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Various antibiotic-resistant bacteria (ARB) are known to induce repeated pulmonary infections and increase morbidity and mortality. A thorough knowledge of antibiotic resistance is imperative for clinical practice to treat resistant pulmonary infections. In this study, we used a reads-based method and an assembly-based method according to the metagenomic next-generation sequencing (mNGS) data to reveal the spectra of ARB and corresponding antibiotic resistance genes (ARGs) in samples from patients with pulmonary infections. A total of 151 clinical samples from 144 patients with pulmonary infections were collected for retrospective analysis. The ARB and ARGs detection performance was compared by the reads-based method and assembly-based method with the culture method and antibiotic susceptibility testing (AST), respectively. In addition, ARGs and the attribution relationship of common ARB were analyzed by the two methods. The comparison results showed that the assembly-based method could assist in determining pathogens detected by the reads-based method as true ARB and improve the predictive capabilities (46% > 13%). ARG-ARB network analysis revealed that assembly-based method could promote determining clear ARGbacteria attribution and 101 ARGs were detected both in two methods. 25 ARB were obtained by both methods, of which the most predominant ARB and its ARGs in the samples of pulmonary infections were Acinetobacter baumannii (ade), Pseudomonas aeruginosa (mex), Klebsiella pneumoniae (emr), and Stenotrophomonas maltophilia (sme). Collectively, our findings demonstrated that the assembly-based method could be a supplement to the reads-based method and uncovered pulmonary infection-associated ARB and ARGs as potential antibiotic treatment targets.
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BACKGROUND: General anesthesia is commonly used in the surgical management of gastrointestinal tumors; however, it can lead to emergence agitation (EA). EA is a common complication associated with general anesthesia, often characterized by behaviors, such as crying, struggling, and involuntary limb movements in patients. If treatment is delayed, there is a risk of incision cracking and bleeding, which can significantly affect surgical outcomes. Therefore, having a proper understanding of the factors influencing the occurrence of EA and implementing early preventive measures may reduce the incidence of agitation during the recovery phase from general anesthesia, which is beneficial for improving patient prognosis. AIM: To analyze influencing factors and develop a risk prediction model for EA occurrence following general anesthesia for primary liver cancer. METHODS: Retrospective analysis of clinical data from 200 patients who underwent hepatoma resection under general anesthesia at Wenzhou Central Hospital (January 2020 to December 2023) was conducted. Post-surgery, the Richmond Agitation-Sedation Scale was used to evaluate EA presence, noting EA incidence after general anesthesia. Patients were categorized by EA presence postoperatively, and the influencing factors were analyzed using logistic regression. A nomogram-based risk prediction model was constructed and evaluated for differentiation and fit using receiver operating characteristics and calibration curves. RESULTS: EA occurred in 51 (25.5%) patients. Multivariate analysis identified advanced age, American Society of Anesthesiologists (ASA) grade III, indwelling catheter use, and postoperative pain as risk factors for EA (P < 0.05). Conversely, postoperative analgesia was a protective factor against EA (P < 0.05). The area under the curve of the nomogram was 0.972 [95% confidence interval (CI): 0.947-0.997] for the training set and 0.979 (95%CI: 0.951-1.000) for the test set. Hosmer-Lemeshow test showed a good fit (χ 2 = 5.483, P = 0.705), and calibration curves showed agreement between predicted and actual EA incidence. CONCLUSION: Age, ASA grade, catheter use, postoperative pain, and analgesia significantly influence EA occurrence. A nomogram constructed using these factors demonstrates strong predictive accuracy.
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The extensive utilization of plastic products in recent years has resulted in a significant contamination of microplastics (MPs). The ingestion of MPs by aquatic and terrestrial organisms facilitates their transmission to mammals through the food chain. Therefore, the toxicity of MPs has attracted widespread attention from researchers. Previous studies have shown a connection between being exposed to polystyrene MPs (PS-MPs) and issues with male reproductive function. Testosterone, a hormone essential for male reproductive function, is produced and secreted by specialized cells known as Leydig cells, which found in the testicular interstitium. In our prior research, we confirmed that exposure to PS-MPs caused a reduction in testosterone levels by interfering with the LH-mediated LHR/cAMP/PKA/StAR pathway, with LHR being pivotal in this mechanism. However, the molecular mechanism underlying PS-MPs-induced reduction of LHR remains unclear. In this study, mice were respectively given drinking water containing 1000 µg/L PS-MPs characterized by diameters of 0.5 µm, 4 µm, and 10 µm for a period of 180 days. Our findings indicated that exposure to PS-MPs resulted in the proliferation of macrophages as well as their polarization towards the M1 phenotype. Additionally, the presence of PS-MPs triggered the release of tumor necrosis factor alpha (TNF-α) from macrophages, thereby activating nuclear factor-κB (NF-κB) signaling pathway within Leydig cells. The translocation of NF-κB into nucleus facilitated its binding to the promoter region of LHR, which consequently led to the repression of LHR transcription. This transcriptional inhibition resulted in a subsequent suppression of testosterone synthesis and secretion. Overall, this study elucidates a theoretical basis for explaining the interference of PS-MPs on the testosterone synthesis and secretion in Leydig cells from the perspective of the interaction between cells in the testicular interstitium.
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INTRODUCTION: The efficacy of multitarget neuroprotective drug DL-3-n-butylphthalide (NBP) in improving cognitive function has been confirmed in patients with vascular cognitive impairment without dementia. However, its efficacy in patients with symptomatic predementia phase of Alzheimer's disease remains uncertain. This study aims to evaluate the efficacy and safety of NBP in improving cognitive function in patients with mild cognitive impairment (MCI) through a clinical randomised controlled trail. METHODS AND ANALYSIS: This study is a 12-month, randomised, double-blind, placebo-controlled, multicentric trial, involving 270 patients with MCI. Subjects are randomly assigned to receive either NBP soft capsule (200 mg, three times per day) or placebo with an allocation ratio of 1:1. The efficacy and safety of NBP are assessed by comparing the results of neuropsychological, neuroimaging and laboratory tests between the two groups. The primary endpoint is the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale after 12 months. All patients will be monitored for adverse events. ETHICS AND DISSEMINATION: This study involving human participants has been reviewed and approved by Ethics Committee of Xuan Wu Hospital (No.2017058). The participants provide their written informed consent to participate in this study. Results will be published in peer-reviewed medical journals and disseminated to healthcare professionals at local and international conferences. PROTOCOL VERSION: V 3.0, 3 September 2022. TRIAL REGISTRATION NUMBER: ChiCTR1800018362.
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Benzofurans , Cognitive Dysfunction , Neuroprotective Agents , Humans , Benzofurans/therapeutic use , Benzofurans/adverse effects , Cognitive Dysfunction/drug therapy , Double-Blind Method , Male , Aged , Female , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/adverse effects , Middle Aged , Treatment Outcome , Randomized Controlled Trials as Topic , Neuropsychological Tests , Cognition/drug effects , Multicenter Studies as TopicABSTRACT
Magnetic skyrmions are topologically nontrivial spin configurations that possess particle-like properties. Earlier research has mainly focused on a specific type of skyrmion with topological charge Q = -1. However, theoretical analyses of 2D chiral magnets have predicted the existence of skyrmion bags-solitons with arbitrary positive or negative topological charge. Although such spin textures are metastable states, recent experimental observations have confirmed the stability of isolated skyrmion bags in a limited range of applied magnetic fields. Here, by utilizing Lorentz transmission electron microscopy, the extraordinary stability of skyrmion bags in thin plates of B20-type FeGe is shown. In particular, it is shown that skyrmion bags embedded within a skyrmion lattice remain stable even in zero or inverted external magnetic fields. A robust protocol for nucleating such embedded skyrmion bags is provided. The results agree perfectly with micromagnetic simulations and establish thin plates of cubic chiral magnets as a powerful platform for exploring a broad spectrum of topological magnetic solitons.
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Objectives: Cerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults. Methods: This study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis. Results: The model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67-0.76) in the training set and 0.69 (95% CI, 0.63-0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50-90% in the training set, and 65-98% in the validation set. Conclusion: A model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.
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Introduction: We sought to characterize cognitive profiles associated with enlarged perivascular spaces (EPVS) among Chinese older adults. Methods: This population-based study included 1191 dementia-free participants (age ≥60 years) in the MIND-China MRI Substudy (2018-2020). We visually evaluated EPVS in basal ganglia (BG) and centrum semiovale (CSO), white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and cortical superficial siderosis. We used a neuropsychological test battery to assess cognitive function. Data were analyzed using general linear models. Results: Greater BG-EPVS load was associated with lower z-scores in memory, verbal fluency, and global cognition (p < 0.05); these associations became non-significant when controlling for other cerebral small vessel disease (CSVD) markers (e.g., WMHs, lacunes, and mixed CMBs). Overall, CSO-EPVS load was not associated with cognitive z-scores (p > 0.05); among apolipoprotein E (APOE) -ε4 carriers, greater CSO-EPVS load was associated with lower verbal fluency z-score, even when controlling for other CSVD markers (p < 0.05). Discussion: The associations of BG-EPVS with poor cognitive function in older adults are largely attributable to other CSVD markers. HIGHLIGHTS: The association of enlarged perivascular spaces (EPVS) with cognitive function in older people is poorly defined.The association of basal ganglia (BG)-EPVS with poor cognition is attributed to other cerebral small vessel disease (CSVD) markers.In apolipoprotein E (APOE) ε4 carriers, a higher centrum semiovale (CSO)-EPVS load is associated with poorer verbal fluency.
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Microcystin-leucine arginine (MC-LR) has been reported to exhibit placental toxicity, leading to potential adverse pregnancy outcomes. Placental abnormalities often coincide with congenital heart defects (CHD). However, the extent to which MC-LR-induced placental abnormalities contribute to CHD and the cellular mechanisms underlying this association remain unknown. In this study, we observed abnormal polarization of placental macrophages in pregnant mice exposed to MC-LR during pregnancy, and the embryos developed cardiac developmental defects that persisted into adulthood. Trophoblast-derived extracellular vesicles (T-EVs) increase in number during pregnancy and act as a critical signal in macrophage polarization. However, MC-LR significantly affected the miRNA expression profile of T-EVs. Upon internalization into macrophages, T-EV-derived miR-377-3p specifically targets the 3'UTR region of NR6A1 to inhibit gene expression. Silencing of transcription suppressor NR6A1 leads to abnormal activation of the downstream mTOR/S6K1/SREBP pathway, inducing metabolic reprogramming and ultimately leading to M1 polarization of macrophages. This study elucidated the placental mechanism underlying MC-LR-induced CHD for the first time, providing insights into the environmental risks associated with CHD.
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Extracellular Vesicles , Macrophages , Microcystins , Trophoblasts , Animals , Female , Pregnancy , Mice , Trophoblasts/drug effects , Extracellular Vesicles/metabolism , Macrophages/drug effects , Microcystins/toxicity , Coronary Disease/chemically induced , Marine Toxins , Prenatal Exposure Delayed Effects , Maternal Exposure/adverse effects , MicroRNAs/metabolism , PlacentaABSTRACT
Background: Alzheimer's disease (AD) is the predominant cause of dementia on a global scale, significantly impacting the health of the elderly population. The pathogenesis of AD is closely linked to neuroinflammation. The present study employs a bibliometric analysis to examine research pertaining to neuroinflammation and AD within the last decade, with the objective of providing a comprehensive overview of the current research profile, hotspots and trends. Methods: This research conducted a comprehensive review of publications within the Science Citation Index Expanded of the Web of Science Core Collection Database spanning the years 2014 to 2024. Bibliometric analyses were performed using VOSviewer (version 1.6.19) and CiteSpace (version 6.3.R1) software to visualize data on countries, institutions, authors, journals, keywords, and references. Results: A total of 3,833 publications on neuroinflammation and AD were included from January 2014 to January 2024. Publications were mainly from the United States and China. Zetterberg, Henrik emerged as the author with the highest publication output, while Edison, Paul was identified as the most cited author. The most productive journal was Journal of Alzheimers Disease, and the most co-cited was Journal of Neuroinflammation. Research hotspot focused on microglia, mouse models, oxidative stress, and amyloid-beta through keyword analysis. Additionally, keywords such as blood-brain barrier and tau protein exhibited prolonged citation bursts from 2022 to 2024. Conclusion: This study provides a comprehensive review of the last 10 years of research on neuroinflammation and AD, including the number and impact of research findings, research hotspots, and future trends. The quantity of publications in this field is increasing, mainly in the United States and China, and there is a need to further strengthen close cooperation with different countries and institutions worldwide. Presently, research hotspots are primarily concentrated on microglia, with a focus on inhibiting their pro-inflammatory responses and promoting their anti-inflammatory functions as a potential direction for future investigations.
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Apolipoprotein E (APOE)is the gene with greatest genetic risk for Alzheimer's disease (AD). We successfully established a human induced pluripotent stem cell(iPSC) line from a woman mutated by APOE gene. The cell line was isolated from this woman's peripheral blood mononuclear cells using a non-integrated Sendai virus, which retained the original genotype, showed a normal karyotype, highly expressed pluripotent markers and could differentiate into three germ layers.
Subject(s)
Apolipoproteins E , Induced Pluripotent Stem Cells , Mutation , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Female , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Cell Line , Cell Differentiation , Karyotype , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/cytologyABSTRACT
Accelerometers are commonly used to measure vibrations for condition monitoring in mechanical and civil structures; however, their high cost and point-based measurement approach present practical limitations. With rapid advancements in computer vision and deep learning, research into tracking the motion of individual pixels with vision cameras has increased. The recently developed CoTracker, a transformer-based model, has demonstrated excellence in motion tracking, yet its performance in measuring structural vibrations has not been fully explored. This paper investigates the efficacy of the CoTracker model in extracting full-field structural vibrations using cameras. It is initially applied to capture the dense point movements in video sequences of a cantilever beam recorded using a high-speed camera. Subsequently, modal analysis using delay-embedding dynamic mode decomposition (DMD) is conducted to extract modal parameters including natural frequencies, damping ratios, and mode shapes. The results, benchmarked against those from a reference accelerometer and the Finite Element Method (FEM) result, demonstrate CoTracker's high potential for general applicability in structural vibration measurements.
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Colorectal cancer (CRC) is one of the most common non-cutaneous malignancies, causing significant mortality and a substantial burden. This study aims to explore the role of KIAA1429 (also known as vir-like m6A methyltransferase associated [VIRMA]) protein in the radioresistance of CRC. CRC cells and a radioresistant cell line were cultured, and KIAA1429 expression was detected. After the down-regulation of KIAA1429, its effect on the radioresistance and ferroptosis of cancer cells was analyzed. The role of ferroptosis in radioresistance was verified. The binding relationship among long non-coding RNA endogenous Bornavirus-like nucleoprotein 3, pseudogene (lncRNA EBLN3P), microRNA (miR)-153-3p, and KIAA1429 was analyzed. KIAA1429 and lncRNA EBLN3P were highly expressed in CRC, while miR-153-3p was poorly expressed. KIAA1429 and lncRNA EBLN3P were further increased/decreased in the radioresistant cells. KIAA1429 knockdown decreased the survival rate of the radioresistant cell line after X-ray irradiation and increased gamma H2A histone family member X (γ-H2AX), ferroptosis, and oxidative stress. A ferroptosis inhibitor alleviated the inhibitory effect of KIAA1429 knockdown on radioresistance. KIAA1429-mediated m6A modification up-regulated lncRNA EBLN3P, and lncRNA EBLN3P increased KIAA1429 by competitively binding to miR-153-3p. miR-153-3p silencing or lncRNA EBLN3P overexpression attenuated the promotion of ferroptosis and the inhibition of radioresistance induced by KIAA1429 knockdown. Overall, KIAA1429-mediated m6A modification up-regulated lncRNA EBLN3P expression, and lncRNA EBLN3P increased KIAA1429 expression by competitively binding to miR-153-3p, thus reducing ferroptosis and increasing the radioresistance of CRC.
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BACKGROUND: Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare the efficacy and safety of intravitreal ranibizumab (IVR) or dexamethasone implant (IDI) monotherapy, as well as the combination of IVR and IDI injections, in patients with ME secondary to branch retinal vein occlusion (BRVO). METHODS: This multicenter, prospective, and comparative study included 292 patients with unilateral ME involvement (total of 292 eyes) secondary to BRVO. The patients were randomly assigned to three groups and followed up for 12 months. Patients in group 1 (n = 96) were treated with 3-dose loading IVR injections followed by a pro re nata (PRN) regimen. Patients in group 2 (n = 98) received IVR combined with IDI injection, followed by IVR PRN regimen. Patients in group 3 (n = 98) were treated with IDI injection, followed by repeated IDI injection based on clinical necessity. Best corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and frequency of injections were recorded and compared between the three groups. RESULTS: At baseline, the three groups did not differ in age, gender, duration of ME, BCVA, IOP, and CRT (P > 0.05). Mean number of total injections per eye within 12 months were 7.1 ± 2.3 (range 4-9) in group 1, 3.7 ± 1.5 (range 2-6) in group 2, and 1.8 ± 0.4 (range 1-3) in group 3. There was a statistical difference in the number of injections between group 1 and group 2 (P = 0.037). Eyes in group 3 received fewer injections than those in group 2, but the difference was not statistically significant (P = 0.052). BCVA improvement and CRT reduction were achieved in all groups and there was no significant difference between the three groups at the end of the 12th month. However, IOP elevation and cataract progression were more frequent in group 3, especially in those patients who received repeated IDI injections. CONCLUSION: Three therapeutic regimens had comparable efficacy in treating ME secondary to BRVO. Combination therapy had an advantage in maintaining good effect with fewer re-injections and complications. TRIAL REGISTRATION INFORMATION: The study complied with the principles of the Declaration of Helsinki and was approved by Xi'an Aier Ancient City Eye Hospital, Xi'an Aier Eye Hospital, and Xianyang Aier Eye Hospital ethics committees (2022SF-367).
Subject(s)
Angiogenesis Inhibitors , Dexamethasone , Drug Implants , Drug Therapy, Combination , Glucocorticoids , Intravitreal Injections , Macular Edema , Ranibizumab , Retinal Vein Occlusion , Tomography, Optical Coherence , Visual Acuity , Humans , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/diagnosis , Ranibizumab/administration & dosage , Male , Female , Dexamethasone/administration & dosage , Macular Edema/etiology , Macular Edema/drug therapy , Macular Edema/diagnosis , Prospective Studies , Middle Aged , Angiogenesis Inhibitors/administration & dosage , Glucocorticoids/administration & dosage , Tomography, Optical Coherence/methods , Treatment Outcome , Aged , Follow-Up StudiesABSTRACT
Single atom catalyst (SAC) is one of the most efficient and versatile catalysts with well-defined active sites. However, its facile and large-scale preparation, the prerequisite of industrial applications, has been very challenging. This dilemma originates from the Gibbs-Thomson effect, which renders it rather difficult to achieve high single atom loading (< 3 mol%). Further, most synthesizing procedures are quite complex, resulting in significant mass loss and thus low yields. Herein, a novel metal coordination route is developed to address these issues simultaneously, which is realized owing to the rapid complexation between ligands (e.g., biuret) and metal ions in aqueous solutions and subsequent in situ polymerization of the formed complexes to yield SACs. The whole preparation process involves only one heating step operated in air without any special protecting atmospheres, showing general applicability for diverse transition metals. Take Cu SAC for an example, a record yield of up to 3.565 kg in one pot and an ultrahigh metal loading 16.03 mol% on carbon nitride (Cu/CN) are approached. The as-prepared SACs are demonstrated to possess high activity, outstanding selectivity, and robust cyclicity for CO2 photoreduction to HCOOH. This research explores a robust route toward cost-effective, massive production of SACs for potential industrial applications.
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Lower respiratory tract infections (LRTIs) represent some of the most globally prevalent and detrimental diseases. Metagenomic next-generation sequencing (mNGS) technology has effectively addressed the requirement for the diagnosis of clinical infectious diseases. This study aimed at identifying and classifying opportunistic pathogens from the respiratory tract-colonizing microflora in LRTI patients using data acquired from mNGS analyses. A retrospective study was performed employing the mNGS data pertaining to the respiratory samples derived from 394 LRTIs patients. Linear discriminant analysis effect size (LEfSe) analysis was conducted to discern the discriminant bacteria. Receiver operating characteristic curves (ROC) were established to demonstrate discriminant bacterial behavior to distinguish colonization from infection. A total of 443 discriminant bacteria were identified and segregated into three cohorts contingent upon their correlation profiles, detection frequency, and relative abundance in order to distinguish pathogens from colonizing microflora. Among them, 119 emerging opportunistic pathogens (cohort 2) occupied an average area under the curve (AUC) of 0.976 for exhibiting the most prominent predictability in distinguishing colonization from infection, 39 were colonizing bacteria (cohort 1, 0.961), and 285 were rare opportunistic pathogens (cohort 3, 0.887). The LTRIs patients appeared modular in the form of cohorts depicting complex microbial co-occurrence networks, reduced diversity, and a high degree of antagonistic interactions in the respiratory tract microbiome. The study findings indicate that therapeutic interventions should target interaction networks rather than individual microbes, providing an innovative perspective for comprehending and combating respiratory infections. Conclusively, this study reports a profile of LRTIs-associated bacterial colonization and opportunistic pathogens in a relatively large-scale cohort, which might serve as a reference panel for the interpretation of mNGS results in clinical practice.
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While a number of p53-MDM2 inhibitors have progressed into clinical trials for the treatment of cancer, their progression has been hampered by a variety of problems, including acquired drug resistance, dose-dependent toxicity, and limited clinical efficiency. To make more progress, we integrated the advantages of MDM2 inhibitors and platinum drugs to construct novel PtIV-RG7388 (a selective MDM2 inhibitor) complexes. Most complexes, especially 5a and 5b, displayed greatly improved antiproliferative activity against both wild-type and mutated p53 cancer cells. Remarkably, 5a exhibited potent in vivo tumor growth inhibition in the A549 xenograft model (66.5%) without apparent toxicity. It arrested the cell cycle at both the S phase and the G2/M phase and efficiently induced apoptosis via the synergistic effects of RG7388 and cisplatin. Altogether, PtIV-RG7388 complex 5a exhibited excellent in vitro and in vivo antitumor activities, highlighting the therapeutic potential of PtIV-RG7388 complexes as antitumor agents.
Subject(s)
Antineoplastic Agents , Proto-Oncogene Proteins c-mdm2 , Tumor Suppressor Protein p53 , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors , Proto-Oncogene Proteins c-mdm2/metabolism , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/antagonists & inhibitors , Animals , Cell Line, Tumor , Mice , Apoptosis/drug effects , Cell Proliferation/drug effects , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/chemical synthesis , Mice, Nude , Xenograft Model Antitumor Assays , Structure-Activity Relationship , Drug Discovery , Mice, Inbred BALB C , Pyrrolidines , para-AminobenzoatesABSTRACT
Bulimia, which means a person has episodes of eating a very large amount of food (bingeing) during which the person feels a loss of control over their eating, is the most primitive reason for being overweight and obese. The extended literature has indicated that childhood emotional abuse has a close relationship with adverse mood states, bulimia, and obesity. To comprehensively understand the potential links among these factors, we evaluated a multiple mediation model in which anxiety/depression and bulimia were mediators between childhood emotional abuse and body mass index (BMI). A set of self-report questionnaires, including the Childhood Trauma Questionnaire (CTQ), Beck Anxiety Inventory, Beck Depression Inventory (BDI), and Eating Disorder Inventory (EDI), was sent out. Clinical data from 37 obese patients (age: 29.65 ± 5.35, body mass index (BMI): 37.59 ± 6.34) and 37 demographically well-matched healthy people with normal body weight (age: 31.35 ± 10.84, BMI: 22.16 ± 3.69) were included in the investigation. We first performed an independent t-test to compare all scales or subscale scores between the two groups. Then, we conducted Pearson correlation analysis to test every two variables' pairwise correlation. Finally, multiple mediation analysis was performed with BMI as the outcome variable, and childhood emotional abuse as the predictive variable. Pairs of anxiety, bulimia, and depression, bulimia were selected as the mediating variables in different multiple mediation models separately. The results show that the obese group reported higher childhood emotional abuse (t = 2.157, p = 0.034), worse mood state (anxiety: t = 5.466, p < 0.001; depression: t = 2.220, p = 0.030), and higher bulimia (t = 3.400, p = 0.001) than the healthy control group. Positive correlations were found in every pairwise combination of BMI, childhood emotional abuse, anxiety, and bulimia. Multiple mediation analyses indicate that childhood emotional abuse is positively linked to BMI (ß = 1.312, 95% CI = 0.482-2.141). The model using anxiety and bulimia as the multiple mediating variables is attested to play roles in the relationship between childhood emotional abuse and obesity (indirect effect = 0.739, 95% CI = 0.261-1.608, 56.33% of the total effect). These findings confirm that childhood emotional abuse contributes to adulthood obesity through the multiple mediating effects of anxiety and bulimia. The present study adds another potential model to facilitate our understanding of the eating psychopathology of obesity.
Subject(s)
Bariatric Surgery , Bulimia , Psychological Tests , Self Report , Adult , Humans , Young Adult , Bulimia/epidemiology , Emotional Abuse , Anxiety/epidemiology , Obesity/epidemiology , Obesity/psychologyABSTRACT
BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.
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OBJECTIVE: The objective of this study was to determine the role of body fat percentage (BFP) changes in diabetes remission (DR) and the association between baseline body composition and its changes after bariatric surgery. METHODS: We analyzed 203 patients with type 2 diabetes who underwent Roux-en-Y gastric bypass. Body composition was measured using a gold-standard-derived predictive equation and magnetic resonance imaging. Body composition changes were calculated as 100 × (baseline value - follow-up value)/baseline value. We verified the results in a laparoscopic sleeve gastrectomy cohort with 311 patients. RESULTS: Compared with non-remission patients in the Roux-en-Y gastric bypass cohort, those who achieved DR showed a higher baseline fat-free mass index (FFMI) and experienced the most significant changes in BFP (p < 0.001). In comparative analyses, BFP changes were significantly better than BMI changes in identifying short- and long-term DR. Linear regression analysis identified FFMI as the most significant baseline variable correlated with BFP changes (p < 0.001). Baseline BMI was positively correlated with changes in BFP but negatively correlated with changes in FFMI. These findings were replicated in the laparoscopic sleeve gastrectomy cohort. CONCLUSIONS: BFP changes determine DR after bariatric surgery, and baseline FFMI is crucial for BFP changes. A low initial BMI is associated with a smaller BFP reduction and greater FFMI loss after bariatric surgery.
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PURPOSE: Sleeve gastrectomy (SG) is a widely used and effective treatment for patients with obesity and comorbid metabolic abnormalities. No specialized tool is available to predict metabolic syndrome (MS) remission after SG. We presented a nomogram that evaluated the probability of MS remission in obese patients 1 year after SG. MATERIALS AND METHODS: Patients with preoperative MS who underwent SG were enrolled in this retrospective study. They were divided into a training set and a validation set. Multivariate logistic regression analysis was performed to identify independent predictors of MS remission, and these predictors were included in the nomogram. Receiver operating characteristic curve was used to evaluate discrimination. Calibration was performed with the Hosmer-Lemeshow goodness-of-fit test. The net benefits of the nomogram were evaluated using decision curve analysis (DCA). RESULTS: Three hundred and eighteen patients with a median age of 34.0 years were analyzed. A training set and a validation set with 159 individuals each were established. A combination of age, preoperative high-density lipoprotein cholesterol, elevated triglycerides and glycated hemoglobin level independently and accurately predicted MS remission. The nomogram included these factors. The discriminative ability was moderate in training and validation sets (Area under curve 0.800 and 0.727, respectively). The Hosmer-Lemeshow X2 value of the nomogram was 8.477 (P = 0.388) for the training set and 5.361 (P = 0.718) for the validation set, indicating good calibration. DCA showed the nomogram had clinical benefits in both datasets. CONCLUSION: Our nomogram could accurately predict MS remission in Chinese patients with obesity 1 year after SG.