Bidirectional Association Between Asthma and Obesity During Childhood and Adolescence: A Systematic Review and Meta-Analysis.

Objective: Co-occurrence of pediatric asthma and obesity has been widely reported, yet the causal directions between these two disorders are still not well-understood. The objective of this meta-analysis is to explore whether there is a possibility of a bidirectional association for these two disorders in children and adolescents. Methods: PubMed, Embase, Web of Science, and CENTRAL databases were searched up to August 2020. Cohort studies reporting the associations of obesity with risk of physician-diagnosed asthma or physician-diagnosed asthma with risk of obesity in children and adolescents were eligible for the review. Results: A total of 3,091 records were identified from the four databases, with final inclusion of nine. Six studies reported the association between obesity and risk of asthma; three studies reported the association between asthma and risk of childhood obesity. As evaluated by the Newcastle-Ottawa quality assessment scale, all studies were assessed as high-quality studies. There was a statistically significant association between obesity and increased risk of physician-diagnosed asthma in children and adolescents. The pooled RR was 1.39 (95% CI: 1.28, 1.50; p < 0.001), with significant heterogeneity across studies (I 2 = 81.7%; p heterogeneity < 0.001). The pooled RR in boys was 1.53 (95% CI: 1.17, 1.99; p = 0.002), but such a significant association was not observed in girls (RR = 1.17, 95% CI: 0.79, 1.72; p = 0.434). For the association of asthma with risk of childhood obesity, the pooled RR was 1.47 (95%CI: 1.25, 1.72; p < 0.001) without statistical heterogeneity (I 2 = 0%, p heterogeneity = 0.652). Conclusion: There is a bidirectional association between obesity and asthma during childhood and adolescence, suggesting that childhood obesity drives an increase in the onset of asthma; meanwhile, childhood asthma may also increase risk of obesity for children and adolescents.

Alleviating airway inflammation by inhibiting ERK-NF-κB signaling pathway by blocking Kv1.3 channels.

Allergic asthma is a chronic inflammatory disease of the airways. T lymphocytes play an important role in the pathogenesis of asthma. The voltage-gated Kv1.3 potassium channel is a target for the preferential inhibition of TEM cells. In this study, we investigate the effects of PAP-1, a selective inhibitor of Kv1.3 channel, on the treatment of the neutrophilic asthma model. PAP-1 (40 mg/kg) was injected intraperitoneally into ovalbumin (OVA)-lipopolysaccharide (LPS)-challenged BALB/c mice. We found that the expression of the Kv1.3 channel in the lung tissues, and the intensity of the Kv current in the asthmatic mice increased clearly compared with those in normal control. PAP-1 significantly reduced airway hyperresponsiveness (AHR), inflammatory cell count in the bronchoalveolar lavage fluids (BALF) and serum, and attenuated airway inflammation in a histological examination of the asthmatic mice. Moreover, PAP-1 inhibited the OVA-LPS-induced imbalance of Th1/Th2, Treg/Th17 lymphocytes, and reduced levels of IL-4 and IL-17, inducing an increase in the production of IFN-γ and IL-10. Furthermore, the activation of the extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) pathway in the lungs of the asthmatic mice was suppressed by PAP-1. We also found that PD-98059, an inhibitor of ERK, had a similar effect with PAP-1 in terms of regulating the imbalance of Th1/Th2, Treg/Th17 cytokines. However, PD-98059 could not further influence cytokine changes when the cells were treated with PAP-1. The results suggest that ERK acts as a downstream regulator of inhibitors of the Kv1.3 channel in neutrophilic asthma. In conclusion, the inhibitor of the Kv1.3 channel has therapeutic potential for treating asthma.

Shikonin alleviates allergic airway remodeling by inhibiting the ERK-NF-κB signaling pathway.

Shikonin is a naphthoquinone extracted from the root of Lithospermum erythrorhizon, and has been reported to suppress allergic airway inflammation in mice. However, the underlying mechanisms are unclear and need to be further elucidated. In this study, shikonin (0.5, 2 or 4mg/kg) was given intraperitoneally to ovalbumin (OVA)-challenged BALB/c mice. We found that the pathological airway remodeling of asthmatic mice was alleviated by shikonin, and the infiltrated inflammatory cells and collagen deposition in their lungs were reduced. Furthermore, the abnormal activation of extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) pathway and the elevation of matrix metalloproteinase 9 (MMP9) in the lung of asthmatic mice were suppressed by shikonin. The inactivation of NF-κB by shikonin was at least in part via inhibiting IκBα activation. In vitro, the treatment of shikonin inhibited the platelet-derived growth factor (PDGF)-induced proliferation of primary airway smooth muscle cells (ASMCs), and induced a G0/G1 arrest in these cells. In addition, ASMCs exposed to PDGF acquired an enhanced migratory ability, and the activities of MMP9 and matrix metalloproteinase 2 (MMP2) and expression of MMP9 of these cells were significantly up-regulated. These PDGF-induced alterations were also inhibited by shikonin. The inhibitory effects of shikonin on the proliferation and migration of ASMCs were comparable to pyrrolidinedithiocarbamate (PDTC), an inhibitor of NF-κB pathway. In conclusion, the present study sheds lights on how shikonin alleviates allergic airway remodeling.

[Seasonal stratification and eutrophication characteristics of a deep reservoir, Longtan Reservoir in subtropical area of China].

In order to reveal the seasonal stratification and eutrophication characteristics of the subtropical large deep reservoir--Longtan Reservoir, the spatial and temporal distribution of environmental factors and eutrophic index were investigated during November (dry period) 2012, April (level period) and July (wet period) 2013. The results suggested that: (1) The stratification structure of Longtan Reservoir was meromictic lake, it had a single thermocline structure in the dry season, the surface layer to the 60 m was a mixomolimnion, 60-80 m was a thermocline, deeper more than 80 m was a monimolimnion. It had a double thermocline structure in flow period and wet period, the surface to 10 m was a mixed layer, 10-20 m was a thermocline, 20-40 m was a mixed layer, 40-60 m was a thermocline, deeper more than 60 m was a mixed layer. (2) The thermal stratification dominated the structure of other environmental factors, the stratification structure limited the water convection, especially the monimolimnion reduced the harm of the endogenous pollution. (3) The trophic level index (TLI) was 23.4-32.8 in the dry period, 27.1-38.6 in the flow period and 26.0-45.1 in the wet period, which were all Mesotropher. The trophic state index of total nitrogen was 60.3-72.5, which was eutropher to hyper eutropher, N: P was 107:1, which was phosphorus limited.

[Changes to surfactant proteins in the bronchoalveolar lavage fluid and serum of children with Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To study the changes to surfactant proteins in the serum and bronchoalveolar lavage fluids (BALF) of children with Mycoplasma pneumoniae pneumonia (MPP) and their significance. METHODS: Self-control method was used in the study. Forty-seven MPP children were divided into single lung infected (n=32) and bilateral lung infected groups (n=15) according to lung CT results. Surfactant proteins SP-A, B, C and D were measured using ELISA in the serum and BALF in the two groups. The correlations between SP-A, B, C and D content in the serum and BALF were evaluated by Spearman correlation analysis. RESULTS: SP-A, B, C and D content in BALF from the majorly infected or infected lung were significantly higher than from the opposite lung and serum (P<0.01). SP-A, B and C content in serum was significantly lower than in BALF from the non-infected lung in the single-side infected lung group (P<0.01 or 0.05), but there was no significant difference between serum SP-D content and BALF SP-D content from the non-infected lung. There were no significant differences in SP-A, B, C and D content in serum and BALF from the minorly infected lung in the bilateral lung infected group. Serum SP-D content was positively correlated with BALF SP-D content from the majorly infected lung in the bilateral lung infected group (P<0.01). CONCLUSIONS: Serum SP-D content may serve as a biomarker for evaluating the severity of pulmonary infection in children with community-acquired pneumonia.

[Impact of disease status on outcomes of allogeneic hematopoietic stem cell transplantation in patients with refractory and relapsed acute myeloid leukemia].

The study was aimed to evaluate the impact of disease status on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with refractory and relapsed acute myeloid leukemia (AML). 32 patients with refractory and relapsed AML received allo-HSCT after myeloablative conditioning regimen, including 17 patients in no-remission (NR) and 15 patients in complete remission (CR) at the time of transplant. Treatment related adverse events, relapse rate and leukemia free survival (LFS) were analyzed. The results showed that the parameters of sex, age, cytogenetic risk and transplant procedures were comparable between the two groups. 30 patients had successful engraftment, except one had graft failure and one died from severe veno-occlusive disease in the NR group. The incidences of aGVHD in NR group and CR group were 47.1% (8 patients) and 33.5% (5 patients) respectively. Out of comparable patients, 5 from 9 patients in NR group developed with cGVHD, and 4 from 11 patients in CR group were subjected to cGVHD. There were no statistic difference in incidences of aGVHD and cGVHD between two group. Compa-red with CR group, NR group had a higher treatment-related mortality (29.4% vs 14.3%, P = 0.392) and relapse rate (42.9% vs 26.7% P = 0.300), but there was no significant difference. With a median follow-up of 13 (1 - 124) months, 6 patients remained alive in both of the two groups, and the 2 year LFS of them were parallel (35.3% vs 40.0%, P = 0.267). Among these 32 patients, overall survival (OS) was better in patients with age < 35 years (P = 0.044) and with the appearance of cGVHD (P = 0.046). It is concluded that allo-HSCT is an effective salvage therapy for patients with refractory and relapsed AML, and the overall outcome seems unrelated to the disease status (NR or CR) before transplantation. As such, for refractory and relapsed AML patients in non-remission, performance of allo-HSCT to achieve long-term survival is feasible.

[Detecting minimal residual disease status in allogeneic hematopoietic stem cell transplantation of patients with high-risk acute leukemia].

OBJECTIVE: To explore the relationship between minimal residual disease (MRD) and the outcome of patients with high-risk acute leukemia (AL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: By 4/5-color multi-parameter flow cytometry (MFC, CD45/SSC gating) for detecting MRD at pre-(day-30) and post-transplant (day +30, +60, +100, 6 months, 9 months and 12 months), the investigators retrospectively analyzed the MRD levels and the prognosis of 90 high-risk patients. According to the MRD cutoff value of 0.1%, the low-level and high-level groups were defined. In the high-level group, the patients were divided into two sub groups according to the subsequent treatment (intervention therapy group and non-intervention therapy group). RESULTS: MRD pre-transplant had no predictive value for the clinical outcome. The patients with high levels of MRD post-transplant (+60 d and +100 d) showed higher relapse rates than those of the low-level group. In addition, regarding MRD +100 d post-transplant, differences were significant among 3 groups (high-level MRD and intervention therapy group, high-level MRD and non-intervention therapy group and low-level MRD group) including 1-year relapse-free survival (RFS) (100% vs 60.87% vs 91.30%, P < 0.05) and 3-year RFS (85.71% vs 44.72% vs 68.48%, P < 0.05). The median time from first high level MRD detected to clinical relapse was 2.5 (1 - 26) months. In the high level MRD group (+100 d post-transplant), 7 of 30 patients received intervention therapy without relapse. However another 23 patients had no intervention treatment and 11 of them relapsed latter (P < 0.05). CONCLUSION: The MFC-based quantification of MRD post-transplant reveals important prognostic information in patients with high-risk AL. MRD check point at day +100 (cutoff: 0.1%) may discriminate different risk populations. Those patients with MRD levels ≥ 0.1% should receive early intervention at an early stage and a low tumor burden so as to reduce the relapse rate and boost survival.

Gracillosides A-F, six new 8,14-seco-pregnane glycosides from Adelostemma gracillimum.

Six new 8,14-seco-pregnane glycosides, gracillosides A-F (1-6), were isolated from the roots of Adelostemma gracillimum (Asclepiadaceae). All of them had the same aglycone as gracigenin with a rare 8,14-seco-pregnane type skeleton in nature and possessed an oligosaccharide chain consisting of four to six sugar units at C-3 of the aglycone. Their structures were determined on the basis of detailed spectroscopic analysis and chemical evidence.