Effects of Fu's subcutaneous needling at myofascial trigger points on pain and lumbar mobility in patients with lumbar disc herniation： a randomized controlled trial. / ç­‹è†œè§¦å‘ç‚¹æµ®é’ˆæ²»ç–—å¯¹è °æ¤Žé—´ç›˜çªå‡ºç—‡æ‚£è€ ç–¼ç—›åŠè °éƒ¨æ´»åŠ¨åº¦å½±å“çš„éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the therapeutic effect of Fu's subcutaneous needling at myofascial trigger points (MTrPs) on pain, lumbar mobility and the quality of life in patients with lumbar disc herniation (LDH), so as to provide clinicians with new ideas and methods in treating LDH. METHODS: One hundred patients with LDH admitted to department of rehabilitation medicine of the affiliated hospital of Chengdu University of Traditional Chinese Medicine from January 2022 to January 2023 were collected as the subjects, and they were randomly divided into an observation group and a control group, 50 cases in each one. In the observation group, the spreading technique of Fu's subcutaneous needling was delivered at MTrP. In the control group, the routine acupuncture was applied to Shenshu (BL23), Weizhong (BL40) and MTrP. The treatment was given 3 times weekly, for 2 weeks in the two groups. The score of visual analogue scale (VAS) was evaluated before treatment, at the moment after the 1st treatment completion and after 2 weeks of treatment, separately, and the inclinometer was adopted to measure the range of motion (ROM) of the lumbar flexion, extension and lateral flexion. The numbers of MTrPs and their distribution were recorded before treatment and after the completion of a 2-week treatment in the two groups. Before treatment and in 4 weeks of follow-up, using SF-36 scale, the score of the quality of life was evaluated. The incidence of adverse effects was recorded. RESULTS: At the moment of the 1st treatment completion and after 2 weeks of treatment, VAS score and ROM of the lumbar region were significantly improved in comparison with those before treatment in the two groups and the improvement was superior in the observation group compared with the control group (P<0.05, P<0.01). After 2 weeks of treatment, the total number of MTrPs and the counts of MTrPs in each muscle zone were reduced when compared with those before treatment (P<0.05). In the observation group, the total number of MTrPs and numbers of MTrPs in the zones of quadratus lumborum, musculi multifidus and musculi iliocostalis lumborum decreased significantly when compared with the control group (P<0.05), while the difference was not significant in the numbers in the zone of musculi glutaeus medius between the two groups. In 4 weeks of follow-up, the scores of SF-36 scale were improved in comparison with those before treatment in each group and the result in the observation was better (P<0.05). No any adverse events occurred during treatment in the two groups. CONCLUSIONS: Fu's subcutaneous needling is effective for reducing the numbers of MTrPs and improving analgesia, ROM of the lumbar region, as well as the long-term quality of life in the patients with LDH.

The mitochondrial protein TIMM44 is required for angiogenesis in vitro and in vivo.

The mitochondrial integrity and function in endothelial cells are essential for angiogenesis. TIMM44 (translocase of inner mitochondrial membrane 44) is essential for integrity and function of mitochondria. Here we explored the potential function and the possible mechanisms of TIMM44 in angiogenesis. In HUVECs, human retinal microvascular endothelial cells and hCMEC/D3 brain endothelial cells, silence of TIMM44 by targeted shRNA largely inhibited cell proliferation, migration and in vitro capillary tube formation. TIMM44 silencing disrupted mitochondrial functions in endothelial cells, causing mitochondrial protein input arrest, ATP reduction, ROS production, and mitochondrial depolarization, and leading to apoptosis activation. TIMM44 knockout, by Cas9-sgRNA strategy, also disrupted mitochondrial functions and inhibited endothelial cell proliferation, migration and in vitro capillary tube formation. Moreover, treatment with MB-10 ("MitoBloCK-10"), a TIMM44 blocker, similarly induced mitochondrial dysfunction and suppressed angiogenic activity in endothelial cells. Contrarily, ectopic overexpression of TIMM44 increased ATP contents and augmented endothelial cell proliferation, migration and in vitro capillary tube formation. In adult mouse retinas, endothelial knockdown of TIMM44, by intravitreous injection of endothelial specific TIMM44 shRNA adenovirus, inhibited retinal angiogenesis, causing vascular leakage, acellular capillary growth, and retinal ganglion cells degeneration. Significant oxidative stress was detected in TIMM44-silenced retinal tissues. Moreover, intravitreous injection of MB-10 similarly induced oxidative injury and inhibited retinal angiogenesis in vivo. Together, the mitochondrial protein TIMM44 is important for angiogenesis in vitro and in vivo, representing as a novel and promising therapeutic target of diseases with abnormal angiogenesis.

SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients. Patients and Methods: A total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 (SERPINA1) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD. Results: SERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1ß, IL-17, and transforming growth factor (TGF)-ß1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1ß levels (r = 0.5188, p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%). Conclusion: The methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1ß levels. These findings may be of diagnostic value.

Changes of circulating biomarkers of inflammation and glycolipid metabolism by CPAP in OSA patients: a meta-analysis of time-dependent profiles.

Background: Continuous positive airway pressure (CPAP) is the first-line therapy for moderate-to-severe obstructive sleep apnea (OSA). Specifying timing of CPAP benefits on OSA-related biomarkers will help to assess the effectiveness of CPAP and to optimize the treatment strategies. Purpose: To explore the time-dependent changes of circulating biomarkers to CPAP treatment in patients with OSA, including inflammatory biomarkers [C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α)] and glycolipid metabolic biomarkers [fasting blood glucose (FBG), fasting insulin (FINS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG)]. Methods: Searches of PubMed and Embase database were completed. Two independent reviewers extracted data from 68 included studies. A meta-analysis was conducted using a random-effect (or fixed-effect) model and standardized mean difference (SMD) model. The timing profiles of circulating biomarkers changes of inflammation and glycolipid metabolism were analyzed based on different CPAP duration, that is, short-term (<3 months), mid-term (3-6 months), and long-term (⩾6 months). Results: Those first improved by short-term treatment include CRP [SMD: 0.73, 95% confidence interval (CI): 0.15-1.31; p = 0.014], TNF-α [SMD: 0.48 (95% CI: 0.10-0.86; p = 0.014)], FBG [SMD: 0.32 (95% CI: 0.07-0.57; p = 0.011)], and LDL [SMD: 0.40 (95% CI: 0.18-0.62; p = 0.000)]. Those first improved by the mid-term or long-term treatment include HDL [SMD: -0.20 (95% CI: -0.36 to -0.03; p = 0.018)] and TC [SMD: 0.20 (95% CI: 0.05-0.34; p = 0.007)]. There were insignificant changes for TG and FINS after short or long CPAP. Conclusion: Our results imply that changes of circulating biomarkers for patients with OSA under CPAP treatment have a time-dependent profile.

Telehealth Technology Application in Enhancing Continuous Positive Airway Pressure Adherence in Obstructive Sleep Apnea Patients: A Review of Current Evidence.

Obstructive sleep apnea (OSA) is a common type of sleep-disordered breathing associated with multiple comorbidities. Continuous positive airway pressure (CPAP) is the first choice for moderate-severe OSA but poor compliance brings a great challenge to its effectiveness. Telehealth interventions ease the follow-up process and allow healthcare facilities to provide consistent care. Fifth-generation wireless transmission technology has also greatly rationalized the wide use of telemedicine. Herein, we review the efficacy of the telehealth system in enhancing CPAP adherence. We recommend applying telemonitoring in clinical practice and advocate the development of a biopsychosocial telemedicine model with the integration of several interventions. Big databases and promising artificial intelligent technologies make clinical decision support systems and predictive models based on these databases possible.

Surfaxin attenuates PM2.5-induced airway inflammation via restoring surfactant proteins in rats exposed to cigarette smoke.

Epidemiologic studies have shown that the fine particulate matter 2.5 (PM2.5) exaggerates chronic airway inflammation involving in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Surfactant proteins (SPs) decreases significantly related to airflow limitation and airway inflammation. However, how to restore the reduction of SPs levels in airway inflammation exposed to PM2.5 has not been well understood. In the present study, the SPs including SPA, SPB, SPC and SPD levels in bronchoalveolar lavage fluid (BALF) were detected from patients with stable COPD. Rats were exposed to cigarette smoke and PM2.5. After given with Surfaxin, the expression of SPs, protein kinase C (PKC) and tight junction protein (ZO-1) in lung tissue and the levels of C-reactive protein (CRP) and fibrinogen (FIB) in plasma was observed. The results showed that SPA, SPB and SPD were significantly lower than those of the control group (p < 0.01). PM2.5 aggravated smoking-induced airway inflammation and oxidative stress demonstrated by pathological changes of lung tissue and increased levels of CRP and PKC in vivo. PM2.5 decreased the expression of all the SPs and ZO-1, which could be significantly restored by Surfaxin. These findings indicate that Surfaxin protects the alveolar epithelium from PM2.5 in airway inflammation through increasing SPs.

Transcriptomics Analysis Identifies the Presence of Upregulated Ribosomal Housekeeping Genes in the Alveolar Macrophages of Patients with Smoking-Induced Chronic Obstructive Pulmonary Disease.

BACKGROUND AND AIMS: Alveolar macrophages (AM) play a crucial role in the development of chronic obstructive pulmonary disease (COPD). The role that AM plays in the molecular pathways and clinical phenotypes associated with tobacco-related emphysema remain poorly understood. Thus, we investigated the transcriptomic profile of AM in COPD patients with a history of smoking and explored the molecular mechanisms associated with enriched pathways and hub genes. METHODS: Four data sets (GSE2125, GSE8823, GSE13896 and GSE130928) were retrieved from the GEO Database. A total of 203 GEO samples (GSM) were collated for this study. About 125 of these cases were classified as smokers (91 as healthy non-COPD smokers and 34 as COPD smokers). Based on the bioinformatics obtained using the R3.6.1 program, the data were successively adopted for differential genetic expression analysis, enrichment analysis (EA), and then protein-protein interaction analysis (PPI) in a STRING database. Finally, Cytoscape 3.8 software was used to screen the hub genes. A further data analysis was performed using a set of 154 cases, classified as 64 healthy non-smokers and 91 as healthy smokers. The same procedures were used as for the COPD dataset. RESULTS: When comparing the data pertaining to COPD-smokers and non-COPD smokers, the top ten genes with the greatest transcriptional differences were found to be NADK, DRAP1, DEDD, NONO, KLHL12, PRKAR1A, ITGAL, GLE1, SLC8A1, SVIL. A GSEA (Gene Set Enrichment Analysis) revealed that these genes manifested an up-regulated ribosomal pathway in contrast with other genes that exhibited an extensive down-regulated pathway. The hub genes were mainly genes encoding ribosomal subunits through PPI. Furthermore, it was found that there is a narrow transcriptional difference between healthy non-smokers and non-COPD smokers and the hub genes identified here are mainly members of the chemokines, including CCL5, CCR5, CXCL9 and CXCL11. CONCLUSION: An elevated activity of the ribosome pathway in addition to the increased expression of ribosomal housekeeping genes (also known as hub genes) were identified with COPD-smokers, and these have the potential to cause a wide range of downstream pathogenetic effects. As for the preclinical phase, non-COPD smokers were found to be characterized by enriched pathways of several chemokines in AM.

Moderate to severe OSA screening based on support vector machine of the Chinese population faciocervical measurements dataset: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnoea (OSA) has received much attention as a risk factor for perioperative complications and 68.5% of OSA patients remain undiagnosed before surgery. Faciocervical characteristics may screen OSA for Asians due to smaller upper airways compared with Caucasians. Thus, our study aimed to explore a machine-learning model to screen moderate to severe OSA based on faciocervical and anthropometric measurements. DESIGN: A cross-sectional study. SETTING: Data were collected from the Shanghai Jiao Tong University School of Medicine affiliated Ruijin Hospital between February 2019 and August 2020. PARTICIPANTS: A total of 481 Chinese participants were included in the study. PRIMARY AND SECONDARY OUTCOME: (1) Identification of moderate to severe OSA with apnoea-hypopnoea index 15 events/hour and (2) Verification of the machine-learning model. RESULTS: Sex-Age-Body mass index (BMI)-maximum Interincisal distance-ratio of Height to thyrosternum distance-neck Circumference-waist Circumference (SABIHC2) model was set up. The SABIHC2 model could screen moderate to severe OSA with an area under the curve (AUC)=0.832, the sensitivity of 0.916 and specificity of 0.749, and performed better than the STOP-BANG (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference, and male gender) questionnaire, which showed AUC=0.631, the sensitivity of 0.487 and specificity of 0.772. Especially for asymptomatic patients (Epworth Sleepiness Scale <10), the SABIHC2 model demonstrated better predictive ability compared with the STOP-BANG questionnaire, with AUC (0.824 vs 0.530), sensitivity (0.892 vs 0.348) and specificity (0.755 vs 0.809). CONCLUSION: The SABIHC2 machine-learning model provides a simple and accurate assessment of moderate to severe OSA in the Chinese population, especially for those without significant daytime sleepiness.

A narrative review of exploring potential salivary biomarkers in respiratory diseases: still on its way.

Saliva is abundant with proteins, metabolites, DNA, and a diverse range of bacterial species. During the past two decades, saliva has emerged as a novel diagnostic and evaluation medium for several diseases. Collection of saliva samples is simple, minimally invasive, and convenient even in infants, children, and patients with anxious. Furthermore, with the development of hypersensitive techniques [e.g., microsensor arrays, enzyme-labeled immunosensors, nanoparticle-labeled immunosensors, capacitive or impedimetric immunosensors, magneto immunosensors, field effect transistor immunosensors, and surface enhanced Raman spectroscopy (SERS)], the sensitivity and accuracy of saliva diagnostic procedures have been improved. Nowadays, saliva has been used as a potential medium for several disease diagnosis and assessment, such as periodontitis, caries, cancers, diabetes mellitus, and cardiovascular diseases. Saliva has been used widely for studying microbiomics, genomics, transcriptomics, proteomics, and metabolomics of respiratory diseases, however, the use of salivary biomarkers for the diagnosis, prognosis, and monitoring of respiratory disease is still in its infancy. Herein, we review the progress of research on salivary biomarkers related to several respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), pneumonia, tuberculosis (TB), Langerhans cell histiocytosis (LCH) and cystic fibrosis (CF). Furthermore, several limitations of saliva test such as the lack of standard protocol for saliva collection and reasonable reference values for saliva test are also mentioned in this review.

Therapeutic Agents Rounding Up the Immunopathology of COVID-19.

COVID-19 pandemic has caused more than 3 million deaths globally during the past year. The direct attack from SARS-CoV-2 and hyperactivated immune response contribute to the progress and deterioration of COVID-19. After the virus invades, the activation and release of cytokines/chemokines cause "cytokine storm", leading to acute respiratory distress syndrome (ARDS) and multiple organs dysfunction syndrome (MODS). Eliminating virus and blocking cytokines are important checkpoints of COVID-19 therapy, and several agents targeting immunopathology, including interferons, thymosin, glucocorticoids and immunoglobulin, have shown therapeutic effects in severe patients with COVID-19. Herein, we reviewed the practice evidences and concluded that several agents rounding up the immunopathology of COVID-19 may be the alternative approaches under the scenario of the lacking of effective antiviral drugs.

Burden of Sleep Disturbance During COVID-19 Pandemic: A Systematic Review.

Coronavirus disease 2019 (COVID-19) pandemic may exert adverse impacts on sleep among populations, which may raise awareness of the burden of sleep disturbance, and the demand of intervention strategies for different populations. We aimed to summarize the current evidence for the impacts of COVID-19 on sleep in patients with COVID-19, healthcare workers (HWs), and the general population. We searched PubMed and Embase for studies on the prevalence of sleep disturbance. Totally, 86 studies were included in the review, including 16 studies for COVID-19 patients, 34 studies for HWs, and 36 studies for the general population. The prevalence of sleep disturbance was 33.3%-84.7%, and 29.5-40% in hospitalized COVID-19 patients and discharged COVID-19 survivors, respectively. Physiologic and psychological traumatic effects of the infection may interact with environmental factors to increase the risk of sleep disturbance in COVID-19 patients. The prevalence of sleep disturbance was 18.4-84.7% in HWs, and the contributors mainly included high workloads and shift work, occupation-related factors, and psychological factors. The prevalence of sleep disturbance was 17.65-81% in the general population. Physiologic and social-psychological factors contributed to sleep disturbance of the general population during COVID-19 pandemic. In summary, the sleep disturbance was highly prevalent during COVID-19 pandemic. Specific health strategies should be implemented to tackle sleep disturbance.

Model for Identifying High Carotid Body Chemosensitivity in Patients with Obstructive Sleep Apnea.

OBJECTIVE: The carotid body (CB) is a major peripheral respiratory chemoreceptor. In patients with obstructive sleep apnea (OSA), high CB chemosensitivity (CBC) is associated with refractory hypertension and insulin resistance and known to further aggravate OSA. Thus, the identification of high CB (hCBC) among OSA patients is of clinical significance, but detection methods are still limited. Therefore, this study aimed to explore the association of CBC with OSA severity and to develop a simplified model that can identify patients with hCBC. METHODS: In this cross-sectional study of subjects who underwent polysomnography (PSG), CBC was measured using the Dejours test. We defined hCBC as a decrease of >12% in respiratory rate (RR) after breathing of pure O2. The association of CBC with OSA severity was explored by logistic regression, and a model for identifying hCBC was constructed and confirmed using receiver operating characteristic analysis. RESULTS: Patients with OSA (n=142) and individuals without OSA (n=38) were enrolled. CBC was higher in patients with OSA than in those without OSA (% decrease in RR, 15.2%±13.3% vs 9.1%±7.5%, P<0.05). Apnea-hypopnea index (AHI), fraction of apnea-hypopnea events in rapid-eye-movement sleep (Fevents-in-REM), and longest time of apnea (LTA) were associated with hCBC independently (odds ratio [OR]=1.048, OR=1.082, and OR=1.024 respectively; all P<0.05). The model for identifying hCBC allocated a score to each criterion according to its OR values, ie, 1 (LTA >48.4 s), 2 (AHI >15.7 events/hour), and 3 (Fevents-in-REM >12.7%). A score of 3 or greater indicated hCBC with a sensitivity of 79.4% and specificity of 88.2%. CONCLUSION: High CBC is associated with the severity of OSA. A simplified scoring system based on clinical variables from PSG can be used to identify hCBC.

Bronchial Variation: Anatomical Abnormality May Predispose Chronic Obstructive Pulmonary Disease.

Noxious particulate matter in the air is a primary cause of chronic obstructive pulmonary disease (COPD). The bronchial tree acts to filter these materials in the air and preserve the integrity of the bronchi. Accumulating evidence has demonstrated that smoking and air pollutants are the most prominent risk factors of COPD. Bifurcations in the airway may act as deposition sites for the retention of inhaled particles, however, little is known concerning the impacts of abnormalities of the bronchial anatomy in the pathogenesis of COPD. Studies have reported significant associations between bronchial variations and the symptoms in COPD. In particular, it has been shown that bronchial variations in the central airway tree may contribute to the development of COPD. In this review, we identified three common types of bronchial variation that were used to formulate a unifying hypothesis to explain how bronchial variations contribute to the development of COPD. We also investigated the current evidence for the involvement of specific genes including fibroblast growth factor 10 (Fgf10) and bone morphogenetic protein 4 (Bmp4) in the formation of bronchial variation. Finally, we highlight novel assessment strategies and opportunities for future research of bronchial variations and genetic susceptibility in COPD and comorbidities. Our data strongly highlight the role of bronchial variations in the development, complications, and acute exacerbation of COPD.

Chronic intermittent hypoxia-induced mitochondrial dysfunction mediates endothelial injury via the TXNIP/NLRP3/IL-1ß signaling pathway.

Oxidative stress and inflammation induced by chronic intermittent hypoxia (CIH) are trigger factors of cardiovascular diseases in patients with obstructive sleep apnea (OSA). This study aimed to investigate the role of CIH-induced mitochondrial dysfunction in vascular endothelial injury both in vivo and in vitro. Human umbilical vein endothelial cells and Sprague Dawley rats were exposed to CIH. CIH promoted the production of intracellular reactive oxygen species, caused mitochondrial dysfunction, and induced cell apoptosis in human umbilical vein endothelial cells. RNA-Seq analysis revealed that the NOD-like receptor signaling pathway was involved in endothelial injury induced by CIH. TXNIP/NLRP3/IL-1ß pathway was found to be upregulated by CIH. Knock-down of TNXIP rescued the endothelial cells from CIH-induced apoptosis, indicating that activation of the TXNIP/NLRP3/IL-1ß pathway mediated the CIH-induced endothelial apoptosis. Administration of the mitochondria-targeted antioxidant mito-TEMPO improved mitochondrial function and suppressed upregulation of the TXNIP/NLRP3/IL-1ß pathway, thereby alleviating CIH-induced endothelial apoptosis. In vivo experiments confirmed the results, where mito-TEMPO was found to ameliorate endothelial injury in rat aortas exposed to CIH. The results imply that CIH-induced mitochondrial dysfunction mediates endothelial injury implication of TXNIP/NLRP3/IL-1ß signaling pathway.

Impact of insomnia and obstructive sleep apnea on the risk of acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major health burden worldwide. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by worsening of patients' respiratory symptoms that requires a modification in medication. This event could accelerate disease progression and increase the risk of hospital admissions and mortality. Both insomnia and obstructive sleep apnea (OSA) are prevalent in patients with COPD, and are linked to increased susceptibility to AECOPD. Improper treatment of insomnia may increase the risk of adverse respiratory outcomes for patients with COPD, while effective continuous positive airway pressure (CPAP) treatment may reduce the risk of AECOPD and mortality in patients with overlap syndrome. Sleep disorders should be considered in clinical management for COPD.

Intracranial-to-central venous pressure gap predicts the responsiveness of intracranial pressure to PEEP in patients with traumatic brain injury: a prospective cohort study.

BACKGROUND: Mechanical ventilation (MV) with positive end-expiratory pressure (PEEP) is commonly applied in patients with severe traumatic brain injury (sTBI). However, the individual responsiveness of intracranial pressure (ICP) to PEEP varies. Thus, identifying an indicator detecting ICP responsiveness to PEEP is of great significance. As central venous pressure (CVP) could act as an intermediary to transduce pressure from PEEP to ICP, we developed a new indicator, PICGap, representing the gap between baseline ICP and baseline CVP. The aim of the current study was to explore the relationship between PICGap and ICP responsiveness to PEEP. METHODS: A total of 112 patients with sTBI undergoing MV were enrolled in this prospective cohort study. ICP, CVP, cerebral perfusion pressure (CPP), static compliance of the respiratory system (Cst), and end-tidal carbon dioxide pressure (PetCO2) were recorded at the initial (3 cmH2O) and adjusted (15 cmH2O) levels of PEEP. PICGap was assessed as baseline ICP - baseline CVP (when PEEP = 3 cmH2O). The patients were classified into the ICP responder and non-responder groups based on whether ICP increment with PEEP adjusted from 3 cmH2O to 15 cmH2O was greater than 20% of baseline ICP. The above parameters were compared between the two groups, and prediction of ICP responsiveness to PEEP adjustment was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with the non-responder group, the responder group had lower PICGap (1.63 ± 1.33 versus 6.56 ± 2.46 mmHg; p <  0.001), lower baseline ICP, and higher baseline CVP. ROC curve analysis suggested that PICGap was a stronger predictive indicator of ICP responsiveness to PEEP (AUC = 0.957, 95%CI 0.918-0.996; p <  0.001) compared with baseline ICP and baseline CVP, with favorable sensitivity (95.24, 95%CI 86.91-98.70%) and specificity (87.6, 95%CI 75.76-94.27%), at a cut off value of 2.5 mmHg. CONCLUSION: The impact of PEEP on ICP depends on the gap between baseline ICP and baseline CVP, i.e. PICGap. In addition, PICGap is a potential predictor of ICP responsiveness to PEEP adjustment in patients with sTBI.

Nocturnal Mean Oxygen Saturation Is Associated with Secondary Polycythemia in Young Adults with Obstructive Sleep Apnea, Especially in Men.

OBJECTIVE: Whether the severity of obstructive sleep apnea (OSA) contributes to clinical polycythemia is uncertain, especially in young adults. This study aimed to assess the correlation between untreated OSA and polycythemia, controlling for multiple confounders, and to observe the difference in both genders. METHODS: All participants underwent nocturnal polysomnography. Medical comorbidities, and demographic and laboratory information were also recorded. The relationship between OSA and concomitant polycythemia in both genders was analyzed. RESULTS: A total of 605 young participants (383 men and 222 women), aged 30.52 ± 7.21 years, were enrolled, with an average body mass index of 32.48 ± 6.06 kg/m2. Although 74.4% of patients were diagnosed with OSA, less than 10% had polycythemia. The levels of hemoglobin and hematocrit increased with the severity of OSA; only men with severe OSA had significantly higher hemoglobin, hematocrit, and polycythemia compared with those in the control group (P < 0.01). Hemoglobin and hematocrit significantly correlated with mean pulse oxygen saturation (SpO2) (P < 0.001), but the correlation coefficients were weaker in women than in men. In logistic regression analysis, mean SpO2, but not the apnea-hypopnea index (AHI), was found to be an independent predictor of polycythemia (P < 0.05). Areas under the receive operator characteristic analysis revealed that the cutoff values of hemoglobin and hematocrit were 155.5g/L and 44.6% (P < 0.001), respectively, for assessing nocturnal hypoxemia in men with OSA. CONCLUSION: Nocturnal mean SpO2 was an independent predictor of polycythemia in young adults. Mean SpO2, compared with the AHI, was more associated with polycythemia. Men were more prone to suffer from polycythemia compared with women. Hemoglobin and hematocrit values might have diagnostic utility for assessing nocturnal hypoxia severity of OSA patients, especially in men.

Sirt1 improves functional recovery by regulating autophagy of astrocyte and neuron after brain injury.

Traumatic brain injury (TBI) triggers neuronal death mechanisms that significantly induce neuronal loss and neurological dysfunction. Our previous study revealed that Sirt1 could improve the neuroprotective effect by reducing the astrocyte activation after TBI. Nevertheless, the underlying mechanisms of Sirt1 attenuating astrocyte activation still remain unclear. The following study examined whether the protection of Sirt1 in nigrostriatal pathway injury is associated with autophagy regulation. We established a nigrostriatal pathway injury in the mouse brain in order to mimic the traumatic brain injury and up-regulated Sirt1 expression by resveratrol. Consequently, we analyzed the effect of Sirt1 up-regulation on LC3 and monitored the LC3 localization in the astrocytes, microglial cells and neurons. We found that the Sirt1 up-regulation by resveratrol increased the expression of LC3 around the lesion site after injury. Confocal results showed that Sirt1 up-regulation increased the expression of LC3 in astrocytes and decreased the expression in the neurons, while low effect was found on the microglial cells. Moreover, compared the resveratrol treatment groups, a typical nucleocytoplasmic localization with strong distribution in the nucleus (in astrocyte and neurons) was observed in the control group (treated with DMSO). To sum up, our data suggested that regulation of Sirt1 expression could enhance autophagy in the astrocytes and decrease the expression in the neurons. This mechanism, which may probably relate to the distribution of LC3 in cytoplasm and nucleus, provides a new theoretical basis for exploring the neuroprotective mechanism of Sirt1 after brain injury.

Neuroprotective effects of matrix metalloproteinases in cerebral ischemic rats by promoting activation and migration of astrocytes and microglia.

Matrix metalloproteinases (MMPs) cleave almost all components of the extracellular matrix (ECM) and cause acute neurovascular disruption and parenchymal destruction. Previously, MMPs inhibition was considered to be a therapeutic strategy in early stages of ischemia. This study was designed to investigate whether early MMPs inhibition could promote the recovery of cerebral ischemia. Male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAO) for 1 h and reperfusion. The rats were divided into three groups: sham + vehicle (S + V) group, MCAO + vehicle (M + V) group, and MCAO + GM6001 (M + G) group. Infarct volume was assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, and the expression of GFAP, IBA1, p-ERK, ERK, and MMP9 were evaluated by Western blot and immunofluorescence staining on 1, 4, 7, and 14 days after MCAO. Neuronal apoptosis was assessed by Fluoro-Jade C staining. The results showed that MMPs inhibition significantly increased the infarct volume and the expressions of GFAP and IBA1 in the M + V group were much higher than those in the M + G group; whereas the expression of p-ERK was upregulated in both the M + V and M + G groups. These findings suggest that MMPs promote the activation and migration of astrocytes and microglia to form protected zone in the penumbra and lessen the infarct volume after cerebral ischemic stroke.