Physicochemical properties and in vitro release of formononetin nano-particles by ultrasonic probe-assisted precipitation in four polar organic solvents.

Although formononetin has a considerable biological activity, its therapeutic use is limited by its low solubility. Formononetin was dissolved in ethanol, methanol, N, N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO) in this investigation, the antisolvent precipitation procedure with the assistance of an external ultrasonic probe was used to manufacture the formononetin nano-particles. The ideal parameters for response surface BBD optimization are as follows: feed volume flow rate of 6 mL/min; ultrasonic power of 860 W; and liquid-liquid ratio of 1:12.5. The formononetin nano-particles have a smaller particle diameter than raw sample; the lowest size can be as small as (329 ± 1.99) nm, which is 45 times smaller than raw. An in vitro digestion test using a solution that simulated intestinal solution revealed that the release rate of the nano-particle was 1.75 times than that of the raw formononetin. The formononetin nano-particles generated by the aforementioned four solvents have the following order of diameter: ethanol > methanol > DMF > DMSO. This study provided a technical reference for the functional food components in deep processing.

Clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride on mild-to-moderate depression.

BACKGROUND: Depression is a common, chronic, and recurrent mood disorder that has become a worldwide health hazard. Fluoxetine hydrochloride, a common treatment method, can inhibit 5-hydroxytryptamine (5-HT) recycling in the presynaptic membrane; however, the efficacy of a single drug is inadequate. At present, mild-to-moderate depression can be treated with acupuncture of ghost caves, but the clinical curative effect of combined therapy with fluoxetine hydrochloride has not been sufficiently reported. AIM: To evaluate the clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride in the treatment of mild-to-moderate depression. METHODS: This retrospective study included 160 patients with mild-to-moderate depression who were admitted to Shanghai Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, between January 2022 and June 2023. Patients were separated into a single-agent group (fluoxetine hydrochloride treatment, n = 80) and a coalition group (fluoxetine hydrochloride treatment combined with acupuncture at ghost points, n = 80). Pre-treatment symptoms were recorded, and the clinical curative effect and adverse reactions [Asberg Antidepressant Side Effects Scale (SERS)] were assessed. Depression before and after treatment [Hamilton Depression Scale (HAMD)-24], neurotransmitter levels [5-HT, norepinephrine (NE), dopamine (DA)], oxidative stress indicators [superoxide dismutase (SOD), malondialdehyde (MDA)], and sleep quality [Pittsburgh Sleep Quality Index (PSQI)] were compared. RESULTS: The total efficacy rate was 97.50% in the coalition group and 86.25% in the single-agent group (P < 0.05). After 2, 4, 6, and 8 wk of treatment, the HAMD, self-rating depression scale, and SERS scores of the coalition and single-agent groups decreased compared with pre-treatment, and the decrease was more significant in the coalition group (P < 0.05). After 8 wk of treatment, the levels of NE, DA, 5-HT, and SOD in the coalition and single-agent groups increased, while the levels of MDA decreased; the increases and decrease in the coalition group were more significant (P < 0.05). The PSQI scores of the coalition and single-agent groups decreased, and the decrease was more significant in the coalition group (P < 0.05). CONCLUSION: Acupuncture at ghost points combined with paroxetine tablets can safely improve depressive symptoms and sleep disorders, regulate neurotransmitter levels, and reduce stress responses in patients with mild-to-moderate depression.

Sensitive detection of H2S based on Ce doped ZnCo2O4 hollow microspheres at low working temperature.

In order to develop a highly efficient H2S gas sensor at low working temperature, in this work, a kind of novel Ce-doped ZnCo2O4 hollow microspheres (Ce/ZnCo2O4 HMSs) were successfully synthesized using a template-free one-pot method, showing a sensitive response toward H2S. The microstructure and morphology of the material were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The gas-sensing performance of the composite was investigated, showing that the ZnCo2O4 doped with 6 mol% Ce had the highest response to 20 ppm H2S at a low operating temperature of 160 °C with a response value of 67.42, which was about 2 times higher than that of original ZnCo2O4. The prepared Ce/ZnCo2O4 HMS sensor in response to H2S exhibited a linear range of 0.1-200 ppm with a low detection limit of 0.1 ppm under the conditions of ambient humidity of 45% and ambient temperature of 20 °C. Meanwhile, it also possessed good selectivity, repeatability and reproducibility. The response value of the sensor decreased by 5.32% after 7 months of continuous monitoring of H2S in an atmospheric environment of a pig farm, indicating that the sensor had a long-term stability and continuous service life with important application prospects.

Serum angiopoietin-2/angiopoietin-1 ratio is associated with cardiovascular and all-cause mortality in peritoneal dialysis patients: a prospective cohort study.

INTRODUCTION: Our objective was to examine the factors associated with the serum angiopoietin-2/angiopoietin-1 (Angpt-2/Angpt-1) ratio in peritoneal dialysis (PD) patients and to investigate the association between Angpt-2/Angpt-1 ratio and cardiovascular and all-cause mortality. METHODS: Patients on PD who were prevalent between January 2014 and April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters, serum angiopoietin-2 and angiopoietin-1 levels. Patients were dichotomized into two groups according to a median of Angpt-2/Angpt-1 ratio and followed up prospectively until the end of the study. RESULTS: A total of 325 patients were enrolled, including 168 males (51.7%) with a mean age of 56.9 ± 14.2 years and a median PD duration of 32.4 (9.8-55.9) months. Multiple linear regression showed pulse pressure (ß = 0.206, p < .001) and high-sensitivity C-reactive protein (hs-CRP) (ß = 0.149, p = .011) were positively correlated with serum Angpt-2/Angpt-1 ratio, while residual renal function (RRF) (ß= -0.219, p < .001) was negatively correlated with serum Angpt-2/Angpt-1 ratio. Multivariate Cox regression analysis showed the high serum Angpt-2/Angpt-1 ratio was an independent predictor of cardiovascular mortality (hazard ratio (HR)=2.467, 95% confidence interval (CI) 1.243-4.895, p = .010) and all-cause mortality (HR = 1.486, 95%CI 1.038-2.127, p = .031). In further subgroup analysis by gender, a significant association was shown in high Angpt-2/Angpt-1 ratio with all-cause mortality in male (p < .05), but not in female patients (p>.05). CONCLUSIONS: High Angpt-2/Angpt-1 ratio is an independent risk factor for cardiovascular and all-cause mortality in PD patients.

Scientific epistemology beliefs and acceptance of Traditional Chinese Medicine: A multigroup analysis based on the UTAUT model in Southern China.

Purpose: This study for the first time delves into the intricate relationship between scientific literacy and the acceptance of traditional Chinese medicine (TCM) by employing a multigroup path analysis based on the Unified Theory of Acceptance and Use of Technology (UTAUT) model. We adopted Scientific Epistemology Belief (SEB) as an indicator for measuring scientific literacy due to its comprehensive reflection of individuals' understanding of scientific knowledge and knowing. In assessing TCM acceptance, we focused on Chinese parents' receptivity towards pediatric TCM, as it offers a more genuine representation of actual inclinations. Methods: A convenience sample of 1016 Chinese parents in Southern China was assessed using online Likert-scale questionnaires on SEB and UTAUT determinants (including performance expectancy, social influence, risk awareness, and facilitating conditions). A K-means cluster analysis was employed to discern distinct SEB profiles, followed by a multigroup path analysis to ascertain UTAUT model variations across these profiles. Results: Five SEB profiles were identified, namely, intermediate, absolutistic, multiplistic, sophisticated, and evidence-based. Evidence-based believers manifested the highest pediatric TCM acceptance, albeit with elements of blind faith, while multiplistic skeptics, prone to questioning everything, displayed the least acceptance. The absolutistic, intermediate, and sophisticated demonstrated moderate TCM acceptance levels, with the intermediate profile outscoring both absolutistic and sophisticated. These findings highlight that individuals with high scientific literacy do not blindly endorse TCM, nor do those with limited scientific understanding fully appreciate TCM's merits. Conclusion: SEB significantly moderates TCM acceptance factors in the UTAUT model, indicating that extremes in scientific knowledge spectrum result in less balanced TCM perspectives. Our findings pave the way for novel insights into harmonizing modern and traditional medical practices.

Material extrusion 3D-printing technology: A new strategy for constructing water-soluble, high-dose, sustained-release drug formulations.

The advantage of low-temperature forming through direct ink writing (DIW) 3D printing is becoming a strategy for the construction of innovative drug delivery systems (DDSs). Optimization of the complex formulation, including factors such as the printing ink, presence of solvents, and potential low mechanical strength, are challenges during process development. This study presents an application of DIW to fabricate water-soluble, high-dose, and sustained-release DDSs. Utilizing poorly compressible metformin hydrochloride as a model drug, a core-shell delivery system was developed, featuring a core composed of 96 % drug powder and 4 % binder, with a shell structure serving as a drug-release barrier. This design aligns with the sustained-release profile of traditional processes, achieving a 25.8 % reduction in volume and enhanced mechanical strength. The strategy facilitates sustained release of high-dose water-soluble formulations for over 12 h, potentially improving patient compliance by reducing formulation size. Process optimization and multi-batch flexibility were also explored in this study. Our findings provide a valuable reference for the development of innovative DDSs and 3D-printed drugs.

Cannabidiol Exerts Sedative and Hypnotic Effects in Normal and Insomnia Model Mice Through Activation of 5-HT1A Receptor.

Cannabis sativa has been used for improving sleep for long history. Cannabidiol (CBD) has drown much attention as a non-addictive psychoactive component in Cannabis sativa extract. However, the effects of CBD on sleep architecture and it's acting mechanism remains unclear. In the present study, we evaluated the sedative-hypnotic effect of cannabidiol (CBD), assessed the effects of CBD on sleep using a wireless physiological telemetry system. We further explored the therapeutic effects of CBD using 4-chloro-dl-phenylalanine (PCPA) induced insomnia model and changes in sleep latency, sleep duration and intestinal flora were evaluated. CBD shortened sleep latency and increases sleep duration in both normal and insomnia mice, and those effects were blocked by 5-HT1A receptor antagonist WAY100635. We determined that CBD increases 5-HT1A receptors expression and 5-HT content in the hypothalamus of PCPA-pretreated mice and affects tryptophan metabolism in the intestinal flora. These results showed that activation of 5-HT1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD. This study validated the effects of CBD on sleep and evaluated its potential therapeutic effects on insomnia.

Fractal Analysis of Left Ventricular Trabeculae in Patients with End-Stage Renal Disease: A Random Survival Tree Analysis.

BACKGROUND: The complexity of left ventricular (LV) trabeculae is related to the prognosis of several cardiovascular diseases. PURPOSE: To evaluate the prognostic value of LV trabecular complexity in patients with end-stage renal disease (ESRD). STUDY TYPE: Prospective outcome study. POPULATION: 207 participants on maintenance dialysis, divided into development (160 patients from 2 centers) and external validation (47 patients from a third center) cohorts, and 72 healthy controls. FIELD STRENGTH: 3.0T, steady-state free precession (SSFP) and modified Look-Locker imaging sequences. ASSESSMENT: All participants had their trabecular complexity quantified by fractal analysis using cine SSFP images. Patients were followed up every 2 weeks until April 2023, or endpoint events happened. Random Forest (RF) and Cox regression models including age, diabetes, LV mass index, mean basal fractal dimension (FD), and left atrial volume index, were developed to predict major adverse cardiac events (MACE). Patients were divided into low- and high-risk groups based on scores derived from the RF model and survival compared. STATISTICAL TESTS: Receiver operating characteristic curve analysis; Kaplan-Meier survival analysis with log rank tests; Harrel's C-index to assess model performance. A P value <0.05 was considered statistically significant. RESULTS: Fifty-five patients (26.57%) experienced MACE during a median follow-up time of 21.83 months. An increased mean basal FD (≥1.324) was associated with a significantly higher risk of MACE. The RF model (C-index: 0.81) had significantly better discrimination than the Cox regression model (C-index: 0.74). Participants of the external validation dataset classified into the high-risk group had a hazard of experiencing MACE increased by 12.29 times compared to those in the low-risk group. DATA CONCLUSION: LV basal FD was an independent predictor for MACE in patients with ESRD. Reliable risk stratification models could be generated based on LV basal FD and other MRI variables using RF analysis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Research hotspots and development trends in volume management of peritoneal dialysis patients: a bibliometrics and visual analysis up to 2022.

OBJECTIVES: Among different renal replacement therapies (RRTs), peritoneal dialysis (PD) is a family based treatment method with multiple advantages, which allowing patients to maintain autonomy, avoiding frequent hospital visits, and preventing the spread of the disease virus. To visually analyze the literatures related to volume management of PD patients through bibliometric methods, to explore research hotspots and development trends in this field. METHODS: The relevant literatures of PD patient volume management in the Web of Science core collection database were retrieved with the terms of peritoneal dialysis, volume management, capacity management, fluid status, and volume overload. The retrieval time was from the establishment of the database to October 2022. CiteSpace 6.1.R3 software was used to visually analyze Country, Institution, Author, Keyword, and draw keyword clusters and keyword emergence maps. RESULTS: A total of 788 articles were included in the analysis, and the annual number of papers was on the rise, with the American, China, and Brirain in the top three, and Peking University and University College London in the top. Keywords cluster analysis showed 11 clusters. In the keyword emergence analysis, the keywords with higher emergence intensity rank are continuous cyclic peritoneal dialysis, ambulatory peritoneal dialysis, and icodextrin. The current research hotspots and trends are in the evaluation of peritoneal dialysis patients' volume status, the selection and adjustment of dialysis prescriptions, and adverse health outcomes. CONCLUSION: The research on peritoneal dialysis volume management in China started late, but it has developed rapidly, and has a firm grasp of current research hotspots. However, there is less cooperation with other countries, so international exchanges and cooperation should be strengthened. At present, the volume assessment methods and dialysis modes are still the research hotspots, paying more attention to the adverse health outcomes of patients.

Left Ventricular Vertical Run-Length Nonuniformity MRI Adds Prognostic Value to MACE in Patients with End-Stage Renal Disease.

BACKGROUND: Vertical run-length nonuniformity (VRLN) is a texture feature representing heterogeneity within native T1 images and reflects the extent of cardiac fibrosis. In uremic cardiomyopathy, interstitial fibrosis was the major histological alteration. The prognostic value of VRLN in patients with end-stage renal disease (ESRD) remains unclear. PURPOSE: To evaluate the prognostic value of VRLN MRI in patients with ESRD. STUDY TYPE: Prospective. POPULATION: A total of 127 ESRD patients (30 participants in the major adverse cardiac events, MACE group). FIELD STRENGTH/SEQUENCE: 3.0 T/steady-state free precession sequence, modified Look-Locker imaging. ASSESSMENT: MRI image qualities were assessed by three independent radiologists. VRLN values were measured in the myocardium on the mid-ventricular short-axis slice of T1 mapping. Left ventricular (LV) mass, LV end-diastolic and end-systolic volume, as well as LV global strain cardiac parameters were measured. STATISTICAL TESTS: The primary endpoint was the incident of MACE from enrollment time to January 2023. MACE is a composite endpoint consisting of all-cause mortality, acute myocardial infarction, stroke, heart failure hospitalization, and life-threatening arrhythmia. Cox proportional-hazards regression was performed to test whether VRLN independently correlated with MACE. The intraclass correlation coefficients of VRLN were calculated to evaluate intraobserver and interobserver reproducibility. The C-index was computed to examine the prognostic value of VRLN. P-value <0.05 were considered statistically significant. RESULTS: Participants were followed for a median of 26 months. VRLN, age, LV end-systolic volume index, and global longitudinal strain remained significantly associated with MACE in the multivariable model. Adding VRLN to a baseline model containing clinical and conventional cardiac MRI parameters significantly improved the accuracy of the predictive model (C-index of the baseline model: 0.781 vs. the model added VRLN: 0.814). DATA CONCLUSION: VRLN is a novel marker for risk stratification toward MACE in patients with ESRD, superior to native T1 mapping and LV ejection fraction. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.

Effects of polystyrene microplastics on Euglena gracilis: Intracellular distribution and the protozoan transcriptional responses.

Microplastics (MPs) introduced into aquatic environments inevitably interact with aquatic organisms such as plankton, potentially yielding adverse effects on the aquatic ecosystem. The extent to which MPs can infiltrate planktonic cells and evoke a molecular response remains largely unknown. In the present study, the internalization of fluorescently labeled polystyrene (PS) MPs on Euglena gracilis cells was investigated, determining the transcriptional responses within protozoa after an 8-day exposure period. The results showed that exposure to 25 mg/L PS-MPs for 8 days, significantly inhibited protozoan growth (P < 0.05) and decreased the chlorophyll a content of E. gracilis. The photosynthetic efficiency of E. gracilis was suppressed by MPs after 4 days, and then recovered to control values by the eighth day. Fluorescence imaging confirmed the presence of MPs in E. gracilis. Transcriptomic analysis revealed the influence of PS-MPs on a diverse range of transcriptional processes, encompassing oxidative phosphorylation, oxidation-reduction process, photosynthesis, and antioxidant enzymes. Notably, a majority of the differentially expressed genes (DEGs) exhibited down-regulation. Furthermore, PS-MPs disturbed the transcriptional regulation of chloroplasts and photosynthesis. These findings indicate a direct interaction between PS-MPs and organelles within E. gracilis cells following internalization, thereby disrupting regular gene expression patterns and posing a substantial environmental risk to the aquatic ecosystem.

Flavonoids contribute most to discriminating aged Guang Chenpi (Citrus reticulata 'Chachi') by spectrum-effect relationship analysis between LC-Q-Orbitrap/MS fingerprint and ameliorating spleen deficiency activity.

To further explore the mechanism of "the longer storage time, the better bioactivity" of aged Guang Chenpi, the dry pericarp of Citrus reticulata 'Chachi' (CRC), a series of activity assessments were performed on spleen deficiency mice. The constituents in CRC with different storage years were analyzed by LC-Q-Orbitrap/MS. A total of 53 compounds were identified, and CRC stored for more than 5 years showed higher flavonoid content, especially that of polymethoxyflavones. Anti-spleen deficiency bioactivity analysis among various CRC with different storage years showed aged CRC (stored for more than 3 years) could significantly alleviate fatigue and depression behaviors much better, increase D-xylose and gastrin secretion, and upregulate the expression of the linking protein occludin in the colon walls. Results from 16S rDNA sequencing showed that aged CRC could downregulate the abundance of Enterococcus, Gemmata, Citrobacter, Escherichia_Shigella, and Klebsiella, which were significantly overrepresented in the model group. Bacteroides, Muribaculum, Alloprevotella, Paraprevotella, Alistipes, Eisenbergiella, and Colidextribacter were downregulated in the model group but enriched in the CRC groups. At last, the spectrum-effect relationship analysis indicated that flavonoids such as citrusin III, homoeriodictyol, hesperidin, nobiletin, and isosinensetin in aged CRC showed the highest correlation with better activity in ameliorating spleen deficiency by regulating gut microbiota. Flavonoids contribute most to discriminating aged CRC and could disclose the basis of "the longer storage time, the better bioactivity" of aged Guang Chenpi.

Clinical risk factors for peritoneal dialysis withdrawal at different dialysis duration.

BACKGROUND: The duration of patients maintained on peritoneal dialysis (PD) varied. This study investigated the clinical risk factors for PD withdrawal at different dialysis duration. METHODS: Patients who initiated PD from 1994 to 2011 were recruited and followed for at least 10 years until 2021. Patients were grouped into four groups according to dialysis duration or time on treatment (TOT) when withdrew PD. RESULTS: A cohort of 586 patients were enrolled (mean age of 54.9 years, median dialysis duration or TOT of 47.9 months). Patients who maintained PD for longer than 10 years were younger, with lower prevalence of diabetes, lower serum C-reactive protein (CRP) level and white blood cell (WBC) count, higher serum albumin and pre-albumin level, higher normalized protein catabolic rate (nPCR) and residual kidney function, and more common use of renin-angiotensin system inhibitors (RASi) at baseline (p < 0.05 for all). Peritonitis related death and ultrafiltration failure related HD transferring increased along with time on PD (p < 0.001). Old age, diabetes, low serum albumin, high WBC count, hypertensive nephropathy, and nonuse of RASi were associated with increased risk of non-transplantation related PD withdrawal (p < 0.05 for all). Low baseline CRP and use of RASi were independent predictors for long-term PD maintenance (p < 0.05 for all). CONCLUSIONS: Long-term PD patients demonstrated young age, low prevalence of diabetes, better nutrition status, absence of inflammation, better residual kidney function, and higher proportion of RASi usage at baseline. Absence of inflammation and use of RASi were independently associated with long-term PD maintenance.

Internet-Based Self-Help Mindful Self-Compassion Intervention for Parents of Children With Cancer: A Pilot Study.

BACKGROUND: Parents of children with cancer may experience persistent psychological distress and impaired physical health throughout their children's diagnosis and treatment. OBJECTIVE: This study aimed to develop a mindful self-compassion program for parents of children with cancer and explore its effect. METHODS: This pre-post-test study without a control group was conducted with 34 Chinese parents of children with cancer, using mixed methods. Participants received a 6-week internet-based self-help mindful self-compassion intervention. Self-compassion, post-traumatic stress symptoms, depression, and sleep quality were measured at baseline and at 10 weeks post-baseline. Semi-structured interviews were conducted with 9 completers within 10 days after the intervention was completed. RESULTS: Significant differences were observed in self-compassion, re-experiencing, physical depressive symptoms, and sleep quality. Two participants reported feeling miserable or recalling distressing experiences, of which one withdrew from the study while the other completed the intervention. CONCLUSION: The program could improve self-compassion, re-experiencing, physical depressive symptoms, and sleep quality in parents of children with cancer, which demonstrated the feasibility of delivering a self-help mindful self-compassion intervention through the internet. Increasing retention rates in future studies merits further discussion.

Assessment of the Prognostic Value of MRI Left Ventricular Global Function Index (LVGFI) in Patients With End-Stage Renal Disease Under Maintenance Dialysis.

BACKGROUND: Left ventricular global function index (LVGFI) integrates LV volumetric and functional parameters. In patients with end-stage renal disease (ESRD), cardiac injury manifests as LV hypertrophy and dysfunction. However, the prognostic value of LVGFI in this population remains unclear. PURPOSE: To investigate the association of LVGFI with major adverse cardiac events (MACE) in patients with ESRD. STUDY TYPE: Prospective. POPULATION: One hundred fifty-eight ESRD patients (mean age: 54.1 ± 14.4 years; 105 male) on maintenance dialysis. FILED STRENGTH/SEQUENCE: 3.0 T, balanced steady-state free precession (bSSFP) cine and modified Look-Locker inversion recovery (MOLLI) sequences. ASSESSMENT: LV volumetric and functional parameters were determined from bSSFP images. LVGFI was calculated as the ratio of stroke volume to global volume and native T1 was determined from MOLLI T1 maps. MACE was recorded on follow up. Models were developed to predict MACE from conventional risk factors combined with LVGFI, GLS, native T1, and LV mass index (LVMI), respectively. Subgroup analyses were further performed in participants with LVEF above median. STATISTICAL TESTS: Cox proportional hazard regression and log-rank test were used to investigate the association between LVGFI and MACE. The predictive models were evaluated and compared using Harrell's C-statistics and DeLong tests. A P value <0.05 was considered statistically significant. RESULTS: Thirty-four MACE occurred during the median follow-up period of 26 months. The hazard of MACE increased by 114% for each 10% decrease in LVGFI in univariable analysis. The predictive model consisting of LVGFI (C-statistic: 0.724) had significantly better predictive performance than the others (all P < 0.001). These results were consistent in patients (N = 79) with LVEF > median (63.54%). DATA CONCLUSION: LVGFI is a novel marker for MACE risk stratification in patients with ESRD and was better able to predict MACE than native T1 mapping and GLS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Fractal analysis: Left ventricular trabecular complexity cardiac MRI adds independent risks for heart failure with preserved ejection fraction in participants with end-stage renal disease.

PURPOSE: To measure left ventricular (LV) trabecular complexity by fractal dimension (FD) in patients with end-stage renal disease (ESRD), and assess whether FD was an independent risk factor for heart failure with preserved ejection fraction (HFpEF), or a significant predictor for adverse outcome in this population. METHODS: The study retrospectively enrolled 104 participants with ESRD who underwent 3.0 T cardiac magnetic resonance imaging (MRI) from June 2018 to November 2020. LV trabeculation was quantified with fractal analysis of short-axis cine slices to estimate the FD. Logistic regression analyses were used to evaluate FD and cardiac MRI parameters and to find independent risk predictors. Cox proportional hazard regression was used to investigate the association between FD and MACE. RESULTS: LV FD was higher in in the HFpEF group than those in the non-HFpEF group, with the greatest difference near the base of the ventricle. Age, minimum left atrial volume index, and LV mean basal FD were independent predictors for HFpEF in patients with ESRD. Combining the mean basal FD with typical predictive factors resulted in a C-index (0.902 vs 0.921), which was not significantly higher. Same improvements were found for net reclassification improvement [0.642; 95% confidence interval (CI), 0.254-1.029] and integrated discrimination index (0.026; 95% CI, 0.008-0.061). Participants with a LV global FD above the cutoff value (1.278) had higher risks of MACE in ESRD patients. CONCLUSIONS: LV trabecular complexity measured by FD was an independent risk factor for HFpEF, and a significant predictor for MACE among patients with ESRD.

Synthesis, anti-leukemia activity, and molecular docking of novel 3,16-androstenedione derivatives.

In this study, we synthesized androsta-4,14-diene-3,16-dione, 12ß-hydroxyandrosta-4,14-diene-3,16-dione, and other 3,16-androstenedione derivatives from commercially available dehydroepiandrosterone as a starting material in 9-13 steps with high yields. The bioactivity of the obtained compounds was evaluated. Compounds 14a and 23a were shown to have high antitumor activity against acute lymphoblastic leukemia cell lines Nalm-6 and BALL-1, respectively. Network pharmacology analysis showed that the anti-leukemia activity of compounds 14a and 23a might be related to the JAK2, ABL1 protein, and PI3K/Akt signaling pathways. The molecular docking of compounds 14a and 23a identified possible active sites, with the lowest docking scores for PTGS2 and MAPK14, respectively. In addition, the absorption, distribution, metabolism, and excretion prediction results revealed the drug-likeness of the two compounds. Therefore, compounds 14a and 23a should be considered anti-leukemia candidates in future studies.

An observational study on the effect of seasonal variation on peritoneal dialysis patients.

Background: Seasonal variation has an impact on plants, wild animals, and also human beings. Data have shown seasonal variation has a significant impact on patients' fluid status, biochemistry results, and outcomes in hemodialysis populations. The relevant data on peritoneal dialysis is scant. Methods: This was a cross sectional study. All patients followed up in our center had a peritoneal equilibration test and PD adequacy test every 6 months. All the peritoneal equilibration test and PD adequacy test data were collected during December 2019 to November 2020. The monthly delivery information of the whole center was collected from 2015 to 2019. Results: There were 366 patients and 604 sets of peritoneal equilibration test and PD adequacy test results in the study. Plasma albumin and phosphate levels were higher in summer. The monthly average outdoor temperature was positively correlated with plasma albumin. There was no seasonal difference in peritoneal dialysis ultrafiltration or urine volume. The percentage of low glucose concentration (1.5%) usage was higher in summer and lower in winter. Conclusion: Plasma albumin and phosphate levels were higher in summer in PD patients. Weaker glucose peritoneal dialysis dialysate was more widely used in summer. Understanding the seasonal variation of peritoneal dialysis is helpful in individualized treatment.

E3 ligase HECTD3 promotes RNA virus replication and virus-induced inflammation via K33-linked polyubiquitination of PKR.

Uncontrolled viral replication and excessive inflammation are the main causes of death in the host infected with virus. Hence inhibition of intracellular viral replication and production of innate cytokines, which are the key strategies of hosts to fight virus infections, need to be finely tuned to eliminate viruses while avoid harmful inflammation. The E3 ligases in regulating virus replication and subsequent innate cytokines production remain to be fully characterized. Here we report that the deficiency of the E3 ubiquitin-protein ligase HECTD3 results in accelerated RNA virus clearance and reduced inflammatory response both in vitro and in vivo. Mechanistically, HECTD3 interacts with dsRNA-dependent protein kinase R (PKR) and mediates Lys33-linkage of PKR, which is the first non-proteolytic ubiquitin modification for PKR. This process disrupts the dimerization and phosphorylation of PKR and subsequent EIF2α activation, which results in the acceleration of virus replication, but promotes the formation of PKR-IKK complex and subsequent inflammatory response. The finding suggests HECTD3 is the potential therapeutic target for simultaneously restraining RNA virus replication and virus-induced inflammation once pharmacologically inhibited.