The erythropoietin (EPO) belongs to the family of angiogenic factors, which is regulated by Hypoxia-inducible factor- 1α (HIF-1α). As known, EPO are expressed in human villi and decidua, but the function is not clear. In this study, we investigated the expression and roles of HIF-1α, EPO and its receptor (EPOR) in the biological functions of trophoblast and decidual stromal cell (DSC) in human early pregnancy. The expression of EPO, EPOR and HIF-1α was evaluated in the villi and deciduas by RT-PCR and immunohistochemistry. Thereafter, we silenced HIF-1α expression in HTR-8/SVneo cell line and decidual stromal cells (DSCs). The effects of EPO on the proliferation and apoptosis of trophoblasts and DSCs, and activation of signal molecules were investigated by BrdU proliferation assay, flow cytometry and western blot, respectively. We have observed that the HIF-1α silence results in the lower expression of EPO in trophoblasts and DSCs. The anti-EPO neutralizing antibody can inactivate the phosphorylation of STAT5 and activate p38 of these cells in a dosage-dependent manner. Furthermore, the expressions of EPO, EPOR and HIF-1α in the villi and decidua from the unexplained miscarriage were significantly lower than that of the normal early pregnancy. This study suggests that HIF-1α may regulate the expression of EPO, which plays a favorable regulatory role in the proliferation and survival of human first-trimester trophoblast cells and DSCs via inactivating p38 and activating STAT5 in an autocrine manner, while the inadequate EPO expression at maternal-fetal interface may lead to pregnancy wastage in humans.
EPO; HIF-1; trophoblast cell; decidual stromal cell; STAT5; p38
Pattern recognition receptors (PPRs) are part of the initial step of a host defense against pathogens in detecting pathogen-associated molecular patterns. However, determinants of the specificity of this recognition by innate immune molecules of invertebrates remain largely unknown. In this study, we investigated the potential involvement of an invertebrate PRR C-type lectin in the antimicrobial response of the crustacean Eriocheir sinensis. Based on the initial expressed sequence tags (EST) of a hepatopancreatic cDNA library, the full-length EsLecF cDNA was cloned and determined to contain a 477-bp open reading frame encoding a putative 158-amino-acid protein. A comparison with other reported invertebrate and vertebrate C-type lectin superfamily sequences revealed the presence of a common carbohydrate recognition domain (CRD). EsLecF transcripts in E. sinensis were mainly detected in the hepatopancreas and were inducible by a lipopolysaccharide (LPS) injection. The recombinant EsLecF (rEsLecF) protein produced via a prokaryotic expression system and affinity chromatography was found to have a wide spectrum of binding activities towards various microorganisms, and its microbial-binding activity was calcium-independent. Moreover, the binding of rEsLecF induced the aggregation of microbial pathogens. Results of the microorganism growth inhibitory assay and antibacterial assay revealed capabilities of rEsLecF in suppressing microorganism growth and directly killing bacteria, respectively. Furthermore, rEsLecF could enhance cellular encapsulation in vitro. Collectively, the findings presented here demonstrated the successful isolation of a novel C-type lectin in a crustacean and highlighted its critical role in the innate immunity of an invertebrate.
Background and Aims
The association between gallstone disease and coronary artery atherosclerotic disease (CAD) remains unclear. To clarify their relationship, patients with CAD newly diagnosed by coronary angiography were investigated in this cross-sectional study.
The study cohort consisted of 1,270 patients undergoing coronary angiography for the first time between January 2007 and September 2011. Patients with ≥50% diameter stenosis in any major coronary artery on coronary angiography were defined as being CAD positive (n = 766) and those with no stenosis as CAD negative (n = 504). Multivariate logistic regression was used to investigate the relationship between gallstone disease and CAD. The odds ratios (OR) of factors associated with CAD were calculated. In addition, CAD-positive and CAD-negative patients were matched one-to-one by age, gender and metabolic syndrome (MetS), and the association between gallbladder disease and CAD was determined.
The prevalence of gallstone disease was significantly higher in CAD-positive than in CAD negative patients (149/766 [19.5%] vs 57/504 [11.3%], P<0.01). Gallstone disease was significantly associated with CAD (adjusted OR = 1.59, 95% confidence interval [CI] 1.10–2.31). Following matched pairing of 320 patients per group, gallstone disease remained significantly associated with CAD (adjusted OR = 1.69, 95% CI: 1.08–2.65).
Gallstone disease is strongly associated with CAD diagnosed by coronary angiography.
The government of China promulgated new medical care reform policies in March 2009. After that, provincial-level governments launched new medical care reform which focusing on local comprehensive medical care reform (LCMR). Anhui Province is an example of an area affected by LCMR, in which the LCMR was started in October 2009 and implemented in June 2010. The objective of this study was to compare the job satisfaction (JS) of community health workers (CHWs) before and after the reform in Anhui Province.
A baseline survey was carried out among 813 community health workers (CHWs) of 57 community health centers (CHCs) (response rate: 94.1%) and an effect evaluation survey among 536 CHWs of 30 CHCs (response rate: 92.3%) in 2009 and 2012 respectively. A self-completion questionnaire was used to assess the JS of the CHWs (by the job satisfaction scale, JSS).
The average scores of total JS and satisfaction with pay, contingent rewards, operating procedures and communication in the effect evaluation survey were statistically significantly higher than those of the baseline survey (P<0.05). The average score of satisfaction with promotion (2.55±1.008) in the effect evaluation survey was statistically significantly lower than that in the baseline survey (2.71±0.730) (P=0.002). In both surveys, the average scores of satisfaction with pay, benefits and promotion were statistically significantly lower than the others (all P<0.05).
After two years’ implementation of the LCMR, CHWs’ total JS have a small improvement. However, CHWs have lower satisfaction in the dimensions of pay, promotion and benefits dimensions before and after the LCMR. Therefore, policy-makers should take corresponding measures to raise work reward of CHWs and pay more attention to CHWs’ professional development to further increase their JS.
Influence of fish oil supplementation on postoperative atrial fibrillation (POAF) was inconsistent according to published clinical trials. The aim of the meta-analysis was to evaluate the effects of perioperative fish oil supplementation on the incidence of POAF after cardiac surgery.
Pubmed, Embase and the Cochrane Library databases were searched. Randomized controlled trials (RCTs) assessing perioperative fish oil supplementation for patients undergoing cardiac surgery were identified. Data concerning study design, patient characteristics, and outcomes were extracted. Risk ratio (RR) and weighted mean differences (WMD) were calculated using fixed or random effects models.
Eight RCTs involving 2687 patients were included. Perioperative supplementation of fish oil did not significantly reduce the incidence of POAF (RR = 0.86, 95%CI 0.71 to 1.03, p = 0.11) or length of hospitalization after surgery (WMD = 0.10 days, 95% CI: 0.48 to 0.67 days, p = 0.75). Fish oil supplementation also did not affect the perioperative mortality, incidence of major bleeding or the length of stay in the intensive care unit. Meta-regression and subgroup analyses indicated mean DHA dose in the supplements may be a potential modifier for the effects of fish oil for POAF. For supplements with DHA >1 g/d, fish oil significantly reduced the incidence of POAF; while it did not for the supplements with a lower dose of DHA.
Current evidence did not support a preventative role of fish oil for POAF. However, relative amounts of DHA and EPA in fish oil may be important for the prevention of POAF.
High-throughput genomic technologies have identified biomarkers and potential therapeutic targets for ovarian cancer. Comprehensive functional validation studies of the biological and clinical implications of these biomarkers are needed to advance them toward clinical use. Amplification of chromosomal region 5q31–5q35.3 has been used to predict poor prognosis in patients with advanced stage, high-grade serous ovarian cancer. In this study, we further dissected this large amplicon and identified the overexpression of FGF18 as an independent predictive marker for poor clinical outcome in this patient population. Using cell culture and xenograft models, we show that FGF18 signaling promoted tumor progression by modulating the ovarian tumor aggressiveness and microenvironment. FGF18 controlled migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This resulted in a tumor microenvironment characterized by enhanced angiogenesis and augmented tumor-associated macrophage infiltration and M2 polarization. Tumors from ovarian cancer patients had increased FGF18 expression levels with microvessel density and M2 macrophage infiltration, confirming our in vitro results. These findings demonstrate that FGF18 is important for a subset of ovarian cancers and may serve as a therapeutic target.
Organisms have sophisticated subcellular compartments containing enzymes that function in tandem. These confined compartments ensure effective chemical transformation and transport of molecules, and the elimination of toxic metabolic wastes1,2. Creating functional enzyme complexes that are confined in a similar way remains challenging. Here we show that two or more enzymes with complementary functions can be assembled and encapsulated within a thin polymer shell to form enzyme nanocomplexes. These nanocomplexes exhibit improved catalytic efficiency and enhanced stability when compared with free enzymes. Furthermore, the co-localized enzymes display complementary functions, whereby toxic intermediates generated by one enzyme can be promptly eliminated by another enzyme. We show that nanocomplexes containing alcohol oxidase and catalase could reduce blood alcohol levels in intoxicated mice, offering an alternative antidote and prophylactic for alcohol intoxication.
Whey acidic proteins (WAP) belong to a large gene family of antibacterial peptides, which are critical in the host immune response against microbial invasion. The common feature of these proteins is a single WAP domain maintained by at least one four-disulfide core (4-DSC) structure rich in cysteine residues. In this study, a double WAP domain (DWD)-containing protein, Es-DWD1, was first cloned from the Chinese mitten crab (Eriocheirsinensis). The full-length Es-DWD1cDNA was 1193 bp, including a 411 bp open reading frame (ORF) encoding 136 amino acids with a signal peptide of 22 amino acids in the N-terminus. A comparison with other reported invertebrate and vertebrate sequences revealed the presence of WAP domains characteristic of WAP superfamilies. As determined by quantitative real-time RT-PCR, Es-DWD1 transcripts were ubiquitously expressed in all tissues, but it was up-regulated in hemocytes post-challenge with pathogen-associated molecular patterns (PAMPs). The mature recombinant Es-DWD1 (rEs-DWD1) protein exhibited different binding activities to bacteria and fungus. Moreover, rEs-DWD1 could exert agglutination activities against Bacillus subtilis and Pichiapastoris and demonstrated inhibitory activities against the growth of Staphylococcus aureus, Aeromonas hydrophila and P. pastoris. Furthermore, rEs-DWD1 showed a specific protease inhibitory activity in B. subtilis. Coating of rEs-DWD1 onto agarose beads enhanced encapsulation of the beads by crab hemocytes. Collectively, the results suggest that Es-DWD1 is a double WAP domain containing protein with antimicrobial and proteinase inhibitory activities, which play significant roles in the immunity of crustaceans.
Signet-ring cell carcinoma (SRCC) can arise from virtually all organs. However, primary SRCC of the breast is very rare. Until 2003, SRCC was placed under ‘mucin-producing carcinomas’ and separated from other carcinomas by the World Health Organization (WHO). To date, only a few cases have been reported. A case of a 46-year-old woman with primary SRCC of the breast is presented in this report. The patient underwent a right modified radical mastectomy with axillary lymph node dissection. Characteristic features and differential diagnosis of this tumor are discussed in the light of pertinent literature.
Signet-ring cell carcinoma breast cancer
The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I− symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels.
mild iodine deficiency; hypothyroxinemia; gestation; lactation; thyroid
Sjögren’s syndrome can involve the central nervous system; however, spontaneous intracranial hemorrhage has rarely been reported as the initial manifestation.
We report a 39-year-old woman with primary Sjögren’s syndrome presenting with intracranial hemorrhage. The diagnosis of primary Sjögren’s syndrome was based on the presence of ocular dryness, salivary gland secretory and excretory dysfunction confirmed with dynamic tracer emission CT, and positive anti-Sjögren’s syndrome A and anti-Sjögren’s syndrome B antibodies.
Primary Sjögren’s syndrome can present with variable central nervous system signs, which may precede the classic sicca symptoms. Therefore, Sjögren’s syndrome-associated indicators should be investigated in patients without the common risk factors for stroke who present with spontaneous intracranial hemorrhage.
Sjögren’s syndrome; Vasculitis; Intracranial hemorrhage; Internal carotid artery; Moyamoya disease; Anti-Sjögren’s syndrome A antibody; Anti-Sjögren’s syndrome B antibody
The aim of the present study was to investigate the immune response induced by Mycobacterium marinum infection in vitro and the potential of M. marinum as an immunotherapy for M. tuberculosis infection.
The potential human immune response to certain bacillus infections was investigated in an immune cell-bacillus coculture system in vitro. As a potential novel immunotherapy, M. marinum was studied and compared with two other bacilli, Bacillus Calmette-Guérin (BCG) and live attenuated M. tuberculosis. We examined the changes in both the bacilli and immune cells, especially the time course of the viability of mycobacteria in the coculture system and host immune responses including multinuclear giant cell formation by Wright-Giemsa modified staining, macrophage polarization by cell surface antigen expression, and cytokines/chemokine production by both mRNA expression and protein secretion.
The M. marinum stimulated coculture group showed more expression of CD209, CD68, CD80, and CD86 than the BCG and M. tuberculosis (an attenuated strain, H37Ra) groups, although the differences were not statistically significant. Moreover, the M. marinum group expressed more interleukin (IL)-1B and IL-12p40 on day 3 (IL-1B: P = 0.003 and 0.004, respectively; IL-12p40: P = 0.001 and 0.011, respectively), a higher level of CXCL10 on day 1 (P = 0.006 and 0.026, respectively), and higher levels of chemokine (C-X-C motif) ligand (CXCL) 8 and chemokine (C motif) ligand (XCL) 1 on day 3 (CXCL8: P = 0.012 and 0.014, respectively; XCL1: P = 0.000 and 0.000, respectively). The M. marinum stimulated coculture group also secreted more tumor necrosis factor (TNF)-α, IL-1β, and IL-10 on day 1 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.000, respectively; IL-10: P = 0.002 and 0.019, respectively) and day 3 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.001, respectively; IL-10: P = 0.000 and 0.000, respectively). In addition, the colony-forming units (an index of viability) of M. marinum in the M. marinum stimulated coculture group was significantly less than that of BCG and H37Ra in their corresponding bacillus stimulated groups (P = 0.037 and 0.013, respectively).
Our results indicated that M. marinum could be a potentially safe and effective immunotherapy.
immunotherapy; Mycobacterium marinum; bacilli; immunity
This study aimed to determine the contribution of individual and contextual socioeconomic status (SES) to the prevalence of diabetes mellitus and glucose intolerance in the adult population in rural southwest China.
A population-based cross-sectional study of diabetes was performed in 4801(2152 men) Chinese adults (≥25 years old). Multilevel logistic regression model was used to examine the association between individuals’ and townships’ variables and the prevalence of diabetes mellitus and glucose intolerance.
The age-and gender-standardized prevalence of diabetes mellitus and glucose intolerance were 7.1% (3.6% for undiagnosed) and 8.8% in adults aged ≥25 years, respectively, and increasing with age. Females were more likely to develop diabetes than males. The probability of developing diabetes increased with BMI. Both contextual and individual educational level and yearly household income were found to be negatively associated with the prevalence of diabetes. Residence in communities with a higher percentage of ethnic minorities was associated with higher prevalence of diabetes. Smoking had a protective effect for diabetes, drinking had a positive association with diabetes mellitus and glucose intolerance.
Diabetes mellitus and glucose intolerance are common in rural adults of southwest China by international standards. These results indicate that diabetes mellitus has become a major public health problem in rural areas in southwest China, and strategies aimed at the prevention and treatment of diabetes mellitus and glucose intolerance are needed.
AIM: To explore the role of CDX2 in the multi-drug resistance (MDR) process of gastric cancer in vitro and in vivo.
METHODS: A cisplatin-resistant gastric cancer cell line with stable downregulation of CDX2 was established. mRNA and protein expression levels of CDX2, survivin, cyclin D1, and c-Myc were detected by western blotting and semi-quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The influence of downregulation of CDX2 on MDR was assessed by measuring IC50 of SGC7901/DDP cells to cisplatin, doxorubicin, and 5-fluorouracil, rate of doxorubicin efflux, apoptosis, and cell cycle progression detected by flow cytometry. In addition, we determined the in vivo effects of CDX2 small interfering RNA (siRNA) on tumor size, and apoptotic cells in tumor tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and hematoxylin and eosin staining.
RESULTS: CDX2 siRNA led to downregulation of endogenous CDX2 mRNA (0.31 ± 0.05 vs 1.10 ± 0.51, 0.31 ± 0.05 vs 1.05 ± 0.21, P = 0.003) and protein (0.12 ± 0.08 vs 0.51 ± 0.07, 0.12 ± 0.08 vs 0.55 ± 0.16, P = 2.57 × 10-4) expression. It significantly promoted the sensitivity of SGC7901/DDP cells to cisplatin (0.12 ± 0.05 vs 0.33 ± 0.08, 0.12 ± 0.05 vs 0.39 ± 0.15, P = 0.001), doxorubicin (0.52 ± 0.13 vs 4.11 ± 1.25, 0.52 ± 0.13 vs 4.05 ± 1.44, P = 2.81 × 10-4), and 5-fluorouracil (0.82 ± 0.13 vs 2.81 ± 0.51, 0.82 ± 0.13 vs 3.28 ± 1.03, P = 1.71 × 10-4). Flow cytometry confirmed that the percentage of apoptotic cells increased after CDX2 downregulation (32.15% ± 2.15% vs 17.63% ± 3.16%, 32.15% ± 2.15% vs 19.3% ± 2.25%, P = 1.73 × 10-6). This notion was further supported by the observation that downregulation of CDX2 blocked entry into the S-phase of the cell cycle (31.53% ± 3.78% vs 65.05% ± 7.25%, 31.53% ± 3.78% vs 62.27% ± 5.02%, P = 7.55 × 10-7). Furthermore, downregulation of CDX2 significantly increased intracellular accumulation of doxorubicin (0.21 ± 0.06 vs 0.41 ± 0.11, 0.21 ± 0.06 vs 0.40 ± 0.08, P = 0.003). In molecular studies, semiquantitative RT-PCR and western blotting revealed that CDX2 downregulation could inhibit expression of c-Myc, survivin and cyclin D1.
CONCLUSION: CDX2 may be involved in regulating multiple signaling pathways in reversing MDR, suggesting that CDX2 may represent a novel target for gastric cancer therapy.
Homeobox gene CDX2; RNA interference; Gastric cancer; Drug resistance; Murine model
Although the platinum regimen is adopted widely nowadays in spite of the excessive side effects, there is still no international standard for palliative chemotherapy of advanced gastric cancer. This meta-analysis assessed the efficacy and tolerability of platinum versus non–platinum chemotherapy as first-line palliative treatment in patients with inoperable, advanced gastric cancer.
Randomized phase II and III clinical trials on first-line palliative chemotherapy in inoperable, advanced gastric cancer were identified by electronic searches of PubMed, Embase, and the Cochrane Controlled Trial Register, and hand searches of relevant abstract books and reference lists. Response rates, overall survival, and toxicity were analyzed. Depending on whether new-generation agents (S-1, taxanes and irinotecan) were utilized, the non–platinum regimens were divided into two subgroup.
Compared to non-platinum regimens containing new-generation agents, the use of platinum-based regimens was associated with better response (risk ratio (RR) = 1.94, 95%CI[1.48, 2.55], p<0.001), an increase of overall survival (hazard ratio (HR) = 0.85, 95%CI[0.78, 0.92], p<0.001), a higher risk of hematological and non-hematological toxicity. No statistically significant increase in response (RR = 1.03, 95%CI [0.85, 1.24], p = 0.76) or overall survival (HR = 1.07, 95%CI [0.88, 1.30], p = 0.49) was found when platinum therapies were compared to new-generation agent based combination regimens. The toxicity of platinum-based regimens was significantly higher for hematologic toxicity, nausea and vomiting, and neurotoxicity, but not for diarrhea and toxic death rate.
New-generation agent based combination regimens achieved similar response rate and overall survival as platinum-based therapy that had generally higher side effects. S-1, taxanes and irinotecan seemed to be valid options for patients with inoperable, advanced gastric cancer as first-line chemotherapy.
The sterile alpha motif (SAM) and HD domain-containing protein-1 (SAMHD1) inhibits the infection of resting CD4+ T cells and myeloid cells by human and related simian immunodeficiency viruses (HIV and SIV). Vpx inactivates SAMHD1 by promoting its proteasome-dependent degradation through an interaction with CRL4 (DCAF1) E3 ubiquitin ligase and the C-terminal region of SAMHD1. However, the determinants in SAMHD1 that are required for Vpx-mediated degradation have not been well characterized. SAMHD1 contains a classical nuclear localization signal (NLS), and NLS point mutants are cytoplasmic and resistant to Vpx-mediated degradation. Here, we demonstrate that NLS-mutant SAMHD1 K11A can be rescued by wild-type SAMHD1, restoring its nuclear localization; consequently, SAMHD1 K11A became sensitive to Vpx-mediated degradation in the presence of wild-type SAMHD1. Surprisingly, deletion of N-terminal regions of SAMHD1, including the classical NLS, generated mutant SAMHD1 proteins that were again sensitive to Vpx-mediated degradation. Unlike SAMHD1 K11A, these deletion mutants could be detected in the nucleus. Interestingly, NLS-defective SAMHD1 could still bind to karyopherin-β1 and other nuclear proteins. We also determined that the linker region between the SAM and HD domain and the HD domain itself is important for Vpx-mediated degradation but not Vpx interaction. Thus, SAMHD1 contains an additional nuclear targeting mechanism in addition to the classical NLS. Our data indicate that multiple regions in SAMHD1 are critical for Vpx-mediated nuclear degradation and that association with Vpx is not sufficient for Vpx-mediated degradation of SAMHD1. Since the linker region and HD domain may be involved in SAMHD1 multimerization, our results suggest that SAMHD1 multimerization may be required for Vpx-mediation degradation.
A susceptibility locus for tuberculosis, a re-emerging infectious disease throughout the world, was previously discovered to exist on chromosome 11p15. IFITM3 gene encoding for interferon inducible transmembrane protein 3, is located at 11p15. It acts as an effector molecule for interferon-gamma, which is essential for anti-tuberculosis immune response. In order to investigate the association between susceptibility to TB and genetic polymorphisms of the IFITM3 core promoter, a case-control study including 368 TB patients and 794 healthy controls was performed in Han Chinese children in northern China. The rs3888188 polymorphism showed significant association with susceptibility to TB. The rs3888188 G allele, acting recessively, was more frequent in TB patients (95% confidence interval: 1.08–1.56, Bonferroni P-value: 0.039). We further assessed the effect of rs3888188 polymorphism on IFITM3 transcription in vitro. As based on luciferase promoter assays, the promoter activity of haplotypes with rs3888188 G allele was lower than that of haplotypes with rs3888188 T allele. Moreover, peripheral-blood mononuclear cells carrying rs3888188 GG genotype showed a reduced IFITM3 mRNA level compared to cells carrying TT or GT genotype. In conclusion, rs3888188, a functional promoter polymorphism of IFITM3, was identified to influence the risk for pediatric TB in Han Chinese population.
Malignant renal subcapsular effusions commonly arise from primary or metastatic renal neoplasms. The current case report presents a rare case of malignancy with a massive renal subcapsular effusion accompanied by a malignant pleural effusion of an unknown primary site, which underwent progression to carcinomatous meningitis during chemotherapy. The type of adenocarcinoma present was determined by effusion cytology. Intravenous chemotherapy (docetaxel plus oxaliplatin and gemcitabine plus cisplatin) were administered; however, the disease still progressed. Time to progression was 9 months during treatment of gefitinib. Comprehensive therapies, including intracavity chemotherapy, immunotherapy and gefitinib, were shown to be effective and prolonged the patient’s survival time.
neoplasms; unknown primary site; pleural effusion; renal; adenocarcinoma
Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).
This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography.
Patients with CAD (n = 231) and without CAD (n = 482) as confirmed by coronary angiography were included. Among them, 574 patients underwent B-ultrosonography were divided into NAFLD group (n = 209) and non-NAFLD group (n = 365). Correlation between FLI and NAFLD was analyzed using pearson’s correlation. The associations between FLI and NAFLD as well as CAD were assessed using logistic regression. The predictive accuracy of FLI for NAFLD was evaluated using receiver operating characteristics (ROC) curve analysis.
FLI was significantly higher in NAFLD group (37.10 ± 1.95) than in non-NAFLD group (17.70 ± 1.04), P < 0.01. FLI correlated with NAFLD (r = 0.372, P < 0.001). The algorithm for FLI had a ROC-AUC of 0.721 (95% CI: 0.678–0.764) in the prediction of NAFLD. Logistic regression analysis showed that FLI was associated with NAFLD (adjusted OR = 1.038, 95% CI: 1.029-1.047, P < 0.01). The proportion of patients with CAD did not differ among the groups of FLI ≤ 30 (32.3%), 30-60 (31.0%), and ≥60 (35.3%). No significant association was found between FLI and CAD (adjusted OR = 0.992, 95% CI: 0.981-1.003 in men and OR = 0.987, 95% CI: 0.963-1.012 in women, P > 0.05).
FLI showed good correlation with NAFLD in patients who underwent coronary angiography, but not with newly diagnosed CAD. This might be underestimated because some patients in non-CAD group may have other underlying cardiovascular diseases.
Fatty liver index; Non-alcoholic fatty liver disease; Coronary artery atherosclerotic disease; Coronary angiography
In situ expression of a foreign antigen and an immune-modulating cytokine by intratumoral DNA electroporation was tested as a cancer therapy regimen. Transgene expression in the tumors sustained for 2–3 wks after intratumoral electroporation with mammalian expression plasmid containing firefly luciferase cDNA. Electroporation with cDNA encoding tetanus toxin fragment C (TetC) induced tetanus toxin-binding antibody, demonstrating immune recognition of the transgene product. Intratumoral electroporation with TetC and IL-12 cDNA after mice were treated with CD25 mAb to remove regulatory T cells induced IFN-γ producing T cell response to tumor associated antigen, heavy inflammatory infiltration, regression of established tumors and immune memory to protect mice from repeated tumor challenge. Intratumoral expression of immune modulating molecules may be most suitable in the neoadjuvant setting to enhance the therapeutic efficacy and provide long term protection.
neoadjuvant immunotherapy; intratumoral DNA electroporation; tumor microenvironment
RBFOX1 is an important splicing factor regulating developmental and tissue-specific alternative splicing in heart, muscle, and neuronal tissues. Constitutional genetic defects in RBFOX1 are implicated in multiple medical conditions.
We identified 14 copy number variants (CNV) involving RBFOX1 from 2,124 consecutive pediatric patients referred for chromosomal microarray analysis (CMA), including 13 intragenic deletions and a single intragenic duplication. The clinical significances of the intragenic deletions of RBFOX1 were evaluated.
Our data strongly supports the associations of intragenic deletions of RBFOX1 with a diversity of neurodevelopmental and neuropsychiatric disorders, and possibly other clinical features.
Microdeletion; Chromosome 16p13.3; RBFOX1; Chromosomal microarray analysis (CMA); Seizures; Developmental delay
To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmonary metabolic activity on post-treatment [18F]-fluorodeoxyglucose positron emission tomography (FDG PET).
We retrospectively studied 101 esophageal cancer patients who underwent restaging FDG PET/CT imaging between 3 and 12 weeks after completing thoracic radiotherapy. The Common Toxicity Criteria version 3 (CTC3) was used to score RP clinical symptoms. Linear regression was applied to the FDG PET/CT images to determine the normalized FDG uptake versus radiation dose. The pulmonary metabolic radiation response (PMRR) was quantified as this slope. Modeling was performed to determine the interaction of PMRR, mean lung dose (MLD), and percentage of lung receiving greater than 20 Gy (V20) with RP outcomes.
Of the 101 patients, 25 had grade 0, 10 had grade 1, 60 had grade 2, 5 had grade 3, and 1 had grade 5 RP symptoms. Logistic regression demonstrated that increased values of both MLD and PMRR were associated with a higher probability of RP clinical symptoms (P=0.032 and P=0.033, respectively). Spearman’s rank correlation found no association between the PMRR and dosimetric parameters (PTV, MLD, V5 through V30). Two-fold cross validation demonstrated the combination of MLD and PMRR was superior to either alone for assessing the development of clinical symptoms of RP. The combined MLD (or V20) and PMRR had a higher sensitivity and accuracy (53.3 and 62.5, respectively) than either alone.
This study demonstrated a significant correlation between RP clinical symptoms and the PMRR measured by FDG PET/CT following thoracic radiotherapy.
radiation pneumonitis; pulmonary injury; computed tomography; positron emission tomography
The primary aim of this study was to quantitatively assess pulmonary radiation toxicity in patients who received thoracic radiotherapy combined with induction and/or concurrent chemotherapy with or without taxanes for esophageal cancer.
Subjects were 139 patients treated at The University of Texas M. D. Anderson Cancer Center for esophageal cancer and who had [18F]-fluorodeoxyglucose positron emission tomography/computed tomography imaging from November 1, 2003 to December 15, 2007, for disease restaging after chemoradiotherapy. Patients were grouped as having had (1) no taxanes, (2) induction or concurrent taxanes, and (3) both induction and concurrent taxanes. Clinical pulmonary toxicity was scored using the NCI Common Terminology Criteria for Adverse Events version 3. Linear regression was applied to the FDG uptake versus radiation dose to determine the pulmonary metabolic radiation response (PMRR) for each case. Clinical toxicity scores and PMRR among groups were evaluated for significance differences.
The crude rates of pneumonitis symptoms were 46%, 62%, and 74% for groups 1, 2, and 3, respectively. The ANOVA test of log(PMRR) by treatment was significant (p=0.0046). Group 3 had 61% higher PMRR compared with group 1 (p=0.002). Group 2 had 38% higher PMRR compared with group 1 (p=0.015). Group 3 had 17% higher PMRR compared with group 2 (p=0.31). A PMRR enhancement ratio of 1.60 (95% CI: 1.19–2.14) was observed for group 3 versus group 1.
Patients given taxanes chemotherapy as induction and concurrent chemotherapy had significantly higher PMRR and clinical pneumonitis symptoms than did patients whose chemotherapy did not include taxanes.
Radiation pneumonitis; taxanes; positron emission tomography
Radish floral bud abortion (FBA) is an adverse biological phenomenon that occurs during reproduction. Although FBA is a frequent occurrence, its molecular mechanism remains unknown. A transcript-derived fragment (TDF72), which was obtained by cDNA amplified fragment length polymorphism (cDNA-AFLP), was up-regulated in the aborted buds and exhibited 89% sequence homology with the AtγVPE gene. In this study, TDF72 was used to clarify the role of VPE in FBA by isolation of the VPE gene RsVPE1 from radish flower buds. The full-length genomic DNA was 2346 bp including nine exons and eight introns. The full-length cDNA was 1825 bp, containing a complete open reading frame (ORF) of 1470 bp, which encoded a predicted protein containing 489 amino acid residues, with a calculated molecular mass of 53.735 kDa. Expression analysis demonstrated that RsVPE1 was expressed in all tested organs of radish at different levels. Highest expression was detected in aborted flower buds, suggesting that RsVPE1 has a role in FBA. In order to analyze the role of RsVPE1 in FBA, RsVPE1 was overexpressed in transgenic Arabidopsis thaliana plants. Aborted flower buds appeared in transgenic plants subjected to heat stress. In addition, RsVPE1 expression in the transgenic plants reached a maximum when subjected to heat stress for 24 h and increased by 2.1-fold to 2.8-fold in three homozygous transgenic lines. These results indicated that RsVPE1 led to FBA when its expression levels exceeded a particular threshold, and provided evidence for the involvement of RsVPE1 in promoting FBA under heat stress.
radish; vacuolar processing enzyme; floral bud abortion; heat stress