Efficacy and safety of self-made WenyangJianpi-qushi Decoction combined with mometasone furoate cream in the treatment of atopic dermatitis of spleen deficiency and dampness accumulation type.

Introduction: This work was to explore the efficacy and safety of self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream in atopic dermatitis (AD) of spleen deficiency and dampness accumulation type. Material and method: 120 patients with this kind of atopic dermatitis were grouped: The Observation group (disease health education + basic treatment + mometasone furoate cream + self-made Decoction) and The Control group (disease health education + basic treatment + mometasone furoate cream), 60 cases in each group. The SCORAD score, serum IgE level, peripheral blood eosinophils, adverse events, recurrence rate, and total effective rate after treatment were observed.Result: Through treatment, SCORAD score of the observation group (29.96 ± 2.88) was lower as against controls (36.04 ± 3.12), p < 0.05. Through treatment, the peripheral blood eosinophil count in the observation group was (311.26 ± 50.19) 106/L, which was lower than (582.71 ± 54.75) 106/L in controls; the serum lgE of the observation group was (712.44 ± 93.32) IU/mL, which was lower than the controls (890.12 ± 81.25) IU/mL, p < 0.05. The Observation group (56/60, 93.33%) demonstrated superior total effective rate to the controls (34/60, 56.67%); The recurrence rate of the observation group was 4/60 (6.67%), which was lower than the controls 16/60 (26.67%), p < 0.05.Conclusion: Self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream to treat atopic dermatitis of spleen deficiency and dampness accumulation type has significant efficacy and good safety.

Aminophylline Improves Ventilator-Induced Diaphragmatic Dysfunction by Targeting IGF-1-FOXO1-MURF1 Pathway.

BACKGROUND: The usage of life-saving mechanical ventilation (MV) could cause ventilator-induced diaphragmatic dysfunction (VIDD), increasing both mortality and morbidity. Aminophylline (AP) has the potential to enhance the contractility of animal skeletal muscle fibers and improve the activity of human respiratory muscles, and the insulin-like growth factor-1 (IGF-1)- forkhead box protein O1 (FOXO1)-muscle RING finger-1 (MURF1) pathway plays a crucial role in skeletal muscle dysfunction. This study aimed to investigate the impact of AP on VIDD and to elucidate the role of the IGF-1-FOXO1-MURF1 pathway as an underlying mechanism. METHODS: Rat models of VIDD were established through MV treatment. IGF-1 lentiviral (LV) interference (LV-IGF-1-shRNA; controlled by lentiviral negative control LV-NC) was employed to inhibit IGF-1 expression and thereby block the IGF-1-FOXO1-MURF1 pathway. Protein and mRNA levels of IGF-1, FOXO1, and MURF1 were assessed using western blot and real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), respectively. Diaphragm contractility and morphometry were examined through measurement of compound muscle action potentials (CMAPs) and hematoxylin and eosin (H&E) staining. Oxidative stress was evaluated by levels of hydrogen peroxide (H2O2), superoxide dismutase (SOD), antioxidant glutathione (GSH), and carbonylated protein. Mitochondrial stability was assessed by measuring the mitochondrial membrane potential (MMP), and mitochondrial fission and mitophagy were examined through protein levels of dynamin-related protein 1 (DRP1), mitofusin 2 protein (MFN2), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), and Parkin (western blot). Apoptosis was evaluated using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay and levels of Bax, B-cell lymphoma 2 (BCL-2), and Caspase-3. Levels of Atrogin-1, neuronally expressed developmentally downregulated 4 (NEDD4), and muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1) mRNA, as well as ubiquitinated protein, were utilized to determine protein degradation. Furthermore, the SUnSET (surface sensing of translation) method was employed to determine rates of protein synthesis. RESULTS: MV treatment upregulated IGF-1 while downregulated FOXO1 and MURF1 (p < 0.05). AP administration reversed IGF-1, FOXO1 and MURF1 (p < 0.05), which was suppressed again by IGF-1 inhibition (p < 0.05), demonstrating the blockage of the IGF-1-FOXO1-MURF1 pathway. MV treatment caused decreased CMAP and cross-sectional areas of diaphragm muscle fibers, and increased time course of CMAP (p < 0.05). Additionally, oxidative stress, cell apoptosis, and protein degradation were increased and mitochondrial stability was decreased by MV treatment (p < 0.05). Conversely, AP administration reversed all these changes induced by MV, but this reversal was disrupted by the blockage of the IGF-1-FOXO1-MURF1 pathway. CONCLUSIONS: In this study, MV treatment induced symptoms of VIDD in rats, which were all effectively reversed by AP regulating the IGF-1-FOXO1-MURF1 pathway, demonstrating the potential of AP in ameliorating VIDD.

IGF-1 Regulates Skeletal Muscle Degradation and Remolding in Ventilator-Induced Diaphragmatic Dysfunction by Mediating FOXO1 Expression.

BACKGROUND: Mechanical ventilation (MV) sustains life in critically ill patients by providing adequate alveolar ventilation. However, prolonged MV could induce inspiratory muscle atrophy known as ventilator-induced diaphragmatic dysfunction (VIDD). Insulin-like growth factor (IGF)-1 has been proven to play crucial roles in regulating skeletal muscle size and function. Meanwhile, the forkhead box protein O1 (FOXO1) has been linked to muscle atrophy. This study aimed to explore the effect of IGF-1 on muscle degradation and remodeling in VIDD and delved into the association of the underlying mechanism involving FOXO1. METHODS: VIDD models were established by treating rats with MV. Adeno-associated virus (AAV) was used for transfection to construct IGF-1 and/or FOXO1 overexpressed rats. There were four groups in this study: normal rats (NC), normal rats with MV treatment (MV), IGF-1-overexpressed rats with MV treatment (MV+IGF-1), and rats overexpressing both IGF-1 and FOXO1 with MV treatment (MV+IGF-1+FOXO1). Protein levels were measured by western blot or enzyme-linked immunosorbent assay (ELISA), and mRNA levels were detected by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). IGF-1 and FOXO1 expression were validated by detecting mRNA and protein levels. Diaphragmatic muscle contractility and morphometry were tested using stimulating electrodes in conjunction with hematoxylin and eosin (H&E) staining. Interleukin (IL)-6 and carbonylated protein were used for evaluating muscle atrophy and oxidation, respectively. Protein degradation was determined by troponin-I level and tyrosine release. Apoptosis was assessed using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay, alongside markers like Bax, B-cell lymphoma 2 (BCL-2), and Cleaved Caspase-3. Atrogin-1, muscle RING finger 1 (MURF1), neuronally expressed developmentally downregulated 4 (NEDD4), muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1), and ubiquitinated protein was used to determine proteolysis. Additionally, protein synthesis was measured by assessing the rates of mixed muscle protein (MMP) and myosin heavy chain (MHC). RESULTS: MV treatment caused IGF-1 downregulation (p < 0.01) and FOXO1 upregulation (p < 0.01). The IGF-1 upregulation downregulated FOXO1 in the MV+IGF-1 group (p < 0.001) while IGF-1 and FOXO1 were both upregulated in the MV+IGF-1+FOXO1 group (p < 0.001). The treatment of MV decreased muscle contractility and cross-sectional areas of diaphragm muscle fibers (p < 0.01). Additionally, IL-6, troponin-1, tyrosine release, carbonylated protein, TUNEL positive nuclei, Bax, Cleaved Caspase-3, Atrogin-1, MURF1, neuronally expressed developmentally downregulated 4 (NEDD4), MUSA1, and ubiquitinated protein levels increased significantly in MV group (p < 0.001) while levels of BCL-2, fractional synthetic rate of MMP and MHC, and type I and type II MHC protein mRNA expression decreased in MV group (p < 0.001). All of these alterations were reversed in the MV+IGF-1 group (p < 0.01), while the IGF-1-induced reversion was disrupted in the MV+IGF-1+FOXO1 group (p < 0.01). CONCLUSIONS: IGF-1 may protect diaphragmatic muscles from VIDD-induced structural damage and function loss by downregulating FOXO1. This action suppresses muscle breakdown and facilitates muscle remodeling in diaphragmatic muscles affected by VIDD.

Electrochemically Driven Phase Transition in LiCoO2 Cathode.

Lithium cobalt oxide (LiCoO2), which has been successfully applied in commercial lithium-ion batteries for portable devices, possesses a theoretical specific capacity of 274 mAh g-1. However, its actual capacity is only half of the theoretical specific capacity, because the charging voltage is restricted below 4.2 V. If a higher charging voltage is applied, an irreversible phase transition of LiCoO2 during delithiation would occur, resulting in severe capacity fading. Therefore, it is essential to investigate the electrochemically driven phase transition of LiCoO2 cathode material to approach its theoretical capacity. In this work, it was observed that LiCoO2 partially degraded to Co3O4 after 150 charging-discharging cycles. From the perspective of crystallography, the conventional cell of LiCoO2 was rebuilt to an orthonormal coordinate, and the transition path from layered LiCoO2 to cubic Co3O4 proposed. The theoretical analysis indicated that the electrochemically driven phase transition from LiCoO2 to Co3O4 underwent several stages. Based on this, an experimental verification was made by doping LiCoO2 with Al, In, Mg, and Zr, respectively. The doped samples theoretically predicted behavior. The findings in this study provide insights into the electrochemically driven phase transition in LiCoO2, and the phase transition can be eliminated to improve the capacity of LiCoO2 to its theoretical value.

[Association of polymorphisms of miR-146a rs2910164 locus with clinical features of rheumatoid arthritis].

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of microRNA-146a (miR-146a) with clinical features of rheumatoid arthritis (RA). METHODS: In 126 patients with RA and 102 matched healthy controls, SNPs of miR-146a rs2910164 locus were determined with a high-resolution melting method. The association of such polymorphisms with disease activity score in 28 joints (DAS28) and clinical features of RA was assessed. RESULTS: The distribution of SNPs of miR-146a rs2910164 among RA patients did not differ from that of the control group. No significant association was found between miR-146a rs2910164 polymorphism with DAS28. However, RA patients with a GG genotype had a greater chance to develop extra-articular manifestations (P<0.01). CONCLUSION: Polymorphisms of miR-146a rs2910164 locus is not an independent risk factor for RA, though its GG genotype may be associated with extra-articular manifestations of RA.

Serum YKL-40 predicts long-term outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

Serum YKL-40, a potential inflammatory marker, is greatly increased at the early stage of ST-segment elevation myocardial infarction (STEMI). Here, we hypothesized that YKL-40 levels at admission could predict the long-term outcomes after STEMI.A total of 324 patients with acute STEMI undergoing primary percutaneous coronary intervention (PCI) were consecutively enrolled and followed for 24 months. The baseline clinical and procedural data were recorded, and serum YKL-40 levels at admission were measured using ELISA method. The endpoint of interest was major adverse cardiac event (MACE), including all-cause death, recurrent myocardial infarction, and hospitalization for heart failure.Patients with elevated serum YKL-40 levels (≥126.8 ng/mL) were more likely to be older and smoker and to present with type 2 diabetes, advanced Killip class, multivessel disease and intra-aortic balloon pump, with increased levels of admission glucose, triglyceride, and high-sensitivity C-reactive protein and decreased level of high-density lipoprotein cholesterol. During the follow-up period, the incidence of MACE was notably higher in the high than in the low YKL-40 groups (28.4% vs 11.1%, P < .001). Kaplan-Meier curve showed that elevated YKL-40 levels were associated with reduced MACE-free survivals (log-rank P < .001). In multivariate Cox regression analysis, we found that high serum YKL-40 level was an independent predictor of MACE after controlling for clinical and angiographic variables (hazard ratio: 1.65, 95% confidence interval: 1.14-2.39, P = .008).The results of our study indicate that serum YKL-40 may be used as a biomarker to predict the long-term outcome after PCI in patients with STEMI.

[Expression and significance of cyclophilin A in synovial fibroblasts from patients with rheumatoid arthritis].

OBJECTIVE: To observe the expression of cyclophilin A (CyPA) and the effects of lipopolysaccharide (LPS) on CyPA expression in synovial fibroblasts (SF) from patients with rheumatoid arthritis (RA) and evaluate the potential significance of CyPA in the regulation of the onset and development of inflammation process in RA patients. METHODS: SF were separated and cultured from synovial tissues of 12 patients with RA, 9 with osteoarthritis (OA) and 5 with knee trauma. The protein and mRNA expression levels of CyPA in SF were detected by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) respectively. Correlation analysis was conducted between the protein expression of CyPA in SFs and clinical parameters. Then the effects of LPS on CyPA in SF from 3 groups were detected. RESULTS: The expression levels of CyPA protein and mRNA in RA group were 0.86 ± 0.47 and 0.54 ± 0.22 respectively, significantly higher than those in OA group (0.40 ± 0.31 and 0.03 ± 0.02, P < 0.05) and trauma group (0.34 ± 0.21 and 0.03 ± 0.01, P < 0.05). The protein expression level of CyPA in SF of RA group had positive correlations with erythroeyte sedimentation rate (ESR), rheumatoid factor (RF) and swelling joint counts (SJC) (P < 0.05). After LPS treatment, CyPA protein and mRNA levels were 2.65 ± 1.16 and 1.82 ± 0.39 in RA SF and they were significantly higher than those in RA SF without LPS treatment (P < 0.05). The CyPA expression of SF from OA and trauma groups slightly decreased after LPS treatment.However the differences were not statistically significant (P > 0.05). CONCLUSION: The expression of CyPA is up-regulated in SF and it is positively correlated with ESR, RF and SJC in RA patients. It indicates that CyPA may be involved in the regulation of the onset and development of inflammation process of RA. And LPS may promote the expression of CyPA in SF of RA patients.

Influence of sinomenine on protein profiles of peripheral blood mononuclear cells from ankylosing spondylitis patients: a pharmacoproteomics study.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease which lacks satisfactory treatment so far. Sinomenine (SIN) is an alkaloid and has recently been utilized in treating multiple rheumatic diseases including AS in China, but its exact mechanism remains to be explored. This study investigated the alteration of proteome in peripheral blood mononuclear cells (PBMCs) from AS patients. METHODS: Thirty AS patients were enrolled in this study. PBMCs from each AS patient were cultured in medium with or without SIN respectively. Then PBMCs proteins from both groups were separated by two-dimensional electrophoresis (2-DE) and analyzed by mass spectrometry (MS). Two differentially expressed proteins were then chosen to be verified using Western blotting. RESULTS: Seven proteins, including a-synuclein (SNCA), calmodulin (CALM), acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A), chloride intracellular channel protein 1 (CLIC1), guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (GNB1), gelsolin (GSN) and histone H2B type 1-M (HISTH2BM) were over-expressed, while coronin- 1A (CORO1A) was under-expressed in the SIN-treated PBMCs. Further bioinformatics search indicated that the changes of SNCA, ANP32A and CLIC1 pertained to apoptosis, while changes of GSN and CORO1A were associated with both apoptosis and inhibition of immunological function. Subsequently GSN and CORO1A were selected to validate by Western blotting and the results were consistent with those of 2-DE. CONCLUSION: There were 8 differentially expressed proteins in the SIN-treated PBMCs, which might shed some light on the mechanism of SIN in the treatment of AS.

[Efficacy of local injection of RhTNFR: Fc in collagen-induced arthritis of rats].

OBJECTIVE: To evaluate the efficacy of recombinant human tumor necrosis factor-α receptor II: IgG fusion protein (RhTNFR:Fc) local injection in collagen-induced arthritis (CIA) of rats. METHODS: Twenty-four CIA rats were randomly divided into 3 groups: single therapy (Group I), multiply therapies (Group II) and control (Group III). Group I received normal saline thrice after a single RhTNFR:Fc local treatment while Groups II and III had 4 times of RhTNFR:Fc or normal saline local injection. The severities of right ankle and systemic inflammation were assessed by arthritis index (AI) at baseline and every week after local injection (visits 1, 2, 3 and 4). Serum C reactive protein (CRP) was measured after the last visit. And right ankles were further examined through radiology and pathology. RESULTS: Local or systemic AI of Group I were significantly lower than that of baseline at visit 1 (P < 0.05), but increased during other visits. And local or systemic AI of Group II gradually decreased at each follow-up, but AI of Group III showed no decline. The radiographic scores (5.70±0.67 and 4.90±0.73), histopathological scores (6.00±0.67 and 3.80±0.91) and serum CRP concentration (7.50±0.87 and 3.09±0.76 µg/ml) of Group I and Group II were lower than those of Group III (6.60±1.26, 7.10±0.7 and 12.15±3.47 µg/ml, P < 0.05). And all these parameters of Group I were higher than those of Group II (P < 0.05). CONCLUSION: Local injection of RhTNFR:Fc can effectively alleviate disease activity of CIA and reduce CRP concentration, radiographic and histopathological scores. Multiple therapies show a better efficacy than single injection.