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Increasing evidence suggests that tissue inhibitor of metalloproteinase 1 (TIMP1) played a pivotal role in immune regulation. Our study focused on examining the expression and function of TIMP1 in humans, particularly in its regulation of tumor-associated macrophages (TAMs) in papillary thyroid carcinoma (PTC). We observed an upregulation of TIMP1 in 16 different types of malignancies, including thyroid cancer. TIMP1 shaped the inflammatory TME in PTC. Inhibiting the expression of TIMP1 has been demonstrated to reduce the malignant biological traits of PTC cells. Furthermore, reducing TIMP1 expression impeded M2 macrophage polarization as well as facilitated M1 macrophage polarization in PTC. ELISA results demonstrated that downregulated TIMP1 expression correlated with decreased levels of IL10 and TGF-ß in cell supernatants. Furthermore, the supernatant from polarized macrophages in the TIMP1-silenced group inhibited the motility of wild-type PTC cells. Therefore, TIMP1 may enhance the progression of PTC by stimulating the PI3K/AKT pathway via the secretion of IL10 and TGF-ß, consequently influencing M2-type polarization in TAMs.
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BACKGROUND: Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification. METHODS: Human intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated ß-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways. RESULTS: Our study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model. CONCLUSIONS: So our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.
Subject(s)
Cellular Senescence , Chondrocytes , Intervertebral Disc Degeneration , Lipid Metabolism , Lipoproteins, LDL , Scavenger Receptors, Class E , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Lipoproteins, LDL/metabolism , Animals , Humans , Scavenger Receptors, Class E/metabolism , Chondrocytes/metabolism , Chondrocytes/pathology , Rats , Male , Calcinosis/metabolism , Calcinosis/pathology , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Disease Models, Animal , Female , Middle Aged , Signal Transduction , Adult , Proteomics/methods , Rats, Sprague-DawleyABSTRACT
Fetal lung adenocarcinoma (FLAC) is a rare malignant tumor with a relatively good prognosis, and the probability of mutation with KRAS is very low. We report a middle-aged female patient with FLAC with KRAS mutation. The primary lesion was implanted with radioactive iodine 125 particles, and the lesion was smaller than before. However, the metastatic lesions progressed rapidly. After chemotherapy with pemetrexed disodium and cisplatin combined with bevacizumab to prevent angiogenesis, the primary lesions continued to shrink, and the metastatic lesions were significantly smaller than before. The patient has been followed up for 5 months and is generally in good condition. We report a case of H-FLAC with KRAS mutation, and its development and prognosis seem to be significantly abnormal from that of ordinary H-FLAC. It also provides a possible effective treatment for unresectable H-FLAC, but further research is needed.
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BACKGROUND: As metastatic papillary thyroid carcinoma becomes increasingly challenging to treat, immunotherapy has emerged as a new research direction. Tumor-associated macrophages (TAMs) influence the occurrence, invasion, and metastasis of tumors. Apolipoprotein E (APOE) can regulate the polarization changes of macrophages and participate in the remodeling of the tumor microenvironment. However, the role of APOE in regulating the polarization and biological functions of TAMs in papillary thyroid carcinoma (PTC) remains unclear, as it acts as a dual biomarker. METHODS: We probed APOE expression in PTC tissues using immunohistochemical staining. A cell co-culture model was established where different APOE-expressing K1 cells were co-cultured with THP-1-derived M0 macrophages. An in-depth analysis of macrophage polarization behavior was performed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Subsequently, the impact of APOE-regulated macrophages on tumor cell behavior, especially proliferation, migration, and invasion, was evaluated utilizing IncuCyte ZOOM system, flow cytometry, colony formation, and scratch experiments. Finally, we used a xenograft model to confirm the effects of APOE on PTC tumorigenesis. RESULTS: Tumor dimensions, stage, and lymphatic metastases were significantly associated with increased APOE expression in PTC tissues. K1 cells were markedly limited in their proliferation, migration, and invasion abilities when APOE expression was silenced, a process mediated by the PI3K/Akt/NF-κB signaling axis. Moreover, APOE is a key facilitator of the enhancement of the anti-inflammatory cytokines IL-10 and TGF-ß1. In PTC cellular models, APOE contributed to the phenotypic shift of THP-1 derived macrophages towards an M2 phenotypic polarization, predominantly through the modulation of IL-10. Furthermore, in vivo studies involving athymic nude mice have demonstrated pivotal role of APOE in tumor progression and the induction of M2-like TAM polarization. CONCLUSION: Our results elucidated that APOE could promote the shift of TAMs from M0-type to M2-type polarization by regulating inflammatory factors expressions in K1 cell through the PI3K/Akt/NF-κB pathway. These findings are crucial for understanding the molecular mechanisms underlying PTC pathogenesis and for developing immunological drugs to treat this disease.
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There is no consensus on the definition of sleep hygiene and its components. We examined the definition of sleep hygiene based on its use in published studies. Four databases (Medline, EMBASE, PsycINFO and CINAHL) were searched from inception until December 31, 2021 for the phrase 'sleep hygiene' in the title or abstract. We identified 548 relevant studies in adults: 250 observational and 298 intervention studies. A definition of sleep hygiene was provided in only 44% of studies and converged on three themes: behavioural factors, environmental factors, and an aspect of control. Sleep hygiene components were explicitly defined in up to 70% of observational studies, but in only 35% of intervention studies. The most commonly considered components of sleep hygiene were caffeine (in 51% of studies), alcohol (46%), exercise (46%), sleep timing (45%), light (42%), napping (39%), smoking (38%), noise (37%), temperature (34%), wind-down routine (33%), stress (32%), and stimulus control (32%), although the specific details of each component varied. Lack of consistency in definitions of sleep hygiene and its components may hinder communication between researchers, clinicians, and the public, and likely limits the utility of sleep hygiene as an intervention.
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Sleep Hygiene , Humans , Exercise , Sleep/physiology , CaffeineABSTRACT
Aim: Recent data have identified specific symptom and polysomnographic profiles associated with cardiovascular disease (CVD) in patients with obstructive sleep apnoea (OSA). Our aim was to determine whether these profiles were present at diagnosis of OSA in patients with established CVD and in those with high cardiovascular risk. Participants in the Sydney Sleep Biobank (SSB) database, aged 30-74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure). In those without established CVD, the Framingham Risk Score (FRS) estimated 10-year absolute CVD risk, categorised as "low" (<6%), "intermediate" (6-20%), or "high" (>20%). Groups were compared on symptom and polysomnographic variables. Results: 629 patients (68% male; mean age 54.3 years, SD 11.6; mean BMI 32.3 kg/m2, SD 8.2) were included. CVD was reported in 12.2%. A further 14.3% had a low risk FRS, 38.8% had an intermediate risk FRS, and 34.7% had a high risk FRS. Groups differed with respect to age, sex and BMI. OSA severity increased with established CVD and increasing FRS. The symptom of waking too early was more prevalent in the higher FRS groups (p=0.004). CVD and FRS groups differed on multiple polysomnographic variables; however, none of these differences remained significant after adjusting for age, sex, and BMI. Conclusion: Higher CVD risk was associated with waking too early in patients with OSA. Polysomnographic variations between groups were explained by demographic differences. Further work is required to explore the influence of OSA phenotypic characteristics on susceptibility to CVD.
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STUDY OBJECTIVES: Recent studies suggest that sleepy patients with obstructive sleep apnea (OSA) are at higher risk for incident cardiovascular disease. This study assessed cardiac autonomic function in sleepy versus non-sleepy patients with OSA using heart rate variability (HRV) analysis. We hypothesized that HRV profiles of sleepy patients would indicate higher cardiovascular risk. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) collected by the Sydney Sleep Biobank were used to study HRV in groups of sleepy (ESSâ ≥â 10) and non-sleepy OSA patients (ESSâ <â 10). HRV parameters were averaged across available ECG signals during N2 sleep. RESULTS: A total of 421 patients were evaluated, with a mean age of 54 (14) years, body mass index of 33 (9) kg/m2, apnea-hypopnea index of 21 (28) events/h, and 66% male. The sleepy group consisted of 119 patients and the non-sleepy group 302 patients. Sleepy patients exhibited lower HRV values for: root mean square successive difference (RMSSD, pâ =â 0.028), total power (TP, pâ =â 0.031), absolute low frequency (LF, pâ =â 0.045), and high-frequency (HF, pâ =â 0.010) power compared to non-sleepy patients. Sleepy patients with moderate-to-severe OSA exhibited lower HRV values for: (RMSSD, pâ =â 0.045; TP, pâ =â 0.052), absolute LF (pâ =â 0.051), and HF power (pâ =â 0.025). There were no differences in other time and frequency domain HRV markers. CONCLUSIONS: This study shows a trend toward parasympathetic withdrawal in sleepy OSA patients, particularly in moderate-to-severe cases, lending mechanistic support to the link between the sleepy phenotype and CVD risk in OSA.
Subject(s)
Electrocardiography , Heart Rate , Polysomnography , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/complications , Male , Heart Rate/physiology , Female , Middle Aged , Adult , Autonomic Nervous System/physiopathology , Disorders of Excessive Somnolence/physiopathologyABSTRACT
INTRODUCTION: Understanding how persons with narcolepsy conceptualize symptoms, daily impact and illness experience is key to facilitating dialogue between patients and healthcare professionals. These concepts are usually explored from the perspective of healthcare professionals/researchers and rarely from the perspective of those with narcolepsy. METHODS: 127 self-reported persons with narcolepsy were recruited from an Australian patient support group. A short demographic survey was completed. All agreed to participate in a subsequent 1:1 semi-structured interview. Saturation was reached after 24 interviews (mean age = 33 years (SD 11) with 44% reporting cataplexy). A multidisciplinary team of researchers/clinicians analyzed interview transcripts using thematic analysis. RESULTS: Participants perceived physical fatigue, sleepiness, and two separate experiences of 'falling asleep/sleep attacks' as distinct symptoms rather than a multidimensional construct (i.e. excessive daytime sleepiness). We also identified two experiences of cataplexy, one triggered by acute emotion and another by a stressor. Participants determined their narcolepsy to be 'well-managed' by the level of functional impairment rather than the frequency of any symptom. Almost all participants described experiencing anticipated stigma and internalized or 'self-' stigma, likely stemming from societal devaluation of sleep and the conflation of sleepiness with laziness. CONCLUSION: Descriptions of common symptoms often differed between participants and the existing literature. These differences likely impact patient-physician communication, with both parties utilizing the same terminology to communicate different concepts. The characterization of stigma in narcolepsy presents opportunities for future research exploring the impact and possible development of interventions to reduce the substantial psychological comorbidity in persons with narcolepsy.
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Cataplexy , Disorders of Excessive Somnolence , Narcolepsy , Humans , Adult , Cataplexy/diagnosis , Sleepiness , Australia , Narcolepsy/diagnosis , Disorders of Excessive Somnolence/diagnosisABSTRACT
The electrocatalytic nitrogen reduction reaction (eNRR) under ambient conditions is deemed a promising alternative for NH3 synthesis. In this paper, an FeP-Fe3O4 nanocomposite electrocatalyst was prepared by phosphating annealing using Fe2O3 as a precursor, and the resulting FeP-Fe3O4 exhibited excellent N2-to-NH3-producing activity over a wide potential window. The highest faradaic efficiency of FeP-Fe3O4 is 11.02% at -0.1 V vs. reversible hydrogen electrode (RHE), and the maximum NH3 yield reaches 12.73 µg h-1 mgcat-1, comparable to or exceeding the reported values in this field. Furthermore, the FeP-Fe3O4 nanocomposite electrocatalyst presents high electrochemical stability, selectivity, and durability.
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STUDY OBJECTIVES: Parents/carers of a child with narcolepsy are often required to become experts in narcolepsy and navigate health care, education, and welfare systems on behalf of their child. Managing pediatric narcolepsy is complex and challenges the child and the entire family, yet few studies have explored carers' experiences. METHODS: Twenty mothers (50% had a child with narcolepsy < 18 years at the time of interview; 85% narcolepsy with cataplexy) participated in a 1:1 semistructured interview. Participation from fathers was sought; however, none were recruited. A multidisciplinary team of researchers/clinicians analyzed interview transcripts using thematic analysis. RESULTS: Mothers perceived that most people misunderstood the whole-person impact of narcolepsy, including their child's peers, teachers, and support networks. Narcolepsy had a substantial psychological impact on both the child and the whole family yet was largely unaddressed by health care professionals, leaving mothers unsure of where to turn for help. Most parents described negative experiences with their child's specialist, often perceiving the specialists to lack knowledge specific to narcolepsy. Information about illness trajectory and support services was limited or inaccessible, fueling many mothers' hopes and fears for their child's future. Mothers also frequently described feelings of abandonment by the health care system. CONCLUSIONS: Our results contextualize the whole-person impact of narcolepsy from the perspective of parents and carers, highlighting the need for proactive inclusion of parents/carers in developing health care policy and practice. It calls for developing tools and resources to capture "well-managed" narcolepsy from the perspective of parents/carers for use in research and clinical practice. CITATION: Schokman A, Cheung J, Klinner C, et al. A qualitative exploration of the lived experience of mothers caring for a child with narcolepsy. J Clin Sleep Med. 2024;20(5):699-707.
Subject(s)
Caregivers , Mothers , Narcolepsy , Qualitative Research , Humans , Narcolepsy/psychology , Mothers/psychology , Female , Child , Caregivers/psychology , Adult , Male , Adolescent , Child, Preschool , Middle AgedABSTRACT
PURPOSE: This study aimed to evaluate the effect of mandibular advancement splint (MAS) therapy on cardiac autonomic function in patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) of three prospective studies were used to study HRV of patients with OSA before and after MAS treatment. HRV parameters were averaged across the entire ECG signal during N2 sleep using 2-min epochs shifted by 30 s. Paired t-tests were used to compare PSG and HRV measures before and after treatment, and the percent change in HRV measures was regressed on the percent change in apnoea-hypopnea index (AHI). RESULTS: In 101 patients with OSA, 72% were Caucasian, 54% men, the mean age was 56 ± 11 years, BMI 29.8 ± 5.3 kg/m2, and treatment duration was 4.0 ± 3.2 months. After MAS therapy, there was a significant reduction in OSA severity (AHI, - 18 ± 16 events per hour, p < 0.001) and trends towards increased low-frequency to high-frequency ratio, low-frequency power, and reduced high-frequency power (LF:HF, - 0.4 ± 1.5, p = 0.01; LF, - 3 ± 16 nu, p = 0.02, HF, 3.5 ± 13.7 nu, p = 0.01). Change in NN intervals correlated with the change in AHI (ß(SE) = - 2.21 (0.01), t = - 2.85, p = 0.005). No significant changes were observed in the time-domain HRV markers with MAS treatment. CONCLUSION: The study findings suggest that successful MAS treatment correlates with changes in HRV, specifically the lengthening of NN intervals, a marker for improved cardiac autonomic adaptability.
Subject(s)
Mandibular Advancement , Sleep Apnea, Obstructive , Male , Humans , Middle Aged , Aged , Female , Occlusal Splints , Prospective Studies , Sleep Apnea, Obstructive/therapy , Heart , Heart Rate/physiologyABSTRACT
OBJECTIVE To investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy (DN) model mice. METHODS Male KK-Ay mice were fed with high-fat and high-sugar diet for two weeks to reproduce the DN model. The successfully modeled mice were randomly grouped into model group, aminoguanidine group (positive control,100 mg/kg) and cornuside group (100 mg/kg), and male C57BL/6J mice were included as normal group, with 6 mice in each group. Administration groups were given relevant medicine intragastrically, and normal group and model group were given a constant volume of normal saline intragastrically, once a day, for 8 consecutive weeks. The levels of fasting blood glucose (FBG), 24 h urinary protein, serum interleukin-12 (IL-12), IL-10, blood urea nitrogen (BUN) and serum creatinine (Scr) were detected; the pathological injury, fibrotic change and glomerular microstructure of renal tissue were observed; the expressions of the receptor of advanced glycation end products (RAGE), collagen type Ⅳ (COL-Ⅳ) and inducible nitric oxide synthase (iNOS) in renal cortex were detected in each group. RESULTS Compared with normal group, the renal cortex of mice in model group showed obvious inflammatory cell infiltration and fibrotic changes; the mesangial hyperplasia of glomerulus was serious and the basement membrane had a large number of irregular dark dense deposits; the levels of FBG and 24 h urinary protein, the serum levels of IL- 12, BUN and Scr, and the expression levels of RAGE, COL-Ⅳ and iNOS in the renal cortex were significantly increased, while the serum level of IL-10 was significantly decreased (P<0.01). Compared with the model group, the renal pathological injuries, fibrotic changes and glomerular microstructure of mice in administration groups were improved significantly, and the above quantitative indexes were generally improved (P<0.05 or P<0.01). CONCLUSIONS Cornuside has a certain protective effect on DN model mice. It can inhibit the inflammatory response, reduce urinary protein excretion, and alleviate renal fibrosis, which may be related to the inhibition of the advanced glycation end products/RAGE signaling pathway.
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Objective:To study the potential mechanism of Ganwei Baihe Decoction in the treatment of gastric ulcer (GU) based on bioinformatics and validate it through animal experiments.Methods:TCMSP, DisGeNET, and GeneCards databases were used to retrieved active components and action targets of Ganwei Baihe Decoction. After obtaining the intersection, protein interaction data of the intersection genes were obtained through the STRING database. A PPI network was constructed by Cytoscape 3.10.0 software and the key genes and key components were obtained. DAVID online analysis database was used for GO functional enrichment and KEGG pathway enrichment analysis of key targets. Animal experiments were used for verification. Totally 36 SD rats were divided into blank group, model group, Omeprazole group and Ganwei Baihe Decoction group according to the random number table method, with 9 rats in each group. After 7 days of gavage of the corresponding drugs to each group of rats, they fasted and but with water for 24 hours, and then re-gavaged once. After 1 hour of administration, a gastric ulcer rat model was prepared by gavage of 80 mg/kg of indomethacin. After 3 hours of administration, anesthesia was used to extract the sample. The expression level of Caspase-3 protein in the gastric tissue of rats was to be determined by Western blot method.Results:There were 234 effective active components with 290 targets in Ganwei Baihe Decoction, and 6 496 therapeutic targets for GU. 213 potential targets for GU were screened out. There were 437 GO function and 153 KEGG pathway enriched entries. Compared with the model group, the protein expression of Caspase-3 in the Ganwei Baihe Decoction group and Omeprazole group decreased ( P<0.05). Conclusion:The mechanism of Ganwei Baihe Decoction in treating GU may be through key components such as quercetin and β-sitosterol acting on key targets such as AKT1 and CASP3, regulating the Apoptosis pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, etc. to exert inhibitory effects on apoptosis.
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As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
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Humans , 1-Alkyl-2-acetylglycerophosphocholine Esterase , Medicine, Chinese Traditional , Atherosclerosis/drug therapy , Lipoproteins , Plaque, Atherosclerotic , BiomarkersABSTRACT
Objective:To explore the distribution characteristics and antibiotic resistance of pathogen in children with hematological disorders and cancers complicated with sepsis in pediatric intensive care unit (PICU).Methods:The clinical data of children with hematological disorders and cancers complicated with sepsis hospitalized at Shenzhen Children′s Hospital affiliated to China Medical University from January 2016 to August 2023 were retrospectively analyzed. Patients were divided into survival group and death group based on the outcome of sepsis on 28 days after diagnosis.Results:A total of 202 sepsis episodes occurred in 176 children were enrolled in this study. Among all, 144 (71.3%) cases of bloodstream infection, 59 (29.2%) cases of pulmonary infection, 21 (10.4%) cases of abdominal infection, 9 (4.5%) cases of soft tissue infection, 9 (4.5%) cases of nervous system infection, and 3 (1.5%) cases of urinary tract infection. A total of 244 pathogenic strains were identified, in which 74 (30.3%) cases were gram-positive bacteria. The top 3 pathogens isolated were Coagulase negative Staphylococcus (21 strains), Staphylococcus aureus (19 strains) and Streptococcus pneumoniae (13 strains). Gram-negative bacteria accounted for 122 (50.0%) strains, in which top 3 were Klebsiella pneumonia (33 strains), Escherichia coli (25 strains), and Pseudomonas aeruginosa (23 strains). Fungi comprised 48 (19.7%) strains:the top 3 were Candida tropicalis (14 strains), Candida albicans (10 strains), Aspergillus and Pneumocystis jirovecii (7 strains each). The incidence of Acinetobacter baumannii, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa were significantly higher in death group compared to survival group[9.0%(6/67)vs. 2.3%(4/177), χ2=3.971 ,P=0.046; 9.0%(6/67)vs. 1.1%(2/177), χ2=7.080 ,P=0.008;16.4%(11/67)vs. 6.8%(12/177), χ2=5.288 ,P=0.021]. The samples of 57 cases were simultaneously detected by both culture and metagenomic next-generation sequencing (mNGS). Pathogens were detected in 25 cases by both culture and mNGS. In 30 cases, pathogen detection were mNGS positive but culture negative. Two cases showed positive results only with culture. A total of 79 (46.8%) strains were multi-drug resistant bacteria, including 27 (34.2%) strains of gram-positive bacteria and 52 (65.8%) strains of gram-negative bacteria. A total of 174 (86.1%) children with sepsis received empirical anti-infective drugs within 24 hours of fever onset. A total of 124 (61.4%) cases were appropriately covered by the initial empirical antibiotics, while 40 (19.8%) cases were not adequately covered and 10 (5.0%) cases had incomplete coverage. Despite the inclusion of pathogenic in the coverage, resistance to initial antibiotics was observed in 22 (10.9%) cases. Fifty-one patients died. Conclusion:The predominant pathogens responsible for sepsis in PICU with hematological disorders and cancers is gram-negative bacteria, followed by gram-positive bacteria and fungi. In comparison to healthy children with sepsis, there is a higher incidence of fungal infections among hematological disorders and cancers. The proportion of multi-drug resistant bacteria infection is high. Early identification and combination of local etiological distribution and drug resistance, along with the empirical selection of appropriate anti-infection treatment strategies, can greatly enhance survival rate.
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Objective:To explore the relationship between school bullying and mental sub-health in middle school students and the potential moderating role of resilience in this relationship.Methods:Totally 792 students aged 10 to 14 years from two middle schools in Wuhan were selected.The Chinese version of Olweus Bully/Victim Questionnaire,Multidimensional Sub-health Questionnaire of Adolescents,and Adolescent Psychological Resilience Scale were used to measure school bullying,mental sub-health,and psychological resilience of students,respectively.Results:Being bullied scores were positively associated with mental sub-health scores(β=1.88).The moderating effect of psychological resilience scores between being the scores of bullied and mental sub-health was statistically significant(β=-0.07).Conclusion:The experience of bullying may be associated with mental sub-health problems of middle school students,and psychological resilience may play a moderating role in the relation-ship between being bullied and mental sub-health.
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Objective:To analyze the robustness of the dose of clinical target volume (CTV) and tolerance dose of normal tissues after applying in-room CT before carbon ion radiotherapy for prostate cancer.Methods:Thirty prostate cancer patients treated with carbon ion in Shanghai Proton and Heavy Ion Center from January 2020 to June 2021 were enrolled in this study. Five in-room CT images of each patient were selected randomly before treatment. Dose distributions were recalculated using the original plan on in-room CT images and dose volume histogram (DVH) parameters were obtained, including V 95% and V 90% of CTV and V 80% of rectum. The values were compared with the dosimetric parameters of the original plan. Statistical analysis was performed by paired or two independent samples t-tests. Results:The dose distribution was recalculated by applying in-room CT. The mean values of V 95% and V 90% of CTV and V 80% of rectum were 98.1%±1.2% ( P<0.001), 99.9%±0.2% ( P=0.001) and (5.8±1.6) ml ( P<0.001), respectively. The differences were statistically significant compared with those of the original plan. The frequency of V 95%≥95%, V 90%≥98% of CTV, and V 80%<10 ml of rectum was 148 (98.7%), 150 (100.0%) and 147 (98.0%), respectively. Conclusion:Based on in-room CT analysis and the patient management and positioning methods of our research center, the uncertainty of target dose and normal tissue dose in the entire process of prostate cancer carbon ion therapy is small, and the robustness is good.
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Polysomnograms (PSGs) contain a wealth of physiological information that is routinely recorded but not utilised in sleep studies. Intermittent hypoxia arising from obstructive sleep apnoea (OSA) events is an important risk in the later development of cardiovascular disease (CVD). Analysis of oximetry patterns from PSG studies may enable early assessment of CVD risk. The aim of this study was to compare associations of different time-domain oximetry patterns with incident CVD in OSA patients. All participants with OSA and no pre-existing CVD at baseline or within the first two years of follow-up, were selected from the Sleep Heart Health Study data and used for analysis (N=2878). We examined oximetry parameters that are calculated from desaturation events and from time series analysis and compared them to incident CVD outcomes using proportional hazards regression models adjusted for age, race, smoking, BMI, and sex. Our results show that were no associations between OSA oximetry parameters and incident CVD for OSA patients.
Subject(s)
Cardiovascular Diseases , Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnosis , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/epidemiology , Sleep , Oximetry/methods , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiologyABSTRACT
Respiratory event related oxygen desaturation area measures have recently shown merit as novel predictors of cardiovascular disease (CVD) outcomes. In this study, we investigate one such measure (hypoxic burden (HB)) and investigate how three different ways of calculating the SpO2 baseline of the HB algorithm impact its ability to predict cardiovascular mortality. The three baseline estimation steps include a pre-event baseline, a record-based baseline, and a fixed baseline. Pulse oximetry signals from the Sleep Heart Health Study and the corresponding CVD outcomes were analyzed. The performance of each baseline method was compared using adjusted Cox proportional hazard regression analysis. Results show that HB with the record-based baseline method returned the best performing results with a hazard ratio (HR) of 1.83 (95% CI: 1.03-3.27, p<0.05) in the fully adjusted model, compared to HB with the pre-event baseline method (HR: 1.60, 95%CI: 0.86-3.00, p>0.05) and HB with the fixed baseline method (HR: 1.73, 95%CI: 0.93-3.22, p>0.05).
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Cardiovascular Diseases , Oxygen Saturation , Humans , Hypoxia , Sleep , Cardiovascular Diseases/diagnosis , AlgorithmsABSTRACT
Reactive oxygen species (ROS) are closely related to the antiviral immune response of plants, while virus can regulate ROS through various pathways to facilitate their own infection or replication. Citrus yellow vein clearing virus (CYVCV) is one of the most devastating viruses affecting lemon (Citrus limon) industry worldwide. However, the pathogenesis of CYVCV remains poorly understood. In this study, direct interaction between the coat protein (CP) of CYVCV and the ascorbate peroxidase 1 of lemon (ClAPX1) was confirmed for the first time by yeast two-hybrid, Bimolecular Fluorescence Complementation, and Co-immunoprecipitation assays. Transient expression of CP in lemon and Nicotiana benthamiana significantly enhanced the enzyme activity of the ClAPX1, and then inhibited the accumulation of H2O2. In addition, overexpression of ClAPX1 in lemon by transgene significantly promoted CYVCV accumulation and depressed the expression of most genes involved in jasmonic acid (JA) signaling pathway. Correspondingly, ClAPX1 silencing by RNA interference inhibited CYVCV accumulation and increased the expression of most genes involved in JA signaling pathway. To our knowledge, this is the first report that viruses regulate ROS by targeting APX directly, thereby suppressing host immune response and promoting viral accumulation, which may be mediated by JA signaling pathway.