The Impact of Sociodemographic Factors on Rates of Tympanostomy Tube Placement for Pediatric Otitis Media.

Objective: To identify the impact of race, ethnicity, and socioeconomic status (SES) on the rate of tympanostomy tube placement. Study Design: Retrospective medical review and population-level analyses. Setting: Tertiary referral center. Methods: Demographic and population-level characteristics (age, gender, race, insurance status, and ZIP code) compared to the regional, health system, and otolaryngology clinic demographics. Results: Among 38,461 children diagnosed with otitis media (OM) 61.4% were white, 27.4% were black, 32.7% had private insurance, and 18.2% were Hispanic. Among patients seen in the pediatric ear, nose, and throat (ENT) clinics, 70.0% were white, 20.0% were black, 46.6% had private insurance, and 14.9% were Hispanic. Further disparity was noted among those receiving tympanostomy tubes: 75.6% white, 15.6% black, 61.9% private insurance, and 11.7% Hispanic. Higher rates of tube placement were noted for those of white race [odds ratio, OR: 1.96, (95% confidence interval, CI: 1.85-2.04), <.001] and non-Hispanic ethnicity [OR: 1.67, (95% CI: 1.56-1.75), <.001]. Geographically, rates of tube placement were significantly lower in areas with higher deprivation indices, areas with lower proportions of white residents, and areas with the lowest median incomes. These markers correlate strongly with black race and Hispanic ethnicity. Lower rates of tube placement were also seen in majority white locales with higher deprivation indices and lower median incomes. Conclusion: Rates of access to pediatric ENT clinics, and of tube placement, are significantly lower for those of Hispanic ethnicity and black race than for non-Hispanic white children. Higher rates of tube placement were noted among white children and those with private insurance. Lower rates of tube placement were seen in areas of lower SES regardless of racial demographics.

Association between pregnancy loss and depressive symptoms in women: a population-based study.

BACKGROUND: Depression is a common mental disorder with a much higher prevalence in women than in men. Although there has been a gradual increase in research on the association between reproductive health and depression, there is still some inconsistency in the evidence of the relationship between pregnancy loss and depression. This study aimed to investigate the relationship between pregnancy loss and depressive symptoms. METHODS: We analyzed data from the 2007-2020 National Health and Nutrition Examination Survey (NHANES), which included female participants aged 20 to 80 years. Pregnancy loss was determined based on participants' self-reported number of pregnancies and pregnancy outcomes. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Multivariate logistic regression, smoothed curve fitting, and generalized additive modeling were used to examine the association between pregnancy loss and depression. We also performed sensitivity analyses and subgroup analyses to verify the robustness and specificity of the findings. RESULTS: A total of 12,873 female participants were included in our study, of which 1,595 (12.39%) were categorized as depressed. Multivariate logistic regression results indicated that experiencing a pregnancy loss increased the risk of prevalence of depression in women (for 1 loss: OR = 1.31, 95% CI 1.15,1.50; for 2 or more losses: OR = 1.58, 95% CI 1.38, 1.81). When sensitivity analyses were performed, an association between pregnancy loss and depression was found in both multivariate linear regressions with PHQ-9 scores as a continuous variable and multivariate logistic regressions with a threshold of 5 PHQ-9 scores. The association between pregnancy loss and depression remained stable across subgroups. CONCLUSION: Pregnancy loss correlated with elevated PHQ-9 scores and a heightened risk of depression in adult women across the United States. Focusing on the incidence of adverse pregnancy events in the female population may help prevent or early recognize the onset of depression.

Association between the serum uric acid/serum creatinine ratio and cognitive function in older adults: NHANES in the United States.

Cognitive impairment can potentially become a significant health concern in older adults. However, early effective diagnostic methods are still lacking. Therefore, we utilized the NHANES database in the US to investigate the relationship between serum uric acid to serum creatinine (SUA/SCR) ratio and cognitive impairment. In our study, a total of 3874 participants were included (2001-2002, 2011-2014). Weighted t tests or chi-square tests were utilized to analyze the basic characteristics of the population. Weighted logistic regression analysis, smooth-fit curves, threshold effects, and subgroup analysis were conducted to investigate the correlation between the SUA/SCR and cognitive impairment. In this study, the SUA/SCR was significantly lower in individuals with cognitive impairment. The logistic regression model, after adjusting for all covariates, revealed that the Q2-Q4 were 0.65 (95% CI 0.49, 0.86), 0.60 (95% CI 0.40, 0.90), 0.55 (95% CI 0.39, 0.77) respectively. This indicates that participants in the Q4 had a 45% reduced risk of cognitive impairment. Smooth-fit curves and threshold effect analysis revealed a nonlinear relationship between SUA/SCR and cognitive impairment, with a turning point at 4.13. Subgroup analysis showed no statistically significant differences in the relationship between SUA/SCR and cognitive impairment among different subgroups (P > 0.05). Our findings indicate a negative correlation between the SUA/SCR and the risk of cognitive impairment in the population of adults aged 60 and above in the US. This suggests that the SUA/SCR holds promise as a potential indicator for cognitive impairment.

Current application and future perspective of CRISPR/cas9 gene editing system mediated immune checkpoint for liver cancer treatment.

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.

Disparities in polysomnography referral in a high-risk cardiac population.

PURPOSE: Obstructive sleep apnea (OSA) is associated with metabolic, cardiovascular, and cerebrovascular comorbidities. Appropriate diagnosis and treatment of OSA might mitigate these comorbidities. This retrospective review sought to assess the impact of sex, age, race, ethnicity, and insurance status on polysomnography (PSG) referral rates. METHODS: An institutional STOP-Bang database of 299,320 patients was filtered for patients admitted to the hospital with an acute cardiac diagnosis between 2015-2020. A cohort of 4,735 patients were risk stratified by STOP-Bang (SB) score and correlations were made between PSG referrals and demographic and clinical variables (sex, age, race, ethnicity, and insurance status). RESULTS: Of the 25.3% of the cohort with high SB scores (5-8) only 21.3% were referred for PSG. Age and female sex were negatively associated with sleep study referrals (p < 0.001). No correlation was found between sleep study referral rates and race or ethnicity. No correlation was found between sleep study referrals and insurance provider. Admitting cardiac diagnosis significantly influenced sleep study referrals with diagnoses of arrhythmias and myocardial infarction being associated with an increased rate of PSG referrals compared to heart failure patients (p < 0.002). CONCLUSIONS: Our study found no significant correlation between PSG referral rates and race, ethnicity, or insurance provider. However, we found low overall rates of PSG referral, with negative correlations between older age and female sex and a high-risk cardiac population. This represents a substantial missed opportunity to identify patients at risk for OSA, obtain a diagnosis, and provider adequate treatment.

Fluorescence Sensing Properties of a Bibranched Cyanostilbene Derivative Containing -NH2 for Trace Water and Picric Acid Determination.

In order to design organic small molecule fluorescent materials with multiple sensing, a bibranched -NH2 modified cyanostilbene derivative (AM) was synthesized. It exhibits solvent and aggregation-induced emission effects, with a solid-state quantum yield of 28%, which is seven times higher than that in THF. The synthesized sample AM demonstrated high sensitivity to trace water via a fluorescence "turn-off" response, achieving a low detection limit of 0.41 µM in THF and 0.80 µM in EtOH. AM also exhibits a "turn-off" response to picric acid, attributed to the photo-induced electron transfer effect it induces. The recognition of picric acid by AM demonstrates specificity and resistance to interference from nitro explosives, with a detection limit of 300 ppb and a linear relationship (R2 = 0.9981) at the range of 0-4 equivalents AM. Such acid recognition can facilitate the design of qualitative test papers and safety inks. Additionally, AM can function as a temperature sensor with a linear relationship (R2 = 0.9976) within the temperature range of 25-110 °C. Leveraging these unique characteristics, a series of methods were proposed for the direct quantitative determination of trace water in nonaqueous solvents, picric acid, and temperature.

Relationships between body image, dyadic coping and post-traumatic growth in breast cancer patients: a cross-sectional study.

Background: The diagnosis and treatment of cancer triggers not only a negative psychological response for the patient, but also a positive psychological outcome. Positive dyadic coping, as a form of coping for mental health outcomes, can maintain or reestablish internal stability between the patient and his or her spouse, resulting in positive physical and psychological changes. However, there is a paucity of research on body image, dyadic coping, and post-traumatic growth in breast cancer patients. The purpose of this study was to explore the relationship and pathways between body image, dyadic coping, and post-traumatic growth in breast cancer patients. Methods: A cross-sectional study was conducted from November 2022 to November 2023 at a tertiary care hospital in Wuxi, Jiangsu, China. This study was conducted among 154 breast cancer patients treated at the Affiliated Hospital of Jiangnan University, all of whom completed demographic and clinical information questionnaires, Body image self-rating questionnaire for breast cancer (BISQ-BC), Dyadic Coping Inventory (DCI) and Post Traumatic Growth Inventory (PTGI). A Pearson correlation analysis was used to explore the relationship between body image, dyadic coping, and post-traumatic growth. Structural equation modeling was used to analyze the path relationships among the three and to explore the mediating role of dyadic coping. Results: The level of body image was negatively correlated with post-traumatic growth (r = -0.462, p < 0.01); and the level of body image was negatively correlated with dyadic coping (r = -0.308, p < 0.01). And dyadic coping was positively associated with post-traumatic growth (r = 0.464, p < 0.01). The structural equation modeling results supported the mediation model with the following model fit indices, chi-square to degrees of freedom ratio (χ2/df = 2.05), goodness of fit index (GFI = 0.93), comparative fit index (CFI = 0.99), canonical fit index (NFI = 0.93), incremental fit index (IFI = 0.99), non-canonical fit index (TLI = 0.99) and the root mean square of the difference in approximation error (RMSEA = 0.03). Body image and dyadic coping directly affected post-traumatic growth (ß = -0.33, p < 0.05; ß = 0.43, p < 0.05). And body image indirectly influenced post-traumatic growth through dyadic coping (ß = -0.17, p < 0.05). Conclusion: Interconnections between body image, dyadic coping, and post-traumatic growth in breast cancer patients. A preliminary validation of the mediating role of dyadic coping between body image and post-traumatic growth, body image can have an impact on dyadic coping, which in turn can have an impact on post-traumatic growth. Whereby higher levels of dyadic coping in patients may also be associated with higher levels of post-traumatic growth, whereas body image disturbance may impede levels of post-traumatic growth.

Prescription Data Mining and Network Pharmacology Study of 1152 Patients with Rectal Prolapse Using Traditional Chinese Medicine.

BACKGROUND: In recent years, the incidence of rectal prolapse has increased significantly due to the sedentary lifestyle and irregular eating habits of modern life. However, there is a lack of clinical studies on the treatment of rectal prolapse with traditional Chinese medicine (TCM) with a large sample size. Therefore, this study investigated the characteristics of rectal prolapse treatment formulas and then studied the network pharmacology of their core therapeutic drugs, which can help to provide a reference for the treatment and postoperative care of rectal prolapse patients. OBJECTIVE: This study aimed to explore the prescription characteristics and the mechanism of action of core drugs in the treatment of rectal prolapse in Chinese medicine through data mining and bioinformatics techniques. METHODS: We collected the diagnosis and treatment information of patients with rectal prolapse from January 2014 to September 2021 in the electronic case database of Nanjing Hospital of TCM, mined the patient information and prescription features using R, screened the active ingredients of the core pairs of drugs and disease drug intersection targets using TCMSP and GnenCard databases, and constructed a Protein-protein interaction (PPI) network using STRING and Cytoscape, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the intersecting targets were performed using Metascape and R. RESULTS: We found that prolapse is easy to occur in people over 50 years old, preferably in autumn and winter. Commonly used therapeutic Chinese medicines include Glycyrrhiza glabra, Radix angelicae sinensis, Radix astragali, Atractylodes macrocephala, and Pericarpium citri reticulatae, which are mostly deficiency tonic medicines, warm in nature, and belong to spleen meridian. The core therapeutic medicinal pair was "Bupleuri radix-Cimicifugae rhizoma". There were 190 common targets of Bupleuri radix and Cimicifugae rhizoma, and 71 intersection targets of the drug pair and prolapse. The main components of the core drugs for the treatment of prolapse may be quercetin, kaempferol, Stigmasterol, etc, and the core targets may be CASP3, AKT1, HIF1A, etc. The total number of GO entries for the intersection targets of "Bupleuri radix-Cimicifugae rhizoma" and diseases was 3495, among which the molecular functions accounted for the largest proportion, mainly Pathways in cancer, IL-18 signaling pathway, etc. KEGG enriched pathway analysis yielded 168 results, and the major pathways were pathways in cancer, lipid and atherosclerosis, IL-17 signaling pathway, etc. Conclusion: This study adopted real-world research methodology and used data mining and bioinformatics technology to mine the medication law of rectal prolapse and its core drug action mechanism from the clinical information of Chinese medicine.

Limited debridement combined with ReCell® Techniques for deep second-degree burns.

BACKGROUND: The purpose of this article is to introduce a method that combines limited debridement and ReCell® autologous cell regeneration techniques for the treatment of deep second-degree burn wounds. METHOD: A total of 20 patients suffered with deep second-degree burns less than 10% of total body surface area (TBSA) who were admitted to our department, from June 2019 to June 2021, participated in this study. These patients first underwent limited debridement with an electric/pneumatic dermatome, followed by the ReCell® technique for secondary wounds. Routine treatment was applied to prevent scarring after the wound healed. Clinical outcomes were scored using the Vancouver Scar Scale (VSS). RESULTS: All wounds of the patients healed completely. One patient developed an infection in the skin graft area and finally recovered by routine dressing changes. The average healing time was 12 days (range: 10-15 days). The new skin in the treated area was soft and matched the colour of the surrounding normal skin and the VSS score ranged from 3~5 for each patient. Of the 20 patients, 19 were very satisfied and 1 was satisfied. CONCLUSIONS: This article reports a useful treatment method that combines electric dermatome-dependent limited debridement and the ReCell® technique for the treatment of deep second-degree burn wounds. It is a feasible and effective strategy that is easy to implement and minimally invasive, and it is associated with a short healing time, mild scar formation and little damage to the donor skin area.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.

A meta-analysis highlights the cross-resistance of plants to drought and salt stresses from physiological, biochemical, and growth levels.

In nature, drought and salt stresses often occur simultaneously and affect plant growth at multiple levels. However, the mechanisms underlying plant responses to drought and salt stresses and their interactions are still not fully understood. We performed a meta-analysis to compare the effects of drought, salt, and combined stresses on plant physiological, biochemical, morphological and growth traits, analyze the different responses of C3 and C4 plants, as well as halophytes and non-halophytes, and identify the interactive effects on plants. There were numerous similarities in plant responses to drought, salt, and combined stresses. C4 plants had a more effective antioxidant defense system, and could better maintain above-ground growth. Halophytes could better maintain photosynthetic rate (Pn) and relative water content (RWC), and reduce growth as an adaptation strategy. The responses of most traits (Pn, RWC, chlorophyll content, soluble sugar content, H2O2 content, plant dry weight, etc.) to combined stress were less-than-additive, indicating cross-resistance rather than cross-sensitivity of plants to drought and salt stresses. These results are important to improve our understanding of drought and salt cross-resistance mechanisms and further induce resistance or screen-resistant varieties under stress combination.

Inhibition of Drp1-mediated mitochondrial fission improves contrast-induced acute kidney injury by targeting the mROS-TXNIP-NLRP3 inflammasome axis.

Acute kidney injury (AKI) is a critical complication known for their extremely high mortality rate and lack of effective clinical therapy. Disorders in mitochondrial dynamics possess a pivotal role in the occurrence and progression of contrast-induced nephropathy (CIN) by activating NLRP3 inflammasome. The activation of dynamin-related protein-1 (Drp1) can trigger mitochondrial dynamic disorders by regulating excessive mitochondrial fission. However, the precise role of Drp1 during CIN has not been clarified. In vivo experiments revealed that inhibiting Drp1 through Mdivi-1 (one selective inhibitor of Drp1) can significantly decrease the expression of p-Drp1 (Ser616), mitochondrial p-Drp1 (Ser616), mitochondrial Bax, mitochondrial reactive oxygen species (mROS), NLRP3, caspase-1, ASC, TNF-α, IL-1ß, interleukin (IL)-18, IL-6, creatinine (Cr), malondialdehyde (MDA), blood urea nitrogen (BUN), and KIM-1. Moreover, Mdivi-1 reduced kidney pathological injury and downregulated the interaction between NLRP3 and thioredoxin-interacting protein (TXNIP), which was accompanied by decreased interactions between TRX and TXNIP. This resulted in increasing superoxide dismutase (SOD) and CAT activity, TRX expression, up-regulating mitochondrial membrane potential, and augmenting ATP contents and p-Drp1 (Ser616) levels in the cytoplasm. However, it did not bring impact on the expression of p-Drp1 (Ser637) and TXNIP. Activating Drp-1though Acetaldehyde abrogated the effects of Mdivi-1. In addition, the results of in vitro studies employing siRNA-Drp1 and plasmid-Drp1 intervention in HK-2 cells treated with iohexol were consistent with the in vivo experiments. Our findings revealed inhibiting Drp1 phosphorylation at Ser616 could ameliorate iohexol -induced acute kidney injury though alleviating the activation of the TXNIP-NLRP3 inflammasome pathway.

Divergent Total Syntheses of Lycorine Alkaloids via a Sequential C-H Functionalization Strategy.

A Pd-catalyzed one-pot sequential C-H functionalization strategy was utilized to prepare four lycorine alkaloids and one pseudo-lycorine alkaloid from the common intermediate 4. By switching the followed oxidative conditions of air, DMSO/H2O/I2, and DMSO/O2, based on the Pd(PPh3)4/K2CO3/toluene catalytic system, three key intermediates 12a, 12b, and 12c with different substitution patterns could be obtained in a well-controlled manner. As a result, four natural products γ-lycorane, hippadine, anhydrolycorinone, and anhydrolycorine as well as a pseudo-lycorine alkaloid Δ(4a,10b)-6-oxodihydrolycorine were successfully synthesized within 10 steps through this divergent route.

Malignancy diagnosis of liver lesion in contrast enhanced ultrasound using an end-to-end method based on deep learning.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is considered as an efficient tool for focal liver lesion characterization, given it allows real-time scanning and provides dynamic tissue perfusion information. An accurate diagnosis of liver lesions with CEUS requires a precise interpretation of CEUS images. However,it is a highly experience dependent task which requires amount of training and practice. To help improve the constrains, this study aims to develop an end-to-end method based on deep learning to make malignancy diagnosis of liver lesions using CEUS. METHODS: A total of 420 focal liver lesions with 136 benign cases and 284 malignant cases were included. A deep learning model based on a two-dimensional convolution neural network, a long short-term memory (LSTM), and a linear classifier (with sigmoid) was developed to analyze the CEUS loops from different contrast imaging phases. For comparison, a 3D-CNN based method and a machine-learning (ML)-based time-intensity curve (TIC) method were also implemented for performance evaluation. RESULTS: Results of the 4-fold validation demonstrate that the mean AUC is 0.91, 0.88, and 0.78 for the proposed method, the 3D-CNN based method, and the ML-based TIC method, respectively. CONCLUSIONS: The proposed CNN-LSTM method is promising in making malignancy diagnosis of liver lesions in CEUS without any additional manual features selection.

Lipidomic and transcriptomic analysis of the increase in eicosapentaenoic acid under cobalamin deficiency of Schizochytrium sp.

Schizochytrium sp. is a heterotrophic microorganism capable of accumulating polyunsaturated fatty acids and has achieved industrial production of docosahexaenoic acid (DHA). It also has the potential for eicosapentaenoic acid (EPA) production. In this study, it was found that the cell growth, lipid synthesis and fatty acid composition of Schizochytrium sp. were significantly affected by the level of cobalamin in the medium, especially with regard to the content of EPA in the fatty acids. The content of EPA in the fatty acids increased 17.91 times, reaching 12.00%, but cell growth and lipid synthesis were significantly inhibited under cobalamin deficiency. The response mechanism for this phenomenon was revealed through combined lipidomic and transcriptomic analysis. Although cell growth was inhibited under cobalamin deficiency, the genes encoding key enzymes in central carbon metabolism were still up-regulated to provide precursors (Acetyl-CoA) and reducing power (NADPH) for the synthesis and accumulation of fatty acids. Moreover, the main lipid subclasses observed during cobalamin deficiency were glycerolipids (including glycerophospholipids), with EPA primarily distributed in them. The genes involved in the biosynthesis of these lipid subclasses were significantly up-regulated, such as the key enzymes in the Kennedy pathway for the synthesis of triglycerides. Thus, this study provided insights into the specific response of Schizochytrium sp. to cobalamin deficiency and identified a subset of new genes that can be engineered for modification.

A novel digital intermediate frequency module for hyperspectral microwave radiometers based on the parallel fast Fourier transform algorithm.

Microwave radiometers, possessing all-day and all-weather operational capabilities, are extensively utilized in the exploration of planetary atmospheres and surfaces. The potential of the hyperspectral detection technology to enhance the precision and resolution of microwave radiometer detection has made it a crucial research focus. This paper introduces an intermediate frequency (IF) module for hyperspectral microwave radiometers. The IF module is constructed with two 6.4 gigabit samples per second sampling-rate analog-to-digital converter (ADC) chips and a Xilinx Virtex-7 field programmable gate array. By implementing a parallel fast Fourier transform algorithm and a pipeline architecture, the IF module can efficiently process all ADC sampling data in real-time, generating 512 channels of output for each ADC. The test results, including linearity, sensitivity, and flatness, are presented and thoroughly analyzed for the IF module. Furthermore, the module is interfaced with the radio frequency front-end of the microwave radiometer to measure hot and cold calibration sources and assess its sensitivity. When combined with a suitable front-end receiver, the IF module can form a radiometer system suitable for various applications of microwave remote sensing.

Prevalence and Factors Contributing to Fear of Recurrence in Breast Cancer Patients and Their Partners: A Cross-Sectional Study.

Objective: The fear of cancer recurrence (FCR) is a generalized psychological problem among cancer patients and their spouses. The purpose of this study is to investigate the current status of cancer recurrence fear among breast cancer patients and their spouses, as well as its predictive factors. Methods: A total of 155 breast cancer patients and their partners between March 2022 to Feb 2023 were selected from Affiliated Hospital of Jiangnan University. The survey was investigated by fear of progression questionnaire-short form (FoP­Q­SF), fear of progression questionnaire-short form for partners (FoP-Q-SF/P), family resilience questionnaire (FaRE), and health literacy management scale (HeLMS). Predictors were assessed using univariate and multivariable regression analyses. Results: 52.9% (n=82) of breast cancer patients and 51.6% (n=80) of their spouses experienced high levels of fear of cancer recurrence (FCR). There was a positive correlation between the FCR of the patients and their spouses, while family resilience and health literacy were statistically significant negative predictive factors for breast cancer patients' fear of cancer recurrence. Conclusion: In summary, the study found that the partner's FCR, health literacy and family resilience were closely related to the FCR in breast cancer patients. Therefore, healthcare workers can reduce the patient's FCR by reducing the FCR in spouses, improving patients' health literacy and family resilience in the future. In practical application, these findings hold significant implications for developing comprehensive care plans and interventions targeting FCR in breast cancer patients. By focusing on patients' partners and providing appropriate support and resources, healthcare professionals can promote patients' psychological well-being and overall health, leading to improved quality of life.

Nuclear to cytoplasmic transport is a druggable dependency in MYC-driven hepatocellular carcinoma.

The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). MYC is considered undruggable to date. Here, we comprehensively identify genes essential for survival of MYChigh but not MYClow cells by a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen uncovers novel MYC synthetic lethal (MYC-SL) interactions and identifies most MYC-SL genes described previously. In particular, the screen reveals nucleocytoplasmic transport to be a MYC-SL interaction. We show that the majority of MYC-SL nucleocytoplasmic transport genes are upregulated in MYChigh murine HCC and are associated with poor survival in HCC patients. Inhibiting Exportin-1 (XPO1) in vivo induces marked tumor regression in an autochthonous MYC-transgenic HCC model and inhibits tumor growth in HCC patient-derived xenografts. XPO1 expression is associated with poor prognosis only in HCC patients with high MYC activity. We infer that MYC may generally regulate and require altered expression of nucleocytoplasmic transport genes for tumorigenesis.

Fluorinated Isoindolinone-Based Glucosylceramide Synthase Inhibitors with Low Human Dose Projections.

Inhibition of glucosylceramide synthase (GCS) has been proposed as a therapeutic strategy for the treatment of Parkinson's Disease (PD), particularly in patients where glycosphingolipid accumulation and lysosomal impairment are thought to be contributing to disease progression. Herein, we report the late-stage optimization of an orally bioavailable and CNS penetrant isoindolinone class of GCS inhibitors. Starting from advanced lead 1, we describe efforts to identify an improved compound with a lower human dose projection, minimal P-glycoprotein (P-gp) efflux, and acceptable pregnane X receptor (PXR) profile through fluorine substitution. Our strategy involved the use of predicted volume ligand efficiency to advance compounds with greater potential for low human doses down our screening funnel. We also applied minimized electrostatic potentials (Vmin) calculations for hydrogen bond acceptor sites to rationalize P-gp SAR. Together, our strategies enabled the alignment of a lower human dose with reduced P-gp efflux, and favorable PXR selectivity for the discovery of compound 12.

[Relationship of triglyceride-glucose index and its derivatives with blood pressure abnormalities in adolescents: an analysis based on a restricted cubic spline model]. / åŸºäºŽé™åˆ¶æ€§ç«‹æ–¹æ ·æ¡æ¨¡åž‹åˆ†æžé’å°‘å¹´ä¸‰é °ç”˜æ²¹-è‘¡è„ç³–æŒ‡æ•°åŠå ¶è¡ç”ŸæŒ‡æ•°ä¸Žè¡€åŽ‹å¼‚å¸¸çš„å ³ç³».

OBJECTIVES: To explore the relationship of triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), and triglyceride-glucose-waist circumference index (TyG-WC) with blood pressure abnormalities in adolescents, providing theoretical basis for the prevention and control of hypertension in adolescents. METHODS: A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys, physical measurements, and laboratory tests. Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG, TyG-BMI, and TyG-WC with blood pressure abnormalities in adolescents. RESULTS: Multivariable logistic regression analysis revealed that after adjusting for confounding factors, the groups with the highest quartile of TyG, TyG-BMI, and TyG-WC had 1.48 times (95%CI: 1.07-2.04), 3.71 times (95%CI: 2.67-5.15), and 4.07 times (95%CI: 2.89-5.73) higher risks of blood pressure abnormalities compared to the groups with the lowest quartile, respectively. Moreover, as the levels of TyG, TyG-BMI, and TyG-WC increased, the risk of blood pressure abnormalities gradually increased (P<0.05). A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.002). Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearit =0.232), and between TyG-WC and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.224). CONCLUSIONS: Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents, with linear or non-linear dose-response relationships.