[Pulmonary Vascular Remodeling Characteristics of Pulmonary Arterial Hypertension Mouse Model Induced by Left Pneumonectomy and Jugular Vein Injection of Monocrotaline Pyrrole].

Objective: To compare and investigate the differences and characteristics of pulmonary vascular remodeling in three mouse models of pulmonary arterial hypertension (PAH) constructed by left pneumonectomy, jugular vein injection of monocrotaline pyrrole, and left pneumonectomy combined with jugular vein injection of monocrotaline pyrrole, to explore for a PAH animal model that approximates the clinical pathogenesis of PAH, and to create a model that will provide sound basis for thorough investigation into the pathogenesis of severe PAH. Methods: 59 male C57/BL mice (10-12 weeks, 24-30 g) were randomized into four groups, a control group ( n=9), a group that had left pneumonectomy (PE, n=15), a group that had jugular vein injection of monocrotaline pyrrole (MCTP, n=15), and the last group that had left pneumonectomy combined with jugular injection of monocrotaline pyrrole (P+M, n=20). To evaluate the effect of modeling and the characteristics of pulmonary vascular remodeling, hemodynamic and morphological parameters, including right ventricular systolic pressure (RVSP), right ventricle/(left ventricle plus septum) (RV/LV+S), percent of wall thickness in the pulmonary artery (WT%), muscularization of non-muscular arteries, neointima formation, and vascular obstruction score (VOS), were measured in each group. Results: 1) Compared with those of the control group, the RVSP, RV/LV+S, WT%, and the degree of small pulmonary arteries muscularization in the P+M group were significantly increased ( P<0.01). The MCTP group had just slightly higher findings for these indicators ( P<0.05), while no significant change in these indicators was observed in the PE group ( P>0.05). 2) Neointima formation in the acinus pulmonary arteries, which caused obvious stenosis of the lumen, was observed in the P+M group, the VOS being 1.25±0.80 points ( P<0.001). In contrast, neointima formation was not observed in the MCTP group or the PE groups, the VOS being 0 point ( P>0.05). Conclusion: Left pneumonectomy combined with jugular intravenous injection of MCTP could induce severe PAH formation in mouse. The model provides a good simulation of neointima formation, the characteristic pathological change of clinical severe PAH.

[The Effects of Ginsenoside Compound K on PDGF-BB-Induced PASMCs Proliferation and Phenotypic Conversion of Pulmonary Arterial Smooth Muscle Cells].

OBJECTIVE: To explore the inhibitory effects of ginsenoside compound K (CK) on pulmonary arterial smooth muscle cells (PASMCs) proliferation and phenotypic conversion in vitro and investigate its related mechanisms. METHODS: PASMCs cultured in vitro were examined in the study. They were induced with platelet-derived growth factor-BB (PDGF-BB) and then treated with CK. The cells were randomly assigned to the control group (receiving no treatment), the model group (PDGF-BB, 20 ng/mL), and the intervention group (20 ng/mL PDGF-BB+5 µmol/L CK). The cell proliferation was measured by CCK-8 assay (on the basis of the above group assignment, concentrations of CK was set at 1, 3, and 5 µmol/L in the intervention group, and the drug group was added, receiving 1, 3, and 5 µmol/L CK, respectively). Cell cycle and apoptosis were examined by flow cytometry. The levels of mRNA and proteins of α-smooth muscle actin ( α-SMA) and smooth muscle 22α ( SM22 α), markers of phenotypic conversion, were detected by quantitative real-time PCR and Western blot. The levels of protein expression related to Wnt/ß-catenin signaling pathway were examined by Western blot. RESULTS: Compared with the model group, CK significantly inhibited PDGF-BB-induced proliferation of PASMCs in a dose-dependent way. The results of 5 µmol/L CK intervention were not significantly different from that of the control group ( P>0.05). Hence, 5 µmol/L CK was chosen for subsequent experiments. Separate treatment of PASMCs with CK at doses of 1, 3, and 5 µmol/L did not reveal any cytotoxicity to PASMCs ( P>0.05). CK also arrested the cell cycle of PASMCs at the G 0/G 1 phase, promoted the apoptosis of PASMCs, and reversed the mRNA and protein expression of α-SMA and SM22 α ( P<0.01). In addition, CK down-regulated the expressions of cyclin D1 and ß-catenin, while it up-regulated the protein expressions of phosphorylated glycogen synthase kinase-3ß (pGSK-3ß)/glycogen synthase kinase-3ß (GSK-3ß) ( P<0.01). CONCLUSION: CK was capable of inhibiting the abnormal proliferation of PASMCs and reversing the phenotypic conversion, and its acting mechanism may be related to the Wnt/ß-catenin signaling pathway, suggesting the therapeutic potential of CK in controlling pulmonary arterial hypertension.

[Clinical Analysis of 86 Cases of Children with Plastic Bronchitis].

OBJECTIVE: To investigate the clinical features of pediatric patients who had plastic bronchitis (PB) and to explore the risk factors for respiratory support in the pediatric patients with PB in order to improve the ability to identify PB in children. METHODS: The basic information and clinical manifestations of 86 children diagnosed with PB at West China Second University Hospital of Sichuan University from March 2014 to December 2019 were collected and analyzed retrospectively. The patients were divided into the respiratory support (RS) group and non-respiratory support (NRS) group as per their need for respiratory support. Logistic regression was conducted to analyze the risk factors for respiratory support in PB patients. RESULTS: A total of 86 children with PB were included in the study, including 62 (72.1%) who were over 3 years old. 57 patients (66.3%) had complications. 56 patients were given respiratory support after admission. All the 86 children had a history of fever and cough, and 76 (88.4%) experienced fever peaks≥39.5°C. Chest imaging showed large lung consolidation or atelectasis in 82 cases (95.3%) and pleural effusion in 63 cases (73.3%). 70 cases (81.4%) were tested positive for pathogens, with the highest infection rate of 68.6% for mycoplasma pneumoniae. There were 30 patients (34.9%) in the NRS group and 56 patients (65.1%) in the RS group. Logistic regression analysis showed that patient being younger than 3 years old ( OR=4.99) and having complications ( OR=7.22) were independent risk factors for respiratory support in children with PB (all P<0.05). CONCLUSIONS: Clinically, severe clinical symptoms combined with other systemic complications, large lung consolidation or atelectasis, pleural effusion, and positive lab results for mycoplasma pneumoniae should be an alert indicating the possibility of having PB. Young age and complications were independent risk factors for respiratory support in PB patients.

[Preliminary Experimental Study of Establishing a Lung Development Model with Specific Pathogen Free Preterm Pigs].

OBJECTIVE: To determine the best time for conducting cesarean section for the establishment of an animal model of lung development with specific pathogen free (SPF) preterm Bama minipigs under the condition of not making medical interventions such as hyperoxia, mechanical ventilation, or medication. METHODS: SPF Bama sows at gestational day (GD) 113, GD107, GD104, GD101, and GD98 were selected and cesarean sections were performed. Then, the viability of the preterm piglets were observed. Based on their general data, viability, and paraffin sections stained with hematoxylin and eosin, the best time for performing cesarean section in order to build a SPF preterm pig model of lung development was determined. RESULTS: Cesarean sections were performed on a total of 7 sows and 55 piglets were delivered, among which 25 were still alive 3 hours after delivery. Seven piglets of GD104 and all piglets of GD107 and GD113 survived, while piglets of GD98 and GD101 all died. The survival rate of piglets of GD104 was 33.33% (7/21). Piglets of GD98 already possessed fully developed physical appearance and lung shape. Piglets from GD104 had better lung expansion and higher density of thin-walled alveoli. The lungs of GD107 piglets were basically fully expanded, and the density of thin-walled alveoli was almost the same as that of normal full-term piglets. CONCLUSIONS: Findings of this study suggest that SPF preterm piglets of GD104 with no specific pathogen exposure and no medical intervention can be used to establish a SPF preterm pig model of lung development.

[Epidemiological features and mechanism of coronavirus disease 2019 in children].

Compared with adults, children tend to have lower incidence rate, hospitalization rate, and mortality rate of coronavirus disease 2019 (COVID-19), while the cause of such age-based differences in disease severity remains unclear. An investigation of pathogenesis in children may help to analyze the therapies for the high-risk population. Human angiotensin-converting enzyme Ⅱ is the main receptor of severe acute respiratory syndrome coronavirus 2 and can limit pulmonary capillary leakage and inflammation mediated by angiotensin 2 and exert a protective effect against acute lung injury. Its expression decreases with age. Regular vaccination and frequent upper respiratory virus infection in children can lead to regular immune activation, and its combination with strong innate immunity can help to achieve virus clearance in the early stage of infection in children with COVID-19. Meanwhile, there are strong regeneration and repair abilities of alveolar epithelial cells in children, which may help with the early recovery of infection. In addition, risk factors, such as underlying cardiopulmonary diseases, obesity, and smoking, are relatively uncommon in children. Social factors, including home quarantine and timely closure of schools, may help to reduce the infection rate in children. However, children with immunodeficiency are a high-risk population and should be closely monitored. Further studies are needed to investigate the immune and protection mechanisms against COVID-19 in children.

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.

[Preventive and Therapeutic Effects of Exogenous Apelin Regulating Autophagy on the Formation of Pulmonary Artery Hhypertension in Rats].

OBJECTIVE: To investigate the effect of exogenous Apelin on pulmonary artery hypertension (PAH) and its related mechanism. METHODS: 26 male SD rats were randomly divided into Control group ( n=6), Model group ( n=10) and Intervention group ( n=10). The rat model of PAH was established by left pneumonectomy combined with monocrotaline injection (PE+MCT) in the Model group and the Intervention group, while the Control group rats were opened chest cavity and injected the same amount of normal saline. From the 2nd week after operation, the Intervention group was intraperitoneally injected with 10 nmol/(kg·d) Apelin-13 for 3 weeks, while the Control group and Model group were injected the same volume of normal saline. The mean pulmonary arterial pressure (mPAP) was measured and the right ventricular hypertrophy index ( RVHI) was calculated in all three groups of rats at the 5th week after operation. The pulmonary tissue HE staining was performed to observe the pulmonary tissue and pulmonary vascular morphology. Protein LC3 was detected by immunofluorescence staining of lung tissues, the mRNA expression level of P62 and Beclin-1 in lung tissues was measured by RT-PCR, and the protein expressions of LC3, LC3-Ⅱ/LC3-Ⅰ, P62 and Beclin-1 in lung tissues were measured by Western blot. RESULTS: Compared with the Control group, the Model group showed increased mPAP and RVHI ( P<0.05), disordered pulmonary tissue structure and thicker pulmonary vascular wall. In Model group rats, expression of LC3 protein and LC3-Ⅱ/LC3-Ⅰ increased in lung tissues, and the expression of Beclin-1 mRNA and the Beclin-1 protein also increased in lung tissues, while the level of P62 mRNA and the expression of P62 protein decreased ( P<0.05). After Apelin-13 intervention, the above indexes were all improved ( P<0.05, compared with the Model group). CONCLUSION: Exogenous Apelin has a certain preventive and therapeutic effect on the formation of PAH, and the mechanism may be related to its inhibition effect on autophagy.

[Association of age distribution with the expression of angiotensin-converting enzyme 2 in lung tissues in severe acute respiratory syndrome coronavirus 2 infection: reflections from the study of RAS pathway expression in mice].

OBJECTIVE: To study the expression of angiotensin-converting enzyme 2 (ACE2) and other key molecules of the RAS pathway in normal mice at different developmental stages, and to provide ideas for understanding the infection mechanism of coronavirus disease 2019 (COVID-19) as well as the diagnosis and treatment of children with COVID-19. METHODS: The mice at different developmental stages were enrolled, including fetal mice (embryonic days 14.5 and 18.5), neonatal mice (0, 3, 7, 14, and 21 days old), young mice (28 and 42 days old), and adult mice (84 days old). The lung tissues of all fetal mice from 4 pregnant mice were collected at each time point in the fetal group. Four mice were sampled in other age groups at each time point. Whole transcriptome resequencing was used to measure the mRNA expression of AGT, ACE, ACE2, Renin, Agtr1a, Agtr1b, Agtr2, and Mas1 in mouse lung tissue. RESULTS: The expression of ACE2 in the lungs showed changes from embryonic stage to adult stage. It increased gradually after birth, reached a peak on day 3 after birth, and reached a nadir on day 14 after birth (P<0.05). The expression of AGT reached a peak on days 0 and 7 after birth and reached a nadir on day 21 after birth (P<0.05). The expression of ACE increased rapidly after birth and reached a peak on day 21 after birth (P<0.05). Agtr1a expression reached a peak on day 21 after birth (P<0.05). Agtr2 expression gradually decreased to a low level after birth. Renin, Agtr1b, and Mas1 showed low expression in lung tissues at all developmental stages. CONCLUSIONS: At different developmental stages of mice, ACE2 has dynamic expression changes, with high expression in early neonatal and adult mice. The other key molecules of the RAS pathway have their own expression patterns. These suggest that the difference in clinical features between children and adults with COVID-19 might be associated with the different expression levels of ACE2 in the different stages, and further studies are needed for the mechanism.

[Effect of low-concentration paclitaxel on collagen deposition outside rat pulmonary artery smooth muscle cells and related mechanism].

OBJECTIVE: To study the effect of low-concentration paclitaxel (PTX) on transforming growth factor-ß1 (TGF-ß1)-induced collagen deposition outside rat pulmonary artery smooth muscle cells (PASMCs) and related mechanism. METHODS: Primary rat PASMCs were divided into a blank control group (n=3), a model group (n=3), and a drug intervention group (n=3). No treatment was given for the blank control group. The model group was treated with TGF-ß1 with a final concentration of 10 ng/mL. The drug intervention group was treated with PTX with a final concentration of 100 nmol/L in addition to the treatment in the model group. MTT colorimetry was used to measure cell proliferation. Quantitative real-time PCR was used to measure the relative mRNA expression of collagen type I (COL-I) and collagen type III (COL-III). ELISA was used to measure the OD value of COL-I and COL-III proteins. Western blot was used to measure the relative protein expression of COL-I, COL-III, and the key proteins of the TGF-ß1/Smad3 signaling pathway (Smad3 and p-Smad3). RESULTS: Compared with the blank control group, the model group had significant increases in proliferation ability, relative mRNA and protein expression of COL-I and COL-III, and relative protein expression of p-Smad3 (P<0.05). Compared with the model group, the drug intervention group had significant reductions in the above indicators, but which were still higher than those in the blank control group (P<0.05). There was no significant difference in the relative protein expression of Smad3 among the three groups (P>0.05). CONCLUSIONS: Low-concentration PTX exerts a marked inhibitory effect on TGF-ß1-induced collagen deposition outside PASMCs, possibly by regulating the phosphorylation of Smad3 protein.

[The Changes of Cytoskeleton during Phenotypic Transition of Pulmonary Artery Smooth Muscle Cells Induced by PDGF-BB].

OBJECTIVE: To study the changes of cytoskeleton during the phenotypic transition of rat pulmonary artery smooth muscle cells (PASMCs) induced by platelet-derived growth factor (PDGF-BB), and to explore the mechanism involved in the process of phenotypic transition of PASMCs. METHODS: PASMCs of Sprague Dawley (SD) rats were cultured and identified by immunohistochemistry (IHC) method. The cells were randomly divided into control group and PDGF-BB treated group (10 ng/mL). RT-qPCR and Western blot were used to detect the mRNA and protein level of marker genes (α-SMA and SM22α) during the process of phenotypic transition of PASMCs. The changes of cytoskeleton were observed by fluorescent microscopy, cell proliferation was measured by CCK-8 method; and cell migration was observed by wound healing assay. RESULTS: Compared with control group, PDGF-BB down-regulated the mRNA and protein expression of α-SMA and SM22α. The fluorescence intensity of cytoskeletal protein was significantly reduced after the treatment of PDGF-BB. In addition, the structure of F-actin was disorganized with a burr-like appearance, and the structures of α-tubulin and ß-tubulin were irregular with co-location appearance. PDGF-BB significantly enhanced the proliferation and migration of PASMCs . CONCLUSION: PDGF-BB could induce a conformation change in cytoskeletal proteins for PASMCs phenotypic transition, and enhance the ability of proliferation and migration of PASMCs.

[Expression of B7 Family Co-inhibitory Molecules in the Establishment of Pulmonary Regional Immunity].

OBJECTIVE: To identify the temporal-spatial expression of B7 family co-inhibitory molecules during lung development, and to explore the roles of B7 family co-inhibitory molecules in the developmental process of pulmonary regional immunity. METHODS: The expression of B7 family co-inhibitory molecules (B7-1, B7-2, B7-H1, B7-DC) in different developmental stages of Rhesus monkey lungs were normalized and calculated by the reads per kilo-base of transcript per million mapped reads (RPKM) method. Immunohistochemical staining was performed to identify the localization and the protein of B7 family co-inhibitory molecules in different developmental phase (canalicular stage, cystic stage, alveolar stage) in mouse. RESULTS: The expression of B7 family co-inhibitory molecules in rhesus monkey were increased during the prenatal period (cystic stage, alveolar stage), the expressions of B7-2 and B7-H1 mRNA were significantly increased in alveolar stage (P<0.05). The results of immuno-histochemistry indicated that B7 family co-inhibitory molecules were mainly expressed in airway epithelial cells, and their protein levels were increased during the prenatal period. The expressions of B7-2, B7-H1 and B7-DC were significantly increased from canalicular stage (P<0.05). The protein of B7-2 was higher in airway than that in bronchus (P<0.05). CONCLUSIONS: B7 family co-inhibitory molecules are mainly expressed in airway epithelial cells, and the expressions are increased during the prenatal period, which suggests that B7 family co-inhibitory molecules are involved possibly in the development of pulmonary regional immunity.

[The Regulation Effects of Carbon Monoxide in Cardiovascular Systems].

As a famous toxic gas, the toxicological mechanism of carbon monoxide has been elucidated. However, carbon monoxide can be synthesized endogenously in human body and play important roles in cardiovascular systems. The results from previous researches of carbon monoxide suggested that carbon monoxide could be an intervention target of many cardiovascular diseases. Future studies are deserved in this area.

[Effect of NF-κB on proliferation of rat pulmonary artery smooth muscle cells inhibited by simvastatin].

OBJECTIVE: To explore the effects of NF-κB on proliferation of rat pulmonary artery smooth muscle cells (PASMC) inhibited by simvastatin. METHODS: PASMC isolated from rats and cultured in vitro were randomly divided into four groups (n=6 each): control, platelet-derived growth factor (PDGF) treatment, PDGF+simvastatin treatment, and PDGF+simvastatin+parthenolide (NF-κB inhibitor) treatment. MTT colorimetric assay and flow cytometry were performed to detect cell proliferation and cell cycle distribution. Immunohistochemistry was performed to detect the expression of NF-κB protein. Real-Time PCR was performed to detect NF-κB mRNA expression. RESULTS: Compared with the control group, MTT values of PASMC at all time points, cell proportion at the S phase and G2+M phase, NF-κB protein and mRNA expression increased significantly in the PDGF group (P<0.05). With the intervention of simvastatin, the levels of above indexes decreased compared with the PDGF group (P<0.05). With the intervention of simvastatin and parthenolide, the levels of above indexes decreased more obviously, but were not significantly different from those in the simvastatin intervention group. CONCLUSIONS: Simvastatin can inhibit proliferation of PASMC and cell cycle process. NF-κB may play an important role in the inhibitory effect of simvastatin on the proliferation of PASMC.

[Mechanisms for reversal of pulmonary hypertension by rapamycin in rats].

OBJECTIVE: To investigate the effects of rapamycin (RAP) on pulmonary hypertension (PH) in rats, and to provide new insights into medication selection for the clinical treatment of PH. METHODS: Fifty male Sprague-Dawley rats were randomly divided into blank control, PH model, solvent control, RAP 1, and RAP 2 groups. A rat model of PH was induced by left pneumonectomy (PE) and monocrotaline (MCT). At 5 days after PH model establishment, the solvent control group and the RAP 1 group received an intramuscular injection of solvent and RAP, respectively. At 35 days after PH model establishment, the RAP 2 group received an intramuscular injection of RAP. The mean pulmonary artery pressure (mPAP) and the right ventricle/left ventricle plus septum weight ratio (RV/LV+S) were measured in each group. Histopathological changes in the right lung were evaluated by hematoxylin-eosin (HE) staining. The relative expression of alpha-smooth muscle actin (α-SMA) and smooth muscle protein 22-alpha (SM22α) in each group was determined using real-time PCR. RESULTS: At 35 days after surgery, the PH model and the solvent control groups had significantly higher mPAP and RV/LV+S than the blank control group, while the RAP 1 and the RAP 2 groups had significantly lower mPAP than the solvent control group (P<0.05). The RV/LV+S in the RAP 1 group was significantly lower than that in the solvent control group (P<0.05); however, there was no significant difference in RV/LV+S between the RAP 2 and the solvent control groups (P>0.05). HE staining in the right lung showed the substantially thickened pulmonary artery wall and narrowed arterial lumen in the PH model and the solvent control groups compared with the blank control group. Different degrees of reversal of the pulmonary artery wall thickening were observed after RAP administration. The results of real-time PCR revealed that the relative expression of α-SMA and SM22α in the PH model and the solvent control groups was significantly lower than in the blank control group, while the relative expression of α-SMA and SM22α in the RAP 1 and the RAP 2 groups was significantly higher than in the solvent control group (P<0.05). CONCLUSIONS: RAP can reverse the increase in pulmonary artery pressure and the right ventricular hypertrophy probably by regulation of the phenotypic conversion of vascular smooth muscle cells.

[Relationship between Hes-1 and airway inflammation and remodeling in a rat model of asthma].

OBJECTIVE: To study the changes of Hes-1, the target gene of Notch signaling pathway, and its relationship with airway inflammation and remodeling in a rat model of asthma. METHODS: Forty-eight rats were randomly divided into an asthma group and a control group. The rats in the asthma group were sensitized and challenged by ovalbumin (OVA), and normal saline was used in the control group. Two groups were further divided into 3 subgroups according to time points after challenging, i.e. 4 weeks, 8 weeks and 12 weeks (n=8 rats each). Pathological changes of lungs were observed by light microscopy and the thickness of bronchial smooth muscle layer (Wam) was measured. The levels of IL-4 and INF-γ in rat serum and bronchoalveolar lavage fluids (BALF) were measured using ELISA. Expression levels of Hes-1 protein and mRNA were determined by immunohistochemistry and quantitative real-time PCR respectively. RESULTS: Together with the extension of challenging, the Wam of rats in the asthma group increased, a decrease of INF-γ level and an increase of IL-4 level in serum and BALF were also observed, and the differences were statistically significant compared with those in the corresponding control group (P<0.05). Hes-1 protein and mRNA levels also increased gradually after OVA challenging and were higher than those in the control group (P<0.05). The levels of Hes-1 protein and mRNA were positively correlated with Wam and IL-4 in serum and BALF, but were inversely correlated with INF-γ in serum and BALF (P<0.05). CONCLUSIONS: Levels of Hes-1 protein and mRNA increased, which were closely related with the levels of airway inflammatory factors and remodeling of airway smooth muscle. Hes-1 may play an important role in the pathogenesis of asthma.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

[Pulmonary vascular remodeling in congenital cardiovascular abnormalities: an eternal topic].

Pulmonary arterial hypertension (PAH) is one of the most severe complications of congenital heart defects with left to right shunt. Pulmonary vascular remodeling (PVR) is extremely essential in PAH. Therefore, prevention and reversion of PVR is one of the most important factors for improving quality of life for children suffering from PAH. In this article we reviewed the emerging research views on PVR from the disciplines of oncology and anti-tumor pharmacy. Two main sections were included. On the one hand, we introduced the "ATM signal turning point hypothesis" from the DNA damage response (DDR) mechanism research in oncology. The hypothesis suggests that the tumor-like proliferation of vascular smooth muscle cells might be the pathological basis of obstructive PAH. On the other hand, a new lung-targeted drug delivery system based on the fact that low concentration of anti-tumor drugs can inhibit angiogenesis without cellular toxicity was introduced. These new research directions could extend current practice in PVR therapy.

Myeloid-derived suppressor cells and pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic pulmonary vascular disorder characterized by an increase in pulmonary vascular resistance and pulmonary arterial pressure. The detailed molecular mechanisms remain unclear. In recent decades, increasing evidence shows that altered immune microenvironment, comprised of immune cells, mesenchymal cells, extra-cellular matrix and signaling molecules, might induce the development of PH. Myeloid-derived suppressor cells (MDSCs) have been proposed over 30 years, and the functional importance of MDSCs in the immune system is appreciated recently. MDSCs are a heterogeneous group of cells that expand during cancer, chronic inflammation and infection, which have a remarkable ability to suppress T-cell responses and may exacerbate the development of diseases. Thus, targeting MDSCs has become a novel strategy to overcome immune evasion, especially in tumor immunotherapy. Nowadays, severe PH is accepted as a cancer-like disease, and MDSCs are closely related to the development and prognosis of PH. Here, we review the relationship between MDSCs and PH with respect to immune cells, cytokines, chemokines and metabolism, hoping that the key therapeutic targets of MDSCs can be identified in the treatment of PH, especially in severe PH.

[Effects of paclitaxel on proliferation and transition of phenotype in platelet-derived growth factor-BB-induced pulmonary vascular smooth muscle cells].

OBJECTIVE: To investigate the effects of paclitaxel on the phenotypic modulation induced by platelet-derived growth factor (PDGF-BB) in rat pulmonary vascular smooth muscle cells (PVSMC). METHODS: The proliferation of PVSMC isolated from SD rats cultured in vitro was induced by PDGF-BB and then intervened by different concentration of paclitaxel. MTT and [³H]-thymidine incorporation were used to detect the changes of cell proliferation. The expression level of alpha-smooth muscle-actin (SM-α-actin) and smooth muscle protein 22alpha (SM22α) were tested by Western blot. Confocal laser scanning microscopy was applied to observe the change of fluorescence intensity. RESULTS: Treatment with PDGF-BB for 24 hours results in a significant increase in [³H]-thymidine incorporation and marked change in phenotype and cytoskeleton, Paclitaxel inhibited the proliferation of PVSMC induced by PDGF-BB, the inhibition rate was 45.4%, 35.4%, 21.6% (P < 0.01) tested by[³H]-thymidine incorporation and 40.0%, 30.0%, 18.0% (P < 0.01) tested by MTT. Meanwhile, the paclitaxel promoted the expression level of SM-α-actin and SM22α. Fluorescence intensity of F-actin decreased significantly. CONCLUSION: Paclitaxel may play an important role in vascular remodeling by changing the phenotypes and cytoskeleton of VSMC stimulated by PDGF-BB.

Mechanical stress induces a scalable circularly polarized LEO satellite antenna with Quadrifilar spiral.

This paper investigates a left-hand circularly polarized (LHCP) antenna and a right-hand circularly polarized (RHCP) antenna on LEO Satellite, which is based on the phase-tuning metasurface. We overcome its inherent limitations in size, weight and power, and designed a high-gain, ultra-lightweight, scalable antenna for small satellite communications. The antenna can generate continuous and large tunability of subwavelength, with low-Q resonators. The simulated and experimental results verify that different capacitance and inductance modes can be effectively generated by rotating the spiral arms of single-arm spiral antennas with corresponding degrees, which greatly simplify the feeding network. The maximum gain of the normal position within the angle of the uplink and downlink is 4~9 dBi higher than that of the ordinary polarized antenna. In addition, the design method proposed to this article is superior to the reference system in terms of impedance bandwidth, axial ratio bandwidth, and operation frequency. The performance achievements of this paper are implemented within the bandwidth of 3 MHz of uplink and downlink, such as impedance bandwidth is 3 MHz with impedance of 50, axial ratio bandwidth is 2.5 MHz, operation frequency of uplink is 240-243 MHz, downlink is 320 MHz and 401 MHz, and the voltage standing wave ratio (VSWR) is less than 2 dB which is so called S parameter, the above parameters can meet the performance index design requirements.