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1.
Front Public Health ; 12: 1351568, 2024.
Article En | MEDLINE | ID: mdl-38689767

Introduction: Physical and mental health problems among pilots affect their working state and impact flight safety. Although pilots' physical and mental health problems have become increasingly prominent, their health has not been taken seriously. This study aimed to clarify challenges and support needs related to psychological and physical health among pilots to inform development of a more scientific and comprehensive physical and mental health system for civil aviation pilots. Methods: This qualitative study recruited pilots from nine civil aviation companies. Focus group interviews via an online conference platform were conducted in August 2022. Colaizzi analysis was used to derive themes from the data and explore pilots' experiences, challenges, and support needs. Results: The main sub-themes capturing pilots' psychological and physical health challenges were: (1) imbalance between family life and work; (2) pressure from assessment and physical examination eligibility requirements; (3) pressure from worries about being infected with COVID-19; (4) nutrition deficiency during working hours; (5) changes in eating habits because of the COVID-19 pandemic; (6) sleep deprivation; (7) occupational diseases; (8) lack of support from the company in coping with stress; (9) pilots' yearly examination standards; (10) support with sports equipment; (11) respecting planned rest time; and (12) isolation periods. Discussion: The interviewed pilots experienced major psychological pressure from various sources, and their physical health condition was concerning. We offer several suggestions that could be addressed to improve pilots' physical and mental health. However, more research is needed to compare standard health measures for pilots around the world in order to improve their physical and mental health and contribute to overall aviation safety.


COVID-19 , Focus Groups , Pilots , Qualitative Research , Humans , Male , Adult , COVID-19/psychology , COVID-19/epidemiology , Pilots/psychology , Middle Aged , Female , Mental Health , Health Status , Adaptation, Psychological , SARS-CoV-2 , Occupational Health
2.
Article En | MEDLINE | ID: mdl-38730034

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

3.
BMC Emerg Med ; 24(1): 78, 2024 May 01.
Article En | MEDLINE | ID: mdl-38693496

OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.


Blood Pressure , Emergency Service, Hospital , Sepsis , Shock, Septic , Humans , Male , Female , Child , Shock, Septic/mortality , Shock, Septic/diagnosis , Shock, Septic/physiopathology , Child, Preschool , Infant , Adolescent , Sepsis/mortality , Sepsis/diagnosis , Sepsis/complications , Sepsis/physiopathology , Retrospective Studies , Organ Dysfunction Scores , Disease Progression , Fever , Hospital Mortality
4.
J Alzheimers Dis ; 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38669531

Background: Neuroinflammation is a major cause of secondary brain injury in intracerebral hemorrhage (ICH). To date, the prognostic value of YKL-40 (chitinase-3-like-1 protein), a biomarker of neuroinflammation, in cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-ICH) remains undiscovered. Objective: To evaluate the relationships between serum YKL-40 and CAA-ICH recurrence. Methods: Clinical and imaging information of 68 first-onset probable CAA-ICH cases and 95 controls were collected at baseline. Serum YKL-40 was measured by Luminex assay. Cox proportional hazards model was used to analyze the associations between YKL-40 level and CAA-ICH recurrence. Results: Serum YKL-40 level was significantly higher in CAA-ICH cases than healthy controls (median [interquartile range, IQR], 46.1 [19.8, 93.4] versus 24.4 [13.9, 59.0] ng/mL, p = 0.004). Higher level of YKL-40 predicted increased risk of CAA-ICH recurrence adjusted for age, ICH volume and enlarged perivascular space score (ePVS) (above versus below 115.5 ng/ml, adjusted hazard ratios 4.721, 95% confidence intervals 1.829-12.189, p = 0.001) within a median follow-up period of 2.4 years. Adding YKL-40 to a model of only MRI imaging markers including ICH volume and ePVS score improved the discriminatory power (concordance index from 0.707 to 0.772, p = 0.001) and the reclassification power (net reclassification improvement 28.4%; integrated discrimination index 11.0%). Conclusions: Serum YKL-40 level might be a candidate prognostic biomarker for CAA-ICH recurrence.

5.
Orphanet J Rare Dis ; 19(1): 155, 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38605407

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.


Benzhydryl Compounds , Glycogen Storage Disease Type I , Sodium-Glucose Transporter 2 Inhibitors , Child , Humans , Antiporters , Follow-Up Studies , Glucose , Glucosides , Glycogen Storage Disease Type I/drug therapy , Hypoglycemia , Monosaccharide Transport Proteins/genetics , Neutropenia , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
6.
Adv Sci (Weinh) ; : e2400642, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38647258

Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone-related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones.

7.
Violence Against Women ; 30(8): 1804-1824, 2024 Jun.
Article En | MEDLINE | ID: mdl-38571462

This study examines how the age of female survivors impacts public perceptions of rape in China. In our online survey experiment, participants consider rape as less serious when the survivor is a middle-aged woman compared to other groups of women (younger, older, or age unknown). Participants also request shorter sentencing when the survivor is a middle-aged woman than a younger woman. In China, moral codes surrounding chastity and respect for elders lead to greater emotional responses toward rape against younger and older survivors than middle-aged survivors. Our study expands studies of rape perception by theorizing public attitudes toward middle-aged survivors.

8.
Sci Rep ; 14(1): 8193, 2024 04 08.
Article En | MEDLINE | ID: mdl-38589544

The study aimed to determine the specific relative biological effectiveness (RBE) of various cells in the hippocampus following proton irradiation. Sixty Sprague-Dawley rats were randomly allocated to 5 groups receiving 20 or 30 Gy of proton or photon irradiation. Pathomorphological neuronal damage in the hippocampus was assessed using Hematoxylin-eosin (HE) staining. The expression level of NeuN, Nestin, Caspase-3, Olig2, CD68 and CD45 were determined by immunohistochemistry (IHC). The RBE range established by comparing the effects of proton and photon irradiation at equivalent biological outcomes. Proton20Gy induced more severe damage to neurons than photon20Gy, but showed no difference compared to photon30Gy. The RBE of neuron was determined to be 1.65. Similarly, both proton20Gy and proton30Gy resulted in more inhibition of oligodendrocytes and activation of microglia in the hippocampal regions than photon20Gy and photon30Gy. However, the expression of Olig2 was higher and CD68 was lower in the proton20Gy group than in the photon30Gy group. The RBE of oligodendrocyte and microglia was estimated to be between 1.1 to 1.65. For neural stem cells (NSCs) and immune cells, there were no significant difference in the expression of Nestin and CD45 between proton and photon irradiation (both 20 and 30 Gy). Therefore, the RBE for NSCs and immune cell was determined to be 1.1. These findings highlight the varying RBE values of different cells in the hippocampus in vivo. Moreover, the actual RBE of the hippocampus may be higher than 1.1, suggesting that using as RBE value of 1.1 in clinical practice may underestimate the toxicities induced by proton radiation.


Proton Therapy , Protons , Rats , Animals , Proton Therapy/methods , Nestin , Relative Biological Effectiveness , Rats, Sprague-Dawley , Hippocampus
9.
BMC Cancer ; 24(1): 435, 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38589858

BACKGROUND: To establish and validate a predictive model combining pretreatment multiparametric MRI-based radiomic signatures and clinical characteristics for the risk evaluation of early rapid metastasis in nasopharyngeal carcinoma (NPC) patients. METHODS: The cutoff time was used to randomly assign 219 consecutive patients who underwent chemoradiation treatment to the training group (n = 154) or the validation group (n = 65). Pretreatment multiparametric magnetic resonance (MR) images of individuals with NPC were employed to extract 428 radiomic features. LASSO regression analysis was used to select radiomic features related to early rapid metastasis and develop the Rad-score. Blood indicators were collected within 1 week of pretreatment. To identify independent risk variables for early rapid metastasis, univariate and multivariate logistic regression analyses were employed. Finally, multivariate logistic regression analysis was applied to construct a radiomics and clinical prediction nomogram that integrated radiomic features and clinical and blood inflammatory predictors. RESULTS: The NLR, T classification and N classification were found to be independent risk indicators for early rapid metastasis by multivariate logistic regression analysis. Twelve features associated with early rapid metastasis were selected by LASSO regression analysis, and the Rad-score was calculated. The AUC of the Rad-score was 0.773. Finally, we constructed and validated a prediction model in combination with the NLR, T classification, N classification and Rad-score. The area under the curve (AUC) was 0.936 (95% confidence interval (95% CI): 0.901-0.971), and in the validation cohort, the AUC was 0.796 (95% CI: 0.686-0.905). CONCLUSIONS: A predictive model that integrates the NLR, T classification, N classification and MR-based radiomics for distinguishing early rapid metastasis may serve as a clinical risk stratification tool for effectively guiding individual management.


Multiparametric Magnetic Resonance Imaging , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/therapy , Radiomics , Biomarkers , Nomograms , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/therapy , Retrospective Studies
10.
J Sci Food Agric ; 2024 Mar 13.
Article En | MEDLINE | ID: mdl-38477402

BACKGROUND: The structural changes of starch would have a more crucial impact on oil absorption and quality changes in starch-rich fruits and vegetables during frying process with enhanced heat transfer (such as infrared frying). In the present study, the influence of integrated ultrasonic and ethanol (US + ethanol) pretreatment on oil uptake in infrared fried (IF) ginkgo seeds was evaluated regarding modifications in the physicochemical properties of starch. The pretreatment was performed with ultrasonic (40 kHz, 300 W) and ethanol osmotic (95%, v/v) treatment individually or integrated for 40 min. RESULTS: The mass transfer in the pretreatment was facilitated by combined ultrasound and ethanol. The swelling power, solubility, and gelatinization degree of starch was significantly increased. Low-frequency-NMR curves and images revealed that the bound water fraction in ginkgo seeds was increased and the water distribution was homogenized. The results of Fourier transform-infrared spectrum and differential scanning calorimeter revealed that the crystalline regions of starch were reduced and the thermal enthalpy was decreased after US + ethanol pretreatment. The total, surface and structural oil content in IF ginkgo seeds with US + ethanol pretreatment was reduced by 29.10%, 34.52% and 29.73%, respectively. The US + ethanol pretreatment led to a thinner crust layer with increased porosity and smaller-sized pores in the IF ginkgo seeds as observed by stereo microscopy and scanning electron microscopy. CONCLUSION: The changes in structural and physicochemical properties of starch by combined ultrasound and ethanol affect the crust ratio and pore characteristics in fried high-starch fruits and vegetables, thereby reducing oil absorption. © 2024 Society of Chemical Industry.

11.
J Cancer Surviv ; 2024 Mar 21.
Article En | MEDLINE | ID: mdl-38512563

PURPOSE: To identify risk factors of chemotherapy-related cognitive impairment (CRCI) and construct and validate a visual prediction model of such for patients with breast cancer. METHODS: A multicenter, descriptive, and cross-sectional design was adopted. Data were collected from ten public tertiary hospitals in China. Cognitive function was assessed by using Functional Assessment of Cancer Therapy-cognitive function. Socio-demographic, clinical, psychological, and physical indicators were also assessed. The logistic prediction model was constructed by fivefold cross-validation. Then, a nomogram was utilized to visualize the prediction model, which was also evaluated via discrimination, calibration, and decision curve analysis. RESULTS: A total of 71 breast cancer patients had CRCI with a prevalence of 9.58%. This visual prediction model was constructed based on education background, exercise frequency, chemotherapy times, and fatigue and demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.882. The calibration curve indicated good agreement between experimental and projected values, and the decision curve proved good clinical applicability. CONCLUSION: Education background, exercise frequency, chemotherapy times, and fatigue were associated with high incidence of CRCI. The prediction model exhibits superior performance and has promise as a useful instrument for assessing the likelihood of CRCI in breast cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: Our findings could provide breast cancer survivors with risk screening based on CRCI predictors to implement prevention and early intervention, and help patients integrate into society and achieve comprehensive recovery.

12.
Biomed Pharmacother ; 173: 116406, 2024 Apr.
Article En | MEDLINE | ID: mdl-38460366

Sanguinarine is a quaternary ammonium benzophenanthine alkaloid found in traditional herbs such as Chelidonium, Corydalis, Sanguinarum, and Borovula. It has been proven to possess broad-spectrum biological activities, such as antitumor, anti-inflammatory, antiosteoporosis, neuroprotective, and antipathogenic microorganism activities. In this paper, recent progress on the biological activity and mechanism of action of sanguinarine and its derivatives over the past ten years is reviewed. The results showed that the biological activities of hematarginine and its derivatives are related mainly to the JAK/STAT, PI3K/Akt/mTOR, NF-κB, TGF-ß, MAPK and Wnt/ß-catenin signaling pathways. The limitations of using sanguinarine in clinical application are also discussed, and the research prospects of this subject are outlined. In general, sanguinarine, a natural medicine, has many pharmacological effects, but its toxicity and safety in clinical application still need to be further studied. This review provides useful information for the development of sanguinarine-based bioactive agents.


Alkaloids , Phosphatidylinositol 3-Kinases , Phosphatidylinositol 3-Kinases/metabolism , Benzophenanthridines/pharmacology , Alkaloids/metabolism , Isoquinolines/pharmacology
13.
Stroke Vasc Neurol ; 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38553035

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a relatively rare and treatable subtype of CAA. We have herein reported a case of CAA-ri with repeated recurrent lobar haemorrhages within a short time as the main manifestations and effectively treated with immunosuppressive therapy. Our case expanded the clinical spectrum of CAA-ri and indicated that leptomeningeal inflammation might be a trigger and bleeding source for recurrent haemorrhage in CAA.

14.
Bioresour Technol ; 399: 130623, 2024 May.
Article En | MEDLINE | ID: mdl-38518876

Livestock manure often contains various pollutants. The aim of this study was to investigate how adding amoxicillin (AMX), Cu, and both AMX and Cu (ACu) affected humification during composting and the microbial mechanisms involved. The cellulose degradation rates were 16.96%, 10.86%, and 9.01% lower, the humic acid contents were 18.71%, 12.89%, and 16.78% lower, and the humification degrees were 24.72%, 24.16%, and 15.73% lower for the AMX, Cu, and ACu treatments, respectively, than the control. Adding AMX and Cu separately or together inhibited humic acid formation and decreased the degree of humification, but the degree of humification was decreased less by ACu than by AMX or Cu separately. The ACu treatment decreased the number of core bacteria involved in humic acid formation and decreased carbohydrate and amino acid metabolism during the maturing period, and thereby delayed humic acid formation and humification. The results support composting manure containing AMX and Cu.


Composting , Humic Substances , Animals , Cattle , Amoxicillin , Soil , Copper , Manure
15.
Ecotoxicol Environ Saf ; 274: 116191, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38460408

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 µg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.


Marine Toxins , Microcystins , Sirtuins , Spermatogonia , Animals , Male , Mice , Apoptosis , Cell Proliferation , DNA Breaks, Double-Stranded/drug effects , DNA Repair , Marine Toxins/metabolism , Marine Toxins/toxicity , Mice, Inbred ICR , Microcystins/metabolism , Microcystins/toxicity , Semen , Sirtuins/drug effects , Sirtuins/metabolism , Spermatogonia/drug effects , Spermatogonia/metabolism
16.
Chem Biodivers ; 21(5): e202400210, 2024 May.
Article En | MEDLINE | ID: mdl-38433548

Currently, natural products are one of the priceless options for finding novel chemical pharmaceutical entities. Ellipticine is a naturally occurring alkaloid isolated from the leaves of Ochrosia elliptica Labill. Ellipticine and its derivatives are characterized by multiple biological activities. The purpose of this review was to provide a critical and systematic assessment of ellipticine and its derivatives as bioactive molecules over the last 60 years. Publications focused mainly on the total synthesis of alkaloids of this type without any evaluation of bioactivity have been excluded. We have reviewed papers dealing with the synthesis, bioactivity evaluation and mechanism of action of ellipticine and its derivatives. It was found that ellipticine and its derivatives showed cytotoxicity, antimicrobial ability, and anti-inflammatory activity, among which cytotoxicity toward cancer cell lines was the most investigated aspect. The inhibition of DNA topoisomerase II was the most relevant mechanism for cytotoxicity. The PI3K/AKT pathway, p53 pathway, and MAPK pathway were also closely related to the antiproliferative ability of these compounds. In addition, the structure-activity relationship was deduced, and future prospects were outlined. We are confident that these findings will lay a scientific foundation for ellipticine-based drug development, especially for anticancer agents.


Ellipticines , Ellipticines/pharmacology , Ellipticines/chemistry , Humans , Structure-Activity Relationship , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Proliferation/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Molecular Structure , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification
17.
Bioorg Med Chem ; 102: 117656, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38422567

Urease is the main virulence factor of infectious gastritis and gastric ulcers. Urease inhibitors are regarded as the first choice for the treatment of such diseases. Based on the triazolone/oxadiazolone skeleton, a urea-like fragment being able to specifically bind the urease activity pocket and prevent urea from hydrolysis, we designed and synthesized 45 triazolones/oxadiazolones as urease inhibitors. Eight compounds were proved to show excellent inhibitory activity against Helicobacter pylori urease, being more potency than the clinically used urease inhibitor acetohydroxamic acid. The most active inhibitor with IC50 value of 1.2 µM was over 20-fold higher potent than the positive control. Enzymatic kinetic assays showed that these novel inhibitors reversibly inhibited urease with a mixed competitive mechanism. Molecular dockings provided evidence for the observations in enzyme assays. Furthermore, these novel inhibitors were proved as drug-like compounds with very low cytotoxicity to mammalian cells and favorable water solubility. These results suggested that triazolone and oxadiazolone were promising scaffolds for the design and discovery of novel urease inhibitors, and were expected as good candidates for further drug development.


Helicobacter pylori , Stomach Ulcer , Animals , Urease , Molecular Docking Simulation , Urea , Enzyme Inhibitors/pharmacology , Mammals/metabolism
18.
Sci Rep ; 14(1): 4243, 2024 02 20.
Article En | MEDLINE | ID: mdl-38378889

SARS-CoV-2 and its variants are widely prevalent worldwide. With frequent secondary and breakthrough infections, immune dysfunction in RA patients, and long-term use of immune preparations, SARS-CoV-2 infection poses a significant challenge to patients and rheumatologists. Whether SARS-CoV-2 infection causes RA flares and what factors aggravate RA flares are poorly studied. A questionnaire survey was conducted on RA patients infected with SARS-CoV-2 after December 7, 2022, in China through a multicenter and inter-network platform regarding general personal condition, primary disease, comorbidity, SARS-CoV-2 vaccination, viral infection, and impact on the primary disease. A total of 306 RA patients were included in this study, and the patient data were analyzed, in which the general condition of RA patients, medication use before SARS-CoV-2 infection and post-infection typing and manifestations, and medication adjustment did not affect the Flare of RA patients after SARS-CoV-2 infection. The control of disease before SARS-CoV-2 infection (OR = 2.10), RA involving pulmonary lesions (OR = 2.28), and the recovery time of COVID-19 (OR = 2.50) were risk factors for RA flare. RA involving pulmonary lesions, control status of disease before infection, and recovery time of COVID-19 disease are risk factors for RA flare after SARS-CoV-2 infection.


COVID-19 , Humans , COVID-19/epidemiology , Retrospective Studies , SARS-CoV-2 , COVID-19 Vaccines , China/epidemiology
19.
Radiat Oncol ; 19(1): 18, 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38317205

PURPOSE: This study seeks to examine the influence of the heartbeat on the position, volume, and shape of the heart and its substructures during various breathing states. The findings of this study will serve as a valuable reference for dose-volume evaluation of the heart and its substructures in radiotherapy for treating thoracic tumors. METHODS: Twenty-three healthy volunteers were enrolled in this study, and cine four-dimensional magnetic resonance images were acquired during periods of end-inspiration breath holding (EIBH), end-expiration breath holding (EEBH), and deep end-inspiration breath holding (DIBH). The MR images were used to delineate the heart and its substructures, including the heart, pericardium, left ventricle (LV), left ventricular myocardium, right ventricle (RV), right ventricular myocardium (RVM), ventricular septum (VS), atrial septum (AS), proximal and middle portions of the left anterior descending branch (pmLAD), and proximal portion of the left circumflex coronary branch (pLCX). The changes in each structure with heartbeat were compared among different respiratory states. RESULTS: Compared with EIBH, EEBH increased the volume of the heart and its substructures by 0.25-3.66%, while the average Dice similarity coefficient (DSC) increased by - 0.25 to 8.7%; however, the differences were not statistically significant. Conversely, the VS decreased by 0.89 mm in the left-right (LR) direction, and the displacement of the RV in the anterior-posterior (AP) direction significantly decreased by 0.76 mm (p < 0.05). Compared with EIBH and EEBH, the average volume of the heart and its substructures decreased by 3.08-17.57% and 4.09-20.43%, respectively, during DIBH. Accordingly, statistically significant differences (p < 0.05) were observed in the volume of the heart, pericardium, LV, RV, RVM, and AS. The average DSC increased by 0-37.04% and - 2.6 to 32.14%, respectively, with statistically significant differences (p < 0.05) found in the right ventricular myocardium and interatrial septum. Furthermore, the displacements under DIBH decreased in the three directions (i.e.,- 1.73 to 3.47 mm and - 0.36 to 2.51 mm). In this regard, the AP displacement of the heart, LV, RV, RVM, LR direction, LV, RV, and AS showed statistically significant differences (p < 0.05). The Hausdorff distance (HD) of the heart and its substructures under the three breathing states are all greater than 11 mm. CONCLUSION: The variations in the displacement and shape alterations of the heart and its substructures during cardiac motion under various respiratory states are significant. When assessing the dose-volume index of the heart and its substructures during radiotherapy for thoracic tumors, it is essential to account for the combined impacts of cardiac motion and respiration.


Heart , Thoracic Neoplasms , Humans , Heart Rate , Respiration , Heart Ventricles , Breath Holding , Radiotherapy Planning, Computer-Assisted/methods
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