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1.
Shock ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38813929

ABSTRACT

BACKGROUND: Early prediction of sepsis onset is crucial for reducing mortality and the overall cost burden of sepsis treatment. Currently, few effective and accurate prediction tools are available for sepsis. Hence, in this study, we developed an effective sepsis clinical decision support system (S-CDSS) to assist emergency physicians to predict sepsis. METHODS: This study included patients who had visited the emergency department (ED) of Taipei Tzu Chi Hospital, Taiwan, between January 1, 2020, and June 31, 2022. The patients were divided into a derivation cohort (n = 70,758) and a validation cohort (n = 27,545). The derivation cohort was subjected to sixfold stratified cross-validation, reserving 20% of the data (n = 11,793) for model testing. The primary study outcome was a sepsis prediction (International Classification of Diseases, Tenth Revision, Clinical Modification) before discharge from the ED. The S-CDSS incorporated the LightGBM algorithm to ensure timely and accurate prediction of sepsis. The validation cohort was subjected to multivariate logistic regression to identify the associations of S-CDSS-based high- and medium-risk alerts with clinical outcomes in the overall patient cohort. For each clinical outcome in high- and medium-risk patients, we calculated the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy of S-CDSS-based predictions. RESULTS: The S-CDSS was integrated into our hospital information system. The system featured three risk warning labels (red, yellow, and white, indicating high, medium, and low risks, respectively) to alert emergency physicians. The sensitivity and specificity of the S-CDSS in the derivation cohort were 86.9% and 92.5%, respectively. In the validation cohort, high- and medium-risk alerts were significantly associated with all clinical outcomes, exhibiting high prediction specificity for intubation, general ward admission, intensive care unit admission, ED mortality, and in-hospital mortality (93.29%, 97.32%, 94.03%, 93.04%, and 93.97%, respectively). CONCLUSION: Our findings suggest that the S-CDSS can effectively identify patients with suspected sepsis in the ED. Furthermore, S-CDSS-based predictions appear to be strongly associated with clinical outcomes in patients with sepsis.

2.
Medicina (Kaunas) ; 60(4)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38674293

ABSTRACT

Background and Objectives: The Taiwan Triage and Acuity Scale (TTAS) is reliable for triaging patients in emergency departments in Taiwan; however, most triage decisions are still based on chief complaints. The reverse-shock index (SI) multiplied by the simplified motor score (rSI-sMS) is a more comprehensive approach to triage that combines the SI and a modified consciousness assessment. We investigated the combination of the TTAS and rSI-sMS for triage compared with either parameter alone as well as the SI and modified SI. Materials and Methods: We analyzed 13,144 patients with trauma from the Taipei Tzu Chi Trauma Database. We investigated the prioritization performance of the TTAS, rSI-sMS, and their combination. A subgroup analysis was performed to evaluate the trends in all clinical outcomes for different rSI-sMS values. The sensitivity and specificity of rSI-sMS were investigated at a cutoff value of 4 (based on previous study and the highest score of the Youden Index) in predicting injury severity clinical outcomes under the TTAS system were also investigated. Results: Compared with patients in triage level III, those in triage levels I and II had higher odds ratios for major injury (as indicated by revised trauma score < 7 and injury severity score [ISS] ≥ 16), intensive care unit (ICU) admission, prolonged ICU stay (≥14 days), prolonged hospital stay (≥30 days), and mortality. In all three triage levels, the rSI-sMS < 4 group had severe injury and worse outcomes than the rSI-sMS ≥ 4 group. The TTAS and rSI-sMS had higher area under the receiver operating characteristic curves (AUROCs) for mortality, ICU admission, prolonged ICU stay, and prolonged hospital stay than the SI and modified SI. The combination of the TTAS and rSI-sMS had the highest AUROC for all clinical outcomes. The prediction performance of rSI-sMS < 4 for major injury (ISS ≥ 16) exhibited 81.49% specificity in triage levels I and II and 87.6% specificity in triage level III. The specificity for mortality was 79.2% in triage levels I and II and 87.4% in triage level III. Conclusions: The combination of rSI-sMS and the TTAS yielded superior prioritization performance to TTAS alone. The integration of rSI-sMS and TTAS effectively enhances the efficiency and accuracy of identifying trauma patients at a high risk of mortality.


Subject(s)
Triage , Wounds and Injuries , Humans , Triage/methods , Triage/standards , Male , Female , Taiwan/epidemiology , Middle Aged , Adult , Wounds and Injuries/mortality , Aged , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Injury Severity Score , Sensitivity and Specificity , Trauma Severity Indices , Shock/mortality , Shock/diagnosis , Length of Stay/statistics & numerical data
3.
ACS Appl Mater Interfaces ; 16(8): 10398-10406, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38380978

ABSTRACT

The rapid evolution of the Internet of Things has engendered increased requirements for low-cost, self-powered UV photodetectors. Herein, high-performance self-driven UV photodetectors are fabricated by designing asymmetric metal-semiconductor-metal structures on the high-quality large-area CsCu2I3 microwire arrays. The asymmetrical depletion region doubles the photocurrent and response speed compared to the symmetric structure device, leading to a high responsivity of 233 mA/W to 355 nm radiation. Notably, at 0 V bias, the asymmetric device produces an open-circuit voltage of 356 mV and drives to a short-circuit current of 372 pA; meanwhile, the switch ratio (Iph/Idark) reaches up to 103, indicating its excellent potential for detecting weak light. Furthermore, the device maintains stable responses throughout 10000 UV-light switch cycles, with negligible degradation even after 90-day storage in air. Our work establishes that CsCu2I3 is a good candidate for self-powered UV detection and thoroughly demonstrates its potential as a passive device.

4.
Zhongguo Zhong Yao Za Zhi ; 49(2): 461-470, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38403322

ABSTRACT

This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 µg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.


Subject(s)
Drugs, Chinese Herbal , Esophageal Neoplasms , Tandem Mass Spectrometry , Mice , Animals , Chromatography, Liquid , Metabolomics , Biomarkers , Esophageal Neoplasms/chemically induced , Esophageal Neoplasms/drug therapy
5.
Medicina (Kaunas) ; 59(11)2023 Nov 09.
Article in English | MEDLINE | ID: mdl-38004023

ABSTRACT

Background and Objectives: In the context of prehospital care, spinal immobilization is commonly employed to maintain cervical stability in head and neck injury patients. However, its use in cases of unclear consciousness or major trauma patients is often precautionary, pending the exclusion of unstable spinal injuries through appropriate diagnostic imaging. The impact of prehospital C-spinal immobilization in these specific patient populations remains uncertain. Materials and Methods: We conducted a retrospective cohort study at Taipei Tzu Chi Hospital from January 2009 to May 2019, focusing on trauma patients suspected of head and neck injuries. The primary outcome assessed was in-hospital mortality. We employed multivariable logistic regression to investigate the relationship between prehospital C-spine immobilization and outcomes, while adjusting for various factors such as age, gender, type of traumatic brain injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and activation of trauma team. Results: Our analysis encompassed 2733 patients. Among these, patients in the unclear consciousness group (GCS ≤ 8) who underwent C-spine immobilization exhibited a higher mortality rate than those without immobilization. However, there was no statistically significant difference in mortality among patients with alert consciousness (GCS > 8). Multivariable logistic regression analysis revealed that advanced age (age ≥ 65), unclear consciousness (GCS ≤ 8), major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and the use of neck collars for immobilization (adjusted OR: 1.850, 95% CI: 1.240-2.760, p = 0.003) were significantly associated with an increased risk of mortality. Subgroup analysis indicated that C-spine immobilization was significantly linked to an elevated risk of mortality in older adults (age ≥ 65), patients with unclear consciousness (GCS ≤ 8), those with major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and individuals in shock (shock index > 1). Conclusions: While our findings do not advocate for the complete abandonment of neck collars in all suspected head and neck injury patients, our study suggests that prehospital cervical and spinal immobilization should be applied more selectively in certain head and neck injury populations. This approach is particularly relevant for older individuals (age ≥ 65), those with unclear consciousness (GCS ≤ 8), individuals experiencing major traumatic injuries (ISS ≥ 16 or RTS ≤ 7), and patients in a state of shock (shock index ≥ 1). Our study employs a retrospective cohort design, which may introduce selection bias. Therefore, in the future, there is a need for confirmation of our results through a two-arm randomized controlled trial (RCT) arises, as this design is considered ideal for addressing this issue.


Subject(s)
Neck Injuries , Spinal Injuries , Humans , Aged , Spinal Injuries/therapy , Injury Severity Score , Retrospective Studies , Neck Injuries/therapy , Immobilization
6.
Front Chem ; 11: 1259569, 2023.
Article in English | MEDLINE | ID: mdl-37867998

ABSTRACT

Drug-induced liver injury (DILI) is one of the most common causes of a drug being withdrawn, and identifying the culprit drugs and the host factors at risk of causing DILI has become a current challenge. Recent studies have found that immune status plays a considerable role in the development of DILI. In this study, DILI-related differentially expressed genes mediated by immunoinflammatory cytokines were obtained from the Gene Expression Omnibus (GEO) database to predict the occurrence of DILI (named the DILI predictive gene set, DILI_PGS), and the predictability of the DILI_PGS was verified using the Connectivity Map (CMap) and LiverTox platforms. The results obtained DILI_PGS from the GEO database could predict 81.25% of liver injury drugs. In addition, the Coexpedia platform was used to predict the DILI_PGS-related characteristics of common host diseases and found that the DILI_PGS mainly involved immune-related diseases and tumor-related diseases. Then, animal models of immune stress (IS) and immunosuppressive (IP) were selected to simulate the immune status of the above diseases. Meanwhile, psoralen, a main component derived from Psoralea corylifolia Linn. with definite hepatotoxicity, was selected as an experimental drug with highly similar molecular fingerprints to three idiosyncratic hepatotoxic drugs (nefazodone, trovafloxacin, and nimesulide) from the same DILI_PGS dataset. The animal experiment results found a single administration of psoralen could significantly induce liver injury in IS mice, while there was no obvious liver function change in IP mice by repeatedly administering the same dose of psoralen, and the potential mechanism of psoralen-induced liver injury in IS mice may be related to regulating the expression of the TNF-related pathway. In conclusion, this study constructed the DILI_PGS with high accuracy to predict the occurrence of DILI and preliminarily identified the characteristics of host factors inducing DILI.

7.
Altern Ther Health Med ; 29(8): 534-539, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37678850

ABSTRACT

Purpose: To study the risk factors affecting amputation and survival in patients with diabetic foot (DF) and to construct a predictive model using the machine learning technique for DF foot amputation and survival and evaluate its effectiveness. Materials and Methods: A total of 200 patients with DF hospitalized in the First Affiliated Hospital of Shantou University Medical College in China were selected via cluster analysis screening, Kaplan-Meier survival calculation, amputation rate and Cox proportional hazards model investigation of risk factors associated with amputation and death. In addition, we constructed various models, including Cox proportional hazards regression analysis, the deep learning method convolution neural network (CNN) model, backpropagation (BP) neural network model, and backpropagation neural network prediction model after optimizing the genetic algorithm. The accuracy of the 4 prediction models for survival and amputation was assessed, and we evaluated the reliability of these computational models based on the size of the area under the ROC curve (AUC), sensitivity and specificity. Results: We found that the 1-year survival rate in patients with DF was 88.5%, and the 1-year amputation rate was 12.5%. Wagner's Classification of Diabetic Foot Ulcers grade, ankle-brachial index (ABI), low-density lipoprotein (LDL), and percutaneous oxygen partial pressure (TcPO2) were independent risk factors for amputation in patients with DF, while cerebrovascular disease, Sudoscan sweat gland function score, glycated hemoglobin (HbA1c) and peripheral artery disease (PAD) were independent risk factors for death in patients with DF. In addition, our results showed that in the case of amputation, the COX regression predictive model revealed an AUC of 0.788, sensitivity of 74.1% and specificity of 83.6%. The BP neural network predictive model identified an AUC of 0.874, sensitivity of 87.0% and specificity of 87.7%. An AUC of 0.909, sensitivity of 90.7% and specificity of 91.1% were found after optimizing the BP neural network prediction model via genetic algorithm. In the deep learning CNN model, the AUC, sensitivity and specificity were 0.939, 92.6%, and 95.2%, respectively. In the analysis of risk factors for death, the COX regression predictive model identified the AUC, sensitivity and specificity as 0.800, 74.1% and 85.9%, respectively. The BP neural network predictive model revealed an AUC, sensitivity and specificity of 0.937, 93.1% and 94.4%, respectively. Genetic algorithm-based optimization of the BP neural network predictive model identified an AUC, sensitivity and specificity of 0.932, 91.4% and 95.1%, respectively. The deep learning CNN model found the AUC, sensitivity and specificity to be 0.861, 82.8% and 89.4%, respectively. Conclusion: To identify risk factors for death, the BP neural network predictive model and genetic algorithm-based optimizing BP neural network predictive model have higher sensitivity and specificity than the deep learning method CNN predictive model and COX regression analysis.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/diagnosis , Prognosis , Reproducibility of Results , Risk Factors , Amputation, Surgical
8.
Chin Med ; 18(1): 102, 2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37592331

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use. AIM OF THE STUDY: Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers. MATERIALS AND METHODS: The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively. RESULTS: The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ's protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9). CONCLUSIONS: Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM.

9.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3556-3564, 2023 Jul.
Article in Chinese | MEDLINE | ID: mdl-37474989

ABSTRACT

This study investigated the effect of Gualou Xiebai Decoction on rats with bleomycin-induced pulmonary fibrosis. The rats were randomly divided into a control group, a model group, a low-dose Gualou Xiebai Decoction group(2.4 g·kg~(-1)), a high-dose Gualou Xiebai Decoction group(4.8 g·kg~(-1)), and pirfenidone group(150 mg·kg~(-1)). The model of pulmonary fibrosis was established by intratracheal instillation of bleomycin in all groups, except the control group. Since the second day of modeling, the corresponding drugs were given to rats by intragastric administration, once a day for 14 d and 28 d. The hematoxylin-eosin(HE) staining was used to evaluate the degree of inflammatory injury in lung tissues. The immunofluorescence staining was used to detect the expression of CD68 and CD163 in lung tissues of rats. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in serum and brochoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay(ELISA). The expression of pyroptosis-related genes in lung tissues of rats was detected by qRT-PCR. The results of HE staining and immunofluorescence staining showed that the lung tissue structure was normal in the control group. In addition, there were alveolar collapse or even closure in lung tissues of rats in the model group, with obvious inflammatory cell infiltration, and the expression of CD68 and CD163 was significantly up-regulated. As compared with the model group, the lung tissue structure of rats in the Gualou Xiebai Decoction groups was significantly improved, with alleviated inflammation, and the expression of CD68 and CD163 was decreased. As compared with the control group, the level of TNF-α in serum and BALF of rats in the model group was significantly increased(P<0.01), the mRNA expression levels of alpha smooth muscle actin(α-SMA), collagen type Ⅰ alpha 1 chain(Col1a1), caspase-1, IL-1ß, IL-18, gasdermin D(Gsdmd), and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in lung tissues were significantly increased(P<0.05, P<0.01), and the mRNA expression level of E-cadherin was significantly decreased(P<0.01). As compared with the model group, the level of TNF-α in serum and BALF was significantly down-regulated in the high-dose Gualou Xiebai Decoction group(P<0.05, P<0.01), and that of IL-10 was up-regulated(P<0.05, P<0.01). The mRNA expression levels of α-SMA, Col1a1, caspase-1, IL-18, Gsdmd, NLRP3 and IL-1ß in lung tissues were significantly decreased(P<0.05, P<0.01) in the high-dose Gualou Xiebai Decoction group, and the mRNA expression level of E-cadherin was significantly increased(P<0.05, P<0.01). In conclusion, Gualou Xiebai Decoction can down-regulate the levels of inflammatory factors and related genes and effectively mitigate pulmonary fibrosis by regulating the pyroptosis pathways.


Subject(s)
Pulmonary Fibrosis , Rats , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/genetics , Interleukin-18 , Interleukin-10 , Tumor Necrosis Factor-alpha/genetics , Pyroptosis , NLR Family, Pyrin Domain-Containing 3 Protein , Caspases , Bleomycin/adverse effects , RNA, Messenger/metabolism , Cadherins
10.
Zhongguo Zhong Yao Za Zhi ; 48(12): 3327-3344, 2023 Jun.
Article in Chinese | MEDLINE | ID: mdl-37382017

ABSTRACT

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.


Subject(s)
IgA Vasculitis , Animals , Rats , IgA Vasculitis/drug therapy , Network Pharmacology , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Metabolomics
11.
DNA Repair (Amst) ; 127: 103512, 2023 07.
Article in English | MEDLINE | ID: mdl-37230009

ABSTRACT

In the baker's yeast Saccharomyces cerevisiae, NuA4 and SWR1-C, two multisubunit complexes, are involved in histone acetylation and chromatin remodeling, respectively. Eaf1 is the assembly platform subunit of NuA4, Swr1 is the assembly platform and catalytic subunit of SWR1-C, while Swc4, Yaf9, Arp4 and Act1 form a functional module, and is present in both NuA4 and SWR1 complexes. ACT1 and ARP4 are essential for cell survival. Deletion of SWC4, but not YAF9, EAF1 or SWR1 results in a severe growth defect, but the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display defects in DNA ploidy and chromosome segregation, suggesting that the defects observed in swc4Δ cells are independent of NuA4 or SWR1-C integrity. Swc4 is enriched in the nucleosome-free regions (NFRs) of the genome, including characteristic regions of RDN5s, tDNAs and telomeres, independently of Yaf9, Eaf1 or Swr1. In particular, rDNA, tDNA and telomere loci are more unstable and prone to recombination in the swc4Δ cells than in wild-type cells. Taken together, we conclude that the chromatin associated Swc4 protects nucleosome-free chromatin of rDNA, tDNA and telomere loci to ensure genome integrity.


Subject(s)
Nucleosomes , Saccharomyces cerevisiae Proteins , Humans , Histones/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , DNA, Ribosomal , Chromatin , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Telomere/genetics , Telomere/metabolism , Genomic Instability , Chromatin Assembly and Disassembly , Histone Acetyltransferases/genetics , Transcription Factors/genetics
12.
Int J Gen Med ; 16: 1681-1693, 2023.
Article in English | MEDLINE | ID: mdl-37181643

ABSTRACT

Background: Gastric cancer is the second most common cause of cancer death worldwide with poor overall prognosis. It is important to study the molecular mechanism of stomach adenocarcinoma (STAD). MAGED4B, a member of the melanoma antigen gene (MAGE) family, is highly expressed in many tumor cells and is associated with tumor progression. Its prognostic value in and the function of the encoded protein are still unclear. Methods: The data of 415 STAD tissues was retrieved from TCGA database, and the expression level of MAGED4B mRNA was evaluated. The correlation between the expression of MAGED4B mRNA and the progression free survival (PFS) time of STAD patients was evaluated by Kaplan Meier analysis. The STAD cell lines with overexpressed and silent MAGED4B were constructed, and the effects of MAGED4B on the viability, migration and proliferation were evaluated by the CCK-8, scratch test and EDU test. The flow cytometry was used to detect apoptosis with overexpressed and silent MAGED4B under the cisplatin treatment, and WB was used to detect the expressions of related proteins, such as TNF-α. Results: The expression level of MAGED4B mRNA in the STAD tissues was higher than that in the normal tissues, and its high expression was related to poor PFS. The overexpression of MAGED4B in the STAD cell lines can promote the vitality, motility and proliferation of the STAD cells, while the silencing of MAGED4B can inhibit the above three cell functions of the STAD cells. The overexpression of MAGED4B can reduce the cisplatin induced apoptosis and increase the cisplatin IC50; the silencing of MAGED4B can promote the cisplatin induced apoptosis and reduce the cisplatin IC50. The overexpression of MAGED4B reduced the protein levels of TRIM27 and TNF- α. Conclusion: MAGED4B could be a valuable prognostic biomarker and a therapeutic target for gastric adenocarcinoma of great interest.

13.
Tzu Chi Med J ; 35(1): 69-77, 2023.
Article in English | MEDLINE | ID: mdl-36866355

ABSTRACT

Objectives: Trauma is one of the leading causes of death and its incidence increases annually. The "weekend effect" and "holiday season effect" on traumatic injury mortality remain controversial, whereby traumatic injury patients admitted during weekends and/or holiday season have a higher risk of in-hospital death. The present study is aimed to explore the association between "weekend effect" and "holiday season effect" and mortality in traumatic injury population. Materials and Methods: This retrospective descriptive study included patients from the Taipei Tzu Chi Hospital Trauma Database between January 2009 and June 2019. The exclusion criterion was age of < 20 years. The primary outcome was the in-hospital mortality rate. The secondary outcomes included intensive care unit (ICU) admission, ICU re-admission, length of stay (LOS) in the ICU, ICU admission duration ≥ 14 days, total hospital LOS, total hospital LOS ≥ 14 days, need for surgery, and re-operation rate. Results: In this study, 11,946 patients were included in the analysis, and 8143 (68.2%) patients were admitted on weekdays, 3050 (25.5%) on weekends, and 753 (6.3%) on holidays. Multivariable logistic regression revealed that the admission day was not associated with an increased risk of in-hospital mortality. In other clinical outcome analyses, we found no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups. The subgroup analysis showed that the association between holiday season admission and in-hospital mortality was noted only in the elderly and shock condition populations. The holiday season duration did not differ in terms of in-hospital mortality. Longer holiday season duration was also not associated with an increased risk of in-hospital mortality, ICU LOS ≥14 days, and total LOS ≥14 days. Conclusion: In this study, we did not find any evidence that weekend and holiday season admissions in the traumatic injury population were associated with an increased risk of mortality. In other clinical outcome analyses, there was no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups.

14.
Transl Androl Urol ; 12(2): 187-196, 2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36915889

ABSTRACT

Background: Male reproductive health has become a serious public health concern, and semen quality is essential to male reproduction. We aimed to investigate geographical differences in the semen quality of sperm donors from northern and southern China by enrolling donors across the country. Methods: A total of 1,012 sperm donors were enrolled in this study between 2015 and 2019. Donors were first divided into two parts based on their birthplace according to the "Qinling-Huaihe" line, and secondly, by their residential latitude. Finally, donors were re-classified into two groups (typically north and south) which contained 667 samples. Results: Statistically significant differences in sperm concentration were observed among men from different latitudes in China (P=0.04). The sperm concentrations of males from 18° to 27° north latitude were significantly lower than those from 36° to 45° and 45° to 54° [median 131, 134, and 146, respectively, P=0.021 (18° to 27° vs. 36° to 45°) and P=0.01 (18° to 27° vs. 45° to 54°)]. Conclusion: We hypothesize environmental pollution and mental stress due to the increased population size may be the main factors underlying differences in the sperm quality of men in northern and southern China.

15.
Medicina (Kaunas) ; 59(2)2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36837595

ABSTRACT

Vomiting-induced pneumomediastinum is a rare presentation and can be a result of alveolar rupture (Mackler effect) or Boerhaave syndrome. Patients diagnosed with Boerhaave syndrome may present with the classic Mackler triad of vomiting, chest pain, and subcutaneous emphysema. However, there exists a large overlap of symptoms accompanying Boerhaave syndrome and the Macklin effect, including retrosternal chest pain, neck discomfort, cough, sore throat, dysphagia, dysphonia, and dyspnea. Boerhaave syndrome is a dangerous condition. Delayed diagnosis of Boerhaave syndrome may worsen sepsis and cause mortality. Therefore, early diagnosis and timely management are important to prevent further complications. Here, we present a case of vomiting-induced pneumomediastinum, which supports the use of bedside ultrasonography to aid in the diagnosis and rapid differentiation of etiology of pneumomediastinum.


Subject(s)
Mediastinal Emphysema , Humans , Female , Mediastinal Emphysema/complications , Point-of-Care Systems , Vomiting , Chest Pain/etiology
16.
Prehosp Emerg Care ; 27(1): 90-93, 2023.
Article in English | MEDLINE | ID: mdl-34874789

ABSTRACT

The assessment of cardiopulmonary resuscitation and teamwork quality in prehospital settings has always been challenging. Currently, commercialized quality-monitored chest pads and single-angle cameras are being used to monitor prehospital the resuscitation quality in patients following out-of-hospital cardiac arrest (OHCA). However, both these methods have drawbacks. In New Taipei City, we introduced the panoramic video camera as a novel method to assess the resuscitation quality of OHCA patients to monitor both technical skills and teamwork. The panoramic video camera enabled a comprehensive evaluation of prehospital resuscitation, thereby allowing team members to evaluate their performance by reviewing the video after resuscitation. This is the first step toward improving the evaluation of prehospital resuscitation. Using this panoramic video camera and a high-speed internet connection, real-time resuscitation feedback from the dispatch center or medical directors can be provided promptly, thus, making prehospital resuscitation safe and efficient.


Subject(s)
Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Humans , Out-of-Hospital Cardiac Arrest/therapy , Emergency Medical Services/methods , Cardiopulmonary Resuscitation/methods
17.
Natl Sci Rev ; 9(11): nwac152, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36478733

ABSTRACT

Intermuscular bones (IBs) are mineralized spicules, present in the myosepta of many, but not all, teleost species. IBs are often small and sharp, and they consequently limit how the fish can be processed; the IBs may cause injury or trauma if lodged in consumers' throats or mouths, and therefore affect the appeal of the fish to many consumers. The development of IBs in teleosts is still not fully understood and the molecular basis of IB development remains to be established. Here, the characteristics of IB tissue are evaluated based on single-cell transcriptomics in wild-type zebrafish. The analysis defined 18 distinct cell types. Differentiation trajectories showed that IBs are derived from tendons and that a core tendon-osteoblast cell lineage is related to IB formation. In particular, the functions of 10 candidate genes were evaluated via CRISPR-Cas9 mutants. Among those, runx2b-/- mutants completely lost IBs, while swimming performance, growth and bone mineral density were not significantly different from runx2b+/+ zebrafish. Comparative single-cell RNA sequencing (scRNA-seq) analysis in runx2b-/- and runx2b+/+ zebrafish revealed the role of osteoblasts in IB formation. In addition, differentially expressed genes were enriched in the transforming growth factor ß/bone morphogenetic protein (TGF-ß/BMP) pathway after runx2b deletion. This study provides evidence for the crucial role of runx2b regulation in IB formation. Genetic breeding can target runx2b regulation and generate strains of commercial fish species without IBs, which can improve the safe consumption and economic value of many farmed fish species.

18.
Shock ; 58(6): 524-533, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36548644

ABSTRACT

ABSTRACT: Objectives: Many prehospital trauma triage scores have been proposed, but none has emerged as a criterion standard. Therefore, a rapid and accurate tool is necessary for field triage. The shock index (SI) multiplied by the AVPU (Alert, responds to Voice, responds to Pain, Unresponsive) score (SIAVPU) reflected the hemodynamic and neurological conditions through a combination of the SI and AVPU. This study aimed to investigate the prediction performance of SI multiplied by the AVPU and to compare the prediction performance of other prehospital trauma triage scores in a population with traumatic injury. Patients and Methods: This study included 6,156 patients with trauma injury from the Taipei Tzu Chi trauma database. We investigated the accuracy of four scoring systems in predicting mortality, intensive care unit (ICU) admission, and prolonged hospital stay (defined as a duration of hospitalization >14 days). In the subgroup analysis, we also analyzed the effects of age, injury mechanism and severity, underlying diseases, and traumatic brain injury. Results: The predictive accuracy of SIAVPU for mortality, ICU admission, and prolonged hospital stay was significantly higher than that of SI, modified SI, and SI multiplied by age in the traumatic injury population, with an area under the receiver operating characteristic curve of 0.738 for mortality, 0.641 for ICU admission, and 0.606 for prolonged hospital stay. In the subgroup analysis, the prediction accuracy of mortality, ICU admission, and prolonged hospital stay of SIAVPU was also better in patients with younger age, older age, major trauma (Injury Severity Score ≥16), motor vehicle collisions, fall injury, healthy, cardiovascular disease, mixed traumatic brain injury, and isolated traumatic brain injury. The best cutoff levels of SIAVPU score to predict mortality, ICU admission, and total length of stay ≥14 days in trauma injury patients were 0.90, 0.82, and 0.80, with accuracies of 88.56%, 79.84%, and 78.62%, respectively. Conclusions: In conclusion, SIAVPU is a rapid and accurate field triage score with better prediction accuracy for mortality, ICU admission, and prolonged hospital stay than SI, modified SI, and SI multiplied by age in patients with trauma. Patients with SIAVPU ≥0.9 should be considered for the highest-level trauma center available within the geographic constraints of regional trauma systems.


Subject(s)
Brain Injuries, Traumatic , Wounds and Injuries , Humans , Retrospective Studies , Injury Severity Score , Trauma Centers , Brain Injuries, Traumatic/diagnosis , Hospitalization , Wounds and Injuries/diagnosis
19.
Front Med (Lausanne) ; 9: 999481, 2022.
Article in English | MEDLINE | ID: mdl-36482909

ABSTRACT

Objectives: Early identification of traumatic brain injury (TBI) patients at a high risk of mortality is very important. This study aimed to compare the predictive accuracy of four scoring systems in TBI, including shock index (SI), modified shock index (MSI), age-adjusted shock index (ASI), and reverse shock index multiplied by the Glasgow Coma Scale (rSIG). Patients and methods: This is a retrospective analysis of a registry from the Taipei Tzu Chi trauma database. Totally, 1,791 patients with TBI were included. We investigated the accuracy of four major shock indices for TBI mortality. In the subgroup analysis, we also analyzed the effects of age, injury mechanism, underlying diseases, TBI severity, and injury severity. Results: The predictive accuracy of rSIG was significantly higher than those of SI, MSI, and ASI in all the patients [area under the receiver operating characteristic curve (AUROC), 0.710 vs. 0.495 vs. 0.527 vs. 0.598], especially in the moderate/severe TBI (AUROC, 0.625 vs. 0.450 vs. 0.476 vs. 0.529) and isolated head injury populations (AUROC 0.689 vs. 0.472 vs. 0.504 vs. 0.587). In the subgroup analysis, the prediction accuracy of mortality of rSIG was better in TBI with major trauma [Injury Severity Score (ISS) ≥ 16], motor vehicle collisions, fall injury, and healthy and cardiovascular disease population. rSIG also had a better prediction effect, as compared to SI, MSI, and ASI, both in the non-geriatric (age < 65 years) and geriatric (age ≥ 65 years). Conclusion: rSIG had a better prediction accuracy for mortality in the overall TBI population than SI, MSI, and ASI. Although rSIG have better accuracy than other indices (ROC values indicate poor to moderate accuracy), the further clinical studies are necessary to validate our results.

20.
RSC Adv ; 12(45): 29516-29524, 2022 Oct 11.
Article in English | MEDLINE | ID: mdl-36320739

ABSTRACT

With the excessive consumption of fossil energy, technologies that transform bio-based resources into materials have received more and more attention from researchers in recent decades. In this paper, a series of poly(ethylene 2,5-tetrahydrofuran dimethyl terephthalate; PEFTs) with different components were synthesized from 2,5-tetrahydrofuran dimethanol (THFDM), terephthalic acid (TPA), and ethylene glycol (EG). Their chemical structures and compositions were determined by FTIR, 1H NMR, and 13C NMR. With the increase in THFDM content, the crystallization, T m, and tensile strength of PEFTs gradually decrease because the introduced THFDM breaks the order of molecular chains, while the thermal stability and T g remain stable. PEFTs seem to present a significant shear thinning phenomenon, which was indicated by the rheological test. Electrospinning technology was used to explore the spinnability of PEFT; it was found that PEFTs have better spinning performance than PET. In addition, due to the good hydrophobicity and porosity of PEFT nanofiber films, they have potential application value in the manufacture of hydrophobic nanofiber and filter films.

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