Relationship between dietary patterns and diabetic microvascular complications in patients with type 2 diabetes mellitus.

OBJECTIVE: This study aimed to investigate the relationship between different dietary patterns and diabetic microvascular complications in patients with type 2 diabetes mellitus. PATIENTS AND METHODS: This study was conducted based on the Chinese Chronic Disease and its Risk Factor Surveillance System. A multi-stage stratified sampling method was used to randomly select two districts (Henghualing District, Taiyuan City, and Yuzi District, Jinzhong City) and two counties (Huguan County, Changzhi City, and Jiang County, Yuncheng City) from the chronic disease surveillance sites in Shanxi Province to collect general information, dietary records, physical measurements, and laboratory tests. In total, 1,227 patients were enrolled according to the study criteria. Factor analysis was performed to construct six dietary patterns, and the relationship between dietary pattern scores and type 2 diabetic microvascular complications was analysed using binary logistic regression after correcting for confounders. RESULTS: (1) Regarding the prevalence of type 2 diabetic microvascular complications and dietary characteristics, the prevalence of microvascular complications in patients with type 2 diabetes mellitus was 55.3% and was higher in urban than in rural areas. The prevalence of diabetic kidney disease (DKD), diabetic retinopathy, and diabetic peripheral neuropathy (DPN) were 21.4%, 12.7%, and 38.0%, respectively. (2) Six dietary patterns were constructed, namely, 'animal protein', 'coarse grains and plant protein', 'nuts and fruits', 'refined grains and vegetables', 'dairy', and 'added sugars', with factor contributions of 15.42%, 9.99%, 8.23%, 8.16%, 7.56%, and 7.28% respectively, explaining 56.64% of the total dietary variation. (3) After adjusting for confounding variables, the results of binary logistic regression indicated that patients in the highest quartile of dietary pattern scores for 'nuts and fruits' experienced a 43.3% lower risk of DKD compared to those in the lowest quartile [odds ratio (OR) = 0.567; 95% confidence interval (CI), 0.359-0.894; p < 0.001]. Similarly, patients in the highest quartile of dietary pattern scores for 'animal protein' had a 42.8% lower risk of DPN compared with those in the lowest quartile (OR = 0.572; 95% CI, 0.388-0.843; p < 0.05). CONCLUSIONS: The results of this study suggest that in patients with type 2 diabetes mellitus, a 'nuts and fruits' dietary pattern reduces the risk of DKD and an 'animal protein' dietary pattern reduces the risk of DPN.

Enhancement of blue and ultraviolet components in PCF-based supercontinuum generation through inter-modal dispersive-wave radiation.

Broadband supercontinuum (SC) light sources generated through nonlinear effects in solid-core photonic crystal fibers (PCFs) have been widely used in spectroscopy, metrology, and microscopy, leading to great application successes. The short-wavelength extension of such SC sources, a longstanding challenge, has been the subject of intensive study over the past two decades. However, the exact mechanism of blue and ultraviolet light generation, especially for some resonance spectral peaks in the short-wavelength regime, is not yet fully understood. Here, we demonstrate that the effect of inter-modal dispersive-wave radiation, which results from phase matching between pump pulses at the fundamental optical mode and packets of linear waves at some higher-order modes (HOMs) propagating in the PCF core, might be one of the critical mechanisms that can result in some resonance spectral components with wavelengths much shorter than that of the pump light. We observed in an experiment that several spectral peaks resided in the blue and ultraviolet regimes of the SC spectrum, whose central wavelengths can be tuned by varying the PCF-core diameter. These experimental results can be interpreted well using the inter-modal phase-matching theory, providing some useful insights into the SC generation process.

[Effects of ascites derived exosomes on the stemness and invasion ability of ovarian cancer stem-like cell].

Objective: To investigate the effects of ovarian cancer ascites-derived exosomes on the stem cell properties and invasion ability of ovarian cancer stem-like cell (OCS-LC). Methods: (1) A2780 cells were induced into OCS-LC in serum-free medium, and authenticating their stem-like properties by sphere-forming test, differentiation test and CD133 marker detection. (2) Exosomes from ascites and A2780 cell were extracted by ultracentrifugation, then authenticating them. The morphology of exosomes was observed by the transmission electron microscope, exosome particle size was measured by nanoparticle tracking analysis (NTA). The expressions of heat shock protein 70 (HSP-70), CD63 and CD9 were detected by western blot. (3) The exosomes from ovarian cancer ascites and tumor cell supernate were co-cultured with OCS-LC. The groups were divided into control group, ascites-derived exosomes (ADE) group (ADE+OCS-LC group), and cells-derived exosomes (CDE) group (CDE+OCS-LC group). The sphere-forming ability was evaluated by sphere-forming cycle, maximum sphere diameter and sphere-forming rate of each group; the expression of CD133 was detected by immunofluorescence staining under microscope; quantitative real-time (qRT)-PCR was used to detected the expression levels of octamer-4 (Oct-4), Nanog mRNA of the signature genes in the stem cells of each group; the metastasis ability of each group was measured by transwell assay. Results: (1) Identification of OCS-LC: sphere-forming experiment showed that the suspension of OCSC single cells was grown in serum-free medium in secondary sphere-forming. Differentiation function experiment showed that OCS-LC were differentiated into adherent A2780 cells by changing the growth mode in serum containing medium. Flow cytometry showed that the proportion of CD133 positive (CD133+) cells in OCS-LC group was (18.9±0.9)%, significantly higher than that of control group (0.6±0.5)% (t=38.570, P<0.01). (2) Under transmission electron microscope, clear lipid bilayer structure was observed in ADE and CDE, and one side presented a concave hemispheric or cup like structure. NTA showed that the diameter of exosomes mainly ranged from 30 to 100 nm, with an average diameter of 67.2 nm. Western blot analysis showed that the specific protein molecules HSP-70, CD63 and CD9 were positive. (3) Three groups' OCS-LC could continue to grow into spheres, and the group of ADE+OCS-LC showed two growth modes, most of the cells continued to grow into spheres, while a small part of cells grew in adherent differentiation. The sphere-forming rate of OCS-LC in the control group, ADE+OCS-LC group, and CDE+OCS-LC group were (1.05±0.20)%, (4.15±0.10)%, and (10.45±0.25)%, the sphere-forming cycle of OCS-LC in the three groups were (15.3±1.5), (10.3±0.6), and (6.7±0.6) days, and the maximum diameters of OCS-LC were (100.3±3.2), (145.2±5.1) and (170.0±2.1) µm, respectively. And the differences were statistically significant (all P<0.05). After co-culture of exosomes with OCS-LC, the sphere-forming ability of cells in the group of CDE+OCS-LC was prior to ADE+OCS-LC group (all P<0.05). Immunofluorescence staining showed that the number of CD133 green fluorescent chromophore cells in OCS-LC groups [(46.2±2.1)%, (58.4±2.2)%] was significantly higher than that in the control group [(26.6±1.5)%] after the addition of exosomes in co-culture, the positive rate of CD133 was higher than that in the control group(F=187.588, P<0.05). The qRT-PCR results showed that the expression levels of Oct-4 mRNA in ADE+OCS-LC and CDE+OCS-LC groups were 3.46±0.24, 4.03±0.31, compared with that in control group (1.04±0.12), the differences were statistically significant (F=134.932, P<0.05). The mRNA expression levels of Nanog were 1.57±0.32, 2.66±0.15, which were significantly higher than that in the control group (1.00±0.07), and the differences were statistically significant (F=49.329, P<0.05). And the expression of both in CDE+OCS-LC group increased more significantly than ADE+OCS-LC group (all P<0.05). The number of invasive cells in the three groups of OCS-LC were: control group 30±5, ADE+OCS-LC group 102±4, CDE+OCS-LC group 210±7, and there were statistically significant differences among three groups (F=820.800, P<0.05). Compared with the control group, the number of invaded cells in the co-culture group were significantly increased (P<0.05), and the CDE+OCS-LC group had the higher cell invasion ability then the ADE+OCS-LC group (t=23.202, P<0.05). Conclusions: Exosomes derived from ovarian cancer ascites could enhance and maintain the stemness of OSC-LC, and promote the invasion of tumor cells. Moreover, CDE is superior to ADE.

[The correlation between serum uric acid levels in the third trimester of pregnancy and adverse pregnancy outcomes].

Objective: To investigate the associations between serum uric acid levels during the third trimester of pregnancy and risks of adverse pregnancy outcomes. Methods: In this retrospective study, a cohort of 7 995 pregnant women who were hospitalized for childbirth from January 2014 to January 2019 were collected to compare pregnancy outcomes between subjects with or without hyperuricemia (HUA). A smooth curve analysis was used to evaluate the relationship between uric acid levels and preterm delivery, low birth weight and smaller than gestational age. Logistic regression analyses were performed to identify risk factors for adverse pregnancy outcomes, and the interaction of the factors. Results: During the third trimester of pregnancy, the uric acid levels of about 10% pregnant women were over 420 µmol/L. In those with HUA, the median neonatal birth weight was 2 590 (1 790, 3 410) g, the probability of premature birth was 49.81%, and the incidence of small than gestational age was 20.41%. These were significantly different from the women without HUA (the median neonatal birth weight: 3300 (2850, 3640) g; the probability of premature birth 23.09%; the incidence of small than gestational age 6.55%, respectively) (All P<0.001). Maternal uric acid levels were negatively correlated with neonatal birth weight, and positively correlated with the risk of smaller than gestational age. It has a U-shaped association with the probability of premature birth, and the lowest probability of premature birth was at 200-400 µmol/L of the uric acid. Risks of low birth weight (adjusted ß=-5.22, 95%CI-6.46--3.99) and smaller than gestational age (adjusted OR=1.03, 95%CI 1.02-1.04) were increased in the function of uric acid levels. High uric acid, hypertension, oligoamnios and preeclampsia were important risk factors for the adverse pregnancy outcomes. The risk of preterm delivery and low birth weight enhanced when hyperuricemia combined with hypertension and preeclampsia. Conclusions: Serum uric acid level can be used as one of reliable markers for predicting adverse pregnancy outcomes, which might provide theoretical basis for clinical intervention in practice.

Circ-ABCB10 acts as an oncogene in glioma cells via regulation of the miR-620/FABP5 axis.

OBJECTIVE: This study aims to investigate the biological function of circular RNA ABCB10 (circ-ABCB10) in regulating the progression of glioma and to study the possible underlying mechanisms. PATIENTS AND METHODS: The expression levels of circ-ABCB10, miR-620 and FABP5 mRNA in glioma tissues, normal surrounding tissues and glioma cell lines were measured by Real-time PCR (RT-PCR). Circ-ABCB10 was silenced by siRNA in glioma cell lines (U87, T98G). The proliferation, migration and invasion of glioma cells were measured by MTT, wound healing and transwell assays, respectively. The relationship between circ-ABCB10, miR-620 and FABP5 was tested by Dual-Luciferase assay. The expression of proteins was measured by Western blot. The cell cycle distribution and apoptosis were measured by flow cytometry. RESULTS: The expression levels of circ-ABCB10 and FABP5 in glioma tissues and cells were significantly higher than those in their normal counterparts. Moreover, the expression of miR-620 was lower in glioma tissues. Silencing of circ-ABCB10 in glioma cells significantly inhibited the proliferation, migration and invasion of glioma cells. Moreover, downregulation of circ-ABCB10 induced cell cycle arrest and apoptosis in glioma cells. Furthermore, inhibition of miR-620 showed the opposite effects to silencing circ-ABCB10 on glioma cells. Dual-Luciferase reporter assays demonstrated that circ-ABCB10 could bind to miR-620 and that FABP5 was a direct target of miR-620. Western blot results showed that circ-ABCB10 could stabilize the expression of FABP5, while miR-620 decreased the expression of FABP5. Furthermore, overexpression of FABP5 abrogated the silencing effects of circ-ABCB10 in glioma cells. CONCLUSIONS: These data suggest that circ-ABCB10 affects glioma progression by regulating the miR-620/FABP5 axis, and circ-ABCB10 might be used as a potential target for the treatment of glioma.

Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death.

High fidelity and effective adaptive changes of the cell and tissue metabolism to changing environments require strict coordination of numerous biological processes. Multicellular organisms developed sophisticated signaling systems of monitoring and responding to these different contexts. Among these systems, oxygenated lipids play a significant role realized via a variety of re-programming mechanisms. Some of them are enacted as a part of pro-survival pathways that eliminate harmful or unnecessary molecules or organelles by a variety of degradation/hydrolytic reactions or specialized autophageal processes. When these "partial" intracellular measures are insufficient, the programs of cells death are triggered with the aim to remove irreparably damaged members of the multicellular community. These regulated cell death mechanisms are believed to heavily rely on signaling by a highly diversified group of molecules, oxygenated phospholipids (PLox). Out of thousands of detectable individual PLox species, redox phospholipidomics deciphered several specific molecules that seem to be diagnostic of specialized death programs. Oxygenated cardiolipins (CLs) and phosphatidylethanolamines (PEs) have been identified as predictive biomarkers of apoptosis and ferroptosis, respectively. This has led to decoding of the enzymatic mechanisms of their formation involving mitochondrial oxidation of CLs by cytochrome c and endoplasmic reticulum-associated oxidation of PE by lipoxygenases. Understanding of the specific biochemical radical-mediated mechanisms of these oxidative reactions opens new avenues for the design and search of highly specific regulators of cell death programs. This review emphasizes the usefulness of such selective lipid peroxidation mechanisms in contrast to the concept of random poorly controlled free radical reactions as instruments of non-specific damage of cells and their membranes. Detailed analysis of two specific examples of phospholipid oxidative signaling in apoptosis and ferroptosis along with their molecular mechanisms and roles in reprogramming has been presented.

[Relationship between morphological characteristics and prognosis of non-nasopharyneal EBV-associated carcinoma].

Objective: To analyze the pathological features and their influence on the clinical outcome of non-nasopharyngeal EBV-associated carcinomas. Methods: One hundred and twenty cases of non-nasopharyngeal EBV-associated carcinoma confirmed by in situ hybridization were identified at Zhejiang Cancer Hospital from January 1, 2006 to May 1, 2018, and the clinicopathological data were collected and analyzed using Kaplan-Meier survival analysis, Cox univariate and multivariate analysis. Results: One hundred and twenty cases were involved in the study; the male to female ratio was 1∶1; patients' age range was 24 to 89 years (median 50 years). The primary sites were large parotid glands (62 cases), lung(26 cases), stomach(15 cases), and others (oral, oropharynx, larynx, cervix, liver; totally 17cases). Non-nasopharyngeal EBV-associated cancer could be divided into two histological types according to the amount of interstitial lymphocytes: type Ⅰ was "lymphoepithelial-like carcinoma" and rich in stromal lymphocytes; type Ⅱ lacked lymphocytic infiltration. Ninety-eight primary tumor samples could be classified morphologically: 43 cases were as type Ⅰ and 55 cases as typeⅡ; the distribution of type Ⅰ was 57.4% (27/47) in large parotid glands, 20.8% (5/24) in lung, 4/13 in stomach, and 7/14 in other sites. Complete treatment and survival data were obtained for 114 patients. According to the TNM staging criteria of WHO, 52 patients were at early stages (Ⅰ-Ⅱ) and 62 were at advanced stages (Ⅲ-Ⅳ); 102 patients underwent surgery. Seventy-four patients received adjuvant chemotherapy before or after surgery, and 52 patients received local radiotherapy. Kaplan-Meier survival analysis showed that patients with type Ⅱ EBV-associated carcinoma had a worse prognosis than patients with type Ⅰtumors (P=0.010 2). In addition, vascular invasion(P=0.021 8),neural recidivism(P=0.000 1),advanced stage(P=0.017 1),lymph node metastasis (P=0.005 0) and chemotherapy (P=0.013 2) were poor prognostic factors; female patients had better survival than male (P=0.028 4). Cox multivariate regression analysis found that lymph node metastasis (95%CI: 1.489-13.830, P=0.007 6) and neural recidivism (95%CI: 1.228-6.544, P=0.014 7) were independent adverse prognostic factors. Cox multivariate regression analysis after stratification by site revealed that radiotherapy was a preferable prognostic factor for EBV-associated carcinoma of the large salivary glands (95%CI: 0.003-0.569, P=0.016 8). Conclusion: EBV associated carcinoma can be divided into two types, for which type Ⅰ was with abundant interstitial lymphocytes and type Ⅱ was lack of interstitial lymphocytes. TypeⅡ EBV-associated carcinoma has a worse prognosis than type Ⅰ. Radiation therapy can prolong the survival time of patients with primary EBV-associated carcinoma of large salivary glands.

[HER2 status in gastric adenocarcinoma of Chinese: a multicenter study of 40 842 patients].

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions: HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

[Survival of patients with primary central nervous system diffuse large B-cell lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens].

Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis. Conclusions: Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.

[Loss of BRCA associated protein 1 expression in malignant mesothelioma and its diagnostic application].

Objective: To investigate the expression of BRCA-associated protein 1 (BAP1) in malignant mesothelioma, non-small cell lung cancer and carcinosarcoma, and its application in the differential diagnosis. Methods: Twenty-two cases of malignant mesothelioma including 17 epithelioid type, 2 sarcomatoid type and 3 biphasic type were collected.As the study control, 80 non-small cell lung cancers infringement pleural membrane(including 40 lung adenocarcinomas and 40 lung squamous cell carcinomas) and 15 carcinosarcomas were included. BAP1 expression was detected using immunohistochemical method. A differential diagnosis antibody panel, including calretinin, WT1, CK5/6, D2-40, CAM5.2, CEA, TTF1, Napsin A, p63 and p40 was tested in all cases. Results: All 80 cases of non-small cell lung cancer and 15 cases of carcinosarcoma were BAP1 positive. In contrast, 64% (14/22) of malignant mesotheliomas lost BAP1 expression (P<0.01). Addition of BAP1 to the mesothelioma marker panel, the diagnostic accuracy of malignant mesothelioma was enhanced to 93%. Focal expression of BAP1 in tumors suggested multiclonal evolution of mesothelioma. Conclusions: Loss of BAP1 expression helps to confirm the diagnosis of malignant mesothelioma whereas all non-small cell lung cancer expresses BAP1. It is therefore recommended that BAP1 can be used in conjunction with other immunohistochemical markers to improve the diagnostic accuracy of malignant mesothelioma.

Characterization of the Microbial Communities in the Ant Lion Euroleon coreanus (Okamoto) (Neuroptera: Myrmeleontidae).

Euroleon coreanus (Okamoto) is widely distributed in China, and the larval stage can be treated as traditional Chinese medicine. However, the host-bacterium relationship remains unexplored, as there is a lack of knowledge on the microbial community of ant lions. Hence, in the current study, we explored the microbial community of the larval ant lion E. coreanus using Illumina MiSeq sequencing. Results indicated that a total of 10 phyla, 126 genera, and 145 species were characterized from the second instars of E. coreanus, and most of the microbes were classified in the phylum Proteobacteria. Cronobacter muytjensii was the most abundant species characterized in the whole body and gut of E. coreanus, and the unclassified species in the genera Brevundimonas and Lactobacillus were relatively more abundant in the head and carcass. In addition, no Wolbachia-like bacteria were detected, whereas bacteria like Francisella tularensis subsp. Holarctica OSU18 and unclassified Rickettsiella were first identified in ant lion E. coreanus.

Small interfering RNA targeting nuclear factor kappa B to prevent vein graft stenosis in rat models.

BACKGROUND: Intimal hyperplasia plays an important role in vein graft stenosis. Inflammatory injury, especially nuclear factor kappaB (NF-κB) gene activation, is highly involved in stenosis progression. We examined whether neointimal hyperplasia and vein graft stenosis could be inhibited by silencing the NF-κB gene with small interference RNA (siRNA). METHODS: Sixty adult male Sprague-Dawley rats were randomly divided into a normal vein group, a vein graft group, a scrambled siRNA group, and an NF-κB siRNA group. We performed reverse interpositional grafting of the autologous external jugular vein to the abdominal aorta. Vein grafts were treated with liposome and gel complexes containing NF-κB siRNA or scrambled siRNA. The levels of monocyte chemoattractant protein -1, tumor necrosis factor-α, and NF-κB p65 in vessel tissues were evaluated after surgery for content of proliferating cell nuclear antigen (PCNA) and vascular wall thickness. RESULTS: NF-κB siRNA treated vein graft showed less neointimal formation and fewer positive PCNA cells (P < .05). In addition there were lower levels of, NF-κB p65 protein and of inflammatory mediators (P < .05) compared with the vein graft group. CONCLUSION: Our study suggested that siRNA transfection suppressed NF-κB expression, reduced inflammatory factors, lessened neointimal proliferation, and suppressed PCNA.

Epidermal growth factor receptor mutations in small cell lung cancer patients who received surgical resection in China.

To know the incidence of epidermal growth factor receptor (EGFR) mutations in small cell lung cancer (SCLC) patients who received surgical resection in mainland China. xTAG technology was used to detect the EGFR exon 19 and exon 21 mutations of 40 patients with SCLC who received surgical treatment in Zhejiang Cancer Hospital from 1998 to 2010. 2 of 40 cases were found with mutations in exon 19 of the EGFR gene. The mutation in exon 19 of the EGFR gene is in a female and non smoking patient which pathology is SCLC combined adenocarcinoma, and the other is male and smoking patient which pathology is SCLC combined squamous cell carcinoma. The EGFR mutation is rare in SCLC patients, and EGFR mutation might occur more often in combined SCLCs than conventional patients.

Distribution of basement membrane in supraglottic carcinoma.

The object of this study was to assess the distribution of basement membrane in supraglottic squamous cell carcinomas. Expression of type IV collagen was detected by immunohistochemistry in resected supraglottic squamous cell carcinomas, and the correlation was examined between expression of type IV collagen and clinicopathological factors and cervical lymph node metastasis of supraglottic squamous cell carcinomas patients. An intact, continuous basement membrane was found in 17 cases (42.5%), while partial or widespread loss of the basement membrane was detected in the other 23 cases (57.5%). Heavily defective basement membrane was much more frequently observed in cases with poor histological differentiation (P < 0.05). Cases with BM destruction were more likely to be accompanied by cervical lymph node metastasis (P < 0.05). These data suggest that assessing the distribution pattern of basement membrane may be helpful in evaluating the malignancy grading of supraglottic squamous cell carcinomas and the potential occurrence of cervical lymph node metastasis.

Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease.

OBJECTIVES: Kashin-Beck disease (KBD) is a disabling osteoarthropathy involving growth cartilage endemic to selenium (Se)-deficient regions in China. Associations between genetic variation in selenoprotein genes and susceptibility to many diseases have recently been investigated but few studies have been performed on KBD. We found four genetic polymorphisms in selenoprotein genes and assessed their association with increased susceptibility to KBD. METHODS: Four polymorphisms including GPX1 (rs1050450), TrxR2 (rs5748469), SEPP1 (rs7579) and DIO2 (rs225014) were analyzed for 161 KBD patients and 312 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or tetra-primer amplification refractory mutation system PCR (Tetra-primer ARMS PCR). Glutathione peroxidase (GPX) activity in whole blood was measured using a GPX assay kit. The mRNA expression of GPX1, nuclear factor-kappaB (NF-kappaB) p65 and p53 in both whole blood and articular cartilage tissue were detected using Real-Time PCR. RESULTS: The genotypic and allelic frequency of GPX1 Pro198Leu was significantly different between KBD patients and controls (P=0.013, P=0.037). A significant increased KBD risk was observed in individuals with Pro/Leu or Leu/Leu (odds ratio=1.781; 95% confidence interval: 1.127-2.814) compared with Pro/Pro. No association was observed between the other three single nucleotide polymorphisms (SNPs) and KBD risk. In addition, GPX enzyme activity in whole blood was lower in the KBD group (P<0.01), and the GPX activity in whole blood decreased significantly in a subgroup of individuals representing Pro/Leu and Leu/Leu compared to Pro/Pro (P<0.01). In whole blood and articular cartilage tissue samples of KBD patients, GPX1 and NF-kappaB p65 mRNA levels were lower (P<0.01) while p53 levels were higher (P<0.001). CONCLUSION: GPX1 Pro198Leu is a potential genetic risk factor in the development of KBD and the GPX1 Leu allele is significantly associated with higher KBD risk among the Chinese Han population and with lower GPX enzyme activity. The expression of apoptosis related molecules in KBD patients significantly differs from controls.

The proteasome inhibitor bortezomib inhibits intimal hyperplasia of autologous vein grafting in rat model.

OBJECTIVE: Increasing evidence indicates that inflammation plays an important role in intimal hyperplasia (IH) induced by autologous vein grafts. The proteasome inhibitor bortezomib shows anti-inflammatory effects, so we used an autologous vein transplantation model to test whether bortezomib inhibits neointimal formation in transplant-induced vasculopathy. MATERIALS AND METHODS: We subjected 88 rats to autologous external jugular vein grafting surgery randomly assigned to be treated with bortezomib or vehicle. After 24 or 72 hours, rats were humanely killed and vein grafts processed for real-time RT-PCR (24 and 72 hours), ELISA (24 hours), or neutrophil chemotaxis assay (24 hours). Subsequently, rats were humanely killed at 1 and 2 weeks after grafting with samples processed for morphometric analysis. RESULTS: Bortezomib significantly inhibited IH at 2 weeks compared with untreated controls (P < .05). Expression of mRNA for vascular cell adhesion molecule-1, intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant 2beta, monocyte chemoattractant-1, interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha markedly increased in injured vessels during the first day after surgery declining over the following 3 days. Bortezomib significantly attenuated gene expression and protein levels of most inflammatory mediators (P < .05), simultaneously inhibiting neutrophil chemotactic activity of vessel homogenates. CONCLUSIONS: Bortezomib inhibited neointimal formation at least partially by attenuating the inflammatory response in transplant-induced vasculopathy. It may become a novel vasoprotective agent in the clinical field.

Factors affecting immunization status of college students in New York City (NYC).

OBJECTIVES: Although immunization is an important public health issue, there have been few studies conducted and minimal information gathered concerning the immunization status of NYC college students. In response to this void, the NYC Department of Health's Bureau of Immunization designed and implemented a study to determine the accessibility of immunization information and service. METHODS: Three hundred and twenty-one college students were asked to complete an immunization survey designed by the researchers in the immunization clinics of New York City. RESULTS: Significant correlations were found between the accessibility of immunization information and immigration status, years of residence in the U.S.A., primary language, as well as school credit completed. Results also indicated that the accessibility of immunization service correlates significantly with ethnicity, immigration status, primary language, years of residence in the U.S.A., accessibility of immunization information, insurance status, employment status, and personal and family income. CONCLUSIONS: The information gathered from this study is useful for public health administration, policy analysis, and program planning.

Self-assembly of frameworks with specific topologies: construction and anion exchange properties of M3L2 architectures by tripodal ligands and silver(I) salts.

Three five-component architectures, compounds 3, 4, and 5 were obtained by self-assembly of tripodal 1,3,5-tris(imidazol-1-ylmethyl )-2,4,6-trimethylbenzene (6) and 1,3,5-tris(benzimidazol-2-ylmethyl)benzene (7) ligands with silver(I) salts. The structures of these novel complexes have been determined by X-ray crystallography. The results of structural analysis indicate that these frameworks have same M3L2 components, but different structures. Compounds 3 and 4 are both M3L2 type cage-like complexes, while the 5 is an open trinuclear complex. The complex 3 is a cylindrical cage with simultaneous inclusion of a perchlorate anion inside of the cage as a guest molecule. Such guests can be exchanged for other anions through the open edge of the cage as evidenced by crystal structure of 4. The results demonstrate that the molecular M3L2 type cage can act as a host for anions and provide a nice example of supramolecular architectures with interesting properties and possible applications.

Prothrombin Scranton: substitution of an amino acid residue involved in the binding of Na+ (LYS-556 to THR) leads to dysprothrombinemia.

Several members of a family from Scranton, Pennsylvania were identified to have normal levels of prothrombin antigen while their prothrombin clotting activity was approximately 50% of normal. There has been no previous history of bleeding or other clinical manifestations in this family. The genomic DNA from the proband was amplified for all exons in the prothrombin gene and analyzed by single strand conformation polymorphism (SSCP)/heteroduplex analysis followed by DNA sequence analysis and restriction enzyme digestion. A mutation at nucleotide 20040 in exon 14 was identified and confirmed by restriction enzyme digestion. This mutation results in the substitution of Thr for Lys at amino acid 556. Amino acid 556 has been reported as one of the key residues for the binding of Na+ in the thrombin portion of the protein.