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1.
Article in English | MEDLINE | ID: mdl-38967327

ABSTRACT

This study attempted to build a prognostic riskscore model for pancreatic cancer (PC) patients based on vesicle-mediated transport protein-related genes (VMTGs). We initially conducted differential expression analysis and Cox regression analysis, followed by the construction of a riskscore model to classify PC patients into high-risk (HR) and low-risk (LR) groups. The GEO GSE62452 dataset further validated the model. Kaplan-Meier survival analysis was employed to analyze the survival rate of the HR group and LR group. Cox analysis confirmed the independent prognostic ability of the riskscore model. Additionally, we evaluated immune status in both HR and LR groups, utilizing data from the GDSC database to predict drug response among PC patients. We identified six PC-specific genes from 724 VMTGs. Survival analysis revealed that the survival rate of the HR group was lower than that of the LR group (P<0.05). Cox analysis confirmed that the prognostic riskscore model could independently predict the survival status of PC patients (P<0.001). Immunological analysis revealed that the ESTIMATE score, immune score, and stroma score of the HR group were considerably lower than those of the LR group, and the tumor purity score of the HR group was higher. The IC50 values of Gemcitabine, Irinotecan, Oxaliplatin, and Paclitaxel in the LR group were considerably lower than those in the HR group (P<0.001). In summary, the VMTG-based prognostic riskscore model could stratify PC risk and effectively predict the survival of PC patients.

2.
J Physiol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953534

ABSTRACT

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

3.
Curr Med Imaging ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956904

ABSTRACT

BACKGROUND: Capitellar injury (CI) includes capitellar cartilage injury (CCI) and capitellar fracture (CF). A comprehensive classification of CI concurrent with radial head fracture (RHF) that can guide surgical strategy is lacking in the literature. Therefore, this study aimed to introduce a comprehensive classification of CI concurrent with RHF and investigate its value. METHODS: A total of 35 patients with CI concurrent with RHF confirmed by surgical exploration were retrospectively analyzed, includingmales in 19 cases and females in 16 cases. RHF was classified according to the Mason classification, and CI was classified into six types, including 3 types of CCI and CF, each based on the site and degrees of injuries (comprehensive classification method proposed in this study). The classification results were analyzed. Two radiologists were selected to independently classify the CI, and the inter- and intra-observer agreements were analyzed with kappa statistics. RESULTS: Mason Type I, II, III, and IV RHF accounted for 14.3%, 48.6%, 37.1%, and 0% of cases, respectively. Type I, II, III, IV, V, and VI CIs accounted for 22.9%, 34.3%, 25.7%, 11.4%, 2.9%, and 2.9% of cases, respectively. Therewas no obvious relationship between the CI and RHF types (p > 0.05). All Type I CIs underwent removal, 9 Type II CIs underwent microfracture repair, and 3 Type II CIs underwent removal. All Type III CIs underwent fixation, one Type IV CI underwent removal, and 3 Type IV CIs underwent fixation, one Type V CI underwent fixation, and one Type VI CI underwent arthroplasty. The inter- and intra-observer kappa coefficients were 0.830 ~ 0.905 and 0.805 ~ 0.892, respectively. At 12 months postoperatively, the elbow function evaluated by MEPS was 91, with an excellent and good rate of 97%. CONCLUSION: Different types of CI differ not only in pathology but also in treatment methods. The CI comprehensive classification put forth in this paper for the first time reflects different types of pathology well, with high consistency and repeatability, and can guide the selection of surgical methods, leading to satisfactory postoperative results.

4.
Angew Chem Int Ed Engl ; : e202409931, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38957113

ABSTRACT

The alkylation of nucleophiles is among the most fundamental and well-developed transformations in chemistry. However, to achieve selective alkylation of complex substrates remains a nontrivial task. We report herein a general and selective alkylation method without using strong acids, bases, or metals. In this method, the readily available phosphinites/phosphites, in combination with ethyl acrylate, function as effective alkylating agents. Various nucleophilic groups, including alcohols, phenols, carboxylic acids, imides, and thiols can be alkylated. This method can be applied in the late-stage alkylation of natural products and pharmaceutical agents, achieving chemo- and site-selective modification of complex substrates. Experimental studies indicate the relative reactivity of a nucleophile depends on its acidity and its steric environment. Mechanistic studies suggest the reaction pathway resembles that of the Arbuzov-Michalis reaction.

5.
Front Pediatr ; 12: 1305639, 2024.
Article in English | MEDLINE | ID: mdl-38978839

ABSTRACT

Purpose: Investigate the clinical/hematological characteristics of children infected with the Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and identify an effective indicator to distinguish coronavirus disease 2019 (COVID-19) severity in children. Methods: A retrospective study was conducted through electronic medical records from pediatric patients. The demographic, clinical, and routine blood test (RBT) features of children diagnosed by real-time PCR for SARS-CoV-2 were collected. Results: Data of 261 patients were analyzed. The most common abnormality shown by RBTs was increased monocyte count (68%). Children had "mild-moderate" or "severe" forms of COVID-19. Prevalence of abnormal neutrophil count (p = 0.048), eosinophil count (p = 0.006), mean corpuscular volume (p = 0.033), mean platelet volume (p = 0.006), platelet-large cell ratio (p = 0.043), and red blood cell distribution width-standard deviation (p = 0.031) were significantly different in the two types. A combination of the neutrophil: lymphocyte ratio (NLR) and eosinophil count for diagnosing severe COVID-19 presented the largest AUC (0.688, 95% CI = 0.599-0.777; p < 0.001), and the AUC increased with a decrease in age. Conclusions: Combination of the NLR and eosinophil count might be a promising indicator for identifying severe COVID-19 in children at infection onset.

6.
Front Public Health ; 12: 1415477, 2024.
Article in English | MEDLINE | ID: mdl-38989125

ABSTRACT

Purpose: Falls are the leading cause of accidental death among older persons, with postmenopausal women facing a greater hazard of falling due to osteoporosis. This study aimed to examine the effects of Taijiquan practice on balance control and functional fitness in at-risk females. Methods: Chinese women who self-reported a tendency to fall and had a baseline one-leg stand test time (4.1 s in the Taijiquan group) below the national average for their age group (60-64 years: 10.9 s, 65-69 years: 9.9 s) were assigned to either a control group (n = 26, mean age = 63.9 years) or a Taijiquan group (n = 24, mean age = 63.9 years). The Taijiquan group participated in a 12-week supervised intervention, while the control group maintained their daily activities. The average duration of each exercise session was 52 min. Static balance and functional fitness were assessed at the beginning and end of the intervention. Results: After 12 weeks, the Taijiquan group significantly outperformed the control group in terms of balance, flexibility, and muscular fitness (all p < 0.05). Participants in the Taijiquan group improved their one-leg stand by 61.0% (+2.5 s, Hedge's g = 0.85), arm curl by 8.3% (+1.7 repetitions, g = 0.53), handgrip strength by 8.3% (+1.9 kg, g = 0.65), and sit-and-reach by 163.2% (+6.2 cm, g = 1.17). Conclusion: The improvement in balance, coupled with other functional fitness benefits, suggests that Taijiquan could serve as a useful exercise for older women with an elevated risk of falling.


Subject(s)
Accidental Falls , Physical Fitness , Postmenopause , Postural Balance , Tai Ji , Humans , Female , Postural Balance/physiology , Accidental Falls/prevention & control , Middle Aged , Aged , Postmenopause/physiology , Physical Fitness/physiology , China
7.
Front Pharmacol ; 15: 1406247, 2024.
Article in English | MEDLINE | ID: mdl-38989148

ABSTRACT

Anthracycline drugs mainly include doxorubicin, epirubicin, pirarubicin, and aclamycin, which are widely used to treat a variety of malignant tumors, such as breast cancer, gastrointestinal tumors, lymphoma, etc. With the accumulation of anthracycline drugs in the body, they can induce serious heart damage, limiting their clinical application. The mechanism by which anthracycline drugs cause cardiotoxicity is not yet clear. This review provides an overview of the different types of cardiac damage induced by anthracycline-class drugs and delves into the molecular mechanisms behind these injuries. Cardiac damage primarily involves alterations in myocardial cell function and pathological cell death, encompassing mitochondrial dysfunction, topoisomerase inhibition, disruptions in iron ion metabolism, myofibril degradation, and oxidative stress. Mechanisms of uptake and transport in anthracycline-induced cardiotoxicity are emphasized, as well as the role and breakthroughs of iPSC in cardiotoxicity studies. Selected novel cardioprotective therapies and mechanisms are updated. Mechanisms and protective strategies associated with anthracycline cardiotoxicity in animal experiments are examined, and the definition of drug damage in humans and animal models is discussed. Understanding these molecular mechanisms is of paramount importance in mitigating anthracycline-induced cardiac toxicity and guiding the development of safer approaches in cancer treatment.

8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(6): 574-577, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38991954

ABSTRACT

OBJECTIVE: To analyze the epidemiological characteristics of hospitalized patients diagnosed with sepsis in a large class III general hospital in Southwest China in a period of 2 years, and to explore the risk factors related to death in patients with sepsis. METHODS: A retrospective study was conducted to select patients with sepsis admitted to Sichuan Provincial People's Hospital from September 1, 2021 to August 31, 2023, and general characteristics such as gender, age, discharge diagnosis, discharge department, hospitalization cost, length of stay, and prognosis during hospitalization were collected. The baseline of two groups of patients was compared, and the risk factors of in-hospital cause of death in patients with sepsis were analyzed by multivariate Logistic regression. RESULTS: A total of 3 568 patients with sepsis were included with median age of 58 (35, 74) years old. Of all patients, there were 2 147 males (60.17%). The median length of hospitalization was 13 (8, 24) days, and the median hospitalization cost was 3.98 (1.87, 8.83) ten thousand yuan. The departments with more than 100 cases of sepsis in 2 years were central intensive care unit (ICU), pediatrics department, nephrology department, emergency medicine department, emergency intensive care unit (EICU), infectious department, respiratory medicine department, hematology department, neonatal care unit and emergency surgical department. A total of 1 210 patients (33.91%) admitted to ICU (including central ICU and EICU). The hospitalization cost of ICU patients were higher [6.7 (3.1, 15.5) ten thousand yuan], the hospitalization duration was longer [9 (3, 17) days], and the mortality was higher [35.29% (427/1 210)]. Among 3 568 patients with sepsis, 448 died and 3 120 survived during hospitalization. The age, male proportion and hospitalization cost of patients with sepsis in the death group were significantly higher than those in the survival group [age (years old): 75 (60, 86) vs. 57 (30, 71), male proportion: 67.86% (304/448) vs. 59.07% (1 843/3 120), hospitalization cost (ten thousand yuan): 6.7 (3.0, 16.9) vs. 3.7 (1.8, 8.1)], the ratio of diabetes mellitus was significantly lower than that of survival group [4.91% (22/448) vs. 10.45% (326/3 120)], the length of hospitalization was shorter than that of survival group [days: 10.0 (3.0, 19.0) vs. 13.0 (8.0, 24.0)], the differences were statistically significant (all P < 0.01). Multivariate Logistic regression analysis showed that male [odds ratio (OR) = 0.75, 95% confidence interval (95%CI) was 0.59-0.96], elder (OR = 1.04, 95%CI was 1.03-1.05) and diabetes (OR = 0.32, 95%CI was 0.19-0.54) were independent risk factors for in-hospital death in patients with sepsis (all P < 0.05). CONCLUSIONS: Sepsis is a heavy burden in Southwest China, especially for ICU, with high mortality, high hospitalization costs, and heavy economic burden on patients and society. Male, elder and diabetes were independent risk factors for in-hospital death of sepsis patients.


Subject(s)
Hospitals, General , Sepsis , Humans , Sepsis/epidemiology , Sepsis/mortality , Male , Female , China/epidemiology , Middle Aged , Aged , Retrospective Studies , Adult , Risk Factors , Tertiary Care Centers , Hospital Mortality , Length of Stay , Hospitalization
9.
World J Psychiatry ; 14(6): 857-865, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38984345

ABSTRACT

BACKGROUND: The diagnosis and treatment of depression in patients with chronic heart failure (CHF) is challenging, with no ideal treatment at present. AIM: To analyze the clinical intervention effect of Xuefu Zhuyu decoction (XFZYD) on CHF complicated with depression. METHODS: The study cohort comprised 116 patients with CHF complicated with depression who received treatment from July 2020 to July 2023, of which 55 received Western medicine (control group) and 61 received XFZYD (research group). Data on clinical effectiveness, traditional Chinese medicine (TCM) syndrome score, cardiac function, negative emotions, and serum inflammatory factors, were collected for comparative analyses. RESULTS: Compared with the control group, the research group had an evidently higher total effective rate. Furthermore, there were marked reductions in TCM symptom score, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, Self-Rating Depression Scale, Hamilton Depression Scale, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 in the research group after treatment, and these were lower than the corresponding values in the control group. Left ventricular ejection fraction was increased and higher in the research group compared with the control group after treatment. CONCLUSION: Our findings conclusively proved that XFZYD was considerably superior to Western medicine for treating CHF complicated with depression because it significantly alleviated patients' symptoms, improved cardiac function, relieved negative emotions, and reduced the levels of serum inflammatory factors.

10.
Adv Sci (Weinh) ; : e2404266, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38986026

ABSTRACT

Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α-Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α-ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long-standing catalysis challenge. Herein, an unprecedented TBD-switched Pd-catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late-stage modify pharmaceuticals, scalability to large-scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd-catalyzed double isocyanide insertion process, thereby selectively providing the desired α-ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α-ketoimine amide are successfully isolated and determined by X-ray analysis, confirming that they are probable intermediates in the catalytic pathway.

11.
Eur J Obstet Gynecol Reprod Biol ; 300: 54-62, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38986273

ABSTRACT

BACKGROUND: It is widely recognized that depression is highly prevalent among women experiencing recurrent spontaneous abortion (RSA), exerting detrimental effects on both the individual and the family. OBJECTIVE: To assess the depression risk and associated factors among women with RSA. DATA SOURCES: Our search strategy encompassed PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), and WANFANG. The research was conducted in May 2022. We included both randomized and nonrandomized studies that reported the prevalence of depression among women with RSA. DATA EXTRACTION AND SYNTHESIS: Two independent evaluators reviewed the titles and abstracts, assessed the full-text papers, extracted data from the included studies, and evaluated their quality using the Newcastle-Ottawa Scale (NOS). We performed random-effects meta-analyses to pool the data. Odds ratios (ORs) and standardized mean differences (SMDs) were combined based on effect sizes for binary and continuous outcomes. MAIN OUTCOMES: To conduct a meta-analysis to understand the risk of depression in women with RSA who were not treated with psychiatric medications, as well as an analysis of potential factors for depressive symptoms. RESULTS: Out of the initially identified 527 papers, a total of 20 studies (N = 13087) that fulfilled the inclusion criteria were selected. Compared to healthy controls, patients with RSA had a significantly higher risk of depression (OR: 4.26, 95 % confidence interval [CI]: 2.44-7.41; SMD: 0.89, 95 % CI: 0.51-1.26). The occurrence of depression among RSA patients was found to be significantly associated with several factors including the severity of depressive symptoms (OR: 3.82, 95 % CI: 2.22-6.59), number of spontaneous miscarriages (SMD: 0.59, 95 % CI: 0.01-1.18), history of therapeutic termination of pregnancy (SMD: 0.20, 95 % CI: 0.09-0.32), history of live birth (SMD: -0.32, 95 % CI: -0.49--0.15), and duration of marriage (SMD: 0.15, 95 % CI: 0.02-0.27). CONCLUSIONS: In clinical practice, it is crucial to provide appropriate psychological interventions for women undergoing RSA. These individuals face a significantly heightened risk of depression, which exhibits strong correlations with various demographic factors such as the severity of depressive symptoms, history of both spontaneous miscarriages and therapeutic termination of pregnancy, number of live births, and duration of marriage. Consequently, women who are suffering RSA deserves more assistance and emotional support.

13.
Biochem Pharmacol ; : 116419, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38996929

ABSTRACT

N6-methyladenosine (m6A) serves as the most abundant posttranscription modification. However, the role of m6A in tumorigenesis and chemotherapeutic drugs sensitivity remains largely unclear. Present research focuses on the potential function of the m6A writer KIAA1429 in tumor development and sorafenib sensitivity in liver cancer. We found that the level of KIAA1429 was significantly elevated in liver cancer tissues and cells and was closely associated with poorer prognosis. Functionally, KIAA1429 promoted the proliferation and Warburg effect of liver cancer cells in vitro and in vivo. RNA-seq and MeRIP-seq analysis revealed the glycolysis was one of the most affected pathways by KIAA1429, and m6A-modified HK1 was the most likely targeted gene to regulate the Warburg effect. KIAA1429 depletion decreased Warburg effect and increased sorafenib sensitivity in liver cancer. Mechanistically, KIAA1429 could affect the m6A level of HK1 mRNA through directly binding with it. Moreover, KIAA1429 cooperated with the m6A reader HuR to enhance HK1 mRNA stability, thereby upregulating its expression. These findings demonstrated that KIAA1429/HK1 axis decreases the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect, which may provide a novel therapeutic target for liver cancer treatment.

14.
Radiother Oncol ; : 110424, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38997092

ABSTRACT

Various genetic and epigenetic changes associated with genomic instability (GI), including DNA damage repair defects, chromosomal instability, and mitochondrial GI, contribute to the development and progression of cancer. These alterations not only result in DNA leakage into the cytoplasm, either directly or through micronuclei, but also trigger downstream inflammatory signals, such as the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Apart from directly inducing DNA damage to eliminate cancer cells, radiotherapy (RT) exerts its antitumor effects through intracellular DNA damage sensing mechanisms, leading to the activation of downstream inflammatory signaling pathways. This not only enables local tumor control but also reshapes the immune microenvironment, triggering systemic immune responses. The combination of RT and immunotherapy has emerged as a captivating avenue to increase the probability of abscopal effects, where distant tumors respond to treatment due to the systemic immunomodulatory effects. This review emphasizes the importance of GI in cancer biology and elucidates the mechanisms by which RT induces GI remodeling of the immune microenvironment. By elucidating the mechanisms of GI and RT-induced immune responses, we aim to emphasize the crucial importance of this approach in modern oncology. Understanding the impact of GI on tumor biological behavior and therapeutic response, as well as the possibility of activating systemic anti-tumor immunity through RT, will pave the way for the development of new treatment strategies and improve prognosis for patients.

15.
bioRxiv ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38948786

ABSTRACT

Liprin-α1 is a widely expressed scaffolding protein responsible for regulating cellular processes such as focal adhesion, cell motility, and synaptic transmission. Liprin-α1 interacts with many proteins including ELKS, GIT1, liprin-ß, and LAR-family receptor tyrosine protein phosphatase. Through these protein-protein interactions, liprin-α1 assembles large higher-order molecular complexes; however, the regulation of this complex assembly/disassembly is unknown. Liquid-liquid phase separation (LLPS) is a process that concentrates proteins within cellular nano-domains to facilitate efficient spatiotemporal signaling in response to signaling cascades. While there is no report that liprin-α1 spontaneously undergoes LLPS, we found that GFP-liprin-α1 expressed in HEK293 cells occasionally forms droplet-like condensates. MS-based interactomics identified Protein Phosphatase 2A (PP2A)/B56δ (PPP2R5D) trimers as specific interaction partners of liprin-α1 through a canonical Short Linear Interaction Motif (SLiM) in its N-terminal dimerization domain. Mutation of this SLiM nearly abolished PP2A interaction, and resulted in significantly increased LLPS. GFP-liprin-α1 showed significantly increased droplet formation in HEK293 cells devoid of B56δ (PPP2R5D knockout), suggesting that PPP2R5D/PP2A holoenzyme inhibits liprin-α1 LLPS. Guided by reported liprin-α1 Ser/Thr phosphorylation sites, we found liprin-α1 phospho-mimetic mutant at serine 763 (S763E) is sufficient to drive its LLPS. Domain mapping studies of liprin-α1 indicated that the intrinsically disordered region, the N-terminal dimerization domain, and the SAM domains are all necessary for liprin-α1 LLPS. Finally, expression of p.E420K, a human PPP2R5D variant causing Houge-Janssens Syndrome type 1 (also known as Jordan's Syndrome), significantly compromised suppression of liprin-α1 LLPS. Our work identified B56δ-PP2A holoenzyme as an inhibitor of liprin-α1 LLPS via regulation at multiple phosphorylation sites.

16.
Cardiovasc Toxicol ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951468

ABSTRACT

Radix Paeoniae Rubra. (Chishao, RPR) and Cortex Moutan. (Mudanpi, CM) are a pair of traditional Chinese medicines that play an important role in the treatment of atherosclerosis (AS). The main objective of this study was to identify potential synergetic function and underlying mechanisms of RPR-CM in the treatment of AS. The main active ingredients, targets of RPR-CM and AS-related genes were obtained from public databases. A Venn diagram was utilized to screen the common targets of RPR-CM in treating AS. The protein-protein interaction network was established based on STRING database. Biological functions and pathways of potential targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Cytoscape was used to construct the drug-compound-target-signal pathway network. Molecular docking was performed to verify the binding ability of the bioactive ingredients and the target proteins. The endothelial inflammation model was constructed with human umbilical vein endothelial cells stimulated with ox-LDL, and the function of RPR-CM in treating AS was verified by CCK-8 assay, enzyme-linked immunosorbent assay, and qPCR. In this study, 12 active components and 401 potential target genes of RPR-CM were identified, among which quercetin, kaempferol and baicalein were considered to be the main active components. A total of 1903 AS-related genes were identified through public databases and four GEO datasets (GSE57691, GSE72633, GSE6088 and GSE199819). There are 113 common target genes of RPR-CM in treating AS. PPI network analysis identified 17 genes in cluster 1 as the core targets. Bioinformatics analysis showed that RPR-CM in AS treatment was associated with multiple downstream biological processes and signal pathways. PTGS2, JUN, CASP3, TNF, IL1B, IL6, FOS, STAT1 were identified as the core targets of RPR-CM, and molecular docking showed that the main bioactive components of RPR-CM had good binding ability with the core targets. RPR-CM extract significantly inhibited the levels of inflammatory factors TNF-α, IL-6, IL-1ß, MCP-1, VCAM-1 and ICAM-1 in HUVECs, and inhibited endothelial inflammation. This study revealed the active ingredients of RPR-CM, and identified the key downstream targets and signaling pathways in the treatment of AS, providing theoretical basis for the application of RPR-CM in prevention and treatment of AS.

17.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 462-465, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38953272

ABSTRACT

Intraspinal metastasis from malignant carcinomas in other body parts is rarely reported.Intraspinal metastases are often epidural,with primary tumors mostly from the lung and prostate.The extramedullary subdural metastasis of thymic carcinoma is particularly rare and prone to misdiagnosis due to overlapping imaging features with primary intraspinal tumors.This article reports one case of intraspinal metastasis of thymic carcinoma,with the main diagnostic clues including a history of thymic carcinoma,fast growth rate,and irregular shape.


Subject(s)
Thymoma , Thymus Neoplasms , Humans , Thymus Neoplasms/pathology , Thymus Neoplasms/diagnostic imaging , Male , Thymoma/pathology , Thymoma/diagnostic imaging , Thymoma/secondary , Spinal Neoplasms/secondary , Spinal Neoplasms/diagnostic imaging , Middle Aged
18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 435-443, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38953268

ABSTRACT

With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification (PTM) has demonstrated increasing potential in medical research.PTM as a novel chemical modification method provides new perspectives for the research on diseases.Succinylation as a novel modification has aroused the interest of more and more researchers.The available studies about succinylation mainly focus on a desuccinylase named sirtuin 5.This enzyme plays a key role in modification and has been preliminarily explored in cardiovascular studies.This paper summarizes the influencing factors and regulatory roles of succinylation and the links between succinylation and other PTMs and reviews the research progress of PTMs in the cardiovascular field,aiming to deepen the understanding about the role of this modification and give new insights to the research in this field.


Subject(s)
Cardiovascular Diseases , Lysine , Protein Processing, Post-Translational , Cardiovascular Diseases/metabolism , Humans , Lysine/metabolism , Succinic Acid/metabolism
19.
ACS Omega ; 9(25): 27104-27112, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38947830

ABSTRACT

The combustion of lithium-ion batteries is characterized by fast ignition, prolonged duration, high combustion temperature, release of significant energy, and generation of a large number of toxic gases. Fine water mist has characteristics such as a high fire extinguishing efficiency and environmental friendliness. In order to thoroughly investigate the temperature control effect of fine water mist on lithium-ion battery fires. This study employs numerical simulation methods, utilizing PyroSim software to simulate the fire process in lithium-ion battery energy storage compartments. First, we focus on the variation patterns of flame, changes in combustion temperature, and heat release rate over time at environmental temperatures of 10, 25, and 35 °C. Subsequently, the suppression of flame, reduction in temperature, and changes in heat release rate are simulated for water mist in lithium-ion battery fires. The simulation results indicate that the environmental temperature has a considerable impact on the flame but a lesser effect on the heat release rate. Fine water mist effectively impedes the spread of thermal runaway between internal battery core cells, leading to a reduction in the flame size and a significant decrease in the maximum temperature and heat release rate. The numerical simulation results can provide scientific guidance for the prevention and control of fires in lithium-ion battery energy storage compartments.

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