Control of wakefulness by lateral hypothalamic glutamatergic neurons in male mice.

The lateral hypothalamus (LH) plays a key role in the maintenance of cortical activation and wakefulness. In the LH, the two main neuronal cell populations consist of excitatory glutamatergic neurons and inhibitory GABAergic neurons. Recent studies have shown that inhibitory LH GABAergic neurons are wake-promoting. However, the mechanism by which excitatory LH glutamatergic neurons contribute to sleep-wake regulation remains unclear. Using fiber photometry in male mice, we demonstrated that LH glutamatergic neurons exhibited high activities during both wakefulness and rapid eye movement sleep. Chemogenetic activation of LH glutamatergic neurons induced an increase in wakefulness that lasted for 6 hr, whereas suppression of LH glutamatergic neuronal activity caused a reduction in wakefulness. Brief optogenetic activation of LH glutamatergic neurons induced an immediate transition from slow-wave sleep to wakefulness, and long-lasting optogenetic stimulation of these neurons maintained wakefulness. Moreover, we found that LH-locus coeruleus/parabrachial nucleus and LH-basal forebrain projections mediated the wake-promoting effects of LH glutamatergic neurons. Taken together, our data indicate that LH glutamatergic neurons are essential for the induction and maintenance of wakefulness. The results presented here may advance our understanding of the role of LH in the control of wakefulness.

Diagnostic accuracy of the Berlin questionnaire and therapeutic effect of nasal continuous positive airway pressure in OSAHS patients with glucose metabolic dysfunction.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with alterations in glucose metabolism. The Berlin questionnaire (BQ) is effective in identifying subjects with high risk of OSAHS. However, its validity in patients with glucose metabolic dysfunction remains unclear. Our study aims to examine the diagnostic efficacy of the BQ in detecting OSAHS in patients with glucose metabolic dysfunction and to explore the effect of nasal CPAP on glucose metabolism. METHODS: Patients with glucose metabolic dysregulation were first asked to complete the BQ and then recruited for polysomnogram (PSG). The diagnostic accuracy of the BQ and the relationships between groups with normal glucose tolerance (NGT), elevated fasting blood glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were analyzed. Subjects with both OSAHS and glucose dysregulation received CPAP treatment and underwent an oral glucose tolerance test. Changes in apnea-hypopnea indices (AHI) and glycemic parameters were calculated to determine the efficacy of CPAP. RESULTS: Glycosylated hemoglobin and insulin levels were statistically different between the high-risk and low-risk groups according to the BQ. For diagnosis of subjects with OSAHS who also had glucose metabolic dysfunction, the sensitivity and specificity of the BQ using AHI cut-off values at 5 events per hour were 73% and 67%. CPAP therapy effectively reduced the blood glucose, HOMA-IR, and insulin levels. CONCLUSIONS: The BQ can be considered to be an effective and economical screening tool for patieints with OSAHS who also have glucose metabolic dysfunction. Treatment with CPAP may improve glycemic parameters.

Heterozygous SOD2 deletion deteriorated chronic intermittent hypoxia-induced lung inflammation and vascular remodeling through mtROS-NLRP3 signaling pathway.

Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2+/-) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1ß elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.

Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea.

Cystic metastatic nasopharyngeal carcinoma presenting as branchial cleft cyst: report of two cases and review of the literature.

PURPOSE: To describe the differential diagnosis between solitary cystic metastatic carcinoma from branchial cleft cyst and provide references for clinicians to treat cystic metastases from primary sites of the head and neck region. MATERIALS AND METHODS: Two cases of cystic metastatic nasopharyngeal carcinoma (NPC) are presented and a review of the relevant English literature on cystic metastasis from head and neck cancer was performed. RESULTS: Two adult patients with a lateral cystic neck mass were initially clinically diagnosed as branchial cleft cysts. Based on the postoperative histopathologic examination and nasopharyngeal blind biopsy, they were finally diagnosed as cystic metastases from occult nasopharyngeal carcinoma. After a review of the literature, diagnostic strategies, histopathologic features, and therapeutic options for cervical cystic metastases were discussed. CONCLUSION: Cervical cystic metastasis of NPC in adults may mimic branchial cleft cyst in clinical, radiological, and even histological features. Surgeons should bear in mind that when lateral neck cysts with characteristics of suspected malignancy are confronted, nasopharynx examination, including blind or random biopsy, is highly recommended before surgery. Metastatic disease should always be considered as a potential differential diagnosis in adult patients with a cystic neck lesion. Correct diagnosis is important so that appropriate surgical and radiotherapeutic treatment can be delivered.

Expression profiling of microRNAs in hippocampus of rats following traumatic brain injury.

The changes of microRNA expression in rat hippocampus after traumatic brain injury (TBI) were explored. Adult SD rats received a single controlled cortical impact injury, and the ipsilateral hippocampus was harvested for the subsequent microarray assay at three time points after TBI: 1st day, 3rd day and 5th day, respectively. We characterized the microRNA expression profile in rat hippocampus using the microRNA microarray analysis, and further verified microarray results of miR-142-3p and miR-221 using quantitative real-time PCR. Totally 205 microRNAs were identified and up-/down-regulated more than 1.5 times. There were significant changes in 17 microRNAs at all three time points post-TBI. The quantitative real-time PCR results of miR-142-3p and miR-221 indicated good consistency with the results of the microarray method. MicroRNAs altered at different time points post-TBI. MiR-142-3p and miR-221 may be used as potentially biological markers for TBI assessment in forensic practice.

Genomic structure analysis and construction of DNA fingerprint for four sheep populations.

The Yongdeng Qishan sheep (QS) is a sheep population found locally in China. To gain in-depth knowledge of its population characteristics, three control groups were chosen, comprising the Lanzhou fat-tailed sheep (LFT), TAN sheep (TAN), and Minxian black fur sheep (MBF), inhabiting the nearby environments. This study genotyped a total of 120 individuals from four sheep populations: QS, LFT, TAN, and MBF. Using Specific-Locus Amplified Fragment Sequencing, we conducted genetic diversity, population structure, and selective sweep analysis, and constructed the fingerprint of each population. In total, there were 782 535 single nucleotide polymorphism (SNP) variations identified, with most being situated within regions that are intergenic or intronic. The genetic diversity analysis revealed that the QS population exhibited lower genetic diversity compared to the other three populations. Consistent results were obtained from the principal component, phylogenetic tree, and population structure analysis, indicating significant genetic differences between QS and the other three populations. However, a certain degree of differentiation was observed within the QS population. The linkage disequilibrium (LD) patterns among the four populations showed clear distinctions, with the QS group demonstrating the most rapid LD decline. Kinship analysis supported the findings of population structure, dividing the 90 QS individuals into two subgroups consisting of 23 and 67 individuals. Selective sweep analysis identified a range of genes associated with reproduction, immunity, and adaptation to high-altitude hypoxia. These genes hold potential as candidate genes for marker-assisted selection breeding. Additionally, a total of 86 523 runs of homozygosity (ROHs) were detected, showing non-uniform distribution across chromosomes, with chromosome 1 having the highest coverage percentage and chromosome 26 the lowest. In the high-frequency ROH islands, 79 candidate genes were associated with biological processes such as reproduction and fat digestion and absorption. Furthermore, a DNA fingerprint was constructed for the four populations using 349 highly polymorphic SNPs. In summary, our research delves into the genetic diversity and population structure of QS population. The construction of DNA fingerprint profiles for each population can provide valuable references for the identification of sheep breeds both domestically and internationally.

Anterior cingulate cortex projections to the dorsal medial striatum underlie insomnia associated with chronic pain.

Chronic pain often leads to the development of sleep disturbances. However, the precise neural circuit mechanisms responsible for sleep disorders in chronic pain have remained largely unknown. Here, we present compelling evidence that hyperactivity of pyramidal neurons (PNs) in the anterior cingulate cortex (ACC) drives insomnia in a mouse model of nerve-injury-induced chronic pain. After nerve injury, ACC PNs displayed spontaneous hyperactivity selectively in periods of insomnia. We then show that ACC PNs were both necessary for developing chronic-pain-induced insomnia and sufficient to mimic sleep loss in naive mice. Importantly, combining optogenetics and electrophysiological recordings, we found that the ACC projection to the dorsal medial striatum (DMS) underlies chronic-pain-induced insomnia through enhanced activity and plasticity of ACC-DMS dopamine D1R neuron synapses. Our findings shed light on the pivotal role of ACC PNs in developing chronic-pain-induced sleep disorders.

Ventral pallidal glutamatergic neurons regulate wakefulness and emotion through separated projections.

Insomnia is often comorbid with depression, but the underlying neuronal circuit mechanism remains elusive. Recently, we reported that GABAergic ventral pallidum (VP) neurons control wakefulness associated with motivation. However, whether and how other subtypes of VP neurons regulate arousal and emotion are largely unknown. Here, we report glutamatergic VP (VPVglut2) neurons control wakefulness and depressive-like behaviors. Physiologically, the calcium activity of VPVglut2 neurons was increased during both NREM sleep-to-wake transitions and depressive/anxiety-like behaviors in mice. Functionally, activation of VPVglut2 neurons was sufficient to increase wakefulness and induce anxiety/depressive-like behaviors, whereas inhibition attenuated both. Dissection of the circuit revealed that separated projections of VPVglut2 neurons to the lateral hypothalamus and lateral habenula promote arousal and depressive-like behaviors, respectively. Our results demonstrate a subtype of VP neurons is responsible for wakefulness and emotion through separated projections, and may provide new lines for the intervention of insomnia and depression in patients.

[Spectrum analysis and measurment research on visual density of the national standard densitometer].

Visual density is an important index for the estimation of photographic film and visual photo. The development of biomedical image and macromolecule image needs high measurement uncertainty of visual density in spectrum characteristic. The ISO standard of visual density measurement conditions was modified in 2001. A series of equipments designed for densitometer enhance the spectral matching between the national standard densitometer and the ISO standard function. And a new measurement formula is given based on theory analysis. According to the measurement data and uncertainty analysis, the combined uncertainties are 0.001 1 (0 < D < 4.0) and 0.003 1 (4.0 < or = D < 6.0).

Role of Vitamin D Receptor Gene Polymorphisms on the Susceptibility to Periodontitis: A Meta-Analysis of a Controversial Issue.

Background: To assess whether vitamin D receptor (VDR) gene polymorphisms influence the susceptibility to periodontitis. Methods: We retrieved 34 relevant studies, comprising a total of 3848 subjects suffering from periodontitis and 3470 controls for this meta-analysis. The pooled data were analyzed using STATA software. Results: Among all ethnic groups examined, the VDR BsmI polymorphism was associated with periodontitis under the recessive model (odds ratio [OR] = 0.722, 95% confidence interval [CI]: 0.532-0.980, p = 0.037). There was also a link between the VDR FokI polymorphism and periodontitis in the overall population (dominant model: OR = 1.459, 95% CI: 1.050-2.028, p = 0.025 and allelic model: OR = 1.386, 95% CI: 1.026-1.874, p = 0.034) and in Chinese participants (dominant model: OR = 1.813, 95% CI: 1.185-2.774, p = 0.006; allelic model: OR = 1.602, 95% CI: 1.044-2.459, p = 0.031) when stratified by race. The FokI variant was also correlated with aggressive periodontitis (AP) (dominant model: OR = 2.204, 95% CI: 1.148-4.231, p = 0.018; allelic model: OR = 2.017, 95% CI: 1.365-2.980, p = 0.000; and recessive model: OR = 2.903, 95% CI: 1.520-5.542, p = 0.001). We also showed a correlation between the VDR TaqI variant and periodontitis susceptibility in Caucasian populations (dominant model: OR = 0.525, 95% CI: 0.318-0.866, p = 0.012). The results revealed that there was no relationship between the VDR ApaI gene polymorphism and periodontitis. Conclusions: There was a link between the VDR BsmI and FokI gene polymorphisms and periodontitis in the overall population. In addition, the FokI polymorphism was correlated with AP. There was a link between the TaqI polymorphism and periodontitis in the Caucasian population. The VDR Apal variant, however, was not correlated with periodontitis.

The antifertility effectiveness of copper/low-density polyethylene nanocomposite and its influence on the endometrial environment in rats.

PURPOSE: The study was conducted to investigate the antifertility effectiveness of copper/low-density polyethylene nanocomposite (nano-Cu/LDPE) and its influence on the endometrial environment in rats. METHODS: One hundred and seventy sexually mature female Sprague-Dawley (SD) rats were randomly divided into five groups: sham-operated control group (SO group, n=10), bulk copper group (Cu group, n=40), LDPE group (n=40), and nano-Cu/LDPE groups I (n=40) and II (n=40). Twenty rats in each group except for the SO group were mated with male rats of proven fertility, from 30 days after insertion, and the antifertility rates (ATs) were observed at Day 11 of pregnancy. The concentrations of prostaglandin E(2) (PGE(2)) and tissue plasminogen activator (tPA) in the endometrium of the remaining rats in each group were measured by using ELISA at the 30th and 60th day after insertion, respectively. RESULTS: ATs in the Cu group and nano-Cu/LDPE groups I and II (100%) were significantly higher than those in the LDPE group (p<.05). Compared with those in the SO group, the concentrations of PGE(2) and tPA in all experimental groups except for PGE(2) levels in the LDPE group were significantly increased at Day 30 after insertion, and these parameters in the nano-Cu/LDPE groups were significantly lower than in the Cu group (p<.05). At Day 60 after insertion, tPA levels were still higher in the Cu and nano-Cu/LDPE groups, but there was no difference in PGE(2) levels in all groups except for the Cu group. CONCLUSION: Nano-Cu/LDPE exhibits satisfactory contraceptive efficacy with less influence on the endometrium PGE(2) and tPA levels.

[Expression patterns of age-related molecule c-kit, HIWI and vimentin in the rat testis and epididymis].

OBJECTIVE: To examine the differences in the expressions of c-kit, HIWI and vimentin in the testis and epididymis of rats aged different months, investigate the regular changes in the expression of characteristic molecules in the ripening and senescent process of the testis and epididymis, and provide experimental evidence for studies on the aging of the male reproductive system. METHODS: Sprague-Dawley male rats were divided into a young group (6-month-old, n=10), an adult group (12-month-old, n=10) and an aged group (24-month-old, n=10). The immunohistochemical SP method was used to examine c-kit, HIWI and vimentin in the testis and epididymis of the rats. RESULTS: The positive immunohistochemical reaction to c-kit was observed mainly in spermatogonia, weakly in other cells and also in the epithelia and lumens of the epididymis. The abundant expression of HIWI was detected in all stages of spermatogenic cells in the testis and epididymis of the 6-month-old and 12-month-old rats. Moreover, spermatogonias and primary spermatocytes displayed intense expression. Sertoli cells, Leydig cells, myoid cells and vascular endothelial cells (VEC) were also HIWI-positive cells. But the positive expression decreased with age in the testis and epididymis of the 24-month-old rats (P > 0.05). vimentin expression was weak in the testis and epididymis of the 6-month-olds but increased significantly in the 24-month-olds (P > 0.01). CONCLUSION: The expressions of c-kit and HIWI decreased in the testis and epididymis of the 24-month-old rats, while vimentin expression increased markedly with age. The results suggest that the aging of the testis and epididymis is closely related to the abnormal transduction of cell signals.

[Relationship between P300 and intelligence quotient in severe head injury patients].

OBJECTIVE: To explore the change of brain cognition function in severe head injury and the correlation between P300 in event-related potential (ERP) and intelligence quotient (IQ). METHODS: Auditory P300 was measured and intelligence quotient was tested by Wechsler Adult Intelligence Scale Revised in China (WAIS-RC) in 40 severe head injury patients. Auditory P300 was measured in 40 normal healthy people as control group. RESULTS: The latencies of P300 in severe head injury patients group were longer than in control group. There was a significant difference between the two groups (P< 0.01). There were significant negative correlations between P300 latency and VIQ and FIQ respectively (r=-0.335,-0.344, P<0.05). CONCLUSION: ERP might be taken as an objective index for measuring the change of the brain cognition function in patients with severe head injury.

[Analysis of the differences in the expression of HSP27 and c-kit between benign prostatic hyperplasia and prostatic cancer tissues].

OBJECTIVE: To examine the differences in the expression of HSP27 and c-kit between benign prostatic hyperplasia (BPH) and prostatic cancer (PCa) tissues and to analyse the relationship between their expression and BPH and PCa, especially the relationship with the occurrence, development, prognosis and treatment of PCa. METHODS: An immunohistochemical staining (SP method) for HSP27 and c-kit was undertaken on 40 BPH and 40 PCa tissues samples. RESULTS: Consistent patterns of cytoplasmic staining for HSP27 were seen in all sections of tissue from BPH. The glandular epithelium stained very strongly positively and the stroma stained positively. The staining for HSP27 in PCa tissues was located in the cytoplasm of glandular epithelia, but the expression of HSP27 in PCa was higher than BPH (P < 0.05). The staining for c-kit in BPH tissues was located in the cytoplasm of smooth muscle cells, and in PCa tissues was located in epithelial cells. The expression of c-kit in PCa tissues was lower than BPH (P < 0.05). The expression level of both HSP27 and c-kit were decreased with the development of grade of PCa (P < 0.05); HSP27 was increased with the development of clinical stage of PCa (P < 0.05 ); c-kit was decreased with the development of clinical stage of PCa (P < 0.05). CONCLUSION: The expression level of HSP27 and c-kit was highly correlated with the process of the development from BPH to PCa, and also correlated with tumor grades and stages. The expression of HSP27 and c-kit may be used as an important pathological index and may be helpful for the treatment of PCa.

[The effects of eucommia ulmoides oliv on catching action of diabetic rats and myelinated nerve fibers in penile tissues].

OBJECTIVE: To explore the pharmacodynamic and pathological mechanism of eucommia ulmoides oliv in improving erectile function. METHODS: Thirty male diabetic rats were randomly divided into three groups: group A (n = 10, escipient group), group B (n = 10, sildenafil group), group C (n = 10, eucommia ulmoides oliv group) and group D (n = 10, the normal control group). After gavage for four weeks, the catching behaviors of all rats were observed, and ultrastructure of myelinated nerve fibers in penile tissue was examined by transmission electron microscope. The expression of neuronal nitric oxide synthase (nNOS) in penile tissues was examined by two steps immunohistochemistry method. RESULTS: Compared with group A, catching frequency of the rats in group C was notably increased (P < 0.05) and the expression of nNOS in penile tissue was significantly (P < 0.001). The examination by transmission electron microscope showed that in the rats' penile tissue of group A, myelinated nerve fibers were irregularly arranged and partially degenerated, and myelin sheaths lamella were splited and exhibited vacuoles or network forms. In group C, there were regular arrangements of myelinated nerve fibers, in which the formation of lamella was clear. CONCLUSION: By remitting the impairement of myelinated nerve fibers and enhancing the expression of nNOS in penile tissue, eucommia ulmoides oliv can improve erectile function of diabetic rats.

[Effect of eucommia ulmoides oliv on SOD activity and alpha-actin expression in the penile tissues of diabetic rats].

OBJECTIVE: To study the effect of aqueous abstract from eucommia ulmoides oliv on the activity of superoxide dismutase (SOD) and alpha-actin expression in the penile tissues of rats with diabetes mellitus (DM) in vitro. METHODS: A diabetes model was established by administration of alloxun twice to Sprague Dawley (SD) rats. Ten diabetic and 10 normal rats were randomly selected and the penile strips of each rat were divided into four equal shares and cultured in two groups, a eucommia ulmoides oliv coculture group (Group A, further dicided into 1 microg/ml, 10 microg/ml and 100 microg/ml subgroups) and a control group (Group B). Seven days later, the activity of SOD in the culture medium was detected by spectrophotometry, and the levels of micro-actin expression in the penile tissues were examined with the immunohistochemical method. RESULTS: Compared with Group B, the activity of SOD in the culture medium in athe 10 and 100 microg/ml subgroups was notably elevated (P < 0.01), and the numbers of immunoreactive positive cells of alpha-actin in the penile tissues remarkably increased (P < 0.01). CONCLUSION: The activity of SOD and alpha-actin expression in the penile tissues of diabetic rats in vitro can be increased by eucommia ulmioides oliv.

[An electron microscope observation for the abnormal ultrastructure of the connecting piece in human spermatozoa from infertile painters].

OBJECTIVES: To investigate possible abnormalities of the sperm neck in eight infertile painters observed by transmission electron microscope. METHODS: Spermatozoa from 8 infertile painters (21-32 years old) were observed by transmission electron microscope. RESULTS: The abnormalities of the connecting piece could be divided into 6 types, among which the anomaly of the connecting piece concomitant with a true nuclemalamic condition was the most serious. CONCLUSIONS: The abnormalities may be related to expression obstacles of nuclear genome and mitochondrial genome, and to anomalous cellular signal transduction during spermiogenesis as well.

Effect of noninvasive positive pressure ventilation on weaning success in patients receiving invasive mechanical ventilation: a meta-analysis.

BACKGROUND: Noninvasive positive pressure ventilation (NIPPV) has been proposed to shorten the duration of mechanical ventilation in intubated patients, especially those who fail initial weaning from invasive mechanical ventilation (IMV). However, there are also some discrepancies in terms of weaning success or failure, incidence of re-intubation, complications observed during study and patient outcomes. The primary objective of this update was to specifically investigate the role of NIPPV on facilitating weaning and avoiding re-intubation in patients intubated for different etiologies of acute respiratory failure, by comparing with conventional invasive weaning approach. METHODS: We searched randomized controlled trials (RCTs) comparing noninvasive weaning of early extubation and immediate application of NIPPV with invasive weaning in intubated patients from PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Knowledge and Springerlink databases. Records from conference proceedings and reference lists of relevant studies were also identified. RESULTS: A total of 11 RCTs with 623 patients were available for the present analysis. Compared with IMV, NIPPV significantly increased weaning success rates (odds ratio (OR): 2.50, 95% confidence interval (CI): 1.46 - 4.30, P = 0.0009), decreased mortality (OR: 0.39, 95%CI: 0.20 - 0.75, P = 0.005), and reduced the incidence of ventilator associated pneumonia (VAP) (OR: 0.17, 95%CI: 0.08 - 0.37, P < 0.00001) and complications (OR: 0.22, 95%CI: 0.07 - 0.72, P = 0.01). However, effect of NIPPV on re-intubation did not reach statistical difference (OR: 0.61, 95%CI: 0.33 - 1.11, P = 0.11). CONCLUSIONS: Early extubation and immediate application of NIPPV is superior to conventional invasive weaning approach in increasing weaning success rates, decreasing the risk of mortality and reducing the incidence of VAP and complications, in patients who need weaning from IMV. However, it should be applied with caution, as there is insufficient beneficial evidence to definitely recommend it in terms of avoiding re-intubation.