Poly(I:C) Exacerbates Airway Goblet Cell Hyperplasia and Lung Inflammation in HDM-Exposed Balb/C Mice by YAP/FOXM1 Pathway.

INTRODUCTION: Respiratory viral infection in childhood is closely associated with asthmatic attacks. Of all predisposing factors, viral infection is the primary contributor to acute childhood asthma exacerbations. However, the mechanisms involved in viral asthma are unclear. This study attempted to provide insights into molecular mechanisms in respiratory virus-induced acute asthma exacerbations. METHODS: House dust mite (HDM) was given by intranasal administration to induce asthma in mice. Poly(I:C) was used to mimic the viral infection. A selective YAP inhibitor, verteporfin (VP), was used to investigate the role of the YAP/FOXM1 pathway. The expression of YAP, FOXM1, cytokines, and inflammatory cells in lung tissue, and bronchoalveolar lavage fluid (BALF) was determined using RT-PCR, immunohistochemical, ELISA, and flow cytometry studies. The methacholine challenge assesses airway hyperresponsiveness. In 16HBE cell experiments, we selectively inhibited YAP and FOXM1 by VP and RCM1, respectively, and detected the expression of YAP and FOXM1. RESULTS: The experimental studies have confirmed the YAP/FOXM1 pathway plays a vital role in the differentiation and proliferation of airway club cells into goblet cells and lung inflammation. Poly(I:C) upregulated the expression of FOXM1 by activating transcription factor YAP in mice airway epithelial cells and then promoted the expression of downstream transcription factors SPDEF/MUC5AC, resulting in airway mucus hypersecretion and hyperresponsiveness. In addition, Poly(I:C) facilitates the expression of inflammatory factors in lung tissue. All of these events induce asthma exacerbations. The in vitro studies have confirmed that YAP positively regulates FOXM1 in airway epithelial cells. CONCLUSION: Poly(I:C) promotes airway epithelial goblet cell hyperplasia, mucus hypersecretion, and airway hyperresponsiveness. It also upregulates the expression of inflammatory factors in lung tissue and BALF in asthmatic mice by the YAP/FOXM1 pathway, resulting in asthma attacks.

Efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children: a real-world study. / æ§æžé»„é¢—ç²’è¾ åŠ©æ²»ç–—å„¿ç«¥æ”¯æ°”ç®¡å“®å–˜ç–—æ•ˆçš„çœŸå®žä¸–ç•Œç ”ç©¶.

OBJECTIVES: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). CONCLUSIONS: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation.

Catalytic Asymmetric Conjugate Addition of Indoles to para-Quinone Methide Derivatives.

A catalytic asymmetric conjugate addition of indoles to o-hydroxyphenyl substituted p-quinone methides has been established in the presence of chiral phosphoric acid, which afforded chiral indole-containing triarylmethanes in generally high yields (54-98%) and good enantioselectivities (90:10-96:4 enantiomeric ratio). The control experiments indicated that o-hydroxyphenyl substituted p-quinone methides had a high possibility to transform into o-quinone methides in the presence of chiral phosphoric acid, and the formation of o-quinone methides might be a necessity for the reaction. This reaction will not only contribute to the research field of catalytic asymmetric transformations of p-quinone methides and o-quinone methides but also provide a useful method for the construction of enantioenriched triarylmethane frameworks.

A catalytic asymmetric interrupted Nazarov-type cyclization of 2-indolylmethanols with cyclic enaminones.

A chiral phosphoric acid-catalyzed asymmetric interrupted Nazarov-type cyclization of C3-alkenyl-substituted 2-indolylmethanols has been established by using cyclic enaminones as nucleophiles, which afforded chiral cyclopenta[b]indole derivatives with excellent diastereoselectivities and moderate to good enantioselectivities. This reaction will not only enrich the research contents of indolylmethanol-involved catalytic asymmetric transformations, but also advance the chemistry of catalytic asymmetric interrupted Nazarov-type cyclizations. In addition, this reaction will also provide a useful method for synthesizing chiral cyclopenta[b]indole derivatives.

The [4 + 2] cyclization/retro-Mannich reaction cascade of para-quinone methide derivatives with Pd-containing 1,4-dipoles.

The first [4 + 2] cyclization/retro-Mannich reaction cascade of para-quinone methides with Pd-containing 1,4-dipoles generated in situ from vinyl benzoxazinanones has been established. The corresponding rearrangement products were obtained in generally good to excellent yields (up to 92% yield). This reaction represents the first example of C[double bond, length as m-dash]C double bond cleavage of para-quinone methides, which will greatly enrich the chemistry of quinone methides.

Apoptosis of bladder transitional cell carcinoma T24 cells induced by adenovirus-mediated inducible nitric oxide synthase gene transfection.

OBJECTIVES: To investigate the effects of adenovirus-mediated inducible nitric oxide synthase gene transfection on bladder transitional cell carcinoma T24 cells, and to provide novel insights and approaches to clinical therapies against bladder transitional cell carcinoma. METHODS: Firstly, construct recombinant adenovirus vector pAd-iNOS of iNOS, followed by transfection of pAd-iNOS into HECK293 packaging cells. Thirdly, harvest recombinant adenovirus rAd-iNOS after amplification and purification procedures. Finally, transfect the recombinant adenovirus rAd-iNOS into human bladder carcinoma T24 cells and examine the effect of rAd-iNOS transfection on apoptosis of T24 and possible mechanism. RESULTS: As shown by this study, the recombinant adenovirus rAd-iNOS was constructed successfully. The virus titer was 5.8×10(8) PFU/mL and recombinant was verified by PCR analysis. Transfection of adenovirus rAd-iNOS into T24 cells could induce secretion of high NO concentration, P53 protein expression up-regulation, as well as promotion of T24 cell apoptosis. CONCLUSIONS: The transfection of human bladder carcinoma T24 cells from recombinant adenovirus rAd-iNOS was confirmed to induce intracellular iNOS over-expression, high production of NO, up-regulation of intracellular P53 expression and promotion of cell apoptosis.

[Effects of budesonide on HIF-1α and VEGF expression and airway remodeling in an asthmatic mouse model].

OBJECTIVE: To study the effects of budesonide on hypoxia inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) expression, angiogenesis and airway remodeling in the chronic asthmatic mouse model. METHODS: Thirty female BALB/c mice were randomly divided into normal control, asthma model and treatment groups (10 in each group).The asthmatic mouse model was established via OVA challenge test. Mice in the treatment group were administered with aerosol budesonide (100 µg/kg) an hour before the OVA challenge test from the 28th day. Mice in the control group were treated with PBS instead of OVA. Hematoxylin and eosin staining was performed to observe thickness of the airway wall. Masson staining was used for examing collagen deposition of lung tissues. Angiogenesis and HIF-1α and VEGF expression were measured using immunohistochemistry and Western blot. The relationship of airway wall thickness and vessel area to HIF-1α and VEGF expression was investigated. RESULTS: Vessel area, collagen deposition of lung tissues and airway wall thickness increased in the asthma model group. Levels of HIF-1α and VEGF were also elevated. Administration of budesonide significantly reduced angiogenesis, collagen deposition of lung tissues and airway wall thickening, as well as expression of HIF-1α and VEGF. The vessel area and airway wall thickness were positively correlated with expression of HIF-1α and VEGF. A positive correlation was also found between the expression of HIF-1α and VEGF. CONCLUSIONS: Budesonide can decease angiogenesis and airway remodeling by inhibiting HIF-1α and VEGF expression in asthmatic mice.

[Effect of balance acupotomy combined with warm needling in treatment of cervical spondylosis of vertebral artery type].

OBJECTIVE: To observe the clinical efficacy of balance acupotomy combined with warm needling in treatment of cervical spondylopathy of vertebral artery type (CSA). METHODS: Ninety patients were randomly divided into a warm needling group, a balance acupotomy group and a combined treatment group, 30 cases in each one. In the warm needling group, warm needling was given, once daily, for 5 days consecutively, with the interval of 2 days every week, and the treatment was conducted for 3 weeks. In the combined treatment group, on the base of the treatment as the warm needling group, the balance acupotomy was exerted, for consecutive 3 weeks. In the balance acupotomy group, the balance acupotomy was adopted, once a week, for 3 weeks consecutively. Clinical efficacy, the mean blood flow velocity of left vertebral artery (LVA), right vertebral artery (RVA) and basilar artery (BA), the pulse index (PI) and the resistance index (RI) were observed in 3 groups separately. The score of vertigo symptom and function was compared before and after treatment in 3 groups. RESULTS: In comparison with before treatment, the score of evaluation scale for cervical vertigo (ESCV) and the mean blood flow velocity of LVA, RVA and BA were all increased (P<0.05). while PI and RI reduced (P<0.05) in each group after treatment. In comparison with those in the warm needling group and the balance acupotomy group, ESCV score and the mean blood flow velocity of LVA, RVA and BA were increased (P<0.05), while PI and RI decreased (P<0.05) in the combined treatment group after treatment. Compared with the balance acupotomy group, the mean blood flow velocity of LVA, RVA and BA was increased (P<0.05), and PI and RI reduced (P<0.05) in the warm needling group after treatment. The total effective rate was 73.3% (22/30) in the warm needling group, 70.0% (21/30) in the balance acupotomy group and 93.3% (28/30) in the combined treatment group respectively. The total effective rate in the combined treatment group was higher than that either in the warm needling group or in the balance acupotomy group (P<0.05). CONCLUSION: Balance acupotomy combined with warm needling may restore the mechanical equilibrium state of the neck, and effectively improve the change of vertebral-basilar artery blood flow and relieve vertigo symptoms in patient with of cervical spondylosis of vertebral artery type.

LncRNA TUG1 promotes bladder cancer malignant behaviors by regulating the miR-320a/FOXQ1 axis.

BACKGROUND: Growing evidence has showed long noncoding RNAs (lncRNAs) play critical roles in bladder cancer (BC) progression. LncRNA taurine upregulated gene 1 (TUG1) was involved in the development of human malignancies. However, the intrinsic and concrete molecular mechanisms of TUG1 in BC remain largely unknown. METHODS: Expression patterns of TUG1, miR-320a and FOXQ1 in BC tissues and cell lines were measured using qRT-PCR and western blot, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. The capacity of cell migration and invasion was evaluated using wound healing and transwell assay. Tumor xenograft assay was performed to further validate the role of TUG1 in BC progression. Dual luciferase reporter assay and FISH analysis were employed to verify the TUG1/miR-320a/FOXQ1 regulatory network. RESULTS: TUG1 was significantly higher expression in BC specimens and cell lines. TUG1 knockdown suppressed BC cells malignant behaviors in vitro and inhibited tumor growth and metastasis in vivo, while TUG1 overexpression promoted BC cells malignant behaviors in vitro. However, the function of miR-320a was opposite to that of TUG1, and miR-320a inhibitor partially eliminated the inhibitory effect of TUG1 knockdown on the malignant behavior of BC cells. As a microRNA sponge, TUG1 actively elevated FOXQ1 expression to sponge miR-320a and subsequently promoted BC cells malignant phenotypes. CONCLUSION: TUG1 may have great potential as therapeutic target for BC, since TUG1 silencing inhibited cell proliferation, migration and invasion in BC, while promoted cell apoptosis, by regulating the miR-320a/FOXQ1 axis.

[Clinical observation of acupotomy combined with warm needling for cervical spondylotic radiculopathy of qi and blood stagnation syndrome].

OBJECTIVE: To observe the clinical effect of acupotomy combined with warm needling on cervical spondylotic radiculopathy (CSR) of qi and blood stagnation syndrome. METHODS: A total of 90 CSR patients were randomly divided into an acupotomy group, a warm needling group and a combined treatment group, with 30 cases in each group. The patients in the acupotomy group were treated with acupotomy, once every 7 days, consecutively for 3 times. The patients in the warm needling group received warm needling, once daily, at the interval of 2 days after consecutive treatments for 5 days, 7 days as one session of treatment and 3 consecutive sessions were required. The patients in the combined treatment group were treated with acupotomy and warm needling, and the methods and the treatment session were same as the the previous two groups. Before and after the treatment, the pain rating index (PRI) of McGill pain questionnaire (MPQ) and the 20-point scale of CSR developed by Yasuhisa Tanaka (CSR20) were adopted in the assessment. The changes of clinical symptoms and functions of patients were observed and the clinical efficacy was assessed in each group. RESULTS: After the treatment, the PRI score was decreased (P<0.05) and the CSR20 score was increased (P<0.05) in the 3 treatment groups when compared with those before the treatment. After the treatment, compared with the acupotomy group and the warm needling group, the PRI score was decreased (P<0.05) and the CSR20 score was increased (P<0.05) in the combined treatment group. The total effective rate was 83.3% (25/30) in the acupotomy group, 76.7% (23/30) in the warm needling group and 93.3% (28/30) in the combined treatment group. The total effective rate in the combined treatment group was higher than those in the acupotomy group and the warm needling group (P<0.05). CONCLUSION: The combined treatment with acupotomy and warm needling may obviously improve the clinical symptoms and physical signs, e.g. pain and numbness in the patients with CSR of qi and blood stagnation syndrome. Its efficacy is remarkably higher than that of the simple application of acupotomy or warm needling.

The addition of alpha amylase improves the quality of Chinese dried noodles.

The effect of α-amylase on the quality attributes of Chinese dried noodles (CDN) was investigated. Adding α-amylase markedly decreased the cooking time and cooking loss of CDN at the level of 12.5 (mg/100 g flour). The elasticity of CDN was increased significantly (P < 0.05) after adding α-amylase. The firmness of noodles with 12.5 mg α-amylase per 100 g flour showed no obvious change compared to the control, whereas it decreased significantly (P < 0.05) when the amount of α-amylase increased to 25 (mg/100 g flour). In addition, the chewiness of CDN with 12.5 mg α-amylase per 100 g flour increased, while it showed a significant (P < 0.05) decreasing trend with further increased α-amylase levels. Starch structural and thermal properties were also changed by α-amylase, which showed increased relative crystallinity, swelling power, but decreased pasting property. The changed starch property restrained the cross-linking of gluten. The decrease in optimal cooking time and increase in elasticity of CDN were due to the increased swelling power and decreased peak time of the starch. In addition, the decreased setback of starch and protein cross-linking degree were responsible for the decreased firmness and chewiness of CDN with α-amylase ranging from 25 to 50 mg/100 g flour. Overall, α-amylase could be used as a functional additive to improve the quality of CDN when the amount was at 12.5 mg/100 g flour.

Rapid Internal Control Reference Recombinase-Aided Amplification Assays for EBV and CMV Detection.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV), two of the most prevalent human herpesviruses, cause a wide spectrum of diseases and symptoms and are associated with serious health problem. In this study, we developed an internal control reference recombinase-aided amplification (ICR-RAA) assay for the rapid detection of EBV and CMV within 30 min. The assay had a sensitivity of 5 and 1 copies/test for EBV and CMV, respectively, with no cross reaction with other pathogens. In comparison with those of the commercial quantitative polymerase chain reaction (qPCR), the sensitivity of the EBV and CMV ICR-RAAs using extracted DNA was 93.33% and 84.84%, respectively; the specificity was 98.75% and 100.00%, respectively; and the Kappa values were 0.930 and 0.892 ( P < 0.05), respectively. In comparison with those of qPCR, the sensitivity of the EBV and CMV ICR-RAAs using the DNA by thermal lysis was 72.22% and 80.00%, respectively; the specificity was 100.00%; and the Kappa values were 0.764 and 0.878 ( P < 0. 05), respectively. Thus, rapid and specific detection of EBV and CMV is possible using ICR-RAA assays.

Revealing the effect mechanism of NaCl on the rheological properties of dough of Chinese traditional hand-stretched dried noodles.

Chinese traditional hand-stretched dried noodle is very popular in China for its unique taste and flavor quality, and NaCl plays a vital role in its processing. The effects of NaCl (1%-6%, w/w) on rheological and gluten properties of dough of Chinese traditional hand-stretched dried noodle were studied. The addition of NaCl (1%-4% w/w) enhanced storage modulus, loss modulus and extensibility of dough, while these rheological parameters started to decreased when NaCl amount reached 5% (w/w). With salt addition increased from 0% to 6% (w/w), the solubility of gluten in SDS medium showed a significant (p < 0.05) decreasing trend, while opposite result was found on the yield and G' of gluten macro polymer. These changes on gluten indicated that the interaction among gluten molecules increased with the increase of salt amount. Excessive salt (5%-6%, w/w) disrupted the gluten network, which was responsible for the reduction of dynamic and extensional properties.

A highly sensitive one-tube nested quantitative real-time PCR assay for specific detection of Bordetella pertussis using the LNA technique.

OBJECTIVES: Bordetella pertussis is a highly contagious respiratory agent and is the causative pathogen of pertussis, which primarily affects children. Current diagnostic techniques for this pathogen have a variety of limitations including a long culture time, low bacterial load, and lack of specificity. METHODS: This article reports the development of a one-tube nested quantitative real-time PCR assay using the locked nucleic acid (LNA) technique (LNA-OTN-q-PCR), targeting the BP485 gene and using a simple inexpensive extraction method. A total of 130 clinical samples from patients with clinically suspected pertussis, collected from the Children's Hospital of Hebei, China, were tested by LNA-OTN-q-PCR assay. RT-PCR and two-step semi-nested PCR assays were performed in parallel for comparison. RESULTS: Only strains of B. pertussis were identified as positive, whereas all of the remaining strains were appropriately identified as negative by the LNA-OTN-q-PCR assay. A single copy per reaction can be detected by the LNA-OTN-q-PCR assay. Additionally, the sensitivity of this method was 100 times that of the RT-PCR assay (100 copies per reaction). Sixty-three of the 130 clinical samples were detected positive by LNA-OTN-q-PCR assay; in contrast, RT-PCR was able to detect only 41 positive samples. Following this, all 63 samples were positively identified by two-step semi-nested PCR. Compared with the two-step semi-nested PCR assay, both the specificity and sensitivity of the LNA-OTN-q-PCR assay using purified DNA and crude extract were 100%. CONCLUSIONS: This assay was able to detect B. pertussis infection with high sensitivity and specificity. This test shows great potential as a promising technique to detect B. pertussis in both clinical laboratories and public health settings.

MicroRNA-124-3p suppresses cell migration and invasion by targeting ITGA3 signaling in bladder cancer.

BACKGROUND: A growing body of studies have demonstrated the aberrant expression of microRNAs (miRNAs) contributes to human tumor metastasis. MicroRNA-124-3p (miR-124-3p), which is down-regulated in various cancers, has been found to be involved in several signaling pathways relevant to tumor cell migration and invasion. However, the roles of miR-124-3p in human bladder cancer remain unclear. This study aims to investigate the functional significance of miR-124-3p and to understand how it targets the integrin receptor, and thus affects the progression of human bladder cancer. METHODS: Clinical specimens from 36 patients and three human bladder cancer cell lines were analyzed for miR-124-3p and integrin α3 (ITGA3) . To investigate the effects of miR-124-3p and ITGA3 on proliferation of bladder cancer cells, the MTT assay, colon-formation assay and flow cytometry were performed. In addition, wound healing assay and transwell assay were carried out to examine the migration and invasion of the bladder cancer cells transfected with miR-124-3p mimics or si-ITGA3. The luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied to validate the miR-124-3p directly binding with ITGA3. Finally, western blot was used to examine the expression level of the proteins involved in FAK/PI3K/AKT and FAK/Src signal pathway as well as epithelial-mesenchymal transition (EMT) process. RESULTS: The down-regulation of miR-124-3p and up-regulation of ITGA3 were observed in clinical specimens and bladder cancer cell lines. Overexpression of miR-124-3p or silencing ITGA3 inhibited tumor cell migration and invasion. Luciferase assay confirmed miR-124-3p directly targets ITGA3, and western blot suggested that miR-124-3p plays a crucial role in the EMT and metastasis of human bladder cancer through FAK/PI3K/AKT and FAK/Src signaling mechanism. Also, by targeting ITGA3, miR-124-3p can modulate the expression of N- and E-cadherin, and thus inhibit the EMT. CONCLUSIONS: By targeting ITGA3 and downstream FAK/PI3K/AKT and FAK/Src signaling pathways, miR-124-3p suppresses cell migration and invasion in bladder cancer. Our study reasonably speculates that miR-124-3p can be potentially developed as a therapeutic target and prognostic biomarker for bladder cancer.

[Expression of neuronal acetylcholine receptor alpha 7 (nAChRalpha7) in peripheral blood CD(4)(+) T lymphocytes from asthmatic children].

OBJECTIVE: To investigate the relationship between the expression of neuronal acetylcholine receptor alpha 7 (nAChRalpha7) and the role of nAChRalpha7 in the development of asthma by detecting the expression of nAChR alpha7 on CD(4)(+) T lymphocytes in the peripheral blood and the level of cytokines IFN-gamma and IL-4 in the blood serum from children with asthma. METHODS: Thirty patients in the asthma group and 20 healthy children in the normal control group were included. Peripheral blood was collected, and the serum was harvested. The expression of nAChRalpha7 on CD(3)(+) and CD(4)(+) cells were detected by flow cytometry. The levels of IFN-gamma and IL-4 in the serum were detected by ELISA. RESULTS: The expression of nAChRalpha7 on CD(4)(+) T lymphocytes from children with asthma was higher than that from normal controls (t = 2.53, P < 0.05). Compared with the control group, the level of IL-4 in the serum of the asthma group was higher (t = 5.42, P < 0.01) but the level of IFN-gamma was lower (t = 4.11, P < 0.01). There were positive correlation between nAChRalpha7 and IL-4 (r = 0.688, P < 0.01) and negative correlation between nAChRalpha7 and IFN-gamma (r = -0.476, P < 0.01). CONCLUSION: nAChRalpha7 was shown to influence the balance of Th1/Th2 and it may play an important role in the development of asthma.

[Construction and expression of replication-deficient recombinant adenovirus vector with hNET gene by adeasy-1 system].

OBJECTIVE: To construct and identify the recombinant replication deficient adenovirus vector which codes for human Norepinephrine Transporter (hNET) gene by using the method of homogenous recombination in bacteria. METHODS: hNET gene was obtained from the recombinant plasmid pCMV5 via Kpn I + Xba I digestion, and subcloned into E1 deleted expression plasmid pAdtrack-CMV shuttle vector, forming transfer vector pAdtrack-CMV-hNET. Then it was linearized with Pme I followed by homologous recombination with bone plasmid pAdEasy-1 in BJ5183 cells to generate recombinant plasmid Ad-hNET. The DNA of identified Ad-hNET was digested with Pac I and transfected to HEK293 cells by liposome-mediated method to package recombinant adenovirus. The PCR technique was applied to detect the target gene and Western Blotting to verify the expression of hNET. The titre of the Ad-hNET was measured with the aid of green fluorescence protein (GFP) expression after multiplication and purification. RESULTS: By sequencing, it was confirmed that the product was the gene of hNET. PCR test, restriction endonuclease digestion and Western Blotting confirmed the successful construction of the recombinants Ad-hNET. The titre of purified recombinant adenovirus Ad-hNET was 1.2 X 10(10) pfu/mL. CONCLUSION: The recombinant adenovirus with the hNET gene was constructed successfully. It will be helpful for the further investigation of its potentiality to be applied in the tumors targeted therapeutic strategy.

Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response.

We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R) induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2-alpha (eIF2α) and activating transcription factor 4 (ATF4). We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 µM) treatment. We found that 100 µM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p)-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

[Application of bronchoscopic lung volume reduction using one-way flap device in sheep model of heterogeneous emphysema].

OBJECTIVE: To evaluate the effectiveness of bronchoscopic lung volume reduction (BLVR) using one way flap device in sheep model of heterogeneous emphysema. METHODS: Six 6-month sheep (weight: 20-30 kg) were treated with localized papain instillations to generate heterogeneous emphysema, subsequently underwent BLVR using one way-flap device at subsegment. Lung functional residual capacity (FRC) was analyzed before and 8 weeks after operation. Animals were euthanized at the 8-week time point. Lungs were removed en bloc and inflated with a super syringe to look for areas of gross collapse. Samples were collected from collapsed and non-collapsed areas, fixed in 10% buffered formalin, made paraffin section and stained with hematoxylin-eosin (HE) to observe morphologic change of bronchi. RESULTS: BLVR was well tolerated without complications, and it reduced lung volumes (change in residual volume 49.5%). There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung,improved respiratory function safely and consistently. CONCLUSION: BLVR using one-way flap device is a minimally invasive procedure and the stimulus of the devices to walls of bronchi is slight, moreover, the technique may attain effectiveness of surgery. Therefore maybe it will be a perspective treatment of chronic obstructive pulmonary disease.

Surveillance and control of post-transmission schistosomiasis in Jiaxing prefecture, Zhejiang province, China.

A surveillance system has been put in place in the Zhejiang province since achieving there the criteria for transmission interruption of schistosomiasis japonica. Suspected patients and special high-risk groups (e.g. the so called 'floating population' and children under 14 years of age) are screened for Schistosoma japonicum using serological tests. Those with positive serological result are subjected to faecal examination and if S. japonicum eggs are found they are treated with praziquantel and followed by regular re-examination until complete cure, i.e. absence of S. japonicum eggs in faecal samples. Patients with advanced schistosomiasis japonica are continuously followed-up. Implementation of the surveillance system from 1995 to 2002 detected two S. japonicum-infected persons; one came from Anhui province and the other from Jiangsu province, but no new infection occurred among local residents. The number of patients with advanced schistosomiasis japonica decreased from 1524 in 1995 to 906 by the end of 2002; a reduction of 40.6%. However, post-transmission schistosomiasis still continues to weigh on the medial resources. We conclude that the surveillance system in Zhejiang province is effective and a useful means for monitoring the endemic situation of schistosomiasis. Hence, it is recommended to be pursued in the years to come.