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OBJECTIVE: Increased proliferation of airway smooth muscle cells (ASMCs) is a key feature of airway remodeling in asthma. This study aims to determine whether brain-derived neurotrophic factor (BDNF) regulates ASMC proliferation and airway remodeling via the transient receptor potential channels (TRPCs)/autophagy axis. METHODS: Human ASMCs were isolated and passively sensitized with human asthmatic serum. Protein levels of BDNF and its receptor TrkB, TRPC1/3/6, autophagy markers, intracellular Ca2+ concentration ([Ca2+]i), LC3 immunofluorescence, cell proliferation, cell cycle population were examined. Wistar rats were sensitized with OVA to establish asthma models. RESULTS: In asthmatic serum-sensitized human ASMCs, BDNF overexpression or recombinant BDNF (rhBDNF) increased TrkB/TRPC1/3/6 axis, [Ca2+]i, autophagy level, cell proliferation, cell number in the S+G2/M phase and decreased cell number in the G0/G1 phase, whereas BDNF knockdown exerted the opposite effects. Furthermore, TRPC channel blocker SKF96365 and TRPC1/3/6 knockdown reversed the effects of the rhBDNF-mediated induction of [Ca2+]i, autophagy level, cell proliferation and cell number in the S+G2/M phase. Moreover, the autophagy inhibitor (3-MA) rescued the rhBDNF-mediated induction of cell proliferation and cell number in the S+G2/M phase. Further in vivo assays revealed that BDNF altered the pathology of airway remodeling, promoted the infiltration of inflammatory cells, promoted the proliferation of ASMCs, and upregulated the protein levels of TrkB, TRPC1/3/6, and autophagy markers in asthma model rats. CONCLUSION: We conclude that BDNF promotes ASMCs proliferation in asthma through TRPC-mediated autophagy induction.

Asunto(s)

Asma , Canales de Potencial de Receptor Transitorio , Animales , Humanos , Ratas , Remodelación de las Vías Aéreas (Respiratorias) , Asma/patología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proliferación Celular , Miocitos del Músculo Liso/metabolismo , Ratas Wistar , Canales de Potencial de Receptor Transitorio/metabolismo

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OBJECTIVE: Transforming growth factor-beta TGF-ß-induced epithelial-mesenchymal transition (EMT) in bronchial epithelial cells contributes to airway wall remodeling in asthma. This study aims to explore the role of amygdalin, an active ingredient in bitter almonds, in TGF-ß-induced EMT in bronchial epithelial cells and to elucidate the possible mechanisms underlying its biological effects. METHODS: An asthmatic mouse model was established through ovalbumin induction. Primary mouse bronchial epithelial cells and a human bronchial epithelial cell line were incubated with transforming growth factor-beta (TGF-ß) to induce EMT, whose phenotype of cells was evaluated by the expressions of EMT markers [alpha-smooth muscle actin (α-SMA), vimentin, and fibronectin] and cell migration capacity. A co-immunoprecipitation assay was performed to assess the ubiquitination of heparanase (HPSE). RESULTS: In asthmatic model mice, amygdalin treatment relieved airway wall remodeling and decreased expressions of EMT markers (α-SMA and vimentin). In TGF-ß-treated bronchial epithelial cells, amygdalin treatment decreased the mRNA and protein levels of EMT markers (α-SMA, vimentin, and fibronectin) without impairing cell viability. Through the Swiss Target Prediction database, HPSE was screened as a candidate downstream target for amygdalin. HPSE overexpression further promoted TGF-ß-induced EMT while the HPSE inhibitor suppressed TGF-ß-induced EMT in bronchial epithelial cells. In addition, HPSE overexpression reversed the inhibitory effect of amygdalin on TGF-ß-induced EMT in bronchial epithelial cells. The following mechanism exploration revealed that amygdalin downregulated HPSE expression by enhancing ubiquitination. CONCLUSION: Our study showed that amygdalin inhibited TGF-ß-induced EMT in bronchial epithelial cells and found that the anti-EMT activity of amygdalin might be related to its regulatory effect on HPSE expression.

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Amigdalina , Asma , Humanos , Ratones , Animales , Factor de Crecimiento Transformador beta/metabolismo , Vimentina/genética , Vimentina/metabolismo , Fibronectinas/metabolismo , Amigdalina/farmacología , Amigdalina/uso terapéutico , Amigdalina/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Transición Epitelial-Mesenquimal , Asma/tratamiento farmacológico , Asma/metabolismo , Células Epiteliales/metabolismo , Factores de Crecimiento Transformadores/metabolismo , Factores de Crecimiento Transformadores/farmacología

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BACKGROUND: Asthma is an inflammatory syndrome characterized by airway hyperresponsiveness, bronchial inflammation, and airway remodeling. Abnormal proliferation of airway smooth muscle cells (ASMCs) is the main pathological feature of asthma. This study investigated the function and mechanism of serine arginine-rich splicing factor 1 (SRSF1) in ASMC proliferation in asthma. METHODS: SRSF1 expressions in the bronchi of ovalbumin-induced asthmatic mice and IgE-treated mouse ASMCs (mASMCs) were evaluated using quantitative real-time PCR and Western blot. The localization and expression of SRSF1 in the bronchi of asthmatic mice were assessed by immunohistochemistry. Functionally, gain- and loss-of-function assays, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were conducted. Mechanistically, RNA degradation assay, RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter gene assays were carried out. RESULTS: SRSF1 was highly expressed in the bronchi of ovalbumin-induced asthma mice and IgE-treated mASMCs and was mainly located in the nucleus. Experiments on the function of SRSF1 showed that the silencing of SRSF1 induced the cell cycle of mASMC arrest and restrained mASMC proliferation. Investigations into the mechanism of SRSF1 revealed that SRSF1 and miR-135a are competitively bound to the 3'UTR region of Cyclin D2 (CCND2). SRSF1 overexpression repressed the degradation of CCND2 mRNA, and miR-135a negatively regulated CCND2 expression. Furthermore, SRSF1 knockdown inhibited ASMC proliferation in asthma mouse models by regulating the levels of miR-135a and CCND2. CONCLUSION: SRSF1 knockdown repressed ASMC proliferation in asthma by regulating miR-135a/CCND2 levels.

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Asma , Ciclina D2 , MicroARNs , Factores de Empalme Serina-Arginina , Animales , Ratones , Asma/genética , Asma/patología , Bronquios/metabolismo , Proliferación Celular/genética , Ciclina D2/metabolismo , Inmunoglobulina E , MicroARNs/genética , Miocitos del Músculo Liso/metabolismo , Ovalbúmina , Factores de Empalme Serina-Arginina/metabolismo

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Activated neutrophil-derived exosomes reportedly contribute to the proliferation of airway smooth muscle cells (ASMCs), thereby aggravating the airway wall remodeling during asthma; however, the specific mechanism remains unclear. Lipopolysaccharide (LPS)-EXO and si-CRNDE-EXO were extracted from the media of human neutrophils treated with LPS and LPS + si-CRNDE (a siRNA targets long non-coding RNA CRNDE), respectively. Human ASMCs were co-cultured with LPS-EXO or si-CRNDE-EXO, and cell viability, proliferation and migration were measured. The interplay of colorectal neoplasia differentially expressed (CRNDE), inhibitor of nuclear factor kappa B kinase subunit beta (IKKß) and nuclear receptor subfamily 2 group C member 2 (TAK1) was explored using RNA immunoprecipitation (RIP) and Co-IP assays. A mouse model of asthma was induced using ovalbumin. CRNDE was upregulated in LPS-EXO and successfully transferred from LPS-treated neutrophils to ASMCs through exosome. Mechanically, CRNDE loaded in LPS-EXO reinforced TAK1-mediated IKKß phosphorylation, thereby activating the nuclear factor kappa B (NF-κB) pathway. Functionally, silencing CRNDE in LPS-EXO, an IKKß inhibitor, and an NF-κB inhibitor all removed the upregulation of cell viability, proliferation and migration induced by LPS-EXO in ASMCs. In the end, the in vivo experiment demonstrated that CRNDE knockdown in neutrophils effectively reduced the thickness of bronchial smooth muscle in a mouse model for asthma. Activated neutrophils-derived CRNDE was transferred to ASMCs through exosomes and activated the NF-κB pathway by enhancing IKKß phosphorylation. The latter promoted the proliferation and migration of ASMCs and then contributed to airway remodeling in asthma.

Asunto(s)

Asma , Neoplasias Colorrectales , ARN Largo no Codificante , Remodelación de las Vías Aéreas (Respiratorias) , Animales , Asma/genética , Proliferación Celular/genética , Neoplasias Colorrectales/metabolismo , Modelos Animales de Enfermedad , Humanos , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Lipopolisacáridos/farmacología , Ratones , Miocitos del Músculo Liso/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Neutrófilos/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo

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Background: Previous studies have revealed the important role of alveolar macrophages (AMs) in the pathogenesis of acute respiratory distress syndrome (ARDS) and potential anti-inflammatory properties of lincRNA-p21. This study aims to study the association between lincRNA-p21 and active AMs to understand the molecular mechanisms of AMs-mediated inflammatory responses in ARDS.Methods: This study was mainly investigated in mice with the intratracheal instillation of lipopolysaccharide (LPS) or LPS-treated AMs. The expression of lincRNA-p21 and classical macrophage markers, IL-12ß and iNOS, was detected by quantitative RT-PCR, while NF-κB p65 translocation was measured by western blotting analysis. And, NF-κB activity was analyzed through luciferase report assays. Gain- and loss-of-function studies were also performed for further investigations.Results: Elevated lincRNA-p21 levels were observed in both LPS-induced ARDS mice and LPS-treated AMs, with upregulated expression of IL-12ß and iNOS, namely M1 activation, and p65 nuclear translocation. Further in vitro studies showed that LPS-induced M1 activation could be counteracted by both lincRNA-p21 inhibition and inhibited NF-κB activation. Moreover, both p65 nuclear translocation and NF-κB activity were promoted by lincRNA-p21 overexpression, while lincRNA-p21 inhibition showed a negative effect on LPS-induced p65 nuclear translocation and increase of NF-κB activity. Additionally, LPS-induced lung injuries could be attenuated by lincRNA-p21 inhibition in vivo.Conclusion: This study revealed elevated lincRNA-p21 levels in LPS-induced ARDS and investigated the potential role of lincRNA-p21 in LPS-induced pro-inflammatory response via NF-κB/p65 mediated pathways, suggesting the potential application of lincRNA-p21 for ADRS therapy.

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Activación de Macrófagos/genética , Macrófagos Alveolares/metabolismo , FN-kappa B/genética , ARN Largo no Codificante/genética , Síndrome de Dificultad Respiratoria/genética , Quinasas p21 Activadas/genética , Animales , Regulación de la Expresión Génica/genética , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , Lesión Pulmonar/genética , Activación de Macrófagos/efectos de los fármacos , Macrófagos Alveolares/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de Señal/genética , Tráquea/efectos de los fármacos , Tráquea/metabolismo , Factor de Transcripción ReIA/genética

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OBJECTIVE@#To observe the effect of electroacupuncture (EA) combined with pill on clinical symptoms, levels of serum sex hormone and Th2 cytokines in patients of decreased ovarian reserve function (DOR) with liver-kidney deficiency, and to compare the efficacy between EA combined with pill and pill alone.@*METHODS@#Sixty patients with DOR were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). The patients in the control group were treated with pill, 1 pill each time, 3 times a day. Based on the treatment of the control group, the patients in the observation group were additionally treated with acupuncture at Guanyuan (CV 4), Zhongji (CV 3), Guilai (ST 29), Zigong (EX-CA 1), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3) and Taichong (LR 3); EA was applied at bilateral Zusanli (ST 36) and Sanyinjiao (SP 6), with continuous wave, in frequency of 20 Hz and current intensity of 1 to 4 mA, for 20 min. The treatment was given 3 times a week. All the patients terminated treatment during menstrual period, and the treatment was given for 3 continuous menstrual cycles. The menstrual condition score and systemic symptom score were compared between the two groups before and after treatment. The levels of serum sex hormones on 2nd to 3rd day of menstruation, including follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), and the serums levels of interleukin (IL) -4 and IL-10 secreted by Th2 cytokines were compared between the two groups before and after treatment.@*RESULTS@#After the treatment, the menstruation condition scores and systemic symptom scores in the two groups were reduced (<0.05), and the scores in the observation group were lower than those in the control group (<0.05). After the treatment, the levels of serum FSH, LH and FSH/LH were reduced (<0.05), and the E2 levels were increased in the two groups (<0.05), and the levels of FSH, LH in the observation group were lower than those in the control group (<0.05), and the E2 level was higher than that in the control group (<0.05). After the treatment, the levels of serum IL-4 and IL-10 in the two groups were increased (<0.05), and the levels of IL-4 and IL-10 in the observation group were higher than those in the control group (<0.05).@*CONCLUSION@#EA combined with pill could significantly improve menstruation, systemic symptoms and serum sex hormone levels in patients of decreased ovarian reserve function with liver-kidney deficiency, which may restore ovarian function by up-regulating the expression of Th2 cytokines.

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AIMS: To explore the role of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in the cell proliferation of airway smooth muscle cells (ASMCs) in asthma. MATERIALS AND METHODS: An asthma rat model was established by ovalbumin sensitization and challenge. The expression of GAS5, miR-10a and BDNF mRNA and protein was determined with qRT-PCR and western blot, separately. The targeting relationship between GAS5 and miR-10a was examined with RNA immunoprecipitation and RNA pull-down assay; the interaction between miR-10a and BDNF was evaluated by luciferase reporter assay. Cell Proliferation Assay (MTS) was used for ASMC proliferation detection. Knock-down of GAS5 was performed in asthmatic rats to determine the effects of GAS5 in vivo. KEY FINDINGS: Compared with control group, the inspiratory resistance and expiratory resistance were increased in asthma group; and the expression of GAS5, miR-10a and BDNF was higher, lower and higher, respectively. The expression of GAS5 and miR-10a was elevated and repressed, respectively, by platelet-derived growth factor-BB (PDGF-BB). GAS5 functioned as a bait of miR-10a. GAS5 regulates BDNF expression through miR-10a. PDGF-BB promotes the cell proliferation of ASMCs through miR-10a/BDNF. Knock-down of GAS5 significantly decreased airway hyperresponsiveness in asthmatic rats. SIGNIFICANCE: The lncRNA GAS5/miR-10a/BDNF regulatory axis played an important role in promoting ASMCs proliferation, thus contributing to asthma.

Asunto(s)

Asma/patología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proliferación Celular , MicroARNs/genética , Miocitos del Músculo Liso/patología , ARN Largo no Codificante/genética , Sistema Respiratorio/patología , Animales , Apoptosis , Asma/genética , Asma/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Células Cultivadas , Regulación Neoplásica de la Expresión Génica , Miocitos del Músculo Liso/metabolismo , Ratas , Sistema Respiratorio/metabolismo , Transducción de Señal

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Objective To report a case of immunodeficiency 41 with lymphoproliferation and autoimmunity (IMD41) and type 10 insulin-dependent diabetes mellitus(IDDM10), caused by mutations of the interleukin 2 receptor α(IL2RA)gene.Methods Clinical symptoms were colleted,while IL2RA gene was sequenced.Results Here we reported a girl of 7 years and 6 months old who came to our hospital presented with lymphadenovarix for 5 years,debilitation for 2 months and alternation of hyperglycemia and hypoglycemia for 20 days. She was subsequently diagnosed with fungal pneumonia and ANCA-associated vasculitis. All exons of IL2RA gene were sequenced. c.340C>T(p.Q114X,paternal,novel mutation),c.64G>A(p.E22X,maternal) were detected. After treatments of dihydrocortisone,voriconazole combined with diabetic diet plus raw cornstarch, the pulmonary lesions reduced, autoantibodies disappeared and the blood glucose returned to normal. Literature review suggested that totally 5 IL2RA gene mutation patients were reported, the major clinical features were recurrent infection(infection of lung, skin, gastrointestinal tract) and immune abnormalities ( such as lymph node disease, autoimmune disease, hepatosplenomegaly,and diabetes mellitus). Conclusion In cases of atypical clinical symptoms, whole exon sequencing helps early diagnosis.

RESUMEN

OBJECTIVE: The mechanism of Schisandrin B on the proliferation and migration of airway smooth muscle cells (ASMCs) in asthmatic rats was explored. METHODS: SD rats were divided into three groups: control (group 1), model (group 2) and model + Schisandrin B (group 3). miR-150 and lncRNA BCYRN1 levels were measured by qRT-PCR. The combination of BCYRN1 and miR-150 was detected by RNA pull down. ASMCs' viability/proliferation/migration were examined by WST-1 assay and 24-well Transwell system. RESULTS: Schisandrin B up-regulated miR-150 expression and down-regulated BCYRN1 expression in sensitized rats. Schisandrin B reversed the expression of miR-150 and BCYRN1 in MV-treated ASMCs. In addition, Schisandrin B inhibited the viability, proliferation and migration of MV-induced ASMCs. We also found miR-150 inhibited BCYRN1 expression which was proved by experiments using ASMCs transfected with miR-150 inhibitor. CONCLUSION: Schisandrin B increased miR-150 expression and decreased BCYRN1, and BCYRN1 expression was inhibited by miR-150, which indicated that Schisandrin B could regulate BCYRN1 through miR-150.

Asunto(s)

Asma , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Lignanos/farmacología , MicroARNs/genética , Miocitos del Músculo Liso/efectos de los fármacos , Compuestos Policíclicos/farmacología , ARN Largo no Codificante/metabolismo , Animales , Asma/tratamiento farmacológico , Asma/genética , Proliferación Celular/genética , Células Cultivadas , Ciclooctanos/farmacología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Miocitos del Músculo Liso/metabolismo , Ratas Sprague-Dawley

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OBJECTIVE: To observe the role of apelin in the prevention of pulmonary hypertension induced by hypoxia in mice. METHODS: Adult male apoE gene knockout (apoE-KO) mice were exposed to isobaric hypoxic chamber (9%~11% O2, regular chow feed, 23 h/d)for 3 weeks to establish hypoxia-induced pulmonary hypertension. Thirty apoE-KO mice were randomly divided into normoxia group, hypoxia group and hypoxic with apelin (10 nmol/(kg·d), ip) group. The concentrations of high density lipoprotein (HDL), low density lipoprotein (LDL)and total cholesterol in plasma were detected by Elisa method. The mRNA levels of ATP-binding cassette transporter A1(ABCA1), low density lipoprotein receptor (LDLR), scavenger receptor class B1 (SR-B1), and HMG-CoA reductase (HMGCR)in liver were measured by real-time PCR. The protein level of peroxisome proliferators-activated receptor gamma (PPARγ) in lung was measured by Western blot. RESULTS: ①The right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 87% and 85% (P<0.05), respectively. RVSP and RV/(LV+S) of apelin group were significantly lower than those of hypoxia group by 39% and 33%(P<0.05), respectively. ②The plasma concentration of HDL and HDL/LDL of apelin group were significantly higher than those of hypoxia group by 21% and 20%(P<0.05), respectively. ③The mRNA levels of LDLR, SR-B1 and ABCA1 in liver of apelin group were significantly up-regulated than those of hypoxia group by 241%, 112% and 69% (P<0.05), respectively, while the mRNA level of HMGCR was down-regulated by 45% (P<0.05). ④The protein level of PPARγ in lung of apelin group was significantly up-regulated than that of hypoxia group by 47% (P<0.05). CONCLUSIONS: Apelin attenuates hypoxia-induced pulmonary hypertension of mice through regulation of lipid metabolism.

Asunto(s)

Apelina/farmacología , Hipertensión Pulmonar/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Transportador 1 de Casete de Unión a ATP/metabolismo , Animales , Colesterol/sangre , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipoxia , Pulmón/metabolismo , Masculino , Ratones , Ratones Noqueados para ApoE , PPAR gamma/metabolismo , Distribución Aleatoria , Receptores Depuradores de Clase B/metabolismo

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BACKGROUND: Long noncoding RNAs (lncRNAs) played important roles in several biological processes through regulating the expression of protein. However, the function of lncRNA BCYRN1 in airway smooth muscle cells (ASMCs) has not been reported. METHODS: Male Sprague-Dawley (SD) rats were divided into control and asthma groups and the ovalbumin (OVA) model was constructed. The expression of BCYRN1 and transient receptor potential 1 (TRPC1) were detected in the ASMCs separated from these rats. Then 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) assay, Roche real-time cell analyzer (RTCA) DP assay and Transwell cell migration assay were performed to detect the effect of BCYRN1 on the viability/proliferation and migration of ASMCs. RNA pull-down assays and RNA immunoprecipitation assay were used to identify and verify the binding between BCYRN1 and TRPC1. Inspiratory resistance and expiratory resistance were measured in OVA challenged rats with BCYRN1 knockdown. RESULTS: We foundthe high expression of BCYRN1 and TRPC1 in asthma groups and ASMCs treated with PDGF-BB. Overexpression of BCYRN1 greatly promoted the proliferation and migration of ASMCs. In addition,TRPC1 overexpression reversed the function of si-BCYRN1 indecreasing the viability/proliferation and migration of ASMCs treated with PDGF-BB. BCYRN1 could up-regulate the protein level of TRPC1 through increasing the stability of TRPC1. Finally, we found that BCYRN1 knockdown reduced the inspiratory resistance and expiratory resistance in OVA challenged rats. CONCLUSION: Our study indicated that BCYRN1 promotedthe proliferation and migration of rat ASMCs in asthma via upregulating the expression of TRPC1.

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Airway smooth muscle cell (ASMC) was known to involve in the pathophysiology of asthma. Schisandrin B was reported to have anti-asthmatic effects in a murine asthma model. However, the molecular mechanism involving in the effect of Schisandrin B on ASMCs remains poorly understood. Sprague-Dawley rats were divided into three groups: rats as the control (Group 1), sensitized rats (Group 2), sensitized rats and intragastric-administrated Schisandrin B (Group 3). The expression of miR-135a and TRPC1 was detected in the rats from three groups. Platelet-derived growth factor (PDGF)-BB was used to induce the proliferation of isolated ASMCs, and the expression of miR-135a and TRPC1 was detected in PDGF-BB-treated ASMCs. Cell viability was examined in ASMCs transfected with miR-135a inhibitor or si-TRPC1. The expression of TRPC1 was examined in A10 cells pretreated with miR-135a inhibitor or miR-135a mimic. In this study, we found that Schisandrin B attenuated the inspiratory and expiratory resistances in sensitized rats. Schisandrin B upregulated the mRNA level of miR-135a and decreased the expression of TRPC1 in sensitized rats. In addition, Schisandrin B reversed the expression of miR-135a and TRPC1 in PDGF-BB-induced ASMCs. Si-TRPC1 abrogated the increasing proliferation of ASMCs induced by miR-135a inhibitor. We also found that miR-135a regulated the expression of TRPC1 in the A10 cells. These results demonstrate that Schisandrin B inhibits the proliferation of ASMCs via miR-135a suppressing the expression of TRPC1.

Asunto(s)

Lignanos/farmacología , MicroARNs/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Compuestos Policíclicos/farmacología , Canales Catiónicos TRPC/biosíntesis , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Asma/tratamiento farmacológico , Asma/metabolismo , Asma/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ciclooctanos/farmacología , Masculino , MicroARNs/genética , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Canales Catiónicos TRPC/genética , Canales Catiónicos TRPC/metabolismo , Regulación hacia Arriba

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AIM: To evaluate the safety and feasibility of laparoscopic abdominoperineal resection compared with the open procedure in multimodality management of rectal cancer. METHODS: A total of 106 rectal cancer patients who underwent open abdominoperineal resection (OAPR) were matched with 106 patients who underwent laparoscopic abdominoperineal resection (LAPR) in a 1 to 1 fashion, between 2009 and 2013 at Fudan University Shanghai Cancer Center. Propensity score matching was carried out based on age, gender, pathological staging of the disease and administration of neoadjuvant chemoradiation. Data regarding preoperative staging, surgical technique, pathological results, postoperative recovery and complications were reviewed and compared between the LAPR and OAPR groups. Perineal closure around the stoma and pelvic floor reconstruction were performed only in OAPR, not in LAPR. Therefore, abdominoperineal resection procedure-specific surgical complications including parastomal hernia and perineal wound complications were compared between the open and laparoscopic procedure. Regular surveillance of the two cohorts was carried out to gather prognostic data. Disease-free survival was analyzed using Kaplan-Meier estimate and log-rank test. Subgroup analysis was performed in patients with locally advanced disease treated with preoperative chemoradiation followed by surgical resection. RESULTS: No significant difference was found between the LAPR group and the OAPR group in terms of clinicopathological features. The operation time (180.8 ± 47.8 min vs 172.1 ± 49.2 min, P = 0.190), operative blood loss (93.9 ± 60.0 mL vs 88.4 ± 55.2 mL, P = 0.494), total number of retrieved lymph nodes (12.9 ± 6.9 vs 12.9 ± 5.4, P = 0.974), surgical complications (12.3% vs 15.1%, P = 0.549) and pathological characteristics were comparable between the LAPR and OAPR group, respectively. Compared with OAPR patients, LAPR patients showed significantly shorter postoperative analgesia (2.4 ± 0.7 d vs 2.7 ± 0.6 d, P < 0.001), earlier first flatus (57.3 ± 7.9 h vs 63.5 ± 9.2 h, P < 0.001), shorter urinary drainage time (6.5 ± 3.4 d vs 7.8 ± 1.3 d, P < 0.001), and shorter postoperative admission (11.2 ± 4.7 d vs 12.6 ± 4.0 d, P = 0.014). With regard to APR-specific complications (perineal wound complications and parastomal hernia), there were no significant differences between the two groups. Similar results were found in the 26 pairs of patients administered neoadjuvant chemoradiation in subgroup analysis. During the follow-up period, no port site recurrences were observed. CONCLUSION: Laparoscopic abdominoperineal resection for multidisciplinary management of rectal cancer is safe, and is associated with earlier recovery and shorter admission time in combination with neoadjuvant chemoradiation.

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Carcinoma de Células en Anillo de Sello/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía , Neoplasias del Recto/cirugía , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Carcinoma de Células en Anillo de Sello/patología , Quimioradioterapia Adyuvante , China , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Tempo Operativo , Complicaciones Posoperatorias/etiología , Neoplasias del Recto/patología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento

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Colonic lymphangioma is an unusual benign malformation. We herein describe two cases. A 36-year-old woman was admitted with one year of intermittent abdominal pain; colonoscopy, abdominopelvic computed tomography and endoscopic ultrasonography (EUS) revealed enlarged cystic masses at the ascending colon. In another 40-year-old man, colonoscopy and EUS revealed an asymptomatic lobulated cystic mass with four small sessile polyps at the sigmoid colon. Both patients underwent laparoscopic segmental colectomy. Both masses were histologically confirmed as cystic lymphangiomas, and the patients were discharged without complications. The management of colonic lymphangioma depends on the individual situation; close surveillance or endoscopic therapy may be appropriate for asymptomatic lesions smaller than 2.5 cm in diameter. Surgical intervention can be considered for larger lesions or in patients who develop complication risks. Laparoscopic segmental colon resection may be recommended to excise relatively large submucosal lesions because it is a definitive, minimally invasive intervention with a fast postoperative recovery.

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Colectomía/métodos , Neoplasias del Colon/cirugía , Laparoscopía , Linfangioma Quístico/cirugía , Adulto , Biopsia , Neoplasias del Colon/patología , Colonoscopía , Endosonografía , Femenino , Humanos , Linfangioma Quístico/patología , Masculino , Tomografía Computarizada por Rayos X , Resultado del Tratamiento

RESUMEN

Recent studies have shown that it is not only the absolute number of involved lymph nodes (LNs) but also the ratio of metastatic lymph node that confers prognostic information. However, the impact of the lymph node ratio (LNR) on the prognosis of rectal cancer treated with preoperative radiotherapy is still not fully studied. In this study, Surveillance, Epidemiology, and End Results (SEER)-registered rectal cancer patients treated with preoperative radiotherapy (preop-RT) with LN metastasis were evaluated using multivariate Cox regression analysis to determine the prognostic role of the LNR. LNR optimal cutoff was identified by X-tile. The rationale of yielding pathological node stage (yp-N stage) and yielding pathological lymph node ratio stage (yp-rN stage) (LNR stage) was further combined for analysis. For the results, X-tile program determined 0.28 and 0.68 as optimal cutoff values in terms of survival in 1,872 rectal cancer patients treated with preoperative radiotherapy. yp-rN was significantly associated with 5-year rectal cancer cause-specific survival (RCSS) (P < 0.001). In a multivariate analysis, yp-rN was a significant independent prognostic factor for RCSS (hazard ratios, 1.277 and 1.631; P < 0.001). yp-rN had a prognostic impact on RCSS in patients with yp-N1 and yp-N2 subgroup. yp-N stage also had influenced on RCSS in all yp-rN stage. The yp-rN stage can be used together with the yp-N stage to select high-risk patients for postoperative treatment.

Asunto(s)

Ganglios Linfáticos/patología , Pronóstico , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Preoperatorio , Neoplasias del Recto/cirugía

RESUMEN

OBJECTIVE: To explore the therapeutic efficacies of inhaled corticosteroids (ICS) plus low-dose theophylline for moderate bronchial asthma. METHODS: A total of 280 patients with moderate bronchial asthma at People's Hospital of Zhengzhou University between January 2011 and December 2011 were recruited and randomized into 2 groups: observation group with inhaled budesonide 400 µg/d plus aminophylline tablet (0.1 g, 3 times/day, oral administration and control group with inhaled budesonide 320 µg/day plus formoterol 9 µg/day. The course of treatment was around 6 months. The forced expiratory volume in one second % predicted (FEV1% predicted), interleukin (IL)-4, IL-5 and IgE of peripheral blood were compared before and after treatment. RESULTS: Before and 6 months after treatment, the values of FEV1 % predicted, IL-4, IL-5 and IgE for the observed group were 68% ± 6% and 76% ± 6%, (14.5 ± 4.4) and (7.2 ± 2.6) ng/L, (27.4 ± 6.2) and (24.2 ± 5.9) ng/L, (771 ± 130) × 10(3) and(592 ± 104) × 10(3) U/L, respectively, while those for the control group were 66% ± 8% and 77% ± 6%, (13.7 ± 4.3) and (7.7 ± 4.0) ng/L, (26.9 ± 5.8) and (24.6 ± 4.8) ng/L, (752 ± 154) and (604 ± 122) × 10(3) U/L, respectively. There were significant improvements in both groups (all P < 0.05). No differences existed between two groups (all P > 0.05). CONCLUSION: Compared with ICS plus inhaled long-acting ß2-agonists (LABA), ICS plus low-dose theophylline shows similar efficacies in the improvement of lung function and the control of airway inflammation for asthmatics.

Asunto(s)

Corticoesteroides/administración & dosificación , Asma/tratamiento farmacológico , Teofilina/administración & dosificación , Administración por Inhalación , Corticoesteroides/uso terapéutico , Adulto , Aminofilina/administración & dosificación , Aminofilina/uso terapéutico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Quimioterapia Combinada , Etanolaminas/administración & dosificación , Etanolaminas/uso terapéutico , Femenino , Fumarato de Formoterol , Humanos , Inmunoglobulina E/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Masculino , Persona de Mediana Edad , Teofilina/uso terapéutico

RESUMEN

OBJECTIVE: To compare the number of harvested perisplenic hilar lymph nodes by laparoscopy-assisted total gastrectomy (LATG) and conventional open total gastrectomy (OTG) for advanced upper and middle gastric cancer. METHODS: Three hundred twelve patients with advanced gastric cancer treated in a single institution between Sept 2008 and Jan 2011 were included in this study. They were divided into two groups: the LATG group and OTG (D2) group. All the surgical operations were performed by one surgeon or under his supervision. The lymph node clearance outcomes of the patients treated by those two surgical procedures were analyzed. RESULTS: The harvested lymph node numbers of the two groups were (29.57 ± 9.62) and (29.38 ± 11.22) respectively, statistically with no significant difference (P = 0.875). The numbers of lymph node dissected around the splenic area in the LATG group and OTG group (Section 10, 11 group) were (2.01 ± 1.34) and (1.33 ± 1.11), respectively, indicating a significant difference (P = 0.000). The numbers of lymph nodes dissected around the celiac region (Section 7, 8, 9, 11p and 12a(2) group) were (7.90 ± 3.41) and (7.22 ± 2.65), respectively, with a non-significant difference (P = 0.050). There were also no significant differences while comparing with the numbers of lymph nodes dissected in the cardiac area (group 1, 2), pyloric region (5, 6 group) and the greater and lesser omentum area (group 3 and 4) between the two groups (P = 0.605, P = 0.248, P = 0.262). CONCLUSION: Short-term results of this study indicate that laparoscopy-assisted total gastrectomy (D2) is better than conventional open surgery in perisplenic hilar lymph node dissection.

Asunto(s)

Gastrectomía/métodos , Laparoscopía , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/cirugía , Neoplasias Gástricas/cirugía , Adulto , Anciano , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Bazo , Estómago , Neoplasias Gástricas/patología