Clinical characteristics and risk factors for mortality in pneumonia-associated acute respiratory distress syndrome patients: a single center retrospective cohort study.

Background: Pathogenic diversity may have contributed to the high mortality of pneumonia-associated acute respiratory distress syndrome (p-ARDS). Metagenomics next-generation sequencing (mNGS) serves as a valuable diagnostic tool for early pathogen identification. However, its clinical utility in p-ARDS remains understudied. There are still limited researches on the etiology, clinical characteristics and risk factors for 28-day mortality in p-ARDS patients. Methods: A single center retrospective cohort study of 75 p-ARDS patients was conducted. Patients were categorized into survival and deceased groups based on their 28-day outcomes. A comprehensive clinical evaluation was conducted, including baseline characteristics, laboratory indicators, outcomes and pathogen identification by mNGS and traditional microbiological testing. We then evaluated the diagnostic value of mNGS and identified clinical characteristics and risk factors for 28-day mortality in p-ARDS. Result: The overall ICU mortality was 26.67%, and the 28-day mortality was 57.33%, with 32 cases (42.67%) in the survival group, and 43 cases (57.33%) in the deceased group. Patients in the deceased group were older than those in the survival group (68(59,73) years vs. 59(44,67) years, P=0.04). The average lengths of ICU and hospital stay were 9(5,13) days and 14(7,21) days, respectively. The survival group had longer lengths of ICU and hospital stay (ICU: 11(7,17) days and hospital: 17(9,27) days) compared to the deceased group (ICU: 8(4,11) days and hospital: 12(6,19) days) (P<0.05). Survival patients exhibited lower Acute Physiology and Chronic Health Evaluation (APACHE) II score on the 3rd and 7th days, higher lymphocyte counts, higher CD3+ and CD8+ T cell counts compared to deceased patients (P<0.05). Multivariate logistic regression analysis identified age, APACHE II scores on 3rd and 7th days, CD8+ T cell count and length of ICU as independent risk factors for 28-day mortality in p-ARDS patients. mNGS demonstrated a significantly higher overall pathogen detection rate (70/75, 93.33%) compared to the traditional method (50/75, 66.67%, P=0.022). The average turnaround time (TAT) for mNGS was significantly shorter at 1(1,1) day compared to 4(3,5) days for the traditional method (P<0.001). Conclusion: Metagenome next-generation sequencing can be used as a valuable tool for identifying pathogens in p-ARDS, reducing diagnostic time and improving accuracy. Early application of mNGS alongside traditional methods is recommended for p-ARDS. Furthermore, older age, higher APACHE II scores, lower lymphocyte counts and lymphocyte subset counts were associated with increased mortality in p-ARDS patients, highlighting the importance of timely assessment of immune status and disease severity, especially in elderly.

Effect of Metagenomic Next-Generation Sequencing on Clinical Outcomes of Patients With Severe Community-Acquired Pneumonia in the ICU: A Multicenter, Randomized Controlled Trial.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) was previously established as a method that can increase the pathogen identification rate in patients with severe community-acquired pneumonia (SCAP). RESEARCH QUESTION: What is the impact on clinical outcomes of mNGS of BAL fluid (BALF) in patients with SCAP in the ICU? STUDY DESIGN AND METHODS: A multicenter, randomized controlled, open-label clinical trial was conducted in 10 ICUs. Patients were randomized in a 1:1 ratio to undergo BALF assessment with conventional microbiological tests (CMTs) only (ie, the CMT group) or BALF assessment with both mNGS and CMTs (ie, the mNGS group). The primary outcome was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a six-category ordinal scale or discharge from the ICU, whichever occurred first. RESULTS: A total of 349 patients were randomized to treatment between January 1, 2021, and November 18, 2022; 170 were assigned to the CMT group and 179 to the mNGS group. In the intention-to-treat analysis, the time to clinical improvement was better in the mNGS group than in the CMT group (10 days vs 13 days; difference, -2.0 days; 95% CI, -3.0 to 0.0 days). Similar results were obtained in the per-protocol analysis. The proportion of patients with clinical improvement within 14 days was significantly higher in the mNGS group (62.0%) than in the CMT group (46.5%). There was no significant difference in other secondary outcomes. INTERPRETATION: Compared with the use of CMTs alone, mNGS combined with CMTs reduced the time to clinical improvement for patients with SCAP. CLINICAL TRIAL REGISTRATION: ChiCTR2000037894.

Seasonal and interannual changes (2005-2021) of lake water quality and the implications for sustainable management in a rapidly growing metropolitan region, central China.

A series of restoration measures such as municipal wastewater treatment and aquaculture closures have been implemented in Wuhan City during recent years. In order to explore the impact of restoration measures and climate change on lake water quality, long-term (2005-2021) water quality data of 47 lakes were explored to reveal spatiotemporal changes in lake water quality. Percentages of polluted lakes were calculated according to six water-quality parameters, including total phosphorus (TP), ammonia nitrogen (NH3-N), chemical oxygen demand (COD), biological oxygen demand (BOD), chemical oxygen demand using potassium permanganate as oxidant (CODMn) and petroleum contamination (PET), at interannual and monthly timescales. At the interannual timescale, percentages of COD, BOD, CODMn and PET pollution decreased significantly, suggestive of water quality improvement during recent years. At the monthly timescale, low percentages of NH3-N and BOD pollution in March 2020 probably resulted from the sharp reduction in human activities during the COVID-19 lockdown. At the monthly timescale, temperature was positively correlated with percentage of CODMn pollution, but negatively correlated with percentage of NH3-N pollution; precipitation was negatively correlated with percentage of BOD pollution. The similarity of water-quality parameters generally decreased with an increase in geographical distance between each pair of lakes. However, the regression coefficients between the similarity of lake water quality and the geographical distance decreased with time, probably resulting from enhanced similarity of water quality parameters among all lakes with rapid urbanization. Our results highlight the importance of active restoration measures for sustainable management of lakes in Wuhan City, as well as in similar developing regions.

Hypoxia formation triggered by the organic matter from subsurface chlorophyll maximum in a large estuary-shelf system.

This study reports, for the first time, the role of shoreward transport of organic matter (OM) from subsurface chlorophyll maximum (SCM) in triggering hypoxia off the Pearl River Estuary (PRE, an outstanding example of typical estuary-shelf systems) based on field measurements. Compared to frequently observed hypoxia driven by surface eutrophication and terrestrial OM during large river discharge, we demonstrate that the upslope-transported SCM played a critical role in forming offshore hypoxia during low river discharge. Together with the plume-sourced OM trapped below the surface plume front, upslope-transported OM originating from the SCM accumulated underneath the pycnocline and consumed dissolved oxygen (DO), enhancing the bottom hypoxia. The DO consumption induced by the SCM-associated OM was estimated to contribute ∼ 26% (±23%) of the DO depletion under the pycnocline. Based on coherent and consistent physical and biogeochemical evidence and reasoning, this study reveals the contribution of SCM to bottom hypoxia off the PRE, which is unreported and likely occurs in other coastal hypoxic systems.

Efficacy of low-dose corticosteroids in patients with acute respiratory distress syndrome: a prospective observational study.

Background: There is still no agreement on whether corticosteroids can reduce mortality in patients with acute respiratory distress syndrome (ARDS). The aim of this study was to investigate the efficacy of low-dose corticosteroid administration in patients with ARDS. Methods: A prospective observational study of patients with ARDS in 17 hospitals in China was performed between March 2016 and February 2018. Propensity score matching was performed to adjust for differences in baseline characteristics between different groups. The effects of corticosteroids were assessed by using the Kaplan-Meier method and a multivariate Cox regression. Results: A total of 527 ARDS patients were enrolled in the study. Sixty-five patients (12.3%) were administered low-dose (methylprednisolone ≤1 mg·kg-1·d-1) corticosteroids. The median dose was equivalent to 0.67 (0.57-0.81) mg/kg methylprednisolone for a median duration of 10 days. The control group included 224 patients (42.5%) who had never receive corticosteroids. In the matched sample, the hospital mortality rates in the low-dose (n=40) and control groups (n=80) were 27.5% and 42.5% (P=0.110), respectively. The length of hospital stay was significantly longer in the low-dose corticosteroid group than in the control group (24.0 vs. 17.0, P=0.002), and the multivariate Cox regression analysis suggested that the low-dose group had a significantly lower risk of death than the control group (HR: 0.48; 95% CI: 0.24-0.97; P=0.040). Conclusions: The administration of low-dose corticosteroids may reduce mortality in patients with ARDS.

Tanreqing Injection Attenuates Macrophage Activation and the Inflammatory Response via the lncRNA-SNHG1/HMGB1 Axis in Lipopolysaccharide-Induced Acute Lung Injury.

The etiology of acute lung injury (ALI) is not clear, and the treatment of ALI presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of ALI and to define the target gene of Tanreqing (TRQ), which is a traditional Chinese medicine formula composed of five medicines, scutellaria baicalensis, bear bile powder, goat horn powder, honeysuckle and forsythia. Macrophage activation plays a critical role in many pathophysiological processes, such as inflammation. Although the regulation of macrophage activation has been extensively investigated, there is little knowledge of the role of long noncoding RNAs (lncRNAs) in this process. In this study, we found that lncRNA-SNHG1 expression is distinctly regulated in differently activated macrophages in that it is upregulated in LPS. LncRNA-SNHG1 knockdown attenuates LPS-induced M1 macrophage activation. The SNHG1 promoter was bound by NF-κB subunit p65, indicative of SNHG1 being a direct transcriptional target of LPS-induced NF-κB activation. SNHG1 acts as a proinflammatory driver that leads to the production of inflammatory cytokines and the activation of macrophages and cytokine storms by physically interacting with high-mobility group box 1 (HMGB1) in ALI. TRQ inhibited NF-κB signaling activation and binding of NF-κB to the SNHG1 promoter. In conclusion, this study defined TRQ target genes, which can be further elucidated as mechanism(s) of TRQ action, and provides insight into the molecular pathogenesis of ALI. The lncRNA-SNHG1/HMGB1 axis is an ideal therapeutic for ALI treatment.

Hotspots of the stokes rotating circulation in a large marginal sea.

Marginal seas, surrounded by continents with dense populations, are vulnerable and have a quick response to climate change effects. The seas typically have alternatively rotating layered circulations to regulate regional heat and biogeochemical transports. The circulations are composed of dynamically active hotspots and governed by the couplings between unique extrinsic inflow and intrinsic dynamic response. Ambiguities about the circulations' structure, composition, and physics still exist, and these ambiguities have led to poor numerical simulation of the marginal sea in global models. The South China Sea is an outstanding example of a marginal sea that has this typical rotating circulation. Our study demonstrates that the rotating circulation is structured by energetic hotspots with large vorticity arising from unique dynamics in the marginal sea and is identifiable by the constraints of Stokes Theorem. These hotspots contribute most of the vorticity and most of energy needed to form and maintain the rotating circulation pattern. Our findings provide new insights on the distinguishing features of the rotating circulation and the dominant physics with the objectives of advancing our knowledge and improving modeling of marginal seas.

Construction and Validation of Prognostic Regulation Network Based on RNA-Binding Protein Genes in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) is a common histologic subtype of non-small cell lung cancer with a poor prognosis. RNA-binding proteins (RBPs) are key modulators in the posttranscriptional regulation and RBP alterations are commonly found in various cancer types. However, its roles in predicting the tumorigenesis and prognosis have not been identified in LUSC. To identify the roles of RBPs in the tumorigenesis and prognosis of LUSC, the RNA sequencing data of patients with LUSC were retrieved from The Cancer Genome Atlas (TCGA) databases. The differential expressed genes (DEGs) were evaluated and identified. The intersection of manually curated RBPs and tumorigenesis-related DEGs was filtered to the univariate Cox regression analysis. The intersection genes with prognostic value were defined as prognostic RNA-binding protein genes (PRBPGs). Based on them, the predicted model was constructed. Its accuracy was tested by the area under the curve (AUC) of the receiver operator characteristic curve and the risk score. In addition, to explore the key regulatory network, the relationship among PRBPGs, target RNA, and absolute quantification of 50 hallmarks of cancer was also identified by Pearson correlation analysis. A total of 311 genes were filtered as the intersection of 1542 manually curated RBPs and tumorigenesis-related DEGs and the results revealed 17 PRBPGs. Based on them, we constructed the predict model with a relatively high accuracy (AUC: 0.739). The Kaplan-Meier survival curve showed the significant prognostic value of risk score (p < 0.001). Moreover, we uncovered the regulatory networks of PHF5A-TOMM22-oxidative phosphorylation, TLR3-CTSO inflammation-related pathway, SECISBP2L-targeted RNA (ADGRF5, TGFBR2, CD302, AC096921.2, AHCYL2, RPS6KA2, SLC34A2, and SFTPB) angiogenesis, and SECISBP2L-AKAP13 signaling (DNA repair, MTORC1 signaling, and MYC targets). The regulation mechanisms and cellular location of key PRBPGs were validated by assay for targeting accessible chromatin with high-throughput sequencing and single-cell RNA sequencing. Our study identifies PRBPGs as reliable indexes in predicting the tumorigenesis and prognosis of patients with LUSC and provides a well-applied model for predicting the overall survival for patients with LUSC. Besides, we also identified the regulatory network among PRBPGs, target RNA, and cancer gene sets in mediating the LUSC tumorigenesis.

Six-Month Outcomes of Post-ARDS Pulmonary Fibrosis in Patients With H1N1 Pneumonia.

Background: Influenza virus is a common pathogen causing community-acquired pneumonia. After H1N1 infection, some patients present with rapid disease progression and various respiratory complications, especially immunocompromised patients and pregnant women. However, most patients have a favorable prognosis. Influenza viruses infect respiratory epithelial cells, leading to diffuse alveolar damage (DAD), which could induce secondary bacterial or fungal infections that could lead to serious complications, such as acute respiratory failure, severe pneumonia, pneumothorax, mediastinal emphysema, acute respiratory distress syndrome (ARDS) and post-ARDS fibrosis. Objective: The short-term mortality rate of ARDS is decreasing, and understanding survivors' posthospitalization outcomes is very important. Our aim was to evaluate the outcomes of 69 patients who survived H1N1 pneumonia with severe respiratory complications and abnormal CT findings and developed post-ARDS pulmonary fibrosis. Materials and methods: The 280 inpatients included in this trial had been diagnosed with H1N1 infection that was confirmed by pharyngeal sputum or swab tests. The data were collected from January 2018 to January 2020 in the First Affiliated Hospital of Zhengzhou University and the Sixth People's Hospital of Zhengzhou. Of these patients, 232 had CT findings indicating pulmonary fibrosis after H1N1 infection, and 69 survived and consented to participate in this study. 6°months after diagnosis, the 69 surviving patients were interviewed and underwent physical examinations, CT scans, 6°min walk tests, and quality-of-life evaluations (SF-36). We analyzed the baseline variables and six-month outcomes of post-ARDS pulmonary fibrosis in patients with H1N1 pneumonia. Results: Of the 69 surviving patients with post-ARDS pulmonary fibrosis, there were 24 females and 45 males, with a mean age of 53.7 ± 16.8°years; 18 patients (26%) had no underlying disease, and 14 (20%) patients had more than one underlying disease. The distance walked in 6°min increased from an average of 451.9°m at 3°months to 575.4°m at 6°months; the mean 36-Item Short Form Survey (SF-36) physical function score increased from an average of 75.3 at 3°months to 77.5 at 6°months; and the average CT score decreased from 31.3 at 3°months to 14.8 at 6°months. Treatment with systemic corticosteroids and the presence of an underlying disease were related to the CT score and the distance walked in 6°min. Conclusion: Among the survivors with pulmonary fibrosis after H1N1 influenza, the 6°min walk test and CT scores continued to be affected after 6°months. The 6°min walk distance and imaging findings improved during the first 6°months. The health-related QoL (HRQoL) scores of H1N1 pneumonia survivors were lower than those of sex- and age-matched controls.

The effect of age on the clinical and immune characteristics of critically ill patients with COVID-19: A preliminary report.

BACKGROUND: In December 2019, a new disease named coronavirus disease 2019 (COVID-19) was occurred. Patients who are critically ill with COVID-19 are more likely to die, especially elderly patients. We aimed to describe the effect of age on the clinical and immune characteristics of critically ill patients with COVID-19. METHODS: We retrospectively included 32 patients with COVID-19 who were confirmed to have COVID-19 by the local health authority and who were admitted to the first affiliated hospital of Zhengzhou University in Zhengzhou, China between January 3 and March 20, 2020. Clinical information and experimental test data were retrospectively collected for the patients. The 32 patients in this study were all in a critical condition and were classified as severe, according to the guidelines of 2019-nCoV infection from the National Health Commission of the People's Republic of China. Data were compared between those <60 years old and ≥60 years old. RESULTS: Of 32 patients, 13 were under 60 years old, and 19 patients were ≥60 years old. The most common symptom among all patients upon admission was fever (93.8%, 30/32). Compared to younger patients, older patients exhibited increased comorbidities. Among patients who were 60 years and older, platelet count, direct bilirubin (DBIL), indirect bilirubin(IBIL), lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) were significantly higher than in younger patients who were less than 60 years old. CD4+ T lymphocytes, CD8+ T lymphocytes, and NKT lymphocytes were decreased, CD4+/CD8+ T lymphocytes were significantly increased in all 32 patients, while there were no evident differences between younger and older patients. The CURB-65 (confusion, urea, respiratory, rate, blood pressure plus age ≥65 years), Acute Physiology and Chronic Health Evaluation (APACHE) II and pH value were significantly higher in older patients than in patients who were under 60 years old. However, the PaO2 and PaO2:FiO2 were lower in older patients than the younger. Compared to patients under 60 years old, patients who were 60 years and older tended to develop ARDS (15 [78.9%] vs 5 [38.5%]), septic shock (7 [36.8%] vs 0 [0.0%]) and were more likely to receive mechanical ventilation (13 [68.4%] vs 3[23.1%]). Dynamic trajectories of seven laboratory parameters were tracked on days 1, 3, 5 and 7, and significant differences in lymphocyte count (P = 0.026), D-dimer (P = 0.010), lactate dehydrogenase (P = 0.000) and C-reactive protein (P = 0.000) were observed between the two age groups. CONCLUSIONS: A high proportion of critically ill patients were 60 or older. Furthermore, rapid disease progression was noted in elderly patients. Therefore, close monitoring and timely treatment should be performed in elderly COVID-19 patients.

Evaluation of Fecal Calprotectin, D-Lactic Acid and Bedside Gastrointestinal Ultrasound Image Data for the Prediction of Acute Gastrointestinal Injury in Sepsis Patients.

Objective: To investigate the early warning and prognostic evaluation of fecal calprotectin (FC), D-lactic acid, and bedside gastrointestinal ultrasound (B-GIUS) data for acute gastrointestinal injury (AGI) in sepsis patients. Main Method: Sepsis patients were grouped based on the presence or absence of AGI into AGI and non-AGI groups. Healthy volunteers of the same period were selected as the control group. FC, B-GIUS data, D-lactic acid, etc. were collected on the 1st, 3rd and 7th days of admission. Twenty-eight-day mortality was recorded. Main Results: FC, D-lactic acid levels, gastric antrum cross-sectional area, and small intestine wall thickness were significantly increased in group A and B (P < 0.05); furthermore, inner-to-outer diameter ratio and cross-sectional area of small intestine were lower than those in the control group (P < 0.05). FC, D-lactic acid, gastric antrum cross-sectional area and small intestine wall thickness in AGI group were higher than those in non-AGI group (P < 0.05). Inner-to-outer diameter ratio and cross-sectional area of small intestine in AGI group were smaller than those in non-AGI group (P < 0.05). There was no difference in the thickness, inner-to-outer diameter ratio nor the cross-sectional area ratio of colon between AGI and non-AGI groups (P > 0.05). AUC for D-lactic acid was 0.881, which was higher than FC's (0.74). When the D-lactic acid cutoff value was 22.16 µmol/L, the sensitivity was 77.9% and the specificity was 92% for the prediction of AGI in sepsis. AUC for the cross-sectional area of the gastrointestinal antrum was 0.657, which was higher than the small intestine thickness's (0.629). When the gastric antrum cross-sectional area was larger than 4.20 cm2, the sensitivity was 64% and the specificity was 65.3%. Conclusion: D-Lactic acid and FC were early diagnostic indicators for sepsis with AGI, and D-lactic acid was the superior indicator. The gastric antrum cross-sectional area and the small intestine wall thickness had an early warning effect, and the prediction of the gastric antrum cross-sectional area was superior to that of the latter. Because it is non-invasive and convenient, B-GIUS can help in the diagnosis of sepsis with AGI.

Fibroblast Growth Factor 21 dependent TLR4/MYD88/NF-κB signaling activation is involved in lipopolysaccharide-induced acute lung injury.

Fibroblast Growth Factor 21 (FGF21) has been reported to reduce inflammation and apoptosis. Inflammation and apoptosis are both the essential mechanisms during development of acute lung injury. This study evaluated whether pre-treatment of FGF21 could alleviate acute lung injury. Mice were pre-treated with FGF21 prior to lipopolysaccharide (LPS) treatment. 24 h later, the lung tissues and BALF were obtained to detect H&E pathology, W/D ratio, pro-inflammatory factors (TNF-α, IL-1ß and IL-6) and apoptosis. In vitro, Human BEAS-2B and THP-1 cells were overexpressed with TLR4 or MYD88 or NF-κB plasmid to detect the inflammation or apoptosis. Data showed that FGF21 was proved to be beneficial for inhibiting inflammation and apoptosis in the LPS- induced Balb/c mice or LPS induced BEAS-2B or THP-1 cells. Furthermore, the data showed that FGF21 suppressed inflammation and apoptosis via inhibition of TLR4/MYD88/NF-κB signaling pathway. Therefore, FGF21 provides a possibility for the treatment of LPS induced acute lung injury.

Regulatory T cell activity in immunosuppresive mice model of pseudomonas aeruginosa pneumonia.

Pseudomonas aeruginosa (PA) pneumonia is a refractory, even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process. We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells, i.e., Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10). Seventy-two BALB/c mice were divided into four groups randomly: control (A), PA pneumonia (B), immunosuppression (C) and immunosuppression with PA pneumonia (D). Mice were sacrificed at 4, 8 and 24 h after establishing experimental models. The pathological changes of lung tissue were graded, and the FOXP3 mRNA and serum IL-10 levels were detected. Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C, but significantly pathological changes were found in groups B and D, especially in group D at 8 h (P<0.05). The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points, which were significantly lower than those in groups B and D (P<0.05). FOXP3 mRNA levels were lowest at 4 h, and there was significant difference between groups B and D (P<0.05). The serum levels of IL-10 in groups A and C were almost normal at the three time points, but decreased significantly in groups B and D (P<0.05). The serum levels of IL-10 decreased to the lowest at 8 h, especially in group D (P<0.05). The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly, which may be associated with Treg cells function disturbance. And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

Effect of intravenous immunoglobulin on the function of Treg cells derived from immunosuppressed mice with Pseudomonas aeruginosa pneumonia.

AIM: The present study aimed to investigate the effect of intravenous immunoglobulin (IVIG) on regulatory T (Treg) cells derived from immunosuppressed mice with Pseudomonas aeruginosa (PA) pneumonia. METHODS: A total of 108 BALB/c mice were randomly divided into the following groups: control group (Control), immunosuppressed group (IS), PA pneumonia group (PA), PA pneumonia in immunosuppressed group (IS + PA), PA pneumonia with IVIG treatment in immunocompetent group (PA + IVIG) and PA pneumonia with IVIG treatment in immunosuppressed group (IS + PA + IVIG). Each group comprised 18 mice. The combined PA pneumonia in immunosuppressed model and the treatment models were established. The mice in each group were sacrificed at 4, 8, and 24 h time points. The general condition and pathological changes in the lung tissues of the mice were monitored. Reverse transcription-polymerase chain reaction was used to detect the forkhead box P3 (FOXP3) mRNA relative expression level in the lung tissues. The enzyme-linked immunosorbent assay was used to detect the serum concentration of active transforming growth factor beta (TGF-ß). RESULTS: No inflammatory response were exhibited in the lung tissues of the mice in Control group and IS group, while varying degrees of acute lung injury were revealed in the mice in PA group, IS + PA group, PA + IVIG group and IS + PA + IVIG group. Lung tissue injury was most apparent at the 8 h time point, and it indicated the greatest effect in IS + PA group. Whereas tissue damages were alleviated in PA + IVIG group and IS + PA + IVIG group compared with IS + PA group. In addition, tissue damage lessened in PA + IVIG group compared with PA group and IS + PA + IVIG group. FOXP3 mRNA expression levels in the lung tissues and the serum concentration of TGF-ß were lower in IS group, PA group, IS + PA group and IS + PA + IVIG group at the 4, 8 and 24 h time points, respectively compared with Control group. FOXP3 mRNA expression levels decreased in PA + IVIG group at the 4h time point and TGF-ß serum concentrations decreased at the 4 and 8h time points compared with Control group, and subsequently increased. CONCLUSIONS: In the immunosuppred model with PA pneumonia, the immune system was greatly compromised. IVIG partially restored the immunosuppressed functions of Treg cells, suppressed the overactivated immune system and ameliorated the development of the disease.

Regulatory T Cell Activity in Immunosuppresive Mice Model of Pseudomonas Aeruginosa Pneumonia / 华中科技大学学报（医学）（英德文版）

Pseudomonas aeruginosa (PA) pneumonia is a refractory,even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process.We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells,i.e.,Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10).Seventy-two BALB/c mice were divided into four groups randomly:control (A),PA pneumonia (B),immunosuppression (C) and immunosuppression with PA pneumonia (D).Mice were sacrificed at 4,8 and 24 h after establishing experimental models.The pathological changes of lung tissue were graded,and the FOXP3 mRNA and serum IL-10 levels were detected.Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C,but significantly pathological changes were found in groups B and D,especially in group D at 8 h (P＜0.05).The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points,which were significantly lower than those in groups B and D (P＜0.05).FOXP3 mRNA levels were lowest at 4 h,and there was significant difference between groups B and D (P＜0.05).The serum levels of IL-10 in groups A and C were almost normal at the three time points,but decreased significantly in groups B and D (P＜0.05).The serum levels ofIL-10 decreased to the lowest at 8 h,especially in group D (P＜0.05).The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly,which may be associated with Treg cells function disturbance.And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.