Suppression of IRF9 Promotes Osteoclast Differentiation by Decreased Ferroptosis via STAT3 Activation.

Osteoporosis is a chronic disease that endangers the health of the elderly. Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but also plays an important role in inflammation, antiviral response, and cell development. However, the exact role of IRF9 in osteoclasts has not been reported. To elucidate the role of IRF9 in osteoclast differentiation, we established the ovariectomized mouse model of postmenopausal osteoporosis and found that IRF9 expression was reduced in ovariectomized mice with overactive osteoclasts. Furthermore, knockdown of IRF9 expression enhanced osteoclast differentiation in vitro. Using RNA sequencing, we identified that the differentially expressed genes enriched by IRF9 knockdown were related to ferroptosis. We observed that IRF9 knockdown promoted osteoclast differentiation via decreased ferroptosis in vitro and further verified that IRF9 knockdown reduced ferroptosis by activating signal transducer and activator of transcription 3 (STAT3) to promote osteoclastogenesis. In conclusion, we identified an essential role of IRF9 in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.

Turning cationic antimicrobial peptide KR-12 into self-assembled nanobiotics with potent bacterial killing and LPS neutralizing activities.

Gram-negative sepsis has become a substantial and escalating global healthcare challenge due to the growing antibiotic resistance crisis and the sluggish development of new antibiotics. LL-37, a unique Cathelicidin species found in humans, exhibits a wide range of bioactive properties, including direct bactericidal effects, inflammation regulation, and LPS neutralization. KR-12, the smallest yet potent peptide fragment of LL-37, has been modified to create more effective antimicrobials. In this study, we designed two myristoylated derivatives of KR-12, referred to as Myr-KR-12N and Myr-KR-12C. These derivatives displayed remarkable ability to spontaneously assemble into nanoparticles when mixed with deionized water. Myristoylated KR-12 derivatives exhibited broad-spectrum and intensified bactericidal activity by disrupting bacterial cell membranes. In particular, Myr-KR-12N showed superior capability to rescue mice from lethal E. coli-induced sepsis in comparison with the conventional antibiotic meropenem. We also confirmed that the myristoylated KR-12 nanobiotic possesses significant LPS binding capacity and effectively reduces inflammation in vitro. In an in vivo context, Myr-KR-12N outperformed polymyxin B in rescuing mice from LPS-induced sepsis. Crucially, toxicological assessments revealed that neither Myr-KR-12N nor Myr-KR-12C nanobiotics induced meaningful hemolysis or caused damage to the liver and kidneys. Collectively, our study has yielded an innovative nanobiotic with dual capabilities of bactericidal action and LPS-neutralization, offering substantial promise for advancing the clinical translation of antimicrobial peptides and the development of novel antibiotics. This addresses the critical need for effective solutions to combat Gram-negative sepsis, a pressing global medical challenge.

[Prognostic value of hemoglobin-to-red cell distribution width ratio in patients with cardiopulmonary resuscitation after out-of-hospital cardiac arrest].

OBJECTIVE: To investigate the prognostic value of hemoglobin-to-red cell distribution width ratio (HRR) in patients with cardiopulmonary resuscitation (CPR) after out-of-hospital cardiac arrest (OHCA). METHODS: A retrospective study was conducted. Patients aged ≥ 18 years with OHCA who were transferred to intensive care unit (ICU) after successful CPR from the emergency room of the First Affiliated Hospital of Zhengzhou University from August 2016 to February 2022 were enrolled. General clinical data, initial vital signs, acute physiology and chronic health evaluation II (APACHE II), Glasgow coma scale (GCS), first laboratory indicators after admission to ICU [including white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb), pH value, lactic acid (Lac), 6-hour lactic acid clearance (LCR), red cell distribution width (RDW), HRR], length of ICU stay were collected. According to whether the patients died in hospital, the patients were divided into survival group and death group. Binary Logistic regression was used to analyze the independent factors influencing the prognosis of patients after CPR. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of independent influencing factors for the prognosis of patients after CPR. RESULTS: A total of 122 patients were enrolled after OHCA CPR, of which 88 died in hospital, the in-hospital mortality was 72.13%. There were no significant differences in age, past medical history, initial vital signs and WBC in ICU between the two groups. Compared with the death group, the survival group had higher GCS score, RBC, Hb, pH value, 6-hour LCR, HRR, lower APACHE II score, Lac, RDW level, and longer length of ICU stay. Multivariate Logistic regression analysis showed that APACHE II score, GCS score, 6-hour LCR, HRR, length of ICU stay were independent factors influencing the prognosis of patients after CPR [APACHE II score: odds ratio (OR) = 0.784, 95% confidence interval (95%CI) was 0.683-0.901, P = 0.001; GCS score: OR = 1.390, 95%CI was 1.059-1.823, P = 0.018; 6-hour LCR: OR = 1.039, 95%CI was 1.015-1.064, P = 0.001; HRR: OR = 2.047, 95%CI was 1.383-3.029, P < 0.001; length of ICU stay: OR = 1.128, 95%CI was 1.046-1.216, P = 0.002]. ROC curve analysis showed that HRR, 6-hour LCR and APACHE II score could predict the prognosis of patients after CPR. The sensitivity was 85.3% and the specificity was 54.5% when the area under the ROC curve (AUC) of HRR was 0.731, and the cut-off value was 8.555. The sensitivity was 88.2% and the specificity was 46.6%, when the AUC of 6-hour LCR was 0.701, and the cut-off value was 28.947%. The sensitivity was 73.9% and the specificity was 79.4% when the AUC of APACHE II score was 0.848, the cut-off value was 22.000. The predictive value of the combination of HRR and 6-hour LCR was higher than that of a single index. The sensitivity was 79.3% and the specificity was 76.1%, when the AUC was 0.796, the cut-off value was 0.296. CONCLUSIONS: HRR, 6-hour LCR and APACHE II score have high prognostic value in patients with OHCA after CPR. HRR < 8.555, 6-hour LCR < 28.947% and APACHE II score > 22.000 indicated poor prognosis.

Suppression of TLR4 prevents diabetic bone loss by regulating FTO-mediated m6A modification.

Toll-like receptor-4 (TLR4) has been implicated in the development and progression of diabetic osteoporosis. However, the mechanisms underlying TLR4-regulated bone metabolism in diabetes are yet to be fully understood. Epigenetic modifications have been indicated as a possible mechanism leading to increased risk of osteoporosis and bone fracture. As N6-methyladenosine (m6A) is the most common epigenetic modification in eukaryotic mRNAs, we hypothesized that TLR4 regulates m6A modification in bone tissues of diabetic rats, thereby potentially explaining the pathogenesis of diabetic bone loss. m6A sequencing (m6A-seq) was performed in samples of the femur of TLR4-wild type (TLR4WT) and TLR4-knockout (TLR4KO) diabetic rats to identify genes with differential m6A modifications that may be associated with the bone loss phenotype. We found that in TLR4KO rats, the rapid weight loss of diabetic rats was prevented, and bone mineral density (BMD) was significantly increased. m6A-seq and Gene Ontology enrichment analysis revealed that m6A-modified genes in the femur of TLR4KO diabetic rats were associated with regulation of biological processes such as osteoclast differentiation. qRT-PCR analysis on the expression levels of the m6A-modified methyltransferases and demethylases demonstrated that only the m6A demethylase fat mass and obesity-associated protein（FTO）was decreased. Using an osteoclast cell model, we confirmed that TLR4-mediated osteoclast differentiation was induced by glycolipid toxicity via inhibition of FTO expression. Taken together, these results suggest that inhibition of TLR4 may prevent diabetic bone loss via regulation of FTO-mediated m6A modification.

MESP2 binds competitively to TCF4 to suppress gastric cancer progression by regulating the SKP2/p27 axis.

Gastric cancer (GC) is a major cause of human deaths worldwide, and is notorious for its high incidence and mortality rates. Mesoderm Posterior Basic Helix-loop-helix (bHLH) transcription factor 2 (MESP2) acts as a transcription factor with a conserved bHLH domain. However, whether MESP2 contributes to tumorigenesis and its potential molecular mechanisms, remain unexplored. Noticeably, MESP2 expression levels are decreased in GC tissues and cell lines compared to those in normal tissue. Further, in vitro and in vivo experiments have confirmed that MESP2 overexpression suppresses GC cell growth, migration, and invasion, whereas MESP2 knockdown results in the exact opposite. Here, we present the first report that MESP2 binds to transcription factor 7-like 2 (TCF7L2/TCF4) to inhibit the activation of the TCF4/beta-catenin transcriptional complex, decrease the occupancy of the complex on the S-phase kinase Associated Protein 2 (SKP2) promoter, and promote p27 accumulation. MESP2 knockdown facilitated tumorigenesis, which was partially suppressed by SKP2 knockdown. Taken together, we conclude that MESP2 binds competitively to TCF4 to suppress GC progression by regulating the SKP2/p27 axis, thus offering a potential therapeutic strategy for future treatment.

Activation of osteoblast ferroptosis via the METTL3/ASK1-p38 signaling pathway in high glucose and high fat (HGHF)-induced diabetic bone loss.

Diabetes mellitus (DM) and osteoporosis are two common diseases that may develop as a cause-and-effect relationship since the incidence of osteoporotic fractures is significantly increased in DM patients. However, the pathophysiology of diabetic osteoporosis is yet to be clearly understood. Iron overload has been reported to lead to bone loss and closely related to osteoporosis. In this study, we hypothesized that high glucose and high fat (HGHF) may induce osteoblastic ferroptosis for the pathogenesis of diabetic osteoporosis and explored the possible molecular mechanisms behind. Using the diabetic rat model established by HGHF feeding with a subsequent intraperitoneal injection of a single low dose of streptozocin, we found that the serum ferritin level (a biomarker for body iron store) was significantly elevated in HGHF-fed rats and the expression of SLC7A11 and GPX4 (inhibitory marker proteins for ferroptosis) was markedly attenuated in the bone tissue of the rats with diabetic bone loss as compared to the normal rats. In an osteoblast cell model, treatment of pre-osteoblastic MC3T3-E1 cells with high glucose and palmitic acid (HGPA) not only suppressed osteoblast differentiation and mineralization but also triggered ferroptosis-related osteoblastic cell death. m6 A-seq revealed that m6 A methylation on ASK1 was 80.9-fold higher in HGPA-treated cells. The expression of p-ASK1 and p-p38 was also significantly elevated in the HGPA-treated cells. Knockout of METTL3 (methyltransferase-like 3), one of the major m6 A methyltransferases, in MC3T3-E1 cells not only abrogated HGPA-induced activation of ASK1-p38 signaling pathway but also attenuated the level of ferroptosis. Therefore, HGHF-induced ferroptosis in osteoblasts may be the main cause of osteoporosis in DM via activation of METTL3/ASK1-p38 signaling pathway, and inhibition of ferroptosis in osteoblasts may provide a potential therapeutic strategy for diabetic osteoporosis.

The characteristics and patterns of e-cigarette use and its association with cigarette cessation intention in a Chinese smoking population: A mediation analysis.

INTRODUCTION: The use of e-cigarettes has become more common in China, but the research on e-cigarettes in China, while growing, is still limited. This study examined the characteristics and patterns of e-cigarette use, and analyzed the possible mediators between cigarette cessation intention and e-cigarette use in a Chinese smoking population. METHODS: This was a cross-sectional study conducted in mainland China. By convenience sampling method, the participants were recruited from 85 major commercial streets of several large cities in China. The study interviewers completed face-to-face interviews and uploaded the completed questionnaires into the online survey platform. The participants were contacted for clarification if any problems were detected. Logistic regression yielded adjusted odds ratios (ORs) for ever use of e-cigarettes. We further conducted a mediation analysis to estimate the effect of possible mediators. RESULTS: From July to August 2020, a total of 738 smokers were invited to participate in this study; 613 smokers were identified as eligible and 609 smokers were included in this analysis. Of them, 24 (3.94%) participants were currently using e-cigarettes, and 165 (27.09%) participants have ever used e-cigarettes. The participants with younger age were more likely to have ever used e-cigarettes, ranging from 37.5% in the 18-29 years age group to 6.5% in the 60-69 years age group. After controlling for demographic characteristics and nicotine dependence, the ever use of e-cigarettes was significantly associated with younger age, higher education level, higher monthly income, previous smoking cessation attempts and quitting intention. With the mediation analysis, the education level is confirmed as a mediating factor, and approximately 42.86% of the effects were mediated through the channel of higher socioeconomic status. CONCLUSIONS: This is the first study to examine the possible mediators between cigarette cessation intention and e-cigarette use in a Chinese smoking population. The findings revealed that high socioeconomic status, particularly higher education level, was a major mediating factor.

ZC3H15 promotes gastric cancer progression by targeting the FBXW7/c-Myc pathway.

Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved eukaryotic protein, which was associated with several cellular processes and was ubiquitously expressed in various human tissues. Recent studies indicated that ZC3H15 was involved in tumorigenesis and may be a potential biomarker in hepatocellular carcinoma (HCC) and acute myeloid leukemia (AML). However, the biological function and molecular mechanism of ZC3H15 in gastric cancer (GC) have not been studied. In this study, we revealed that ZC3H15 was highly expressed in GC and high ZC3H15 expression was closely linked to poor survival of patients with GC. We found that ZC3H15 promoted cell proliferation, migration, and invasion by increasing c-Myc expression. Next, we found that ZC3H15 could modulate c-Myc protein stability by suppressing the transcription of FBXW7, which was mainly responsible for c-Myc degradation. Moreover, silencing of FBXW7 in ZC3H15-knockdown GC cells could partly abrogate the effects induced by ZC3H15 downregulation. Taken together, our data unearth the important roles of ZC3H15 in GC development and suggest that ZC3H15 may be a potential target for the treatment of GC.

PHF14 knockdown causes apoptosis by inducing DNA damage and impairing the activity of the damage response complex in colorectal cancer.

The abnormal expression or mutation of the plant homeodomain finger protein 14 (PHF14), a recently discovered PHD finger protein, has been reported to link to a wide range of disorders, like the aetiology and pathophysiology of multiple malignancies. Its detailed biological functions, however, still remain unclear. Herein, we discovered that PHF14 expression is strongly associated with the gastrointestinal tumor grade and gastrointestinal disorders, especially colorectal cancer (CRC), with high PHF14 expressions indicating a poor prognosis. Additionally, the mutation rate of PHF14 in CRC patients accounts for a striking proportion of 18%. PHF14 is also implicated in the expression of several oncogenes. In vitro, PHF14 was significantly expressed in patient tissues and in various CRC cell lines, and its expression was closely associated with cell proliferation and growth. Knockdown of PHF14 mediated severe DNA damage and activation of the ATR-CHK1-H2A.X pathway, leading to apoptosis. Strikingly, PHF14 interacted with KIF4A and contributes to the formation of BRCA2/Rad51 foci, indicating that PHF14 is a newly discovered factor that may participate in the formation and recruitment of DNA damage response complexes. These impairments, however, could be alleviated by restoring PHF14 expression. Importantly, inhibiting PHF14 expression in CRC cells might reduce carcinogenesis in vivo. In conclusion, PHF14 is necessary for CRC cell proliferation and growth, and therefore, it might be used as a novel biomarker and therapeutic target for the disease.

Effects of different exercise programs on cardiorespiratory fitness and body composition in college students.

OBJECTIVE: The cardiorespiratory fitness (CRF) of college students is showing a downward trend, this study aimed to explore the effects of three exercise programs on CRF and body composition indicators in college students. METHODS: A total of 50 non-smoking, healthy and physically inactive students were recruited from campus in Beijing, China, and randomly assigned to 4 groups: low-intensity continuous training with blood flow restriction (LICT-BFR, n = 13), moderate-intensity continuous training (MICT, n = 13), high-intensity interval training (HIIT, n = 12), and no exercise control (n = 12), the intervention continued for 8 weeks. Body composition and aerobic capacity were measured before and after the intervention. RESULTS: Exercise groups reached significant improvements in maximal oxygen uptake (VO2max, p < 0.01) and a decrease in body fat percentage (p < 0.05) comparing to the control group. The fat mass and visceral fat area reduced significantly (p < 0.05) with a muscle mass growth (p < 0.05) in the LICT-BFR and MICT groups comparing to the control group. Changes of fat and muscle mass were trivial in the HIIT group (p = 0.842, p = 0.247). CONCLUSION: All three exercise programs can improve the CRF of college students, with LICT-BFR has the most profound effects, and MICT is more beneficial for body composition improvement than other programs. From an overall perspective, LICT-BFR should be the ideal choice, however, due to limited equipment, college students can choose MICT or HIIT according to their situations.

Glycolipid toxicity induces osteogenic dysfunction via the TLR4/S100B pathway.

Diabetes can cause bone metabolism disorders and osteoporosis. The occurrence of both diabetes mellitus and osteoporosis increases the disability and mortality of elderly individuals due to pathological fracture. Abnormal metabolism of nutrientsis considered to be one of the important mechanisms of diabetes mellitus-induced osteoporosis. This study preliminarily explored the roles of TLR4 (Toll-like receptor 4) and S100B in osteogenic dysfunction induced by glycolipid toxicity. In this study, a diabetic rat model and TLR4-knockdown diabetic rat model were used in vivo. MC3T3-E1 cells in a high glucose and palmitic acid environment were used as glycolipid toxicity cell models in vitro. We investigated the effects of TLR4 and S100B on osteogenesis by overexpression or inhibition of TLR4 and S100B in vitro. We found that when TLR4 or S100B was inhibited, ALP and OCN were significantly up-regulated and p-ERK was significantly down regulated in the glycolipid model. These results suggest that TLR4/S100B may play a role in reducing glycolipid toxicity by regulating ERK phosphorylation.

Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo.

BACKGROUND: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. METHODS: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the pharmacokinetic parameters of approved targeted drugs were summarized in combination with the FDA's drug instructions. Targeting drugs are divided into two categories: small molecule inhibitors and monoclonal antibodies. Novel targeting drugs and their mechanisms of action, which have been developed in recent years, are summarized. The distribution and metabolic processes of each drug in the human body are reviewed. RESULTS: In this review, we found that the distribution and metabolism of small molecule kinase inhibitors (TKI) and monoclonal antibodies (mAb) showed different characteristics based on the differences of action mechanism and molecular characteristics. TKI absorbed rapidly (Tmax ≈ 1-4 h) and distributed in large amounts (Vd > 100 L). It was mainly oxidized and reduced by cytochrome P450 CYP3A4. However, due to the large molecular diameter, mAb was distributed to tissues slowly, and the volume of distribution was usually very low (Vd < 10 L). It was mainly hydrolyzed and metabolized into peptides and amino acids by protease hydrolysis. In addition, some of the latest drugs are still in clinical trials, and the in vivo process still needs further study. CONCLUSION: According to the summary of the research progress of the existing targeting drugs, it is found that they have high specificity, but there are still deficiencies in drug resistance and safety. Therefore, the development of safer and more effective targeted drugs is the future research direction. Meanwhile, this study also provides a theoretical basis for clinical accurate drug delivery.

Early Percutaneous Dilational Tracheostomy in Trauma Patients After Anterior Cervical Fusion: Propensity-Matched Cohort Study.

BACKGROUND: Patients with cervical spinal cord injuries (CSCIs) may be required to undergo tracheostomy. However, in patients undergoing anterior cervical fusion (ACF), percutaneous dilational tracheostomy (PDT) may be delayed given the risk of cross-contamination. We aimed to evaluate the risk of surgical site infection (SSI) in early PDT in patients with traumatic CSCI after ACF. METHODS: All trauma patients admitted to the intensive care unit from 2008 to 2018 were retrospectively analyzed. Patients with CSCIs who underwent both ACF and PDT were identified, with or without posterior cervical fusion. Cases were classified as having undergone early PDT (≤4 days after ACF) versus late PDT (>4 days after ACF). Propensity scores were matched, and outcomes were compared between matched groups to reduce confounding by indication. RESULTS: From a total of 133 enrolled patients, a well-balanced propensity-matched cohort of 68 patients was defined. On the basis of the comparison of outcomes after matching, no significant difference in SSI was observed between both groups. There was no patient with SSI in the early PDT group (0%), whereas there were 2 SSI patients (5.9%) in the late PDT group (P = 0.493): The tracheostomy site was involved in 1, and the posterior approach site was involved in the other. Early PDT was associated with a shorter duration of mechanical ventilation (P = 0.042). There were no significant differences in the length of intensive care unit stay and hospital mortality between groups. CONCLUSIONS: Early PDT within 4 days after ACF did not increase the risk of SSI compared with late PDT in patients with traumatic CSCIs.

Noninvasive Ventilation as a Weaning Strategy in Subjects with Acute Hypoxemic Respiratory Failure.

BACKGROUND: Weaning through noninvasive ventilation (NIV) after early extubation may facilitate invasive ventilation withdrawal and reduce related complications in patients with hypercapnic respiratory failure. However, the effects of NIV weaning are uncertain in patients with acute hypoxemic respiratory failure (AHRF). We aimed to investigate whether NIV weaning could reduce hospital mortality and other outcomes compared with invasive weaning in subjects with hypoxemic AHRF. METHODS: We searched medical literature databases for relevant articles published from inception to February 2019. Randomized controlled trials that adopted NIV as a weaning strategy compared with invasive weaning in hypoxemic AHRF were included. The primary outcome was hospital mortality. The secondary outcomes included ICU mortality, the ICU stay, weaning time, duration of ventilation, extubation failure, and adverse events. RESULTS: Six relevant studies, which involved 718 subjects, were included. There was no significant effect of NIV weaning on hospital mortality compared with invasive weaning (risk ratio 0.94, 95% CI 0.65-1.36; P = .74), whereas there was a significant effect of NIV weaning on shortening the ICU stay (mean difference -3.95, 95% CI -6.49 to -1.40, P = .002) and on decreasing adverse events without affecting the weaning time (standardized MD -0.04, 95% CI -0.21 to 0.14; P = .68). CONCLUSIONS: The strategy of NIV weaning did not decrease hospital mortality in subjects with hypoxemic AHRF, but it did shorten the ICU lengths of stay and reduce adverse events.

[Non-invasive ventilation with helmet in patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the effect and tolerance of non-invasive ventilation (NIV) with helmet in patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the effect on improving blood gas, alleviating dyspnea and the occurrence of complications. METHODS: Patients with AECOPD and respiratory failure admitted to emergency intensive care unit (EICU) and respiratory intensive care unit (RICU) of the First Affiliated Hospital of Zhengzhou University from January 1st, 2018 to May 31st, 2019 were enrolled. After obtaining the informed consent of the patients or their authorized family members, the patients were divided into two groups: the helmet group and the facial mask group by random number table. NIV was carried out by using helmet or facial mask, respectively. During the course of NIV (immediately, 1 hour, 4 hours and at the end of NIV), the tolerance score, blood gas analysis, heart rate (HR), respiratory rate (RR) of patients were monitored, and the incidence of tracheal intubation, in-hospital mortality and complications were observed. Kaplan-Meier survival curve was plotted to analyze the 30-day cumulative survival of the two groups. RESULTS: A total of 82 patients with AECOPD and respiratory failure were included during the study period. After excluding patients with the oxygenation index (PaO2/FiO2) > 200 mmHg (1 mmHg = 0.133 kPa), with tracheal intubation or invasive ventilation, suffering from acute myocardial infarction, severe trauma within 2 weeks, excessive secretion, sputum discharge disorder or refusal to participate in the study, 26 patients were finally enrolled in the analysis, randomly assigned to the helmet group and the facial mask group, with 13 patients in each group. The PaO2/FiO2 after NIV of patients in both groups was increased significantly as compared with that immediately after NIV, without significant difference between the two groups, but the increase in PaO2/FiO2 at the end of NIV compared with immediately after NIV in the helmet group was significantly higher than that in the facial mask group (mmHg: 75.1±73.2 vs. 7.7±86.0, P < 0.05). RR at each time point after NIV in the two groups was lower than that immediately after NIV, especially in the helmet group. There were significant differences between the helmet group and facial mask group at 1 hour, 4 hours, and the end of NIV (times/min: 17.5±4.1 vs. 23.1±6.3 at 1 hour, 16.2±2.5 vs. 20.0±5.5 at 4 hours, 15.5±2.5 vs. 21.2±5.9 at the end of NIV, all P < 0.05). The NIV tolerance score of the helmet group at 4 hours and the end was significantly higher than that of the facial mask group (4 hours: 3.9±0.3 vs. 3.3±0.9, at the end of NIV: 3.8±0.6 vs. 2.9±0.9, both P < 0.05). There was no significant difference in the improvement of pH value, arterial partial pressure of carbon dioxide (PaCO2), or HR between helmet group and facial mask group. The total number of complications (cases: 3 vs. 8) and the nasal skin lesions (cases: 0 vs. 4) in the helmet group were significantly less than those in the facial mask group (both P < 0.05). Only 2 patients in the helmet group received endotracheal intubation, and 1 of them died; 5 patients in the facial mask group received endotracheal intubation, and 3 of them died; there was no significant difference between the two groups (both P > 0.05). The Kaplan-Meier survival curve analysis showed that the cumulative survival rate of 30 days in the helmet group was lower than that in the facial mask group, but the difference was not statistically significant (Log-Rank test: χ2 = 1.278, P = 0.258). CONCLUSIONS: NIV with helmet has better comfort for patients with AECOPD combined with respiratory failure, and better effect on improving oxygenation and relieving dyspnea, and its effect on carbon dioxide emissions is not inferior to that of traditional mask NIV.

High-flow nasal cannula versus conventional oxygen therapy in patients with dyspnea and hypoxemia before hospitalization.

Introduction: Patients with dyspnea and hypoxemia are common in emergency departments. However, it is unknown whether high-flow nasal cannula (HFNC) reduces the risk of requiring more advanced ventilation support and whether HFNC relieves dyspnea better than conventional oxygen therapy (COT).Areas covered: We searched the PubMed, Cochrane Library, Ovid, and Embase databases from inception to 1 September 2019 to identify relevant-randomized controlled trials comparing the effect of HFNC with COT in emergency departments regarding the severity of dyspnea, hospitalization rate, intubation rate, and hospital mortality. We identified four studies. HFNC was associated with a lower rate of requiring more advanced ventilation. HFNC reduced the rate of dyspnea, lowered the dyspnea scale score, and decreased patients' respiratory rate significantly. However, there was insufficient evidence to show a significant effect on HFNC regarding patients' oxygenation and hospital mortality.Expert opinion: For patients with dyspnea and hypoxemia before hospitalization, the short-term effect of HFNC was undeniable. HFNC reduced the risk of requiring more advanced ventilation and relived dyspnea better than COT. HFNC might be considered as a first-line therapy even before making a clear diagnosis for dyspnea.More studies are needed to explore the effect of HFNC on oxygenation and patients' prognosis.

On the Unreported-Profile-is-Negative Assumption for Predictive Cheminformatics.

In cheminformatics, compound-target binding profiles has been a main source of data for research. For data repositories that only provide positive profiles, a popular assumption is that unreported profiles are all negative. In this paper, we caution the audience not to take this assumption for granted, and present empirical evidence of its ineffectiveness from a machine learning perspective. Our examination is based on a setting where binding profiles are used as features to train predictive models; we show (1) prediction performance degrades when the assumption fails and (2) explicit recovery of unreported profiles improves prediction performance. In particular, we propose a framework that jointly recovers profiles and learns predictive model, and show it achieves further performance improvement. The presented study not only suggests applying matrix recovery methods to recover unreported profiles, but also initiates a new missing feature problem which we called Learning with Positive and Unknown Features.