Correlation between white blood cell count and intestinal resection in patients with acute mesenteric vein thrombosis.

OBJECTIVE: Acute mesenteric vein thrombosis (AMVT) is an acute abdominal disease with onset, rapid progression, and extensive intestinal necrosis that requires immediate surgical resection. The purpose of this study was to determine the risk factors for nosocomial intestinal resection in patients with AMVT. METHODS: We retrospectively analysed 64 patients with AMVT diagnosed by CTA at the Affiliated Hospital of Kunming University of Science and Technology from January 2013 to December 2021. We compared patients who underwent intestinal resection (42 patients) with those who did not undergo intestinal resection (22 patients). The area under the ROC curve was evaluated, and a forest map was drawn. RESULTS: Among the 64 patients, 6 (9.38%) had a fever, 60 (93.75%) had abdominal pain, 9 (14.06%) had a history of diabetes, 8 (12.5%) had a history of deep vein thrombosis (DVT), and 25 (39.06%) had ascites suggested by B ultrasound or CT after admission. The mean age of all patients was 49.86 ± 16.25 years. The mean age of the patients in the enterectomy group was 47.71 ± 16.20 years. The mean age of the patients in the conservative treatment group (without enterectomy) was 53.95 ± 15.90 years. In the univariate analysis, there were statistically significant differences in leukocyte count (P = 0.003), neutrophil count (P = 0.001), AST (P = 0.048), total bilirubin (P = 0.047), fibrinogen (P = 0.022) and DD2 (P = 0.024) between the two groups. The multivariate logistic regression analysis showed that admission white blood cell count (OR = 1.153, 95% CI: 1.039-1.280, P = 0.007) was an independent risk factor for intestinal resection in patients with AMVT. The ROC curve showed that the white blood cell count (AUC = 0.759 95% CI: 0.620-0.897; P = 0.001; optimal threshold: 7.815; sensitivity: 0.881; specificity: 0.636) had good predictive value for emergency enterectomy for AMVT. CONCLUSIONS: Among patients with AMVT, patients with a higher white blood cell count at admission were more likely to have intestinal necrosis and require emergency enterectomy. This study is helpful for clinicians to accurately determine whether emergency intestinal resection is needed in patients with AMVT after admission, prevent further intestinal necrosis, and improve the prognosis of patients.

Smad3 promotes cancer progression by inhibiting E4BP4-mediated NK cell development.

TGF-ß is known to influence tumour progression. Here we report an additional role of Smad3 in the tumour microenvironment regulating cancer progression. Deletion or inhibition of Smad3 in the tumour microenvironment suppresses tumour growth, invasion and metastasis in two syngeneic mouse tumour models. Smad3-/- bone marrow gives rise to an expanded NK cell population with enhanced tumour-suppressive activities in vivo, and promotes differentiation of NK cells ex vivo. We identify E4BP4/NFIL3 as a direct Smad3 target gene critical for NK cell differentiation. Smad3 suppresses transcription of IFN-γ via E4BP4 in a T-bet independent manner. Therefore disruption of Smad3 enhances both the E4BP4-mediated NK cell differentiation and anti-cancer effector functions in vivo and in vitro. Furthermore, systemic treatment with a Smad3 inhibitor SIS3 effectively suppresses cancer progression. In summary, suppression of NK cell-mediated immunosurveillance via the Smad3-E4BP4 axis contributes to cancer progression. We propose targeting Smad3-dependent tumour microenvironment may represent an effective anti-cancer strategy.

TGF-ß/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis.

Myofibroblasts are a main cell-type of collagen-producing cells during tissue fibrosis, but their origins remains controversial. While bone marrow-derived myofibroblasts in renal fibrosis has been reported, the cell origin and mechanisms regulating their transition into myofibroblasts remain undefined. In the present study, cell lineage tracing studies by adoptive transfer of GFP+ or dye-labelled macrophages identified that monocyte/macrophages from bone marrow can give rise to myofibroblasts via the process of macrophage-myofibroblast transition (MMT) in a mouse model of unilateral ureteric obstruction. The MMT cells were a major source of collagen-producing fibroblasts in the fibrosing kidney, accounting for more than 60% of α-SMA+ myofibroblasts. The MMT process occurred predominantly within M2-type macrophages and was regulated by TGF-ß/Smad3 signalling as deletion of Smad3 in the bone marrow compartment of GFP+ chimeric mice prevented the M2 macrophage transition into the MMT cells and progressive renal fibrosis. In vitro studies in Smad3 null bone marrow macrophages also showed that Smad3 was required for TGF-ß1-induced MMT and collagen production. In conclusion, we have demonstrated that bone marrow-derived fibroblasts originate from the monocyte/macrophage population via a process of MMT. This process contributes to progressive renal tissue fibrosis and is regulated by TGF-ß/Smad3 signalling.

Latent transforming growth factor-ß1 protects against bleomycin-induced lung injury in mice.

Transforming growth factor (TGF)-ß1 is a potent mediator known to induce lung fibrosis. However, the role of latent TGF-ß1 in lung inflammation and fibrosis is unclear. To investigate the role of circulating latent TGF-ß1 in bleomycin-induced lung injury, lung disease was induced in keratin-5 promoter-driven TGF-ß1(wt) transgenic (Tg) mice by bleomycin. The role of latent TGF-ß1 in pulmonary inflammation and fibrosis was examined at Days 7 and 28 after administration of bleomycin. Compared with littermate wild-type (WT) mice, TGF-ß1(wt) Tg mice had over twofold-higher levels of latent TGF-ß1 in both plasma and lung tissue, and were protected from bleomycin-induced pulmonary inflammation, such as up-regulation of IL-1ß, TNF-α, and macrophage chemotactic protein-1, and infiltration of CD3(+) T cells and F4/80(+) macrophages. In addition, the severity of lung fibrosis with massive collagen matrix accumulation was markedly reduced in TGF-ß1(wt) Tg mice. These protective effects were associated with higher levels of Smad7 and inactivation of both NF-κB and TGF-ß/Smad3 signaling pathways, in addition to an increase in forkhead box P3 (Foxp3)-dependent regulatory T cells, but inhibition of T helper 17-mediated lung injury. In summary, mice overexpressing latent TGF-ß1 are protected from bleomycin-induced lung injury. Triggering the Smad7 negative feedback mechanism to inhibit both NF-κB and TGF-ß/Smad signaling pathways, and enhancing the regulatory T cell response to counter-regulate T helper 17-mediated lung injury, are potential mechanisms by which latent TGF-ß1 protects against bleomycin-induced lung injury.

[Validity of Caprini risk assessment model in identifying high venous thromboembolism risk patients among hospitalized medical patients].

OBJECTIVE: To test the validity of Caprini risk assessment model in identifying high venous thromboembolism (VTE) risk patients among hospitalized medical patients. METHODS: A retrospective case-control study was performed among hospitalized medical patients admitted into West China Hospital, Sichuan University from January 2010 and December 2011. A total of 218 patients with definite VTE during hospitalization were recruited. And 394 controls were randomly selected from the patients without VTE admitted into the same departments within the same period. The risks of both cases and controls were retrospectively assessed with the Caprini risk assessment model. RESULTS: The average Caprini cumulative risk score in cases was significant higher than that in controls (4.9 ± 2.6 vs 3.2 ± 2.0, P = 0.000). There was no significant difference in the risk of VTE between the patients at a low risk by Caprini model and those at a moderate risk (OR = 1.26, 95%CI: 0.62-2.56). Compared with a low risk, those with a high risk were associated with 2.00-fold increased risk of VTE (95%CI: 1.10-3.61), a highest risk was associated with 5.76-fold increased risk of VTE (95%CI: 3.24-10.24) (both P < 0.05) . When further stratifying the highest risk level with cumulative risk score ≥ 5 into 5-6, 7-8, and ≥ 9 risk level, the patients with score 5-6 were associated with 4.15-fold increased risk of VTE (95%CI: 2.28-7.56), those with score 7-8 11.13-fold increased risk of VTE (95%CI: 4.88-25.36) and those with score ≥ 9 21.00-fold increased risk of VTE (95%CI: 6.34-69.52) compared with low risk counterparts. CONCLUSION: Caprini risk assessment model can effectively and quantitatively assess the risk of VTE among hospitalized medical patients based on their individual VTE risk factors.

Relationship between 6-minute walk test and pulmonary function test in stable chronic obstructive pulmonary disease with different severities.

BACKGROUND: The relationship between the 6-minute walk test (6MWT) and pulmonary function test in stable chronic obstructive pulmonary disease (COPD) remains unclear. We evaluate the correlation of 6MWT and spirometric parameters in stable COPD with different severities. 6MWT data assessed included three variables: the 6-minute walk distance (6MWD), 6-minute walk work (6MWORK), and pulse oxygen desaturation rate (SPO(2)%). METHODS: 6MWT and pulmonary function test were assessed for 150 stable COPD patients with different severities. Means and standard deviations were calculated for the variables of interest. Analysis of variance was performed to compare means. Correlation coefficients were calculated for 6MWT data with the spirometric parameters and dyspnea Borg scale. Multiple stepwise regression analysis was used to screen pulmonary function-related predictors of 6MWT data. RESULTS: The three variables of 6MWT all varied as the severities of the disease. The 6MWD and 6MWORK both correlated with some spirometric parameters (positive or negative correlation; the absolute value of r ranging from 0.34 to 0.67; P < 0.05) in severe and very severe patients, and the SPO2% correlated with the dyspnea Borg scale in four severities (r = -0.33, -0.34, -0.39, -0.53 respectively; P < 0.05). The 6MWD was correlated with the 6MWORK in four severities (r = 0.56, 0.57, 0.72, 0.81 respectively, P < 0.05), and neither of them correlated with the SPO(2)%. The percent of predicted forced expiratory volume in 1 second (FEV(1)% predicted) and residual volume to total lung capacity ratio (RV/TLC) were predictors of the 6MWD, and the maximum voluntary ventilation (MVV) was the predictor of the 6MWORK. CONCLUSIONS: 6MWT correlated with the spirometric parameters in severe and very severe COPD patients. 6MWT may be used to monitor changes of pulmonary function in these patients.

Validation of the Caprini risk assessment model in Chinese hospitalized patients with venous thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE) occurs frequently in at-risk hospitalized patients, and prophylaxis of VTE is significantly underused. We sought to preliminarily assess the validity of Caprini risk assessment model, a famous individual VTE risk assessment model, in Chinese hospitalized patients with VTE. MATERIALS AND METHODS: We undertook a retrospective study combined with a follow-up study among 347 confirmed VTE patients from a Chinese hospital. RESULTS: Compared with the other two risk assessment models (RAMs), Caprini model can classify much more VTE patients into high or highest risk level and the differences were statistically significant (Caprini model vs Kucher model, p<0.0001; Caprini model vs the Padua Prediction Score, p<0.0001). Caprini model exhibited much more effect at assessing patient's VTE risk among surgical patients than nonsurgical patients(average risk score, 5.71 ± 2.54 vs 4.36 ± 2.51, p<0.0001; by Wilcoxon rank sum test, p=0.001 in favor of the prediction effect of the RAM in surgical patients). Kaplan-Meier analysis showed that patients classified into low and highest risk level by Caprini model had increased hazard for VTE recurrence when compared with patients classified into moderate and high risk level, but the result was not statistically significant (p=0.222). CONCLUSIONS: Our study preliminarily suggests that the Caprini risk assessment model is a practical and effective tool to assess the risk of VTE among unselected Chinese inpatients and may also be useful in predicting the risk of VTE recurrence. However, future studies with control group and prospective validation of the model in Chinese inpatients are needed.

Long-term non-invasive positive pressure ventilation in severe stable chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: The evidence for non-invasive positive pressure ventilation (NIPPV) used in patients with severe stable chronic obstructive pulmonary disease (COPD) is insufficient. The aim of the meta-analysis was to assess the treatment effects of long-term NIPPV on gas change, lung function, health-related quality of life (HRQL), survival and mortality in severe stable COPD patients. METHODS: Randomized controlled trials (RCTs) and crossover studies comparing the treatment effects of NIPPV with conventional therapy were identified from electronic databases and reference lists from January 1995 to August 2010. Two reviewers independently assessed study quality. Data were combined using Review Manager 5.0. Both pooled effects and 95% confidence intervals were calculated. RESULTS: Five RCTs and one randomized crossover study with a total of 383 severe stable COPD patients were included. NIPPV improved gas change significantly when using a higher inspiratory positive airway pressures. The weighted mean difference (WMD) for the partial pressure of carbon dioxide in artery (PaCO2) was -3.52 (-5.26, -1.77) mmHg and for the partial pressure of oxygen in artery (PaO2) 2.84 (0.23, 5.44) mmHg. There were significant improvements in dyspnea and sleep quality, but gained no benefits on lung function. The standardized mean difference (SMD) for the forced expiratory volume in 1 second (FEV(1)) was 0.00 (0.29, 0.29). And the benefits for exercise tolerance, mood, survival and mortality remained unclear. CONCLUSIONS: Patients with severe stable COPD can gain some substantial treatment benefits when using NIPPV, especially improvements in gas change, dyspnea and sleep quality. Studies of high methodological quality with large population, especially those based on a higher inspiratory positive airway pressures are required to provide more evidences.

Salmeterol/fluticasone treatment reduces circulating C-reactive protein level in patients with stable chronic obstructive pulmonary disease.

BACKGROUND: Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting beta(2)-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients. METHODS: An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups (1:1) to receive either the combination of 50 microg salmeterol and 500 microg fluticasone twice daily (n = 61), or the combination of 206 microg albuterol and 36 microg ipratropium q.i.d (n = 61) over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment. RESULTS: Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein (-1.73 vs. 0.08 mg/L, respectively, P < 0.05) after 6-month treatment. Forced expiratory volume in one second (FEV(1)) and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV(1) and St George's Respiratory Questionnaire total scores compared with those who did not (185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P < 0.01). CONCLUSION: Salmeterol/fluticasone treatment reduced circulating C-reactive protein concentration in clinically stable moderate-to-severe chronic obstructive pulmonary disease patients after 6-month treatment.

Helicobacter pylori seroprevalence in patients with obstructive sleep apnea syndrome among a Chinese population.

OBJECTIVE: To investigate the seroprevalence of Helicobacter pylori (H. pylori) in patients with obstructive sleep apnea syndrome (OSAS), and to determine any association between H. pylori infection and severity of OSAS. METHODS: Two hundred and forty-three subjects were recruited in this cross-sectional study at the Department of Respiratory Medicine in the West China Hospital, Sichuan, P. R. China, from October 2006 to April 2008. Polysomnography (PSG) was used to determine the apnea-hypopnea index (AHI), and enzyme-linked immunosorbent assay was used to test H. pylori IgG. According to the AHI, subjects were divided into 4 groups: the control group (AHI < 5/hours), patients with mild OSAS group (AHI: 5-14/hours), moderate OSAS group (AHI: 15-29/hours), and severe OSAS group (AHI: > or = 30/hours). RESULTS: The prevalence of H. pylori infection in patients with OSAS was 75.5%, and in the controls it was 53.4% (p=0.000). The prevalence of H. pylori infection in patients with mild OSAS was 57.1%, with moderate OSAS was 76.5%, and with severe OSAS was 90.9%. There were significant differences between patients with moderate and severe OSAS and the controls, as well as among the mild, moderate, and severe OSAS groups. CONCLUSION: Helicobacter pylori infection may be associated with OSAS. In addition, increased severity of OSAS might be associated with higher seroprevalence of H. pylori.

[Interventions of enalapril on airway inflammation in rat models induced by acrolein].

OBJECTIVE: To observe the effect of enalapril on airway inflammation in rat models induced by inhaling acrolein and to explore its mechanism. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 4 groups (n = 6): 1) control group (inhaled 0.9% normal saline for 3 hours, twice every day); 2) enalapril self-control group [intragastrically administrated enalapril 0.5 mg/(kg x d) only]; 3) model group (stimulated with 4 mg/L acrolein for 3 hours, twice every day); 4) enalapril interventive group [inhaled acrolein and intragastrically administrated enalapril 0.5 mg/(kg x d)]. Lung tissue was acquired after the rats were sacrificed on the 21st day. Histopathology examination of lung tissue section stained with HE. Nuclear factor-kappa B and angiotensin II were assayed by immunohistochemistry. Nuclear factor-kappa B were also detected by Western blot. IL-8 and TNF-alpha in BALF were estimated by ELISA. RESULTS: Compared with the control group and the enalapril interventive group, the expression of Ang II and NF-kappa B in the model group was significantly increased (all P < 0.05). Compared with the control group and the enalapril interventive group, the ratio of NF-kappa B nuclear translocation in the model group was remarkably increased. Neutrophils and the level of IL-8 and TNF-alpha in BALF were higher in model group than those in control group. Enalapril can suppress them significantly. CONCLUSION: Acrolein inhalation could upregulate the expression of Ang II and NF-kappa B and also increase nuclear translocation ratio of NF-kappa B. Enalapril can suppress the airway inflammation induced by acrolein.