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OBJECTIVES: Schizophrenia is associated with an increased risk of suicide. Few studies have investigated the risk of suicide across different ages, likely due to limitations around sample size. METHODS: From the National Health Insurance Research Database in Taiwan, this study identified 195,787 patients with schizophrenia from January 1, 2000, to December 31, 2019. During the study period, 3848 patients died from suicide. We calculated the standardized mortality ratio (SMR) for suicide stratified by age. In this age-stratified, nested case-control study, risk set sampling was used to match each case with 4 living controls by age, sex, and the year of the first diagnosis with schizophrenia. Conditional logistic regression was used for estimating age-stratified risk profiles. RESULTS: The SMR was the highest in the <25 years age group (52.8) and inversely correlated with age. Unemployment was associated with an increased risk of suicide in the 25 to 34, 35 to 44, 45 to 54, and 55 to 64 years age groups. Depressive and sleep disorders before suicide were more common among suicide cases with schizophrenia than among controls across all age groups. Drug-induced and alcohol-induced mental disorders were significantly associated with suicide but were observed only in the age group younger than 54. Heart disease, pneumonia, and moderate or severe renal disease were risk factors for suicide in the age groups less than 65. CONCLUSIONS: The risk factors for suicide differ by age. This study's findings can be used to optimize health-care interventions for preventing suicide in patients with schizophrenia.
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Backgrounds: Hematocrit is found an independent risk factor for acute kidney injury (AKI) in certain patients, but this effect in patients with acute myocardial infarction (AMI) is unclear. We aim to identify the relationship between hematocrit and AKI in patients with AMI. Methods: The patient data for the discovery and validation cohorts were extracted from the electronic Intensive Care Unit database and the Medical Information Mart for Intensive Care III database, respectively, to identify the relationship between hematocrit and AKI. With normal hematocrit as the reference, patients were divided into five groups based on the initial hematocrit value. The primary outcome was AKI during hospitalization. A multivariable logistic regression and a marginal effect analysis were used to evaluate the relationship between hematocrit and AKI. Results: In this study, a total of 9692 patients diagnosed with AMI were included, with 7712 patients in the discovery cohort and 1980 patients in the validation cohort. In the discovery cohort, hematocrit in 30-33%, 27-30% or < 27% were independent risk factors for AKI in the multivariate logistic analysis, with odds ratio (OR) of 1.774 (95% confidence interval [CI]: 1.203-2.617, p = 0.004), 1.834 (95% CI: 1.136-2.961, p = 0.013) and 2.577 (95% CI: 1.510-4.397, p < 0.001), respectively. Additionally, in the validation cohort, low hematocrit levels independently contributed to an increased risk of AKI among patients with AMI. During the analysis of marginal effects, a significant negative linear relationship between hematocrit levels and AKI was observed. Conclusions: Decreased hematocrit was an independent risk factor for AKI in patients with AMI. The relationship between hematocrit and AKI was negative linear.
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(1) Background: Diabetes mellitus (DM) induces oxidative stress and inflammation with negative effect on pregnancy outcomes. This study aimed to determine whether DM increases the risk of pregnancy loss and to identify other potential risk factors; (2) Methods: We identified female patients diagnosed with DM from 2000-2015 in the Taiwanese National Health Insurance Research Database according to the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9 CM) code 250. The event was pregnancy loss, defined as ICD-9 CM codes 630-639, which was tracked until 31 December 2015. The control group included 4-fold more non-DM female patients who were matched for age and disease severity. Multivariate Cox regression was employed to determine the risk factors associated with pregnancy loss; (3) Results: The hazard ratio (HR) for the risk of pregnancy loss due to DM was 1.407 (95% confidence interval: 1.099-1.801, p = 0.007), and the risk factors for older age, gynecological disorders and inflammation disorders were included. (4) Conclusions: The study concluded that women with DM have a greater risk of experiencing pregnancy loss. Healthcare providers should proactively manage and educate diabetic patients to reduce their risk of pregnancy loss. Understanding other probable risk factors can help in developing targeted interventions and support systems for women to improve pregnancy outcomes.
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As a remote and non-contact stimulus, light offers the potential for manipulating the polarization of ferroelectric materials without physical contact. However, in current research, the non-contact write-read (erase) process lacks direct observation through the stable current as output signal. To address this limitation, we investigated the photoinduced polarization switching capabilities of the cyanide-bridged compound [Fe2Co] using visible light, leading to the achievement of rewritable polarization. By subjecting [Fe2Co] crystals to alternating irradiation with 785â nm and 532â nm light, the polarization changes exhibited a distinct square wave pattern, confirming the reliability of the writing and erasing processes. Initialization involved exposing specific crystal units to 532â nm light for storing "1" or "0" information, while reading was accomplished by scanning the units with 785â nm light, resulting in brief current pulses for "1" states and no current signal for "0" states. This research unveils new possibilities for optical storage systems, paving the way for efficient and rewritable data storage and retrieval technologies, such as the next-generation memories.
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Cercis chinensis Bunge, commonly used as an ornamental plant, is native to southeastern China and extensively cultivated in gardens across major cities in the country. In August 2023, a new high-incidence disease was discovered at Huangshan University in Huangshan, Anhui Province, China. The symptoms initially began as small brown spots, which gradually expanded into large irregular brown spots with black-brown edges. The disease was investigated at both Jilingshan Park and Huangshan University, where C. chinensis Bunge was planted, revealing an average incidence rate of was 85 % at these sites. Seventy two leaf tissue samples (3 to 4 mm²) were collected from the margins of the lesion and subjected to surface sterilization with 75% ethanol for 30 seconds followed by 1% sodium hypochlorite for 90 seconds. Subsequently, the tissues were rinsed with sterile H2O, placed on potato dextrose agar (PDA) medium, and incubated at 25â for 5 days. The same fungus was isolated from 90% of the tissues, and pure cultures were obtained by monosporic isolation. Representative isolates ZJ 2-1, ZJ 2-2 and ZJ 2-3 were selected for morphological and molecular characterization. The colonies displayed a color range from white to gray, with white margins and aerial hyphae, while the reverse side of the colonies appeared gray to brown. Conidia were cylindrical, aseptate, with obtuse to slightly rounded ends, measuring 15.8±1.8×4.7±0.56 µm (n = 50). The morphological characteristics were generally consistent with those of Colletotrichum gloeosporioides species complex (Weir et al. 2012). Five conserved regions of isolates (ZJ 2-1, ZJ 2-2 and ZJ 2-3), including the internal transcribed spacer (ITS), glutamine synthase (GS), calmodulin (CAL), actin (ACT), and chitin synthase 1(CHS1) gene regions, were amplified using specific primers ITS1/ITS4 (Gardes et al. 1993), GSR1/GSF1 (Guerber et al. 2003), CL1C/CL2C (Li et al. 2018), ACT-512F/ACT-783R, and CHS-79F/CHS-345R (Zhu et al. 2019), respectively. Using the BLAST, ITS, GS, CAL, ACT and CHS1 gene sequences (GenBank accession nos. PP514751, PP448025, PP448026, PP448027 and PP448028, respectively) were 100% (594 out of 594 bp), 100% (864 out of 864 bp), 100% (299 out of 299 bp), 100% (732 out of 732 bp) and 100% (282 out of 282 bp) identical to C. gloeosporioides (GenBank accession nos. JX010152, JX010085, JX009818, JX009731 and JX009531, respectively). A Maximum Likelihood phylogenetic tree, constructed by combining all sequenced loci in MEGA7, showed that the isolates ZJ 2-1, ZJ 2-2 and ZJ 2-3 clustered within the C. gloeosporioides clade with 99% bootstrap support (Fig. S1). To fulfill Koch's postulates, five C. chinensis Bunge plants were tested for pathogenicity in the field with isolates ZJ 2-1, ZJ 2-2 and ZJ 2-3 at Huangshan University. Twelve leaves from each tree were wounded and inoculated with mycelial plugs (approximately 4 mm in diameter) and 10 µl of a spore suspension (1.0 × 106 conidia/ml) of C. gloeosporioides. Inoculation with sterile PDA plugs and pure water on leaves of each tree served as negative controls. Plastic bags were used to wrap the leaves, and sterile H2O was sprayed into the bags to maintain moisture conditions (Zhang et al.2020). The experiment was repeated two times, and within 5 days, all inoculated points displayed lesions similar to those observed in the field, whereas controls remained asymptomatic (Fig. S2). The same fungus was reisolated from these lesions with a frequency of 100%. Consequently, the pathogen responsible the disease in C. chinensis Bunge was identified as C. gloeosporioides. To the best of our knowledge, this is the first report of C. gloeosporioides causing leaf blight on C. chinensis Bunge in China. This study provides valuable insights for implementing targeted measures to control leaf blight on C. chinensis Bunge and lays a foundation for the prevention and treatment of the disease.
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BACKGROUND: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. METHODS: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations. RESULTS: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. CONCLUSION: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients.
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Background: Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8+ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8+ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC. Methods: TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN+CD8+ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI. Results: The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8+ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8+ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN+CD8+ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8+ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8+ T cells. Conclusion: LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy.
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CircRNAs participates in the development and occurrence of multiple tumor types. However, the specific effects and underlying mechanisms of circRNA in intrahepatic cholangiocarcinoma (ICC) progression and recurrence remain poorly understood. CircRNA sequencing was performed to screen circRNAs related to ICC recurrence after surgery using 53 ICC frozen tumor specimens. We found that compared with patients who experienced postsurgical recurrence, circFOXP1 had high expression in tumor tissues from patients with no postoperative recurrence. Functional experiments revealed that circFOXP1 inhibited ICC progression in vitro and in vivo. We then found that circFOXP1 inhibited ICC progression via encoding a novel protein, circFOXP1-231aa. Mechanistically, circFOXP1-231aa directly interacted with OTUD4, which regulates NCOA4 protein stability via deubiquitination modification, and thereby enhances ferroptosis of ICC cells. Examination of clinical ICC samples found positive correlations between circFOXP1 expression levels and levels of OTUD4 and NCOA4. These three factors are predictors of prognosis in patients with ICC. Collectively, we identified circFOXP1 encoded circFOXP1-231aa, which interacted with OTUD4 to suppress ubiquitination of NCOA4 and, thereby, promoted ferroptosis and inhibited ICC recurrence.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Ferroptose , Fatores de Transcrição Forkhead , Recidiva Local de Neoplasia , RNA Circular , Animais , Humanos , Camundongos , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/cirurgia , Linhagem Celular Tumoral , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/cirurgia , Ferroptose/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Coativadores de Receptor Nuclear , Prognóstico , Proteínas Repressoras , RNA Circular/genética , RNA Circular/metabolismo , UbiquitinaçãoRESUMO
BACKGROUND: Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks. METHODS: According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015. RESULTS: A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001). CONCLUSION: This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.
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Hospitalização , Medicina Tradicional Chinesa , Osteoporose , Humanos , Feminino , Masculino , Osteoporose/mortalidade , Osteoporose/complicações , Idoso , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , Taiwan/epidemiologia , Fraturas Ósseas/mortalidade , Fraturas Ósseas/cirurgia , Modelos de Riscos Proporcionais , Idoso de 80 Anos ou maisRESUMO
Background: Patients with asthma experience more physical, psychological, and financial burdens; a link between asthma and suicidality has been reported in research. Purpose: This study analyzed the medical utilization and comorbidity before their self-injurious behavior in patients with asthma. Methods: We enrolled 186,862 patients newly diagnosed with asthma between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 500 case subjects had ever conducted self-injurious behaviors during the study period. Based on a nested case-control study, each case was matched with 10 controls derived from the asthma cohort to analyze differences between them and their medical use models. Results: The results indicated that, compared to the control group, the cases presented higher frequencies of outpatient visits and hospitalizations. Regarding comorbidity, the cases had more cardiovascular diseases (adjusted odds ratio [aOR]=1.58; p<0.001), bipolar disorder (aOR=2.97; p<0.001), depression (aOR=4.44; p<0.001), and sleep disorder (aOR=1.83; p<0.001) than the controls. Conclusion: The evidence-based information serves as a reference for medical staff to reduce the occurrence of self-injurious behavior in patients with asthma.
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BACKGROUND: Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied. AIM: This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia. METHOD: This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent. RESULTS: This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association. CONCLUSIONS: Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population.
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We have experimentally investigated the mechanism of the exchange bias in 2D van der Waals (vdW) ferromagnets by means of the anomalous Hall effect (AHE) together with the dynamical magnetization property. The temperature dependence of the AC susceptibility with its frequency response indicates a glassy transition of the magnetic property for the Te-rich FeGeTe vdW ferromagnet. We also found that the irreversible temperature dependence in the anomalous Hall voltage follows the de Almeida-Thouless line. Moreover, the freezing temperature of the spin-glass-like phase is found to correlate with the disappearance temperature of the exchange bias. These important signatures suggest that the emergence of magnetic exchange bias in the 2D van der Waals ferromagnets is induced by the presence of the spin-glass-like state in FeGeTe. The unprecedented insights gained from these findings shed light on the underlying principles governing exchange bias in vdW ferromagnets, contributing to the advancement of our understanding.
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BACKGROUND: Diabetic foot ulcer (DFU) is one of the main chronic complications caused by diabetes, leading to amputation in severe cases. Bacterial infection affects the wound healing in DFU. METHODS: DFU patients who met the criteria were selected, and the clinical data were recorded in detail. The pus exudate from the patient's foot wound and venous blood were collected for biochemical analysis. The distribution of bacterial flora in pus exudates of patients was analyzed by 16S rRNA sequencing, and the correlation between DFU and pathogenic variables, pyroptosis and immunity was analyzed by statistical analysis. Then, the effects of key bacteria on the inflammation, proliferation, apoptosis, and pyroptosis of polymorphonuclear leukocytes were investigated by ELISA, CCK-8, flow cytometry, RT-qPCR and western blot. RESULTS: Clinical data analysis showed that Wagner score was positively correlated with the level of inflammatory factors, and there was high CD3+, CD4+, and low CD8+ levels in DFU patients with high Wagner score. Through alpha, beta diversity analysis and species composition analysis, Corynebacterium accounted for a large proportion in DFU. Logistics regression model and Person correlation analysis demonstrated that mixed bacterial infections could aggravate foot ulcer, and the number of bacteria was closely related to inflammatory factors PCT, PRT, immune cells CD8+, and pyroptosis-related proteins GSDMD and NLRP3. Through in vitro experiments, Corynebacterium inhibited cell proliferation, promoted inflammation (TNF-α, PCT, CRP), apoptosis and pyroptosis (IL-1ß, LDH, IL-18, GSDMD, NLRP3, and caspase-3). CONCLUSION: Mixed bacterial infections exacerbate DFU progression with a high predominance of Corynebacterium, and Corynebacterium promotes inflammation, apoptosis and pyroptosis to inhibit DFU healing.
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Infecções Bacterianas , Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/microbiologia , RNA Ribossômico 16S/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Bactérias , Inflamação , SupuraçãoRESUMO
We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.
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Consenso , Dislipidemias , Humanos , Taiwan/epidemiologia , Dislipidemias/tratamento farmacológico , Dislipidemias/terapia , Diabetes Mellitus/terapia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Guias de Prática Clínica como Assunto/normas , LDL-Colesterol/sangueRESUMO
The tumor-associated macrophages (TAMs) play multifaceted roles in the progression of hepatocellular carcinoma (HCC). However, the involvement of circular RNAs in the interplay between TAMs and HCC remains unclear. Based on Transwell co-culturing and circular RNA sequencing, this study revealed that TAMs enhanced tumor glycolysis and progression by upregulating circMRCKα in HCC cells. Patients with HCC who exhibited elevated circMRCKα levels presented significantly reduced overall survival and greater cumulative recurrence. Notably, we identified a novel functional peptide of 227 amino acids named circMRCKα-227aa, encoded by circMRCKα. Mechanistically, circMRCKα-227aa bound to USP22 and enhanced its protein level to obstruct HIF-1α degradation via the ubiquitin-proteasome pathway, thereby augmenting HCC glycolysis and progression. In clinical HCC samples, a positive correlation was observed between the expression of circMRCKα and the number of infiltrating CD68+ TAMs and expression of USP22. Furthermore, circMRCKα emerged as an independent prognostic risk factor both individually and in conjunction with CD68+ TAMs and USP22. This study illustrated that circMRCKα-227aa, a novel TAM-induced peptide, promotes tumor glycolysis and progression via USP22 binding and HIF-1α upregulation, suggesting that circMRCKα and TAMs could be combined as therapeutic targets in HCC.
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Carcinoma Hepatocelular , Glicólise , Neoplasias Hepáticas , RNA Circular , Macrófagos Associados a Tumor , Animais , Feminino , Humanos , Masculino , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Peptídeos/metabolismo , Prognóstico , RNA Circular/genética , RNA Circular/metabolismo , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Miotonina Proteína Quinase/genéticaRESUMO
BACKGROUND: Post-stroke pneumonia (PSP) is common among stroke patients. PSP occurring after hospital discharge continues to increase the risk of poor functional outcomes and death among stroke survivors. Currently, there is no prediction model specifically designed to predict the occurrence of PSP beyond the acute stage of stroke. This study aimed to explore the use of machine learning (ML) methods in predicting the risk of PSP after hospital discharge. METHODS: This study analyzed data from 5,754 hospitalized stroke patients. The dataset was randomly divided into a training set and a holdout test set, with a ratio of 80:20. Several clinical and laboratory variables were utilized as predictors and different ML algorithms were employed to model time-to-event data. The ML model's predictive performance was compared to existing risk-scoring systems. A model-agnostic method based on Shapley additive explanations was utilized to interpret the ML model. RESULTS: The study found that 5.7% of the study patients experienced pneumonia within one year after discharge. Based on repeated 5-fold cross-validation on the training set, the random survival forest (RSF) model had the highest C-index among the various ML algorithms and traditional Cox regression analysis. The final RSF model achieved a C-index of 0.787 (95% confidence interval: 0.737-0.840) on the holdout test set, outperforming five existing risk-scoring systems. The top three important predictors were the Glasgow Coma Scale score, age, and length of hospital stay. CONCLUSIONS: The RSF model demonstrated superior discriminative ability compared to other ML algorithms and traditional Cox regression analysis, suggesting a non-linear relationship between predictors and outcomes. The developed ML model can be integrated into the hospital information system to provide personalized risk assessments.
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Pneumonia , Acidente Vascular Cerebral , Humanos , Alta do Paciente , Aprendizado de Máquina , Pneumonia/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Análise de SobrevidaRESUMO
Type 1 diabetes (T1D) is characterized by lymphocyte infiltration into the pancreatic islets of Langerhans, leading to the destruction of insulin-producing beta cells and uncontrolled hyperglycemia. In the nonobese diabetic (NOD) murine model of T1D, the onset of this infiltration starts several weeks before glucose dysregulation and overt diabetes. Recruitment of immune cells to the islets is mediated by several chemotactic cytokines, including CXCL10, while other cytokines, including SDF-1α, can confer protective effects. Global gene expression studies of the pancreas from prediabetic NOD mice and single-cell sequence analysis of human islets from prediabetic, autoantibody-positive patients showed an increased expression of metallothionein (MT), a small molecular weight, cysteine-rich metal-binding stress response protein. We have shown that beta cells can release MT into the extracellular environment, which can subsequently enhance the chemotactic response of Th1 cells to CXCL10 and interfere with the chemotactic response of Th2 cells to SDF-1α. These effects can be blocked in vitro with a monoclonal anti-MT antibody, clone UC1MT. When administered to NOD mice before the onset of diabetes, UC1MT significantly reduces the development of T1D. Manipulation of extracellular MT may be an important approach to preserving beta cell function and preventing the development of T1D.
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Diabetes Mellitus Tipo 1 , Estado Pré-Diabético , Humanos , Camundongos , Animais , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/prevenção & controle , Camundongos Endogâmicos NOD , Metalotioneína/genética , Metalotioneína/metabolismo , Quimiocina CXCL12RESUMO
Fine particulate matter (PM2.5) from vehicle exhaust is typically emitted at breathing height and thus imposes severe adverse effects on human health and air quality. However, there is currently limited knowledge on the characteristics of PM2.5 in exhaust, specifically its chemical components, at different ambient temperatures. Particulate emissions from typical light-duty gasoline vehicles (LDGVs) were investigated on a chassis dynamometer according to the Worldwide Harmonized Light-Duty Test Cycle at ambient temperatures of 38 °C, 28 °C, 15 °C, 5 °C and - 7 °C. The results showed a significant increase in particulate mass (PM) and particle number (PN) emissions with decreasing ambient temperature, particularly during cold starts below 5 °C. The particle size distributions exhibited distinct bimodal patterns, with accumulation-mode (AM) particles (60-125 nm) dominating the gasoline direct injection (GDI) distribution and nucleation-mode (NM) particles (8-12 nm) dominating the port fuel injection (PFI) distribution. AM particles were more temperature-sensitive than NM particles. Lower temperatures produced higher emissions of elements, carbonaceous components, and large-ring polycyclic aromatic hydrocarbons, while water-soluble ions showed an opposite trend. The total toxic equivalent, primarily influenced by benzo[a]pyrene, was significantly higher at -7 °C. The penalty distribution of LDGV PM and PN, defined by comparing the emissions at the various temperatures to those at regulated temperatures (23-30 °C), exhibited notable temporal heterogeneity (winter > autumn > spring > summer) and spatial heterogeneity (northern China > southern China). These findings are essential for establishing more stringent vehicle emission standards and improving emission models in cold environments.
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Hematopoietic stem cell transplantation (HSCT) has benefited an increasing number of patients with hematological disease in the clinic. It is a curative therapy for malignant and nonmalignant hematological diseases. With the advancement and further clinical application of HSCT in recent years, the life expectancy of patients has increased, but complications have become more common. The occurrence of ocular complications is receiving increasing attention because they can seriously affect the quality of life of patients. Ocular complications require increased attention from clinicians because of their negative impact on patients and increasing incidence. Most of recent reports on posttransplant ocular complications involve ocular manifestations of graft-versus-host disease (GVHD), and a few ocular complications that do not originate from GVHD have also been reported. This review summarizes the diagnosis, scoring criteria, pathophysiology, and clinical manifestations of and common therapies for ocular graft-versus-host disease(oGVHD) after HSCT, and includes a description of some rare cases and novel therapies.
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Extensive real-data indicate that human motion exhibits novel patterns and has a significant impact on the epidemic spreading process. The research on the influence of human motion patterns on epidemic spreading dynamics still lacks a systematic study in network science. Based on an agent-based model, this paper simulates the spread of the disease in the gathered population by combining the susceptible-infected-susceptible epidemic process with human motion patterns, described by moving speed and gathering preference. Our simulation results show that the emergence of a hysteresis loop is observed in the system when the moving speed is slow, particularly when humans prefer to gather; that is, the epidemic prevalence of the systems depends on the fraction of initial seeds. Regardless of the gathering preference, the hysteresis loop disappears when the population moves fast. In addition, our study demonstrates that there is an optimal moving speed for the gathered population, at which the epidemic prevalence reaches its maximum value.