradiated breasts. Eight of 51 irradiated breasts and 2 of 42 non-irradiated breasts had reconstruction failure (HR 3.59, 95% CI 0.78-16.41, p = 0.084). Among irradiated breasts, hypofractionation was significantly associated with reconstruction failure (HR 4.99, 95% CI 1.24-20.05, p = 0.024), as was older patient age (HR 1.14, 95% CI 1.05-1.24, p = 0.002). CONCLUSIONS: IMPT following IBR spared underlying organs and had low rates of acute toxicity. Reconstruction complications are more common in irradiated breasts, and reconstructive outcomes appear comparable with photon literature. Hypofractionation was associated with higher reconstruction failure rates. Further investigation of optimal dose-fractionation after IBR is needed.

[Effect of famine exposure on the risk of chronic disease in later life among population in Harbin].

Objective: To study the relations between famine exposure and the risk of chronic diseases as diabetes mellitus, obesity, hypertension, coronary heart disease and stroke in the population of Harbin. Methods: Our data was collected from the baseline survey-the China Kadoorie Biobank project (CKB) in Harbin. Retrospective cohort study design was used. Related risks on chronic diseases including diabetes mellitus, obesity, hypertension, coronary heart disease and stroke, were compared among the famine exposed or non-exposed people, respectively by logistic analysis method. Results: After adjusted for factors as age, sex, physical activity, smoking, alcohol intake, diet, family history of diseases, it appeared that the factor 'famine exposure' had increased the risks of diseases as obesity (OR=1.204, 95%CI: 1.104-1.313, P<0.01), hypertension (OR=1.315, 95%CI: 1.210-1.429, P<0.01) and coronary heart disease (OR=1.495, 95%CI: 1.369-1.632, P<0.01). The lower the age of population being exposed to famine, the greater the risk of the development of all kinds of chronic diseases. Conclusions: Famine exposure appeared a risk factor for obesity, hypertension, and coronary heart disease. It is of great significance to ensure the life-long nutrition of the people, especially in the early and adolescent stages, to prevent obesity, hypertension, and coronary heart disease in their later lives.

Folic acid is necessary for proliferation and differentiation of C2C12 myoblasts.

Folic acid, a water soluble B vitamin, plays an important role in cellular metabolic activities, such as functioning as a cofactor in one-carbon metabolism for DNA and RNA synthesis as well as nucleotide and amino acid biosynthesis in the body. A lack of dietary folic acid can lead to folic acid deficiency and result in several health problems, including macrocytic anemia, elevated plasma homocysteine, cardiovascular disease, birth defects, carcinogenesis, muscle weakness, and walking difficulty. However, the effect of folic acid deficiency on skeletal muscle development and its molecular mechanisms are unknown. We, therefore, investigated the effect of folic acid deficiency on myogenesis in skeletal muscle cells and found that folic acid deficiency induced proliferation inhibition and cell cycle breaking as well as cellular senescence in C2C12 myoblasts, implying that folic acid deficiency influences skeletal muscle development. Folic acid deficiency also inhibited differentiation of C2C12 myoblasts and induced deregulation of the cell cycle exit and many cell cycle regulatory genes. It inhibited expression of muscle-specific marker MyHC as well as myogenic regulatory factor (myogenin). Moreover, immunocytochemistry and Western blot analyses revealed that DNA damage was more increased in folic acid-deficient medium-treated differentiating C2C12 cells. Furthermore, we found that folic acid resupplementation reverses the effect on the cell cycle and senescence in folic acid-deficient C2C12 myoblasts but does not reverse the differentiation of C2C12 cells. Altogether, the study results suggest that folic acid is necessary for normal development of skeletal muscle cells.

Postoperative outcomes following cardiac surgery in non-anaemic iron-replete and iron-deficient patients - an exploratory study.

Iron deficiency anaemia is strongly associated with poor outcomes after cardiac surgery. However, pre-operative non-anaemic iron deficiency (a probable anaemia precursor) has not been comprehensively examined in patients undergoing cardiac surgery, despite biological plausibility and evidence from other patient populations of negative effect on outcome. This exploratory retrospective cohort study aimed to compare an iron-deficient group of patients undergoing cardiac surgery with an iron-replete group. Consecutive non-anaemic patients undergoing elective coronary artery bypass grafting or single valve replacement in our institution between January 2013 and December 2015 were considered for inclusion. Data from a total of 277 patients were analysed, and were categorised by iron status and blood haemoglobin concentration into iron-deficient (n = 109) and iron-replete (n = 168) groups. Compared with the iron-replete group, patients in the iron-deficient group were more likely to be female (43% vs. 12%, iron-replete, respectively); older, mean (SD) age 64.4 (9.7) vs. 63.2 (10.3) years; and to have a higher pre-operative EuroSCORE (median IQR [range]) 3 (2-5 [0-10]) vs. 3 (2-4 [0-9]), with a lower preoperative haemoglobin of 141.6 (11.6) vs. 148.3 (11.7) g.l-1 . Univariate analysis suggested that iron-deficient patients had a longer hospital length of stay (7 (6-9 [2-40]) vs. 7 (5-8 [4-23]) days; p = 0.013) and fewer days alive and out of hospital at postoperative day 90 (83 (80-84 [0-87]) vs. 83 (81-85 [34-86]), p = 0.009). There was no evidence of an association between iron deficiency and either lower nadir haemoglobin or higher requirement for blood products during inpatient stay. After adjusting the model for pre-operative age, sex, renal function, EuroSCORE and haemoglobin, the mean increase in hospital length of stay in the iron-deficient group relative to the iron-replete group was 0.86 days (bootstrapped 95%CI -0.37 to 2.22, p = 0.098). This exploratory study suggests there is weak evidence of an association between non-anaemic iron deficiency and outcome after cardiac surgery after controlling for potentially confounding variables.

Defective expression of polarity protein Par3 promotes cervical tumorigenesis and metastasis.

OBJECTIVES: The aim of this study was to investigate whether the partition-defective 3 protein (Par3) regulates cervical carcinoma growth and metastasis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to analyze the expression of Par3 protein in samples from 89 cervical squamous cell carcinoma (CSCC) patients among Uyghur women. The specific short hairpin (shRNA) vector as well as eu- karyotic expression vector of PARD3 was transfected into SiHa cell lines. The variation of migration and invasion after transfection was determined using Transwell assays, cell cycle, and apoptosis were assayed by flow cytometry, respectively. RESULTS: The incidence of CSCC was associated with reduced expression of Par3. Downregulation of Par3 was significantly associated with more advanced tumors (i.e., higher histological grade, lymph node involvement, and higher tumor stages) (p < 0.05 for all). Lost expression of Par3 promotes prolif- eration, inhibits apoptosis, and enhances migration and invasion. Loss of Par3 induces MMP9 expression and epithelial to mesenchymal transition (EMT) related genes (N-cadherin, E-cadherin, and ß-catenin) expression changed in SiHa cells. CONCLUSIONS: The reduced Par3 expression in cervical cancer indicates tumor-suppressive properties of Par3 that may be a marker of poor prognosis in cervical cancer patients, and the molecular determinants of epithelial polarity which have tumorigenesis enhancing impact, might through EMT.

Decreasing high postprandial stearic acid in impaired fasting glucose by dietary regulation.

BACKGROUND/OBJECTIVES: The objective of this study was to determine the postprandial change in free fatty acid (FFA) profiles in subjects with impaired fasting glucose (IFG), and to evaluate the effect of low glycemic index (GI) load on postprandial FFA profiles and inflammation. SUBJECTS/METHODS: First, 50 IFG and 50 healthy subjects were recruited; and 2 -h postprandial changes in FFA profiles were determined. Second, the 50 IFG subjects then received three different loads: glucose load (GL), high glycemic index (HGI) load and low glycemic index (LGI) load, respectively. FFA profile, glucose, insulin, glucagon-like peptide 1 (GLP-1) and inflammatory biomarkers were assayed at 0, 30, 60, 90 and 120 min. RESULTS: Postprandial stearic acid (C18:0) increased compared with baseline in all subjects, whereas the change in postprandial C18:0 was more marked in IFG subjects than in healthy subjects. Compared with subjects who received the GL and HGI load, the area under the curve for insulin, GLP-1, C18:0 and tumor necrosis factor-alpha significantly decreased and adiponectin increased in subjects who received the LGI load. CONCLUSIONS: The rise in postprandial C18:0 in IFG subjects was inhibited by LGI load.

A novel membrane-permeant cADPR antagonist modified in the pyrophosphate bridge.

A concise method for the formation of cyclopyrophosphate of cIDPRE as well as sulfur and selenium-substituted pyrophosphate cIDPRE analogues (P(1)(S)-cIDPRE, P(1)(Se)-cIDPRE, P(2)(S)-cIDPRE and P(2)(Se)-cIDPRE) was reported and one of the P(S)-diastereoisomers, P(1)(S)-cIDPRE-1, is a novel membrane-permeant cADPR antagonist.

Analysis on the clinical features of 22 basaloid squamous cell carcinoma of the lung.

BACKGROUND: Basaloid squamous cell carcinoma of the lung is a rare and highly malignant tumor mostly observed in the proximal bronchi. Basaloid squamous cell carcinoma of the lung cases typically show rapid clinical progression, very poor prognosis and special pathological morphology. This project aimed to examine the clinical features of basaloid squamous cell carcinoma of the lung and the factors related to its prognosis; and to compare survival outcomes between basaloid squamous cell carcinoma and poorly differentiated squamous cell carcinomas (PDSC). METHODS: Between January 2004 and December 2008, pathological sections from basaloid squamous cell carcinoma and PDSC of the lung were collected and retrospectively analyzed at Tianjin Medical University Cancer Institute and Hospital. Data analysis was performed using Statistical Package for the Social Sciences (SPSS11.0). The Kaplan-Meier method was used to calculate the survival rate. Log-rank test was used to compare the differences in survival rate between the two groups. The factors influencing prognosis were analyzed using the Cox proportional hazard model. RESULTS: A total of 120 pathological sections were used in the analysis of this study-22 from basaloid squamous cell carcinoma cases and 98 from PDSC cases. Compared to the PDSC group, the basaloid squamous cell carcinoma group had a larger proportion of female patients (p = 0.001); however it had higher proportion of male smokers (p = 0.003). There were no statistically significant differences in survival rate between the two groups (χ2 = 1.200, p = 0.273). Additionally, prognosis of basaloid squamous cell carcinoma is significantly influenced by treatment mode and clinical stages of the tumor. The post-operation mortality hazard of patients treated with a combination chemotherapy and radiotherapy was 1.296 times higher than other treatment modes (p = 0.025). Increases in post-operation mortality hazard ratio were also associated with more advanced clinical stage of tumors (χ2 trend = 11.907, p = 0.000). CONCLUSIONS: This study demonstrated that basaloid squamous cell carcinoma and PDSC have very similar clinical features, and there are no significant differences in survival rates between the two groups. Hence, we conclude that in the short term, the same clinical treatments and therapeutic modes can be administered to patients with basaloid squamous cell carcinoma and PDSC of the lung.

Detection of human cytomegalovirus antigen and DNA in lymph nodes and peripheral blood mononuclear cells of patients with angioimmunoblastic lymphadenopathy with dysproteinemia.

The cause of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) remains unknown. It is characterized by acute onset, severe constitutional symptoms, cervical or generalized lymphadenopathy, lymphopenia, and polyclonal hypergammaglobulinemia, all of which are highly suggestive of a viral origin. Using immunohistochemical methods, employing murine monoclonal antibody as the primary antibody, we detected human cytomegalovirus antigen in the lymph nodes of eight of 11 patients with AILD. Cytomegalovirus DNA was also detected in the peripheral blood mononuclear cells by DNA dot hybridization in all five of the patients with AILD who were tested using this technique. None of the lymph nodes from the 11 patients stained positive for the rubella virus antigen. Based on the above evidence and the similarity of the immunologic abnormalities found in both AILD and cytomegalovirus infection, the possible role of cytomegalovirus as one of the causative agents for AILD is proposed.