The Relationship Between Prognostic Nutritional Indexes and the Clinical Outcomes of Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: Nutritional status is related to the clinical outcomes of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The aim of this study was to investigate the association between nutritional status, measured by the prognostic nutritional index (PNI), and adverse hospitalization outcomes in patients with AECOPD. Methods: Consecutive AECOPD patients admitted to the First Affiliated Hospital of Sun Yat-sen University between January 1, 2015 to October 31, 2021 were enrolled. We collected the clinical characteristics and laboratory data of patients. Multivariable logistic regression models were developed to assess the relationship between the baseline PNI and adverse hospitalization outcomes. A generalized additive model (GAM) was used to identify any non-linear relationship. In addition, we performed a subgroup analysis to tested the robustness of the results. Results: A total of 385 AECOPD patients were involved in this retrospective cohort study. Based on the tertiles of PNI, patients in the lower tertiles of PNI showed more worse outcome incidence (30 [23.6%] versus 17 [13.2%] versus 8 [6.2%]; p < 0.001). Multivariable logistic regression analysis revealed that the PNI were independently associated with adverse hospitalization outcomes after adjustment for confounding factors (Odds ratio [OR] = 0.94, 95% CI: 0.91 to 0.97, P < 0.0001). After adjusting for confounders, smooth curve fitting showed a saturation effect, suggesting that the relationship between the PNI and adverse hospitalization outcomes was nonlinear. Two-piecewise linear regression model suggested that the incidence of adverse hospitalization outcomes significantly decreased with PNI level up to the inflection point (PNI = 42), and PNI was not associated with adverse hospitalization outcome after that point. Conclusion: Decreased PNI levels at admission were determined to be associated with adverse hospitalization outcomes in patients with AECOPD. The results obtained in this study may potentially assist clinicians optimize risk evaluations and clinical management processes.

Association of Red Cell Index and Adverse Hospitalization Outcomes in Chronic Obstructive Pulmonary Disease Patients with Acute Exacerbation: A Retrospective Cohort Study.

Purpose: Previous studies have shown that the red cell index (RCI) can be considered as a simple and useful method to evaluate respiratory function. However, at present its association with adverse hospitalization outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not fully understood. Our study aimed to examine the relationship between adverse hospitalization outcomes and RCI among AECOPD patients. Patients and Methods: We performed a retrospective analysis of consecutive patients from January 2015 to October 2021. In this study, RCI was the independent variable, measured at baseline, and adverse hospitalization outcome was the dependent variable. According to the RCI median (RCI=2.221), we divided 377 patients into two roughly equal groups (188 and 189, respectively). Next, the association between RCI and adverse hospitalization outcomes was explored using multivariable logistic regression models. To identify any non-linear relationship, a generalized additive model (GAM) was employed. Results: With a total of 377 patients with AECOPD, we divided them into two roughly equal groups to compare the clinical factors and RCI levels. The patients in the higher RCI group showed poorer outcome incidence (18 [9.57%] vs 31 [16.40%]; p = 0.049). After accounting for potential confounders, the results showed that RCI was positively associated with adverse hospitalization outcomes (odds ratio [OR] = 1.15, 95% CI: 1.01-1.32). In addition, a non-linear relationship was detected between RCI and adverse hospitalization outcomes, which had an inflection point of 3.2. There were odds ratios and confidence intervals of 0.8 (0.7-1.0) and 1.3 (1.2-1.4) on the left and right sides of the inflection point, respectively. Conclusion: The RCI and adverse hospitalization outcomes exhibited a non-linear relationship in the AECOPD patients. RCI is strongly positively correlated with adverse hospitalization outcomes when it was greater than 3.2.

[Interaction between glycogen synthase kinase-3ß and endoplasmic reticulum stress is involved in high glucose-induced injury in human umbilical vein endothelial cells].

OBJECTIVE: To explore the role of the interaction between glycogen synthase kinase-3ß (GSK-3ß) and endoplasmic reticulum stress (ERS) in the high glucose (HG)-induced injury in human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs treated with 40 mmol/L glucose for 24 h were examined for expression levels of GSK-3ß, GRP78, CHOP and cleaved caspase-3 protein using Western blotting. The cell viability was examined using CCK-8 assay and cell apoptosis was detected with Hoechst 33258 nuclear staining and photofluorography. The intracellular level of reactive oxygen species (ROS) was measured with dichlorfluoresein staining and photofluorography. Mitochondrial membrane potential (MMP) was tested by rhodamine 123 (Rh123) staining and photofluorography. RESULTS: Treatment of HUVECs with 40 µmol/L glucose for 3-24 h activated GSK-3ß in a time-dependent manner, leading to significantly down-regulated expression of phosphorylated (p)-GSK-3ß (P<0.05). HG exposure of the cells for 1-24 h induced ERS, evidenced by time-dependently up-regulated expression of GRP78 and CHOP (P<0.05). LiCl, an inhibitor of GSK-3ß, attenuated HG-induced ERS and significantly lowered the expression levels of GRP78 and CHOP (P<0.01). 4-PBA, an inhibitor of ERS, obviously ameliorated the activation of GSK-3ß by HG as shown by the increase in p-GSK-3ß expression level (P<0.01). HG exposure for 24 h induced obvious injuries in HUVECs, which exhibited decreased cell viability, increased cell apoptosis, increased expression of cleaved caspase-3 and ROS generation, and loss of MMP. Pretreatment of the cells with LiCl or 4-PBA for 60 min before HG exposure significantly lessened the cell injuries (P<0.01). CONCLUSION: Interactions between GSK-3ß and ERS occur in HUVECs exposed to HG and participate in HG-induced cell injuries.

Case-Control Study on Impact of the Telomerase Reverse Transcriptase Gene Polymorphism and Additional Single Nucleotide Polymorphism (SNP)- SNP Interaction on Non-Small Cell Lung Cancers Risk in Chinese Han Population.

AIMS: To investigate the impact of telomerase reverse transcriptase (TERT) gene polymorphism and additional SNP-SNP interaction on non-small cell lung cancer (NSCLC) risk in Chinese population. METHODS: A total of 828 participants (526 males, 302 females), with a mean age of 71.3 ± 15.7 years old, were selected, including 410 NSCLC patients and 418 normal participants. Logistic regression was performed to investigate association between single nucleotide polymorphism (SNP) and NSCLC risk. Generalized multifactor dimensionality reduction (GMDR) was used to analysis the interaction among four SNPs. RESULTS: Non-small cell lung cancer risk was significantly higher in carriers of G allele of the rs2736100 polymorphism than those with TT (TG + GG vs. TT, adjusted OR (95%CI = 1.68 (1.28-2.07). In addition, we also found that NSCLC risk was also significantly higher in carriers of A allele of the rs2736098 polymorphism than those with GG (GA + AA vs. GG, adjusted OR (95%CI) = 1.52 (1.19-1.93). GMDR analysis indicated that there was a significant two-locus model (P = 0.0100) involving rs2736098 and rs2736100, indicating a potential gene-gene interaction between rs2736098 and rs2736100. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%. We found that patients with GA or AA of rs2736098 and TG or GG of rs2736100 genotype have the highest NSCLC risk, compared to patients with GG of rs2736098 and TT of rs2736100 genotype, OR (95%CI) was 2.52 (1.68-3.68), after covariates adjustment. CONCLUSIONS: Minor allele of rs2736098 and rs2736100 in TERT gene and interaction between the two SNP were associated with increased risk of NSCLC risk.

The serum glucan level and pathological changes of antifungal treatment for lower respiratory tract infection of Candida albicans.

Due to the fact that Candida albicans colonizes in the upper respiratory tracts of healthy people, whether or not its isolation from airway secretions is sufficient to warrant treatment remains controversial. The animal models of immunosuppressive rats with pulmonary candidiasis were established by the intratracheal inoculating suspensions of C. albicans, and the animals were divided into the following three groups: (1) antifungal treatment group, (2) saline control group, and (3) blank control group. We noted the following in our studies: (1) The fungal load of the saline control group gradually increased such that it was higher than those of the antifungal treated group and was significant from the fourth day of treatment (P < 0.01). (2) The serum (1,3)-ß-D-glucan (BG) in the saline control group also gradually increased so that it was significantly higher than found with the treated group by the sixth day of treatment (P < 0.05), and in fact, the rank of pulmonary colony count and BG in the two groups at different time points showed an almost perfect linear correlation. (3) The median survival period of the rats in the antifungal treated group and saline control group was 15 and 8 days respectively, no rats died in the blank control group. (4) The lung lesions from the saline control group gradually became more aggravated than those in the antifungal treated group; no significant pathological changes were found in the blank control group. Antifungal treatment (micafungin) is capable of efficaciously decreasing the lung fungal burden, and continuous monitoring of BG is useful for the evaluation of therapeutic effect of antifungals. Infection of C. albicans with associated pathological damage implies the need for antifungal therapy.

Evaluation of galactomannan enzyme immunoassay and quantitative real-time PCR for the diagnosis of invasive pulmonary aspergillosis in a rat model.

Since there is no consensus about the most reliable assays to detect invasive aspergillosis from samples obtained by minimally invasive or noninvasive methods, we compared the efficacy of an enzyme-linked immunosorbent assay (ELISA) for galactomannan (GM) detection and quantitative real-time PCR assay (qRT-PCR) for the diagnosis of invasive pulmonary aspergillosis. Neutropenic, male Sprague-Dawley rats (specific pathogen free; 8 weeks old; weight, 200 ± 20 g) were immunosuppressed with cyclophosphamide and infected with Aspergillus fumigatus intratracheally. Tissue and whole blood samples were harvested on days 1, 3, 5, and 7 post-infection and examined with GM ELISA and qRT-PCR. The A. fumigatus DNA detection sequence was detected in the following number of samples from 12 immunosuppressed, infected rats examined on the scheduled days: day 1 (0/12), day 3 (0/12), day 5 (6/12), and day 7 (8/12) post-infection. The sensitivity and specificity of the qRT-PCR assay was 29.2% and 100%, respectively. Receiver operating characteristic curve (ROC) analysis indicated a Ct (cycle threshold) cut-off value of 15.35, and the area under the curve (AUC) was 0.627. The GM assay detected antigen in sera obtained on day 1 (5/12), day 3 (9/ 12), day 5 (12/12), and day 7 (12/12) post-infection, and thus had a sensitivity of 79.2% and a specificity of 100%. The ROC of the GM assay indicated that the optimal Ct cut-off value was 1.40 (AUC, 0.919). The GM assay was more sensitive than the qRT-PCR assay in diagnosing invasive pulmonary aspergillosis in rats.

Interleukin-12 and interleukin-2 alone or in combination against the infection in invasive pulmonary aspergillosis mouse model.

Aspergillus fumigatus is an intracellular opportunistic fungus causing invasive pulmonary mycosis, characterised by hyphal invasion and destruction of pulmonary tissue. Th1 cytokines could enhance fungicidal activity. The effects from the combination of interleukin-12 (IL-12) and IL-2 are rarely known in invasive pulmonary aspergillosis infection. To assess the cleaning of A. fumigatus infection in the pulmonary tissues by IL-12 and IL-2, interferon-γ (IFN-γ) was detected in the sera using ELISA, quantification of IFN-γ mRNA using real-time RT-PCR and lung Colony-forming unit was assayed by cultivation. Morphology was analysed by histopathological examination. Our results showed that IL-12 and/or IL-2 could enhance the IFN-γ expression in the pulmonary tissue, reduce the colony load in the pulmonary tissue and increase the survival rate of mouse. The combination of IL-12 and IL-2 could assist in increasing the IFN-γ expression in the pulmonary tissue, but neither reduce colony load in the pulmonary tissue nor increase the survival rate of mouse significantly. It was demonstrated that IL-12 and IL-2 were strong immunomodulatory cytokines as a prerequisite for protecting the host from infectious agents.

Retrospective analysis on the impact of tuberculosis on patients with systemic lupus erythematosus (SLE).

Up to now, there have been few reports concerning changes in lupus activity and immune indices of tuberculosis in patients with systemic lupus erythematosis (SLE). A retrospective investigation was given to survey the case data of SLE patients companied with tuberculosis that were treated in our hospital from 2001 to 2010 and compared with that of sex- and age-matched patients with single SLE. Changes in autoantibodies, lupus activity, inflammatory indices, positive rates of tuberculin (PPD) test and tuberculosis antibody (TB-Ab) of both groups were observed. It was indicated by results that ANA antibody level and positive rates of anti-Sm, anti-SSA and anti-SSB antibodies were significantly lower in the TB group than those in the control group (P < 0.05); C3 and C4 levels were significantly higher in the TB group than those in the control group; damage of hematological system (predominantly platelet) was less severe in the TB group than that in the control group (P < 0.05); no significant differences in IgG, IgM and IgA were noted between two groups (P > 0.05); ESR, C-reactive protein and LDH levels were significantly higher in the TB group than those in the control group (P < 0.05); PPD-IgG were significantly higher in the TB group than those in the control group (P < 0.05). These results suggested that after SLE patients were infected with tuberculosis, immune function was altered and lupus activity was inhibited as well.

Combined APACH II score and arterial blood lactate clearance rate to predict the prognosis of ARDS patients.

OBJECTIVE: To explore the easily applicable indicators of practical value to evaluate the prognosis of acute respiratory distress syndrome (ARDS). METHODS: Blood and biochemical tests and blood-gas analyses were performed upon entry into the ICUs, 12 h, 24 h, 48 h and 72 h after that in 72 ARDS patients (who were admitted to the ICUs of our hospital from January 2000 to December 2009). Then APACHE II scores were achieved by combining relevant physiological parameters and laboratory results. RESULTS: There was a statistical difference between the death group and survival group at different time points upon entering the ICUs in terms of APACHE II score, alveolar-arterial oxygen difference and arterial blood lactate clearance rate. PaO(2)/FiO(2) values were recorded to be statistically different between the death group and survival group 24 h, 48 h and 72 h, respectively after entry into the ICUs. In addition, registered linear regression existed between APACHE II score, alveolar-arterial oxygen difference or PaO(2)/FiO(2) value and time. APACHE II score 24 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve (AUC) standing respectively at 0.919 and 0.955. Arterial blood lactate clearance rate 12 h, 24 h, 48 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve (AUC) at 0.918, 0.918, 0.909 and 0.991, respectively. CONCLUSIONS: APACHE II score applied in combination with arterial blood lactate clearance rate is of clinical significance in assessing the prognosis of ARDS patients.

[Analysis of the risk factors of pulmonary fungal infections related to mechanical ventilation and prognosis of the patients].

OBJECTIVE: To investigate the risk factors of pulmonary fungal infections related to mechanical ventilation and the prognosis of patients. METHODS: A retrospective case-controlled study was conducted to analyze the culture results of the pulmonary secretions in patients with pulmonary fungal and nonfungal infections in association with mechanical ventilations. The risk factors of pulmonary fungal infections related to mechanical ventilation were identified and their impact on the clinical outcome of the patients was evaluated. RESULTS: Of the 127 patients included in this study, 81 (63.78%) were positive and 46 (36.22%) negative for pulmonary fungal infections according to the diagnostic criteria of ventilator-associated pneumonia (VAP). The mortality of the patients with fungal infection was 82.7%, significantly higher than that of patients with non-fungal infection (67.39%, chi2=3.910, P<0.05). Univariate analysis and multivariate logistic regression showed that such factors as old age, duration of mechanical ventilation, tracheal intubation or incision for over 7 days, diabetes, blood glucose over 6.1 mmol/L, multi-organ dysfunction, combined use of antibiotics, at least 3-time changes antibiotics, administration of glucocorticosteroid for over 7 days, and immunodepressant use were all the independence risk factors of pulmonary fungal infection related to mechanical ventilation. Old age, multi-organ dysfunction, blood glucose over 6.1 mmol/L, glucocorticosteroid use for over 7 days, anesthetic use for over 3 days and high APACHE III scores were the risk factors for mortality in patients with the infections. CONCLUSIONS: Pulmonary fungal infection associated to mechanical ventilation is often the results of presence of multiple risk factors, and early identification of these factors for timely antifungal treatment may improve the prognostics of the patients and help reduce the mortality rate.

[An experimental study of the therapeutic effect of interleukin-2 and interleukin-12 with and without amphotericin B on pulmonary fungal infection].

OBJECTIVE: To study the therapeutic effect of interleukin-2 (IL-2) and interleukin-12 (IL-12) with and without amphotericin B on pulmonary fungal infection of mice. METHODS: A mouse model of pulmonary invasive aspergillus fumigatus (IPA) infection was established and the mice were divided into different groups, treated with IL-2 and IL-12 with and without amphotericin B. The survival number of mice in 15 days and the colony count of lung tissue in the different groups were observed. RESULTS: IL-2, IL-12 and amphotericin B showed synergistic effect in prolonging the survival of the infected mice and reducing the colony count in the lung tissue. CONCLUSION: IL-2 and IL-12 are effective adjuvant therapeutic agents in the immunosuppressed hosts.