Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection. Participants were randomly assigned, in a 2:1 ratio, to receive ziresovir (at a dose of 10 to 40 mg, according to body weight) or placebo, administered twice daily, for 5 days. The primary end point was the change from baseline to day 3 (defined as 48 hours after the first administration) in the Wang bronchiolitis clinical score (total scores range from 0 to 12, with higher scores indicating greater severity of signs and symptoms). The intention-to-treat population included all the participants with RSV-confirmed infection who received at least one dose of ziresovir or placebo; the safety population included all the participants who received at least one dose of ziresovir or placebo. RESULTS: The intention-to-treat population included 244 participants, and the safety population included 302. The reduction from baseline in the Wang bronchiolitis clinical score at day 3 was significantly greater with ziresovir than with placebo (-3.4 points [95% confidence interval {CI}, -3.7 to -3.1] vs. -2.7 points [95% CI, -3.1 to -2.2]; difference, -0.8 points [95% CI, -1.3 to -0.3]; P = 0.002). The reduction in the RSV viral load at day 5 was greater in the ziresovir group than in the placebo group (-2.5 vs. -1.9 log10 copies per milliliter; difference, -0.6 log10 copies per milliliter [95% CI, -1.1 to -0.2]). Improvements were observed in prespecified subgroups, including in participants with a baseline bronchiolitis score of at least 8 and in those 6 months of age or younger. The incidence of adverse events related to the drug or placebo was 16% with ziresovir and 13% with placebo. The most common adverse events that were assessed by the investigator as being related to the drug or placebo were diarrhea (in 4% and 2% of the participants, respectively), an elevated liver-enzyme level (in 3% and 3%, respectively), and rash (in 2% and 1%). Resistance-associated mutations were identified in 15 participants (9%) in the ziresovir group. CONCLUSIONS: Ziresovir treatment reduced signs and symptoms of bronchiolitis in infants and young children hospitalized with RSV infection. No safety concerns were identified. (Funded by Shanghai Ark Biopharmaceutical; AIRFLO ClinicalTrials.gov number, NCT04231968.).

The role of LDH and ferritin levels as biomarkers for corticosteroid dosage in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: This study explored the relationship between inflammatory markers and glucocorticoid dosage upon admission. METHODS: We conducted a retrospective analysis of 206 patients with refractory Mycoplasma pneumoniae pneumonia (RMPP) admitted to a Children's Hospital from November 2017 to January 2022. Patients were categorized into three groups based on their methylprednisolone dosage: low-dose (≤ 2 mg/kg/d), medium-dose (2-10 mg/kg/d), and high-dose (≥ 10 mg/kg/d). We compared demographic data, clinical manifestations, laboratory findings, and radiological outcomes. Spearman's rank correlation coefficient was used to assess relationships between variables. RESULTS: The median age was highest in the low-dose group at 7 years, compared to 5.5 years in the medium-dose group and 6 years in the high-dose group (P < 0.001). The body mass index (BMI) was also highest in the low-dose group at 16.12, followed by 14.86 in the medium-dose group and 14.58 in the high-dose group (P < 0.001). More severe radiographic findings, longer hospital stays, and greater incidence of hypoxia were noted in the high-dose group (P < 0.05). Additionally, significant increases in white blood cells, C-reactive protein, procalcitonin, lactate dehydrogenase (LDH), alanine transaminase, aspartate transaminase, ferritin, erythrocyte sedimentation rate, and D-dimer levels were observed in the high-dose group (P < 0.05). Specifically, LDH and ferritin were markedly higher in the high-dose group, with levels at 660.5 U/L and 475.05 ng/mL, respectively, compared to 450 U/L and 151.4 ng/mL in the medium-dose group, and 316.5 U/L and 120.5 ng/mL in the low-dose group. Correlation analysis indicated that LDH and ferritin levels were significantly and positively correlated with glucocorticoid dose (Spearman ρ = 0.672 and ρ = 0.654, respectively; P < 0.001). CONCLUSIONS: Serum LDH and ferritin levels may be useful biomarkers for determining the appropriate corticosteroid dosage in treating children with RMPP.

Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

Electrochemical Deposition and Etching of Quasi-Two-Dimensional Periodic Membrane Structure.

In this paper, two experimental procedures are reported, namely electro-deposition in the ultrathin liquid layer and chemical micro-etching. Firstly, a large area quasi-two-dimensional periodic membrane with adjustable density is deposited on a Si substrate driven by half-sinusoidal voltage, which is composed of raised ridges and a membrane between the ridges. The smaller the voltage frequency is, the larger the ridge distance is. The height of a raised ridge changes synchronously with the amplitude. The grain density distribution of membrane and raised ridge is uneven; the two structures change alternately, which is closely related to the change of growth voltage and copper ion concentration during deposition. The structural characteristics of membrane provide favorable conditions for micro-etching; stable etching speed and microscope real-time monitoring are the keys to achieve accurate etching. In the chemical micro-etching process, the membrane between ridges is removed, retaining the raised ridges, thus a large scale ordered micro-nano wires array with lateral growth was obtained. This method is simple and controllable, can be applied to a variety of substrates, and is the best choice for designing and preparing new functional materials. This experiment provides a basis for the extension of this method.

Efficacy of mesenchymal stromal cells intraspinal transplantation for patients with different degrees of spinal cord injury: A systematic review and meta-analysis.

BACKGROUND AIMS: Several studies have reported that mesenchymal stromal cells (MSCs) may improve neurological functions in patients with spinal cord injury (SCI). In this study, we conducted a systematic review and meta-analysis to summarize the effects of MSC treatment on different degrees of severity of SCI. METHODS: Systematic searching of studies reporting outcomes of MSCs on specific injury severities of patients with SCI was performed in The National Library of Medicine (MEDLINE), Embase and Cochrane for published articles up to the 6 July 2022. Two investigators independently reviewed the included studies and extracted the relevant data. The standardized mean differences of American Spinal Injury Association (ASIA) motor score, ASIA light touch scores, ASIA pinprick scores and the Barthel index between baseline and follow-ups were pooled. RESULTS: A total of eight studies were included. A large majority focused on patients with ASIA grade A classification. The pooled mean differences of ASIA motor scores, ASIA light touch scores, ASIA pinprick scores and the Barthel index were -2.78 (95% confidence interval [CI] -5.12 to -0.43, P = 0.02), -18.26 (95% CI -26.09 to -10.43, P < 0.01), -17.08 (95% CI -24.10 to -10.07, P < 0.01) and -4.37 (95% CI -10.96 to 2.22, P = 0.19), respectively. CONCLUSIONS: MSC transplantation was a significantly effective therapy for patients with SCI with ASIA grade A. In the future, further studies are warranted to confirm the potential beneficial effects of MSC therapy.

Development and validation of a nomogram for predicting severe respiratory syncytial virus-associated bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and is related to the severity of the disease. This study aimed to develop and validate a nomogram for predicting severe bronchiolitis in infants and young children with RSV infection. METHODS: A total of 325 children with RSV-associated bronchiolitis were enrolled, including 125 severe cases and 200 mild cases. A prediction model was built on 227 cases and validated on 98 cases, which were divided by random sampling in R software. Relevant clinical, laboratory and imaging data were collected. Multivariate logistic regression models were used to determine optimal predictors and to construct nomograms. The performance of the nomogram was evaluated by the area under the characteristic curve (AUC), calibration ability and decision curve analysis (DCA). RESULTS: There were 137 (60.4%) mild and 90 (39.6%) severe RSV-associated bronchiolitis cases in the training group (n = 227) and 63 (64.3%) mild and 35 (35.7%) severe cases in the validation group (n = 98). Multivariate logistic regression analysis identified 5 variables as significant predictive factors to construct the nomogram for predicting severe RSV-associated bronchiolitis, including preterm birth (OR = 3.80; 95% CI, 1.39-10.39; P = 0.009), weight at admission (OR = 0.76; 95% CI, 0.63-0.91; P = 0.003), breathing rate (OR = 1.11; 95% CI, 1.05-1.18; P = 0.001), lymphocyte percentage (OR = 0.97; 95% CI, 0.95-0.99; P = 0.001) and outpatient use of glucocorticoids (OR = 2.27; 95% CI, 1.05-4.9; P = 0.038). The AUC value of the nomogram was 0.784 (95% CI, 0.722-0.846) in the training set and 0.832 (95% CI, 0.741-0.923) in the validation set, which showed a good fit. The calibration plot and Hosmer‒Lemeshow test indicated that the predicted probability had good consistency with the actual probability both in the training group (P = 0.817) and validation group (P = 0.290). The DCA curve shows that the nomogram has good clinical value. CONCLUSION: A nomogram for predicting severe RSV-associated bronchiolitis in the early clinical stage was established and validated, which can help physicians identify severe RSV-associated bronchiolitis and then choose reasonable treatment.

A Polymer Network Layer Containing Dually Anchored Ionic Liquids for Stable Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries with high sulfur utilization, long-cycle life, and dendrite-free features hold great promise for the development of next-generation energy storage devices of high energy density. Considerable efforts have been committed to solving the polysulfide shuttle problem toward highly stable Li-S batteries. Here, a unique polymer network containing dually anchored ionic liquids (DA-PIL) is devolped to improve the cycling performance and coulombic efficiency of Li-S batteries. This DA-PIL electrolyte incorporates the amphiphilicity of both the polysulfides anion and lithium cation, creating an ionic function layer on polypropylene separator. Noteworthily, the DA-PIL network is "clean" in the sense that no free ionic specifies are introduced to the electrolyte system. The DA-PIL layer not only enables strong supression against polysulfide shuttling but simultaneously allows fast lithium transportation owing to cooperate electrostatic interaction among anchored cations and anions. The DA-PIL layer functionalized on a polypropylene separator can boost excellent stability of Li-S battery with >1600 h cycling test at 0.25 mA cm-2 . The Li-S cell with DA-PIL layer delivers a higher discharge capacity of 827.4 mAh g-1 at 1C. A discharge capacity of 630.6 mAh g-1 is retained after 1000 cycles.

A retrospective study of the clinical characteristics of 9 children with pulmonary embolism associated with Mycoplasma pneumoniae pneumonia.

OBJECTIVE: The aim of this study was to analyze the clinical characteristics and treatment of children with Mycoplasma pneumoniae pneumonia (MPP) who also present with pulmonary embolism (PE). METHODS: This retrospective analysis examined the demographic data, clinical manifestations, laboratory tests, imaging characteristics, therapy, and prognosis of nine cases of children with Mycoplasma pneumoniae pneumonia (MPP) complicated by pulmonary embolism (PE). The study focused on patients admitted to the respiratory department of Tianjin Children's Hospital between January 2018 and December 2021. RESULTS: The age range of the patients was 3 to 8 years old, with a median age of 7.5 years. The median number of days from pulmonary infection to the diagnosis of embolism was 14 days. All patients had refractory Mycoplasma pneumoniae pneumonia (RMPP). Among them, three patients reported chest pain, one of whom had hemoptysis, while five patients had dyspnea, and six patients experienced radiating pain at unusual sites. Five out of the nine children tested positive for lupus anticoagulant (LA), five for anticardiolipin antibody (ACA), three for anti-2-glycoprotein antibody IgM, four for reduced protein S or protein C activity, and three for elevated coagulation factor VIII. Moreover, six out of the nine children tested positive for antinuclear antibodies. All the children underwent CT pulmonary angiograms, which revealed filling defects. After sequential low-molecular heparin anticoagulation with rivaroxaban, nine children in this study showed a good prognosis, with two of them receiving thrombolytic therapy for combined cardiac embolism. Follow-up at 0.5-9 months showed the gradual resolution of the emboli in all 9 children, with no thrombotic recurrences and normalized autoantibodies and thrombophilia markers. CONCLUSIONS: The majority of cases involving Mycoplasma pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) were diagnosed with refractory MPP (RMPP). However, PE did not always occur in the advanced stages of the disease. Most patients presented with transient autoantibody positivity, abnormal coagulation, and fibrinolytic balance. With timely treatment, the prognosis of MPP combined with PE is generally good. Additionally, rivaroxaban treatment has been shown to be safe and effective.

Development and validation of a nomogram to predict plastic bronchitis in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: Early identification of plastic bronchitis (PB) is of great importance and may aid in delivering appropriate treatment. This study aimed to develop and validate a nomogram for predicting PB in patients with refractory Mycoplasma pneumoniae pneumonia (RMPP). METHODS: A total of 547 consecutive children with RMPP who underwent fiberoptic bronchoscopy (FOB) intervention from January 2016 to June 2021 were enrolled in this study. Subsequently, 374 RMPP children (PB: 137, without PB: 237) from January 2016 to December 2019 were assigned to the development dataset to construct the nomogram to predict PB and 173 RMPP children from January 2020 to June 2021 were assigned to the validation dataset. The clinical, laboratory and radiological findings were screened using Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression was applied to construct a nomogram. The performance of the nomogram was evaluated by discrimination, calibration and clinical utility. Comparsion of ROC analysis and decision curve analysis (DCA) between nomogram and other models was performed to evaluate the discrimination ability and clinical utility. RESULTS: The development dataset included 374 patients with a mean age of 6.6 years and 185(49.5%) were men. The validation dataset included 173 patients and the mean age of the dataset was 6.7 years and 86 (49.7%) were men. From 26 potential predictors, LASSO regression identified 6 variables as significant predictive factors to construct the nomogram for predicting PB, including peak body temperature, neutrophil ratio (N%), platelet counts (PLT), interleukin-6 (IL-6), actic dehydrogenase (LDH) and pulmonary atelectasis. The nomogram showed good discrimination, calibration and clinical value. The mean AUC of the nomogram was 0.813 (95% CI 0.769-0.856) in the development dataset and 0.895 (95% CI 0.847-0.943) in the validation dataset. Through calibration plot and Hosmer-Lemeshow test, the predicted probability had a good consistency with actual probability both in the development dataset (P = 0.217) and validation dataset (P = 0.183), and DCA showed good clinical utility. ROC analysis indicated that the nomogram showed better discrimination ability compared with model of peak body temperature + pulmonary atelactsis and another model of N% + PLT + IL-6 + LDH, both in development dataset (AUC 0.813 vs 0.757 vs 0.754) and validation dataset (AUC 0.895 vs 0.789 vs 0.842). CONCLUSIONS: In this study, a nomogram for predicting PB among RMPP patients was developed and validated. It performs well on discrimination ability, calibration ability and clinical value and may have the potential for the early identification of PB that will help physicians take timely intervention and appropriate management.

Community-acquired Pseudomonas aeruginosa pneumonia manifested by bloody pleural effusion in a previously healthy infant: A case report.

BACKGROUND: Community-acquired Pseudomonas aeruginosa pneumonia in immunocompetent children is a rare occurrence. METHODS: A retrospective analysis of the clinical manifestations, imaging characteristics, laboratory examinations, and treatment of a child with community-acquired Pseudomonas aeruginosa pneumonia presented with bloody pleural effusion. RESULTS: The 1-year-old previously healthy patient, who developed community-acquired pneumonia caused by Pseudomonas aeruginosa and influenza virus. The patient manifested bloody pleural effusion although his condition improved after anti-infective therapy and closed thoracic drainage. After 10 days of hospitalization, his symptoms worsened, accompanied by hemoptysis, and the pathogen developed resistance to carbapenems. The antibiotic strategy was adjusted to combined antipseudomonal regimen. He developed low-grade fever and was extubated, although these manifestations and imaging were eventually alleviated. CONCLUSIONS: Community-acquired Pseudomonas aeruginosa pneumonia in children may be non-septic, with bloody pleural effusion as presentation, and the disease may progress after 10 days of treatment due to drug resistance in Pseudomonas aeruginosa. Early extubation should be considered after adequate drainage.

[Mediating role of IL-10 in the association between health-risk behaviors and depressive symptoms of college students].

OBJECTIVE: To examine the relationship between health-risk behaviors and depressive symptoms among college students, and explore the mediating role of plasma IL-10 level in the relationship between the two. METHODS: Freshman students in two universities in Hefei City, Anhui Province and Shangrao City, Jiangxi Province were recruited between April and May 2019, and follow-up investigation was conducted 6 months later. Health risk behaviors were measured based on the Young Risk Behavior Surveillance System(YRBSS) questionnaire, and depressive symptoms was evaluated by using the Depression Anxiety Stress Scale(DASS-21) among college students at baseline and 6 months follow-up survey. Plasma interleukin-10(IL-10) level was measured at baseline. Univariate analysis was used to compare the correlation between health risk behaviors and depressive symptoms among college students. Binary Logistic regression analyzed the relationship between health risk behaviors, IL-10 and depressive symptoms. The mediation model was used to explore the mediating role of IL-10 levels in the association between health risk behaviors and depressive symptoms. RESULTS: At baseline, boys reported a higher rate of depressive symptoms than that of girls(χ~2=6.33, P=0.01); higher rates of depressive symptoms were observed in students who were from a family with a low perceived economic status(χ~2=7.31, P=0.03)or in poor health(χ~2=6.71, P=0.04). Participants who reported low physical activity(χ~2=19.09, P<0.01), smoking(χ~2=7.03, P<0.01), and poor sleep quality(χ~2=68.78, P<0.01)at baseline were more likely to experience depressive symptoms. Multiple health-risk behaviors at baseline were positively correlated with depressive symptoms among college students. After adjusting gender, self-reported family economy and self-rated health, the regression model showed that plasma IL-10 at baseline was negatively associated with the prevalence of depressive symptoms(OR=0.36, 95% CI 0.18-0.72) and the incidence of depressive symptoms after 6 months(OR=0.20, 95% CI 0.08-0.49). Structural equation model showed that health-risk behaviors was negatively correlated to IL-10 level(ß=-0.13, SE=0.04), IL-10 negatively predicted depressive symptoms at follow-up(ß=-0.09, SE=0.04), and IL-10 play a mediating role between health risk behavior and depressive symptoms. CONCLUSION: Health risk behaviors are positively correlated with depressive symptoms among college students. Plasma IL-10 level at baseline was negatively associated with the incidence of depressive symptoms after 6 months, and IL-10 level at baseline has a partial mediating effect between baseline health risk behavior clustering and depressive symptoms at follow-up.

Ordered Mesoporous Silica Pyrolyzed from Single-Source Self-Assembled Organic-Inorganic Giant Surfactants.

We report the preparation of hexagonal mesoporous silica from single-source giant surfactants constructed via dihydroxyl-functionlized polyhedral oligomeric silsesquioxane (DPOSS) heads and a polystyrene (PS) tail. After thermal annealing, the obtained well-ordered hexagonal hybrid was pyrolyzed to afford well-ordered mesoporous silica. A high porosity (e.g., 581 m2/g) and a uniform and narrow pore size distribution (e.g., 3.3 nm) were achieved. Mesoporous silica in diverse shapes and morphologies were achieved by processing the precursor. When the PS tail length was increased, the pore size expanded accordingly. Moreover, such pyrolyzed, ordered mesoporous silica can help to increase both efficiency and stability of nanocatalysts.

A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19).

To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in pediatric patients. A meta-analysis was carried out to identify studies on COVID-19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included. Children of all ages were at risk for COVID-19. The main illness classification ranged as: 20% (95% confidence interval [CI]: 14%-26%; I2 = 91.4%) asymptomatic, 33% (95% CI: 23%-43%; I2 = 95.6%) mild and 51% (95% CI: 42%-61%; I2 = 93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45%-57%; I2 = 78.9%) and cough 41% (95% CI: 35%-47%, I2 = 81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64%-75%; I2 = 58.5%), lymphopenia 16% (95% CI: 11%-21%; I2 = 76.9%) and elevated creatine-kinase MB 37% (95% CI: 25%-48%; I2 = 59.0%). The frequent imaging features were normal images 41% (95% CI: 30%-52%; I2 = 93.4%) and ground-glass opacity 36% (95% CI: 25%-47%; I2 = 92.9%). Among children under 1 year old, critical cases account for 14% (95% CI: 13%-34%; I2 = 37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18%-67%; I2 = 0.0%) cases that may also need attention. Pediatric patients with COVID-19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1 year old.

Protective Strategy to Boost the Stability of Aminated Graphene in Fenton-like Reactions.

Improving the stability of aminated metal-free catalysts is a big challenge in Fenton-like reactions. Herein, trinuclear iron cluster (Fe3 cluster)-protected aminated graphene (Fe3-NH2-GR) is designed by a protective strategy. By protecting with the Fe3 cluster, the lone pair electrons of amino groups are protected and the N content of Fe3-NH2-GR can be fixed steadily. In peroxymonosulfate (PMS)-based Fenton-like reactions with a fixed-bed reactor, the lifetime of Fe3-NH2-GR is two times longer than that of aminated graphene (NH2-GR) under the same conditions. The deactivation kinetics shows that both Fe3-NH2-GR and NH2-GR follow zero-order kinetics and the deactivation rate constants of Fe3-NH2-GR are lower than that of NH2-GR at every period. Moreover, Fe3-NH2-GR still maintains 50% phenol degradation after 40 h rather than being constantly deactivated as NH2-GR. This stable activity is attributed to the formation of -O-NO2, while the N content will be lost in NH2-GR. This protective strategy by the Fe3 cluster provides a reliable method to enhance the efficiency and stability of carbon catalysts in Fenton-like reactions.

Clinical characteristics of refractory mycoplasma pneumoniae pneumonia in children treated with glucocorticoid pulse therapy.

BACKGROUND: To observe the effect of corticosteroids in the treatment of children with refractory Mycoplasma pneumoniae pneumonia (RMPP) under different doses, to summarize the clinical features of children treated with glucocorticoid pulse therapy. METHODS: The clinical data of 125 children with RMPP hospitalized in Tianjin Children's Hospital from September 2018 to October 2019 were retrospectively analyzed. They were divided into two groups according to the dose of hormone. Compare the clinical features, laboratory findings, and imaging between the two groups, and use meaningful related indicators as ROC curves to find reference indicators for pulse therapy. RESULTS: (1) The median age of the group II was older than that of the group I(P < 0.05). (2) We found more severe presentations, higher incidence of extra-pulmonary complications and more serious radiological findings in group II, which needed oxygen more often, higher the hormone, higher usage rate of gamma globulin, higher usage rate of bronchoscopy, and higher incidence of plastic bronchitis(P < 0.05). (3) WBC, CRP, LDH, FER, D-D dimer, APTT, TT, PCT, IL-6 and the percentage of neutrophils in peripheral blood in Group II were higher than those in Group I(P < 0.05). (4) In ROC curve analysis, CRP, LDH, FER, and neutrophils of leukocyte classification were independent related factors that could be used as valuable predictors of methylprednisolone pulse therapy for RMPP in children. The cut-off values were CRP44.45 mg/L, LDH590IU/L, FER411ng/L, and neutrophils in leukocyte classification were 73.75%, respectively. CONCLUSION: CRP ≥ 44.45 mg/L, LDH ≥ 590 IU/L, FER ≥ 411 ng/L, neutrophil≥73.75%, lung consolidation, and pleural effusion may be predictors that guide the treatment of RMPP with pulse dose of GC.

Efficacy and safety of omalizumab in children with moderate-to-severe asthma: a meta-analysis.

OBJECTIVE: To assess the efficacy and safety of omalizumab in children with moderate-to-severe asthma. DATA SOURCES: We systematically searched MEDLINE, EMBASE, and Cochrane for randomized controlled trials (RCTs ) (inception to January 2020). STUDY SELECTIONS: All RCTs which were conducted in childhood and adolescence with asthma and compared the efficacy or safety of omalizumab were adopted. RESULTS: Three studies with four publications including 1380 pediatric patients met our criteria. For children with moderate-to-severe asthma, omalizumab decreased asthma exacerbations rate (OR 0.51, 95% CI: 0.44-0.58, p < 0.001) compared with placebo with no evidence of heterogeneity. Omalizumab reduced the rate of asthma exacerbations 0.58) with treatment period ≥30 weeks (p for heterogeneity = 0.03). Omalizumab treated patients had an excellent or good response rate of treatment effectiveness assessed by physicians (2.75, 2.45-3.09) and a bigger reduction in the dosage of inhaled corticosteroid (ICS) at the end of follow-up. For children with severe asthma, omalizumab also reduced the likelihood of asthma exacerbations and increased the odd of treatment effectiveness rated as excellent or good. Patients receiving omalizumab had a lower incidence of severe adverse events (0.36, 0.22-0.57). CONCLUSIONS: These findings suggested that omalizumab had beneficial effects on moderate-to-severe asthma in children. Patients may benefit more from long-term use of omalizumab. In addition, omalizumab reduces the rate of serious adverse events requiring hospitalizations.

Ginsenoside Rg3 inhibits pulmonary fibrosis by preventing HIF-1α nuclear localisation.

BACKGROUND: Excessive fibroblast proliferation during pulmonary fibrosis leads to structural abnormalities in lung tissue and causes hypoxia and cell injury. However, the mechanisms and effective treatment are still limited. METHODS: In vivo, we used bleomycin to induce pulmonary fibrosis in mice. IHC and Masson staining were used to evaluate the inhibitory effect of ginsenoside Rg3 in pulmonary fibrosis. In vitro, scanning electron microscopy, transwell and wound healing were used to evaluate the cell phenotype of LL 29 cells. In addition, biacore was used to detect the binding between ginsenoside Rg3 and HIF-1α. RESULTS: Here, we found that bleomycin induces the activation of the HIF-1α/TGFß1 signalling pathway and further enhances the migration and proliferation of fibroblasts through the epithelial mesenchymal transition (EMT). In addition, molecular docking and biacore results indicated that ginsenoside Rg3 can bind HIF-1α. Therefore, Ginsenoside Rg3 can slow down the progression of pulmonary fibrosis by inhibiting the nuclear localisation of HIF-1α. CONCLUSIONS: This finding suggests that early targeted treatment of hypoxia may have potential value in the treatment of pulmonary fibrosis.

Severe erosive lesion of the glenoid in gouty shoulder arthritis: a case report and review of the literature.

BACKGROUND: Gout is a metabolic disease characterized by recurrent episodes of acute arthritis. Gout has been reported in many locations but is rarely localized in the shoulder joint. We describe a rare case of gouty arthritis involving bilateral shoulder joints and leading to severe destructive changes in the right shoulder glenoid. CASE PRESENTATION: A 62-year-old male was referred for pain and weakness in the right shoulder joint for two years, and the pain had increased in severity over the course of approximately nine months. A clinical examination revealed gout nodules on both feet and elbows. A laboratory examination showed a high erythrocyte sedimentation rate (ESR), high levels of C-reactive protein and hyperuricemia, and an imaging examination showed severe osteolytic destruction of the right shoulder glenoid and posterior humeral head subluxation. In addition, the left humeral head was involved and had a lytic lesion. Because a definite diagnosis could not be made for this patient, a right shoulder biopsy was performed. The pathological examination of the specimen revealed uric acid crystal deposits and granulomatous inflammation surrounding the deposits. After excluding infectious and neoplastic diseases, the patient was finally diagnosed with gouty shoulder arthritis. CONCLUSIONS: Gout affecting the bilateral shoulder joints is exceedingly uncommon, and to our knowledge, severe erosion of the glenoid has not been previously reported. When severe erosion is present, physicians and orthopedic surgeons should consider gouty shoulder arthritis according to previous medical history and clinical manifestations.

Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis : C-SOUND study, a 26-week multicenter double-blind randomized placebo-controlled trial in China.

BACKGROUND: Single 6 ml Hylan G-F 20 injection, is indicated for knee osteoarthritis patients who have failed to respond to non-pharmacologic therapy and/or simple analgesics. To obtain more thorough understanding of the clinical efficacy and safety, a randomized clinical trial was conducted comparing intra-articular (IA) administration of single 6 ml Hylan G-F 20 injection versus placebo in knee OA patients of Chinese ethnicity. METHODS: This was a randomized, multi-center, double-blind, placebo-controlled clinical trial conducted in 21 centers across China. Four hundred forty adults with knee OA received a single 6 ml Hylan G-F 20 or placebo injection and were evaluated for clinical efficacy and safety outcomes over 26 weeks. Western Ontario and McMaster Universities OA (WOMAC) A1 index, treatment-emergent adverse events (TEAEs) and standard safety parameters were measured at pre-injection, and at weeks 1, 4, 8, 12, 16, 20 and 26 post-injection. RESULTS: Four hundred forty patients (male: 98 [22.3%]; female: 342 [77.7%]) were randomized. The mean age [standard deviation (SD)] was 61.5 (7.9) years. All patients were of East Asian ethnicity. Mean WOMAC A1 score at baseline was 5.3 (1.2) and 5.2 (1.3) in single 6 ml Hylan G-F 20 injection and placebo groups, respectively. Significant reductions of WOMAC A1 score were observed in both treatment groups when compared to baseline at 26 weeks post-injection, with the mean reduction of [standard error (SE)/percentage] -2.146 (0.108)/- 40.5% and - 2.271 (0.110) /- 43.7% in the single 6 ml Hylan G-F 20 injection and the placebo groups, respectively. Additionally, clinically important reductions in pain at 26 weeks was reported in 67.0 and 68.2% in single 6 ml Hylan G-F 20 injection and placebo groups (p = 0.36). Regarding safety, TEAEs were similar between the two treatment groups (hylan G-F 20 single: 61.5%; placebo: 64.5%). CONCLUSIONS: While the magnitude of the effect of a single 6 ml Hylan G-F 20 injection in this study is consistent with previously published literature with respect to the efficacy and safety of the drug, the current study shows a strong IA placebo effect and did not established superiority of single 6 ml Hylan G-F 20 injection over IA placebo in Chinese knee OA patients. TRIAL REGISTRATION: Prospectively registered Jun 16, 2017 at www.clinicaltrials.gov ( NCT03190369 ).

Overexpression of RAPGEF3 enhances the therapeutic effect of dezocine in treatment of neuropathic pain.

Pain is a significant problem worldwide that affects the quality of life of patients. Dezocine is a non-addictive analgesic drug with kappa-opioid antagonist activity and has been successfully used to alleviate of postoperative pain. In addition, dezocine has an analgesic effect similar to that of morphine, alleviating moderate to severe pain. Rap guanine nucleotide exchange factor 3 (RAPGEF3) is a guanine nucleotide exchange factor for GTPases Rap1 and Rap2, which could enhance the activity of Rap1 to promote cell adhesion and axon regeneration, as well as promote neurite extension by interacting with nerve growth factors. Here, we first observed that overexpression of RAPGEF3 increased cell viability, as shown by a CCK-8 assay, and recovered brain function in rats. The expression of inflammation-related factors at the mRNA level was detected using qPCR, and the concentration of these factors in a cultured cell medium and rat serum samples were decreased as shown by ELISA after RAPGEF3 overexpression. Through western blotting, we further found that pro-inflammatory proteins were decreased, and these effects might be mediated by inhibition of the Ras/p-38 MAPK signaling pathway. Taken together, we speculated that RAPGEF3overexpression enhances the therapeutic effect of dezocine on neuropathic pain by inhibiting the inflammatory response through inhibition of the Ras/p-38 MAPK signaling pathway.