scTPC: a novel semisupervised deep clustering model for scRNA-seq data.

MOTIVATION: Continuous advancements in single-cell RNA sequencing (scRNA-seq) technology have enabled researchers to further explore the study of cell heterogeneity, trajectory inference, identification of rare cell types, and neurology. Accurate scRNA-seq data clustering is crucial in single-cell sequencing data analysis. However, the high dimensionality, sparsity, and presence of "false" zero values in the data can pose challenges to clustering. Furthermore, current unsupervised clustering algorithms have not effectively leveraged prior biological knowledge, making cell clustering even more challenging. RESULTS: This study investigates a semisupervised clustering model called scTPC, which integrates the triplet constraint, pairwise constraint, and cross-entropy constraint based on deep learning. Specifically, the model begins by pretraining a denoising autoencoder based on a zero-inflated negative binomial distribution. Deep clustering is then performed in the learned latent feature space using triplet constraints and pairwise constraints generated from partial labeled cells. Finally, to address imbalanced cell-type datasets, a weighted cross-entropy loss is introduced to optimize the model. A series of experimental results on 10 real scRNA-seq datasets and five simulated datasets demonstrate that scTPC achieves accurate clustering with a well-designed framework. AVAILABILITY AND IMPLEMENTATION: scTPC is a Python-based algorithm, and the code is available from https://github.com/LF-Yang/Code or https://zenodo.org/records/10951780.

Associations between sarcopenia and circulating branched-chain amino acids: a cross-sectional study over 100,000 participants.

BACKGROUND: Emerging evidence suggests that alterations in BCAA metabolism may contribute to the pathogenesis of sarcopenia. However, the relationship between branched-chain amino acids (BCAAs) and sarcopenia is incompletely understood, and existing literature presents conflicting results. In this study, we conducted a community-based study involving > 100,000 United Kingdom adults to comprehensively explore the association between BCAAs and sarcopenia, and assess the potential role of muscle mass in mediating the relationship between BCAAs and muscle strength. METHODS: Multivariable linear regression analysis examined the relationship between circulating BCAAs and muscle mass/strength. Logistic regression analysis assessed the impact of circulating BCAAs and quartiles of BCAAs on sarcopenia risk. Subgroup analyses explored the variations in associations across age, and gender. Mediation analysis investigated the potential mediating effect of muscle mass on the BCAA-muscle strength relationship. RESULTS: Among 108,017 participants (mean age: 56.40 ± 8.09 years; 46.23% men), positive associations were observed between total BCAA, isoleucine, leucine, valine, and muscle mass (beta, 0.56-2.53; p < 0.05) and between total BCAA, leucine, valine, and muscle strength (beta, 0.91-3.44; p < 0.05). Logistic regression analysis revealed that increased circulating valine was associated with a 47% reduced sarcopenia risk (odds ratio = 0.53; 95% confidence interval = 0.3-0.94; p = 0.029). Subgroup analyses demonstrated strong associations between circulating BCAAs and muscle mass/strength in men and individuals aged ≥ 60 years. Mediation analysis suggested that muscle mass completely mediated the relationship between total BCAA, and valine levels and muscle strength, partially mediated the relationship between leucine levels and muscle strength, obscuring the true effect of isoleucine on muscle strength. CONCLUSION: This study suggested the potential benefits of BCAAs in preserving muscle mass/strength and highlighted muscle mass might be mediator of BCAA-muscle strength association. Our findings contribute new evidence for the clinical prevention and treatment of sarcopenia and related conditions involving muscle mass/strength loss.

Revelation of the dynamic progression of hypoxia-reoxygenation injury by visualization of the lysosomal hydrogen peroxide.

Hydrogen peroxide (H2O2) plays an important role in pathological conditions, such as cerebral ischemia-reperfusion (I-R) injury. Fluorescent probes may serve as valuable tools to detect the amount, temporal and spatial distribution of H2O2 in living cells. To investigate the role of lysosomal H2O2 involved in cerebral I-R injury, we designed and synthesized a lysosome-targetable two-photon fluorescent probe ztl-4, through expansion and substitution of the original pyridazinone scaffold, conjugation of electronic-donating aromatic ring and precise terminal modification of the alkyl linker. The probe ztl-4 exhibited fast, sensitive and highly selective response toward H2O2. ztl-4 could image exogenous H2O2 in SH-SY5Y cells and brain slices. In addition, ztl-4 was located in lysosomes with high colocalization coefficient compared with LysoTracker. ztl-4 was further applied for detecting the endogenous generation of H2O2 in SH-SY5Y cells subjected to oxygen and glucose deprivation (OGD) or OGD/reoxygenation (OGD/R) injury. Both OGD- and OGD/R-induced cell injury caused a time-dependent increase of H2O2 production within lysosomes. Moreover, OGD/R-treated cells showed much more amount of H2O2 than OGD-treated cells, indicating that reoxygenation will promote H2O2 accumulation in lysosomes of post-hypoxia cells. Therefore, the probe is suitable for monitoring the dynamic changes of lysosomal H2O2 in cells.

Rational Design of Fluorescent Phthalazinone Derivatives for One- and Two-Photon Imaging.

Phthalazinone derivatives were designed as optical probes for one- and two-photon fluorescence microscopy imaging. The design strategy involves stepwise extension and modification of pyridazinone by 1) expansion of pyridazinone to phthalazinone, a larger conjugated system, as the electron acceptor, 2) coupling of electron-donating aromatic groups such as N,N-diethylaminophenyl, thienyl, naphthyl, and quinolyl to the phthalazinone, and 3) anchoring of an alkyl chain to the phthalazinone with various terminal substituents such as triphenylphosphonio, morpholino, triethylammonio, N-methylimidazolio, pyrrolidino, and piperidino. Theoretical calculations were utilized to verify the initial design. The desired fluorescent probes were synthesized by two different routes in considerable yields. Twenty-two phthalazinone derivatives were synthesized and their photophysical properties were measured. Selected compounds were applied in cell imaging, and valuable information was obtained. Furthermore, the designed compounds showed excellent performance in two-photon microscopic imaging of mouse brain slices.

Development of novel proteasome inhibitors based on phthalazinone scaffold.

In this study we designed a series of proteasome inhibitors using pyridazinone as initial scaffold, and extended the structure with rational design by computer aided drug design (CADD). Two different synthetic routes were explored and the biological evaluation of the phthalazinone derivatives was investigated. Most importantly, electron positive triphenylphosphine group was first introduced in the structure of proteasome inhibitors and potent inhibition was achieved. As 6c was the most potent inhibitor of proteasome, we examined the structure-activity relationship (SAR) of 6c analogs.

Discovery of a potent and highly specific ß2 proteasome inhibitor from a library of copper complexes.

We reported the synthesis, characterization and biological activity of several copper(II) Schiff base complexes, which exhibit high proteasome inhibitory activities with particular selectivity of ß2 subunit. Structure-activity relationships information obtained from complex Na2[Cu(a4s1)] demonstrated that distinct bonding modes in ß2 and ß5 subunits determines its selectivity and potent inhibition for ß2 subunit.

[Contrast-enhanced ultrasonography of hepatic alveolar echinococcosis in rats: the correaltion of imaging fratures and histologic microvascular density].

OBJECTIVE: To correlate the characteristic images of hepatic alveolar echinococcosis (HAE) in rats using contrast-enhanced ultrasonography (CEUS) and microvascular density (MVD) in the surrounding invasion range of HAE lesions. METHODS: Thirty Wistar rats were infected with Echinococcus multolocularis suspension (approximately 800 protoscoleces in 0.2 ml per rat) through abdominal opening injection in liver. Three months after the inoculation, rats with hepatic E. multilocularis infection were examined by conventional and contrast-enhanced ultrasonography. The location, size, shape, boundary, inner echogenicity, and blood flow of the lesions, signal intensity and dynamic enhancement pattern were recorded. The positive rats were sacrificed and their livers were obtained. The structure of HAE lesions was observed by HE staining. Immunohistochemistry staining was performed on the infiltrative region of HAE lesion and the expression of CD34 in the surrounding hepatic parenchyma. Scoring was based on the percentage of positively stained cells and stain intensity. The correlation of MVD and the characteristic images of HAE using CEUS was analyzed. RESULTS: Twenty-three Wistar rats with hepatic E. multilocularis infection were killed, and 27 HAE lesions was found. The largest diameter of HAE lesion was 2.24 cm, and the average size was (0.97 +/- 0.48) cm. The shape of HAE lesions was round, oval, or irregular. HAE lesions presented a complex internal echo pattern. Spot-like color flow signal was observed in the tissues around the lesions, no blood flow signal was observed in HAE lesions. In 25 lesions, a circular rim-like enhancement belt was visualized at the periphery during early arterial phase, and honeycomb enhancement appeared in the other two lesions. The positive expression rate of CD34 in infiltrative zones surrounding HAE lesions was 99.2% (118/119), with 17.6% (21/119) of strong positive, 73.1% (87/119) of moderate positive, 8.4% (10/119) of weak positive, and 0.8% (1/119) of negative, respectively. In normal liver tissues, the positive expression rate of CD34 was 25.2% (30/119), no strong positive was found, with 4.2% (5/119) of moderate positive, 21.0% (25/119) of weak positive, and 74.8% (89/119) of negative, respectively. The sonographic infiltrative region in HAE lesion correlated with microvascular density (r = 0.238, P < 0.05). CONCLUSION: There is a positive correlation between the circular rim-like enhancement belt surrounding HAE lesions and the microvascular density in the rat model.

Oxidized mitochondrial DNA activates the cGAS-STING pathway in the neuronal intrinsic immune system after brain ischemia-reperfusion injury.

In the context of stroke and revascularization therapy, brain ischemia-reperfusion injury is a significant challenge that leads to oxidative stress and inflammation. Central to the cell's intrinsic immunity is the cGAS-STING pathway, which is typically activated by unusual DNA structures. The involvement of oxidized mitochondrial DNA (ox-mtDNA)-an oxidative stress byproduct-in this type of neurological damage has not been fully explored. This study is among the first to examine the effect of ox-mtDNA on the innate immunity of neurons following ischemia-reperfusion injury. Using a rat model of transient middle cerebral artery occlusion and a cellular model of oxygen-glucose deprivation/reoxygenation, we have discovered that ox-mtDNA activates the cGAS-STING pathway in neurons. Importantly, pharmacologically limiting the release of ox-mtDNA into the cytoplasm reduces inflammation and improves neurological functions. Our findings suggest that targeting ox-mtDNA release may be a valuable strategy to attenuate brain ischemia-reperfusion injury following revascularization therapy for acute ischemic stroke.

Blocking cerebral lymphatic system reduces central and peripheral inflammatory response in ischemic stroke.

Reduced blood supply to the brain activates the intracranial inflammatory response, a key contributor to secondary brain damage in ischemic stroke. Post-stroke, activation of peripheral immune cells leads to systemic inflammatory responses. Usingin vivo approaches, we investigated meningeal lymphatics' role in central immune cell infiltration and peripheral immune cell activation. The bilateral deep cervical lymph nodes (dCLNs) were removed 7 days before right middle cerebral artery occlusion in Sprague Dawley (SD) rats. At 3, 24, and 72 h post-intervention, brain immune cell infiltration and microglial and astrocyte activation were measured, while immune cells were classified in the spleen and blood. Inflammatory factor levels in peripheral blood were analyzed. Simultaneously, reverse verification was conducted by injecting AAV-vascular endothelial growth factor C (AAV-VEGFC) adenovirus into the lateral ventricle 14 days before middle cerebral artery occlusion (MCAO) induction to enhance meningeal lymph function. Blocking meningeal LVs in MCAO rats significantly reduced infarct area and infiltration, and inhibited microglia and pro-inflammatory astrocytes activation. After removing dCLNs, CD4+ T lymphocytes, CD8+ T lymphocytes, B lymphocytes, macrophages, and neutrophils in the spleen and blood of MCAO rats decreased significantly at different time points. The levels of inflammatory factors IL-6, IL-10, IL-1ß, and TNF-α in plasma decreased significantly. Tests confirmed the results, and AAV-VEGFC-induced MCAO rats provided reverse validation.

Rapid and accurate screening of cystic echinococcosis in sheep based on serum Fourier-transform infrared spectroscopy combined with machine learning algorithms.

Cystic echinococcosis (CE) in sheep is a serious zoonotic parasitic disease caused by Echinococcus granulosus sensu stricto (s.s.). Presently, the screening technology for CE in sheep is time-consuming and inaccurate, and novel screening technology is urgently needed. In this work, we combined machine-learning algorithms with Fourier transform infrared (FT-IR) spectroscopy of serum to establish a quick and accurate screening approach for CE in sheep. Serum samples from 77 E. granulosus s.s.-infected sheep to 121 healthy control sheep were measured by FT-IR spectrometer. To optimize the classification accuracy of the serum FI-TR method for the E. granulosus s.s.-infected sheep and healthy control sheep, principal component analysis (PCA), linear discriminant analysis, and support vector machine (SVM) algorithms were used to analyze the data. Among all the bands, 1500-1700 cm-1 band has the best classification effect; its diagnostic sensitivity, specificity, and accuracy of PCA-SVM were 100%, 95.74%, and 96.66%, respectively. The study showed that serum FT-IR spectroscopy combined with machine learning algorithms has great potential for rapid and accurate screening methods for the CE in sheep.

Evaluation of the Metabolic Activity of the Infiltration and Proliferation Areas of Hepatic Alveolar Echinococcosis in Rats Using Contrast-Enhanced Ultrasound.

This study evaluated the value of contrast-enhanced ultrasound (CEUS) in assessing the metabolic activity of infiltration and proliferation areas of hepatic alveolar echinococcosis (HAE) in rats. CEUS was performed on Wistar rats with HAE. The average grayscale value of the HAE lesion in peripheral infiltration and proliferation areas (PIPAs) and the adjacent normal liver tissue was analyzed quantitatively. Contrast imaging was classified as highly increased enhancement, moderately increased enhancement, and equal or decreased enhancement. Microvessel density (MVD) in the PIPAs was classified as strongly positive, moderately positive, and weakly positive. The metabolic activity of HAE in the PIPAs was classified as high activity, moderate activity, and low activity according to the MVD classification results. The kappa test was combined with the metabolic activity level of the PIPAs to analyze the consistency of CEUS intensity and MVD. CEUS can score the metabolic activity of the infiltration and proliferation areas around HAE lesions, and provides a basis for clinical treatment and follow-up visits. CEUS could be used as a more economical and effective imaging option for evaluating the metabolic activity of HAE lesions.

Comparative efficacy of targeted structural patterns of electroencephalography neurofeedback in children with inattentive or combined attention deficit hyperactivity disorder.

OBJECTIVE: To evaluate and compare the effects of three courses of different structural patterns of electroencephalography neurofeedback on predominantly inattentive attention deficit hyperactivity disorder (ADHD-PI) and combined ADHD (ADHD-CT). METHODS: Thirty-eight ADHD-PI and ADHD-CT children were selected and completed three courses of different structural patterns of electroencephalography neurofeedback according to their ADHD type. Before and after each course, relative power value of electroencephalography, including θ, ß, α, SMR and their ratios (θ/ß, θ/α), and eighteen integrated visual and auditory continuous performance test (IVA/CPT) quotients were obtained and compared. Data were analyzed by SPSS software, and p < .05 was considered statistically significant. RESULTS: After one course, θ, three IVA/CPT quotients in both types and two comprehensive quotients in ADHD-CT changed significantly (all p < .05). After two courses, θ/α, θ/ß and five IVA/CPT quotients in both types, θ and α in ADHD-PI, four comprehensive quotients, and four respond control quotients in ADHD-CT varied significantly compared to before treatment and after one course (all p < .05). After three courses, α, ß, θ, θ/α, θ/ß and ten IVA/CPT quotients in both types changed significantly compared to before treatment and after one course (all p < .05). In addition, six IVA/CPT quotients in both types after three courses were significantly higher than those after two courses (all p < .05). CONCLUSION: Different structural patterns of electroencephalography neurofeedback targeted for ADHD-CT and ADHD-PI were both effective and feasible. Three courses of EEG neurofeedback were most effective.

Early Diagnosis of Cerebral Ischemia Reperfusion Injury and Revelation of Its Regional Development by a H3R Receptor-Directed Probe.

In vivo imaging of cerebral hydrogen peroxide (H2O2) may facilitate early diagnosis of cerebral ischemia reperfusion injury (CIRI) and a revelation of its pathological progression. In this study, we report our rational design of a brain-targeting fluorescent probe using the basis of a pyridazinone scaffold. A structure-activity relationship study reveals that PCAB is the best candidate (Ki = 15.8 nM) for a histamine H3 receptor (H3R), which is highly expressed in neurons of the central nervous system. As a two-photon fluorescent probe, PCAB exhibits a fast, selective reaction toward both extra- and intracellular H2O2 in SH-SY5Y cells under oxygen glucose deprivation and resupply. In vivo fluorescent imaging of a middle cerebral artery occlusion mouse confirms that PCAB is an ultrasensitive probe with potent blood-brain barrier penetration, precise brain targeting, and fast detection of CIRI.

Evaluation of the clinical outcomes of telehealth for managing diabetes: A PRISMA-compliant meta-analysis.

INTRODUCTION: The objective of this study was to systematically review the literature and perform a meta-analysis comparing the clinical outcomes of telehealth and usual care in the management of diabetes. METHODS: Multiple strategies, including database searches (MEDLINE, PsycINFO, PubMed, EMBASE, and CINAHL), searches of related journals and reference tracking, were employed to widely search publications from January 2005 to December 2017. The change in hemoglobin A1c (HbA1c) levels was assessed as the primary outcome, and changes in blood pressure, blood lipids, body mass index (BMI), and quality of life were examined as secondary outcomes. RESULTS: Nineteen randomized controlled trials (n = 6294 participants) were selected. Telehealth was more effective than usual care in controlling the glycemic index in diabetes patients (weighted mean difference = -0.22%; 95% confidence intervals, -0.28 to -0.15; P < .001). This intervention showed promise in reducing systolic blood pressure levels (P < .001) and diastolic blood pressure levels (P < .001), while no benefits were observed in the control of BMI (P = .79). For total cholesterol and quality of life, telehealth was similar or superior to usual care. CONCLUSION: Telehealth holds promise for improving the clinical effectiveness of diabetes management. Targeting patients with higher HbA1c (≥9%) levels and delivering more frequent intervention (at least 6 times 1 year) may achieve greater improvement.

A dual-mediated liposomal drug delivery system targeting the brain: rational construction, integrity evaluation across the blood-brain barrier, and the transporting mechanism to glioma cells.

As the global population ages, cancer rates increase worldwide, and degenerative diseases of the central nervous system (CNS), brain tumors, and inflammation threaten human health more frequently. We designed a dual-mediated (receptor-mediated and adsorption-mediated) liposome, named transferrin-cell penetrating peptide-sterically stabilized liposome (TF-CPP-SSL), to improve therapy for gliomas through combining molecular recognition of transferrin receptors (TF-Rs) on the blood-brain barrier (BBB) and glioma cells with the internalization and lysosomal escaping ability of CPP. Based on the systematic investigation of structure-activity relations on the cellular level, we constructed TF-CPP-SSL rationally by conjugating TF and CPP moieties to the liposomes via PEG3.4K and PEG2.0K, respectively, and found the optimum densities of TF and CPP were 1.8% and 4%, respectively. These liposomes had the highest targeting efficacy for brain microvascular endothelial cell and C6 cell uptake but avoided capture by normal cells. Fluorescence resonance energy transfer technology and coculture models of BBB and glioma C6 cells indicated that TF-CPP-SSL was transported across the BBB without drug leakage, liposome breakup, or cleavage of ligand. TF-CPP-SSL offered advantages for crossing the BBB and entering into glioma C6 cells. Real-time confocal viewing revealed that TF-CPP-SSL was entrapped in endosomes of glioma C6 cells and then escaped from lysosomes successfully to release the liposomal contents into the cytosol. Entrapped contents, such as doxorubicin, could then enter the nucleus to exert pharmacological effects.

[Prevalence rate of ovine hepatic cystic echinococcosis in Quaker Wusu area of Bayinbuluke of Xinjiang, 2014].

OBJECTIVE: To investigate the prevalence rate of ovine hepatic cystic echinococcosis (HCE) in sheep in Quaker Wusu area of Bayinbuluke of Xinjiang by ultrasonography and provide evidence for the prevention and control of HCE in sheep. METHODS: The prevalence screening of HCE in sheep was conducted based on ultrasound images in this area in July 2014. The sheep were divided into different groups by dental age to calculate the age specific prevalence rate of HCE and analyzed the correlation between the dental age and the prevalence rate. RESULTS: The total prevalence rate of HCE in sheep in this area was 36.9%. The prevalence rates of none-calcified HCE and calcified HCE were 7.3% and 29.6%, respectively. The prevalence rates of none-calcified HCE in different age groups were 1.2% (1-2 years old), 1.4% (2-3 years old), 14.0% (3-4 years old), 10.0% (4-5 years old), 15.6% (5-6 years old) and 4.2% (>6 years old) respectively. The prevalence rate of calcified HCE in different age groups were 9.9% (1-2 years old), 16.2% (2-3 years old), 31.6% (3-4 years old), 47.8% (4-5 years old), 42.2% (5-6 years old) and 41.7% (>6 years old) respectively. The prevalence rate of HCE in 1-2 years old group was lower than those in other groups, the prevalence rate of HCE in age groups >3 years increased significantly. There was positive correlation between the prevalence rate of HCE and dental age (r = 0.372, R(2) = 0.107, F = 44.176, P = 0.000). CONCLUSION: HCE is highly endemic in Quaker Wusu area. The prevalence rate of HCE is low in sheep with young age and high in sheep aged 3-4 years. It is necessary to conduct early prevention of HCE in sheep in this area.

Expression of Hypoxia-Inducible Factor-1α in the Infiltrative Belt Surrounding Hepatic Alveolar Echinococcosis in Rats.

Our main aims were to investigate hypoxia inducible factor-1α (HIF-1α) expression in the surrounding invasion range of hepatic alveolar echinococcosis (HAE) lesions and determine the pathological basis of angiogenesis. In total, 23 Wistar rats with hepatic echinococcus multilocularis infection were killed and their livers, which contained 27 HAE lesions, obtained. Specimen segments were generated from 119 paraffin blocks. Comparative analysis of the tissue samples containing HAE nodules and hepatic parenchyma of the surrounding region was performed with the immunohistochemical SP method in this animal experiment. Expression patterns of HIF-1α in the surrounding invasion range and the hepatic parenchyma were compared. The HIF-1α positive expression rate was 97.5% (116/119 samples). Expression of HIF-1α in the actively multiplying infiltrative region of the HAE lesions was significantly higher than that in hepatic parenchyma (P < 0.05). Overexpression of HIF-1α in the actively multiplying infiltrative region of HAE lesions in rats is closely related to angiogenesis and microvasculature. The sensitivity of HIF-1α facilitates its application as a representative maker of HAE. Our data indicate that the invasion range of HAE lesions is based on extrusion and compression, and induces anoxia and ischemia in hepatic tissue. Thus, HIF-1α provides a valuable index for evaluating HAE activity, and induces anoxia and ischemia in hepatic tissue.

[Effects of inhaled nitric oxide on rabbits with meconium aspiration pneumonia].

OBJECTIVE: To evaluate effects of inhaled nitric oxide (iNO) on the expression of lung neutrophil adhesion molecule CD(11b) in experimental meconium aspiration pneumonia treated with conventional mechanical ventilation under room air or 100% O(2). METHODS: Rabbits were randomly allocated to 10 groups (n = 60), 6 of each group. Control or meconium aspiration pneumonia model groups were inhaled with room air or 100% O(2). Six treatment groups were treated with continuous NO inhalation at the doses of 6 x 10(-6), 10 x 10(-6) and 20 x 10(-6), respectively for 12 hours under room air or 100% O(2). The ratio of wet/dry (W/D) lung weight, alveolar septal width (ASW), myeloperoxidase (MPO) activity and lung injury score were measured. The expression of CD(11b) in neutrophils of the bronchoalveolar lavage fluid (BALF) was detected with flow cytometry. RESULTS: After 12 hours ventilation, the oxygenation was maintained better in treatment groups under different O(2) concentrations than that in model groups. Inflammatory evidence was found in lungs from all the model groups and treatment groups, which was characterized by serious inflammatory cell infiltration in alveolar space and hyaline membrane formation. The lung inflammation was decreased in all groups with nitric oxide inhalation. The ratio of W/D lung weight and ASW among different groups had no significant difference. MPO activities were significantly decreased in groups treated with 10 x 10(-6) and 20 x 10(-6) iNO compared with the model groups [with the concentration of 21% O(2), (1.8 +/- 0.2) U/g vs (4.4 +/- 0.5) U/g and (2.0 +/- 0.1) U/g vs (4.4 +/- 0.5) U/g;with the concentration of 100% O(2), (1.7 +/- 0.4) U/g vs (2.8 +/- 0.5) U/g and (1.4 +/- 0.3) U/g vs (2.8 +/- 0.5) U/g, P < 0.05, respectively]. MPO activities in the 20 x 10(-6) iNO group under 100% O(2) were significantly reduced compared with those under 21%O(2) [(1.4 +/- 0.3) U/g vs (2.0 +/- 0.1) U/g, P < 0.05]. Nitric oxide inhalation with the doses of 10 x 10(-6) and 20 x 10(-6) significantly decreased the expression of CD(11b) (MFI) in neutrophils of the BALF compared with the expressions in model groups without NO treatment (with 21% O(2), 121 +/- 20 vs 392 +/- 204 and 112 +/- 30 vs 392 +/- 204; with 100% O(2), 113 +/- 24 vs 293 +/- 65 and 102 +/- 14 vs 293 +/- 65, P < 0.05, respectively). Under the same iNO dose (10 x 10(-6) or 20 x 10(-6)) no statistic difference was found between groups of different inspired oxygen concentrations (21% and 100%). CONCLUSIONS: Inhaled nitric oxide with the doses of 10 x 10(-6) to 20 x 10(-6) could significantly down-regulate the CD(11b) expression in neutrophil of the BALF and reduce the neutrophil sequestration and MPO activity in rabbit lungs, which may decrease the lung inflammation process in meconium aspiration pneumonia.