In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

BACKGROUND:In clinical practice,Cibotium barometz and Epimedium have shown significant efficacy in the treatment of rheumatoid arthritis,but the complex active ingredients contained in the two have an unclear mechanism of action at the molecular level for the treatment of rheumatoid arthritis. OBJECTIVE:Based on network pharmacology and molecular docking technology,to establish a collagen-induced arthritis model and to verify the potential targets and pathways of Cibotium barometz and Epimedium in the treatment of rheumatoid arthritis,providing reliable experimental evidence for the use of clinical formulas with Cibotium barometz and Epimedium as the main components. METHODS:Utilizing traditional Chinese medicine research platforms,traditional Chinese medicine encyclopedias,and databases of traditional Chinese medicine and chemical components from the Shanghai Institute of Organic,effective ingredients were retrieved and identified.3D molecular formulas were obtained from the PubChem platform and target predictions were made using PharmMapper and SwissTargetPrediction.Disease targets for rheumatoid arthritis were obtained from gene databases such as DrugBank,GeneCards,and OMIM.The intersections of targets and Cibotium barometz and Epimedium were plotted using VENNY 2.1 after calibration with the Uniport database.A protein-protein interaction network graph was constructed using the STRING platform.Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the Metascape platform for data visualization.A four-layered network model of traditional Chinese medicine,ingredients,targets,diseases,and pathways was constructed using Cytoscape 3.9.0.The main effective ingredients were docked with core targets using AutoDock-Vina software to explore the best binding targets.A type II collagen+adjuvant-induced arthritis rat model was established,and the effects of Cibotium barometz and Epimedium on relevant pathway targets and inflammatory cell factors were observed after 21 days of intervention. RESULTS AND CONCLUSION:A total of 28 active ingredients from Cibotium barometz and Epimedium were selected,yielding 288 intersection targets for rheumatoid arthritis.The main ingredients included isobavachalcone,cibotium,and epimedium.The main targets included protein kinase 1 for serine/threonine(AKT1),tumor necrosis factor,and vascular endothelial growth factor A.Gene ontology analysis yielded 2 232 biological processes,mainly related to serine protein phosphorylation,positive regulation of serine/threonine protein kinase,and reactive oxygen metabolism.Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 202 pathways,mainly involving the PI3K/AKT signaling pathway and epidermal growth factor receptor signaling pathway,which may exert therapeutic effects by regulating synovial cell apoptosis and proliferation and suppressing inflammatory factors.Molecular docking results showed the strongest binding activity and stable structure of Cibotium barometz and Epimedium with AKT1 and estrogen receptor transcription factor 1,which was closely related to apoptosis and proliferation and inflammatory signaling pathways such as PI3K/AKT.Cibotium barometz and Epimedium reduced the expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the serum of collagen-induced arthritis rat models.Cibotium barometz and Epimedium reduced the expression of p-PI3K,p-AKT,and p-FOXO1 in the synovium of collagen-induced arthritis rat models.The results indicate that the combination of Cibotium barometz and Epimedium may exert therapeutic effects by inhibiting the proliferation of synovial cells and suppressing the expression of inflammatory factors via the PI3K/AKT/FOXO1 signaling pathway.This may be closely related to the occurrence of inflammation and bone destruction in rheumatoid arthritis,and provides a reference for the rational use and development of new drugs in clinical practice.

Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.

Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.

Pafolacianine is a fluorescent agent that specifically targets folate receptors,employed in the treatment of adult ovarian cancer patients to support the detection of malignant growths during surgical interventions.Pafolacianine binds to cancer cells expressing folate receptors,accumulating within folate-receptor-positive tumor tissue through receptor-mediated endocytosis.It can be excited by near-infrared fluorescence imaging,facilitating the surgical removal of tumors during procedures.This article gives an introduction to the mechanism of action,pharmacokinetics,clinical studies,and safety aspects of Pafolacianine.

Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.