B and N Codoped Cellulose-Supported Ag-/Bi-Doped Mo(S,O)3 Trimetallic Sulfo-Oxide Catalyst for Photocatalytic H2 Evolution Reaction and 4-Nitrophenol Reduction.

Cellulose plays a significant role in designing efficient and stable cellulose-based metallic catalysts, owing to its surface functionalities. Its hydroxyl groups are used as anchor sites for the nucleation and growth of metallic nanoparticles and, as a result, improve the stability and catalytic activity. Meanwhile, cellulose is also amenable to surface modifications to be more suitable for incorporating and stabilizing metallic nanoparticles. Herein, the Ag-/Bi-doped Mo(S,O)3 trimetallic sulfo-oxide anchored on B and N codoped cellulose (B-N-C) synthesized by a facile approach showed excellent stability and catalytic activity for PHER at 573.28 µmol/h H2 with 25 mg of catalyst under visible light, and 92.3% of the 4-nitrophenol (4-NP) reduction was achieved within 135 min by in situ-generated protons. In addition to B and N codoping, our use of the calcination method for B-N-C preparation further increases the structural disorders and defects, which act as anchoring sites for Ag-/Bi-doped Mo(S,O)3 nanoparticles. The Ag-/Bi-doped Mo(S,O)3@B-N-C surface active site also stimulates H2O molecule adsorption and activation kinetics and reduces the photogenerated charge carrier's recombination rate. The Mo4+ → Mo6+ electron hopping transport and the O 2p and Bi 6s orbital overlap facilitate the fast electron transfer by enhancing the electron's lifetime and photoinduced charge carrier mobility, respectively. In addition to acting as a support, B-N-C provides a highly conductive network that enhances charge transport, and the relocated electron in B-N-C activates the H2O molecule, which enables Ag-/Bi-doped Mo(S,O)3@B-N-C to have appreciable PHER performance.

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.

High flow nasal cannula versus conventional oxygen therapy in postoperative patients at high risk for pulmonary complications: A systematic review and meta-analysis.

BACKGROUND: The effects of high flow nasal cannula (HFNC) on postoperative patients at high risk for pulmonary complications(PC) are controversial. We aimed to further determine the effectiveness of HFNC in postoperative patients at high risk for PC by comparison to conventional oxygen therapy (COT). METHODS: We performed a comprehensive search that compared HFNC with COT in postoperative patients at high risk for PC. The main outcomes were length of hospital stay (hospital LOS) and respiratory complications. RESULTS: Six trials with a total of 733 patients were pooled in our final studies. Except for Hospital LOS (I2  = 53%, χ2  = 8.51, P = .07) and rate of intubation or non-invasive ventilation (NIV) for respiratory failure (RF) (I2  = 49%, χ2  = 1.97, P = .16) between HFNC and COT, no significant heterogeneity was found in outcome measures. Compared with COT, HFNC was associated with a lower rate of intubation or NIV for RF (RR 0.23, 95% CI 0.08-0.66, P = .006) and rate of hypercapnia (RR 0.37, 95% CI 0.20-0.68, P = .002). As for the Hospital LOS, ICU LOS, rate of requirement of O2 after discontinuous and hypoxemia, HFNC did not show any advantage over COT. Trial Sequential Analysis (TSA) for Hospital LOS showed that monitoring boundaries were finally not surpassed and required information size (RIS) was not met. CONCLUSIONS: The available randomised controlled trials (RCTs) suggest that, among the postoperative patients at high risk for PC, HFNC therapy compared with the COT significantly reduces rate of incubation or NIV for RF and rate of hypercapnia, meanwhile is safely administered. Further large-scale, multicenter, randomised and controlled studies are needed to confirm our results.

Performance of brief ICF-sleep disorders and obesity core set in obstructive sleep apnea patients.

BACKGROUND: Clinical questionnaires are mainly applied as screening tools for identification of the Obstructive sleep apnea (OSA) patients. Little attention has been paid to assess the body functions and health status of the patients. International Classification of Functioning, Disability and Health (ICF) was designed for better understanding and describing functioning and disability of patients. This study adopted the Brief ICF-Sleep Disorders and Obesity Core Set to evaluate the impairment of functioning and health status of OSA patients. METHODS: Five hundred ninety-two participants were enrolled in this cross-sectional study. Data were collected using Brief ICF-Sleep Disorders and Obesity Core Set Polysomnography was performed and basic characteristics of the patients were recorded. RESULTS: The scores for the component Body Functions and Code b130, b134, b140, b440, b530, s330, d160, d240, d450 of the two core sets were significantly different among the patients divided by apnea-hypopnea index (AHI) or oxygen saturation (SaO2) nadir, but the frequency of code s330, d160, d240, d450 was low. The Body Functions component of the both sets were closely related to neck circumference (NC), body mass index (BMI), apnea-hypopnea index (AHI) of the OSA patients. Body Functions of the Brief ICF-Sleep Disorders performed better with a threshold of 4 with sensitivity, specificity and area under the receiver operating characteristic curve (AUC) as 0.62, 0.74, 0.68(AHI ≥ 5), 0.69, 0.63, 0.66 (AHI ≥ 15), 0.75, 0.56, 0.66 (AHI ≥ 30), 0.56, 0.70, 0.63 (SaO2 nadir≤90%), 0.67, 0.66, 0.66 (SaO2 nadir<85%), 0.71, 0.59, 0.65 (SaO2 nadir<80%), separately. CONCLUSION: The Body Functions component of both two sets could be an evaluation tool of impairment of body functions for OSA patients. The Brief ICF-Sleep Disorders Body Functions component performed better with a threshold of 4 and might provide a new insight for physicians to assess OSA patients.

Upregulation of CASP9 through NF-κB and Its Target MiR-1276 Contributed to TNFα-promoted Apoptosis of Cancer Cells Induced by Doxorubicin.

：Under some conditions, nuclear factor-κB (NF-κB) has a pro-apoptotic role, but the mechanisms underlying this function remain unclear. This study demonstrated that NF-κB directly binds to CASP9 and miR1276 in tumor necrosis factor α (TNFα)-treated HeLa and HepG2 cells. NF-κB upregulated CASP9 expression, whereas downregulated miR1276 expression in the TNFα-treated cells. The miR1276 repressed CASP9 expression in both cells. As a result, a typical NF-κB-mediated coherent feed-forward loop was formed in the TNFα-treated cells. It was proposed that the NF-κB-mediated loop may contribute to cell apoptosis under certain conditions. This opinion was supported by the following evidence: TNFα promoted the apoptosis of HeLa and HepG2 cells induced by doxorubicin (DOX). CASP9 was significantly upregulated and activated by TNFα in the DOX-induced cells. Moreover, a known inhibitor of CASP9 activation significantly repressed the TNFα promotion of apoptosis induced by DOX. These findings indicate that CASP9 is a new mediator of the NF-κB pro-apoptotic pathway, at least in such conditions. This study therefore provides new insights into the pro-apoptotic role of NF-κB. The results also shed new light on the molecular mechanism underlying TNFα-promotion of cancer cells apoptosis induced by some anticancer drugs such as DOX.

Impact of ovariectomy on neurotransmitter receptors BDNF/TrkB and endoplasmic reticulum molecular chaperones in rat hypoglossal nucleus.

Currently hypoglossal nerve-genioglossus axis is the major research core of OSA pathogenesis. The pathogenesis of OSA incidence changes before and after menopause needs to be clarified further. Little is known about the influences of ovariectomy on hypoglossal motoneurons. In the research, we utilized a rat ovariectomy model to evaluate the expression changes of 5-HT2A and α1-Adrenergic receptors in the hypoglossal nucleus and to explore the involvement of BDNF/TrkB signaling and endoplasmic reticulum molecular chaperones in the hypoglossal nucleus. Results indicated that the expression of 5-HT2A and α1-Adrenergic receptors reduced dramatically in the hypoglossal nucleus of ovariectomized rats. The apoptosis level of hypoglossal motor neurons increased markedly in the OVX groups. The up-regulated expression of BDNF and down-regulated expression of TrkB were found in the OVX groups. Ovarian insufficiency resulted in the activation of UPR and the loss of CANX-CALR cycle. Estrogen replacement could restore these changes partially. Estrogen level influences the expression of neurotransmitter receptors, and regulates BDNF/TrkB signaling compensation and endoplasmic reticulum homeostasis, which might be one of the pathogenesis of menopausal female OSA. The results reveal a new perspective for studying female OSA from the view of hypoglossal nerve and hormonal changes and attempt to propel 17ß-estradiol toward a feasible therapy for female OSA. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-024-00520-5.

A Comprehensively Prognostic and Immunological Analysis of PARP11 in Pan-cancer.

Poly (ADP ribose) polymerase family member 11(PARP11) has important immune regulatory functions in viral infection and tumor immune response. Particularly, PARP11 showed protumor activities in multiple preclinical murine models. However, no systematic pan-cancer analysis has been conducted to explore PARP11 function. In this study we used multiple databases to assess PARP11 expression, which associations with clinical outcomes, immune checkpoint factors, prognostic significance, genomic characteristics, and immunological aspects. The analysis revealed varying expression levels of PARP11 across different cancer types and a significant correlation between its expression and immune cell infiltration. Insights from the CellMiner database suggest a strong link between PARP11 expression and sensitivity to anticancer drugs, highlighting its potential as a therapeutic target. Moreover, PARP11 expression correlates with patient survival during anti-PD1 and anti-CTLA4 treatments, suggested that PARP11 would be a predictor of immune checkpoint inhibitor (ICI) treatment. In summary, PARP11 would be a potential immunoregulatory target and a diagnosis and prognosis marker for certain types of cancers. The detailed mechanisms of PARP11 in tumor immune responses need to be further investigated.

Performance of the Activities and Participation component of International Classification of Functioning, Disability and Health Sleep Disorders Brief Core Set in patients with obstructive sleep apnea.

Background: Limitation of daily activities and impairment of working memory have received less attention in the clinical diagnosis and prognostic assessment of obstructive sleep apnea (OSA). In this study, the Activities and Participation component of the International Classification of Functioning, Disability and Health (ICF) Sleep Disorders Brief Core Set was evaluated for its performance in predicting impaired work ability in OSA patients. Methods: A total of 221 subjects were recruited into this cross-sectional study. ICF Sleep Disorders Brief Core Set, polysomnography, and neuropsychological tests were applied for data acquisition. Data analysis was performed by regression analysis and receiver operating characteristic (ROC) construction. Results: The scores for the component Activities and Participation were significantly different between the no OSA/OSA group, and were elevated as the severity of OSA increased. Scores were positively correlated with apnea-hypopnea index (AHI), trail making test (TMT), and negatively correlated with symbol digit modalities test (SDMT) correct. The component Activities and Participation performed better with the threshold of 4 in the prediction of impaired attention and work ability in severe OSA [AHI ≥30 events/h, bottom 10% of TMT part B (TMTb) scores as the diagnostic criteria], with area under the curve, sensitivity and specificity as 0.909, 71.43% and 96.72%, respectively. Conclusions: The Activities and Participation component of the ICF Sleep Disorders Brief Core Set could have the potential to predict the impairment of attention and work ability in OSA patients. It provides a new perspective for the identification of OSA patients' disturbances in daily activities and improving the overall assessment level.

Sulfur Substitution and Defect Engineering in an Unfavored MnMoO4 Catalyst for Efficient Hydrogen Evolution under Visible Light.

A novel and nonstoichiometric Mn1-xMo(S,O)4-y oxysulfide catalyst with oxygen vacancies and a partial Mo6+-to-Mo4+ transition after the substitution of sulfur was synthesized for an efficient photocatalytic hydrogen evolution reaction (PHER). With appropriate sulfur substitution, a MnMoO4 semiconductor with a wide band gap was converted to Mn1-xMo(S,O)4-y with a narrow gap and a suitable band position for PHER. MnMo oxysulfide of 50 mg achieved a high PHER rate of 415.8 µmol/h under visible light, an apparent quantum efficiency (AQE) of 4.31% at 420 nm, and a solar-to-hydrogen (STH) conversion efficiency of 1.28%. Oxygen vacancies (VO) surrounded by low coordination metal atoms act as active reaction sites, which strengthen water adsorption and activation. Here, we demonstrate that sulfur substitution of MnMoO4 for lowering its wide band gap can not only disturb the strict periodicity of the lattice but also the valence states of Mn and Mo for enhancing PHER via material design.

Protective effects of progesterone on pulmonary artery smooth muscle cells stimulated with Interleukin 6 via blocking the shuttling and transcriptional function of STAT3.

BACKGROUND: Sex hormone paradox is a crucial but unresolved issue in the field of pulmonary artery hypertension (PAH), and is thought to be related to different pathogenic factors. Inflammation is one of pathological mechanisms of PAH development. However, effects of sex hormones on the pulmonary vasculature under the condition of inflammation are still elusive. METHODS: Interleukin-6 (IL-6) was used as a representative inflammatory stimulator. Effects of 17ß-estradiol or progesterone on human pulmonary artery smooth muscle cells (PASMCs) were measured under the condition of IL-6. Cell functions of proliferation and migration were measured by Alarmar Blue, EdU assay, wound-healing assay and transwell chambers. We explored further mechanisms using western blot, immunofluorescence, co-immunoprecipitation, qPCR and chromatin immunoprecipitation. RESULTS: Our results revealed that IL-6 promoted the proliferation of PASMCs, but progesterone could reverse the adverse effect of IL-6. The protective effect was dependent on progesterone receptor (PGR). By interacting with signal transducer and activator of transcription 3 (STAT3), activated PGR could reduce the IL-6-induced nuclear translocation of STAT3 and prevent STAT3-chromatin binding in PASMCs, leading to the decreased transcription of downstream CCND1 and BCL2. Alternatively, progesterone slightly decreased the phosphorylation of pro-proliferative Erk1/2 and Akt kinases and upregulated the anti-proliferative pSmad1-Id1/2 axis in IL-6-incubated PASMCs. CONCLUSIONS: Progesterone played a protective role on PASMCs in the context of IL-6, by blocking the functions of STAT3. Our findings might assist in explaining the clinical phenomenon of better prognosis for women with PAH.

Non-invasive ventilation intervention during exercise training in individuals with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

OBJECTIVE: evidence is inconsistent for the effect of non-invasive ventilation (NIV) for individuals with chronic obstructive pulmonary disease (COPD) during exercise training. This review aimed to determine the effect of NIV in COPD individuals during exercise training on exercise capacity, quality of life, functional performance and symptoms. MATERIAL AND METHODS: we searched for studies evaluating the effect of NIV on COPD individuals during exercise training published until May 2020 in 6 electronic databases (PubMed, Embase, Cochrane Library, Web of Science, clinical trial registers and Wanfang). The included studies were appraised with the Cochrane Risk of Bias tool and Downs and Black criteria. The primary outcomes were improvement in 6-min walking distance and quality of life. Mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated. RESULTS: among 855 identified articles, reports for 15 studies with heterogeneous populations were eligible, with 520 individuals: 257 in the NIV group and 263 in the control group. Across studies, NIV intervention during exercise training affected exercise performance (6-min walking distance: SMD: 0.33, 95% CI: 0.06; 0.59, P=0.02; quality of life: SMD: -0.77, 95% CI: -1.01; -0.53, P<0.001). In the analysis of dyspnea, pooled estimates demonstrated improvement in the NIV versus control group. NIV intervention was also better than exercise alone in ameliorating oxygen saturation, PaO2, PaCO2, blood lactate level and breath rate. The groups did not differ in duration of exercise, BODE index, minute ventilation, heart rate and systolic blood pressure. CONCLUSIONS: our review suggests that NIV is a relevant adjuvant for exercise training in COPD individuals because the intervention could improve exercise performance and quality of life. The current results also demonstrate the importance of further investigations of higher methodological quality to assess the effect on exercise capacity and quality of life.

Respiratory physicians' awareness and referral of pulmonary rehabilitation in China: a cross-sectional study.

BACKGROUND: Pulmonary rehabilitation (PR) has demonstrated physiological, symptom reducing, psychosocial, and health care savings benefits in multiple outcome areas for patients with chronic respiratory diseases. Physicians' PR awareness and PR referral practices are key in PR promotion. However, PR awareness and referral among respiratory physicians in China have rarely been studied. This study aims to explore respiratory physicians' perceptions towards PR and assess the referral of PR in China. METHODS: A self-administered questionnaire was distributed via WeChat and emails to respiratory physicians in hospitals to assess their attitudes toward and knowledge of PR and identify treatment barriers. The study was conducted from June through October 2019. RESULTS: As reported in the 520 questionnaires collected through October 2019 most respondents had heard about PR, and many had knowledge of PR practice, but relatively few had referred patients to PR before having responded to the survey. Education, region of practice, and duration of practice are significant factors that influenced the participating respiratory physicians' awareness of PR. The percentage of referral was influenced by physicians' education, region, and duration of practice. The absence of PR facilities was the main barrier to respiratory physicians' referral of patients to PR. CONCLUSIONS: Chinese respiratory physicians' awareness of PR and referral to PR remain insufficient to support the delivery of PR to patients with chronic respiratory diseases. PR training for respiratory physicians and building PR centers are necessary to remedy these conditions.

Essential Genes and MiRNA-mRNA Network Contributing to the Pathogenesis of Idiopathic Pulmonary Arterial Hypertension.

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease. Owing to its high fatality rate and narrow therapeutic options, identification of the pathogenic mechanisms of IPAH is becoming increasingly important. Methods: In our research, we utilized the robust rank aggregation (RRA) method to integrate four eligible pulmonary arterial hypertension (PAH) microarray datasets and identified the significant differentially expressed genes (DEGs) between IPAH and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to analyze their functions. The interaction network of protein-protein interaction (PPI) was constructed to explore the correlation between these DEGs. The functional modules and hub genes were further identified by the weighted gene coexpression network analysis (WGCNA). Moreover, a miRNA microarray dataset was involved and analyzed to filter differentially expressed miRNAs (DE-miRNAs). Potential target genes of screened DE-miRNAs were predicted and merged with DEGs to explore a miRNA-mRNA network in IPAH. Some hub genes were selected and validated by RT-PCR in lung tissues from the PAH animal model. Results: A total of 260 DEGs, consisting of 183 upregulated and 77 downregulated significant DEGs, were identified, and some of those genes were novel. Their molecular roles in the etiology of IPAH remained vague. The most crucial functional module involved in IPAH is mainly enriched in biological processes, including leukocyte migration, cell chemotaxis, and myeloid leukocyte migration. Construction and analysis of the PPI network showed that CXCL10, CXCL9, CCR1, CX3CR1, CX3CL1, CXCR2, CXCR1, PF4, CCL4L1, and ADORA3 were recognized as top 10 hub genes with high connectivity degrees. WGCNA further identified five main functional modules involved in the pathogenesis of IPAH. Twelve upregulated DE-miRNAs and nine downregulated DE-miRNAs were identified. Among them, four downregulated DEGs and eight upregulated DEGs were supposed to be negatively regulated by three upregulated DE-miRNAs and three downregulated DE-miRNAs, respectively. Conclusions: This study identifies some key and functional coexpression modules involved in IPAH, as well as a potential IPAH-related miRNA-mRNA regulated network. It provides deepening insights into the molecular mechanisms and provides vital clues in seeking novel therapeutic targets for IPAH.

LncRNA NEAT1 contributes to the acquisition of a tumor like-phenotype induced by PM 2.5 in lung bronchial epithelial cells via HIF-1α activation.

The hazards of particulate matter (PM2.5) on human respiratory health have been previously reported. However, the molecular mechanisms underlying PM2.5-induced lung carcinogenesis have rarely been studied. In the present study, we explored the effects of PM2.5 on the epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like properties in lung bronchial epithelial cells. We found that exposure of PM2.5 enhanced lung bronchial epithelial cell proliferation and EMT. In addition, the expression level of CSC-like biomarkers, CD133 and CD44, was significantly elevated by PM2.5 in vitro. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to participate in lung cancer. Loss of NEAT1 represses the malignant transformation of BEAS-2B and HBE cells induced by PM2.5. NEAT1 interacts with microRNA (miR)-582-5p, and miR-582-5p reverses the pro-tumor effects of NEAT1 overexpression. Hypoxia-inducible factor (HIF)-1α is an important transcription factor in the pathological responses to hypoxia. HIF-1α was a predicted target for miR-582-5p, and a direct correlation between them was identified. Inhibitors of miR-582-5p rescued HIF-1α expression, which was attenuated by a lack of NEAT1. In conclusion, PM2.5 increased NEAT1 expression, which, by binding with miR-582-5p, released HIF-1α and promoted EMT and the acquisition of CSC-like characteristics.

Clinical risk factors for mortality of hospitalized patients with COVID-19: systematic review and meta-analysis.

BACKGROUND: New evidence from retrospective cohort studies on risk of death from COVID-19 infection became available. We aimed to systematically review the clinical risk factors for fatal outcome of COVID-19. METHODS: We performed meta-analysis, using PubMed, EMBASE and Cochrane databases from December 1 2019 to June 10 2020. The meta-analysis summarized clinical, laboratory, radiological features, and complications of non-survivors with confirmed COVID-19. In addition, a fixed- or random-effects model was adopted based on the heterogeneity among studies. We also used funnel-plot with Egger's tests to screen potential publication bias. RESULTS: In total, twenty studies with 15,408 COVID-19 cases were included in our meta-analysis. Male, current smoking, and older age were associated with in-hospital death. Patients aged 60 years or over had the highest pooled ORs [OR 4.94 (2.89, 8.44)]. Non-survivors were more likely to have diabetes, hypertension, cardiovascular disease (CVD), respiratory disease, or chronic kidney disease (CKD). Respiratory disease had the highest pooled ORs [OR 2.55 (2.14, 3.05)]. Dyspnea [OR 3.31 (1.78, 6.16); I2 : 83%] and fatigue [OR 1.36 (1.07, 1.73); I2 : 0%] were associated with increased risk of death. Increased white blood cell count, decreased lymphocyte and platelet counts, were also associated with increased risk of death. Biomarkers of coagulation function, inflammation, liver and kidney function, cardiac and muscle injury were also elevated in nonsurvivors. CONCLUSIONS: Male, current smoking patients aged 60 years or over might face a greater risk of in-hospital death and the comorbidities such as diabetes, hypertension, CVD, respiratory disease, and CKD could also influence the prognosis of the COVID-19. Clinical feature such as dyspnea and fatigue could imply the exacerbation and even death. Our findings highlighted early markers of mortality which were beneficial to identify fatal COVID-19.

The effect of coagulation factors in 2019 novel coronavirus patients: A systematic review and meta-analysis.

BACKGROUND: The role of coagulation dysfunction in Severe Coronavirus Disease 2019 (COVID-19) is inconsistent. We aimed to explore the impact of coagulation dysfunction amongst patients with COVID-19. METHODS: We searched PubMed, Cochrane and Embase databases from December 1, 2019 to April 27, 2020 following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data about coagulation (Platelets, PT, APTT, fibrin, fibrinogen degradation products, D-dimer), prevalence of coagulation dysfunction and mortality were extracted. Meta regression was used to explore the heterogeneity. RESULTS: Sixteen observational studies were included, comprising 2, 139 patients with confirmed COVID-19. More severe COVID-19 cases tended to have higher mean D-dimer (SMD 0.78, 95% CI 0.53 to 1.03, P < .001). The similar pattern occurred with PT and fibrin, with a contrary trend for PLTs. Coagulation dysfunction was more frequent in severe cases compared to less severe (SMD 0.46, 95% CI 0.25 to 0.67, P < .001). Higher mortality was associated with COVID-19-related coagulopathy (RR 10.86, 2.86 to 41.24, P < .001). Prevalence of ARDS was increased in more severe patients than less severe cases (RR 16.52, 11.27 to 24.22, P < .001). PT, fibrin and D-dimer levels elevated significantly in non-survivors during hospitalization. CONCLUSION: Presence of coagulation dysfunction might be associated with COVID-19 severity, and coagulopathy might be associated with mortality. Coagulation markers including PT, fibrin and D-dimer may imply the progression of COVID-19. This illuminates the necessity of effectively monitoring coagulation function for preventing COVID-19-related coagulopathy, especially in severe patients. For the obvious heterogeneity, the quality of the evidence is compromised. Future rigorous randomized controlled trials that assess the correlation between coagulation and COVID-19 are needed. TRIAL REGISTRATION: PROSPERO (CRD42020183514).

Impact of histaminergic H3 receptor antagonist on hypoglossal nucleus in chronic intermittent hypoxia conditions.

RATIONALE: The hypoglossal nucleus (HN) controls the movement of the genioglossus (GG) muscle whose dysfunction leads to airway occlusion and occurrence of obstructive sleep apnea (OSA). Histamine produced by the tuberomammillary nucleus (TMN) has a potent excitatory action on GG muscle activity. OBJECTIVES: The aim of the study was to investigate the role histaminergic neurons play in the regulation of the genioglossus. METHODS: C57BL/6 mice were exposed to chronic intermittent hypoxia (CIH) for 3 weeks to resemble OSA. The histamine H3 receptor (H3R) antagonist ciproxifan was applied to increase histamine in the brain. Histamine levels and GG activity were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electromyogram (EMG) separately. Neuronal activity and repair ability of the HN and TMN and key proteins of histamine were analyzed by immunohistochemistry and western blots. RESULTS: Significant decline of histamine level and GG activity of the HN and TMN induced by CIH exposure could be ameliorated by ciproxifan. Application of ciproxifan could also partly reverse the decline of the histidine decarboxylase (HDC) by CIH. CONCLUSIONS: This investigation studied the impacts of ciproxifan on the HN and TMN in CIH conditions and revealed that the negative effects on the HN and TMN caused by CIH could be partly ameliorated by ciproxifan, which might open new perspectives for the development of pharmacological treatment for OSA.

Serum cartilage oligomeric matrix protein is decreased in patients with pulmonary hypertension: a potential protective factor.

Cartilage oligomeric matrix protein (COMP) was a protective factor in the cardiovascular system. Previous studies showed that hypoxia led to decreased COMP in rat models of pulmonary hypertension. However, the expression pattern of COMP in the pulmonary hypertension population was unclear. A total of 35 patients newly diagnosed with pulmonary hypertension and 70 controls were enrolled in the study. Circulating COMP concentrations of serum samples were measured by enzyme-linked immunosorbent assay and were analyzed the association with multiple clinical variables. Serum COMP concentrations in the pulmonary hypertension group were significantly declined in comparison with age- and sex-matched normal controls, especially in the female subgroup. No significant difference of COMP concentrations was observed in the etiological classification, heart function classification, and risk stratification. Major hemodynamic parameters, six-minute walk distance, N-terminal pro brain natriuretic peptide, and short-term prognosis were not statistically associated with COMP. However, some echocardiography parameters, like tricuspid annular plane systolic excursion and mean right atrial pressure, were found the negative relation to COMP concentrations. In conclusion, serum COMP levels were decreased in the patients with pulmonary hypertension, which was in accordance with its known biological effects. Its association with long-term prognosis was worth further exploring.

Dysfunction of adaptive immunity is related to severity of COVID-19: a retrospective study.

BACKGROUND: In December of 2019, coronavirus disease 2019 (Covid-19) was reported in Wuhan, China, and has now rapidly swept around the world. Much research has been carried out since the outbreak, but few studies have focused on the dysfunction of the adaptive immunity. METHODS: In this retrospective and multi-center study, 373 patients with laboratory-confirmed COVID-19 from Shanghai Public Health Clinical Center and Affiliated Hospital of Putian University were recruited. Demographic, clinical, radiological features, and laboratory data were recorded and analyzed at admission and at discharge. Results of immunological tests were followed up until the patients were discharged. RESULTS: Of the 373 patients with COVID-19 pneumonia, 322 were in the non-severe group and 51 were in the severe group. Number of T cells, CD4+ and CD8+ T cells, and total lymphocytes declined remarkably upon admission and elevated when the patients were discharged. At admission, counts of total lymphocytes, T cells, CD4+ and CD8+ T cells, and levels of C3 and C4 in the severe group were lower than those in the non-severe group, whereas the neutrophil to lymphocyte ratio (NLR) was higher in the severe group. Counts of T cells, CD4+ and CD8+ T cells, and total lymphocytes were negatively correlated with lactate dehydrogenase and C-reactive protein. CONCLUSION: COVID-19 might target adaptive immunity and cause a decrease in lymphocytes, especially T cells and subsets. Physicians should pay close attention to the adaptive immunity of patients upon admission. Monitoring NLR, T lymphocytes, and subsets would help physicians with the proper diagnosis and treatment of COVID-19.The reviews of this paper are available via the supplemental material section.

Assessment of knowledge, attitude, and practice towards pulmonary rehabilitation among COPD patients: A multicenter and cross-sectional survey in China.

BACKGROUND: Pulmonary rehabilitation (PR) has been recognized to be an evidence-based treatment recommended for chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate COPD patients' knowledge, attitudes and practices towards PR in China. METHODS: 1138 COPD patients from 13 hospitals were enrolled in this cross-sectional study. A questionnaire designed based on an official statement was completed by the participants. Effects of PR in patients were investigated. RESULTS: Mean score of the knowledge portion was only 7.76, while 46.22% of the participants believed they needed PR. Attendance rate was 24.69%. Financial conditions and hospitalization were contributing factors for scores, attendance rate, and belief in demands for PR therapy. Severe pulmonary function impairment indicated more demands for PR (OR = 0.18) and higher uptake rate (OR = 0.30). There was a weak correlation between smoking status (rho = -0.060), diagnosis year (rho = 0.094), frequency of exacerbations (rho = 0.059) and grades. High CAT score is a facilitator for attitudes towards PR (OR = 0.022). 93.24% of patients claimed that their exercise tolerance improved with PR therapy. The improvements were positively associated with needs (rho = 0.20), family support (rho = 0.22), grades (rho = 0.18), and monthly income of the family (rho = 0.14), but negatively correlated with age (rho = -0.16), exacerbations (rho = -0.15), and CAT score (rho = -0.13). CONCLUSIONS: This study suggested poor perception, disbelief in the need for PR, and limited uptake of PR among COPD patients in China, and revealed the significant factors involved. The findings of this study may assist health professionals in developing targeted strategies to promote PR and improve access and uptake of PR.