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1.
Ophthalmol Ther ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020238

ABSTRACT

INTRODUCTION: The purpose of the study was to explore the possible correlations between the anterior segment parameters derived from anterior segment swept-source optical coherence tomography (AS-SS-OCT) with the surgically induced corneal astigmatism (CSIA) calculated from total keratometry (TK) measured by AS-SS-OCT. METHODS: Seventy-one eyes of 67 patients with age-related cataract who underwent phacoemulsification combined with intraocular lens implantation with 2.2-mm incision were included. The CSIA values were calculated from anterior keratometry (CSIAKant) and TK (CSIATK) measured by AS-SS-OCT, respectively. Hotelling's T2 test was used to evaluate the difference. The correlation of CSIA with various parameters derived from AS-SS-OCT was tested with the Spearman correlation coefficient. RESULTS: The centroid of CSIAKant and of CSIATK were 0.31 ± 0.55 D @ 54° and 0.41 ± 0.59 D @ 51°, with no significant difference (F = 1.283, p = 0.281, Hotelling's T2). The mean absolute CSIAKant and CSIATK were 0.58 ± 0.24 D and 0.65 ± 0.28 D. Spearman test showed that the magnitude of CSIAKant was negatively correlated with preoperative peripheral corneal thickness (PCT, p = 0.045) and the magnitude of anterior keratometry (p = 0.044). The magnitude of CSIATK was negatively correlated with preoperative central corneal thickness (CCT, p = 0.003) and preoperative PCT (p = 0.015). CONCLUSIONS: The increased thickness of the peripheral cornea is correlated with the decrease in the magnitude of the CSIA. The correlation we identified between the corneal thickness and the CSIA indicated that certain preoperative parameters should be considered for the prediction of CSIA for a more precise refractive outcome.

2.
Clin Exp Med ; 24(1): 153, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38972923

ABSTRACT

Rheumatoid arthritis (RA) is a common autoimmune rheumatic disease that causes chronic synovitis, bone erosion, and joint destruction. The autoantigens in RA include a wide array of posttranslational modified proteins, such as citrullinated proteins catalyzed by peptidyl arginine deiminase4a. Pathogenic anti-citrullinated protein antibodies (ACPAs) directed against a variety of citrullinated epitopes are abundant both in plasma and synovial fluid of RA patients. ACPAs play an important role in the onset and progression of RA. Intensive and extensive studies are being conducted to unveil the mechanisms of RA pathogenesis and evaluate the efficacy of some investigative drugs. In this review, we focus on the formation and pathogenic function of ACPAs.


Subject(s)
Anti-Citrullinated Protein Antibodies , Arthritis, Rheumatoid , Humans , Arthritis, Rheumatoid/immunology , Anti-Citrullinated Protein Antibodies/immunology , Autoantigens/immunology , Synovial Fluid/immunology , Synovial Fluid/metabolism
3.
BMC Med Educ ; 24(1): 759, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010040

ABSTRACT

BACKGROUND: International student education has become an important part of higher education and an important symbol to measure the level of higher education. To change the traditional teaching model, here we introduced a combination of Case-Based Learning (CBL)and Flipped Classroom (FC) into the pathophysiology course for international students. This study aimed to explore whether the active learning ability and critical thinking ability of international students can be improved, based on this new teaching model, improving the innovation ability of teachers' team and students' attitude to the reform. METHODS: The two chapters of Cardiac Insufficiency and Apoptosis in Pathophysiology are designed as a CBL + FC teaching method. Distribute the Self-assessment Scale on Active Learning and Critical Thinking (SSACT) and satisfaction questionnaire to international students to evaluate teaching reform based on CBL + FC. RESULTS: Compared with the traditional classroom, the online flipped classroom based on CBL has significantly improved the learning enthusiasm, as these students are required to independently complete literature review, actively participate in classroom teaching, learn to use multiple learning strategies, and collaborate with other students to complete PowerPoint (PPT)production. At the same time, the students' ability to raise problems and solve problems has been greatly improved by analyzing clinical cases; By consulting the literature, the theoretical knowledge learned can be better applied to clinical analysis. The results of the satisfaction survey also show that international students are more likely to accept the flipped classroom teaching mode. CONCLUSIONS: This teaching mode will stimulate the learning motivation of international students, enhance teaching attraction and increase teaching interaction; At the same time, the CBL + FC teaching method can strengthen the evaluation of international students' in and out of class and online learning, enhance students' active learning ability and critical thinking ability, promote the development of personalized learning, and integrate with international medical education.


Subject(s)
Problem-Based Learning , Thinking , Humans , Problem-Based Learning/methods , Students, Medical , Curriculum , Models, Educational , Surveys and Questionnaires , Educational Measurement , Education, Medical, Undergraduate/methods , Male
4.
Cancers (Basel) ; 16(14)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39061136

ABSTRACT

CAR-T cell-based therapies have demonstrated remarkable efficacy in treating malignant cancers, especially liquid tumors, and are increasingly being evaluated in clinical trials for solid tumors. With the FDA's initiative to advance alternative methods for drug discovery and development, full human ex vivo assays are increasingly essential for precision CAR-T development. However, prevailing ex vivo CAR-T cell-mediated cytotoxicity assays are limited by their use of radioactive materials, lack of real-time measurement, low throughput, and inability to automate, among others. To address these limitations, we optimized the assay using multimodality imaging methods, including bioluminescence, impedance tracking, phase contrast, and fluorescence, to track CAR-T cells co-cultured with CD19, CD20, and HER2 luciferase reporter cancer cells in real-time. Additionally, we varied the ratio of CAR-T cells to cancer cells to determine optimal cytotoxicity readouts. Our findings demonstrated that the CAR-T cell group effectively attacked cancer cells, and the optimized assay provided superior temporal and spatial precision measurements of ex vivo CAR-T killing of cancer cells, confirming the reliability, consistency, and high throughput of the optimized assay.

5.
Brain Behav ; 14(7): e3633, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39054262

ABSTRACT

OBJECTIVE: In vascular dementia (VD), memory impairment caused by the damage of synaptic plasticity is the most prominent feature that afflicts patients and their families. Treadmill exercise has proven beneficial for memory by enhancing synaptic plasticity in animal models including stroke, dementia, and mental disorders. The aim of this study was to examine the effects of treadmill exercise on recognition memory and structural synaptic plasticity in VD rat model. METHODS: Male Sprague-Dawley rats were randomly assigned into four groups: control group (C group, n = 6), vascular dementia group (VD group, n = 6), treadmill exercise and vascular dementia group (Exe-VD group, n = 6), and treadmill exercise group (Exe group, n = 6). Four-week treadmill exercise was performed in the Exe-VD and Exe groups. Then, the common carotid arteries of rats in the VD and Exe-VD groups were identified to establish the VD model. Behavior tests (open-field test and novel recognition memory test) were adopted to evaluate anxiety-like behavior and recognition memory. Transmission electron microscopy and Golgi staining were performed to observe synaptic ultrastructure and spine density in the hippocampus. RESULTS: Our study demonstrated that VD rat exhibited significantly anxiety-like behavior and recognition impairment (p < .01), while treadmill exercise significantly alleviated anxiety-like behavior and improved recognition memory in VD rat (p < .01). Transmission electron microscopy revealed that hippocampal synapse numbers were significantly decreased in the VD group compared to the control group (p < .05). These alterations were reversed by treadmill exercise, and the rats exhibited healthier synaptic ultrastructure, including significantly increased synapse (p < .05). Meanwhile, golgi staining revealed that the spine numbers of the hippocampus were significantly decreased in the VD group compared to the control group (p < .05). When compared with the VD group, hippocampal spine numbers were significantly increased in the Exe-VD group (p < .05). CONCLUSION: The improvement of VD-associated recognition memory by treadmill exercises is associated with enhanced structural synaptic plasticity in VD rat model.


Subject(s)
Dementia, Vascular , Disease Models, Animal , Hippocampus , Memory Disorders , Neuronal Plasticity , Physical Conditioning, Animal , Rats, Sprague-Dawley , Recognition, Psychology , Animals , Neuronal Plasticity/physiology , Male , Hippocampus/physiopathology , Recognition, Psychology/physiology , Rats , Physical Conditioning, Animal/physiology , Memory Disorders/physiopathology , Memory Disorders/etiology , Memory Disorders/therapy , Dementia, Vascular/physiopathology , Dementia, Vascular/therapy , Synapses/physiology , Anxiety/therapy , Anxiety/physiopathology
6.
Sci Rep ; 14(1): 15431, 2024 07 04.
Article in English | MEDLINE | ID: mdl-38965239

ABSTRACT

To detect the contaminate of faucets in hospitals and the splash during hand washing, and to explore the reasonable layout of hand washing pools. Two faucets with roughly the same spatial layout in the ICU of a third-class first-class general hospital were selected, and the farthest splashing distance and specific splashing points were measured by color paper. Samples were detected by ATP detection technology and routine microbial detection method, and the contaminate of faucets was analyzed. After 72 h of daily hand-washing activities, the furthest distance to the splash point was about 100 cm around the faucet, and the place 40-110 cm around the faucet was contaminated seriously. The farthest distance that the splash point reached was about 80 cm around the faucet with the center of the circle, and the area 40-60 cm around the faucet was heavily contaminated. The distance from the water outlet of the long handle and the short handle faucet to the detection point had a high negative correlation (r = - 0.811, P < 0.001) and a moderate negative correlation (r = - 0.475, P = 0.001) with the number of splash points, respectively. The qualified rates of ATP detection and microbial culture were 25% and 15%, respectively. Pseudomonas aeruginosa, Staphylococcus epidermidis, and other pathogenic bacteria were detected in the water outlet of the faucet and the surrounding environment. Safe hand hygiene facilities are one of the important guarantees of hand hygiene effect. Clean objects and objects related to patients should not be placed within 1 m range near the water outlet of faucet. Anti-splash baffle should be installed as much as possible when conditions permit to reduce the contaminate caused by splash during hand washing.


Subject(s)
Hand Disinfection , Intensive Care Units , Humans , Cross Infection/prevention & control
7.
Int Ophthalmol ; 44(1): 233, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886282

ABSTRACT

PURPOSE: Intraocular irrigating solution is extensively applied in cataract surgery. This paper explored the difference and relationship between optical coherence tomography (OCT) and optical quality analysis system (OQAS) parameters induced by compound electrolyte intraocular irrigating solution (CEIIS) or Ringer lactate (RL) solution during uncomplicated cataract surgery. METHODS: Totally 200 senior cataract patients were randomly divided into the CEIIS and RL groups (N = 100 patients/group). The anterior chamber was irrigated by CEIIS or RL during phacoemulsification. Patients were subdivided into diabetes mellitus (DM)+ and DM- groups. The central macular thickness (CMT), hyper reflective foci (HF), modulation transfer function cutoff frequency (MTF cutoff), Strehl ratio (SR), objective scatter index (OSI), and OQAS values (OVs) at 100%, 20%, and 9% contrast levels were measured preoperatively and 1 day and 1 week after operation using spectral-domain optical coherence tomography and OQAS II, respectively. Best-corrected visual acuity (BCVA) was assessed using the Snellen scale, followed by statistical analysis of its logarithm of the minimal angle of resolution. RESULTS: There were no significant differences in clinical characteristics between the CEIIS and RL groups. Both groups exhibited notably increased postoperative CMT, MTF cutoff, SR, OV at 100%, 20%, and 9% contrast levels, and reduced OSI, indicating CEIIS and RL improved postoperative visual quality. CEIIS surpassed RL solution in improving postoperative visual quality, decelerating the increase of macular HF numbers and CMT in DM+ patients and postoperative BCVA. There was no difference between CEIIS and RL in long-term vision improvement. CONCLUSION: CEIIS surpasses RL in postoperative visual recovery and retards increases of macular HF numbers and CMT in senior DM+ cataract patients.


Subject(s)
Phacoemulsification , Ringer's Lactate , Tomography, Optical Coherence , Visual Acuity , Humans , Female , Male , Aged , Tomography, Optical Coherence/methods , Ringer's Lactate/administration & dosage , Phacoemulsification/methods , Middle Aged , Therapeutic Irrigation/methods , Electrolytes/administration & dosage , Recovery of Function , Cataract/complications , Prospective Studies , Ophthalmic Solutions/administration & dosage
9.
Cancers (Basel) ; 16(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38893085

ABSTRACT

Recent studies highlight the integral role of the interferon gamma receptor (IFNγR) pathway in T cell-mediated cytotoxicity against solid but not liquid tumors. IFNγ not only directly facilitates tumor cell death by T cells but also indirectly promotes cytotoxicity via myeloid phagocytosis in the tumor microenvironment. Meanwhile, full human ex vivo immune checkpoint drug screening remains challenging. We hypothesized that an engineered gamma interferon activation site response element luciferase reporter (GAS-Luc2) can be utilized for immune checkpoint drug screening in diverse ex vivo T cell-solid tumor cell co-culture systems. We comprehensively profiled cell surface proteins in ATCC's extensive collection of human tumor and immune cell lines, identifying those with endogenously high expression of established and novel immune checkpoint molecules and binding ligands. We then engineered three GAS-Luc2 reporter tumor cell lines expressing immune checkpoints PD-L1, CD155, or B7-H3/CD276. Luciferase expression was suppressed upon relevant immune checkpoint-ligand engagement. In the presence of an immune checkpoint inhibitor, T cells released IFNγ, activating the JAK-STAT pathway in GAS-Luc2 cells, and generating a quantifiable bioluminescent signal for inhibitor evaluation. These reporter lines also detected paracrine IFNγ signaling for immune checkpoint-targeted ADCC drug screening. Further development into an artificial antigen-presenting cell line (aAPC) significantly enhanced T cell signaling for superior performance in these ex vivo immune checkpoint drug screening platforms.

10.
J Nanobiotechnology ; 22(1): 368, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918787

ABSTRACT

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.


Subject(s)
Bone Cements , Calcitonin Gene-Related Peptide , Calcium Phosphates , Osteogenesis , Swine, Miniature , Animals , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Bone Cements/pharmacology , Bone Cements/chemistry , Mice , Swine , Calcitonin Gene-Related Peptide/metabolism , Osteogenesis/drug effects , Bone Regeneration/drug effects , Spine/surgery , Ganglia, Spinal/metabolism , Ganglia, Spinal/drug effects , Cell Line , Magnesium/pharmacology , Magnesium/chemistry
11.
Foods ; 13(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38890861

ABSTRACT

Efficient thawing can preserve the quality of frozen hairtail (Trichiurus lepturus) close to that of fresh hairtail. In contrast to air thawing (AT) and radio-frequency thawing (RT), this study looked at how graphene oxide (GO) and graphene magnetic (GM) nanoparticles paired with RT affect the microstructure and protein conformation of hairtails after thawing. The results suggested that GM-RT can reduce the myofibrillar protein (MP) damage and be more effective than other thawing treatments, like AT, RT, and GO-RT, in maintaining the microstructure of hairtail. The particle size and zeta potential showed that GM-RT could reduce the aggregation of MP during the thawing process compared to other thawing methods. Moreover, the texture of the hairtail after GM-RT exhibited higher hardness (1185.25 g), elasticity (2.25 mm), and chewiness (5.75 mJ) values compared to other thawing treatments. Especially compared with RT, the GM-RT treatment displayed significant improvements in hardness (27.24%), a considerable increase in springiness (92.23%), and an increase in chewiness (57.96%). GO-RT and GM-RT significantly reduced the centrifugal loss. The scanning electron microscopy results demonstrated that the effect of GM-RT was more akin to that of a fresh sample (FS) and characterized by a well-organized microstructure. In conclusion, GM-RT effectively diminished the MP aggregation and improved the texture of thawed fish. It can be regarded as a viable alternative thawing technique to enhance MP stability, which is vital for preserving meat quality.

12.
J Ethnopharmacol ; 333: 118444, 2024 Oct 28.
Article in English | MEDLINE | ID: mdl-38851473

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Qiju Dihuang Pill (QDP) is a traditional Chinese medicine prescription for the treatment of eye diseases. Novel literature reports that copper-induced cell death, called as cuproptosis, is a copper-dependent and differs distinctly from other types of cell death. AIM OF THE STUDY: The present study aims to investigate whether QDP could protect lens epithelial cells via alleviating copper-induced death in diabetic cataract. MATERIALS AND METHODS: The different concentration of QDP medicated serum was administrated on high glucose (HG)-induced human lens epithelial cells (HLECs). The copper concentration was tested using Elabscience Copper Assay kit. The proliferation was detected using CCK-8 and EdU assays. The molecular binding was identified using RIP-PCR and luciferase reporter assay. RESULTS: Results indicated that HG culture condition triggered the copper concentration and repressed the proliferation of HLECs. Then, the elesclomol-Cu (Es-Cu) administration up-regulated the copper concentration and inhibited the proliferation, and cuproptosis inhibitor tetrathiomolybdate (TTM) could specifically reverse the consequence. QDP treatment reduced the copper concentration and cuproptosis-related genes (SLC31A1, FDX1). MeRIP-Seq and RIP-PCR confirmed that QDP reduced the stability of SLC31A1 mRNA through m6A modified site, and copper actually synergized the molecular binding efficiency. Rescue assay verified the role of QDP and SLC31A1 on HLECs' cuproptosis characteristic. CONCLUSION: This research identified the protective role of QDP on HG-induced HLECs in DC through decreasing m6A/SLC31A1-mediated cuproptosis in DC. This finding provides novel insights into mechanisms for QDP and sheds light on the multifaceted role of traditional prescription on DC.


Subject(s)
Cataract , Cell Proliferation , Copper , Drugs, Chinese Herbal , Epithelial Cells , Lens, Crystalline , Humans , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Cataract/drug therapy , Drugs, Chinese Herbal/pharmacology , Lens, Crystalline/drug effects , Lens, Crystalline/cytology , Lens, Crystalline/metabolism , Cell Proliferation/drug effects , Diabetes Complications/drug therapy , Glucose/metabolism , Cell Line , Cells, Cultured
13.
Nat Microbiol ; 9(7): 1828-1841, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38886583

ABSTRACT

Bacteriophages have evolved diverse strategies to overcome host defence mechanisms and to redirect host metabolism to ensure successful propagation. Here we identify a phage protein named Dap1 from Pseudomonas aeruginosa phage PaoP5 that both modulates bacterial host behaviour and contributes to phage fitness. We show that expression of Dap1 in P. aeruginosa reduces bacterial motility and promotes biofilm formation through interference with DipA, a c-di-GMP phosphodiesterase, which causes an increase in c-di-GMP levels that trigger phenotypic changes. Results also show that deletion of dap1 in PaoP5 significantly reduces genome packaging. In this case, Dap1 directly binds to phage HNH endonuclease, prohibiting host Lon-mediated HNH degradation and promoting phage genome packaging. Moreover, PaoP5Δdap1 fails to rescue P. aeruginosa-infected mice, implying the significance of dap1 in phage therapy. Overall, these results highlight remarkable dual functionality in a phage protein, enabling the modulation of host behaviours and ensuring phage fitness.


Subject(s)
Phage Therapy , Pseudomonas Infections , Pseudomonas Phages , Pseudomonas aeruginosa , Viral Proteins , Pseudomonas aeruginosa/virology , Pseudomonas aeruginosa/pathogenicity , Pseudomonas aeruginosa/genetics , Animals , Mice , Pseudomonas Phages/genetics , Pseudomonas Phages/physiology , Pseudomonas Infections/therapy , Pseudomonas Infections/microbiology , Pseudomonas Infections/immunology , Virulence , Viral Proteins/genetics , Viral Proteins/metabolism , Biofilms/growth & development , Cyclic GMP/metabolism , Cyclic GMP/analogs & derivatives , Female , Bacteriophages/physiology , Bacteriophages/genetics
14.
J Pediatr Endocrinol Metab ; 37(6): 505-515, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38700489

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity. RESULTS: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I2=96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I2=94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I2>50 %). CONCLUSIONS: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia.


Subject(s)
Diabetes Mellitus, Type 1 , Exercise , Hypoglycemic Agents , Insulin Infusion Systems , Insulin , Humans , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Child , Insulin/administration & dosage , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Adolescent , Blood Glucose/analysis , Hypoglycemia/prevention & control , Prognosis
15.
Food Chem Toxicol ; 189: 114746, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38768936

ABSTRACT

Diesel exhaust particle (DEP) exposure induces a variety of toxicological effects through oxidative stress and inflammation responses. This research investigated the mechanisms underlying DEP-induced GC-1spg cells oxidative stress by examining ROS accumulation, antioxidant defense systems activation, mitochondrial dysfunction, and the Nrf2/Keap1/HO-1 pathway response. Subsequently, we further evaluated the ATP levels, ATP5α synthase activity and ATP5α synthase S-sulfhydrated modification in DEP-exposed GC-1 spg cells. The results showed that DEP exposure significantly inhibited cell proliferation and viability, increased intracellular ROS production, decreased MMP, down-regulated antioxidant capacity, activated the Nrf2/Keap1/HO-1 pathway. However, DEP-induced oxidative stress was partially alleviated by GSH and exogenous H2S. In addition, DEP exposure induced ATP depletion and ATP5α synthase inactivity in GC-1 spg cells, accompanied by ATP5α synthase S-sulfhydrated modification. In conclusion, our research showed that DEP may incapacitate mitochondria through oxidative stress injury, leading to GC-1 spg cells oxidative stress. This process may be associated with the reduction of ATP5α1 S-sulfhydrated modification. It provides a new perspective for the research of the mechanism related to male reproductive toxicity due to air pollution.


Subject(s)
Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , Oxidative Stress , Particulate Matter , Vehicle Emissions , Oxidative Stress/drug effects , Vehicle Emissions/toxicity , Animals , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Mice , Particulate Matter/toxicity , Mitochondrial Proton-Translocating ATPases/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Cell Line , Mitochondria/drug effects , Mitochondria/metabolism , Cell Survival/drug effects , Adenosine Triphosphate/metabolism , Cell Proliferation/drug effects
16.
Article in English | MEDLINE | ID: mdl-38721987

ABSTRACT

The COVID-19 pandemic has significantly affected the psychological well-being of individuals worldwide. Previous research has indicated that values and beliefs, particularly social axioms, are associated with psychological responses during crises. However, most of the studies have focused on specific regions; the impact of social axioms on a global scale remains unclear. We conducted a multinational study comprising stratified samples of 18,171 participants from 35 cultures. Using multilevel modeling, we examined the associations between social axioms, personal worry, normative concerns, trust, and individuals' psychological responses to the pandemic. The results showed that greater personal worry and normative concerns predicted more negative psychological responses. Furthermore, the study also identified significant buffering effects at the societal level, as cultures with higher overall levels of fate control, religiosity, or reward for application exhibited weaker associations between personal worry and negative responses. Our findings reveal the influence of social axioms on psychological responses during the pandemic, with varying effects across cultures. The buffering effects of fate control, religiosity, and reward for application underscore the importance of considering cultural differences and individual variability when examining the impact of social axioms on psychological outcomes.

17.
Clin Epidemiol ; 16: 329-343, 2024.
Article in English | MEDLINE | ID: mdl-38798915

ABSTRACT

Objective: Partially observed confounder data pose challenges to the statistical analysis of electronic health records (EHR) and systematic assessments of potentially underlying missingness mechanisms are lacking. We aimed to provide a principled approach to empirically characterize missing data processes and investigate performance of analytic methods. Methods: Three empirical sub-cohorts of diabetic SGLT2 or DPP4-inhibitor initiators with complete information on HbA1c, BMI and smoking as confounders of interest (COI) formed the basis of data simulation under a plasmode framework. A true null treatment effect, including the COI in the outcome generation model, and four missingness mechanisms for the COI were simulated: completely at random (MCAR), at random (MAR), and two not at random (MNAR) mechanisms, where missingness was dependent on an unmeasured confounder and on the value of the COI itself. We evaluated the ability of three groups of diagnostics to differentiate between mechanisms: 1)-differences in characteristics between patients with or without the observed COI (using averaged standardized mean differences [ASMD]), 2)-predictive ability of the missingness indicator based on observed covariates, and 3)-association of the missingness indicator with the outcome. We then compared analytic methods including "complete case", inverse probability weighting, single and multiple imputation in their ability to recover true treatment effects. Results: The diagnostics successfully identified characteristic patterns of simulated missingness mechanisms. For MAR, but not MCAR, the patient characteristics showed substantial differences (median ASMD 0.20 vs 0.05) and consequently, discrimination of the prediction models for missingness was also higher (0.59 vs 0.50). For MNAR, but not MAR or MCAR, missingness was significantly associated with the outcome even in models adjusting for other observed covariates. Comparing analytic methods, multiple imputation using a random forest algorithm resulted in the lowest root-mean-squared-error. Conclusion: Principled diagnostics provided reliable insights into missingness mechanisms. When assumptions allow, multiple imputation with nonparametric models could help reduce bias.

18.
Arch Med Sci ; 20(2): 506-516, 2024.
Article in English | MEDLINE | ID: mdl-38757038

ABSTRACT

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease characterized by dryness of the eyes and mouth. The histological feature is mononuclear cell infiltration in exocrine glands, primarily salivary and lachrymal glands. As the disease progresses, some other tissues and organs may be involved and extraglandular manifestations ensue. The major current treatments are palliative and empirical, and in most cases the outcomes are not satisfactory. Emerging data indicate a critical role of lymphocytes in its development and progression. While pioneering work targeting B cells has demonstrated some encouraging results, more trials are warranted to validate the safety and efficacy. In addition, modulation of T cell function with abatacept ameliorates the severity of pSS. Furthermore, clinical trials to inhibit important cytokines involved in its formation have been carried out. In this article, we summarize and compare current biological therapies in order to find new and effective treatments for pSS.

19.
Sci Rep ; 14(1): 8868, 2024 04 17.
Article in English | MEDLINE | ID: mdl-38632326

ABSTRACT

A retrospective cohort study was conducted to observe the correction effect of Toric intraocular lens (IOL) implantation in cataract eyes with specific types of irregular corneal astigmatism. Thirty-four eyes with either the "asymmetric bow-tie" pattern (Type I) or the "angled bow-tie" pattern (Type II) were included. Corneal topography was assessed using Pentacam HR, and changes in preoperative corneal astigmatism, visual acuity, manifest refraction, and objective visual quality were measured and compared. The average uncorrected distance visual acuity improved significantly from 0.86 ± 0.40 logMAR to 0.22 ± 0.15 logMAR (P < 0.001). Preoperative corneal astigmatism of 2.05 ± 0.90 D was corrected to a postoperative residual astigmatism of 0.78 ± 0.57 D (P < 0.001), with 32% of eyes within 0.50 D. The residual astigmatism prediction errors in Type I and Type II cases were (0.97 ± 0.68 D) and (0.66 ± 0.37 D), respectively (P = 0.100). The mean spherical equivalent prediction error in Type II cases (0.07 ± 0.36 D) was significantly smaller than that in Type I cases (- 0.29 ± 0.52 D) (P = 0.030). This study concludes that Toric IOL implantation effectively corrects specific types of irregular corneal astigmatism in cataract surgery. Eyes with the "angled bow-tie" pattern show higher accuracy in refractive predictions compared to eyes with the "asymmetric bow-tie" pattern.


Subject(s)
Astigmatism , Cataract , Corneal Diseases , Lenses, Intraocular , Phacoemulsification , Humans , Astigmatism/surgery , Lens Implantation, Intraocular , Retrospective Studies , Refraction, Ocular , Corneal Diseases/surgery
20.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 152-157, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38678612

ABSTRACT

The purpose of this study was to explore the effects of regulatory B-cells (Breg) on intracranial aneurysms by mediating IL-1ß/IL-1R pathways.  The study involved 60 patients undergoing angiography in a hospital from January to June 2022, divided into two groups: 30 with intracranial aneurysms (observation group) and 30 without (control group). Researchers extracted peripheral blood mononuclear cells (PBMC) to analyze the proportion of CD19+CD24hiCD38hiB cells using flow cytometry. These cells, along with T-cells and regulatory T-cells (Treg), were isolated through magnetic bead cell sorting. Following co-culture, the proliferation of T-cells and their related secretory factors were assessed. Additionally, Breg cells, treated with an IL-1R receptor blocker or IL-1R expression adenovirus, were studied to evaluate the levels of IL-10 and TGF-ß. In the study, the observation group showed lower levels of CD19+CD24hiCD38hiB cells, IL-10, and TGF-ß in PBMC than the control group (P<0.05). T-cell proportions were similar in both groups pre and post co-culture (P>0.05). Post co-culture, IFN-γ decreased while IL-4 increased in both groups. The observation group had higher IFN-γ and lower IL-4 than the control group (P<0.05). TNF-α in CD8+T cells, and granzyme B and perforin mRNA levels decreased post co-culture but were higher in the observation group (P<0.05). IL-10 and TGF-ß in Treg cells increased in both groups post co-culture but were lower in the observation group (P<0.05). The observation group also had fewer CD19+IL-1R+IL-10+B cells (P<0.05). After IL-1R blocker addition, IL-10 and TGF-ß in the supernatant decreased in the observation group (P<0.05). Following transfection, IL-1 and TGF-ß levels increased compared to the blank group (P<0.05). The function of peripheral blood CD19+CD24hiCD38hiB cells is impaired in patients with intracranial aneurysms, which may be related to IL-1ß/IL-1R pathways disorder.


Subject(s)
B-Lymphocytes, Regulatory , Interleukin-1beta , Intracranial Aneurysm , Receptors, Interleukin-1 , Female , Humans , Male , B-Lymphocytes, Regulatory/immunology , B-Lymphocytes, Regulatory/metabolism , Cell Proliferation , Coculture Techniques , Interleukin-10/metabolism , Interleukin-1beta/metabolism , Intracranial Aneurysm/immunology , Intracranial Aneurysm/pathology , Intracranial Aneurysm/metabolism , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/immunology , Receptors, Interleukin-1/metabolism , Receptors, Interleukin-1/genetics , Signal Transduction , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Transforming Growth Factor beta/metabolism
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