Corrigendum: Effectiveness, safety, and treatment pattern of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia: interim analysis from a multicenter, prospective, real-world study (Actualize Study).

[This corrects the article DOI: 10.3389/fphar.2024.1398953.].

NAD+ homeostasis and its role in exercise adaptation: A comprehensive review.

Nicotinamide adenine dinucleotide (NAD+) is a crucial coenzyme involved in catalyzing cellular redox reactions and serving as a substrate for NAD+-dependent enzymes. It plays a vital role in maintaining tissue homeostasis and promoting healthy aging. Exercise, a well-established and cost-effective method for enhancing health, can influence various pathways related to NAD+ metabolism. Strategies such as supplementing NAD+ precursors, modulating NAD+ synthesis enzymes, or inhibiting enzymes that consume NAD+ can help restore NAD+ balance and improve exercise performance. Various overlapping signaling pathways are known to play a crucial role in the beneficial effects of both NAD+ and exercise on enhancing health and slowing aging process. Studies indicate that a combined strategy of exercise and NAD+ supplementation could synergistically enhance athletic capacity. This review provides an overview of current research on the interactions between exercise and the NAD+ network, underscoring the significance of NAD+ homeostasis in exercise performance. It also offers insights into enhancing exercise capacity and improving aging-related diseases through the optimal use of exercise interventions and NAD+ supplementation methods.

Effectiveness, safety, and treatment pattern of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia: interim analysis from a multicenter, prospective, real-world study (Actualize Study).

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

Nature and success: Outdoor play is linked to school readiness.

BACKGROUND: and Purpose: Outdoor play is widely acknowledged for its benefits to physical health and psychological well-being, yet its relationship with school readiness remains understudied in preschoolers. To address this gap in the literature, this study investigated how outdoor play relates to cognitive and psychosocial development among a nationally representative sample of preschoolers. MATERIALS AND METHOD: Data on the duration of outdoor play (on weekdays and weekends) and specific cognitive and psychosocial outcome variables (i.e., early learning skills, self-regulation, social-emotional development, and flourishing) were collected via questionnaires provided to the caregivers of preschoolers. Logistic regressions were performed to examine the associations between outdoor play with cognitive and psychosocial outcomes while adjusting for covariates and calculate the odds ratio with 95 % confidence intervals (CI). RESULTS: Among the 10,682 preschoolers (i.e., 3-5y) included in this study (i.e., 5558 boys, Mage = 3.98 ± 0.99 years), there was a lower percentage of preschoolers engaged in outdoor play for over 3 h per day on weekdays (33.39 %) compared to weekends (56.85 %). Outdoor play in preschoolers is positively associated with various domains of school readiness, and engaging in outdoor play for more than 3 h per day is associated with more beneficial outcomes. CONCLUSION: The findings of this cross-sectional study suggest that promoting outdoor play among preschoolers can be an effective strategy for enhancing cognitive, social, and emotional development in this age group although further intervention studies are required to buttress this assumption empirically.

Evaluation the role of insulin signaling pathway in reproductive toxicity of dispersed diesel particulate extract under environmental conditions.

Diesel particulate extract (DPE), which is a significant constituent of airborne particle pollution, has a strong association with the development of cancer and respiratory diseases. Fulvic acid (FA), a plentiful organic macromolecule found in water, has the capability to modify particle surface charge and adsorption capacity when combined with minerals. Nevertheless, there is a scarcity of data regarding the influence of their interaction on DPE toxicity. To examine the impact of environmental factor on the toxic effects of DPE, we used the Caenorhabditis elegans (C. elegans) model to investigate the reproductive toxicity of DPE and FA on insulin signaling pathway. C. elegans were subjected to a semi-fluid medium (NGG) containing different concentrations of DPE or DPE + FA in order to assess germline apoptosis and the expression of important genes in the insulin signaling pathway. Through several mutant strains, we found that daf-2, age-1, pdk-1, akt-1 and daf-16 were involved in DPE-induced apoptosis. Furthermore, and the expression levels of these genes significantly altered. The ratio of daf-16 translocation to nucleation, as well as the amount of reactive oxygen species (ROS), exhibited a dose-response relationship, however, the presence of FA could altered these effects. The results revealed that the insulin signaling pathway plays a vital role in mediating the harmful effects caused by DPE, whereas environmental factors have a substantial impact on its toxicity. Moreover, it was noted that semi-fluid medium could effectively replicate three-dimensional exposure circumstances closely resembling those observed in actual situations.

Modified Suture-Button Latarjet Procedure With Coracoacromial Ligament and Pectoralis Minor Preservation Achieves Good Clinical Outcomes at 2-Year Follow-Up: Case Series of Latarjet Technique.

PURPOSE: To evaluate whether the modified suture-button Latarjet procedure with coracoacromial ligament (CAL) and pectoralis minor (PM) preservation could achieve excellent outcomes at the 2-year follow-up. METHODS: During January 2019 to January 2021, the data of patients who underwent modified suture-button Latarjet with CAL and PM preservation in our department were collected. The glenoid bone loss of these patients was greater than 20% or greater than 10% with high demands for exercise. Partial coracoid osteotomy was based on the results of a preoperative 3-dimensional computed tomography evaluation of the glenoid defect area and corresponding coracoid process morphology. The preoperative and postoperative clinical results were assessed. The minimal clinically important difference (MCID) was used to compare improvement in clinical outcomes. Graft-glenoid union and remodeling were assessed using postoperative 3-dimensional computed tomography, and magnetic resonance imaging was performed to confirm the integrity of the CAL and PM postoperatively. RESULTS: In total, 35 patients were included in this study; the mean follow-up time was 26.9 ± 1.9 months. No case of recurrent dislocation or sublaxity. Significant improvements were observed in mean visual analog scale (VAS) scores for pain during motion, American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and Walch-Duplay score (P < .001). The percentage of patients achieving at least an MCID improvement in clinical outcomes was VAS 85.71%, ASES 97.14%, Rowe 100%, and Walch-Duplay 97.14%. Thirty-three patients (94.3% of all cases) were able to return to their preoperative sport levels, 34 grafts (97.1%) achieved bone union (1 soft union) in 6.3 ± 2.2 months, and the coracoid grafts restored 97.1 ± 4.0% of the perfect-fitting circle at the last follow-up. Postoperative computed tomography scan showed that 31 grafts (88.6%) were placed ideally in vertical view. In the axial view, 25 grafts (82.9%) were flushed to the glenoid, whereas 1 and 5 grafts were fixed medially and laterally, respectively. The CAL and PM were visualized postoperatively. No arthropathy was observed in any patient at the last follow-up. CONCLUSIONS: The modified suture-button Latarjet procedure with CAL and PM preservation obtained good clinical and radiological results without recurrence or complications. A substantial number of patients (>85%) achieved the MCID for the VAS, ASES, Rowe, and Walch-Duplay scores. In addition, the malpositioned graft (17.1%) did not cause arthropathy of the joints at 2-year follow-up. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Meeting 24-h movement behavior guidelines is associated with academic engagement, social-emotional functioning in obese/overweight youth.

BACKGROUND: The 24-h movement behavior (24-HMB) guidelines suggest that the integration of adequate sleep (SL), increased physical activity (PA), and limited screen time (ST) has general health benefits. However, associations of meeting integrated guidelines with academic engagement and social-emotional functioning among obese/overweight youth have yet to be fully examined. Thus, we aimed to investigate the associations between meeting 24-HMB guidelines and the above-presented outcome measures among this unique group. METHODS: In this cross-sectional study, 2800 children and adolescents (youth aged 6-17 years old) that were retrieved from the National Survey of Children's Health (NSCH) were included for data analysis. Exposure of interests included adherence to 24-HMB guideline(s), while indicators of academic engagement and social-emotional functioning were operationalized. Furthermore, multiple logistic regression was conducted while adjusting for social-demographic variables including age, sex, ethnicity, household income, parental education level and mental health status. RESULTS: The percentages of meeting 24-HMB guidelines varied greatly across different combinations: 1399 participants (49.96 %) met 1 of the 3 guidelines, 580 participants (20.91 %) met 2 guidelines, while only 91 participants (2.94 %) met all 3 guidelines. Meeting integrated guidelines was selectively associated with higher odds of indicators (showing interest/curiosity in learning, caring about school performance, and completing all required homework) of academic engagement. Additionally, Meeting SL + ST guideline (OR = 0.52, 95%CI: 0.29-0.93, p < 00.05) was associated with lower odds of serious difficulty in concentrating, remembering, and making decisions, while meeting ST + SL guideline (OR = 1.67, 95%CI: 1.03-2.69, p < 00.05) was more likely to be good at making and keeping friendships. Furthermore, meeting all 3 guidelines was associated with less argumentative behaviors (OR = 0.58, 95%CI: 0.33-0.99, p < 00.05) and a higher level of resilience (OR = 3.51, 95%CI: 1.88-6.54, p < 00.01), while meeting any two integrated guidelines was associated with a higher level of resilience (OR = 1.72, 95%CI: 1.09-2.71, p < 00.05). CONCLUSION: Findings have indicated the role of meeting 24-HMB guidelines, especially integrated guidelines in the healthy development of obese/overweight youth. Policymakers should implement a long-term plan for this unique group to engage in physical activity, achieve enough sleep, and limit screen time.

Intersection of Race, Rurality, and Income in Defining Access to Minimally Invasive Lung Surgery.

BACKGROUND: Race is a potent influencer of health care access. Geography and income may exert equal or greater influence on patient outcomes. We sought to define the intersection of race, rurality, and income and their influence on access to minimally invasive lung surgery in Medicare beneficiaries. METHODS: Centers for Medicare and Medicaid Services data were used to evaluate patients with lung cancer who underwent right upper lobectomy, by open, robotic-assisted thoracic surgery (RATS), or video-assisted thoracic surgery (VATS) between 2018 and 2020. International Classification of Diseases, 10th Edition, was used to define diagnoses and procedures. We excluded sublobar, segmental, wedge, bronchoplasty, or reoperative patients with nonmalignant or metastatic disease or a history of neoadjuvant chemotherapy. Risk adjustment was performed using inverse probability of treatment weighting (IPTW) propensity scores with generalized linear models and Cox proportional hazards models. RESULTS: The cohort comprised 13,404 patients, 4291 open (32.1%), 4317 RATS (32.2%), and 4796 VATS (35.8%). Black/urban patients had significantly higher RATS and VATS rates (P < .001), longer long-term survival (P = .007), fewer open resections (P < .001), and lower overall mortality (P = .007). Low-income Black/urban patients had higher RATS (P = .002), VATS (P < .001), longer long-term survival (P = .005), fewer open resections (P < .001), and lower overall mortality compared with rural White patients (P = .005). CONCLUSIONS: Rural White populations living close to the federal poverty line may suffer a burden of disparity traditionally observed among poor Black people. This suggests a need for health policies that extend services to impoverished, rural areas to mitigate social determinants of health.

Analysis of risk factors and development of predictive model for malnutrition in patients with traumatic brain injury.

Malnutrition is a highly prevalent complication in patients with traumatic brain injury (TBI), and it is closely related to the prognosis of patients. Accurate identification of patients at high risk of malnutrition is essential. Therefore, we analyzed the risk factors of malnutrition in patients with TBI and developed a model to predict the risk of malnutrition. A retrospective collection of 345 patients with TBI, and they were divided into malnutrition and comparison groups according to the occurrence of malnutrition. Univariate correlation and multifactor logistic regression analyses were performed to determine patients' malnutrition risk factors. We used univariate and logistic regression (forward stepwise method) analyses to identify significant predictors associated with malnutrition in patients with TBI and developed a predictive model for malnutrition prediction. The model's discrimination, calibration, and clinical utility were evaluated using the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). A total of 216 patients (62.6%) developed malnutrition. Multifactorial logistic regression analysis showed that pulmonary infection, urinary tract infection, dysphagia, application of NGT, GCS score ≤ 8, and low ADL score were independent risk factors for malnutrition in patients with TBI (P < 0.05). The area under the curve of the model was 0.947. Calibration plots showed good discrimination of model calibration. DCA showed that the column line plot models were all clinically meaningful when nutritional interventions were performed over a considerable range of threshold probabilities (0-0.98). Malnutrition is widespread in patients with TBI, and the nomogram is a good predictor of whether patients develop malnutrition.

Deciphering the epidemiological dynamics: Toxoplasma gondii seroprevalence in mainland China's food animals, 2010-2023.

Background: Toxoplasma gondii (T. gondii) is a significant protozoan pathogen among food animals. Despite the threat to public health by T. gondii infections, there's limited understanding of its seroprevalence and trends in food animals across mainland China. This study aimed to estimate the seroprevalence of T. gondii infections among swine, sheep, goats, chickens, and cattle in mainland China from 2010 to 2023. Methods: We searched cross-sectional studies published between 2010 and 2023 that reported the prevalence of T. gondii in food animals from databases including PubMed, Embase, Web of Science, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang data, and the China Science and Technology Journal Database (CQVIP). We performed subgroup analyses to explore the impact of different factors on the seroprevalence of T. gondii. Pooled estimates of T. gondii seroprevalence were calculated with a random-effects model. Results: An analysis of 184 studies involving 211985 animals revealed a T. gondii overall seroprevalence of 15.3% (95% CI: 13.1-17.8). Although the seroprevalence of food animals across mainland China was relatively stable from 2010 to 2023, notable variations were observed across different animal types and regions (P < 0.01), along with changes in geographical distribution. Sample type, detection method, animal age, and history of abortion were identified as key risk factors for T. gondii seroprevalence. Conclusion: The study conducted a meta-analysis on the seroprevalence of T. gondii in mainland China's Food Animals from 2010 to 2023, and identified key risk factors. These findings advance our understanding of T. gondii infection dynamics, offering critical insights for developing control strategies and guiding public health policies.

The risk factors for arteriovenous fistula dysfunction in maintenance hemodialysis patients: A cross-sectional study.

INTRODUCTION: Arteriovenous fistula (AVF) dysfunction is a prevalent complication among maintenance hemodialysis patients. However, the factors influencing AVF patency remain unclear. To address this, we conducted a study aimed at identifying factors contributing to AVF dysfunction in this patient population. METHODS: The study compared clinical data, vascular calcification score, and laboratory data focusing on blood cell composition and coagulation in 100 maintenance hemodialysis patients in whom an AVF had been inserted from January through September of 2022. The patients were divided into a group in which the AVF functioned without issues and a group in which the AVF was dysfunctional, defined as not able to provide a blood flow of greater than 200 mL/min. FINDINGS: Patients in the 2 groups (56 in the dysfunctional AVF group and 44 in the group with satisfactory AVF function) were similar demographically. Compared with the normally functioning AVF group, the AVF dysfunction group exhibited significantly higher Agatston calcium scores (20.5 [1.28, 298] median [Q1, Q3] vs. 1.14 [0.00, 11.6]; p = 0.01), elevated triglyceride levels (1.1 [0.6, 1.2] mmol/L vs. 0.5 [0.3, 0.8]; p < 0.01), increased prothrombin activity (113 ± 22.1% vs. 99.4 ± 23.1; p < 0.01), lower prothrombin time (10.4 [9.8, 10.8] s vs. 11.0 [10.3, 11.5]; p < 0.01), higher red blood cell (RBC) counts (3.5 ± 0.7 · 1012/L vs. 3.0 ± 0.7; p < 0.01), and elevated hemoglobin levels (98.0 ± 21.8 g/L vs. 84.9 ± 24.2; p < 0.01). Higher C-reactive protein (20.2 [3.3, 20.2] mg/L vs. 17.8 [6.2, 17.8]; p = 0.01) and procalcitonin levels (0.9 [0.4, 0.9] ng/mL vs. 0.5 [0.2, 0.7]; p < 0.01) were also noted. Logistic regression analysis indicated that platelet/lymphocyte ratio, monocyte/lymphocyte ratio, and RBC count were factors associated with AVF dysfunction. Increased monocyte/lymphocyte ratio and RBC count correlated with higher risk, while a higher platelet/lymphocyte ratio was associated with lower risk. DISCUSSION: Arteriovenous fistula dysfunction in maintenance hemodialysis patients is associated with higher proportions of specific hematological parameters, particularly elevated RBC count, and altered platelet/lymphocyte and monocyte/lymphocyte ratios.

Paradoxical Embolic Stroke Following Percutaneous Transluminal Angioplasty in a Hemodialysis Patient.

Paradoxical embolism is a medical condition characterized by the migration of an embolus from a venous source into the systemic circulation. This occurs through a specific cardiac abnormality known as a right-to-left shunt, ultimately resulting in the possibility of arterial embolism. Patent foramen ovale (PFO) is the most common cause of intracardiac shunting. We reported a rare case of a 56-year-old man on hemodialysis with PFO and arteriovenous fistula dysfunction who suffered a paradoxical embolic ischemic stroke after percutaneous transluminal angioplasty. This case emphasized the potential risk of paradoxical embolism in hemodialysis patients with vascular access problems. We aimed to highlight the importance of searching for PFO, as it may serve as a possible source of embolism in these patients.

Characteristics and Prognostic Factors of SARS-CoV-2 Omicron Variant Infection in Hemodialysis Patients: A Single-Center Study in China.

INTRODUCTION: This study aimed to evaluate the characteristics and prognostic factors for coronavirus disease 2019 (COVID-19) patients on maintenance hemodialysis (HD). METHODS: All admitted HD patients who were infected with SARS-CoV-2 from December 1, 2022, to January 31, 2023, were included. Patients with pneumonia were further classified into the mild, moderate, severe, and critical illness. Clinical symptoms, laboratory results, radiologic findings, treatment, and clinical outcomes were collected. Independent risk factors for progression to critical disease and in-hospital mortality were determined by the multivariate regression analysis. The receiver operating characteristic analysis with the area under the curve was used to evaluate the predictive performance of developing critical status and in-hospital mortality. RESULTS: A total of 182 COVID-19 patients with HD were included, with an average age of the 61.55 years. Out of the total, 84 (46.1%) patients did not have pneumonia and 98 (53.8%) patients had pneumonia. Among patients with pneumonia, 48 (49.0%) had moderate illness, 26 (26.5%) severe illness, and 24 (24.5%) critical illness, respectively. Elder age [HR (95% CI): 1.07 (1.01-1.13), p <0.01], increased levels of lactate dehydrogenase (LDH) [1.01 (1.003-1.01), p <0.01], and C-reactive protein (CRP) [1.01 (1.00-1.01), p = 0.04] were risk factors for developing critical illness. Elder age [1.11 (1.03-1.19), p = 0.01], increased procalcitonin (PCT) [1.07 (1.02-1.12), p = 0.01], and LDH level [1.004 (1-1.01), p = 0.03] were factors associated with increased risk of in-hospital mortality. CONCLUSION: Age, CRP, PCT, and LDH can be used to predict negative clinical outcomes for HD patients with COVID-19 pneumonia.

Exploring the environmental factor fulvic acid attenuates the ecotoxicity of graphene oxide under food delivery exposure.

There is limited understanding of nanoparticle potential ecotoxicity, particularly regarding the influence of environmental factors that can be transferred through the food chain. Here, we assessed the transfer behavior and the ecotoxicity of commercially manufactured graphene oxide nano-materials (GO, <100 nm) in a food chain perspective spanning from Escherichia coli (E. coli) to Caenorhabditis elegans (C. elegans) under simulated environmental conditions. Our findings revealed that E. coli preyed upon GO, subsequently transferring it to C. elegans, with a discernible distribution of GO observed in the digestive system and reproductive system. Accumulated GO generated serious ecological consequences for the higher level of the food chain (C. elegans). More importantly, GO and the resulting injurious effects of germ cells could be transferred to the next generation, indicating that GO exposure could cause genetic damage across generations. Previous research has demonstrated that GO can induce degradation of both the inner and outer cell membranes of E. coli, which is then transmitted to C. elegans through the food chain. Additionally, fulvic acid (FA) possesses various functional groups that enable interaction with nanomaterials. Our findings indicated that these interactions could mitigate ecotoxicity caused by GO exposure via food delivery, and this approach could be extended to modify GO in a way that significantly reduced its toxic effects without compromising performance. These results highlighted how environmental factors could attenuate ecological risks associated with nanomaterial transmission through the food chain.

Risk factors for arteriovenous fistula dysfunction in hemodialysis patients: a retrospective study.

Arteriovenous fistula (AVF) is the first choice of vascular access in hemodialysis (HD) patients. However, the correlations between patient factors and the arteriovenous fistula patency remain unclear. Therefore, our study investigates the risk factors associated with AVF dysfunction in HD patients. A total of 233 end-stage renal disease (ESDR) patients who met the study inclusion criteria in the Nephrology Department of Hunan Provincial People's Hospital between December 2020 and June 2022 were included in this study. The baseline demographic, clinical and laboratory parameters were collected at the time of AVF creation and analyzed. Of the 233 ESRD patients, 146 (62.7%) were male and the mean age was 56.11 ± 12.14 (21-82) years. The patients were followed for a median time of 14 months. Kaplan-Meier analysis showed a 6-, 12- and 24-month post-placement survival of 87.1%, 82.8% and 80.7%, respectively. Univariate Cox regression analysis revealed weight (HR, 1.03; P = 0.03) as a predictor for the loss of vascular access functionality. In addition, multivariate Cox regression analysis further demonstrated that sex (HR, 3.41; P = 0.03), weight (HR 1.08; P < 0.01) and phosphorus level (HR: 3.03; P = 0.01) are independent risk factors for AVF dysfunction. AVF dysfunction is highly associated with several risk factors including weight, phosphorus level, and sex. Positive intervention strategies targeting these potential factors, such as weight loss or oral phosphate binders could improve the long-term success of AVF.

Molecular mechanism of Danshenol C in reversing peritoneal fibrosis: novel network pharmacological analysis and biological validation.

OBJECTIVE: The primary objective of this study is to elucidate the molecular mechanism underlying the reversal of peritoneal fibrosis (PF) by Danshenol C, a natural compound derived from the traditional Chinese medicine Salvia miltiorrhiza. By comprehensively investigating the intricate interactions and signaling pathways involved in Danshenol C's therapeutic effects on PF, we aim to unveil novel insights into its pharmacological actions. This investigation holds the potential to revolutionize the clinical application of Salvia miltiorrhiza in traditional Chinese medicine, offering promising new avenues for the treatment of PF and paving the way for evidence-based therapeutic interventions. METHODS: Firstly, we utilized the YaTCM database to retrieve the structural formula of Danshenol C, while the SwissTargetPrediction platform facilitated the prediction of its potential drug targets. To gain insights into the genetic basis of PF, we acquired the GSE92453 dataset and GPL6480-9577 expression profile from the GEO database, followed by obtaining disease-related genes of PF from major disease databases. R software was then employed to screen for DEG associated with PF. To explore the intricate interactions between Danshenol C's active component targets, we utilized the String database and Cytoscape3.7.2 software to construct a PPI network. Further analysis in Cytoscape3.7.2 enabled the identification of core modules within the PPI network, elucidating key targets and molecular pathways critical to Danshenol C's therapeutic actions. Subsequently, we employed R to perform GO and KEGG pathway enrichment analyses, providing valuable insights into the functional implications and potential biological mechanisms of Danshenol C in the context of PF. To investigate the binding interactions between the core active components and key targets, we conducted docking studies using Chem3D, autoDock1.5.6, SYBYL2.0, and PYMOL2.4 software. We applied in vivo and in vitro experiments to prove that Danshenol C can improve PF. In order to verify the potential gene and molecular mechanism of Danshenol C to reverse PF, we used quantitative PCR, western blot, and apoptosis, ensuring robust and reliable verification of the results. RESULTS: ① Wogonin, sitosterol, and Signal Transducer and Activator of Transcription 5 (STAT5) emerged as the most significant constituents among the small-molecule active compounds and gene targets investigated. ②38 targets intersected with the disease, among which MAPK14, CASP3, MAPK8 and STAT3 may be the key targets; The results of GO and KEGG analysis showed that there was a correlation between inflammatory pathway and Apoptosis. ④Real-time PCR showed that the mRNA expressions of MAPK8 (JNK1), MAPK14 (P38) and STAT3 were significantly decreased after Danshenol C treatment (P < 0.05), while the mRNA expression of CASP3 was significantly increased (P < 0.05)⑤Western blot showed that protein expressions of CASP3 and MAPK14 were significantly increased (P < 0.05), while the expression of STAT3 and MAPK8 was decreased after Danshenol C treatment (P < 0.05). ⑥There was no significant difference in flow analysis of apoptosis among groups. CONCLUSION: The findings suggest that Danshenol C may modulate crucial molecular pathways, including the MAPK, Apoptosis, Calcium signaling, JAK-STAT signaling, and TNF signaling pathways. This regulation is mediated through the modulation of core targets such as STAT3, MAPK14, MAPK8, CASP3, and others. By targeting these key molecular players, Danshenol C exhibits the potential to regulate cellular responses to chemical stress and inflammatory stimuli. The identification of these molecular targets and pathways represents a significant step forward in understanding the molecular basis of Danshenol C's therapeutic effects in PF. This preliminary exploration provides novel avenues for the development of anti-PF treatment strategies and the discovery of potential therapeutic agents. By targeting specific core targets and pathways, Danshenol C opens up new possibilities for the development of more effective and targeted drugs to combat PF. These findings have the potential to transform the landscape of PF treatment and offer valuable insights for future research and drug development endeavors.

Transplant Candidate Outcomes After Declining a DCD Liver in the United States.

BACKGROUND: In the context of the organ shortage, donation after circulatory death (DCD) provides an opportunity to expand the donor pool. Although deceased-donor liver transplantation from DCD donors has expanded, DCD livers continue to be discarded at elevated rates; the use of DCD livers from older donors, or donors with comorbidities, is controversial. METHODS: Using US registry data from 2009 to 2020, we identified 1564 candidates on whose behalf a DCD liver offer was accepted ("acceptors") and 16 981 candidates on whose behalf the same DCD offers were declined ("decliners"). We characterized outcomes of decliners using a competing risk framework and estimated the survival benefit (adjusted hazard ratio [95% confidence interval]) of accepting DCD livers using Cox regression. RESULTS: Within 10 y of DCD offer decline, 50.9% of candidates died or were removed from the waitlist before transplantation with any type of allograft. DCD acceptors had lower mortality compared with decliners at 10 y postoffer (35.4% versus 48.9%, P < 0.001). After adjustment for candidate covariates, DCD offer acceptance was associated with a 46% reduction in mortality (0.54 [0.49-0.61]). Acceptors of older (age ≥50), obese (body mass index ≥30), hypertensive, nonlocal, diabetic, and increased risk DCD livers had 44% (0.56 [0.42-0.73]), 40% (0.60 [0.49-0.74]), 48% (0.52 [0.41-0.66]), 46% (0.54 [0.45-0.65]), 32% (0.68 [0.43-1.05]), and 45% (0.55 [0.42-0.72]) lower mortality risk compared with DCD decliners, respectively. CONCLUSIONS: DCD offer acceptance is associated with considerable long-term survival benefits for liver transplant candidates, even with older DCD donors or donors with comorbidities. Increased recovery and utilization of DCD livers should be encouraged.

Association of physical activity and fitness with executive function among preschoolers.

It is well-documented in the literature that high levels of regular physical activity (PA), low levels of sedentary behavior (SB), and high levels of cardiorespiratory fitness (CRF) are associated with superior cognitive functioning, especially with regard to older populations. However, concerning other age groups (e.g., preschoolers) the available evidence documenting such a positive relationship is relatively scarce. Thus, this study aimed to investigate the association of time spent in different PA intensity zones and CRF with executive functions (EFs) in preschool-age children. To this end, preschoolers (n = 127) aged 3 to 6 years were recruited from 9 kindergarten classes in 2 districts of Shenzhen, China. The amount and the intensity of PA were assessed via accelerometry, and the CRF level was quantified by the 20-meter shuttle run test. EFs including inhibitory control and working memory were assessed using the one-on-one iPad-based Early Year Toolbox. Results suggested that children who had a higher CRF level ("impulse control" scores: ß = 0.34, p < .001; "Go" accuracy: ß = 0.31, p < .001; "No-Go" accuracy: ß =0.28, < .001) and spentmore time in moderate-to-vigorous physical activity (MVPA) ("impulse control" scores: ß = 0.50, p < .001; No-Go" accuracy: ß = 0.52, p < .001) had higher scores on inhibitory control tasks, and those who had a higher CRF level had higher scores on a working memory task (ß = 0.24, p < .05). The findings are discussed in light of the positive roles of MVPA and CRF for promoting EFs, but also consider the disproportionate association of PA and CRF with working memory relative to inhibition.

Hypotension and cognitive impairment among the elderly: Evidence from the CLHLS.

BACKGROUND: While high blood pressure has been linked to cognitive impairment, the relationship between low blood pressure, especially hypotension, and cognitive impairment has not been well studied. Therefore, this study aimed to assess the prevalence of hypotension and cognitive impairment in the seniors of China, and the association between hypotension and cognitive function impairment. METHODS: The data was derived from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Systolic blood pressures (SBP) and diastolic blood pressures (DBP) were measured by objective examination. The Chinese version of the Mini-Mental State Examination (CMMSE) was used to evaluate the cognitive impairment of the elderly. Generalized linear models were conducted to evaluate the association of hypotension with cognitive impairment. RESULTS: The prevalence of hypotension and cognitive impairment in the Chinese elderly were 0.76% and 22.06%, respectively. Participants with hypotension, lower SBP, and lower DBP, had odds ratios of 1.62, 1.38, and 1.48 for cognitive impairment, respectively. Besides, the CMMSE scores decreased by 2.08, 0.86, and 1.08 in the elderly with hypotension, lower SBP, and DBP, compared with those with non-hypotension, higher SBP, and DBP, respectively. Subgroup analyses showed that the association of cognitive impairment with hypotension was stronger in Chinese elderly who had decreased activity of daily living. Moreover, there was statistical evidence of a nonlinear dose-response relationship of SBP and DBP with cognitive impairment (Pnonlinear < 0.05). CONCLUSION: Hypotension was a potential risk factor for cognitive impairment of the Chinese elderly, especially for those having decreased activity of daily living. Blood pressure management should be conducted to prevent them from cognitive impairment.