Magnolia Officinalis Alcohol Extract Alleviates the Intestinal Injury Induced by Polygala Tenuifolia Through Regulating the PI3K/AKT/NF-κB Signaling Pathway and Intestinal Flora.

Purpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer's disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT. Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques. Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1ß, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas). Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.

Tuberculosis Prevalence Trends from a Predictive Modelling Study - 10 High-Burden Countries, 1980-2035.

What is already known about this topic?: Given the challenges presented by drug-resistant strains of tuberculosis (TB) and the rising mobility of the population, achieving the objective of eradicating TB appears uncertain. What is added by this report?: The examination of TB incidence trends in 10 high-burden countries (HBCs) indicated a steady rise in cases, with India and China jointly accounting for nearly 70% of the burden. Projections for the future show diverse trajectories in these countries, with potential difficulties in reaching the TB elimination target, especially in Nigeria, Congo, and South Africa. What are the implications for public health practice?: The number of TB cases is on the rise. It is crucial to learn from successful strategies to improve TB prevention and control worldwide through collaborative efforts.

Interaction between Aß and tau on reversion and conversion in mild cognitive impairment patients: After 2-year follow-up.

Background: The role of amyloid-ß (Aß) and tau in reversion and conversion in patients with mild cognitive impairment (MCI) remains unclear. This study aimed to investigate the influence of cerebrospinal fluid (CSF) Aß and tau on reversion and conversion and the temporal sequence of their pathogenicity in MCI patients. Methods: 179 MCI patients were recruited from the Alzheimer's Disease Neuroimaging Initiative database and classified into two groups based on cognitive changes after follow-up: reversal group (MCI to cognitively normal) and conversion group (MCI to Alzheimer's disease). CSF biomarkers and cognitive function were measured at baseline and 2-year follow-up. Partial correlation was used to analyze the association between CSF biomarkers and cognitive function, and multivariable logistic regression to identify independent risk factors for cognitive changes at baseline and 2-year follow-up. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of these risk factors for cognitive changes. Results: The differences in cognitive function and CSF biomarkers between the two groups remained consistent with baseline after 2-year follow-up. After controlling for confounding variables, there was still a correlation between CSF biomarkers and cognitive function at baseline and 2-year follow-up. Multivariable regression analysis found that at baseline, only Aß level was independently associated with cognitive changes, while Aß and tau were both predictive factors after 2-year follow-up. ROC curve analysis revealed that the combination of Aß and tau [area under the curve (AUC) 0.91, sensitivity 84%, specificity 86%] in predicting cognitive changes after 2-year follow-up had better efficacy than baseline Aß alone (AUC 0.81). Conclusion: Aß may precede Tau in causing cognitive changes, and the interaction between the two mediates cognitive changes in patients. This study provides new clinical evidence to support the view that Aß pathology precedes tau pathology, which together contribute to the changes in cognitive function.

Cost-effectiveness analysis of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma.

BACKGROUND: To evaluate the cost-effectiveness of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma (HCC) from the perspective of the Chinese health service system. METHODS: A lifetime partitioned survival model (PSM) was developed to cost-effectively analyze Tislelizumab vs Sorafenib as the first-line treatment of unresectable HCC. The clinical and safety data were derived from a recently randomized clinical trial (RATIONALE-301). Utilities were collected from the published literature. Costs were obtained from an open-access database (http://www.yaozh.com) and previous studies. The model cycle was 21 days, according to the RATIONALE-301 study, and the simulation period was patients' lifetime. Long-term direct medical costs and quality-adjusted life-years (QALYs) were determined. The incremental cost-effectiveness ratio (ICER) was used as the evaluation index. one-way sensitivity analysis (OSWA) and probabilistic sensitivity analysis (PSA) were used to analyze the uncertainty of parameters and to adjust and verify the stability of the baseline results. RESULTS: The Tislelizumab group generated a cost of $39,746.34 and brought health benefits to 2.146 QALYs, while the cost and utility of the Sorafenib group were $26750.95 and 1.578 QALYs, respectively. The Tislelizumab group increased QALYs by 0.568, the incremental cost was $12995.39, and the ICER was $22869.64/QALY, lower than the willingness to pay threshold (WTP). OSWA results showed that the utility of progressed disease (PD), cost of Camrelizumab, and cost of Tislelizumab were the main factors affecting the ICER. PSA results showed that, within 1000 times the Monte Carlo simulation, the cost of the Tislelizumab group was lower than three times the per capita gross domestic product (GDP) of China ($37653/QALY). The cost-effectiveness acceptability curves (CEAC) revealed that when WTP was no less than $12251.00, the Tislelizumab group was the dominant scheme, and the economic advantage grew with an increasing WTP. When WTP ≥ $19000.00, the Tislelizumab group became the absolute economic advantage. CONCLUSION: Under the current economic conditions in China, the Tislelizumab therapeutic scheme is more cost-effective than the Sorafenib therapeutic scheme for treating patients with unresectable HCC.

Dual p-n Z-scheme heterostructure boosted superior photoreduction CO2 to CO, CH4 and C2H4 in In2S3/MnO2/BiOCl photocatalyst.

The creation of a Z-scheme heterojunction is a sophisticated strategy to enhance photocatalytic efficiency. In our study, we synthesized an In2S3/MnO2/BiOCl dual Z-scheme heterostructure by growing BiOCl nanoplates on the sheets of In2S3 nanoflowers, situated on the surface of MnO2 nanowires. This synthesis involved a combination of hydrothermal and solution combustion methods. Experiments and density functional theory (DFT) calculations demonstrated that the In2S3/MnO2/BiOCl composite exhibited notable photo reduction performance and photocatalytic stability. This was attributed to the pivotal roles of BiOCl and MnO2 in the composite, acting as auxiliaries to enhance the electronic structure and facilitate the adsorption/activation capacity of CO2 and H2O. The yield rates of CO, CH4, and C2H4 over In2S3/MnO2/BiOCl as the catalyst were 3.94, 5.5, and 3.64 times higher than those of pure In2S3, respectively. Photoelectrochemical analysis revealed that the dual Z-scheme heterostructure, with its oxygen vacancies and large surface area, enhanced CO2 absorption and active sites on the nanoflower/nanowire intersurfaces. Consequently, the dual Z-scheme charge transfer pathway provided efficient channels for boosting electron transfer and charge separation, resulting in high C2H4, CH4, and CO yields of formed and exihibits an promising photoreduction rate of CO2 to CO (51.2 µmol/g.h), CH4 (42.4 µmol/g.h) and C2H4 (63.2 µmol/g.h), respectively. DFT, in situ Diffuse reflectance infrared fourier transform spectroscopy, and temperature-programmed desorption tests were employed to verify the intermediates pathway. The study proposed a potential photocatalytic mechanism based on these findings.

MAD-Former: A Traceable Interpretability Model for Alzheimer's Disease Recognition Based on Multi-Patch Attention.

The integration of structural magnetic resonance imaging (sMRI) and deep learning techniques is one of the important research directions for the automatic diagnosis of Alzheimer's disease (AD). Despite the satisfactory performance achieved by existing voxel-based models based on convolutional neural networks (CNNs), such models only handle AD-related brain atrophy at a single spatial scale and lack spatial localization of abnormal brain regions based on model interpretability. To address the above limitations, we propose a traceable interpretability model for AD recognition based on multi-patch attention (MAD-Former). MAD-Former consists of two parts: recognition and interpretability. In the recognition part, we design a 3D brain feature extraction network to extract local features, followed by constructing a dual-branch attention structure with different patch sizes to achieve global feature extraction, forming a multi-scale spatial feature extraction framework. Meanwhile, we propose an important attention similarity position loss function to assist in model decision-making. The interpretability part proposes a traceable method that can obtain a 3D ROI space through attention-based selection and receptive field tracing. This space encompasses key brain tissues that influence model decisions. Experimental results reveal the significant role of brain tissues such as the Fusiform Gyrus (FuG) in AD recognition. MAD-Former achieves outstanding performance in different tasks on ADNI and OASIS datasets, demonstrating reliable model interpretability.

HCN1 in the lateral habenula contributes to morphine abstinence-induced anxiety-like behaviors in male mice.

Anxiety disorders, common symptoms during morphine withdrawal, are important negative reinforcement factors leading to relapse. Lateral habenula serves as a negative reinforcement center, however its role in morphine withdrawal-induced anxiety remains uncovered. The hyperpolarization activated cyclic nucleotide-gated (HCN) channels have been reported to be important in emotion processing and addiction, but the role of HCN in anxiety from drug protracted abstinence remains elusive. In this study, by using behavioral test, Western blot, immunofluorescence, electrophysiology and virus-mediated regulation of HCN, we found that: (1) Intra-LHb injection of selective HCN blocker ZD7288 alleviated anxiety-like behaviors in morphine protracted abstinent male mice. (2) The LHb neuronal activity was increased by morphine protracted abstinence. (3) LHb neurons were inhibited by ZD7288 and activated by 8-Br-cAMP respectively, which were enhanced by morphine withdrawal. (4) HCN1 in the LHb was upregulated by morphine withdrawal. (5) Virus-mediated overexpression of HCN1 in the LHb was sufficient to produce anxiety-like behaviors in male mice and virus-mediated knockdown of HCN1 in the LHb prevented the anxiety-like behaviors in male mice. The findings reveal that selective blockade of HCN1 channels in the LHb may represent a therapeutic approach to morphine withdrawal-induced anxiety.

Septin9 DNA methylation is associated with breast cancer recurrence or metastasis.

OBJECTIVE: We aimed to explore the prognostic value of Septin9 DNA methylation in breast cancer. METHODS: Breast cancer patients with and without recurrence or metastasis and matched non-breast cancer patients were screened retrospectively from 2014 to 2016. Bisulfite conversion and fluorescence quantitative methylation-specific polymerase chain reaction were used to detect the Septin9 methylation status and distribution levels in patient breast tissues. RESULTS: Septin9 DNA methylation was more frequent in breast cancer tissues than in non-breast cancer tissues, but was not significantly correlated with any relevant breast cancer patient clinicopathological characteristic. Septin9 methylation rates were higher in patients with recurrence or metastasis. Septin9 methylation, tumor size, lymph node status, and progesterone receptor (PR) expression could influence prognosis. Septin9 methylation was significantly associated with worse disease-free survival in breast cancer patients, with receiver operating characteristic curve analysis indicating that it had good prognostic ability, with an area under the curve (AUC) value of 0.719. The AUC values increased when Septin9 methylation was combined with tumor size, lymph node status, and PR to predict prognosis. CONCLUSIONS: Septin9 DNA methylation was an independent predictors of breast cancer prognostic risk. This could possibly help improve comprehensive prognosis prediction methods when combined with other risk factors.

Cylindrin from Imperata cylindrica inhibits M2 macrophage formation and attenuates renal fibrosis by downregulating the LXR-α/PI3K/AKT pathway.

Imperata cylindrica, a medicinal plant used in Traditional Chinese Medicine, has been used to treat chronic kidney disease. Extracts of I. cylindrica display anti-inflammatory, immunomodulatory, and anti-fibrotic properties. However, the active components of the extracts and their protective mechanisms have not been fully elucidated. In this study, we explored the ability of cylindrin, the main active compound extracted from I. cylindrica, to protect against renal fibrosis and to investigate the potential mechanisms involved. At high doses, cylindrin exerted protective effects against folic acid-induced kidney fibrosis in mice. Bioinformatic analysis predicted the LXR-α/PI3K/AKT pathway as a target of regulation by cylindrin. This was supported by our in vitro and in vivo results showing that cylindrin significantly downregulated the expression of LXR-α and phosphorylated PI3K/AKT in M2 macrophages and mouse renal tissues. Furthermore, high-dose cylindrin inhibited M2 polarization of IL-4-stimulated macrophages in vitro. Our results suggest that cylindrin alleviates renal fibrosis by attenuating M2 macrophage polarization through inhibition of the PI3K/AKT pathway via downregulation of LXR-α.

Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway.

Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with ferroptosis inducer (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells both in vitro and in vivo via induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and cytosolic reactive oxygen species (ROS). In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the phosphatidylinositol 3 kinase (PI3K)-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC.

Transmissibility of tuberculosis among students and non-students: an occupational-specific mathematical modelling.

BACKGROUND: Recently, despite the steady decline in the tuberculosis (TB) epidemic globally, school TB outbreaks have been frequently reported in China. This study aimed to quantify the transmissibility of Mycobacterium tuberculosis (MTB) among students and non-students using a mathematical model to determine characteristics of TB transmission. METHODS: We constructed a dataset of reported TB cases from four regions (Jilin Province, Xiamen City, Chuxiong Prefecture, and Wuhan City) in China from 2005 to 2019. We classified the population and the reported cases under student and non-student groups, and developed two mathematical models [nonseasonal model (Model A) and seasonal model (Model B)] based on the natural history and transmission features of TB. The effective reproduction number (Reff) of TB between groups were calculated using the collected data. RESULTS: During the study period, data on 456,423 TB cases were collected from four regions: students accounted for 6.1% of cases. The goodness-of-fit analysis showed that Model A had a better fitting effect (P < 0.001). The average Reff of TB estimated from Model A was 1.68 [interquartile range (IQR): 1.20-1.96] in Chuxiong Prefecture, 1.67 (IQR: 1.40-1.93) in Xiamen City, 1.75 (IQR: 1.37-2.02) in Jilin Province, and 1.79 (IQR: 1.56-2.02) in Wuhan City. The average Reff of TB in the non-student population was 23.30 times (1.65/0.07) higher than that in the student population. CONCLUSIONS: The transmissibility of MTB remains high in the non-student population of the areas studied, which is still dominant in the spread of TB. TB transmissibility from the non-student-to-student-population had a strong influence on students. Specific interventions, such as TB screening, should be applied rigorously to control and to prevent TB transmission among students.

Hospitality's ethical values and unethical employee behaviour: The mediating roles of work values and the moderating role of perceived organisational support.

In recent years, hotels have occasionally engaged in unethical behaviour. This has become an urgent problem that requires a solution. Based on social exchange theory, this study constructs a theoretical model of the relationship between hospitality's ethical values and unethical behaviour. According to 543 questionnaires, the findings indicate that hospitality's ethical values negatively affect the unethical behaviour of employees. Work values played a part in the intermediary role between the two, and perceived organisational support significantly positively moderated the relationship between hospitality's ethical values and unethical behaviour. By exploring the logical relationship between hotels' and employees' morality, this study expands the research content and theoretical framework of unethical employee behaviour and helps to bridge the work values of hotels and individuals. Furthermore, it helps to build a good hotel ethical value system, which can effectively reduce and suppress the emergence of unethical employee behaviour.

A network pharmacology approach to evaluate the synergistic effect of dihydromyricetin and myricitrin in vine tea on the proliferation of B16F10 cells.

Aim of the study: Although vine tea has demonstrated broad-spectrum anti-cancer properties, its main active compounds, dihydromyricetin (DMY) and myricitrin (MYT), exert weaker effects than the tea extracts. This study aimed to investigate the synergistic inhibitory effects of DMY and MYT on B16F10 cell proliferation and their synergistic inhibitory effects. Methods: The effect of vine tea extracts (VTEs) and their active compounds on B16F10 cells was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence staining, and flow cytometry. The synergistic effects were calculated by the combination index (CI), and its mechanism was discussed by network pharmacology. Results: Different VTEs varied in their inhibition of B16F10 cell growth, with IC50 values ranging from 4.45 to 12.95 µg/mL, Among these, Guangzhou Qingyuan (Level 2), appeared to have the most potent inhibitory effect. The IC50 value of mix-use of DMY and MYT was 19.94∼64.4 µM, of which DMY: MYT = 8:1 had the minimum IC50 value of 19.94 µM. Combinations in the 1:1∼8:1 range had stronger effects than the isolated active compound. When they were mixed at the ratio of 1:4∼8:1, CI < 1, showing a synergistic effect. The combination of DMY and MYT also significantly inhibited the tyrosinase activity in B16F10 cells, consistent with its impact on cell proliferation. The eight potential targets were identified by network pharmacology regulating melanin metabolism, tyrosine metabolism, and melanogenesis signaling. According to the analysis of protein-protein interactions, TP53, TNF, and TYR might be critical targets for preventing and treating melanoma. Conclusion: We found that DMY and MYT induced apoptosis of B16F10 cells, and their combined application had a significant synergistic effect. The present findings indicated that vine tea had a multi-pathway and multi-target impact on the prevention and treatment of melanoma.

Efficacy of metoprolol plus atorvastatin for carotid atherosclerosis and its influence on carotid intima-media thickness and homocysteine level.

OBJECTIVE: To analyze the effects of metoprolol (MET) plus atorvastatin (ATO) on carotid intima-media thickness (IMT) and homocysteine (Hcy) level in carotid atherosclerosis (CAS) patients. METHODS: In this retrospective study, 90 patients with CAS admitted to the Hangzhou Ninth People's Hospital between January 2019 and July 2021 were enrolled, including 40 cases (control group, the Con) treated with MET and 50 cases treated with the combination therapy of MET plus ATO (Research group, the Res). The efficacy and related influencing factors were observed and compared. The clinical effects (IMT, plaque score), Hcy level, inflammatory cytokines (ICs; matrix metalloproteinase-9 [MMP-9], high-sensitivity C-reactive protein [hs-CRP]), blood lipid indices (low-/high- density lipoprotein cholesterol [LDL-C/HDL-C], total cholesterol [TC], triglyceride [TG]) and coagulation markers (thrombin time [TT], prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen [FIB]) of the two groups were observed and compared. RESULTS: The results identified a statistically higher overall response rate in the Res group. Age, coronary heart disease, cerebral infarction and plaque score were confirmed to be closely related to the efficacy of CAS. In addition, statistically lower post-treatment IMT, plaque score, MMP-9, hs-CRP, LDL-C, TG, TC and FIB while higher PT, TT and APTT were determined in the Res group compared with the pre-treatment values and the Con group. CONCLUSIONS: MET plus ATO can significantly improve efficacy, reduce IMT and plaque score of patients with CAS, as well as improve inflammatory factors, blood lipid indices and coagulation markers, for which it deserves clinical promotion.

Assessing the Impacts of Meteorological Factors on COVID-19 Pandemic Using Generalized Estimating Equations.

Background: Meteorological factors have been proven to affect pathogens; both the transmission routes and other intermediate. Many studies have worked on assessing how those meteorological factors would influence the transmissibility of COVID-19. In this study, we used generalized estimating equations to evaluate the impact of meteorological factors on Coronavirus disease 2019 (COVID-19) by using three outcome variables, which are transmissibility, incidence rate, and the number of reported cases. Methods: In this study, the data on the daily number of new cases and deaths of COVID-19 in 30 provinces and cities nationwide were obtained from the provincial and municipal health committees, while the data from 682 conventional weather stations in the selected provinces and cities were obtained from the website of the China Meteorological Administration. We built a Susceptible-Exposed-Symptomatic-Asymptomatic-Recovered/Removed (SEIAR) model to fit the data, then we calculated the transmissibility of COVID-19 using an indicator of the effective reproduction number (Reff ). To quantify the different impacts of meteorological factors on several outcome variables including transmissibility, incidence rate, and the number of reported cases of COVID-19, we collected panel data and used generalized estimating equations. We also explored whether there is a lag effect and the different times of meteorological factors on the three outcome variables. Results: Precipitation and wind speed had a negative effect on transmissibility, incidence rate, and the number of reported cases, while humidity had a positive effect on them. The higher the temperature, the lower the transmissibility. The temperature had a lag effect on the incidence rate, while the remaining five meteorological factors had immediate and lag effects on the incidence rate and the number of reported cases. Conclusion: Meteorological factors had similar effects on incidence rate and number of reported cases, but different effects on transmissibility. Temperature, relative humidity, precipitation, sunshine hours, and wind speed had immediate and lag effects on transmissibility, but with different lag times. An increase in temperature may first cause a decrease in virus transmissibility and then lead to a decrease in incidence rate. Also, the mechanism of the role of meteorological factors in the process of transmissibility to incidence rate needs to be further explored.

Shigellosis seasonality and transmission characteristics in different areas of China: A modelling study.

Objective: In China, the burden of shigellosis is unevenly distributed, notably across various ages and geographical areas. Shigellosis temporal trends appear to be seasonal. We should clarify seasonal warnings and regional transmission patterns. Method: This study adopted a Logistic model to assess the seasonality and a dynamics model to compare the transmission in different areas. The next-generation matrix was used to calculate the effective reproduction number (R eff) to quantify the transmissibility. Results: In China, the rate of shigellosis fell from 35.12 cases per 100,000 people in 2005 to 7.85 cases per 100,000 people in 2017, peaking in June and August. After simulation by the Logistic model, the 'peak time' is mainly concentrated from mid-June to mid-July. China's 'early warning time' is primarily focused on from April to May. We predict the 'peak time' of shigellosis is the 6.30th month and the 'early warning time' is 3.87th month in 2021. According to the dynamics model results, the water/food transfer pathway has been mostly blocked off. The transmissibility of different regions varies greatly, such as the mean R eff of Longde County (3.76) is higher than Xiamen City (3.15), higher than Chuxiong City (2.52), and higher than Yichang City (1.70). Conclusion: The 'early warning time' for shigellosis in China is from April to May every year, and it may continue to advance in the future, such as the early warning time in 2021 is in mid-March. Furthermore, we should focus on preventing and controlling the person-to-person route of shigellosis and stratified deploy prevention and control measures according to the regional transmission.

Kidney-Derived Methylated PAX2 Sequences in the Urine of Healthy Subjects as a Convenient Model for Optimizing Methylation-Based Liquid biopsy.

Although urine-based liquid biopsy has received considerable attention, there is a lack of a simple model to optimize assay parameters, including cell-free DNA (cfDNA) extraction, bisulfite modification, and bis-DNA recovery after conversion for methylation analysis in urine. The primary aim of this work was to establish a practical model by developing a quantitative methylation-sensitive PCR (qMS-PCR) assay for PAX2 based on hypermethylated PAX2 cfDNA that could be detected in healthy human urine. We first studied the methylation status of PAX2 in kidney tissues and whole blood, followed by an assessment of commercial kits for bisulfite conversion and bis-DNA recovery. Furthermore, we investigated the influence of urine storage and collection conditions on the preservation of methylated PAX2 in urine samples by qMS-PCR. As expected, PAX2 methylation was identified in urine but not in blood. Two commercial kits (CellCook and Zymo Research) had similar conversion efficiency and bis-DNA recovery. Urine storage for up to 5 days did not change PAX2 methylation estimates. Overall, cold storage of urine samples and the CellCook urine container maintained higher levels of methylated PAX2 compared to urine kept at room temperature and the conventional tubes, respectively. These findings highlight the importance of using the correct approaches/kits and optimizing experimental conditions as a diagnostic tool in the clinical setting. Our study provides insights on the development of urine-based liquid biopsy with DNA methylation as a universal biomarker.

An Easy-to-Use Public Health-Driven Method (the Generalized Logistic Differential Equation Model) Accurately Simulated COVID-19 Epidemic in Wuhan and Correctly Determined the Early Warning Time.

Introduction: Modeling on infectious diseases is significant to facilitate public health policymaking. There are two main mathematical methods that can be used for the simulation of the epidemic and prediction of optimal early warning timing: the logistic differential equation (LDE) model and the more complex generalized logistic differential equation (GLDE) model. This study aimed to compare and analyze these two models. Methods: We collected data on (coronavirus disease 2019) COVID-19 and four other infectious diseases and classified the data into four categories: different transmission routes, different epidemic intensities, different time scales, and different regions, using R2 to compare and analyze the goodness-of-fit of LDE and GLDE models. Results: Both models fitted the epidemic curves well, and all results were statistically significant. The R2 test value of COVID-19 was 0.924 (p < 0.001) fitted by the GLDE model and 0.916 (p < 0.001) fitted by the LDE model. The R2 test value varied between 0.793 and 0.966 fitted by the GLDE model and varied between 0.594 and 0.922 fitted by the LDE model for diseases with different transmission routes. The R2 test values varied between 0.853 and 0.939 fitted by the GLDE model and varied from 0.687 to 0.769 fitted by the LDE model for diseases with different prevalence intensities. The R2 test value varied between 0.706 and 0.917 fitted by the GLDE model and varied between 0.410 and 0.898 fitted by the LDE model for diseases with different time scales. The GLDE model also performed better with nation-level data with the R2 test values between 0.897 and 0.970 vs. 0.731 and 0.953 that fitted by the LDE model. Both models could characterize the patterns of the epidemics well and calculate the acceleration weeks. Conclusion: The GLDE model provides more accurate goodness-of-fit to the data than the LDE model. The GLDE model is able to handle asymmetric data by introducing shape parameters that allow it to fit data with various distributions. The LDE model provides an earlier epidemic acceleration week than the GLDE model. We conclude that the GLDE model is more advantageous in asymmetric infectious disease data simulation.

Nursing Observation of Improved Administration Route of Protamine Sulfate Neutralizing Heparin.

In this study, we have evaluated and examined various nursing effects of improved administration of protamine sulfate neutralizing heparin after cardiopulmonary bypass. For this purpose, retrospective analysis was made about the nursing records and clinical data of 216 patients who underwent cardiac operation under cardiopulmonary bypass in our hospital from January 2018 to December 2020. Among the enrolled patients, 118 patients were given subinterval administration of protamine sulfate neutralizing heparin via aortic root with the assistance of the scrub nurse at the end of cardiac surgery (improved group). A total of 98 patients were administered by the circulating nurse via the central vein (regular group). The changes of body temperature, blood pressure, oxygen saturation before and after heparin neutralization, and the total volume of thoracic drainage within 24 hours after operation were observed in the two groups, so as to evaluate the application effect of the improved administration of protamine sulfate neutralizing heparin from the perspective of nursing. There was no significant difference in age, gender, and other basic characteristics between the two groups (P > 0.05). The volume of drainage in the improved group and the regular group within 24 hours after surgery was 234 ± 26.3 ml and 307 ± 31.8 ml, respectively, P < 0.01, and the difference was statistically significant. The incidence of adverse reactions in the improved group was much lower than that in the regular group, P < 0.01. The administration route of the improved group was beneficial to maintain the stability of hemodynamics when using the protamine sulfate to neutralize heparin, which is worthy of clinical nursing promotion.