Analysis of network expression and immune infiltration of disulfidptosis-related genes in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a globally prevalent respiratory disease, and programmed cell death plays a pivotal role in the development of COPD. Disulfidptosis is a newly discovered type of cell death that may be associated with the progression of COPD. However, the expression and role of disulfidptosis-related genes (DRGs) in COPD remain unclear. METHODS: The expression of DRGs was identified by analyzing RNA sequencing (RNA-seq) data in COPD. Further, COPD patients were classified into two subtypes by unsupervised cluster analysis to reveal their differences in gene expression and immune infiltration. Meanwhile, hub genes associated with disulfidptosis were screened by weighted gene co-expression network analysis. Subsequently, the hub genes were validated experimentally in cells and animals. In addition, we screened potential therapeutic drugs through the hub genes. RESULTS: We identified two distinct molecular clusters and observed significant differences in immune cell populations between them. In addition, we screened nine hub genes, and experimental validation showed that CDC71, DOHH, PDAP1, and SLC25A39 were significantly upregulated in cigarette smoke-induced COPD mouse lung tissues and bronchial epithelial cells (BEAS-2B) treated with cigarette smoke extract. Finally, we predicted 10 potential small molecule drugs such as Atovaquone, Taurocholic acid, Latamoxef, and Methotrexate. CONCLUSION: We highlighted the strong association between COPD and disulfidptosis, with DRGs demonstrating a discriminative capacity for COPD. Additionally, the expression of certain novel genes, including CDC71, DOHH, PDAP1, and SLC25A39, is linked to COPD and may aid in the diagnosis and assessment of this condition.

Tibial transverse transport induces mobilization of endothelial progenitor cells to accelerate angiogenesis and ulcer wound healing through the VEGFA/CXCL12 pathway.

BACKGROUND: Tibial transverse transport (TTT) can promote the healing of chronic foot ulcers, but the specific cellular and molecular mechanisms by which TTT promotes wound healing remain unclear. METHODS: New Zealand White rabbits were selected to induce foot ulcer models. The treatment included unilateral TTT surgery and bilateral TTT surgery. Observation of tissue neovascularization structure by HE staining and CD31 immunofluorescence detection. Collagen fiber formation was detected through the Masson staining. The mobilization of endothelial progenitor cell (EPCs) were analyzed by VEGFR2 immunofluorescence detection and flow cytometry detection of the number of VEGFR2/Tie-2-positive cells in peripheral blood. ELISA and qPCR assay were performed to detect VEGFA and CXCL12 levels. RESULTS: The complete healing time of ulcer surfaces in sham, unilateral and bilateral TTT groups was about 22 days, 17 days and 13 days, respectively. TTT treatment significantly increased the deposition of granulation tissue and epithelialization of wounds. It also led to an increase in collagen fiber content and the level of the microvascular marker CD31. Furthermore, TTT treatment upregulated the levels of VEGFA and CXCL12 in peripheral blood and wound tissues, as well as increased the expression of VEGFR2 in wound tissues and the proportion of VEGFR2/Tie-2 in peripheral blood. Moreover, these effects of TTT treatment in the bilateral group was more significant than that in the unilateral group. CONCLUSIONS: TTT may facilitate wound fibroblasts to release VEGFA and CXCL12, causing EPC mobilization, thus promoting angiogenesis and ulcer wound healing.

FOXC1 Promotes Osteoblastic Differentiation of Bone Marrow Mesenchymal Stem Cells via the Dnmt3b/CXCL12 Axis.

Bone defects have remained a clinical problem in current orthopedics. Bone marrow mesenchymal stem cells (BM-MSCs) with multi-directional differentiation ability have become a research hotspot for repairing bone defects. In vitro and in vivo models were constructed, respectively. Alkaline phosphatase (ALP) staining and alizarin red staining were performed to detect osteogenic differentiation ability. Western blotting (WB) was used to detect the expression of osteogenic differentiation-related proteins. Serum inflammatory cytokine levels were detected by ELISA. Fracture recovery was evaluated by HE staining. The binding relationship between FOXC1 and Dnmt3b was verified by dual-luciferase reporter assay. The relationship between Dnmt3b and CXCL12 was explored by MSP and ChIP assays. FOXC1 overexpression promoted calcium nodule formation, upregulated osteogenic differentiation-related protein expression, promoted osteogenic differentiation, and decreased inflammatory factor levels in BM-MSCs, and promoted callus formation, upregulated osteogenic differentiation-related protein expression, and downregulated CXCL12 expression in the mouse model. Furthermore, FOXC1 targeted Dnmt3b, with Dnmt3b knockdown decreasing calcium nodule formation and downregulating osteogenic differentiation-related protein expression. Additionally, inhibiting Dnmt3b expression upregulated CXCL12 protein expression and inhibited CXCL12 methylation. Dnmt3b could be binded to CXCL12. CXCL12 overexpression attenuated the effects of FOXC1 overexpression and inhibited BM-MSCs osteogenic differentiation. This study confirmed that the FOXC1-mediated regulation of the Dnmt3b/CXCL12 axis had positive effects on the osteogenic differentiation of BM-MSCs.

Efflux pump Rv1258c activates novel functions of the oxidative stress and via the VII secretion system ESX-3-mediated iron metabolic pathway in Mycobacterium tuberculosis.

Oxidative stress and iron metabolism are essential for Mycobacterium tuberculosis (M.tb) survival in host cells. The efflux pump Rv1258c belongs to the major facilitator superfamily (MFS) and can actively pump drugs to promote certain drug resistance in M.tb. In this study, we compared H37RvΔRv1258c with wild-type (WT) M.tb H37Rv. The qRT-PCR results suggested that Rv1258c is potentially involved in the iron metabolic pathway by regulating the expression of ESX-3, which is required for iron uptake. Protein-Protein Affinity Predictor (PPA-Pred2) and the artificial intelligence program AlphaFold 2 were used for prediction and showed that Rv1258c has direct interactions with PPE4 and EccD3 but weak interactions with EccB3. This was further determined via protein-protein interaction analysis of the yeast two-hybrid expression system. By comparing mutant H37RvΔRv1258c strains with WT strains, we discovered that the absence of Rv1258c led to elevated intracellular H+ potential and NAD+/NADH ratios in M.tb, thereby resulting in oxidative stress. We hypothesize that the efflux pump Rv1258c not only has the function of regulating drug resistance in M.tb but also has a novel function in activating oxidative stress and regulating ESX-3-associated iron metabolism in M.tb.

Comparison of different internal fixation models in ankle arthrodesis using 3D finite-element analysis.

BACKGROUND: The purpose of this study is to use three-dimensional finite-element analysis to better understand the biomechanical features of various internal fixators for ankle arthrodesis. METHODS: We used finite-element analysis to compare four different types of internal fixations in ankle arthrodesis: Group A had three crossed screws (Ø6.5 mm); Group B had two crossed screws (Ø6.5 mm) and an anterior plate (Ø2.7 mm); Group C only had an anterior anatomical plate (Ø3.5 mm); Group D had one anterior anatomical plate (Ø3.5 mm) and one posterior-lateral screw (Ø6.5 mm). We adopted Ansys 21.0 software to analyze and compare the four types in terms of the displacement of the arthrodesis surface and the stress peak and stress distribution of these models under intorsion, extorsion, dorsiflexion torque, and neutral vertical load. RESULTS: ① Displacement of the arthrodesis surface: In Group A, the maximum displacement was larger than Group D under neutral vertical load and dorsiflexion torque but less than it under intorsion and extorsion torque. In Group B, the maximum displacement against dorsiflexion, neutral vertical load, intorsion, and extorsion was less than that in the other three fixation models. In Group C, the maximum displacement against the above four loading patterns were significantly higher than that in another three fixation models. ② Stress peak and stress distribution: based on the stress distribution of the four models, the peak von Mises stress was concentrated in the central sections of the compression screws, plate joints, and bending parts of the plates. CONCLUSIONS: The fixation model consisting of two crossed screws and an anterior outperformed the other three fixation models in terms of biomedical advantages; thus, this model can be deemed a safe and reliable internal fixation approach for ankle arthrodesis.

Diacerein plus glucosamine hydrochloride improves the safety and efficacy and inhibit inflammatory factors in the treatment of knee osteoarthritis.

OBJECTIVES: The aim of this study is to elucidate the safety and efficacy of diacerein (DIA) plus glucosamine hydrochloride (GlcN·HCl) in the treatment of knee osteoarthritis (KOA) and their effect on inflammatory factors (IFs). METHODS: Retrospectively, 116 KOA patients admitted between August 2018 and August 2021 were selected. Among them, 55 cases received DIA monotherapy (control group, Con) and 61 cases received DIA + GlcN·HCl (observation group, Obs). The efficacy, safety, scores of Lequesne Index, and Visual Analogue Scale (VAS), as well as the levels of IFs of the two groups were observed and compared. Further, Cox regression was used to perform an in-depth analysis of factors influencing the occurrence of complications in patients with KOA. RESULTS: The analyses revealed a higher overall response rate and a lower adverse event rate in the Obs group compared with the Con group, with statistical significance. Decreased scores of Lequesne Index and VAS and levels of IFs were determined in the Obs after treatment, which were all significantly lower compared with those of the Con. Cox regression analysis identified that TNF-α, IL-1ß, hs-CRP, and treatment mode affected the occurrence of complications in KOA patients. CONCLUSIONS: DIA + GlcN·HCl can significantly inhibit the inflammation level in KOA, with definite curative effects and a favorable safety profile.

Optimization of Vibration Pretreatment Microwave Curing in Composite Laminate Molding Process.

Vibration pretreatment microwave curing is a high-quality and efficient composite out-of-autoclave molding process. Focusing on interlaminar shear strength, the effects of pretreatment temperature, pretreatment time and vibration acceleration on the molding performance of composite components were analyzed sequentially using the orthogonal test design method; a scanning electron microscope (SEM) and optical digital microscope (ODM) were used to analyze the void content and fiber-resin bonding state of the specimens under different curing and molding processes. The results show that the influence order of the different vibration process parameters on the molding quality of the components was: vibration acceleration > pretreatment temperature > pretreatment time. Within the parameters analyzed in this study, the optimal vibration pretreatment process parameters were: pretreatment temperature of 90 °C, pretreatment time of 30 min, and vibration acceleration of 10 g. Using these parameters, the interlaminar shear strength of the component was 82.12 MPa and the void content was 0.37%. Compared with the microwave curing process, the void content decreased by 71.8%, and the interlaminar shear strength increased by 31.6%. The microscopic morphology and mechanical properties basically reached the same level as the standard autoclave process, which achieved a high-quality out-of-autoclave curing and molding manufacturing of aerospace composite components.

Macrophage-targeted nanoparticles mediate synergistic photodynamic therapy and immunotherapy of tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that poses a serious global public health threat. Due to the high incidence of adverse reactions associated with conventional treatment regimens, there is an urgent need for better alternative therapies. CpG oligodeoxynucleotides (CpG ODNs) are synthetic oligodeoxyribonucleotide sequences. They can induce a Th1-type immune response by stimulating Toll-like receptors (TLRs) in mammalian immune cells, thus killing Mtb. However, due to the negative charge and easy degradation of CpG ODNs, it is necessary to deliver them into cells using nanomaterials. PCN-224 (hereinafter referred to as PCN), as a metal-organic framework based on zirconium ions and porphyrin ligands, not only has the advantage of high drug loading capacity, but also the porphyrin molecule in it is a type of photosensitizer, which allows these nanocomposites to play a role in photodynamic therapy (PDT) while delivering CpG ODNs. In addition, since Mtb mainly exists in macrophages, targeting anti-TB agents to macrophages is helpful to improve the anti-TB effect. Phosphatidylserine (PS) is a biological membrane phospholipid that is normally found on the inner side of cell membranes in, for example, plant and mammalian cells. When apoptosis occurs, PS can flip from the inner side of the cell membrane to the surface of the cell membrane, displaying a specific "eat-me" signal that can be recognized by specific receptors on macrophages. Therefore, we can use this macrophage-targeting property of PS to construct bio-inspired targeted drug delivery systems. In this study, we constructed PCN-CpG@PS nanocomposites. PCN-CpG@PS, combining PDT and immunotherapy, is designed to target macrophages at the site of a lesion and kill latent Mtb. We physically characterized the nanocomposites and validated their bactericidal ability in vitro and their ability to stimulate the immune system in vivo. The results demonstrated that the targeted nanocomposites have certain in vitro antituberculosis efficacy with good safety.

Risk Factors for Length of Hospital Stay in Acute Exacerbation Chronic Obstructive Pulmonary Disease: A Multicenter Cross-Sectional Study.

Background/Purpose: A patient's length of hospital stay (LHS) is associated with the severity and outcome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, identification of patients with prolonged LHS at an early stage can potentially reduce the risk of adverse events and treatment costs in patients with AECOPD. Therefore, this study aimed to explore the independent predictors of prolonged LHS in AECOPD patients. Patients and Methods: This multicenter cross-sectional study was conducted at two tertiary hospitals between January 2019 and August 2020. Demographic data, underlying diseases, symptoms, and laboratory findings were collected. Univariate analysis was used to identify variables with significant differences. A collinearity diagnostic was applied to the selected variables before the establishment of the regression model. Ordinal logistic regression was performed to explore the independent risk factors for prolonged LHS in patients with AECOPD. Results: In total, 598 patients with AECOPD were screened. Finally, the LHS of 111, 218, and 100 patients was <7, 7-10, and ≥11 days, respectively. Significant differences in the 12 variables were found in the univariate analysis. Because collinearities among white blood cells (WBC), neutrophils (NS), and NS% were observed, WBC and NS% were excluded. Subsequently, an ordinal logistic regression model identified that rates of hypertension and chronic cor pulmonale (CCP), neutrophil-lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR) were independent predictors of prolonged LHS in AECOPD patients. Conclusion: Collectively, our results showed that inflammatory status, hypertension, and CCP were independently associated with LHS in patients with AECOPD. These data indicate that early and appropriate administration of antibiotics and anti-inflammatory drugs is essential for reducing LHS. Hypertension and CCP were independent predictors of worse outcomes in patients with AECOPD. Therefore, advanced management and care should be provided to AECOPD patients with hypertension and/or CCP on admission.

Study on the Action Mechanism of Dkk-1, TGF-ß1 and TNF-α Expression Levels in Dupuytren's Contracture.

BACKGROUND: The biological mechanism of Dupuytren's contracture needs to be further studied in order to minimize postoperative recurrence and provide a pathological basis for the development of new therapeutic targets. METHODS: HE staining, immunohistochemistry, PCR and western blotting were performed in pathological palmar aponeurosis specimens and normal palmar aponeurosis tissues for comparative study. RESULTS: (1) TNF-α expression was up-regulated: TNF-α mRNA was more highly expressed in the pathological tissues of DD patients than in the CT group, P < 0.05, and the difference between the two groups was statistically significant; (2) Dkk-1 expression was down-regulated: Dkk-1 mRNA was lower expressed in the pathological tissues of DD patients than in the CT group, P < 0.05, and the difference between the two groups was statistically significant; (3) TGF-ß1 expression was up-regulated: TGF-ß1 mRNA was higher expressed in the pathological tissues of DD patients than in the CT group, P < 0.05, and the difference between the two groups was statistically significant; (4) Pearson correlation analysis suggested that TNF-α expression was positively correlated with TGF-ß1 expression, TNF-α expression was negatively correlated with DKK-1 expression, and TGF-ß1 expression was negatively correlated with DKK-1 expression. CONCLUSION: TNF-α, DKK-1 and TGF-ß1 may play a role in the pathogenesis of palmar aponeurosis contracture, and there is a relationship between them. The study of the relationship between the three and their related signaling pathways provides a therapeutic target and a basis for the prevention and early treatment of palmar aponeurotic contracture.

Rv1258c acts as a drug efflux pump and growth controlling factor in Mycobacterium tuberculosis.

The possible role of efflux pump as a survival mechanism in Mycobacterium tuberculosis (M. tb) is gaining an increasing attention. Previously, Rv1258c (Tap) and its certain mutations confer the clinically relevant drug resistance. In this study, we found new mutations of Rv1258c in G195C, T297P and I328T. Effect of modulating T297P and I328T on the drug resistance by knockout and complement in M. tb H37Rv showed that M. tb ΔRv1258c showed a slightly lower MIC for rifampin, ethambutol, ofloxacin, amikacin, capreomycin and streptomycin than M. tb H37Rv WT and the complement. Rv1258c T297P and Rv1258c I328T showed an increased drug resistance to ethambutol and capreomycin than the complement of Rv1258c WT. Most importantly, M. tb ΔRv1258c exhibited a slow growth in the normal culture medium. TMT-based quantitative proteomics analysis of M. tb ΔRv1258c and WT showed that the knockout of Rv1258c greatly down-regulated the expression of the ribosome system and one of the special five type VII secretion systems, ESX-3, which impaired the bacterial growth. These results indicate that the newly found T297P and I328T mutations of Rv1258c contributed to an increased resistance to ethambutol and capreomycin, and Rv1258c as growth controlling factor influencing the growth of M. tb.

Single-nucleotide polymorphisms and activities of indoleamine 2,3-dioxygenase isoforms, IDO1 and IDO2, in tuberculosis patients.

PURPOSE: To explore the role and effects of the single-nucleotide polymorphisms (SNPs) of the two functionally related indoleamine 2,3-dioxygenase (IDO) isoforms on IDO activity in the Chinese Han ethnic population. METHODS: A total of 151 consecutive patients of Chinese Han ethnicity (99 men and 52 women; average age 51.92 ± 18.26 years) with pulmonary TB admitted to Beijing Chest Hospital between July 2016 and February 2017 were enrolled in the study. The serum levels of tryptophan (Trp) and its metabolites, IDO1 and IDO2 mRNA levels, and the relationship of IDO1 and IDO2 SNPs with the serum Kyn/Trp ratio in TB patients and healthy controls were examined by LC/ESI-MS/MS analysis. Genomic DNA was isolated from whole blood, and the PCR products were sequenced and analyzed. RESULTS: In Chinese Han participants, only IDO2 had SNPs R248W and Y359X that affected IDO activity, as determined by the serum Kyn/Trp ratio. IDO1 and IDO2 mRNA levels were inversely related in TB patients and healthy controls. CONCLUSIONS: IDO2 SNPs and the opposite expression pattern of IDO1 and IDO2 affected IDO activity in Chinese Han TB patients.

The Treatment Experience of Different Types of Flaps for Repairing Soft Tissue Defects of the Heel.

OBJECTIVE: To summarize the clinical application effects of three different types of flaps for repairing soft tissue defects of the heel, and to discuss the importance of tissue repair and heel reconstruction. METHODS: A total of 46 cases with skin tissue defects of the heel with deep tissue exposure were treated. The reasons for the defect were trauma (n = 26), burns and electric shocks (n = 12), chronic ulcers (n = 2), postoperative infection of the calcaneus and Achilles tendon (n = 5), and tumor resection (n = 1). The scope of wound defect was 2.0×2.5 to approximately 15.0×20.0 cm. The flaps used were medial plantar island flaps (n = 9), distal pedicled sural neurovascular island flaps (n = 23), and free anterolateral thigh (perforator) flaps (n = 14). The flap cutting range was 3.0×3.5 to approximately 16.0×22.0 cm. RESULTS: After surgery, all 46 flaps survived. In two cases, patients experienced partial epidermal necrosis at the distal end of the flap that healed after local dressing exchange, and after this treatment, the complete skin grafts survived. Follow-up was conducted in 40 cases, with an average follow-up duration of 8.2 months (3-44 months) and the two-point discrimination of 5-14 mm. The average American Orthopaedic Foot and Ankle Society scale was 89.2 points with good flap color and texture, satisfactory appearance, and normal gait. CONCLUSION: The repair method should be selected according to the"5-zone method": The plantar medial island flap is suitable for small area (<5 cm) of medial, posterior and plantar defects. The distal pedicled sural neurovascular flap is suitable for lateral, posterior, and medium-range (6-10 cm) joint area defects. The free anterolateral thigh perforator flap is suitable for large-scale (>10 cm) joint area defects.

Osteogenic and antibacterial dual functions of a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffold.

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.

Recent advances in functionalized upconversion nanoparticles for light-activated tumor therapy.

Upconversion nanoparticles (UCNPs) are a class of optical nanocrystals doped with lanthanide ions that offer great promise for applications in controllable tumor therapy. In recent years, UCNPs have become an important tool for studying the treatment of various malignant and nonmalignant cutaneous diseases. UCNPs convert near-infrared (NIR) radiation into shorter-wavelength visible and ultraviolet (UV) radiation, which is much better than conventional UV activated tumor therapy as strong UV-light can be damaging to healthy surrounding tissue. Moreover, UV light generally does not penetrate deeply into the skin, an issue that UCNPs can now address. However, the current studies are still in the early stage of research, with a long way to go before clinical implementation. In this paper, we systematically analysed recent advances in light-activated tumor therapy using functionalized UCNPs. We summarized the purpose and mechanism of UCNP-based photodynamic therapy (PDT), gene therapy, immunotherapy, chemo-therapy and integrated therapy. We believe the creation of functional materials based on UCNPs will offer superior performance and enable innovative applications, increasing the scope and opportunities for cancer therapy in the future.

Changes of Anti-tuberculosis Herbs Formula During Past Three Decades in Contrast to Ancient Ones.

OBJECTIVE: To investigate the evolution of herbal medicine in treating tuberculosis (TB) and encourage anti-TB drug discovery and development. METHODS: In this study, 477 ancient traditional Chinese medicine formulae were collected from the Dictionary of Traditional Chinese Medicine Prescriptions and 172 modern Chinese medicine formulae (from 1986 to 2016) were collected by searching 4 databases: WanFang Data Knowledge Service Platform, China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP) and Chinese Bio-medical Literature and Retrieval System (SinoMed) in Chinese. We restricted the search to publications in Chinese. Further data analysis was done using the Traditional Chinese Medicine Inheritance Support System version 2 Software. RESULTS: There were 425 herbs in the 477 ancient formulae and 257 herbs in the 172 modern formulae. Half of the top 30 herbs were shared by both modern and ancient prescriptions. They are Radix Ophiopogonis, Astragalus membranaceus, Fritillaria cirrhosa, Dried rehmannia glutinosa, Poria cocos, Angelica sinensis, Prepared rehmannia glutinosa, Platycodon Root, Radix paeoniae alba, Schisandra chinensis, Bighead atractylodes rhizome, Rhizoma anemarrhenae, Cortex lycii radicis and Radix Scutellariae. Only two groups of herbs with a high correlation coefficient were found in both modern and ancient prescriptions, the Dried rehmannia glutinosa with Radix ophiopogonis, and Radix ophiopogonis with Prepared rehmannia glutinosa. There were 9 and 15 core herb combinations in modern and ancient prescriptions, respectively, but no one was found simutaniously in both modern and ancient prescriptions. CONCLUSIONS: Although there were wide variations in the herb groups and herb combinations in the formulae, half of the top 30 herbs were found in both modern and ancient prescriptions. The core herb combinations in modern and ancient prescriptions could help us to improve the priscription for treatment of TB.

Clinical Differences between Eosinophilic and Noneosinophilic Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Multicenter Cross-Sectional Study.

METHODS: A total of 643 AECOPD patients were enrolled in this multicenter cross-sectional study. Finally, 455 were included, 214 in the normal-eosinophil AECOPD (NEOS-AECOPD) group, 63 in the mild increased-eosinophil AECOPD (MEOS-AECOPD) group, and 138 in the severe increased-eosinophil AECOPD (SEOS-AECOPD) group. Demographic data, underlying diseases, symptoms, and laboratory findings were collected. Multiple logistic regression analysis was performed to identify the independent factors associated with blood eosinophils (EOS). Correlations between blood EOS and its associated independent factors were evaluated. RESULTS: The significant differences in 19 factors, including underlying diseases, clinical symptoms, and laboratory parameters, were identified by univariate analysis. Subsequently, multiple logistic regression analysis revealed that lymphocyte%, neutrophil% (NS%), procalcitonin (PCT), and anion gap (AG) were independently associated with blood EOS in AECOPD. Both blood EOS counts and EOS% were significantly correlated with lymphocyte%, NS%, PCT, and AG. CONCLUSIONS: Collectively, blood EOS was independently associated with lymphocyte%, NS%, PCT, and AG in AECOPD patients. Lymphocyte% was lower, and NS%, PCT, and AG were higher in eosinophilic AECOPD. Our results indicate that viral-dominant infections are the probable major etiologies of eosinophilic AECOPD. Noneosinophilic AECOPD is more likely associated with bacterial-dominant infections. The systemic inflammation in noneosinophilic AECOPD was more severe.

Monocyte chemotactic protein-inducing protein 1 negatively regulating asthmatic airway inflammation and mucus hypersecretion involving γ-aminobutyric acid type A receptor signaling pathway in vivo and in vitro.

BACKGROUND: Mounting evidence, consistent with our previous study, showed that γ-aminobutyric acid type A receptor (GABAAR) played an indispensable role in airway inflammation and mucus hypersecretion in asthma. Monocyte chemotactic protein-inducing protein 1 (MCPIP1) was a key negative regulator of inflammation. Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases. However, the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied. This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells, and its potential mechanism. METHODS: In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were chosen. Interleukin (IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells. MCPIP1 Lentiviral vector (LA-MCPIP1) and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells, respectively. MCP-1, thymic stromal lymphopoietin (TSLP), mucin 5AC (MUC5AC), MCPIP1, and GABAARß2 expressions were measured in both lung and BEAS-2B cells. Immunofluorescence staining was performed to observe the expression of GABAARß2 in cells. RESULTS: MCPIP1 was up-regulated by LA-MCPIP1 (P < 0.001) and plasmid-MCPIP1 (P < 0.001) in lung and cells, respectively. OVA-induced airway inflammation and mucus hypersecretion, OVA-enhanced MCP-1, TSLP, MUC5AC, and GABAARß2 expressions, and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice (all P < 0.001). IL-13-enhanced MCP-1, TSLP, MUC5AC, and GABAARß2 expressions, and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells (all P < 0.001). CONCLUSION: The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells, involving GABAAR signaling pathway.