Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study.

BACKGROUND: Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment. METHODS: This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate. RESULTS: Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (P=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted P values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (P<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events. CONCLUSIONS: The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05404373.

Vaccination status for mild and asymptomatic infections with SARS-CoV-2 Omicron BA.2 variant in Shanghai.

This study aimed to evaluate the effects of different vaccine regimens on mild and asymptomatic infections with SARS-CoV-2 Omicron BA.2 variant in Shanghai. All asymptomatic patients and those with mild symptoms of Omicron infections were recruited from three major Fangcang shelter hospitals between March 26, 2022 and May 20, 2022. Nucleic acid for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction methods in nasopharyngeal swabs was assessed every day during the hospitalization. The value of cycle threshold lower than 35 was considered as positive result of SARS-CoV-2. A total of 214 592 cases were included in this study. The proportion of the asymptomatic patients was 76.90% and 23.10% of the recruited patients had mild symptoms. The median (interquartile range [IQR]: 25-75) duration of viral shedding (DVS) was 7 (5-10) days among all participants. The DVS varied greatly among different age groups. Children and the elderly had longer DVS compared with the adults. The booster shot of inactivated vaccine contributed to the shorter DVS in patients aged ≥70 years compared with the unvaccinated patients (8 [6-11] vs. 9 [6-12] days, p = 0.002]. Full inactivated vaccine regimen contributed to the shorter DVS in patients aged 3-6 years (7 [5-9] vs. 8 [5-10] days, p = 0.001]. In conclusion, the full inactivated vaccine regimen on children aged 3-6 years and booster inactivated vaccine regimen on the elderly aged ≥70 years appeared to be effective in reducing DVS. The booster vaccine regimen should be rigorously promoted and implemented.

Racial differences in the associations of urinary phthalate metabolites with depression risk.

OBJECTIVE: This study aimed to investigate the composite effects of different kinds of phthalates on depression risk in the U.S population. METHODS: 11731 participants were included from the National Health and Nutrition Examination Survey (NHANES), a national cross-sectional survey. Twelve urinary phthalate metabolites were used to evaluate the level of phthalates exposure. Phthalates levels were devided into four quartiles. High phthalate was defined as having values in the highest quartile. RESULTS: Urinary mono-isobutyl phthalate (MiBP) and mono-benzyl phthalate (MBzP) were estimated as the independent risk factors for depression by mutivariate logistic regression analyses. Compared with the lowest quartile group of MiBP or MBzP, an incrementally higher risk of depression and moderate/severe depression was observed in the highest quartile (all Ptrend <0.05). It was observed that incrementally higher risk of depression and moderate/severe depression were associated with more numbers of high phthalates parameter (Ptrend <0.001 and Ptrend = 0.003, respectively). A significant interaction between race (Non-Hispanic Black vs. Mexican American) and 2 parameters (having value in the highest quartile of both MiBP and MBzP) was detected for depression (Pinteraction = 0.023) and moderate/severe depression (Pinteraction = 0.029). CONCLUSION: Individuals with more numbers of high phthalates parameter were at higher risk of depression and moderate/severe depression. Non-Hispanic Black participants were more likely to be affected by high levels of MiBP and MBzP exposure than Mexican American participants.

Comparison of respiratory pathogens in children with community-acquired pneumonia before and during the COVID-19 pandemic.

BACKGROUND: Multifaceted non-pharmaceutical interventions during the COVID-19 pandemic have not only reduced the transmission of SARS-CoV2, but have had an effect on the prevalence of other pathogens. This retrospective study aimed to compare and analyze the changes of respiratory pathogens in hospitalized children with community-acquired pneumonia. METHODS: From January 2019 to December 2020, children with community-acquired pneumonia were selected from the Department of Respiratory Medicine, Shanghai Children's Medical Center. On the first day of hospitalization, sputum, throat swabs, venous blood samples from them were collected for detection of pathogens. RESULTS: A total of 2596 children with community-acquired pneumonia were enrolled, including 1871 patients in 2019 and 725 in 2020. The detection rate in 2020 was lower than in 2019, whether single or multiple pathogens. Compared with 2019, the detection rate of virus, especially parainfluenza virus, influenza virus and respiratory syncytial virus, all decreased in 2020. On the contrary, the prevalence of human rhinovirus was much higher than that in 2019. In addition, the positivity rate for bacteria did not change much over the two years, which seemed to be less affected by COVID-19. And Mycoplasma pneumoniae which broke out in 2019 has been in low prevalence since March 2020 even following the reopening of school. CONCLUSIONS: Strict public health interventions for COVID-19 in China have effectively suppressed the spread of not only SARS-CoV2 but parainfluenza virus, influenza virus and Mycoplasma pneumonia as well. However, it had a much more limited effect on bacteria and rhinovirus. Therefore, more epidemiological surveillance of respiratory pathogens will help improve early preventive measures.

Clinical Experience with 30 Bridging Bronchus Patients with Airway Stenosis and Congenital Heart Disease.

The indications and surgical techniques for airway stenosis (AS) repair among patients with bridging bronchus (BB) and congenital heart disease (CHD) have not been fully established. We sought to provide our experience with tracheobronchoplasty in a large series of BB patients with AS and CHD. Eligible patients were retrospectively enrolled from June 2013 to December 2017 and were followed up to December 2021. Epidemiological, demographic, clinical, imaging, surgical management, and outcome data were obtained. 5 tracheobronchoplasty techniques including 2 novel modified ones were performed. We included 30 BB patients with AS and CHD. Tracheobronchoplasty was indicated in them. 27 (90%) patients underwent tracheobronchoplasty. But 3 (10%) refused AS repair. 4 subtypes of the BB and 5 main sites of AS were identified. 6 (22.2%) cases, including one death, had severe postoperative complications associated with being underweight at surgery, preoperative mechanical ventilation, and more types of CHD. 3 cases were lost to follow-up. 18 (78.3%) of the survivors remained asymptomatic, and 5 (21.7%) had stridor, wheezing, or polypnea after exercise. 2 patients out of the three who did not undergo airway surgery died, and the one survivor had a poor quality of life. Good outcomes can be achieved in BB patients with AS and CHD who undergo proper tracheobronchoplasty techniques guided by specified criteria, but severe postoperative complications should be well managed.

[Clinical phenotype and genetic analysis of a child with 14q12q13 microdeletion syndrome manifesting as congenital hypothyroidism].

OBJECTIVE: To analyze the clinical phenotype and genetic etiology for a child featuring congenital hypothyroidism (CH). METHODS: Whole exome sequencing (WES), copy number variation (CNV) sequencing and chromosomal microarray analysis (CMA) were carried out for a newborn infant who had presented at Linyi People's Hospital for CH. Clinical data of the child was analyzed, in addition with a literature review. RESULTS: The main characteristics of the newborn infant had included peculiar face, vulvar edema, hypotonia, psychomotor retardation, recurrent respiratory tract infection with laryngeal wheezing and feeding difficulties. Laboratory test indicated hypothyroidism. WES suggested a CNV deletion on chromosome 14q12q13. CMA further confirmed a 4.12 Mb deletion at chromosome 14q12q13.3 (32649595_36769800), which has encompassed 22 genes including NKX2-1, the pathogenic gene for CH. The same deletion was found in neither of her parents. CONCLUSION: Through the analysis of clinical phenotype and genetic variant, the child was diagnosed with 14q12q13.3 microdeletion syndrome.

Time to Mycoplasma Pneumoniae RNA Clearance for Wheezy vs. Non-Wheezy Young Children with Community-Acquired Pneumonia.

OBJECTIVES: We sought to investigate the dynamics of Mycoplasma pneumoniae (Mp) RNA in hospitalized young children with community-acquired pneumonia (CAP) and to explore whether Mp RNA clearance differed for wheezy and non-wheezy group after the onset of azithromycin treatment. METHODS: We included hospitalized young children (1-72 months of age) with CAP caused by Mp infection. Mp RNA was detected as soon as the patient was admitted and the dynamics of Mp-RNA were monitored after the beginning of azithromycin treatment on Days 4, 7, 14 and 28. RESULTS: Among 40 hospitalized young children with Mycoplasma pneumoniae pneumonia (Mpp), 16 had wheezing. Time to first positive Mp-RNA confirmation after symptom onset of Mpp was similar for the wheezy group (median 7 days, interquartile range 7-10.5) and the non-wheezy group (median 7 days, interquartile range 5.8-8.3). The duration of positive Mp-RNA detection after the onset of azithromycin treatment was shorter among the wheezy group than in the non-wheezy group (median 4 vs. 7 days; hazard ratio 2.083; 95% confidence interval: 1.023-4.244). CONCLUSIONS: Mp-RNA clearance was significantly faster among Mpp young children with wheezing than in those without wheezing after the onset of azithromycin treatment.Lay summaryWe sought to investigate the dynamics of Mycoplasma pneumoniae (Mp) RNA in hospitalized young children with community-acquired pneumonia and to explore whether Mp RNA clearance differed for wheezy and non-wheezy group after the onset of azithromycin treatment. Our study suggested that Mp-RNA clearance was significantly faster among Mycoplasma pneumoniae pneumonia young children with wheezing than in those without wheezing after the onset of azithromycin treatment.

PNPLA3 I148M mediates the regulatory effect of NF-kB on inflammation in PA-treated HepG2 cells.

Both PNPLA3 I148M and hepatic inflammation are associated with nonalcoholic fatty liver disease (NAFLD) progression. This study aimed to elucidate whether PNPLA3 I148M is involved in NF-kB-related inflammation regulation in NAFLD. HepG2 cells homozygous for the PNPLA3 I148M mutation were used. The human PNPLA3 promoter sequence was screened for NF-kB binding sites using the MATCH and PATCH tools. NF-kB-mediated transcriptional regulation of the PNPLA3 gene was assessed by luciferase reporter assay, EMSA and ChIP-qPCR. Wild-type (I148I) and mutant (M148M) PNPLA3 were overexpressed using stable lentivirus-mediated transfection. The pCMV vector and siRNA were transiently transfected into cells to direct NF-kB overexpression and PNPLA3 silencing, respectively. A putative NF-kB binding site in the human PNPLA3 promoter was shown to be necessary for basal and NF-kB-driven transcriptional activation of PNPLA3 and protein/DNA complex formation. Supershift analysis demonstrated a protein/DNA complex specifically containing the NF-kB p65 and p50 subunits. ChIP-qPCR confirmed the endogenous binding of NF-kB to the human PNPLA3 promoter in response to NF-kB overexpression and palmitic acid (PA) challenge. The silencing of PNPLA3 blocked the overexpression of NF-kB or PA-induced TNF-α up-regulation. Moreover, mutant PNPLA3 overexpression prevented NF-kB inhibitor-induced down-regulation of TNF-α expression in PA-treated HepG2 cells. Finally, the overexpression of mutant but not wild-type PNPLA3 increased TNF-α expression and activated the ER stress-mediated and NF-kB-independent inflammatory IRE-1α/JNK/c-Jun pathway. Human PNPLA3 was shown to be a target of NF-kB, and PNPLA3 I148M mediated the regulatory effect of NF-kB on inflammation in PA-treated HepG2 cells, most likely via the IRE-1α/JNK/c-Jun ER stress pathway.

A Novel, Widespread qacA Allele Results in Reduced Chlorhexidine Susceptibility in Staphylococcus epidermidis.

Chlorhexidine gluconate (CHG) is a topical antiseptic widely used in health care settings. In Staphylococcus spp., the pump QacA effluxes CHG, while the closely related QacB cannot due to a single amino acid substitution. We characterized 1,050 cutaneous Staphylococcus isolates obtained from 173 pediatric oncology patients enrolled in a multicenter CHG bathing trial. CHG susceptibility testing revealed that 63 (6%) of these isolates had elevated CHG MICs (≥4 µg/ml). Screening of all 1,050 isolates for the qacA/B gene (the same qac gene with A or B allele) by restriction fragment length polymorphism (RFLP) yielded 56 isolates with a novel qacA/B RFLP pattern, qacA/B273 The CHG MIC was significantly higher for qacA/B273 -positive isolates (MIC50, 4 µg/ml; MIC range, 0.5 to 4 µg/ml) than for other qac groups: qacA-positive isolates (n = 559; MIC50, 1 µg/ml; MIC range, 0.5 to 4 µg/ml), qacB-positive isolates (n = 17; MIC50, 1 µg/ml; MIC range, 0.25 to 2 µg/ml), and qacA/B-negative isolates (n = 418, MIC50, 1 µg/ml; MIC range, 0.125 to 2 µg/ml) (P = 0.001). A high proportion of the qacA/B273 -positive isolates also displayed methicillin resistance (96.4%) compared to the other qac groups (24.9 to 61.7%) (P = 0.001). Whole-genome sequencing revealed that qacA/B273 -positive isolates encoded a variant of QacA with 2 amino acid substitutions. This new allele, named qacA4, was carried on the novel plasmid pAQZ1. The qacA4-carrying isolates belonged to the highly resistant Staphylococcus epidermidis sequence type 2 clone. By searching available sequence data sets, we identified 39 additional qacA4-carrying S. epidermidis strains from 5 countries. Curing an isolate of qacA4 resulted in a 4-fold decrease in the CHG MIC, confirming the role of qacA4 in the elevated CHG MIC. Our results highlight the importance of further studying qacA4 and its functional role in clinical staphylococci.

Evidence of correlation between TGFBR2 gene expression mediated by NF-κb signaling pathways and Kawasaki disease in children.

BACKGROUND: We explored the correlation between the TGFBR2 gene that is mediated by NF-κb signaling pathways and the pathogenesis of Kawasaki disease in children. METHODS: In this study, 43 children with Kawasaki disease from April 2014 to January 2016 at our hospital were selected as the observation group, and 42 healthy children were selected as the control group. The mRNA expression levels of NF-κb gene and TGFBR2 gene in different groups were detected using fluorescence quantitative PCR. The protein expression levels of the NF-κb and TGFBR2 were detected using enzyme-linked immunosorbent assay (ELISA) in different groups. The expression levels of NF-κb and TGFBR2 in the observation group and the control group were detected using immunohistochemistry. RESULTS: Compared to the control group, the mRNA expression levels of NF-κb and TGFBR2 were 12.3 times and 27.5 times as high as those in the control group respectively and there were significant differences between the two groups (P<0.05). ELISA results showed that there were significant differences between the protein expression levels of NF-κb and TGFBR2 in the control group (0.87±0.12, 1.25±0.18 µg/L) and those in the observation group (3.27±0.17, 8.16±0.22 µg/L) (P<0.05). Western-blotting results showed that the expression levels of the NF-κB and TGFBR2 in children with Kawasaki disease were significantly higher than those in healthy subjects (P<0.05). Immunohistochemistry results showed that the positive cell rate of TGFBR2 (89.7%) was significantly higher in children with Kawasaki disease than that in healthy children (4.5%); there was significant difference between the two groups (P<0.05). CONCLUSIONS: The TGFBR2 may be involved in the pathogenesis of Kawasaki disease in children through NF-κb signaling pathways.

The SRE Motif in the Human PNPLA3 Promoter (-97 to -88 bp) Mediates Transactivational Effects of SREBP-1c.

Patatin-like phospholipase domain containing 3 (PNPLA3) is a non-secreted protein primarily expressed in liver and adipose tissue. Recently, numerous genetic studies have shown that PNPLA3 is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD). However, the mechanism involved in transcriptional regulation of the PNPLA3 gene remains unknown. We performed a detailed analysis of the human PNPLA3 gene promoter and identified two novel cis-acting elements (SRE and NFY binding motifs) located at -97/-88 and -26/-22 bp, respectively. Overexpression of SREBP-1c in HepG2 cells significantly increased PNPLA3 promoter activity. Mutation of either of the putative SRE or NFY binding motifs blocked the transactivation effects of SREBP-1c on the promoter. Overexpression of SREBP-1c and NFY together increased PNPLA3 promoter activity twice as much as that of SREBP-1c or NFY expression alone. This result suggests that SREBP-1c and NFY synergistically transactivate the human PNPLA3 gene. The ability of SREBP-1c and NFY to bind these cis-elements was confirmed using gel shift analysis. Putative SRE and NFY motifs also mediated synergistic insulin-induced transactivation of the PNPLA3 promoter in HepG2 cells. Additionally, the ability of SREBP-1c to bind to the PNPLA3 promoter was increased by insulin in a dose-dependent manner. Moreover, the treatment of HepG2 cells with the PI3K inhibitor LY294002 led to reduced insulin promoter-activating ability accompanied by a decrease in PNPLA3 and SREBP-1c protein expression. These results demonstrate that SREBP-1c is a direct activator of the human PNPLA3 gene and insulin transactivates the PNPLA3 gene via the PI3K-SREBP-1c/NFY pathway in HepG2 cells.

Association of serum occludin levels and perihematomal edema volumes in intracranial hemorrhage patients.

BACKGROUND AND PURPOSE: Perihematomal edema (PHE) is one of the severe secondary damages following intracranial hemorrhage (ICH). Studies showed that blood-brain barrier (BBB) injury contributes to the development of PHE. Previous studies showed that occludin protein is a potential biomarker of BBB injury. In the present study, we investigated whether the levels of serum occludin on admission are associated with PHE volumes in ICH patients. METHODS: This cross-sectional study included 90ICH patients and 32 healthy controls.The volumes of hematoma and PHE were assessed using non-contrast cranial CT within 30 min of admission. Blood samples were drawn on admission, and the levels of baseline serum occludin were detected using enzyme-linked immunosorbent assay. Partial correlation analysis and multiple linear regression analysis were performed to evaluate the association between serum occludin levels and PHE volumes in ICH patients. RESULTS: The serum occludin levels in ICH patients were much higher than health controls (median 0.27 vs. 0.13 ng/mL, p < 0.001). At admission, 34 ICH patients (37.78%) had experienced a severe PHE (≥30 mL), and their serum occludin levels were higher compared to those with mild PHE (<30 mL) (0.78 vs. 0.21 ng/mL, p < 0.001). The area under the receiver operating characteristics curve (ROC) of serum occludin level in predicting severe PHE was 0.747 (95% confidence interval CI 0.644-0.832, p < 0.001). There was a significant positive correlation between serum occludin levels and PHE volumes (partial correlation r = 0.675, p < 0.001). Multiple linear regression analysis showed that serum occludin levels remained independently associated with the PHE volumes after adjusting other confounding factors. CONCLUSION: The present study showed that serum occludin levels at admission were independently correlated with PHE volumes in ICH patients, which may provide a biomarker indicating PHE volume change.

The combination model of serum occludin and clinical risk factors improved the efficacy for predicting hemorrhagic transformation in stroke patients with recanalization.

Background: and Purpose: Hemorrhagic transformation (HT) is one of the severe complications in acute ischemic stroke, especially for the patients who undergo recanalization treatment. It is crucial to screen patients who have high risk of HT before recanalization. However, current prediction models based on clinical factors are not ideal for clinical practice. Serum occludin, a biomarker for cerebral ischemia-induced blood-brain barrier disruption, has potential for predicting HT. This study was to investigate whether the combination of serum occludin and clinical risk factors improved the efficacy of predicting HT. Methods: This was a single-center prospective observational study. Baseline clinical data and blood samples of recanalization patients were collected upon admission to our hospital. The level of serum occludin was measured using enzyme-linked immunosorbent assay. The diagnosis of HT was confirmed by CT scans within 36 h post recanalization. Results: A total of 324 patients with recanalization were enrolled and 68 patients presented HT occurrence. HT patients had the higher level of baseline occludin than patients without HT (p < 0.001). Multivariate regression analysis showed that serum occludin level, Alberta Stroke Program Early CT Scores and endovascular therapy were independent risk factors (p < 0.05) for HT after adjusting potential confounders. The combination of serum occludin and clinical risk factors significantly improved the accuracy of predicting HT [area under the curve (AUC, 0.821 vs 0.701, p < 0.001), and net reclassification improvement (31.1 %), integrated discrimination improvement (21.5 %), p < 0.001] compared to a model employing only clinical risk factors. The modified AUC (0.806) of combined model based on 10-fold-cross-validation was still higher than clinical risk model (0.701). Conclusion: The combination of serum occludin and clinical risk factors significantly improved the prediction efficacy for HT, providing a novel potential prediction model to screen for patients with high risk of HT before recanalization in acute ischemic stroke.

Blood brain barrier-targeted lipid nanoparticles improved the neuroprotection of Ferrostatin-1 against cerebral ischemic damage in an experimental stroke model.

Cerebral ischemic stroke is a serious disease with high mortality and disability rates. However, few neuroprotective drugs have been used for ischemic stroke in the clinic. Two main reasons may be responsible for this failure: difficulty in penetrating the blood-brain barrier (BBB) and easily inactivated in the blood circulation. Ferroptosis, a lipid oxidation-related cell death, plays significant roles in cerebral ischemia-reperfusion injury. We utilized RVG29, a peptide derived from Rabies virus glycoprotein, to obtain BBB-targeted lipid nanoparticles (T-LNPs) in order to investigate whether T-LNPs improved the neuroprotective effects of Ferrostatin-1 (Fer1, an inhibitor of ferroptosis) against cerebral ischemic damage. T-LNPs significantly increased BBB penetration following oxygen/glucose deprivation exposure in an in vitro BBB model and enhanced the fluorescence distribution in brain tissues at 6 h post-administration in a cerebral ischemic murine model. Moreover, T-LNPs encapsulated Fer1 (T-LNPs-Fer1) significantly enhanced the inhibitory effects of Fer1 on ferroptosis by maintaining the homeostasis of NADPH oxidase 4 (NOX4) and glutathione peroxidase 4 (GPX4) signals in neuronal cells after cerebral ischemia. T-LNPs-Fer1 significantly suppressed oxidative stress [heme oxygenase-1 expression and malondialdehyde (the product of lipid ROS reaction)] in neurons and alleviated ischemia-induced neuronal cell death, compared to Fer1 alone without encapsulation. Furthermore, T-LNPs-Fer1 significantly reduced cerebral infarction and improved behavior functions compared to Fer1-treated cerebral ischemic mice after 45-min ischemia/24-h reperfusion. These findings showed that the T-LNPs helped Fer1 penetrate the BBB and improved the neuroprotection of Fer1 against cerebral ischemic damage in experimental stroke, providing a feasible translational strategy for the development of clinical drugs for the treatment of ischemic stroke.

The correlation between selenium intake and lung function in asthmatic people: a cross-sectional study.

Objective: This study aimed to examine the correlation between selenium intake and lung function in asthmatic people. Methods: A total of 4,541 individuals in the US National Health and Nutrition Examination Survey (NHANES) were included in this study. Multivariate linear regression, variance inflation factor, restricted cubic splines and quantile regression were used to analyze the relationship between Se intake and lung function. We divided selenium intake into four levels based on quartiles: Q1: Se ≤ 76.75 mcg/d; Q2: 76.75-105.1 mcg/d; Q3: 105.1-137.65 mcg/d; and Q4: Se ≥137.65 mcg/d. Results: Asthma was negatively associated with the Ratio of Forced Expiratory Volume 1st Second to Forced Vital Capacity (FEV1/FVC) (ß = -0.04, 95% CI: -0.06 to -0.02) and FEV1 (ß = -215, 95% CI: -340 to -90). Se intake was positively associated with Forced Expiratory Volume 1st Second (FEV1) (ß =3.30 95% CI: 2.60 to 4.00) and Forced Vital Capacity (FVC) (ß =4.30, 95% CI: 3.50 to 5.10). In asthmatic individuals, the positive effects of Se intake on FVC were enhanced with increasing Se intake, while the positive effects of Se intake on FEV1 varied less dramatically. High Se intake (Q4 level, above 137.65 mcg/d) improved FVC (ß = 353, 95% CI: 80 to 626) and FEV1 (ß = 543, 95% CI: 118 to 969) in asthmatic patients compared to low Se intake (Q1 level, below 76.75 mcg/d). At the Q2 level (76.75-105.1 mcg/d) and Q4 level (Se ≥137.65 mcg/d) of Se intake, the correlation between FEV1 and asthma disappeared. Conclusion: Our research has revealed a positive correlation between selenium intake and lung function in asthma patients and the strength of this positive correlation is related to the amount of selenium intake. We recommend that asthma patients consume 137.65 mcg to 200 mcg of selenium daily to improve pulmonary function while avoiding the adverse effects of selenium on the human body.

The neuroprotective role of prolonged normobaric oxygenation applied during ischemia and in the early stage of reperfusion in cerebral ischemic rats.

BACKGROUND: Recanalization is the main treatment option for ischemic stroke. However, prognosis remains poor for about half of patients after recanalization, possibly due to the "no-reflow" phenomenon at the early phase of recanalization. Normobaric oxygenation (NBO) during ischemia can reportedly maintain the partial pressure of oxygen and exert a protective effect in ischemic brain tissue. OBJECTIVES AND METHODS: This study investigated whether prolonged NBO treatment during ischemia and the early phase of reperfusion (i/rNBO) has neuroprotective effects and to elucidate the underlying mechanisms in rats with middle cerebral artery occlusion plus reperfusion. RESULTS: NBO treatment significantly elevated the level of O2 in the atmosphere and arterial blood without altering the level of CO2. The infarcted cerebral volume was significantly reduced by application of i/rNBO as compared to iNBO (applied during ischemia) or rNBO (applied at the early phase of reperfusion), indicating better protective effects of i/rNBO. i/rNBO more effectively suppressed s-nitrosylation of MMP-2 (amplifying inflammation) as compared to iNBO and rNBO, dramatically downregulated the cleavage of poly(ADP-ribose)polymerase-1 (PARP-1, acting as the substrate of MMP-2), and suppressed neuronal apoptosis, as determined by the TUNEL assay and staining for NeuN. These results demonstrated that application of i/rNBO in the early stage of reperfusion significantly alleviated neuronal apoptosis via suppression of the MMP-2/PARP-1 pathway. CONCLUSIONS: The mechanism underlying the neuroprotective role of i/rNBO involved prolonged NBO treatment for cerebral ischemia, suggesting that i/rNBO may allow expansion of the time window for NBO application in stroke patients following vascular recanalization.

Outcomes of Holmium Laser, Cryoablation, and Budesonide Inhalation for Treating Severe Central Airway Stenosis in Infants.

BACKGROUND: Central airway stenosis (CAS) in infants is characterized by dysphonia, dyspnea, cyanosis, repeated apnea, and infection. This case series study aimed to evaluate the safety and efficacy of holmium laser, cryoablation and budesonide inhalation in treating infants with severe CAS. METHODS: This retrospective study reviewed medical records data of 28 infants with severe CAS who underwent holmium laser treatment with cryoablation and/or balloon dilatation and budesonide inhalation therapy at Shanghai Children's Medical Center between June 2014 and May 2020. Outcomes were defined as treatment success when the stenotic area was <25% for the normal age group with stable reopening diameter at one-year follow-up. RESULTS: Patients' mean age was 12.8 ± 8.8 months and 17 (60%) were male. Sixteen cases had web-like stenosis and 12 had scar contracture stenosis. Among 16 patients with web-like stenosis, 8 (50%) underwent balloon dilation with cryotherapy and 8 (50%) underwent balloon dilation only; treatment success was achieved in 10 (62.5%) cases and after revised treatments in 5 (31.25%) cases. Among 12 patients with scar contracture stenosis, 6 (50%) underwent balloon dilation with cryotherapy, 4 (33.3%) underwent cryotherapy and 2 (16.7%) underwent balloon dilation only; treatment success was achieved in 3 (23.1%) cases and after 1-4 revised treatments in 8 (61.5%) cases. Symptoms of the 2 unsuccessful (7.1%) cases were relieved after tracheal stent insertion. Neither severe adverse events nor complications were observed during follow-up. CONCLUSION: Holmium laser with cryoablation followed by budesonide inhalation therapy safely and effectively cleans stenotic tissues and maintains airway reopening. Balloon dilation after holmium laser is recommended for treating web-like stenosis.

Emergency Angioplasty or Stenting for Stroke Patients with Intracranial Atherosclerotic Large Vessel Occlusion.

AIM: Mechanical thrombectomy (MT) has become the gold standard for the treatment of large vessel occlusion (LVO) in acute ischemic stroke. However, it remains controversial whether emergency angioplasty or stenting in patients with intracranial atherosclerotic stenosis (ICAS) should be adopted. Thus, we performed a retrospective analysis of clinical data to determine whether emergency angioplasty or stenting is necessary. METHODS: We retrospectively analyzed data from patients undergoing MT with ICAS-related LVO of the acute anterior circulation between 2017 and 2019. Eligible patients were divided into two treatment groups: those who received rescue angioplasty or stenting [Patients treated with rescue angioplasty or stenting (PTAS) group] and those who received thrombectomy alone (non-PTAS group). The primary outcomes were good prognosis at 90 days (mRS: 0-2). Mortality, symptomatic intracranial hemorrhage, and reocclusion rate were evaluated as secondary outcomes. RESULTS: A total of 184 patients with severe stenosis after MT were enrolled, including 64 patients receiving rescue angioplasty or stenting and 120 patients without rescue angioplasty or stenting. Compared with the non-PTAS group, a better functional outcome (mRS0-2) (51.6% vs. 35.0%, adjusted odds ratio: 2.11, 95% confidence interval [CI]: 1.22-4.29; P=0.02), lower 7-day National Institutes of Health Stroke Scale [6 (3-12.75) vs. 10 (4-16); P=0.04], lower 24-h neurological deterioration rate (7.8% vs. 21.7%, P=0.02), and lower 24-h reocclusion rate were observed in the PTAS group (6.3% vs. 17.5%, P=0.03). There were no significant differences in mortality or incidence of symptomatic intracerebral hemorrhage. CONCLUSION: Emergency angioplasty or stenting could be a safe and feasible therapeutic option with better outcomes for stroke patients with ICAS-related LVO.

Huashi baidu granule in the treatment of pediatric patients with mild coronavirus disease 2019: A single-center, open-label, parallel-group randomized controlled clinical trial.

Background: Since late February 2022, a wave of coronavirus disease 2019 (COVID-19) mainly caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly appeared in Shanghai, China. Traditional Chinese medicine treatment is recommended for pediatric patients; however, the safety and efficacy remain to be confirmed. We conducted a single-center, open-label, parallel-group randomized controlled trial to assess the efficacy and safety of a Chinese herb compound, Huashi Baidu granule (HSBDG) in pediatric patients with laboratory-confirmed mild COVID-19. Methods: 108 recruited children (aged 3-18 years) with laboratory-confirmed mild COVID-19 were randomly allocated 2:1 to receive oral HSBDG for five consecutive days (intervention group) and to receive compound pholcodine oral solution for five consecutive days (control group). The negative conversion time of SARS-CoV-2 nucleic acid and symptom scores were recorded. Results: The median negative conversion time of SARS-CoV-2 nucleic acid was significantly shorter in the intervention group than in the control group (median days [interquartile range (IQR)]: 3 [3-5] vs. 5 [3-6]; p = 0.047). The median total symptom score on day 3 was significantly lower in the intervention group than in the control group (median total symptom score [IQR]: 1 [0-2] vs. 2 [0-3]; p = 0.036). There was no significant differences in the frequency of antibiotic use and side effects between the two groups. Conclusion: HSBDG is a safe, effective oral Chinese herbal compound granule, which shows a good performance within the Omicron wave among pediatric patients.

Early crystallization of amorphous selenium under high pressure studied by synchrotron XRD method.

The amorphous selenium (a-Se) was studied via x-ray diffraction (XRD) under pressures ranging from ambient pressure up to 30 GPa at room temperature to study its high-pressure behavior. Two compressional experiments on a-Se samples, with and without heat treatment, respectively, were conducted. Contrary to the previous reports that a-Se crystallized abruptly at around 12 GPa, in this work we report an early partially crystallized state at 4.9 GPa before completing the crystallization at around 9.5 GPa based onin-situhigh pressure XRD measurements on the a-Se with 70 °C heat treatment. In comparison, crystallization pressure on another a-Se sample without thermal treatment history was observed to be 12.7 GPa, consistent with the previously reported crystallization pressure. Thus, it is proposed in this work that prior heat treatment of a-Se can result in an earlier crystallization under high pressure, which helps to understand the possible mechanism caused by the previous controversial reports on pressure induced crystallization behavior in a-Se.