The role of autophagy regulated by the PI3K/AKT/mTOR pathway and innate lymphoid cells in eosinophilic chronic sinusitis with nasal polyps.

BACKGROUND: The PI3K/Akt/mTOR pathway and autophagy are important physiological processes. But their roles in eCRSwNP remains controversial. METHODS: In this study, we used the eCRSwNP mouse model, PI3K/Akt/mTOR pathway inhibitors, and autophagy inhibitors and activators to investigate the regulatory effects of the PI3K/Akt/mTOR pathway on autophagy, and their effects on eosinophilic inflammation, and tissue remodeling. The role of ILC2s in eCRSwNP was also studied, and the relationship between ILC2s and autophagy was preliminarily determined. RESULTS: Our results show that eosinophilic inflammation in eCRSwNP mice could be inhibited by promoting the autophagy; otherwise, eosinophilic inflammation could be promoted. Meanwhile, inhibition of the PI3K/Akt/mTOR pathway can further promote autophagy and inhibit eosinophilic inflammation. Meanwhile, inhibiting the PI3K/Akt/mTOR pathway and promoting autophagy can reduce the number of ILC2s and the severity of tissue remodeling in the nasal polyps of eCRSwNP mice. CONCLUSIONS: We conclude that the PI3K/Akt/mTOR pathway plays roles in eosinophilic inflammation and tissue remodeling of eCRSwNP, in part by regulating the level of autophagy. The downregulation of autophagy is a pathogenesis of eCRSwNP; therefore, the recovery of normal autophagy levels might be a new target for eCRSwNP therapy. Furthermore, autophagy might inhibit eosinophilic inflammation and tissue remodeling, in part by reducing the number of ILC2s.

Study on the methods of visualizing bloodstains after thermal exposure.

To establish the correlation between thermal conditions imposed on bloodstains and visualizing effect of enhancement techniques, infrared photography and four chemical enhancement reagents were used to visualize bloodstains following thermal exposure. A black tile was selected as the substrate to intensify the visualization challenge, with a Cone Calorimeter serving as the standardized heating source to control thermal conditions. Compared with standard photography, infrared photography is proven to be a valuable complement to chemical reagents, showing significant advantages in visualizing bloodstains after thermal exposure. However, it is worth noting that infrared image fell short of standard image when bloodstains displayed raised, embossed morphology or when bloodstains almost disappeared under specific conditions. The enhancement effectiveness was found to be strongly correlated with thermal conditions imposed on bloodstains, and the morphology evolution of bloodstains during heating affected the chemical enhancement effect additionally, especially when the bulge morphology was formed, and it was observed that reagents were more effective after removing the dense shell of the bulge. Among the four selected chemical enhancement reagents, fluorescein performed exceptionally well, maintaining its effectiveness even for bloodstains heated at 641°C for 10 min. TMB demonstrated its visualizing ability for bloodstains heated at 396°C for 5 min and heated at 310°C for 20 min. BLUESTAR® followed afterwards, while luminol performed worst. The correlation between thermal conditions imposed on bloodstains and the corresponding visualizing effectiveness of enhancement techniques provides important references for detecting bloodstains at fire scenes.

A cross-dataset adaptive domain selection transfer learning framework for motor imagery-based brain-computer interfaces.

Objective. In brain-computer interfaces (BCIs) that utilize motor imagery (MI), minimizing calibration time has become increasingly critical for real-world applications. Recently, transfer learning (TL) has been shown to effectively reduce the calibration time in MI-BCIs. However, variations in data distribution among subjects can significantly influence the performance of TL in MI-BCIs.Approach.We propose a cross-dataset adaptive domain selection transfer learning framework that integrates domain selection, data alignment, and an enhanced common spatial pattern (CSP) algorithm. Our approach uses a huge dataset of 109 subjects as the source domain. We begin by identifying non-BCI illiterate subjects from this huge dataset, then determine the source domain subjects most closely aligned with the target subjects using maximum mean discrepancy. After undergoing Euclidean alignment processing, features are extracted by multiple composite CSP. The final classification is carried out using the support vector machine.Main results.Our findings indicate that the proposed technique outperforms existing methods, achieving classification accuracies of 75.05% and 76.82% in two cross-dataset experiments, respectively.Significance.By reducing the need for extensive training data, yet maintaining high accuracy, our method optimizes the practical implementation of MI-BCIs.

Establishment and validation of a predictive model of immune tolerance after pediatric liver transplantation (ITPLT): A multicenter cohort study.

Side-effect of life-long immunosuppressants (IS) administration is a major obstacle for the long-term survival of pediatric liver transplantation (LT) recipients. Immunotolerance is the status that recipients discontinued IS with normal liver function and intrahepatic histology. So far, only a few clinical parameters were identified related with tolerance but failed to accurately discriminate tolerant recipients in clinical practice. Here we aimed to provide a comprehensive view of pre- and post-LT risk factors associated with the achievement of tolerance after pediatric LT and established a tolerance predictive nomogram (ITPLT) with high accuracy and specificity. We enrolled 2228 pediatric recipients who received LT in XX Hospital between October 2006 and December 2020. All participants survived over 3 years after transplantation with comprehensive and intact medical history and follow-up data. They were randomly assigned to training and validation cohorts in accordance with a ratio of 1:1. Univariate and multivariable Logistic regression were used to identify clinical factors associated with post-LT immune tolerance and establish a predictive model. The model was further validated in an independent external validation cohort from YY Hospital. Among all participants, 6% recipients successfully tapered IS with intact allograft function. The most common reason for IS discontinuity was pneumonia. Univariate analysis identified 15 clinical factors associated with tolerance achievement, including age at LT, follow-up time, preoperative total bilirubin, creatinine, INR, CYP polymorphism, types of transplantation, massive postoperative ascites, episodes of acute rejection, and the severity of EBV and CMV infection. Using multivariable Logistic regression, we established the predictive ITPLT model for post-LT tolerance, which included seven easily accessible clinical factors (age at LT, CYP3A5 genotype, types of transplantation, post-LT massive ascites, preoperative INR, creatinine, and total bilirubin levels). Then we visualized the model using nomogram. The c-statistics for predicting tolerance achievement in the training, internal validation, and external validation cohorts were 0.854, 0.787, and 0.746 respectively. Multiple pre- and post-LT clinical factors affected the process of immune remodeling after pediatric liver transplantation. The predictive ITPLT model, composed of seven easily accessible clinical factors, could comprehensively reveal the effect of these clinical parameters on immune remodeling and accurately identify tolerant recipients after pediatric LT. The application of ITPLT could facilitate the individualized IS strategy in the future.

Conformal frequency selective rasorber in S, C, X-band with low backward-scattering.

In this paper, a polarization-insensitive high transmittance bandpass filter with low radar cross section (RCS) in both S- and X-band is proposed. This is the first study to use the partition layout loading approach for conformal structures with transmissive windows, reducing the operating band RCS. Curved structures have stronger radiation at a smaller angle to the incident wave, and that is how their scattering differs from uniform scattering from flat structures. The structure is divided by analyzing the radiative contribution of different regions. The surface was discussed in regions according to surface angles, and a new partition layout loading method was used to suppress the side currents and decreased backward scattering, achieving a backward RCS reduction of more than 10 dB at 4-8 GHz (66.7%). The bandpass layer operating at 6.9 GHz is designed through equivalent circuit theory. In combination with the lossy layer, absorption above 0.8 at 3.7-5.6 GHz and 9.1-12.5 GHz was achieved. Further, the structure was fashioned into a curved surface with varying curvature, demonstrating its effective absorption and transmission properties across different curvatures. A 15 × 15 cell structure was designed and fabricated, and there was good agreement between the test results and simulation results. The proposed structure has important applications in radomes, conformal structures, and electromagnetic shielding.

Modeling and biological evaluation of pegmolesatide, a novel and potent erythropoiesis-stimulating agent.

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the in vitro effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests. The findings indicate that pegmolesatide exhibited the same stimulating effect on erythropoiesis as EPO with fewer side effects than EPO and CEPO.

A study of the effect of natural brown cotton gauze on the healing of infected wounds.

BACKGROUND: Medical dressings are designed to promote wound healing and reduce infection. The aim of project is to investigate the effect of natural brown colored cotton dressings on the healing of infected wounds in E.coli animals. MATERIALS AND METHODS: In this study, degreased white cotton gauze was used as the control group, with degreased brown cotton gauze and degreased bleached brown cotton gauze as the experimental group 1 and experimental group 2, to investigate the effect on the repair of post-infectious wound damage in animals by establishing an infected wound model in rats with E.coli as the infecting organism. RESULTS: The ability to promote healing of infected wounds was investigated by analyzing the wound healing status, macroscopic wound healing rate, hematoxylin-eosin staining, Masson staining, secretion of inflammatory factors by Elisa assay. The result showed that at day 14 of wound healing, the macroscopic wound healing rate was greater than 98% for all three groups of dressings; the collagen content reached 49.85 ± 5.84% in the experimental group 1 and 53.48 ± 5.32% in the experimental group 2, which was higher than the control group; brown cotton gauze promotes skin wound healing by shortening the inflammatory period in both groups. The expression of three inflammatory factors THF-α, IL-2, and IL-8 and three cytokines MMP-3, MMP-8, and MMP-9 were lower than that of the control group. CONCLUSIONS: It was found that natural brown cotton gauze has better repairing and promoting healing effect on infected wounds. It opens up the application of natural brown cotton gauze in the treatment of infected wounds.

Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex.

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called "R78C", combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial.

A auto-segmented multi-time window dual-scale neural network for brain-computer interfaces based on event-related potentials.

OBJECTIVE: Event-related potentials (ERPs) are cerebral responses to cognitive processes, also referred to as cognitive potentials. Accurately decoding ERPs can help to advance research on brain-computer interfaces (BCIs). The spatial pattern of ERP varies with time. In recent years, convolutional neural networks (CNNs) have shown promising results in electroencephalography (EEG) classification, specifically for ERP-based BCIs. APPROACH: This study proposes an auto-segmented multi-time window dual-scale neural network (AWDSNet). The combination of a multi-window design and a lightweight base network gives AWDSNet good performance at an acceptable cost of computing. For each individual, we create a time window set by calculating the correlation of signed R-squared values, which enables us to determine the length and number of windows automatically. The signal data are segmented based on the obtained window sets in sub-plus-global mode. Then, the multi-window data are fed into a dual-scale CNN model, where the sizes of the convolution kernels are determined by the window sizes. The use of dual-scale spatiotemporal convolution focuses on feature details while also having a large enough receptive length, and the grouping parallelism undermines the increase in the number of parameters that come with dual scaling. MAIN RESULTS: We evaluated the performance of AWDSNet on a public dataset and a self-collected dataset. A comparison was made with four popular methods including EEGNet, DeepConvNet, EEG-Inception, and PPNN. The experimental results show that AWDSNet has excellent classification performance with acceptable computational complexity. SIGNIFICANCE: These results indicate that AWDSNet has great potential for applications in ERP decoding.

Targeting dendritic cell activation: the therapeutic impact of paeoniflorin in cortosteroid-dependent dermatitis management.

This study investigates the mechanism through which paeoniflorin inhibits TSLP expression to regulate dendritic cell activation in corticosteroid-dependent dermatitis treatment. Utilizing databases like TCMSP, we identified paeoniflorin's components, targets, and constructed networks. Molecular docking and gene enrichment analysis helped pinpoint key targets and pathways affected by paeoniflorin. In vitro and in vivo models were used to study CD80, CD86, cytokines, T-cell activation, skin lesions, histopathological changes, TSLP, CD80, and CD86 expression. Our study revealed paeoniflorin's active constituent targeting IL-6 in corticosteroid-dependent dermatitis. In vitro experiments demonstrated reduced TSLP expression, CD80, CD86, and cytokine secretion post-paeoniflorin treatment. In vivo, paeoniflorin significantly decreased skin lesion severity, cytokine levels, TSLP, CD80, and CD86 expression. The study highlights paeoniflorin's efficacy in inhibiting TSLP expression and suppressing dendritic cell activation in corticosteroid-dependent dermatitis, suggesting its potential as a therapeutic intervention. Additionally, it offers insights into the complex molecular mechanisms underlying paeoniflorin's anti-inflammatory properties in treating corticosteroid-dependent dermatitis.

Real-world drug treatment models of novel targeted drugs in Chinese patients with gynecological cancer from 2017 to 2021: A cross-sectional analysis.

Objective: The significance of novel anti-tumor pharmaceuticals in the treatment of gynecological tumors is growing, but there is no consensus regarding the optimal drug delivery strategy for gynecological tumors. This study seeks to investigate the treatment models of novel anti-tumor drugs in patients with gynecological cancer in China over the past five years, with a particular emphasis on the trend and rationality of their use. Method: We conducted a cross-sectional analysis of data from a China Medical Association-supervised hospital prescription analysis cooperation initiative. The data was derived from prescriptions written for patients diagnosed with cancer between January 2017 and December 2021. The required information for patients was extracted. Our study included 2308 patients that were diagnosed as gynecological tumors which were treated with novel antineoplastic targeted drugs. Patients were categorized by age and region. Then, the selection, application, and indications of the most essential treatment pharmaceuticals were investigated. We evaluated anti-tumor prescription information based on the recommended drug labeling protocol and the most recent domestic and international guidelines.Excel 2013 and SPSS (version 25; SPSS Inc., Chicago, IL, United States) were utilized to conduct statistical analysis.In addition，we also used Sankey diagram to evalute the relation between novel antineoplastic targeted drugs and corresponding diagnoses. Result: The top three cities for the 2308 patients included in this study were Guangzhou (28.51%), Hangzhou (21.79%), and Beijing (20.06%). In the past five years, the average age of medication patients was 55.61-year-old, with 37.86% of women aged of 51-60. Each patient's primary treatment regimens were statistically analyzed, yielding a total of 16 single-drug and combination-drug primary treatment regimens. Bevacizumab, Olaparib, Trastuzumab, Apatinib, and Arotinib were the top five treatment strategies. The maximum proportion, up to 0.74%, was attributed to the combination of human epidermal growth factor receptor-2 inhibitor (HER2i), including Trastuzumab and Parostuzumab. Vascular endothelial growth factor receptor inhibitor (VEGFRi), including Bevacizumab and Apatinib was the most frequently prescribed medication for outpatients in major cities across the country. According to the 5-year change in time, poly adenosine diphosphate ribose polymerase inhibitor (PARPi) rated first in terms of usage, with Olaparib ranking first with the highest concentration of 33.44% and Niraparib ranking second overall with the fastest growth in 2021. The quantity of VEGFRi variants utilized was the greatest, and their proportion of total usage increased annually. The top five drugs by total drug costs were Bevacizumab, Carelizumab, Olaparib, Trastuzumab, and Apatinib. However, the top five drugs by per capita drug cost were Olaparib + Bevacizumab, Bevacizumab + Sidilimab, Arrotinib + Olaparib, Olaparib, and Patuzumab + Trastuzumab. Conclusion: The incidence rate of gynecological tumor patients rises with age, and the cost of drug treatment has risen annually over the past five years, which is also related to the rising incidence rate of tumors in recent years. Bevacizumab rates first in the drug treatment scheme for the application of novel anti-tumor targeted drugs, which may be related to the widespread use of VEGFRi drugs in gynecological and reproductive tumors. Breast cancer and adenocarcinoma are at the top of the female cancer incidence spectrum, which may explain why HER2i multi-drug combination regimen rates highest among multi-drug combination regimens. Future research may concentrate on how novel anti-tumor targeted drugs can minimize the economic burden and maximize the benefits of patient treatment for patients with gynecological cancer.

The "4+4" Medical Education Pilot Program at PUMC: Implementation, Performance, and Prospects.

Peking Union Medical College (PUMC) launched the "4+4" Clinical Medicine Pilot Class in 2018, admitting students with non-medical backgrounds from top universities, aligning with national medical talent training policies to foster diverse and eager learners in medicine. On the occasion of the graduation of the first class of the "4+4" clinical medical pilot program at PUMC in 2023, we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students, faculties, and management staff of the pilot class. This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting, and demonstrates the achievements of the pilot class in terms of student academic background structure, knowledge acquisition and skill learning, scientific research ability, and course evaluation. The results indicated that the pilot class had met the national demand for the "medicine + x" talent training model. More specifically, with a diverse academic backgrounds, the pilot class graduates had academic levels comparable to the eight-year medical education graduates, and their scientific research abilities were satisfactory. The pilot program at PUMC will optimize the curriculum setting, strengthen the construction of faculty, learning resources, and teaching facilities, reform the academic evaluation methods, thus deepening the reform of medical education and improving the "4+4" MD program as a novel medical education model.

Functional insights of digestion, absorption, and immunity in different segments of the intestine in Hemibarbus labeo from transcriptomic analysis.

The intestine is an important organ for food digestion and absorption and body immunity in fish. In this study, we investigated the abundance of transcripts from different segments of the intestinal tract using transcriptome sequencing technology in Hemibarbus labeo, to provide functional insights into digestion, absorption, and immunity in the anterior intestine (AI), middle intestine (MI), and posterior intestine (PI). We found 5646 differentially expressed genes (DEGs), which were significantly enriched to GO terms of carbohydrate metabolic process, transmembrane transport, iron ion binding, lipid metabolic process, and KEGG pathway of fat digestion and absorption, mineral absorption, protein digestion and absorption, vitamin digestion and absorption, indicating that the digestion and absorption function of food is different in AI, MI, and PI. In practice, most genes, enriched in the KEGG pathway for digestion and absorption of nutrients, are upregulated in AI and MI, indicating stronger roles for food digestion and absorption in these segments. Furthermore, we found that genes involved in the KEGG pathway of lysosome and endocytosis pathway are upregulated in PI, suggesting stronger antigen-presenting capabilities in PI. However, some cytokine receptor genes, including ccr4, cxcr2, tnfrsf9, il6r, csf3r, and cxcr4, are highly expressed in AI, reflecting the regional immune specialization in different segments. This study provides functional insights into digestion, absorption, and immunity in different segments of the intestine and supports the regional functional specialization within different segments of the intestine in H. labeo.

Sucralose triggers insulin resistance leading to follicular dysplasia in mice.

Sucralose, the extensively utilized sweetener, might lead to metabolic disorders with prolonged consumption, but it remains uncertain if sucralose has any impact on female reproductive health. We incorporated sucralose into drinking water and observed food intake, body weight, estrous cycle, follicular development, serum hormones, and insulin sensitivity of mice. The mice did not experience any changes in their food intake or body weight after consuming sucralose. However, they displayed irregularities in the estrous cycle, marked by a reduced count of primordial, primary, and secondary follicles, coupled with a significant increase in the number of antral follicles. There was a decline in follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4) levels, while testosterone (T) and luteinizing hormone (LH) levels surged, leading to a notable elevation in the LH / FSH ratio. Sucralose also induced insulin resistance, as evidenced by elevated insulin levels and impaired insulin tolerance, which responded to an increase in bacterial-derived serum endotoxin. By eliminating insulin resistance with rosiglitazone (RSG), eradicating intestinal flora-derived endotoxins with neomycin (NEO), or enhancing intestinal barrier function with indole-3-carbinol (I3C), the abnormalities in estrous cycle, disruptions in follicular development, hormonal imbalances and elevation in serum endotoxins induced by sucralose were successfully reversed. The present study indicates that sucralose-induced follicular dysplasia in mice is probably related to impaired intestinal permeability, infiltration of endotoxins, initiation of systemic inflammation, and insulin resistance.

Vitamin C Drives Reentrant Actin Phase Transition: Biphasic Exocytosis Regulation Revealed by Single-Vesicle Electrochemistry.

Unveiling molecular mechanisms that dominate protein phase dynamics has been a pressing need for deciphering the intricate intracellular modulation machinery. While ions and biomacromolecules have been widely recognized for modulating protein phase separations, effects of small molecules that essentially constitute the cytosolic chemical atmosphere on the protein phase behaviors are rarely understood. Herein, we report that vitamin C (VC), a key small molecule for maintaining a reductive intracellular atmosphere, drives reentrant phase transitions of myosin II/F-actin (actomyosin) cytoskeletons. The actomyosin bundle condensates dissemble in the low-VC regime and assemble in the high-VC regime in vitro or inside neuronal cells, through a concurrent myosin II protein aggregation-dissociation process with monotonic VC concentration increase. Based on this finding, we employ in situ single-cell and single-vesicle electrochemistry to demonstrate the quantitative modulation of catecholamine transmitter vesicle exocytosis by intracellular VC atmosphere, i.e., exocytotic release amount increases in the low-VC regime and decreases in the high-VC regime. Furthermore, we show how VC regulates cytomembrane-vesicle fusion pore dynamics through counteractive or synergistic effects of actomyosin phase transitions and the intracellular free calcium level on membrane tensions. Our work uncovers the small molecule-based reversive protein phase regulatory mechanism, paving a new way to chemical neuromodulation and therapeutic repertoire expansion.

Magnetic surface-imprinted polymer microspheres coupled with HPLC-MS/MS for sensitive detection of amphetamine-type drugs in water.

Magnetic surface imprinted polymer microspheres (Fe3O4@MIPs) were successfully synthesized via Pickering emulsion polymerization, utilizing N-Methylphenethylamine as a surrogate template for amphetamine-type drugs. Fe3O4@MIPs not only possessed excellent dispersibility and enough magnetic properties in aqueous solutions, but also displayed good selectivity towards six amphetamines, with an imprinting factor ranging from 1.8 to 2.6. The adsorption kinetics closely aligned with the pseudo-second-order model, and the adsorption efficiency exceeds 80 % for each amphetamine at equilibrium. Fe3O4@MIPs were then employed as the efficient adsorbents for the extraction of amphetamine drugs. Extraction parameters, including sample pH, the mass of adsorbent, and the type and volume of eluting solvent, were carefully optimized. In combination with the high performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-MS/MS), a selective magnetic solid-phase extraction (MISPE) method utilizing Fe3O4@MIPs was developed for the detection of six amphetamines in water samples. The limits of detection and limits of quantitation were determined to be 5.2∼23 ng L-1 and 17∼77 ng L-1, respectively. Recoveries for the six target drugs from lake water and sewage samples fell within the range of 87.2∼110 %. Additionally, the MISPE-HPLC-MS/MS method exhibited excellent repeatability, with a precision below 8.5 % at two spiking levels. The prepared Fe3O4@MIPs possessed the advantages of high selectivity, straightforward preparation, facile separation and good reusability, and was highly suitable for the efficient extraction of amphetamine-type substances in complex environmental water.

A new evaluation system for drug-microbiota interactions.

The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug-microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug-microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug-microbiota interactions.

Prognostic value of lymphocytes in patients with breast cancer receiving radiotherapy after breast-conserving surgery: A post hoc analysis of a phase III randomized trial.

PURPOSE: To evaluate the prognostic value of peripheral lymphocyte count (PLC) in the breast cancer patients after breast-conserving surgery (BCS) with radiotherapy (RT). METHODS AND MATERIALS: This post hoc analysis was performed using data of 628 patients from a phase III, randomized controlled trial comparing hypofractionated RT (HFRT) with conventional fractionated RT (CFRT) after BCS. PLCs were obtained before, during, and after RT until the 1-year follow-up. The optimal cut-off PLCs were determined using the maxstat package in R. Survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 275 (46.1 %) patients developed lymphopenia during RT, among them, 17 (2.8 %) had grade 3 lymphopenia and no one developed grade 4 lymphopenia. With a median follow-up of 110.8 months, patients with pre-RT PLCs of < 1.77 × 109/L had a significantly lower 10-year breast cancer-specific survival (BCSS) rate (P = 0.013) and overall survival (OS) rate (P = 0.026). Patients with a nadir PLC of < 1.35 × 109/L had a significantly poorer 10-year OS rate (P = 0.048). Multivariate analysis showed that a pre-RT PLC of < 1.77 × 109/L was an independent factor influencing BCSS and OS, while the effect of the nadir PLC did not remain significant. Neither PLC nor lymphopenia recovery at post-RT 1, 3, and 6 months and 1 year was associated with survival. CONCLUSIONS: Radiation-induced lymphopenia in patients with breast cancer after BCS tends to be mild. The lower pre-RT PLC predicted poorer survival.

Correlation between diameter of esophageal varices and early rebleeding following endoscopic variceal ligation: a multicenter retrospective study based on artificial intelligence-based endoscopic virtual rule.

Background and objective: Bleeding following endoscopic variceal ligation (EVL) may occur as a result of numerous factors, including a diameter of esophageal varices (EV) that is too large to be completely ligated. The present study aimed to develop an artificial intelligence-based endoscopic virtual ruler (EVR) to measure the diameter of EV with a view to finding more suitable cases for EVL. Methods: The present study was a multicenter retrospective study that included a total of 1,062 EVLs in 727 patients with liver cirrhosis with EV, who underwent EVL from April 2016 to March 2023. Patients were divided into early rebleeding (n = 80) and non-rebleeding groups (n = 982) according to whether postoperative bleeding occurred at 6 weeks. The characteristics of patient baseline data, the status of rebleeding at 6 weeks after surgery and the survival status at 6 weeks after rebleeding were analyzed. Results: The early rebleeding rate following 1,062 EVL procedures was 7.5%, and the mortality rate at 6 weeks after bleeding was 16.5%. Results of the one-way binary logistic regression analysis demonstrated that the risk factors for early rebleeding following EVL included: high TB (P = 0.009), low Alb (P = 0.001), high PT (P = 0.004), PVT (P = 0.026), HCC (P = 0.018), high Child-Pugh score (P < 0.001), Child-Pugh grade C(P < 0.001), high MELD score(P = 0.004), Japanese variceal grade F3 (P < 0.001), diameter of EV (P < 0.001), and number of ligature rings (P = 0.029). Results of the multifactorial binary logistic regression analysis demonstrated that Child-Pugh grade C (P = 0.007), Japanese variceal grade F3 (P = 0.009), and diameter of EV (P < 0.001) may exhibit potential in predicting early rebleeding following EVL. ROC analysis demonstrated that the area under curve (AUC) for EV diameter was 0.848, and the AUC for Japanese variceal grade was 0.635, which was statistically significant (P < 0.001). Thus, results of the present study demonstrated that EV diameter was more optimal in predicting early rebleeding following EVL than Japanese variceal grade criteria. The cut-off value of EV diameter was calculated to be 1.35 cm (sensitivity, 70.0%; specificity, 89.2%). Conclusion: If the diameter of EV is ≥1.4 cm, there may be a high risk of early rebleeding following EVL surgery; thus, we recommend caution with EVL.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study.

OBJECTIVE: This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. METHODS: A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. RESULTS: After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION: The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.