[Analysis of clinical effect of blood purification on acute benzene-based thinner poisoning].

Objective: To investigate the clinical significance of blood purification on changes in serum toxicant concentration and prognosis of acute benzene-based thinner poisoning. Methods: A total of 44 patients with acute benzene-based thinner poisoning admitted to the emergency department of Characteristic Medical Center of Armed Police from August 2013 to August 2020 were collected and divided into a blood purification group (24 cases) and a conventional treatment group (20 cases) , the general data, toxicant concentrations and prognosis of the two groups of patients were analyzed, and logistic regression analysis was performed on the influencing factors of the prognosis to explore the clinical effect of blood purification. Results: The concentration of poisons in the blood purification group at 24 hours after treatment was significantly lower than that in the conventional treatment group (t=6.76, P<0.001) , and the reduction in the concentration of poisons was significantly higher than that in the conventional treatment group (t=3.33, P=0.002) . The overall improvement rate in the blood purification group was 91.7% (22/24) , which was higher than that in the conventional treatment group (60.0%, 12/20) . Logisitic regression analysis showed that blood purification treatment method was the main factor affecting the prognosis of patients (OR=7.605×10(-5), 95%CI: 6.604×10(-8)-0.087, P=0.008) , and the toxic dose was a synergistic effect on the prognosis of patients factor (OR=1.038, 95%CI: 1.008-1.068, P=0.011) . Conclusion: Early blood purification treatment in patients with acute benzene-based thinner poisoning can rapidly reduce blood toxin concentration, avoid disease progression, and ultimately improve patient prognosis.

POMC gene expression, polymorphism, and the association with reproduction traits in chickens.

Reproduction trait is one of the most important economic traits in poultry industry. This study was aimed to investigate the mRNA expression levels, single nucleotide polymorphisms (SNP) of POMC gene, and the association with reproduction traits in chickens. Five SNP (g.958 G > A, g.1374 G > C, g.1393 G > A, g.1817 C > T, and g.1918G > A) were detected in introns of POMC gene in 317 Zhenning yellow chickens. Association analysis revealed that g.958 G > A and g.1817 C > T showed significantly associations with fertilization rate, hatching rate of hatching eggs, and hatching rate of fertilized eggs in chickens. Simultaneously, g.1374 G > C and g.1918G > A were both associated with egg weight at 300 D of age (P < 0.05). The SNP of g.958 G > A, g.1393 G > A, and g.1817 C > T were all associated with E2 hormone levels (P < 0.05). The result of mRNA expression levels in different tissues showed that POMC mRNA expression level in the pituitary was higher than those in the other tissues and varied in different genotypes. In conclusion, the results in this study provided new evidences that polymorphisms of the POMC gene have potential effects on reproduction traits in chickens. The 5 SNP detected in this study could be potential markers for improving reproduction traits in chickens.

[Surgical treatment for esophageal cancer during the outbreak of COVID-19].

Since December 2019, unexplained pneumonia has appeared in Wuhan City, Hubei Province, and a new type of coronavirus infection was confirmed as COVID-19. COVID-19 spread rapidly nationwide and abroad. The COVID-19 has brought huge impacts to all the people and walks of life, especially to the medical and health systems. It has also brought great challenges to the treatment of patients with cancer. Esophageal cancer is a common malignant tumor in China and most of the patients are in the middle and advanced stage when diagnosed, with immunosuppressive and poor prognosis. The selection of surgical procedures and perioperative managements of esophageal cancer require all thoracic surgeons work together to figure out a reasonable system of surgical treatment and emergency response.

[Short-term effects of air pollution on lung function of school-age children in Hangzhou].

A total of 1 685 school-age children selected from Hangzhou received lung function testing to evaluate the short-term effects of air pollution on their lung function. The results showed that in every 10 µg/m(3) increase of average concentration of PM(2.5) and PM(10) on the day of the test and the day before the test,peak expiratory flow (PEF) decreased 0.039 (95%CI: 0.012-0.067) L/s and 0.031 (95% CI:0.011-0.051) L/s,respectively. When the average concentration of SO(2) increased 10 µg/m(3) on the day of test and the day prior to the test, PEF and 75% of the forced vital capacity that has not been exhaled (MEF(75)) decreased 0.437 (95%CI: 0.217-0.658) L/s and 0.396 (95%CI: 0.180-0.613) L/s. After being adjusted for NO(2),with every 10 µg/m(3) increase of average concentration of PM(2.5) and PM(10) on the day of the test and the day before the test,PEF and MEF(75) decreased 0.056 (95%CI: 0.028-0.085), 0.053(95%CI: 0.027-0.081) and 0.047 (95%CI: 0.026-0.068) L/s,0.044 (95%CI: 0.023-0.065) L/s on the day before the test, respectively. The results indicate that air pollution have short-term and lag effects on lung function of school-age children in Hangzhou.

Down-regulation of microRNA-21 inhibits cell proliferation and invasion of high-invasion liver cancer stem cells.

OBJECTIVE: Cancer stem cells (CSCs) play critical roles in tumorigenesis, tumor recurrence and metastasis. This study aims to investigate the effects of small interfere microRNA-21 RNA (miR-21 RNAi) on cell proliferation, invasive ability of high-invasion liver cancer stem cells (H-ILCSCs), HCCLM3 and HL-7702 cells. MATERIALS AND METHODS: pLVX-shRNA2 lentiviral vector system was established, packaged and transfected into H-ILCSCs, HCCLM3 and HL-7702 cells. Cell counting kit-8 (CCK-8) assay was performed to observe cell viabilities of cells. Transwell assay was conducted to evaluate the invasion potential of H-ILCSCs, HCCLM3 and HL-7702 cells. Quantitative PCR (qPCR) assay was used to examine the miR-21 levels in different cell lines. RESULTS: pLVX-anti-miR21 lentiviral vector system was successfully established. miR-21 levels were down-regulated in anti-miR-21 gene steady expression cell lines compared to untreated cells (p<0.05). miR-21 levels were significantly lower in H-ILCSC2-LV-anti-miR-21 group compared to HCCLM3-anti-miR-21 and HL7702-anti-miR-21 (p<0.05). miR-21 inhibition significantly decreased cell proliferation and invasion compared to untreated cells (p<0.05). Cell proliferation and invasive ability of H-ILCSC2-LV-anti-miR-21 group were significantly higher compared to HCCLM3-anti-miR-21 and HL7702-anti-miR-21 (p<0.05). There were even not effects of miR-21 RNAi treatment on the cell proliferation and invasion of HL-7702 cells. CONCLUSIONS: The down-regulation of miR-21 significantly inhibited the cell proliferation and invasion abilities of H-ILCSCs and HCCLM3 cells, and illustrated higher effects on H-ILCSCs.

[Emphasizing the application of genetic diagnosis in branchio-oto-renal syndrome].

Summary Branchio-oto-renal syndrome (BOR) is an autosomal dominant genetic disorder characterized by branchial fistulas, hearing impairment, renal malformations and auricular anomalies. Pathogenic mutations have been discovered in several genes such as EYA1, SIX5, and SIX1. However, it has a high penetrance with variable expressivity. The clinical and genetical heterogeneity is widespread amongst and within families. In this review, we describe the clinical manifestations and pathogenic genes with copy number variations in detail, and emphasize the criteria clinically and genetically to provide the basis for clinical diagnosis of BOR and genetic counseling.

INSR gene polymorphisms correlate with sensitivity to platinum-based chemotherapy and prognosis in patients with epithelial ovarian cancer.

This study aimed to investigate the correlation between INSR gene polymorphisms on platinum-based chemotherapy sensitivity and prognosis in epithelial ovarian cancer (EOC). A total of 339 EOC patients receiving postoperative chemotherapy were recruited for the study. Tag single-nucleotide polymorphism of INSR gene was screened from HapMap combined with available literature. Frequency distribution of genotypes and alleles in INSR gene was sequenced by ABI3100-Avant. Compared with CC+GC genotype, INSR rs2252673 GG genotype and rs3745546 CC genotype showed less platinum-based chemotherapy sensitivity in EOC patients (odds ratio (OR)=0.269, 95% confidence interval (CI)=0.159~0.456; OR=0.445, 95% CI=0.214~0.926, respectively), as well as serous EOC patients (OR=0.083, 95% CI=0.024~0.278; OR=0.235, 95%CI=0.053~1.041, respectively). The clinical characteristics including age, clinical stage, histological grade and residual lesion size were significantly related with chemosensitivity to platinum drugs and mortality in EOC patients. According to Kaplan-Meier curve, compared with CC+GC genotype, rs2252673 GG genotype showed significantly decreased survival rate in EOC patients (P<0.05). Cox regression model indicated that rs2252673, age and clinical stage were independent risk factors for the prognosis in EOC (all P<0.05). These findings indicate that INSR rs2252673 and rs3745546 polymorphisms were associated with sensitivity to platinum-based chemotherapy in EOC patients and rs2252673 polymorphism may be an independent risk factor for EOC prognosis.

Downregulation of miR-218 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling.

Epithelial-mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis. Overexpression of miR-218 inhibited cell migration and invasion as well as the EMT process. Of particular importance, miR-218 was involved in the metastatic process of lung cancer cells in vivo by suppressing local invasion and distant colonization. We identified Slug and ZEB2 as direct functional targets of miR-218. Inverse correlations were observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples. In addition, overexpression of miR-218 in H1299 increased chemosensitivity of cells to cisplatin treatment through suppression of Slug and ZEB2. These findings highlight an important role of miR-218 in the regulation of EMT-related traits and metastasis of lung cancer in part by modulation of Slug/ZEB2 signaling, and provide a potential therapeutic strategy by targeting miR-218 in NSCLC.

Anti-tumor activity of dendritic cell-cytokine induced killer cells (DC-CIKs) sensitized to HER2 against HER-positive breast cancer cells.

This study aimed to investigate the cytotoxicity of cytokine-induced killer cells (CIKs) and Her2 epitope peptide-sensitized dendritic cells (DCs), when co-cultured with Her2-positive MCF-7 cells. DCs were separated from the Her epitope peptide-sensitized peripheral blood; the Her epitope combines directly with the MHC-II molecule on the DC surface. The DCs were co-cultured with autologous CIKs. Lactate dehydrogenase (LDH) and ELISA kits were used to detect cytotoxicity of CIKs against MCF-7 breast cancer cells; IL-12 and IFN-γ levels were also analyzed in the supernatant of the culture medium. CIKs activated by DCs sensitized by anchored Her polypeptide antigen have greater cytotoxicity against MCF-7 than CIKs alone or non-anchored antigen sensitized DCs-CIKs (P < 0.01); the IL-12 and IFN-γ levels in the supernatant were higher than that of the control (P < 0.01). In conclusion, DCs anchored by polypeptide antigen alone or in combination with effector cells can be used to develop therapeutic DC vaccines against breast cancer.

Clinical and epidemiological survey and analysis of the first case of human infection with avian influenza A(H7N9) virus in Hangzhou, China.

To investigate and report on the clinical and epidemiological characteristics of the first case of human infection with avian influenza A(H7N9) virus in Hangzhou, China. A field epidemiological survey was used to study the first case in Hangzhou. The patient was a 39-year-old male chef with a history of exposure to a farm product market and to poultry prior to the onset of disease on 15 March 2013. He had diarrhea, chills, pyrexia, and intermittent cough with freshly red foamy bloody sputum early in his disease. His fever > 39 °C continued for a week with rapid progression. Computed tomography findings showed extensive bilateral consolidation, followed by multiorgan failure. The patient died on the morning of 27 March. His infection was eventually confirmed 1 week later on 3 April. Flu-like symptoms including fever and cough were found in 46 of his 138 close contacts. This was the first case of human infection with avian influenza A(H7N9) virus in Hangzhou. None of the close contacts had onset of the disease. The case patient's condition progressed rapidly. The source of infection might be his exposure to the farm product market, but the mode of exposure remains unclear.

Effective reinforcement of electrical conductivity and strength of carbon nanotube fibers by silver-paste-liquid infiltration processing.

A carbon-nanotube (CNT)/silver/polymer composite fiber was fabricated using carbon nanotube fiber (CNTF) to infiltrate silver-paste liquid for effective reinforcement of electrical conductivity and strength of the CNT fibers. The as-obtained composite fiber is still flexible with a content of 43 wt% CNTs. Scanning electronic microscopy (SEM) observation shows that the silver-paste layer covering on the surface of the CNTF and polymer infiltrated into the CNTFs. The electrical conductivity and strength of the achieved composite fiber were effectively improved. Mechanical measurement of the composite fiber gave a strength of 940 MPa, 2.7 times that of a reference CNTF. The electrical conductivity of the composite fiber is 5.0 × 10(5) S m(-1), 2.6 times that of the referenced CNTF. Additionally, through control of the fabrication process, a coaxial fiber comprising a silver-paste "tube" and pure CNT fiber can be achieved. This route for making composite fibers is easy and controllable, apt for development of high-performance fibers.

Structures and characterizations of bundles of collapsed double-walled carbon nanotubes.

The performance of carbon nanotube fibers (CNTFs) significantly depends on the packing styles of carbon nanotube (CNT) bundles. Revealing the structures and characterizations of CNT bundles is contributive to understanding the structures, properties and even the formation of CNTFs during chemical vapor deposition (CVD) processing. In this paper, bundles consisting of collapsed double-walled carbon nanotubes (CDWNT) in continuous CNTFs fabricated from CVD processing were characterized and analyzed by transmission electronic microscopy (TEM) and x-ray diffraction (XRD). TEM observations show that the continuous CNTFs are composed of CDWNT-bundle units. CDWNT-bundle units of 10-20 nm in thickness contain near numbers of collapsed tubes. The degree of collapse of the CDWNTs varies with their location in the bundle and their own diameter. CDWNT-bundle units pack side by side or face to face, assembling into super-bundles with diameters of 200-300 nm. XRD patterns show that three novel and strong peaks appear at 10°-15°, 21.3° and 23.7°, respectively, corresponding to CDWNT two side pores (10°-15°) and CDWNT layers (21.3° and 23.7°), which indicates the collapsed tube structures in CNTFs are common characterizations. Finally, a collapse mechanism is discussed from the observation and analysis.

Down-regulation of TSG101 by small interfering RNA inhibits the proliferation of breast cancer cells through the MAPK/ERK signal pathway.

We designed to investigate the effects of down-regulating the tumor susceptibility gene 101 (TSG101) on the proliferation and apoptosis of the human breast cancer MCF-7 cell line, and the role of the MAPK/ERK signal pathway in this process. The siRNA against TSG101 was transfected into the breast cancer MCF-7 cell line using Lipofectamine 2000. After TSG101 knockdown, the proliferation of MCF-7 cells was measured by the MTT assay. The cell cycle distribution and apoptosis were examined by using flow cytometry while cell migration was measured using a transwell assay. The protein level of p-ERK was further assessed by immunofluorescence and western blotting. Our results are as following, the MCF-7 cells transfected with TSG101 siRNA proliferated significantly slower and exhibited significantly increased rates of apoptosis compared to the control cells. In the TSG101 siRNA transfected cells, the percentage of cells in the G0/G1 and S phase of the cell cycle was significantly higher and lower, respectively, compared to the control cells. Moreover, the migration ability of TSG101 siRNA transfected cells was lower than the control groups. Lastly, the level of p-ERK protein in TSG101 siRNA transfected cells was significantly decreased compared with the control cells. In conclusion, TSG101 knockdown in breast cancer cells induces apoptosis and inhibits proliferation. The TSG101 depleted cells are arrested at the G1/S transition of the cell cycle. The migration of breast cancer cells is also impaired by TSG101 siRNA. TSG101 may play a biological role through modulation of the MAPK/ERK signaling pathway in breast cancer.

Prediction of atmospheric degradation data for POPs by gene expression programming.

Quantitative structure-activity relationship models for the prediction of the mean and the maximum atmospheric degradation half-life values of persistent organic pollutants were developed based on the linear heuristic method (HM) and non-linear gene expression programming (GEP). Molecular descriptors, calculated from the structures alone, were used to represent the characteristics of the compounds. HM was used both to pre-select the whole descriptor sets and to build the linear model. GEP yielded satisfactory prediction results: the square of the correlation coefficient r(2) was 0.80 and 0.81 for the mean and maximum half-life values of the test set, and the root mean square errors were 0.448 and 0.426, respectively. The results of this work indicate that the GEP is a very promising tool for non-linear approximations.

Preclinical factors affecting the pharmacokinetic behaviour of tanshinone IIA, an investigational new drug isolated from Salvia miltiorrhiza for the treatment of ischaemic heart diseases.

Tanshinone IIA (TSIIA) is a major active triterpenoid isolated from Salvia miltiorrhiza. The purposes of this study were to investigate various preclinical factors that determined the pharmacokinetics of TSIIA. After oral dosing at 6.7, 20, and 60 mg kg(-1), TSIIA was detected mainly as glucuronidated conjugate (TSIIAG) with only small amounts of the unchanged in the plasma. TSIIA was predominantly excreted into the bile and faeces as TSIIAG, and urine to a minor extent. The C(max) and AUC(0-)(t) of TSIIAG after i.p. administration were significantly lower than those after intragastric administration. The plasma concentration-time profiles of TSIIA following oral dosing of TSIIA showed multiple peaks. The C(max) and AUC(0-)(t) of TSIIA and its glucuronides in rats with intact bile duct were significantly lower than those of rats with bile duct cannulation. Studies from the linked-rat model and intraduodenal injection of bile containing TSIIA and its metabolites indicate that TSIIA glucuronides underwent hydrolysis and the aglycone was reabsorbed from the gut and excreted into the bile as conjugates. TSIIA had a wide tissue distribution, with a very high accumulation in the lung, but very limited penetration into the brain and testes. TSIIA was metabolized by rat CYP2C, 3A and 2D, as ticlopidine, ketoconazole and quinidine all inhibited TSIIA metabolism in rat liver microsomes. Taken collectively, these findings indicate that multiple factors play important roles in determining the pharmacokinetics of TSIIA.

Roles for negative cell regulator 14-3-3sigma in control of MDM2 activities.

The 14-3-3sigma, upregulated by p53 in response to DNA damage, can have a positive-feedback impact driving p53 activities and is a human cancer epithelial marker downregulated in various tumors. However, the precise roles of 14-3-3sigma during tumorigenesis are not well characterized. Here, we show that 14-3-3sigma is a critical regulator of murine double minute oncogene (MDM2). 14-3-3sigma interacts with MDM2 at the RING domain. The C-terminal region of 14-3-3sigma binds to MDM2 very efficiently. Importantly, 14-3-3sigma overexpression leads to destabilization of MDM2 through enhancing MDM2 self-ubiquitination and accelerating turnover rate. Conversely, loss of 14-3-3sigma results in a significant increase in MDM2 protein. Moreover, live-cell images indicated that 14-3-3sigma can affect the location of MDM2 from the nucleus to the cytoplasm, and that MDM2-mediated cytoplasmic localization of p53 can be reversed by the presence of 14-3-3sigma. Significantly, we further showed that 14-3-3sigma causes MDM2 downregulation, thereby stabilizing p53 and inhibiting tumor growth in animal tumors. Also, 14-3-3sigma blocks MDM2-mediated retinoblastoma degradation and p53 NEDDylation. Our results provide evidence that 14-3-3sigma is a pivotal MDM2 regulator involved in blocking a variety of activities of MDM2.

Negative cell cycle regulator 14-3-3sigma stabilizes p27 Kip1 by inhibiting the activity of PKB/Akt.

The 14-3-3sigma (sigma) protein is a human cancer marker downregulated in various tumors, but its function has not been fully established. 14-3-3sigma is a negative regulator of cell cycle when overexpressed, but it is not clear whether 14-3-3sigma regulates cyclin-dependent kinase inhibitor p27(Kip1) to negatively affect cell cycle progression. Protein kinase B/Akt is a crucial regulator of oncogenic signal and can phosphorylate p27(Kip1) to enhance p27(Kip1)degradation, thereby promoting cell growth. Here, we show that 14-3-3sigma-mediated cell cycle arrest concurred with p27(Kip1) upregulation and Akt inactivation. We show that 14-3-3sigma blocks Akt-mediated acceleration of p27(Kip1) turnover rate. 14-3-3sigma inhibits Akt-mediated p27(Kip1) phosphorylation that targets p27(Kip1) for nuclear export and degradation. 14-3-3sigma inhibits cell survival and tumorigenicity of Akt-activating breast cancer cell. Low expression of 14-3-3sigma in human primary breast cancers correlates with cytoplasmic location of p27(Kip1). These data provide an insight into 14-3-3sigma activity and rational cancer gene therapy by identifying 14-3-3sigma as a positive regulator of p27 and as a potential anticancer agent.

Serum fatty acid composition in primary school children is associated with serum cholesterol levels and dietary fat intake.

OBJECTIVE: To examine the serum fatty acid composition, serum cholesterol levels, and dietary fat intake associated with body composition in primary school children of both urban and rural regions in Taiwan. DESIGN: Subjects were randomly stratified by region and primary school. The sample consisted of 870 children aged 10 and 11 y old. The sample was equally distributed between an urban region (Kaohsiung City) and a rural region (Yunlin County). The gender ratio of samples from each area was matched. Food record-assisted 24-h dietary recalls and serum lipid measurements were collected for each child, and associations between serum total cholesterol (TC) and fatty acids composition as well as between body mass index (BMI) and triceps skinfold (TSF) were evaluated for both urban and rural regions. RESULTS: Compared with students in the urban region, those in the rural region had significantly lower total fat intake, BMI, TSF, TC, and LDL cholesterol (LDL-C) and higher HDL-cholesterol (HDL-C) (P<0.05). Increased total fat (P<0.05) as a proportion of total energy was associated with increased TC and LDL-C. Lauric, myristic, and oleic acid levels in the serum of urban boys were significantly higher (P=0.0001, 0.0003, and 0.0398, respectively) than those of rural boys. In girls, the different fatty acid compositions affected TC concentrations, and palmitic and stearic acids of serum in the high-TC group were significantly lower (P=0.0179 and 0.0001, respectively) than those in the low-TC group. CONCLUSIONS: Urban children had a dietary fat intake that both quantitatively and qualitatively differed from the traditional rural Chinese diet in Taiwan as reflected in rural children. Consumption of total fat was positively associated with BMI, TSF, TC, and LDL-C levels in Taiwanese children aged 10 and 11 y. SPONSORSHIP: This study was partly sponsored by a research grant from the Department of Health, Taiwan, ROC.

Light-independent inactivation of dengue-2 virus by carboxyfullerene C3 isomer.

Carboxyfullerene (C60) is known as a photosensitizer for virus inactivation. Its regioisomer with C3 symmetry, named the C3 isomer, could also inactivate the dengue-2 virus without light when the dose of C3 isomer was increased to 40 microM, indicating the possible involvement of a light-independent mechanism. Further analysis showed that the C3 isomer blocked viral replication at the attachment and penetration stages, suggesting that a direct interaction between the C3 isomer and the virion is required for inactivation. The C3 isomer with a bipolar structure showed better lipid interaction and dengue-2 virus suppression than D3, another isomer that contains evenly distributed hydrophilic side chains. Moreover, the C3 isomer selectively inactivated enveloped viruses (viz., dengue-2 virus and Japanese encephalitis virus) instead of nonenveloped viruses (viz., enterovirus 71 and coxsackievirus B3). Collectively, these findings support the hypothesis that C3 isomer suppression of enveloped viruses is effected through its hydrophobic interaction with the viral lipid envelope. Our report, which demonstrates the light-dependent and -independent mechanisms of C60 on viral inactivation, will aid in the development of novel anti-viral agents for use against enveloped viruses.