ObjectiveTo study the therapeutic mechanism of Xihuang Wan for hyperplasia of mammary glands based on network pharmacology， molecular docking， and cell experiments. MethodsThe active ingredients and targets of Xihuang Wan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and A Bioinformatics Annotation daTabase for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and supplemented by searching against PubChem and Swiss Target Prediction. The targets of differential metabolites in tissues and urine were obtained from previous metabolomics studies through PubChem and Swiss Target Prediction. GeneCards， Online Mendelian Inheritance in Man （OMIM）， PharmGKB， Therapeutic Target Database （TTD）， Drunbank were searched for the targets of hyperplasia of mammary glands. After the common targets were obtained via Veeny2.1.0， the STRING database was used to analyze the protein-protein interactions， and Cytoscape was used for the core target analysis and visualization. Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG） were employed for enrichment analysis. Molecular docking was carried out in Autodock， and cell experiments were conducted to verify the prediction results. In the cell experiments， estradiol and progesterone （E₂+P） were used to intervene in human mammary epithelial/MCF-10A cells， and thus the MCF-10A cell proliferation model was established. The cells were then treated with Xihuang Wan-medicated serum. The cell counting kit-8 （CCK-8） was used to measure the cell proliferation， and flow cytometry was used to detect apoptosis. The mRNA and protein levels of key factors in MCF-10A cells were determined by real-time PCR and Western blot， respectively. ResultsThe results of network pharmacology showed that 90 active ingredients and 316 common targets were obtained， from which 20 core targets and 38 corresponding active ingredients were screened out. The results of GO and KEGG enrichment analyses showed that Xihuang Wan exerted effect against hyperplasia of mammary glands by regulating a variety of biological processes， which may be related to protein kinase B （Akt）-related molecular functions， estrogen signaling pathway， prolactin signaling pathway and other biological processes. The results of molecular docking showed that estrogen receptor 1 （ESR1）， serine/threonine kinase 1 （Akt1）， non-receptor tyrosine kinase （SRC）， and signal transducer and activator of transcription 3 （STAT3） all had strong binding activity with the nine active ingredients， suggesting that Xihuang Wan exert the effect through the ESR1/SRC/phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway and the Janus kinase （JAK）/STAT3 signaling pathway. The results of cell experiments showed that E₂+P intervention in MCF-10A cells promoted the proliferation of MCF-10A cells （P<0.05）， while the Xihuang Wan-medicated serum inhibited the proliferation of MCF-10A cells exposed to E₂+P （P<0.05）. Flow cytometry showed that the Xihuang Wan-medicated serum promoted the apoptosis of MCF-10A cells exposed to E₂+P （P<0.01）. The results of Real-time PCR showed that the Xihuang Wan-medicated serum down-regulated the mRNA levels of PI3K， Akt， JAK2， and STAT3 in MCF-10A cells treated with E₂+P （P<0.01）. The results of Western blot showed that the Xihuang Wan-medicated serum inhibited the expression of p-PI3K/PI3K， p-Akt/Akt， p-JAK2/JAK2， and p-STAT3/STAT3 in MCF-10A cells treated with E₂+P （P<0.05）. ConclusionXihuang Wan may exert the effect against hyperplasia of mammary glands by inhibiting the proliferation and promoting the apoptosis of MCF-10A cells， which may related to the inhibition of the activation of PI3K/Akt and JAK2/STAT3 signaling pathways.

Objective Based on the “excellent” performance achieved by our institution in the 2024 national intercomparison of monitoring individual dose from external exposure, this paper systematically summarizes key technical elements and optimization experiences in instrument calibration, operational protocols, and data analysis, aiming to provide methodological references and practical support for continuously enhancing the accuracy and reliability of individual dose monitoring. Methods As a participant in the intercomparison activity, our laboratory strictly followed the technical protocol formulated by the Chinese Center for Disease Control and Prevention. Results In the 2024 national intercomparison of monitoring individual dose from external exposure, the measurement results met the criteria of single-group performance \begin{document}$ \left|{P}_{i}\right| $\end{document} ≤ 0.10 and comprehensive performance B² + S² ≤ 0.10², and were rated as excellent. Conclusion The accuracy and reliability of monitoring individual dose from external exposure depend on the precision of instrument calibration, standardization of operations, and strictness of quality control. The effectiveness of the above quality control methods has been confirmed by the practice of our laboratory. These methods can be used to ensure the accuracy of measurement results.

Nucleic acid elements are essential functional sequences that play critical roles in regulating gene expression, optimizing pathways, and enabling gene editing to enhance the production of target products in biomanufacturing. Therefore, the design and optimization of these elements are crucial in constructing efficient cell factories. Artificial intelligence (AI) provides robust support for biomanufacturing by accurately predicting functional nucleic acid elements, designing and optimizing sequences with quantified functions, and elucidating the operating mechanisms of these elements. In recent years, AI has significantly accelerated the progress in biomanufacturing by reducing experimental workloads through the design and optimization of promoters, ribosome-binding sites, terminators, and their combinations. Despite these advancements, the application of AI in biomanufacturing remains limited due to the complexity of biological systems and the lack of highly quantified training data. This review summarizes the various nucleic acid elements utilized in biomanufacturing, the tools developed for predicting and designing these elements based on AI algorithms, and the case studies showcasing the applications of AI in biomanufacturing. By integrating AI with synthetic biology and high-throughput techniques, we anticipate the development of more efficient tools for designing nucleic acid elements and accelerating the application of AI in biomanufacturing.
Artificial Intelligence ; Synthetic Biology ; Nucleic Acids/genetics* ; Algorithms ; Gene Editing ; Promoter Regions, Genetic ; Biotechnology/methods*

Objective : To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance. Methods : Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups. Results: t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05). Conclusion Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.

Intravascular large B-cell lymphoma (IVLBCL), a rare subtype of non-Hodgkin lymphoma, is classified as an independent subtype of extranodal diffuse large B-cell lymphoma (DLBCL) in the 2008 World Health Organization (WHO) Classification (Turner et al., 2010). The 5th edition of the World Health Organization (WHO 2022) classification of hematolymphoid tumors retains this subtype (Alaggio et al., 2022). IVLBCL, which is characterized by neoplastic lymphocyte proliferation within the lumen of small blood vessels, tends to invade organs, such as the nervous system, skin, bone marrow (BM), and lung (D'Angelo et al., 2019; Satoh et al., 2019; Vásquez et al., 2019; Fukami et al., 2020).
Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Vascular Neoplasms/therapy*

Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

Huaihuasan， first recorded in Experiential Prescriptions for Universal Relief （Pu Ji Ben Shi Fang）， is a classic prescription for the treatment of ''hematochezia due to intestinal wind''. In 2018， it was included by the National Administration of Traditional Chinese Medicine as one of the first 100 classic prescriptions. This formula consists of four ingredients， i.e.， Sophorae Flos， Platycladi Cacumen， Schizonepetae Spica， and Aurantii Fructus. It is known for its ability to clear the intestines， dispel wind， cool the blood， and stop bleeding. In modern clinical practice， Huaihuasan， often with modifications， is widely used to treat various digestive tract diseases， including ulcerative colitis （UC）， with significant long-term effects. UC is a chronic， non-specific inflammatory bowel disease. Currently， Western medicine primarily treats UC with glucocorticoids， aminosalicylates， and immunosuppressants， which have good short-term efficacy but numerous adverse reactions， high recurrence rates， and the need for lifelong medication. Modern clinical studies have shown that Huaihuasan can significantly improve symptoms of UC， such as abdominal pain and diarrhea， reduce disease activity scores （Sutherland）， promote intestinal mucosal healing， alleviate anxiety and depression， and significantly improve the quality of life of patients. Pharmacological studies have shown that the main active components of Huaihuasan include quercetin， rutin， kaempferol， naringenin， and volatile oils. These compounds exert their effects by inhibiting inflammatory responses and protecting the intestinal mucosal barrier. They also exhibit antioxidant properties and regulate various signaling pathways， including tumor necrosis factor-α （TNF-α）， interleukin-2 （IL-2）， interleukin-4 （IL-4）， interleukin-1β （IL-1β）， monocyte chemoattractant protein-1 （MCP-1）， nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， and the KRAS-regulated mitogen-activated protein kinase （MEK）-extracellular signal-regulated kinase （ERK） pathway. These multi-target pathways improve UC symptoms， inhibit inflammation-cancer transition， and help maintain intestinal homeostasis. However， the precise mechanism of action has not yet been systematically elucidated. This paper reviews the research progress on Huaihuasan and main ingredients from its component drugs， focusing on their effects against UC. It also discusses current research limitations and suggests strategies for improvement， aiming to provide a reference for further studies on Huaihuasan in the treatment of UC and the development of new drugs.

Objective:To examine the attentional processing of verbal emotional information in college students with subclinical depression.Methods:Fifty college students were recruited(24 with subclinical depression group and 26 in the control group)were recruited from a university in Liaoning Province to investigate the atten-tional bias of subclinically depressed college students towards verbal emotional information(experiment 1).In addi-tion,48 college students(20 with subclinical depression and 28 in the control group)were recruited to investigate the attention disengagement of subclinically depressed college students from verbal emotional information(experi-ment 2).In experiment 1,two groups passively viewed words and recorded the eye movement data of emotional words.In experiment 2,two groups were asked to watch the emotional word-neutral word pair.When color borders were presented around neutral words,the attention disengagement latency that was the time taken by the eye saccade from emotional words to neutral words was recorded.Results:The results of experiment 1 showed that the total fix-ation duration of negative words in the subclinical depression group was longer than that in the control group(P＜0.01).The results of experiment 2 showed that attention disengagement latency of negative words in the subclinical depression group was longer than that in the control group(P＜0.05).Conclusion:College students with subclini-cal depression exhibit attentional bias towards negative verbal information and difficulties in attentional disengage-ment.

In order to establish a competitive chemiluminescent enzyme-linked immunoassay for rapid and quantitative detection of Senecavirus A antibodies,the polystyrene plate was coated with inactivated Senecavirus A antigen,and the monoclonal antibodies against Senecavirus A VP2 and VP3 proteins labeled by horseradish peroxidase(HRP)were used as the competitive enzymic anti-bodies of the antibodies in the serum samples.The standard curve of the calibrator prepared by di-lution of positive serum was drawn to achieve quantitative detection.The successfully established SVA competitive CLEIA reported the result within 45 minutes.The maximum dilution of 1∶2 048 for calibrator serum was still detectable with no cross-reaction with the standard positive serum of other five kinds of virus antigens such as foot-and-mouth disease.The coefficient of variation within batches was less than 10％,and the coefficient of variation between batches was less than 15％,which showed good repeatability and stability.The positive and negative coincidence rates were 95.30％and 97.57％,respectively,and the total coincidence rate was 96.88％,showing high consistency.The SVA competitive CLEIA assay established in this study can be used for the rapid quantitative detection of Senecavirus A antibodies,filling the gap in the domestic rapid quantitative detection of SVA antibodies.

Objective:To study on the relationship between serum levels of SC and SV and insulin resistance in elderly gestational diabetes mellitus.Methods:120 elderly patients with GDM were treated in Obstetrics Department of Yantai Yuhuangding Hospital from Jun. 2019 to Jun. 2021. The healthy women (58 cases) and normal pregnant women (58 cases) were selected as the control group at the same time, and the clinical data and serum samples of subjects were collected. The levels of serum SC, SV, FPG and HbAlc were measured, the HOMA-IR of the aged GDM was calculated, and the difference of serum index expression among the subjects in each group was analyzed. The relationship between serum SC, SV and insulin resistance was analyzed by Person correlation, and the risk factors of GDM were analyzed by Logistic regression.Results:: There was significant difference in HbAlc, HOMA-IR, FPG, SC, and SV among the three groups. The levels of each index in the elderly GDM group were significantly higher than those in the normal pregnancy group and the healthygroup ( P<0.05). Pearson analysis showed that SC ( P=0.558, 0.626, 0.672), SV ( P=0.576, 0.663, 0.696) was positively correlated with HbAlc, HOMA-IR, FPG in elderly patients with GDM ( P<0.001). Logistic regression analysis showed that SC, SV was risk factors for GDM in elderly pregnant women. Conclusion:There is a positive correlation between serum SC, SV level and insulin resistance, which are risk factors for GDM in elderly pregnant women.