The Association of Glycemic Index, Glycemic Load, and Daily Carbohydrates Intake with the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Glycemic index (GI), glycemic load (GL) and daily carbohydrates intake have been associated with a variety of cancers, but their implications in hepatocellular carcinoma (HCC) remain controversial. The purpose of our study is to investigate the association of GI, GL and daily carbohydrates intake with the risk of HCC. Methods: Systematic searches were conducted in PubMed, Embase and Web of Science until November 2020. According to the degree of heterogeneity, random effect model or fixed effect model was chosen to obtain the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results: Four cohort studies and three case-control studies were eventually included. The pooled results showed no significant association of GI (RR = 1.11, 95% CI = 0.80-1.53), GL (RR = 1.09, 95% CI = 0.76-1.55), and daily carbohydrates intake (RR = 1.09, 95% CI = 0.84-1.32) with the risk of HCC in the general population. Subgroup analysis revealed that in hepatitis B virus (HBV) or/and hepatitis C virus (HCV)-positive group, GI was irrelevant to the risk of HCC (RR = 0.65, 95% CI = 0.32-1.32), while a high GL diet was associated with a higher risk of HCC (RR = 1.52, 95% CI = 1.04-2.23). In contrast, in HBV and HCV-negative group, both GI (RR = 1.23, 95% CI = 0.88-1.70) and GL (RR = 1.17, 95% CI = 0.83-1.64) were not associated with the risk of HCC. Conclusion: A high GL diet increases the risk of HCC in those with viral hepatitis. A low GL diet is recommended for them to reduce the risk of HCC.

Construction of cellulose-based highly sensitive extended-gate field effect chiral sensor.

Chiral recognition is an emerging field of modern chemical analysis, and the development of health-related fields depends on the production of enantiomers. Cellulose is a kind of natural polymer material with certain chiral recognition ability. Limited by the chiral recognition ability of natural cellulose itself, more cellulose derivatives have been gradually developed for chiral recognition and separation. Based on the difference in action between cellulose derivatives and enantiomers, this work synthesized cellulose-tris(4-methylphenylcarbamate) (CMPC) chiral recognition mediators and a CMPC-functionalized extended-gate organic field effect transistor (EG-OFET) was constructed for the first time. Three chiral molecules were selected as model analytes to evaluate the enantiomeric recognition ability of the platform, including threonine (Thr), 2-chloromandelic acid (CA), and 1,2-diphenylethylenediamine (DPEA). The detection limit for 1,2-diphenylethylenediamine (DPEA) is down to 10-13 M. Through the amplification effect of the EG-OFET platform, the difference in the interaction between CMPC and three chiral molecules with different structures is converted into a current signal output. At the same time, the enantiomer discrimination mechanism of CMPC was further studied by means of spectroscopy and nuclear magnetic resonance.

Efficacy and Safety of Aspirin for Prevention of Hepatocellular Carcinoma: An Updated Meta-analysis.

Background and Aims: Previous meta-analyses have shown that aspirin use may reduce the risk of hepatocellular carcinoma (HCC). However, the optimal dose, frequency, and duration of aspirin use or the safety and efficacy of aspirin in target populations for HCC prevention remain unclear. The study aim was to investigate the efficacy and safety of aspirin for prevention of HCC. Methods: Publications were retrieved by a comprehensive literature research of several databases. Based on a random-effects model, hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship between aspirin use and HCC risk was assessed with a restricted cubic spline model. Results: Twenty-two studies were included in the meta-analysis. Aspirin use was associated with a reduced risk of HCC (HR=0.64, 95% CI: 0.56-0.75). The effect was robust across sex and age; however, women and the non-elderly had the greatest benefit from aspirin use. The preventive effect was well reproduced in those with comorbidities. Daily use and long-term use of aspirin appeared to offer greater benefits. Aspirin 100 mg/d was associated with maximum reduction of HCC risk. Aspirin use did slightly increase the risk of bleeding (HR=1.14, 95% CI: 1.02-1.27). Conclusions: Our meta-analysis confirmed that use of aspirin significantly reduced the incident risk of HCC. Regular and long-term aspirin use offers a greater advantage. Aspirin use was associated with an increased risk of bleeding. We recommend 100 mg/d aspirin as a feasible dose for further research on primary prevention of HCC in a broad at-risk population.

The Prognostic Value of Natural Killer Cells and Their Receptors/Ligands in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Natural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear. Methods: Several electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI). Results: 26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57-0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57+ NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56+ NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear. Conclusion: NK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.

Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Preliminary studies have suggested that soluble programmed death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) have prognostic implications in many malignant tumors. However, the correlation between sPD-1/sPD-L1 level and prognosis of hepatocellular carcinoma (HCC) is still unclear. METHODS: We searched several electronic databases from database inception to October 7, 2021. Meta-analyses were performed separately for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), time to progression (TTP), and tumor-free survival (TFS). Random effects were introduced to this meta-analysis. The correlation between sPD-1/sPD-L1 level and prognosis was evaluated using hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS: A total of 11 studies (1291 patients) were incorporated into this meta-analysis, including seven on sPD-L1, two on sPD-1, and two about both factors. The pooled results showed that high sPD-L1 level was associated with worse OS (HR = 2.46, 95%CI 1.74-3.49, P < 0.001; I2 = 31.4, P = 0.177) and poorer DFS/RFS/TTP/TFS of patients with HCC (HR = 2.22, 95%CI 1.47-3.35, P < 0.001; I2 = 66.1, P = 0.011), irrespective of method of detection, study type, treatment, cut-off value and follow-up time. In contrast, the level of sPD-1 was not correlated to the OS (HR = 1.19, 95%CI 0.55-2.56, P = 0.657) and DFS/TFS of patients with HCC (HR = 0.94, 95%CI 0.36-2.49, P = 0.906). CONCLUSION: sPD-L1 rather than sPD-1 could be a good predictor for recurrence and survival after treatment for HCC. More high-quality prospective studies are warranted to assess the prognostic value of sPD-1 or sPD-L1 for HCC.

Modified high-flow nasal cannula oxygen therapy versus conventional oxygen therapy in patients undergoing bronchoscopy: a randomized clinical trial.

BACKGROUND: Hypoxemia frequently occurs during bronchoscopy. High-flow nasal cannula (HFNC) oxygen therapy may be a feasible alternative to prevent the deterioration of gas exchange during bronchoscopy. With the convenience of clinical use in mind, we modified an HFNC using a single cannula. This clinical trial was designed to test the hypothesis that a modified HFNC would decrease the proportion of patients with a single moment of peripheral arterial oxygen saturation (SpO2) < 90% during bronchoscopy. METHODS: In this single-center, prospective randomized controlled trial, hospitalized patients in the respiratory department in need of diagnostic bronchoscopy were randomly assigned to a modified HFNC oxygen therapy group or a conventional oxygen therapy (COT) group. The primary outcome was the proportion of patients with a single moment of SpO2 < 90% during bronchoscopy. RESULTS: Eight hundred and twelve patients were randomized to the modified HFNC (n = 406) or COT (n = 406) group. Twenty-four patients were unable to cooperate or comply with bronchoscopy. Thus, 788 patients were included in the analysis. The proportion of patients with a single moment of SpO2 < 90% during bronchoscopy in the modified HFNC group was significantly lower than that in the COT group (12.5% vs. 28.8%, p < 0.001). There were no significant differences in the fraction of inspired oxygen between the two groups. The lowest SpO2 during bronchoscopy and 5 min after bronchoscopy in the modified HFNC group was significantly higher than that in the COT group. Multivariate analysis showed that a baseline forced vital capacity (FVC) < 2.7 L (OR, 0.276; 95% CI, 0.083-0.919, p = 0.036) and a volume of fluid instilled > 60 ml (OR, 1.034; 95% CI, 1.002-1.067, p = 0.036) were independent risk factors for hypoxemia during bronchoscopy in the modified HFNC group. CONCLUSIONS: A modified HFNC could decrease the proportion of patients with a single moment of SpO2 < 90% during bronchoscopy. A lower baseline FVC and large-volume bronchoalveolar lavage may predict desaturation during bronchoscopy when using a modified HFNC. Trial registration ClinicalTrials. Gov: NCT02606188. Registered 17 November 2015.

Sex and regional disparities in incidence of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis.

BACKGROUND: Recent studies have identified an increased risk of hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH). Sex and regional disparities in incidence of HCC in AIH continue to be reported worldwide. Nevertheless, the magnitude of this gap remains unknown. METHOD: We searched several databases including PubMed, Embase, Web of Science, Cochrane Library, Wanfang Data, CNKI and SinoMed. Incidence rates of HCC in AIH were combined and analyzed following the EBayes method. Incidence rate ratios were pooled to assess the sex differences. The impact of population difference, sex, age, cirrhotic condition was further analyzed with subgroup analysis and linear regression analysis. RESULT: 39 studies meeting our eligibility criteria were chosen for the analysis. The pooled incidence rate of HCC in AIH was 3.54 per 1000 person years (95% CI 2.76-4.55). Pooled IRR for the risk of HCC in male AIH patients compared to female was 2.16 (95% CI 1.25-3.75), with mild heterogeneity among studies. The pooled HCC incidence rate in AIH by continents was as follows: Europe 2.37 per 1000 person-years (95% CI 1.45-3.88), Asia 6.18 per 1000 person-years (95%CI 5.51-6.93), North America 2.97 per 1000 person-years (95%CI 2.40-3.68), Oceania 2.60 (95%CI 0.54-7.58). The pooled HCC incidence rate in AIH-related cirrhosis by continent was as follows: Europe 6.35 per 1000 person-years (95%CI 3.94-10.22), Asia 17.02 per 1000 person-years (95%CI 11.18-25.91), North America 10.89 per 1000 person-years (95%CI 6.69-17.74). CONCLUSION: A higher HCC incidence in AIH was observed among male and in Asian populations. Cirrhosis status at AIH diagnosis is significantly associated with an increased incidence rate for HCC, and routine HCC surveillance is recommended for patients with AIH cirrhosis, especially for those in Asia.

Clinical Benefit of Antiviral Agents for Hepatocellular Carcinoma Patients With Low Preoperative HBV-DNA Loads Undergoing Curative Resection: A Meta-Analysis.

BACKGROUND AND AIMS: The clinical benefit of adjuvant antiviral therapy after curative therapy for HCC in patients with high preoperative HBV-DNA loads has been studied widely but that in patients with low preoperative HBV-DNA loads remains controversial. The purpose of this study was to determine the effect of antiviral treatment prophylaxis on HBV reactivation, overall survival (OS), and postoperative liver function in patients with low preoperative HBV-DNA levels undergoing curative resection. METHODS: A meta-analysis was conducted by searching Web of Science, PubMed, Embase, and Cochrane Library until May 2020. We used REVMAN for data analysis and completed the study under the PRISMA guidelines. RESULTS: Three randomized trials and seven cohort studies, comprising of 1,131 individuals, were included in the meta-analysis. Antiviral treatment significantly reduced the rate of HBV reactivation after curative treatment of HCC, with a pooled risk ratio of 0.12 (95% c.i. 0.07 to 0.21; P < 0.00001). The trials were consistently favorable for the antiviral group, with a pooled hazard ratio of 0.52 (95% c.i. 0.37 to 0.74; P = 0.0002) in respect of OS rate. However, by pooling the data from studies that reported ALT on the 30th day postoperatively, the result didn't reach statistical significance (mean difference -4.38, 95% c.i. -13.83 to 5.07; P = 0.36). The I² values of the heterogeneity test for the above three comparisons are zero. CONCLUSION: Antiviral therapy during curative resection is effective in reducing HBV reactivation and improving OS rate in HCC patients with low viral load.

Effects of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α overexpression on hepatocellular carcinoma survival: A systematic review with meta-analysis.

BACKGROUND AND AIM: The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF-1α and HIF-2α overexpression with the prognosis and clinicopathological features of HCC. METHODS: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model. RESULTS: Twenty-two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF-1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53-2.00)] and DFS [HR = 1.64 (95% CI: 1.34-2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36-2.48)], tumor size [OR = 1.36 (95% CI: 1.12-1.66)], and tumor number [1.74 (95% CI: 1.34-2.25)]. In contrast, HIF-2α overexpression was not associated with the prognosis and clinicopathological features of HCC. CONCLUSION: Our data provided compelling evidence of a worse prognosis of HCC in HIF-1α overexpression patients but not HIF-2α overexpression ones.

Influenza A virus exposure may cause increased symptom severity and deaths in coronavirus disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19. METHODS: Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups. RESULTS: Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir. CONCLUSIONS: The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.

Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma.

The E3 ubiquitin ligase TRIM4 has been reported to regulate the assembly of the antiviral signalling complex, induce mitochondrial aggregation and sensitize cells to H2O2-induced death. However, the relationship between TRIM4 and human malignancies, including hepatocellular carcinoma (HCC), is unclear. In this study, we detected the expression of TRIM4 in 134 pairs of HCC tissues and peritumoural tissues and investigated the association of TRIM4 expression with the prognosis of HCC. We found that the TRIM4 expression was much lower in HCC tissues than in peritumoural tissues and was significantly associated with vascular invasion, tumour capsule and Hong Kong Liver Cancer (HKLC) stage. Univariate and multivariate analyses revealed that the TRIM4 expression was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS) in our HCC cohort. Patients with higher TRIM4 expression had a lower incidence of intrahepatic recurrence and a higher OS rate (p<0.001 and p<0.01, respectively). These results were further validated in another independent cohort of 200 HCC patients. In conclusion, the TRIM4 level in HCC tissues is an independent prognostic factor for HCC patients. Close clinical monitoring is recommended for patients with low TRIM4 expression.

Effects of epithelial cell injury of the lower respiratory tract in the pathogenesis of allergic responses in a rat model.

BACKGROUND: Asthma is a complex disease involving genetic and environment interactions. Atopy is a strong risk factor for asthma. The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials. To explore the effects of airway epithelium on asthma, we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier, which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma. METHODS: Thirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group: control group, asthma group, ovalbumin (OVA) + OVA group, lipopolysaccharide (LPS) group and LPS + OVA group. In the control group, 0.9% saline was injected intraperitoneally on day 1. Fourteen days later, the rats were exposed to aerosolized 0.9% saline. In the asthma group, the rats were sensitized with an injection of 10 mg of OVA, followed by an aerosolized 2% OVA challenge 14 days later. The OVA + OVA group was sensitized by an inhalation 2% OVA, 20 minutes a day, from day 1 to day 7, and then OVA challenged in the same way as the asthma group. In the LPS group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with saline as in the control group. While in the LPS + OVA group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with OVA as in the asthma group. The expression of interleukin (IL)-4, interferon-gamma (IFN-γ) and thymic stromal lymphopoietin (TSLP) in the lungs was detected by reverse transcription polymerase chain reaction (RT-PCR) and the pulmonary pathological changes were also observed. The level of IL-4, IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Bronchoalveolar lavage fluid (BALF) was collected to conduct differential cell counts. Flow cytometry analysis was also used to count Th1 and Th2 cells. RESULTS: The pathological changes in the LPS + OVA group were similar to the asthma group, while in other groups, the pathological changes were not obvious. The ratio of lymphocytes in BALF, IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS + OVA groups were higher than in the control group and the OVA + OVA group (P < 0.05). The level of IgE was higher in the asthma, LPS and LPS + OVA groups than in the control group and the OVA + OVA group (P < 0.05). By flow cytometry analysis, the Th1/Th2 ratio was lower in the LPS + OVA and asthma groups than in other groups (P < 0.05). CONCLUSIONS: The experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses. This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.

[Retrospective analysis of relationship between radiological features and prognoses of pneumocystis pneumonia in non-AIDS immunocompromised patients].

OBJECTIVE: To elucidate the relationship between the radiological features and prognoses of pneumocystis pneumonia (PCP) in non-acquired immunodeficiency syndrome (non-AIDS) immunocompromised patients. METHODS: Retrospective analyses were performed for the radiological features and prognoses of 36 non-AIDS immunocompromised PCP patients hospitalized at Peking University First Hospital from April 2006 to April 2010. There were 24 males and 12 females with an average age of (51.7 ± 18.9) years. RESULTS: All patients underwent chest photographic examinations and chest computed tomography (CT) was performed on 29 of them. The overall case fatality rate (CFR) of 36 patients was 33.3% (12/36). At the start of anti-PCP treatment, there were normal chest radiography (n = 7), bilateral diffuse infiltration (n = 21), bilateral diffuse consolidation (n = 8), aerothorax, mediastinal emphysema or pneumohypoderma (n = 6) and numbers of deceased patients (n = 0, 8, 5 and 5 respectively). The CFRs of the patients with normal chest radiography and aerothorax, mediastinal emphysema or pneumohypoderma were both statistically significant as compared with the overall rate (P < 0.05). At the start of anti-PCP treatment, there were bilateral diffuse ground glass opacities (GGO) (n = 29), "mosaic sign" (n = 19), air bronchogram (n = 19), pulmonary consolidation (n = 17), bilateral pleural effusion (n = 7), thickened lobular septa (n = 6), cystic lesions (n = 5), aerothorax, mediastinal emphysema or pneumohypoderma (n = 4) and numbers of deceased patients (n = 8, 5, 5, 5, 2, 2, 2 and 4 respectively). The CFRs of the patients with aerothorax, mediastinal emphysema or pneumohypoderma were statistically significant as compared with the overall rate (P < 0.05). CONCLUSIONS: The major radiological features of PCP in non-AIDS immunocompromised patients are bilateral diffuse infiltration. And bilateral diffuse GGO on chest CT scans are usually accompanied with "mosaic" sign, air bronchogram or pulmonary consolidation. The prognoses are excellent for the patients with normal chest radiograph and poor for those with aerothorax, mediastinal emphysema or pneumohypoderma.

Effects of N-acetylcysteine on Clara cells in rats with cigarette smoke exposure.

BACKGROUND: The number of Clara cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure. METHODS: Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS + NAC group) oral intake of NAC 80 mg x kg(-1) x d(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The mRNA expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay. RESULTS: Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3 +/- 14.7 vs. 53.7 +/- 11.5, P < 0.05). The Clara cell particles in cytoplasm decreased in the CS group (P < 0.05). The percentage of CC16-positive cells in bronchioles in the CS group (27.8 +/- 4.3 and 29.5 +/- 2.4 in terminal bronchioles and respiratory bronchioles, respectively) significantly decreased as compared with the control group (37.1 +/- 3.8 and 43.8 +/- 5.8 in terminal bronchioles and respiratory bronchioles, respectively) (P < 0.05). No significant difference was observed in GSH level ((181 +/- 26) nmol/L in the control group vs. (170 +/- 18) nmol/L in the CS group) between the two groups. After treatment with NAC, the pathologic score of small airways (24.1 +/- 17.5) decreased (P < 0.05). Clara cell particles in cytoplasm of Clara cells increased and GSH level in plasma ((213 +/- 40) nmol/L vs. (170 +/- 18) nmol/L in the CS group) increased too (P < 0.05), while the increase in the proportions of CC16 positive cells in bronchioles (30.1 +/- 6.4 and 34.3 +/- 6.3 in terminal bronchioles and respiratory bronchioles, respectively) did not reach the statistical significance (P > 0.05). No significant difference was found in the expression of CC16 mRNA among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r = -0.592, P < 0.05), but not with GSH level. CONCLUSIONS: One-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16.

Invasive pulmonary aspergillosis in patients with antineutrophil cytoplasmic antibody associated vasculitis.

BACKGROUND AND AIMS: Invasive pulmonary aspergillosis (IPA) has been reported as a severe opportunistic infection in immunocompromised patients without neutropenia or cancer. Patients with antineutrophil cytoplasmic antibody associated vasculitis (AAV) with immunosuppressive treatment are susceptible to IPA, but only few cases were reported in the literature. We retrospectively analyze the clinical characteristics of our patients with IPA in AAV. METHODS: Hospitalized patients with AAV who developed IPA were selected. Their clinical data were retrospectively reviewed and possible risk factors for development of IPA were investigated. RESULTS: Seven of 157 patients with AAV were identified to have IPA. Two patients were classified as Wegener granulomatosis and 5 as microscopic polyangiitis with a mean age at 68.6 +/- 10.9 years. After immunosuppressive therapy, 7 patients developed IPA within 2 approximately 13 weeks. They had 1 or more risk factors increasing susceptibility to Aspergillus. Pre-existing chronic respiratory diseases were found in 5 patients. Despite intensive antifungal therapy, only 3 patients survived. The patients who died were older, with more severe lung injury and lower hemoglobin level. CONCLUSIONS: AAV patients with immunosuppressive therapy are susceptible to Aspergillus infection. Monitoring and prophylactic antifungal therapy should be recommended for patients at high risk.

[Idiopathic pulmonary hemosiderosis in adults: report of two cases and literature review].

OBJECTIVE: To describe the clinical, radiological and pathological characteristics of idiopathic pulmonary haemosiderosis (IPH) in adults and to evaluate the methods of diagnosis and treatment. METHODS: Two patients were successfully diagnosed and treated in our hospital and the literature on the subject was reviewed. RESULTS: Two adult patients (19 and 34 years old) diagnosed in our hospital had 5 and 10 years of history of hemoptysis respectively, and chest CT showed bilateral diffuse alveolar opacities over mid and lower zones. Tests of antinuclear antibodies (ANAs), rheumatoid factor (RF), antineutrophilic cytopasmic antibodies (ANCA) and Anti-glomerular basement membrane (anti-GBM) antibody were negative. Haemosiderin-laden macrophages were found in bronchoalveolar lavage fluid (BALF) whose color was yellow. Microscopic examination of the lung tissue specimens obtained by transbronchial lung biopsy (TBLB) revealed hemorrhage and numerous hemosiderin-laden macrophages in the alveoli and no vasculitis or capillaritis were seen. These findings were consistent with a diagnosis of IPH. Steroid therapy had good effects. CONCLUSION: IPH is a diagnosis of exclusion of other causes of diffuse alveolar hemorrhage (DAH). IPH adults have relatively good drug responses and relatively good prognoses.

[Idiopathic pulmonary alveolar proteinosis: report of three cases and literature review].

To describe the clinical, radiological and pathological characteristics of idiopathic pulmonary alveolar proteinosis (I-PAP) and to evaluate the methods of diagnosis and treatment. Three patients were successfully diagnosed and treated in our hospital and the literature on the subject was reviewed. Three patients, two males and one female (mean age 46 years), were diagnosed averagely in 4 months. Two severe patients presented with progressive dyspnea and type I respiratory failure, and one mild patient only with dry cough and hypoxemia. Chest X-ray radiographs all showed perihilar "butterfly" shadow and chest CT scans showed diffused ground-glass opacities (GGO), typically with "map" changes and "crazy paving" patterns. All the patients underwent bronchoscope, branchoalveolar lavage fluid (BALF) had grossly opaque and/or milky appearance and its sediment was periodic acid-Schiff stain positive. Trans-bronchoscopic lung biopsy (TBLB) specimens were obtained and under light microscopy alveoli and some of the small bronchioles were filled with eosinophilic proteinaceous material with needle-like clefts. By electron microscopy numerous cellular debris and extracellular multilamellated bodies were found. Two severe patients were successfully treated with sequential whole-lung lavage and one required repeated lavages. I-PAP is rare and prone to be misdiagnosed. The radiological features may indicate the diagnosis and examinations of TBLB and BALF can make the accurate diagnosis. Whole-lung lavage is the most effective therapy by now and granulocyte-macrophage colony-stimulating factor (GM-CSF) may be beneficial in some patients.

[Retrospective analysis of three cases of pulmonary mucormycosis].

OBJECTIVE: To describe the clinical characteristics of pulmonary mucormycosis and to evaluate the approaches to its diagnosis and treatment. METHODS: Three cases of pulmonary mucormycosis were successfully diagnosed by histopathologic examination of infected tissues obtained by fiberoptic bronchoscopy in this hospital. The clinical features of the cases were analyzed and the literature reviewed. RESULTS: Three patients were all farmers and two of them had had diabetic ketoacidosis. The first patient died from massive hemoptysis one day after the diagnosis was confirmed. The second patient was cured by large doses of intravenous amphotericin B (total dosage 2 g). The third patient presented with right middle bronchial stenosis after right upper lobectomy because of squamous carcinoma, and was cured by amphotericin B (1.5 g) combined with interventional therapy under fiberoptic bronchoscopy. The two patients were followed for 0.5 - 1 year without relapse. CONCLUSIONS: The mortality of pulmonary mucormycosis is high. Fiberoptic bronchoscopy is a useful diagnostic method for histopathologic examination. Successful treatment of pulmonary mucormycosis includes early diagnosis, control of underlying diseases and surgical intervention of isolated lesions combined with large dosage of amphotericin B.