Effectiveness analysis of three-drug combination therapies for refractory focal epilepsy.

Selecting appropriate antiseizure medications (ASMs) for combination therapy in patients with drug-resistant epilepsy (DRE) is a complex task that requires an empirical approach, especially in patients receiving polytherapy. We aimed to analyze the effectiveness of various three-drug combinations in a group of patients with DRE under real-world conditions. This single-center, longitudinal observational study investigated patients with drug-resistant focal epilepsy who received three-drug regimens in the outpatient clinic of Tongji Hospital from September 2019 to December 2022. The effectiveness of each triple regimen was evaluated by the seizure-free rate and within-patient ratio of the seizure frequency (a seizure frequency ratio [SFR]<1 indicated superior efficacy). The independent t-test or Mann-Whitney U test was used for effectiveness analysis, and P values were adjusted by the Benjamini-Hochberg method for multiple comparisons. A total of 511 triple trials comprising 76 different regimens were conducted among 323 enrolled patients. Among these triple regimens, lamotrigine (LTG)/valproic acid (VPA)/topiramate (TPM) was the most frequently prescribed (29.4%, n â€‹= â€‹95). At the last clinical visit, 14.9% (n â€‹= â€‹48) of patients achieved seizure freedom after receiving triple therapy. LTG/VPA/TPM and LTG/VPA/levetiracetam (LEV) exhibited the highest seizure-free rates at 17.9% and 12.8%, respectively. These two regimens also had significantly lower median SFRs of 0.48 (interquartile range [IQR], 0.17-0.85; adjusted P â€‹< â€‹0.001) and 0.63 (IQR, 0.21-1.04; adjusted P â€‹< â€‹0.01), respectively. LTG/VPA/perampanel (PER) was another promising regimen that showed marginal effectiveness (median SFR â€‹= â€‹0.67; adjusted P â€‹= â€‹0.053). LTG/VPA/phenobarbital had the highest incidence of regimen-specific side effects (40.0%, 4/10), while the incidence of side effects from LTG/VPA/LEV was minimal (5.1%, 2/39). In conclusion, LTG/VPA/TPM and LTG/VPA/LEV exhibited superior efficacy and good tolerability in treating patients with DRE. Our results provide preliminary insights into the selection of ASMs for three-drug combination therapies in this clinically challenging population.

Origination of the chiroptical effect in plasmonic nano-structures in the view of quasi-normal mode theory.

General chiroptical effects describe all of the interaction differences between light carrying opposite spins and chiral matters, such as circular dichroism, optical activity, and chiral Raman optical activity, and have been proven to hold great promise for extensive applications in physics, chemistry, and biology. However, the underlying physical mechanism is usually explained intangibly by the twisted currents in chiral geometry, where the cross coupling between the electric and magnetic dipoles breaks the degeneracy of the helicity eigenmodes. In this Letter, we construct a clear sight on the origination of the chiroptical effect in the view of the eigenstates of a non-Hermitian system, i.e., quasi-normal modes (QNMs). The intrinsic chiroptical effect comes from the chiral QNMs, which have distinct excitation and emission differences in both phase and intensity for lights carrying opposite spins, while the extrinsic chiroptical effect coming from the achiral QNMs requires specific illumination and observation conditions, where the low symmetrical QNM can generate chiroptical effects in both absorption and scattering, but the highly symmetrical QNMs can only generate chiroptical effects in scattering through the coherent superposition of several QNMs. Our findings offer an in-depth understanding of the chiroptical effect and have the potential to bring broad inspiration to the design and applications of chiroptical effects.

Development and Validation of Deep Learning Model for Intermediate-Stage Hepatocellular Carcinoma Survival with Transarterial Chemoembolization (MC-hccAI 002): a Retrospective, Multicenter, Cohort Study.

Background: There are few effective prediction models for intermediate-stage hepatocellular carcinoma (IM-HCC) patients treated with transarterial chemoembolization (TACE) to predict overall survival (OS) is available. The learning survival neural network (DeepSurv) was developed to showed a better performance than cox proportional hazards model in prediction of OS. This study aimed to develop a deep learning-based prediction model to predict individual OS. Methods: This multicenter, retrospective, cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007, to December 31, 2016. Patients were divided into a training set(n=1075) and a test set(n=269) at a ratio of 8:2 to develop a deep learning-based algorithm (deepHAP IV). The deepHAP IV model was externally validated on an independent cohort(n=414) from the other three centers. The concordance index, the area under the receiver operator characteristic curves, and the calibration curve were used to assess the performance of the models. Results: The deepHAP IV model had a c-index of 0.74, whereas AUROC for predicting survival outcomes of 1-, 3-, and 5-year reached 0.80, 0.76, and 0.74 in the training set. Calibration graphs showed good consistency between the actual and predicted OS in the training set and the validation cohort. Compared to the other five Cox proportional-hazards models, the model this study conducted had a better performance. Patients were finally classified into three groups by X-tile plots with predicted 3-year OS rate (low: ≤ 0.11; middle: > 0.11 and ≤ 0.35; high: >0.35). Conclusion: The deepHAP IV model can effectively predict the OS of patients with IM-HCC, showing a better performance than previous Cox proportional hazards models.

Higher Vocational Nursing Students' Clinical Core Competence in China: A Cross-Sectional Study.

Introduction: Understanding the clinical core competence of nursing students in higher vocational colleges is crucial for adjusting the nursing core curriculum and training of nursing professionals. However, little is known about the level of clinical core competence of higher vocational nursing students in China. Objective: To investigate nursing students' clinical core competence in the school of nursing and health at a vocational and technical college in Guangdong, China. Methods: The Core Competency Scale for Registered Nurses in China was used to evaluate the clinical core competence of higher vocational nursing students from February to March 2022. Data were analyzed by descriptive statistics, Mann-Whitney U test and Kruskal-Wallis test. Results: A total of 1,120 nursing students were investigated, 1,069 were valid questionnaires, and the response rate was 95.4%. The total score of core competence score of higher vocational nursing students was 176.55 ± 43.95, only 43.3% of students obtained an overall score more than 178, and 47.7% of students scored between 116 and 178 scores. The lowest score was on critical thinking and scientific research (2.72 ± 0.77) following by clinical nursing (2.85 ± 0.80), which had differences in gender, category of students, and years of study. There were differences in the total average score of core competence in terms of gender and category of students. Leadership and interpersonal relationships differ significantly by gender, while professional development, teaching, and coaching differ significantly by category of student. Conclusions: The findings revealed the core competence of higher vocational nursing students is at a medium level. Moreover, critical thinking and scientific research, and clinical nursing ability are significantly insufficient.

Characterization of preclinical Alzheimer's disease model: spontaneous type 2 diabetic cynomolgus monkeys with systemic pro-inflammation, positive biomarkers and developing AD-like pathology.

BACKGROUND: The key to the prevention and treatment of Alzheimer's disease (AD) is to be able to predict and diagnose AD at the preclinical or early stage, but the lack of a preclinical model of AD is the critical factor that causes this problem to remain unresolved. METHODS: We assessed 18 monkeys in vivo evaluation of pro-inflammatory cytokines and AD pathological biomarkers (n = 9 / type 2 diabetic mellitus (T2DM) group, age 20, fasting plasma glucose (FPG) ≥ 100 mg/dL, and n = 9 / negative control (NC) group, age 17, FPG < 100 mg/dL). Levels of pro-inflammatory cytokines and AD pathological biomarkers was measured by ELISA and Simoa Technology, respectively. 9 monkeys evaluated ex vivo for AD-like pathology (n = 6 / T2DM group, age 22.17, FPG ≥ 126 mg/dL, and n = 3 / NC group, age 14.67, FPG < 100 mg/dL). To evaluate the pathological features of AD in the brains of T2DM monkeys, we assessed the levels of Aß, phospho-tau, and neuroinflammation using immunohistochemistry, which further confirmed the deposition of Aß plaques by Bielschowsky's silver, Congo red, and Thioflavin S staining. Synaptic damage and neurodegeneration were assessed by immunofluorescence. RESULTS: We found not only increased levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) in peripheral blood (PB) and brain of T2DM monkeys but also changes in PB of AD pathological biomarkers such as decreased ß-amyloid (Aß) 42 and Aß40 levels. Most notably, we observed AD-like pathological features in the brain of T2DM monkeys, including Aß plaque deposition, p-tau from neuropil thread to pre-neurofibrillary tangles (NFTs), and even the appearance of extracellular NFT. Microglia were activated from a resting state to an amoeboid. Astrocytes showed marked hypertrophy and an increased number of cell bodies and protrusions. Finally, we observed impairment of the postsynaptic membrane but no neurodegeneration or neuronal death. CONCLUSIONS: Overall, T2DM monkeys showed elevated levels of peripheral and intracerebral inflammation, positive AD biomarkers in body fluids, and developing AD-like pathology in the brain, including Aß and tau pathology, glial cell activation, and partial synaptic damage, but no neuronal degeneration or death as compared to the healthy normal group. Hereby, we consider the T2DM monkeys with elevation of the peripheral pro-inflammatory factors and positive AD biomarkers can be potentially regarded as a preclinical AD model.

The impact of brominated flame retardants (BFRs) on pulmonary function in US adults: a cross-sectional study based on NHANES (2007-2012).

Brominated flame retardants (BFRs) are a group of chemicals widely used in various applications to prevent or slow down the spread of fire. However, they have adverse effects on human health. There is a relative scarcity of population-based studies regarding BFRs, particularly their impact on the respiratory system. This study aimed to investigate the influence of BFRs on pulmonary function using data from the National Health and Nutrition Examination Survey. The study found that elevated serum concentrations of certain BFRs were associated with pulmonary ventilatory dysfunction. Adjusted analyses revealed positive correlations between PBDE47, PBDE183, and PBDE209 concentrations and ventilatory dysfunction. The analysis of mixed BFRs showed a positive relationship with pulmonary ventilation dysfunction, with PBDE47 making the most significant contribution. Our study demonstrates that both individual and combined BFRs exposure can lead to impaired pulmonary ventilation function. These findings provide evidence of the adverse effects of BFRs on lung function, emphasizing the importance of further investigating the potential health consequences of these compounds. Further large-scale longitudinal studies are needed to investigate this relationship in the future.

Generation of Functional and Mature Sympathetic Neurons from Human Pluripotent Stem Cells via a Neuroepithelial Route.

The sympathetic nervous system (SNS) is a crucial branch of the autonomic nervous system (ANS) that is responsible for regulating visceral function and various physiological processes. Dysfunction of the SNS can lead to various diseases, such as hypertension and metabolic disorders. However, obtaining sympathetic neurons from human tissues for research is challenging. The current research aimed at recapitulating the process of human sympathetic neuron development and achieved the successful establishment of a stepwise, highly efficient in vitro differentiation protocol. This protocol facilitated the generation of functional and mature sympathetic neurons from human pluripotent stem cells (hPSCs) using a chemical-defined induction medium. Initially, each differentiation stage was refined to derive sympathoadrenal progenitors (SAPs) from hPSCs through neural epithelial cells (NECs) and trunk neural crest stem cells (NCSCs). hPSC-derived SAPs could be expanded in vitro for at least 12 passages while maintaining the expression of SAP-specific transcription factors and neuronal differentiation potency. SAPs readily generated functional sympathetic neurons (SymNs) when cultured in the neuronal maturation medium for 3-4 weeks. These SymNs expressed sympathetic markers, exhibited electrophysiological properties, and secreted sympathetic neurotransmitters. More importantly, we further demonstrated that hPSC-derived SymNs can efficiently regulate the adipogenesis of human adipose-derived stem cells (ADSCs) and lipid metabolism in vitro. In conclusion, our study provided a simple and robust protocol for generating functional sympathetic neurons from hPSCs, which may be an invaluable tool in unraveling the mechanisms of SNS-related diseases.

S-9-PAHSA's neuroprotective effect mediated by CAIII suppresses apoptosis and oxidative stress in a mouse model of type 2 diabetes.

BACKGROUND: With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. METHODS: This in vivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. RESULTS: S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. CONCLUSION: S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.

Acquisition of a stable and transferable plasmid coharbouring hypervirulence and MDR genes with low fitness cost: Accelerating the dissemination of ST11-KL64 CR-HvKP.

OBJECTIVES: This study aimed to delineate the ability of a plasmid, pS130-4, which harboured both hypervirulence and multidrug resistance genes, to disseminate within Klebsiella pneumoniae, as well as its potential formation mechanism. METHODS: We employed whole-genome sequencing to decipher the genetic architecture of pS130-4. Its capability to conjugate and transfer was assessed through a series of experiments, including plasmid stability, competitive growth, and growth curve analysis. Its expression stability was further evaluated using drug sensitivity, larval survival, and biofilm formation tests. RESULTS: pS130-4 contained four intact modules typical of self-transmissible plasmids. BLAST analysis revealed a sequence identity exceeding 90% with other plasmids from a variety of hosts, suggesting its broad prevalence. Our findings indicated the plasmid's formation resulted from IS26-mediated recombination, leading us to propose a model detailing the creation of this conjugative fusion plasmid housing both blaKPC-2 and hypervirulence genes. Our conjugation experiments established that pS130-4, when present in the clinical strain S130, was self-transmissible with an estimated efficiency between 10-5 and 10-4. Remarkably, pS130-4 showcased a 90% retention rate and did not impede the growth of host bacteria. Galleria mellonella larval infection assay demonstrated that S130 had pronounced toxicity when juxtaposed with high-virulence control strain NTUH-K2044 and low-toxicity control strain ATCC700603. Furthermore, pS130-4's virulence remained intact postconjugation. CONCLUSION: A fusion plasmid, encompassing both hypervirulence and multidrug resistance genes, was viable within K. pneumoniae ST11-KL64 and incurred minimal fitness costs. These insights underscored the criticality of rigorous monitoring to pre-empt the escalation and distribution of this formidable super-plasmid.

Investment analysis of the private firm under different financial arrangements in infrastructure projects.

This study investigates the impact of various financial arrangements on the investment behavior of the private firm in PPP (Public-Private Partnership) projects. The results manifest that: first, the private firm will invest in the project earlier under long-term debt financing than under short-term debt financing or all equity financing; second, the investment boundary of the private sector decreasing with the probability of obtaining long-term debt financing under short-term debt financing, while increasing with the probability of obtaining long-term debt financing under long-term debt financing; third, the optimal debt level under short-term debt financing displays a U-shaped relationship with the refinancing risk probability; fourth, under short-term debt financing, the difference in the optimal capital structure between projects with different volatility of cash flow is larger when the refinancing risk probability is lower; and fifth, the private firm may exit the project earlier under short-term debt financing than under long-term debt financing. These results can help us to understand the investment behavior of the private firm under different financial arrangements.

Anaplastic Lymphoma Kinase (ALK) Inhibitors Show Activity in Colorectal Cancer With ALK Rearrangements: Case Series and Literature Review.

Anaplastic lymphoma kinase (ALK) rearrangement is a well-known driver oncogene detected in approximately 5% of non-small cell lung cancer. However, ALK rearrangement is much less frequent in other solid tumors outside the lungs, such as colorectal cancer (CRC); thus, the optimal management of CRC with ALK rearrangements has yet to be established. In this report, we describe 2 cases of ALK-positive CRC, both of which benefited from ALK tyrosine kinase inhibitor (ALK-TKI) therapy. Case 1 was a postoperative patient with poorly differentiated colon adenocarcinoma, who was diagnosed with metastatic relapse shortly after surgery. Both fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab combined with 5-fluorouracil, l-leucovorin, and irinotecan (FOLFIRI) proved ineffective against the disease. The patient was then treated with ensartinib, as the CAD-ALK fusion gene was detected by genomic analysis. The patient was initially treated with ensartinib monotherapy for 9 months, then with ensartinib combined with local radiotherapy and fruquintinib for another 4 months for isolated hilar hepatic lymph node metastasis. The patient experienced disease progression with an acquired ALK G1202R resistance mutation that responded well to lorlatinib. Case 2 involved a 72-year-old man with advanced colon cancer (pT4bN2aM1b, stage IV) harboring an EML4-ALK fusion. The patient underwent resection of the right colon tumor due to intestinal obstruction, but the disease continued to progress after 12 courses of FOLFIRI and bevacizumab chemotherapy. However, the patient responded remarkably well to alectinib. Our report emphasizes the importance of gene detection in the treatment of malignant tumors, and the significance of ALK mutations in CRC.

Wall-mounted folding chairs to promote resident physician sitting at the hospital bedside.

BACKGROUND: Sitting at the bedside may improve patient-clinician communication; however, many clinicians do not regularly sit during inpatient encounters. OBJECTIVE: To determine the impact of adding wall-mounted folding chairs inside patient rooms, beyond any impact from a resident education campaign, on the patient-reported frequency of sitting at the bedside by internal medicine resident physicians. DESIGN, SETTING, AND PARTICIPANTS: Prospective, controlled pre-post trial between 2019 and 2022 (data collection paused 2020-2021 due to COVID-19) at an academic hospital in Baltimore, Maryland. Folding chairs were installed in two of four internal medicine units and educational activities were delivered equally across all units. MAIN OUTCOME AND MEASURES: Patient-reported frequency of sitting at bedside, assessed as means on Likert-type items with 1 being "never" and 5 being "every single time." We also examined the frequency of other patient-reported communication behaviors. RESULTS: Two hundred fifty six and 206 patients enrolled in the pre and post-intervention periods, respectively. The mean frequency of patient-reported sitting by resident physicians increased from 1.8 (SD 1.2) to 2.3 (1.2) on education-only units (absolute difference 0.48 [95% CI: 0.21-0.75]) and from 2.0 (1.3) to 3.2 (1.4) on units receiving chairs (1.16, [0.87-1.45]). Comparing differences between groups using ordered logistic regression adjusting for clustering within residents, units with added chairs had greater increases in sitting (odds ratio 2.05 [1.10-3.82]), spending enough time at the bedside (2.43 [1.32-4.49]), and checking for understanding (3.04 [1.44-6.39]). Improvements in sitting and other behaviors were sustained on both types of units. CONCLUSIONS: Adding wall-mounted folding chairs may help promote effective patient-clinician communication.

PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer.

Breast cancer is the second leading cause of death in women worldwide, with triple-negative breast cancer (TNBC) having the worst prognosis. Although there are numerous studies on TNBC, there is no effective treatment for it, and it is still a major problem today. Studies on PIWI-interacting RNAs (piRNAs) are increasing and investigating the mechanism of piRNAs in the proliferation and metastasis of TNBC may lead to new potential treatment targets. Here, we identified a novel piRNA, piR-YBX1, which was downregulated in TNBC compared to matched normal breast tissue. Overexpression of piR-YBX1 significantly inhibited the proliferation, migration, invasion ability of TNBC cells both in vivo and in vitro. Mechanistically, piR-YBX1 could bind directly to mRNA of Y-box binding protein 1 (YBX1) and overexpression of piR-YBX1 downregulated YBX1 in both mRNA and protein levels, while the function of piR-YBX1 could be partly rescued by overexpression of YBX1. In addition, YBX1 could bind to RAF1 which is the key molecule in the MAPK signaling pathway, and overexpression of piR-YBX1 inhibited the p-MEK and p-ERK1/2, which can be reverted by YBX1. In conclusion, our findings discovered that the piR-YBX1/YBX1/MAPK axis suppresses the proliferation and metastasis of TNBC and therefore piR-YBX1 has the potential to be an effective therapeutic agent for breast cancer.

Association between lactate-to-albumin ratio and 28-days all-cause mortality in patients with sepsis-associated liver injury: a retrospective cohort study.

BACKGROUND: The mortality rate of sepsis-associated liver injury (SALI) is relatively high, but there is currently no authoritative prognostic criterion for the outcome of SALI. Meanwhile, lactate-to-albumin ratio (LAR) has been confirmed to be associated with mortality rates in conditions such as sepsis, heart failure, and respiratory failure. However, there is a scarcity of research reporting on the association between LAR and SALI. This study aimed to elucidate the association between LAR and the 28-day mortality rate of SALI. METHODS: In this retrospective cohort study, data were obtained from the Medical Information Mart for Intensive Care IV (v2.2). Adult patients with SALI were admitted to the intensive care unit in this study. The LAR level at admission was included, and the primary aim was to assess the relationship between the LAR and 28-day all-cause mortality. RESULTS: A total of 341 patients with SALI (SALI) were screened. They were divided into a survival group (241) and a non-survival group (100), and the 28-day mortality rate was 29.3%. Multivariable Cox regression analysis revealed that for every 1-unit increase in LAR, the 28-day mortality risk for SALI patients increased by 21%, with an HR of 1.21 (95% CI 1.11 ~ 1.31, p < 0.001). CONCLUSIONS: This study indicates that in patients with SALI, a higher LAR is associated with an increased risk of all-cause mortality within 28 days of admission. This suggests that LAR may serve as an independent risk factor for adverse outcomes in SALI patients.

The profile of genome-wide DNA methylation, transcriptome, and proteome in streptomycin-resistant Mycobacterium tuberculosis.

Streptomycin-resistant (SM-resistant) Mycobacterium tuberculosis (M. tuberculosis) is a major concern in tuberculosis (TB) treatment. However, the mechanisms underlying streptomycin resistance remain unclear. This study primarily aimed to perform preliminary screening of genes associated with streptomycin resistance through conjoint analysis of multiple genomics. Genome-wide methylation, transcriptome, and proteome analyses were used to elucidate the associations between specific genes and streptomycin resistance in M. tuberculosis H37Rv. Methylation analysis revealed that 188 genes were differentially methylated between the SM-resistant and normal groups, with 89 and 99 genes being hypermethylated and hypomethylated, respectively. Furthermore, functional analysis revealed that these 188 differentially methylated genes were enriched in 74 pathways, with most of them being enriched in metabolic pathways. Transcriptome analysis revealed that 516 genes were differentially expressed between the drug-resistant and normal groups, with 263 and 253 genes being significantly upregulated and downregulated, respectively. KEGG analysis indicated that these 516 genes were enriched in 79 pathways, with most of them being enriched in histidine metabolism. The methylation level was negatively related to mRNA abundance. Proteome analysis revealed 56 differentially expressed proteins, including 14 upregulated and 42 downregulated proteins. Moreover, three hub genes (coaE, fadE5, and mprA) were obtained using synthetic analysis. The findings of this study suggest that an integrated DNA methylation, transcriptome, and proteome analysis can provide important resources for epigenetic studies in SM-resistant M. tuberculosis H37Rv.

Association of hysterectomy with nonalcoholic fatty liver disease among US women.

BACKGROUND: A postmenopausal rise in the rates of nonalcoholic fatty liver disease (NAFLD) has been reported in women. This study thus sought to further probe the association of hysterectomy with NAFLD. METHODS: The data utilized in this investigation were attained from the 2017-March 2020 cycle of the National Health and Nutrition Examination Survey (NHANES), reflecting a strategic utilization of comprehensive health and nutrition information in the US population, to conduct a cross-sectional examination of the relationship between self-reported hysterectomy and NAFLD. Subjects included in this study were women aged 20 years or older. The multivariable logistic regression methodologies were utilized to determine the pertinent odds ratios (ORs) and their associated 95% confidence intervals (CIs). RESULTS: Of the 2,868 subjects enrolled in this study (mean age: 51.3 years, 95%CI: 50.0-52.6 years), 22.1% (95%CI: 19.7-24.7%) reported having undergone a hysterectomy, while 31.1% (95%CI: 28.1-34.1%) exhibited elastographic evidence of NAFLD, and 3.8% (95%CI: 2.6-5.6%) exhibited clinically significant fibrosis (CSF). Relative to women with no history of hysterectomy, those that had undergone hysterectomy exhibited a higher odd of NAFLD (OR:1.66, 95%CI: 1.24-2.21) in a multivariable model fully adjusted for age, ethnicity, body mass index, female hormone use, oophorectomy, diabetes, hyperlipidemia, and smoking status. Subgroup analyses revealed a stronger association among women who were not obese (OR:2.23, 95%CI:1.61-3.11), women who were not affected by diabetes (OR:1.76, 95%CI: 1.25-2.46), and without hyperlipidemia (OR: 1.87, 95%CI: 1.10-3.16). No significant association of hysterectomy with NAFLD encompassing CSF was identified. CONCLUSIONS: The results of the present nationally representative analysis suggested an association between hysterectomy and increased NAFLD prevalence among US women. Knowledge of this relationship may better aid clinical efforts to screen for and manage NAFLD.

Analysis of the correlation between serum Klotho and FeNO: a cross-sectional study from NHANES (2007-2012).

BACKGROUND: Klotho is an anti-aging protein that has multiple functions and may play a key role in the pathogenesis and progression of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Fractional Exhaled Nitric Oxide (FeNO) is a non-invasive and novel biomarker that has the advantages of being simple, fast and reproducible. It can effectively assess the degree of airway inflammation in diseases such as asthma and COPD. Despite these insights, the relationship between serum Klotho levels and FeNO has not been explored yet. METHODS: Leveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, we investigated the correlation between FeNO and serum Klotho levels. This association was scrutinized both as continuous variables and within quartile distributions, utilizing the Kruskal-Wallis H test. The correlation between the two variables was assessed through Spearman rank analysis. Employing survey weight-adjusted linear regression models, we gauged the strength of these associations. RESULTS: This study included 6,527 participants with a median FeNO level of 14.5 parts per billion (ppb). We found that FeNO levels varied significantly across different quartiles of Klotho protein (H = 7.985, P = 0.046). We also found a significant positive correlation between serum Klotho levels and FeNO levels in the whole population (Spearman's rho = 0.029, P = 0.019). This correlation remained significant after adjusting for covariates such as age, gender, lung function, smoking status, alcohol use, BMI, cardiovascular disease (including hypertension, heart failure, coronary heart disease, and myocardial infarction), diabetes, inflammatory markers, serum vitamin D level and BUN (P < 0.05 for all). Furthermore, this correlation was stronger at the high (K3) and super high (K4) levels of Klotho than at the low (K1) and medium (K2) levels (ß = 1.979 ppb and ß = 1.993 ppb for K3 and K4 vs. K1, respectively; 95% CI: 0.497 ~ 2.953 and 95% CI: 0.129 ~ 2.827, respectively; P = 0.007 and P = 0.032, respectively). The ß coefficient for serum Klotho was 0.002 ppb/pg/ml. CONCLUSIONS: Our study illuminates a positive correlation between serum Klotho levels and FeNO. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.

Photodynamic antibacterial application of TiO2/curcumin/hydroxypropyl-cyclodextrin and its konjac glucomannan composite films.

Although photodynamic therapy (PDT) has great advantages for the treatment of bacterial infections, photosensitizers (PSs) often have many disadvantages that limit their application. Improving the shortcomings of PSs and developing efficient PDT antimicrobial materials remain serious challenges. In this study, a nanocomposite drug (TiO2/curcumin/hydroxypropyl-cyclodextrin, TiO2/Cur/HPCD) was constructed and combined with konjac glucomannan to form composite films (TiO2/Cur/HPCD films, KTCHD films). The stabilities of TiO2 and Cur were improved in the presence of HPCD. The particle size of TiO2/Cur/HPCD was approximately 33.9 nm, and the addition of TiO2/Cur/HPCD enhanced the mechanical properties of the films. Furthermore, TiO2/Cur/HPCD and KTCHD films exhibited good biocompatibility and PDT antibacterial effects. The antibacterial rate of TiO2/Cur/HPCD was 74.46 % against MRSA at 500 µg/mL and 99.998 % against E. coli at 400 µg/mL, while it was adsorbed on the surface of bacteria to improve the effectiveness of the treatment. In addition, studies in mice confirmed that TiO2/Cur/HPCD and KTCHD films can treat bacterial infections and promote wound healing, with a highest wound healing rate of 84.6 % in the KTCHD-10 films + Light group on day 12. Overall, TiO2/Cur/HPCD is a promising nano-antibacterial agent and KTCHD films have the potential to be employed as antibacterial and environment-friendly trauma dressings.

A Bibliometric and Visual Analysis of Single Nucleotide Polymorphism Studies in Depression.

BACKGROUND: Genetic polymorphism has been proven to have an important association with depression, which can influence the risk of developing depression, the efficacy of medications, and adverse effects via metabolic and neurological pathways. Nonetheless, aspects of the association between single nucleotide polymorphisms and depression have not been systematically investigated by bibliometric analysis. OBJECTIVE: The aim of this study was to analyze the current status and trends of single nucleotide polymorphism research on depression through bibliometric and visual analysis. METHODS: The Web of Science Core Collection was used to retrieve 10,043 articles that were published between 1998 and 2021. CiteSpace (6.1 R4) was used to perform collaborative network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection. RESULTS: The most productive and co-cited journals were the Journal of Affective Disorders and Biological Psychiatry, respectively, and an analysis of the references showed that the most recent research focused on the largest thematic cluster, "5-HT", reflecting the important research base in this area. "CYP2D6" has been in the spotlight since its emergence in 2009 and has become a research hotspot since its outbreak in 2019. However, "BDNF ", "COMT ", "older adults", "loci", and "DNA methylation" are also the new frontier of research, and some of them are currently in the process of exploration. CONCLUSION: These findings offer a useful perspective on existing research and potential future approaches in the study of the association between single nucleotide polymorphisms and depression, which may assist researchers in selecting appropriate collaborators or journals.