Purpose: To evaluate the potential molecular mechanisms involved in refractory asthma in an animal model, and the potential therapeutic effect of MAPK1 knockdown on the disease.Methods: Eighteen female Institute of Cancer Research (ICR) mice, aged 8 - 10 weeks, were randomly divided into three groups: control, asthma model and refractory asthma, with 6 mice in each group. The expression of MAPK1 was knocked down in mice using an adenoviral vector. Subsequently, the methylation levels of MAPK1 promoter in mouse lung tissue were determined using methylation assays. Hematoxylin and eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining were used to determine inflammatory and histological changes in lung tissues. Levels of immune cells were determined using flow cytometry, while Western blotting was used to measure the protein expression levels of ERK1/2, JNK, MEK1/2 and p38.Results: Methylation assay results show that mean methylation level of cg11335969 locus was significantly reduced in the refractory asthma mouse model (p < 0.05). The levels of IgG1 and IgM in refractory asthmatic mice were reduced after MAPK1 knockdown. There was a significantly reduced degree of lung lesions in mice (p < 0.05), as was reflected in effectively decreased histopathological changes. Protein levels of ERK1/2, JNK, MEK1/2 and p38, and the levels of neutrophils, dendritic cells, and macrophages were significantly decreased (p < 0.05).Conclusion: There is hypermethylated modification of MAPK1 at cg11335969 site in refractory asthma mouse model. Knockdown of MAPK1 attenuates inflammation and tissue damage, and reverses abnormal immune cell numbers in refractory asthma mice. Thus, MAPK1 inhibition may be a novel strategy for ameliorating immune abnormalities in refractory asthma.

Purpose: To determine the underlying mechanisms of action of Astragalus membranaceus in lumbar disc herniation (LDH) treatment.Methods: This study utilized network pharmacology analysis and STRING database to identify compound targets and visualize PPI network. Furthermore, an LDH model was induced in human nucleus pulposus cells using lipopolysaccharide (LPS), and then the vital target genes were evaluated in this model treated with active components of Astragalus membranaceus.Results: Network pharmacology analysis indicates that several key proteins, including vascular endothelial growth factor A (VEGF A), AKT1, JUN, prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin-6 (IL-6), matrix metallopeptidase 9 (MMP9), interleukin-1β (IL-1β), C-X-C motif chemokine ligand 8 (CXCL8), epidermal growth factor (EGF) and matrix metallopeptidase 2 (MMP2) may play essential roles in LDH treated with Astragalus membranaceus. The active components in Astragalus membranaceus suppressed the production of IL-1β and IL-6, and increased the expressions of VEGF A, MMP9 and MMP2 in LPS-induced LDH model.Conclusion: The active components of Astragalus membranaceus effectively inhibits inflammation in LPS-induced LDH model, indicating that Astragalus membranaceus is a potential therapeutic candidate for LDH treatment.

Purpose: To evaluate the mechanism and effect of Procyanidin A1 (PCA1) in gestational diabetes mellitus (GDM).Methods: Human trophoblast cell line HTR-8/Svneo was treated with 25 mM glucose for 24 h, and the effect of PCA1 on HTR-8/SVneo cell viability and proliferation was determined by CCK-8 assay and EdU proliferation kit. The expression of BAX, Bcl-2, cleaved Caspase-3 and cleaved caspase-9 was determined by western blotting. Cell apoptosis was assessed by Annexin V-FITC/ PI staining. Cellular generation of reactive oxygen species (ROS) was determined by ROS assay kit while superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) were determined by the corresponding assay kits. The effect of PCA1 on Nrf2/HO-1 pathway was evaluated by determining the expression of Keap1, Nfr2, and HO-1.Results: Procyanidin A1 (PCA1) increased the viability of high glucose (HG) -induced HTR-8/SVneo cells and promoted cell proliferation. Furthermore, PCA1 significantly inhibited HG-induced BAX, cleaved caspase-3, and cleaved caspase-9 expression, resulting in further reduction in HG-induced cell apoptosis. High glucose (HG) induced a significant increase in intracellular ROS levels, and this HGinduced oxidative stress was inhibited by PCA1. Furthermore, PCA1 activated Nrf2/HO-1 pathway and this was responsible for its proliferative, anti-apoptosis and anti-oxidative effects.Conclusion: Procyanidin A1 promotes proliferation, and inhibits apoptosis and oxidative stress induced by high glucose in trophoblast cells by activating Nrf2/HO-1 signaling pathway. Therefore, it is a potential drug for the treatment of GDM.

Purpose: To study the effects of Jade Wind-Barrier Powder on peripheral blood interferon-γ (INF-γ), immunoglobulin and sputum mucin in children with asthma.Methods: Sixty-six children with asthma in remission stage were randomly separated into study and control groups. The control group was treated with budesonide formoterol powder inhaler, while the study group was orally administered Jade Wind-Barrier Powder. The therapeutic effects, and INF-γ, immunoglobulin and mucin levels in sputum, as well as pulmonary function parameters in both groups were determined. The number of acute relapses of asthma and duration of wheezing were counted in the patients. The relative effectiveness of Jade Wind-Barrier Powder in the treatment of asthma in the children was also assessed.Results: The overall response rate (ORR) in the study group was 93.94 %, which was higher than in the control group (75.76 %, p < 0.05). Over the 6-month period of follow-up, the frequency of acute attacks of asthma in the study group was significantly lower while the duration of wheezing during attack was also shorter than in the control group. After treatment, pulmonary function indices in the study group were higher, whereas mucin 5AC (MUC5AC), mucin 5B (MUC5B) and mucin 1 (MUC1) levels in sputum were lower than in the control group (p < 0.05).Conclusion: Jade Wind-Barrier Powder exerts therapeutic effect in children with asthma. However, further clinical trials across multi-centers are required to validate it its use in clinical practice.

Purpose: To determine the efficacy of sevoflurane + sufentanil combination anesthesia in pediatric surgery for removal of tracheal foreign bodies, and its effect on hemodynamics.Methods: A total of 128 children with airway foreign bodies were assigned to control and study groups, each with 64 children. The control patients received slow intravenous injection of propofol (3 mg/kg). The study group was given 5 % sevoflurane and a slow intravenous injection of sufentanil (0.3 μg/kg). Hemodynamic parameters (diastolic blood pressure, systolic blood pressure and heart rate) were recorded before induction of anesthesia, at the time of intubation, during placement of a rigid bronchoscope (when the lens was placed), during removal of foreign bodies, and when extubating. Complications in children in the two groups after the removal of airway foreign body were recorded.Results: At the times of intubation and extubation, blood pressure and heart rate were significantly increased in both groups, but appreciably lower values were seen in study group. The major complications in pediatric airway foreign body removal in two groups were vomiting, bronchospasm and holding of breath.Conclusion: In children with airway extraction, sevoflurane, in combination with sufentanil produced better anesthetic effect and less impact on hemodynamics than propofol. Moreover, the children woke up faster and had fewer complications. The combined anesthesia is safe and reliable. However, the clinical application of this combined anesthesia requires larger-sample clinical studies.

Purpose: To evaluate the effect of allogeneic platelet-rich plasma (PRP) on ulcer wound surface in streptozotocin-induced diabetic rats.Methods: A total of 20 male Sprague-Dawley (SD) rats were procured as skin ulcer as well as diabetes models, and randomly divided into control and PRP groups, respectively. Their wound surfaces were smeared with 0.9 % normal saline or an equal concentration of allogeneic PRP, respectively, and the pathological changes in the wound tissues were examined with the aid of hematoxylin-eosin (H&E) staining. Also, the expression levels of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in wound tissues were determined using enzyme-linked immunosorbent assay (ELISA).Results: Both purulent exudation and swelling of the wound surface were milder in the PRP group than in the control group, and the PRP group showed greater redness on the wound surface and more pronounced signs of epithelialization of the wound surface and its margins (p < 0.05). Wound healing rate in PRP group was higher than in the control group while the number of fibroblasts and new microvessels in the wound surface in the PRP group were greater than in the control group, accompanied by slighter inflammatory response compared to the control group. Furthermore, the PRP group expressed lower MMP-2, MMP-2/TIMP-2 ratio, and higher TGF-β1 and TIMP-2 levels than in the control group (p < 0.05).Conclusion: Allogeneic PRP treatment contributes to the healing of ulcer wound surface in diabetic rats, a process mediated by TGF-β1/MMP-2/TIMP-2 signaling pathway. Thus, PRP is a potential therapeutic agent for the management of diabetic ulcer wounds.

Purpose: To investigate the effect of Jaceosidin in ulcerative colitis (UC).Methods: An ulcerative colitis cell model was established by stimulating normal human colon mucosal epithelial cell lines (NCM460 cells) with lipopolysaccharide (LPS). The cells were treated with 5, 10, 20 or 40 μM Jaceosidin. Cell viability was performed using cell counting kit 8 (CCK8) assay. Oxidative stress was measured with superoxide dismutase (SOD), lipid peroxidation MDA, reduced glutathione (GSH), oxidized glutathione (GSSG), and human myeloperoxidase enzyme-linked immunoassay (ELISA) kits. The mRNA levels were determined by quantitative polymerase chain reaction (qPCR) assay, while protein levels of SIRT1, NRF2, NLRP3, caspase-1, TNF-α, IL-1β, and IL-6 were determined by western blotting.Results: Jaceosidin significantly inhibited oxidative stress and accumulation of inflammatory cytokines in LPS-induced NCM460 cells, as well as NLRP3-mediated cell pyroptosis (p < 0.05). Jaceosidin also inhibited activation of NLRP3 inflammasome by activating SIRT1/NRF2 pathway, thereby preventing NCM460 cell pyroptosis.Conclusion: Jaceosidin inhibits NLRP3-mediated pyroptosis, thus suggesting that jaceosidin is a potential lead for UC secondary to NLRP3 inflammasome.

Purpose: To determine the efficacy and safety of irbesartan plus calcitriol in the treatment of IgA nephropathy, and its effect on inflammatory injury and complement systemMethods: Differences in renal function, inflammatory response, immune function, complement factor levels, clinical efficacy, and incidence of adverse reactions between IgA nephropathy patients treated with irbesartan (control, n = 50) and those treated with irbesartan + calcitriol (study group, n = 50) after 2 and 12 months, were retrospectively analyzed. As treatment progressed, protein in 24-h urine, and creatinine and BUN in both groups were gradually reduced.Results: The serum levels of complement factors C1q and C3 in both groups gradually increased, while C4 level gradually decreased. Relative to pre-treatment, at 2- and 12-months post-treatment, serum levels of C1q and C3 in both groups were raised, while C4 level decreased (p < 0.05). Relative to control, serum C1q and C3 in the study group were raised, while C4 level was decreased (p < 0.05). Relative to the control group, total treatment effectiveness in the study group increased at 2- and 12- months post-treatment (p < 0.05). There was no significant difference in the incidence of adverse reactions between the control and study groups during the treatment.Conclusion: Treatment with irbesartan + calcitriol significantly improves renal function in patients with IgA nephropathy, reduces inflammatory response, and improves immune function and clinical effectiveness with high safety profile. More clinical trials should be carried out to validate the findings of this study.

Cancer is one of the leading causes of death worldwide. The rising global death from cancer requires novel approaches for treating various types of cancer. Numerous malignancies are now being treated more effectively by immunotherapy. Dostarlimab is an example of an immune checkpoint inhibitor (ICI) that works by blocking the programmed cell death protein-1 receptor (PD-1). Dostarlimab has shifted the paradigm of treatment of cancer from using conventional therapies to a new, promising approach. This new approach increases the options of therapies and chances to achieve a higher response rate. Dostarlimab is a novel antibody, that prevents the binding of ligands to PD-1 on T-cells. Dostarlimab has demonstrated encouraging outcomes in the treatment of various cancers such as endometrial cancer, rectal cancer, and non–small cell lung cancer (NSCLC). The cure rate with dostarlimab in some types of cancer, such as rectal cancer, is 100 %. This review presents a recent understanding of the use of dostarlimab in clinical trials and opens up the doors for clinicians and investigators about future possibilities of using dostarlimab either alone or combined with other anticancer medications to treat various cancers.

Purpose: To determine the role of Fragile X-related protein-1 (FXR1) in colon cancer progression and its relationship to patients’ survival.Methods: A total of 164 colorectal cancer (CRC) patients, admitted to the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China between 2006 and 2008, were included in this study. Immunohistochemistry was used to semi-quantitatively analyze the intensity and extent of immunological staining of diaminobenzidine-stained paraffin blocks of CRC samples. The study also retrieved COAD mRNA and patients’ clinical data from TCGA and cultured human colon cancer cell lines (SW480, SW620, HCT8, HCT116, and Caco2) in RPMI 1640 medium to assess the propensity of CRC cells to proliferate, invade the tumorigenicity in BALB/c nude mice.Results: The prognosis of CRC patients was inversely linked with the expression of FXR1. Additionally, FXR1 knockdown in CRC cells reduced cellular growth, colony development and tumorigenesis. After presenting BALB/c nude mice with tumors in FXR1 knockdown, the cells displayed higher E-cadherin levels (p < 0.01) as well as decreased TGF-1 (p < 0.01) and N-cadherin levels (p < 0.001).Conclusion: Fragile X-related protein-1 is an oncogene in colon cancer and its knockdown inhibits HCT116 cells from behaving malignantly. Thus, FXR1 is a potential treatment option for CRC.