All-cause mortality in moderate and severe COVID-19 patients with myocardial injury receiving versus not receiving azvudine: a propensity score-matched analysis.

Omicron is currently the dominant strain of severe acute respiratory syndrome coronavirus 2, but little is known about the characteristics and management of omicron related myocardial injury, particularly the potential benefit of the antiviral agent azvudine. Methods: Patients with confirmed and suspected coronavirus disease 2019 (COVID-19) admitted to Wuhan Union Hospital from December 7, 2022, to December 30, 2022, were included in this study. Cox regression was conducted to identify risk factors for all-cause mortality. A propensity score-matched analysis was performed at a 1:1 ratio with a caliper of 0.1 pooled standard deviations of relevant confounders. Results: The final analysis included a total of 332 patients (167 confirmed cases and 165 suspected cases), 42.77% (142/332) of the patients were 80 years of age or older and 68.67% (228/332) of them were men, 158 patients were treated with azvudine. In the matched cohort, the total mortality was 30.30% (60/198), 40 (20.20%, 40/198) patients received noninvasive ventilation and 22 (11.11%, 22/198) received invasive ventilation, 34 (17.17%, 34/198) patients were admitted to intensive care unit (ICU). The rate of shock, multiple organ damages and arrhythmia were 11.62% (23/198), 20.20% (40/198), and 12.12% (24/198), respectively. There was no significant difference on these clinical outcomes in patients treated with azvudine or not. Azvudine reduced early mortality (within 14 days from admission) (hazard ratio: 0.37, 95% confidence interval: 0.18-0.77) even after adjusting for other treatments including glucocorticoids, immunoglobin and anticoagulant therapy, but not the final in-hospital mortality of patients. Conclusions: Patients with COVID-19-related myocardial injury had a high mortality of about 30.30% (60/198). Azvudine improved the early survival of the patients but not final mortality.

A sensing platform based on zinc-porphyrin derinative in hexadecyl trimethyl ammonium bromide (CTAB) microemulsion for highly sensitive detection of theophylline.

A new porphyrin-based sensing platform in hexadecyl trimethyl ammonium bromide (CTAB) microemulsion is developed for highly sensitive detection of theophylline. In this sensing system, the zinc-porphyrin-cinnamic acid conjugate (Zn-TPPCA) works as fluorescence probe while theophylline can decrease fluorescence intensity of the probe. Further studies indicate the linear relationship between the fluorescence quenching value and the concentration of theophylline within a given range. And the introduction of CTAB microemulsion can greatly enhance sensibility and stability of this detecting system and facilitate the detection of theophylline. On the basis above, a highly sensitive sensing platform for theophylline is created with a low limit of detection (LOD) of 0.0083 µg mL-1 under the optimal detection conditions. And further application of this method in determination of commercially available theophylline preparation shows excellent results. Subsequent studies on quenching mechanism indicate that static quenching appears between Zn-TPPCA and theophylline. Therefore, this work provides not only a highly sensitive method for determination of theophylline but also further evidence for creation of biosensors for drugs with porphyrin derivatives.

Bisdemethoxycurcumin Protects Small Intestine from Lipopolysaccharide-Induced Mitochondrial Dysfunction via Activating Mitochondrial Antioxidant Systems and Mitochondrial Biogenesis in Broiler Chickens.

Bisdemethoxycurcumin is one of the three curcuminoids of turmeric and exhibits good antioxidant activity in animal models. This study is aimed at investigating the effect of bisdemethoxycurcumin on small intestinal mitochondrial dysfunction in lipopolysaccharide- (LPS-) treated broilers, especially on the mitochondrial thioredoxin 2 system and mitochondrial biogenesis. A total of 320 broiler chickens were randomly assigned into four experimental diets using a 2 × 2 factorial arrangement with diet (0 and 150 mg/kg bisdemethoxycurcumin supplementation) and stress (saline or LPS challenge) for 20 days. Broilers received a dose of LPS (1 mg/kg body weight) or sterile saline intraperitoneally on days 16, 18, and 20 of the trial. Bisdemethoxycurcumin mitigated the mitochondrial dysfunction of jejunum and ileum induced by LPS, as evident by the reduced reactive oxygen species levels and the increased mitochondrial membrane potential. Bisdemethoxycurcumin partially reversed the decrease in the mitochondrial DNA copy number and the depletion of ATP levels. Bisdemethoxycurcumin activated the mitochondrial antioxidant response, including the prevention of lipid peroxidation, enhancement of manganese superoxide dismutase activity, and the upregulation of the mitochondrial glutaredoxin 5 and thioredoxin 2 system. The enhanced mitochondrial respiratory complex activities in jejunum and ileum were also attributed to bisdemethoxycurcumin treatment. In addition, bisdemethoxycurcumin induced mitochondrial biogenesis via transcriptional regulation of proliferator-activated receptor-gamma coactivator-1alpha pathway. In conclusion, our results demonstrated the potential of bisdemethoxycurcumin to attenuate small intestinal mitochondrial dysfunction, which might be mediated via activating the mitochondrial antioxidant system and mitochondrial biogenesis in LPS-treated broilers.

Bisdemethoxycurcumin attenuates lipopolysaccharide-induced intestinal damage through improving barrier integrity, suppressing inflammation, and modulating gut microbiota in broilers.

Bisdemethoxycurcumin has good antioxidant and anti-inflammatory effects and has been widely used as food and feed supplements in the form of curcuminoids. However, the beneficial effect of individual bisdemethoxycurcumin on preventing lipopolysaccharide (LPS)-induced inflamed intestinal damage is unclear. The present study aimed to investigate whether dietary bisdemethoxycurcumin supplementation could attenuate LPS-induced intestinal damage and alteration of cecal microbiota in broiler chickens. In total, 320 one-day-old male Arbor Acres broiler chickens with a similar weight were randomly divided into four treatments. The treatments were designed as a 2 × 2 factorial arrangement: basal diet (CON); 150 mg/kg bisdemethoxycurcumin diet (BUR); LPS challenge + basal diet (LPS); LPS challenge + 150 mg/kg bisdemethoxycurcumin diet (L-BUR). Results showed that dietary bisdemethoxycurcumin supplementation attenuated the LPS-induced decrease of average daily feed intake. LPS challenge compromised the intestinal morphology and disrupted the intestinal tight junction barrier. Dietary bisdemethoxycurcumin supplementation significantly increased villus length:crypt depth ratio and upregulated the mRNA expression of intestinal tight junction proteins. Moreover, a remarkably reduced mRNA expression of inflammatory mediators was observed following bisdemethoxycurcumin supplementation. The cecal microbiota analysis showed that bisdemethoxycurcumin supplementation increased the relative abundance of the genus Faecalibacterium while decreased the relative abundance of the genera Bacteroides and Subdoligranulum. In conclusion, dietary bisdemethoxycurcumin supplementation could counteract LPS-induced inflamed intestinal damage in broiler chickens by improving intestinal morphology, maintaining intestinal tight junction, downregulating pro-inflammatory mediators, and restoring cecal microbiota.

Dietary bisdemethoxycurcumin supplementation attenuates lipopolysaccharide-induced damages on intestinal redox potential and redox status of broilers.

This study was conducted to investigate the beneficial effects of bisdemethoxycurcumin (BDC) on growth performance, glutathione (GSH) redox potential, antioxidant enzyme defense, and gene expression in lipopolysaccharide (LPS)-challenged broilers. A total of 320, male, 1-day-old broilers were randomly assigned to 4 treatment groups including 8 replicates with 10 birds per cage in a 2 × 2 factorial arrangement: BDC supplementation (a basal diet with 0 or 150 mg/kg BDC) and LPS challenge (intraperitoneal injection of 1 mg/kg body weight saline or LPS at 16, 18, and 20 d of age). Results showed that dietary BDC supplementation prevented the LPS-induced decrease in ADG of broilers (P < 0.05). Compared to the saline-challenged group, LPS-challenged broilers showed higher jejunal and ileal malondialdehyde (MDA), protein carbonyl (PC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents (P < 0.05). Dietary BDC supplementation alleviated LPS-induced increases in jejunal 8-OHdG, ileal MDA, and PC contents (P < 0.05). LPS challenge impaired the small intestinal antioxidant system, as evident by the decreases of GSH and total thiol contents, as well as superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase (GR), and glutathione S-transferase (GST) activities. On the other hand, LPS challenge also increased GSH redox potential and oxidized glutathione (GSSG) contents (P < 0.05). Dietary BDC supplementation increased jejunal and ileal GSH contents, SOD activities, jejunal GR activity, and ileal GST activity, while it decreased jejunal and ileal redox potential, and jejunal GSSG contents (P < 0.05). Dietary BDC supplementation significantly alleviated the downregulation of mRNA expression levels of jejunal and ileal copper and zinc superoxide dismutase, catalytic subunit of γ-glutamylcysteine ligase, nuclear factor erythroid-2-related factor 2, heme oxygenase 1, NAD(P)H quinone oxidoreductase 1, and jejunal catalase and GR induced by LPS challenge (P < 0.05). In conclusion, BDC demonstrated favorable protection against LPS-induced small intestinal oxidative damages, as indicated by the improved growth performance, decreased GSH redox potential, enhanced antioxidant enzyme activities, and upregulated antioxidant-related gene expression.

Dietary taurine supplementation attenuates lipopolysaccharide-induced inflammatory responses and oxidative stress of broiler chickens at an early age.

This study was conducted to investigate the effect of taurine as a prophylactic treatment on antioxidant function and inflammatory responses of broilers challenged with lipopolysaccharide (LPS). A total of 256 one-day-old male Arbor Acres broiler chicks were randomly assigned to four treatments with eight replicates of eight birds (eight birds per cage). Four treatment groups were designated as follows: 1) in the CON group, broilers fed a basal diet; 2) in the LPS group, LPS-challenged broilers fed a basal diet; 3) in the LPS + T1 group, LPS-challenged broilers fed a basal diet supplemented with 5.0 g/kg taurine; and 4) in the LPS + T2 group, LPS-challenged broilers fed a basal diet supplemented with 7.5 g/kg taurine. The LPS-challenged broilers were intraperitoneally injected with 1 mg/kg body weight (BW) of LPS at 16, 18, and 20 d of age, whereas the CON group received an injection of sterile saline. The results showed that broilers injected with LPS exhibited decreased (P < 0.05) the average daily gain (ADG) and the 21-d BW (P < 0.05), while taurine supplementation alleviated the negative effects of LPS. Additionally, the LPS-induced increases (P < 0.05) in serum alanine transaminase and aspartate transaminase activities were reversed by taurine supplementation. The taurines could alleviate the hepatic oxidative stress, with the presence of lower content of malondialdehyde (P < 0.05), higher content of glutathione (P < 0.05), and an increased glutathione peroxidase (GSH-Px) activity (P < 0.05). The concentrations of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the liver were measured by ELISA kits, and the result showed that dietary taurine supplementation prevented these cytokines increases in the liver of LPS-induced broilers. Taurine reduced the genes expression of IL-1ß, TNF-α, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase, whereas it boosted the expression levels of antioxidant-related genes (nuclear factor erythroid 2-related factor 2, heme oxygenase-1, glutamate-cysteine ligase catalytic subunit, and GSH-Px) in the liver of LPS-induced broilers. In conclusion, dietary taurine supplementation in broilers mitigated LPS-induced defects in ADG, oxidative stress, and inflammatory responses.

Ultrasound location of pulmonary nodules in video-assisted thoracoscopic surgery for precise sublobectomy.

BACKGROUND: We investigated the clinical value of accurate sublobectomy of pulmonary nodules using video-assisted thoracoscopy (VATS). In June 2017 to June 2019, single lung nodule patients who accepted thoracoscopic resection were included. Palpation and intraoperative ultrasound (IU) were used to localize lung nodules, and the success rate, location time and safety compared. Performance of lung nodule ultrasound was assessed. The success rate of IU localization of pulmonary nodules with different properties was studied. RESULTS: A total of 33 cases with single pulmonary nodules were included in the study, and 32 cases (97%) were successfully located by IU as opposed to 16 cases (48.5%) located by palpation (P < 0.05). Clear hypoechoic ultrasound images of nodules were obtained in all 32 cases, and the diameter of pulmonary nodules on ultrasound and CT were found to have a significant correlation (R = 0.860, P = 0.000). The average positioning time of IU was lower than that of the palpation group (P < 0.05). No complications occurred during ultrasound examination. The success rate of intraoperative ultrasonic localization between the pure ground-glass opacity (p-GGO) group and the mixed-ground-glass opacity (m-GGO) group was 90%, 100% (P = 0.526). CONCLUSIONS: In thoracoscopic surgery, IU can locate pulmonary nodules accurately, efficiently and safely, and also has a high degree of accuracy in locating different types of pulmonary nodules.

Curcumin Alleviates IUGR Jejunum Damage by Increasing Antioxidant Capacity through Nrf2/Keap1 Pathway in Growing Pigs.

The purpose of this study was to explore the effects of curcumin on IUGR jejunum damage. A total of 24 IUGR and 12 normal-birth weight (NBW) female crossbred (Duroc × Landrace × Large White) piglets were randomly assigned into three groups at weaning (26 days): IUGR group, NBW group, and IUGR + CUR group, which were fed diets containing 0 mg/kg (NBW), 0 mg/kg (IUGR) and 200 mg/kg (IUGR + CUR) curcumin from 26 to 115 days of age. Results showed that dietary supplementation with 200 mg/kg curcumin significantly increased the total superoxide dismutase (T-SOD) activity and decreased the malondialdehyde (MDA) content in the jejunum of IUGR pigs (p < 0.05). Results of real-time PCR showed that the IUGR + CUR group significantly increased the gene expression of NF-E2-related factor 2 (Nrf2) (p < 0.05), and increased the glutamate-cysteine ligase catalytic subunit (GCLC), superoxide dismutase 1 (SOD1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone dehydrogenase 1 (NQO1) mRNA expression compared with the IUGR group (p < 0.05). Western blot results showed that dietary supplementation with 200 mg/kg curcumin significantly increased the protein levels of Nrf2 and NQO1. Compared with the IUGR group, pigs in IUGR + CUR group showed significantly decreased the levels of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and interferon gamma (IFNγ) (p < 0.05), and increased the interleukin-2 (IL-2) level (p < 0.05). Dietary supplementation with 200 mg/kg curcumin significantly reduced cysteinyl aspartate specific proteinase 3 (caspase3), BCL2-associated X protein (bax), B-cellCLL/lymphoma 2 (bcl2), and heat-shock protein 70 (hsp70) mRNA expression, and increased occludin (ocln) mRNA expression (p < 0.05). In conclusion, dietary supplementation with 200 mg/kg curcumin can alleviate jejunum damage in IUGR growing pigs, through Nrf2/Keap1 pathway.

Dietary Leucine Supplementation Restores Serum Glucose Levels, and Modifying Hepatic Gene Expression Related to the Insulin Signal Pathway in IUGR Piglets.

This study aimed to investigate the effects of leucine with different levels on the insulin resistance in intrauterine growth restriction/retardation (IUGR) piglets. Thirty-two weaned piglets were arranged in a 2 × 2 factorial design and four treatments (n = 8) were as follow: (1) normal weaned piglets fed a basal diet (CONT), (2) IUGR weaned piglets fed a basal diet (IUGR), (3) normal weaned piglets fed a basal diet with the addition of 0.35% l-leucine (C-LEU), and (4) IUGR fed a basal diet with the addition of 0.35% l-leucine (I-LEU) for a 21-days trial. The results showed that compared to the IUGR group, the I-LEU group had higher final body weight and body weight gain, higher serum glucose concentrations, and higher serum insulin concentrations (p < 0.05). The gene expression of phosphatidylinositol 3-kinase p110 gamma, protein kinase adenosine monophosphate-activated γ 3-subunit, glycogen synthase kinase-3 alpha, and glucose transporter type 2 were increased in the I-LEU group as compared to the IUGR group (p < 0.05). It was concluded that dietary leucine supplementation restored serum glucose concentrations, increased insulin and creatinine concentrations, and enhanced protein kinase adenosine monophosphate-activated γ 3-subunit and glucose transporter type 2 expression, suggesting that leucine might play a positive role in hepatic lipid metabolism and glucose metabolism in IUGR.

Comparative Studies on the Antioxidant Profiles of Curcumin and Bisdemethoxycurcumin in Erythrocytes and Broiler Chickens.

The aim of this study was to investigate the antioxidant effects of curcumin and bisdemethoxycurcumin in both 2,20-azobis(2-amidinopropane) dihydrochloride (AAPH)-treated erythrocytes and broiler chickens. In experiment 1, chicken erythrocytes were employed to determine the antioxidant protection against AAPH treatment. Significant differences in hemolysis, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were observed between the control and curcuminoids-treated groups. In experiment 2, a total of 480 Arbor Acres broilers with the similar body weights were used. All of the birds were fed basal diet and basal diet with 150 mg/kg curcumin or bisdemethoxycurcumin, respectively. The results showed that curcuminoids significantly increased ADG, serum antioxidant capacity, the glutathione redox potential of small intestine, the gene expression of Nrf2, and its related antioxidant enzymes. Besides, curcumin and bisdemethoxycurcumin increased the antioxidant activities of serum, diet, and excreta while using the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt and ferric-reducing antioxidant power methods. It was concluded that bisdemethoxycurcumin, acting like curcumin, exerted good free radical scavenging activity in erythrocytes and improved the redox status in broilers, although there were some slight differences in their efficiency of antioxidant activities.

Whole exome sequencing identifies a rare variant in DAAM2 as a potential candidate in idiopathic pulmonary ossification.

BACKGROUND: Diffuse pulmonary ossification (DPO) is a rare disease characterized by bone tissue formation in the lung. DPO can be classified into idiopathic pulmonary ossification (IPO) and secondary pulmonary ossification. Cases with no identified etiology are classified as IPO. Variants of dishevelled associated activator of morphogenesis 2 (DAAM2) have been reported to be involved in the bone-resorption of osteoclasts. METHODS: Whole exome sequencing (WES) was used on samples from a patient with IPO and his healthy parents. The effects of all variants were determined using functional predictors (PolyPhen-2, SIFT, FATHMM and MutationTaster); variants existing only in the patient were further screened compared with his healthy parents. RESULTS: Forty deleterious variants, including 25 single nucleotide variants (SNVs) and 15 insertions and deletions (indels), were identified by WES. Finally, DAAM2 (c.G2960T:p.R987L) was screened by pathway analysis. CONCLUSIONS: We identified a novel variant of DAAM2 (c.G2960T:p.R987L) that might participate in the disease process of IPO.

Effect of Bamboo Leaf Extract on Antioxidant Status and Cholesterol Metabolism in Broiler Chickens.

The objective of this study was to investigate the effects of dietary bamboo leaf extract (BLE) on antioxidant status and cholesterol metabolism in broilers. One-day-old male Arbor Acres (576) broilers were randomly divided into six groups. A control group was fed a basal diet, while five experimental groups were supplemented with 1.0, 2.0, 3.0, 4.0, and 5.0g BLE per kg feed in their basal diets. The result indicated that BLE supplementation linearly improved eviscerated yield and decreased abdominal fat (p < 0.05). A significant decrease of serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) content was observed with BLE supplementation (p < 0.05). BLE supplementation linearly improved the total antioxidant capacity and catalase activity in both serum and liver (p < 0.05). Glutathione peroxidase was quadratically increased in serum and linearly increased in the liver with BLE supplementation (p < 0.05). The malonaldehyde content in liver showed a linear and quadratic decrease with BLE supplementation (p < 0.05). BLE supplementation up-regulated the mRNA expression of cholesterol 7- alpha hydroxylase and low-density lipoprotein receptor and downregulated 3-hydroxy3-methyl glutamates coenzyme A reductase mRNA expression in the liver. The antioxidant enzyme mRNA expressions were all up-regulated by BLE supplementation in the liver. In conclusion, supplemental BLE improved antioxidant status and cholesterol metabolism in broilers, which eventually led to a decrease of serum TG, LDL-c content, and abdominal fat deposition.

Peripheral blood CD4+ T cell populations by CD25 and Foxp3 expression as a potential biomarker: reflecting inflammatory activity in chronic obstructive pulmonary disease.

Background: The temporally dynamic changes of CD25 and Foxp3 expression in CD4+ T cells are initiated by T cell receptor (TCR) signals strength or frequency. There is a deficiency of peripheral markers for assessing COPD activity, and the current study was conducted to explore whether peripheral CD4+ T cell populations based on CD25 and Foxp3 expression could serve as an indicator for COPD inflammatory activity. Methods: The distribution and phenotypic characteristics of CD4+CD25±Foxp3± T cells from peripheral blood in different populations were determined by flow cytometry. The model for the differentiation of CD4+ T cells populations by CD25 and Foxp3 expression was explored in vitro. Results: The frequencies of peripheral CD4+CD25+Foxp3- T cells and CD4+CD25+Foxp3+ T cells were increased in AECOPD patients, whereas the frequency of CD4+CD25-Foxp3+ T cells was increased in SCOPD patients without receiving systemic treatment. Phenotypic analysis revealed that CD4+CD25+Foxp3- T cells, CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells had received antigenic stimulation and resembled central memory or effector memory T cells. The differentiation of CD4+ T cells populations by CD25 and Foxp3 expression was dictated by TCR signals. The paired study indicated that the frequencies of CD4+CD25+Foxp3- T cells, CD4+CD25+Foxp3+ T cells and CD4+CD25- Foxp3+ T cells were decreased while the frequency of CD4+CD25-Foxp3- T cells were increased in the same patients from AECOPD to convalescence. Conclusions: Collectively, we propose that the dynamic changes of CD4+ T cell populations by CD25 and Foxp3 expression could function as potential biomarkers for reflecting inflammatory activity in COPD.

Generation and Immune Regulation of CD4+CD25-Foxp3+ T Cells in Chronic Obstructive Pulmonary Disease.

The imbalance of CD4+Foxp3+ T cell subsets is reportedly involved in abnormal inflammatory immune responses in patients with chronic obstructive pulmonary disease (COPD). However, the possible role of CD4+CD25-Foxp3+ T cells in immune regulation in COPD remains to be investigated. In the current study, distribution and phenotypic characteristics of CD4+CD25-Foxp3+ T cells from peripheral blood were determined by flow cytometry; the origin, immune function and ultimate fate of CD4+CD25-Foxp3+ T cells were further explored in vitro. It was observed that circulating CD4+CD25-Foxp3+ T cells were significantly increased in stable COPD patients (SCOPD) and resembled central memory or effector memory T cells. Compared with peripheral CD4+CD25+Foxp3+ T cells, peripheral CD4+CD25-Foxp3+ T cells showed a lower expression of Foxp3, CTLA-4, HELIOS, and TIGIT, but a higher expression of CD127 and KI-67, suggesting that CD4+CD25-Foxp3+ T cells lost the expression of Tregs-associated molecules following the reduction in CD25. Unexpectedly, our study found that transforming growth factor-ß1 (TGFß1) decreased CD25 expression and played a critical role in the generation of CD4+CD25-Foxp3+ T cells from CD4+CD25+Foxp3+ T cells. Phenotypic analysis further revealed that both inducible and peripheral CD4+CD25-Foxp3+ T cells exhibited the features of activated conventional T cells. Importantly, memory CD4+CD25-Foxp3+ T cells facilitated the proliferation and differentiation of naïve CD4+ T cells into Th17 cells in the presence of IL-1ß, IL-6, IL-23, and TGFß1. Finally, a fraction of CD4+CD25-Foxp3+ T cells, exhibiting instability and plasticity, were converted to Th17 cells when subjected to Th17 cell-polarizing condition. Taken together, we propose that TGFß1 is responsible for the generation of CD4+CD25-Foxp3+ T cells, and these cells functionally exert an auxiliary effect on Th17 cells generation and might perpetuate chronic inflammation in COPD.

BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-ß pathway in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by continuous flow limitation and the immune system including macrophages and regulatory T lymphocytes (Tregs) is involved in COPD pathogenesis. In our previous study, we investigated that TGF-ß/BAMBI pathway was associated with COPD by regulating the balance of Th17/Treg. However, the role of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a pseudoreceptor of TGF-ß signalling pathway, in regulating the immune system of COPD patients has not been fully studied. Hence, we speculate that the pseudoreceptor BAMBI may play roles in the regulation of M2 macrophages to induce the differentiation of CD4+ naïve T cells into Tregs and influence the immune response in COPD. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy nonsmokers (n = 12), healthy smokers (n = 10) and COPD patients (n = 20). Naïve CD4+ T cells and monocytes-induced macrophages were used for coculture assays. The phenotypic characteristics of macrophages and Tregs were determined by flow cytometry. The expression levels of BAMBI and the TGF-ß/Smad pathway members in M2 macrophages were measured by a Western blot analysis. The monocyte-derived macrophages were stimulated with cigarette smoke extract (CSE, concentration of 0.02%) to simulate the smoking process in humans. pCMV-BAMBI was transfected into monocyte-derived M2 macrophages for subsequent co-culture assays and signalling pathway analysis. RESULTS: Our results showed that M2 macrophages could induce the differentiation of Tregs through the TGF-ß/Smad signalling pathway. In addition, monocyte-derived macrophages from COPD patients highly expressed BAMBI, and had a low capacity to induce Tregs differentiation. The expression of BAMBI and the forced expiratory volume in 1 second (FEV1%) were negatively correlated in COPD. Furthermore, overexpression of BAMBI promoted the conversion of M2 macrophages to M1 macrophages via the TGF-ß/Smad pathway. CONCLUSIONS: We demonstrated that BAMBI could promote the polarization process of M2 macrophages to M1 macrophages via the TGF-ß/Smad signalling pathway and that overexpression of BAMBI could decrease the ability of M2 macrophages to induce Treg differentiation. These findings may provide a potential mechanism by which blocking BAMBI could improve immune function to regulate COPD inflammatory conditions.

[Preliminary Study on the Biological Markers for I-IIb Stage Non-small Cell Lung Cancer Based on a Serum-peptidomics].

BACKGROUND: Non-small cell lung cancer (NSCLC) have the highest incidence of lung cancer which treatment principles are diagnosis and treatment as early as possible. Because of its insidious onset and lack of specific markers for early screening, most patients are at an advanced stage when diagnosed which results in a low 5-year survival rate and poor prognosis. Therefore Exploring a sensitive biomarker is the focus of current diagnosis and treatment of lung cancer. The aim of this study is to investigate the biological markers in serum of patients with I-IIb stage NSCLC by differential peptidomics analysis. METHODS: The serum peptidome was compared and analyzed among the groups of normal health controls, benign lung diseases and early stage NSCLC patients using a nano ultra-performance liquid chromatography combined with a quadrupole-orbitrap mass spectrometer. The differentially expressed polypeptides were identified and analyzed quantitatively to screen the tumor biomarkers for the early diagnosis of NSCLC patients. RESULTS: According to the Swiss-Prot database, a total of 545 polypeptides originated from 118 proteins were identified. The spectral numbers of serum polypeptides in each group were compared and a total of 201 polypeptides differentially expressed were found. Following a quantitative analysis of the above peptides, we found that there were 7 peptides with the coefficient of variation (CV) less than 30% and among them the peptide of QGAKIPKPEASFSPR from ITIH4 was down-regulated and the peptide of CDDYRLC from MGP was up-regulated in NSCLC group. CONCLUSIONS: The tumor biomarkers obtained by serum peptidome technology can provide a new clue for early diagnosis of NSCLC and the specific peptides hydrolyzed from ITIH4 and MGP may be the serum biological markers for early NSCLC patients.

Hydroxysafflor yellow A inhibits rat vascular smooth muscle cells proliferation possibly via blocking signal transduction of MEK-ERK1/2 / 中华心血管病杂志

<p><b>OBJECTIVE</b>To elucidate the effect of hydroxysafflor yellow A ( HYSA) on the proliferation of vascular smooth muscle cells (VSMCs) and the related mechanism.</p><p><b>METHODS</b>VSMCs derived from SD rats were treated with DMEC culture medium (Control), 10 ng/ml PDGF (PDGF group), pretreatment with HYSA at different doses (1, 5, 10, 20, 40, 60 µmol/L) for 24 h then cotreatment with PDGF. After 24 h, MTT assay, Western blot and immunohistochemical staining were performed to evaluate the inhibitory effects of HYSA on VSMCs proliferation.</p><p><b>RESULTS</b>HYSA inhibited PDGF induced VSMCs proliferation in a dose-dependent manner, dowregulated proliferating cell nuclear antigen (PCNA) expression and blocked PDGF activated PDGFR-MEK-ERK1/2 signaling pathway.</p><p><b>CONCLUSIONS</b>HYSA inhibits VSMCs proliferation possibly via downregulating the expression of PCNA and blocking MEK-ERK1/2 signal transduction in VSMCs.</p>

Changes of serum albumin level and systemic inflammatory response in inoperable non-small cell lung cancer patients after chemotherapy.

AIM: Hypoalbuminemia and systemic inflammatory response (SIR) parameters are a key role in the prognosis of cancer patients. We aim to investigate the changes of serum albumin level and SIR after chemotherapy, in patients with inoperable non-small cell lung cancer (NSCLC). The hypothesis is that improved serum albumin level may be beneficial to the SIR parameters and will reduce chemotherapy-induced toxicity. PATIENTS AND METHODS: Forty-nine stage III b or stage IV inoperable NSCLC patients were divided into two groups, depending on whether albumin administration was given before chemotherapy. The Karnofsky performance score (KPS), nutritional status including body mass index (BMI), and serum albumin level were evaluated. SIR was evaluated by investigating the changes of the C-reactive protein (CRP), calculating the neutrophil lymphocyte ratio (NLR), and the platelet lymphocyte ratio (PLR), before and after chemotherapy. The chemotherapy-induced toxicity was also evaluated. RESULTS: In the group of patients without albumin administration before chemotherapy, the serum albumin level was significantly decreased (P<0.05) and the CRP level was significantly increased than before (P<0.05). Significant correlations were noted between hypoalbuminemia and CRP increase (r=0.533 P<0.05), between hypoalbuminemia and NLR≥5 (r=0.574 P<0.01) after chemotherapy. Patients with hypoalbuminemia developed more severe chemotherapy-induced toxicity symptoms. In the group of patients with albumin administration before chemotherapy, there was no significant difference in serum albumin level before and after chemotherapy (P>0.05), even though the patients may have been malnourished or diagnosed with pleural effusions. There were no significant changes in the SIR parameters. CONCLUSION: Early assessment of the serum albumin level in patients with inoperable NSCLC and their improvement in the serum albumin level may suggest that there are beneficial effects after chemotherapy.

Corrosive induced carcinoma of esophagus after 58 years.

Patients with corrosive induced esophageal strictures have an increased risk of esophageal carcinoma. We present a case of a 61-year-old man who ingested sulfuric acid at the age of 3 years and then developed dysphagia at late follow-up. In 2010, he presented to the outpatient clinic with weight loss and worsening dysphagia to both solids and liquids. A barium swallow radiograph and endoscopy demonstrated a long stricture in the middle third of the esophagus. Ivor-Lewis esophagectomy was undertaken via an upper midline abdominal incision and a right thoracotomy, and pathologic examination of the resection specimen confirmed a well-differentiated esophageal squamous cell carcinoma. Twenty-two months postoperatively, he reports no dysphagia, and no tumor recurrence was evident during follow-up.

Neoadjuvant chemoradiotherapy could improve survival outcomes for esophageal carcinoma: a meta-analysis.

BACKGROUND: The effectiveness of neoadjuvant chemoradiotherapy in patients with resectable esophageal carcinoma remains controversial. AIMS: The purpose of this study was to assess the effect of neoadjuvant chemoradiotherapy on operable esophageal carcinoma. METHODS: We searched PubMed, EMBASE and Web of Science and identified all randomized controlled trials published up until July 2011 that directly compared chemoradiotherapy followed by surgery with surgery alone. The risk ratio (RR) with its corresponding 95 % confidence interval (CI) was the principal measure of effects. RESULTS: Twelve randomized controlled trials that met our inclusion criteria were identified. Chemoradiotherapy followed by surgery was associated with significantly improved 1-year (RR = 0.86, 95 % CI = 0.74-0.98, P = 0.03), 3-year (RR = 0.82, 95 % CI = 0.73-0.92, P = 0.0007) and 5-year (RR = 0.83, 95 % CI = 0.72-0.96, P = 0.01) survival times compared with surgery alone. Subgroup analysis suggested that this benefit was associated with concurrent chemoradiotherapy but not sequential chemoradiotherapy. Neoadjuvant chemoradiotherapy could improve 3- and 5-year survival outcomes for squamous cell carcinoma but not those for adenocarcinoma. Postoperative morbidity (RR = 0.97, 95 % CI = 0.86-1.09, P = 0.56) and mortality (RR = 1.56, 95 % CI = 0.97-2.50, P = 0.07) did not increase in patients treated by chemoradiotherapy. CONCLUSIONS: Our findings revealed that compared with surgery alone, neoadjuvant chemoradiotherapy was associated with improved 1-, 3- and 5-year survival times, but not associated with increased postoperative morbidity and mortality in patients with esophageal carcinoma.