Ulcerative colitis（UC） is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa， and its complex pathogenesis involves immune abnormality， oxidative stress and other factors. The nuclear transcription factor E₂-related factor 2（Nrf2）， encoded by the Nfe212 gene， plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1（HO-1） and quinone oxidoreductase 1（NQO1）， but also enhances the activity of glutathione-S-transferase（GST） and superoxide dismutase 1（SOD1）， effectively eliminating reactive oxygen species（ROS） accumulated in the body， and mitigating oxidative stress-induced damage to intestinal mucosa. In addition， Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response， cell apoptosis and autophagy pathways， thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this， this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2， the molecular mechanism of activation， the protective effect in the pathological process of UC， and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory， promoting autophagy， inhibiting apoptosis， protecting the intestinal mucosal barrier， and promoting intestinal mucosal repair， providing new ideas and methods for the multi-faceted treatment of UC.

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*

OBJECTIVE: To investigate the effect of innovative perioperative pain management on prostate cancer patients with hematuria undergoing prostatic artery embolization (PAE). METHODS: A total of 60 patients undergoing PAE in the Interventional Therapy Department of General Hospital of Eastern Theater Command from May 2024 to January 2025 were selected by convenience sampling method and randomly divided into the intervention group and the control group, with 30 patients in each group. The control group received traditional pain management of nursing. An innovative perioperative pain management was performed in intervention group including preoperative "body-mind-pain" holistic assessment and preparation, intraoperative humanistic care and real-time support, postoperative multimodal analgesia and rehabilitation, dynamic monitoring and closed-loop feedback. The pain degree after 6 hours, 1 day, 3 days and 1 week of the operation, and the quality of life after 1 week of operation, as well as nursing satisfaction at discharge were compared between the two groups. RESULTS: The VAS scores of the intervention group were significantly lower than those of the control group after 6 hours, 1 day, 3 days and 1 week of operation (P<0.05). One week after the operation, the quality of life in the observation group was higher than that of the control group significantly (P<0.05). The nursing satisfaction of the observation group was significantly higher than that of the control group at discharge(P<0.05). CONCLUSION The application of innovative perioperative pain management can alleviate pain of patients with PAE, which improves the quality of life and nursing satisfaction of patients, and is conducive to the rehabilitation of patients.
Humans ; Male ; Embolization, Therapeutic ; Hematuria/therapy* ; Prostatic Neoplasms/surgery* ; Pain Management/methods* ; Quality of Life ; Prostate/blood supply* ; Perioperative Care ; Pain, Postoperative ; Middle Aged ; Aged ; Pain Measurement

OBJECTIVE: To evaluate the application effect of mindfulness-based stress reduction (MBSR) therapy on the patients treated with image fusion-guided transperineal prostate biopsy. METHODS: A total of 160 patients who underwent image fusion-guided transperineal prostate biopsy in the Urology Department from April 2023 to April 2024 were included. Patients were randomly assigned to a control group and an observation group, with 80 cases in each group. The control group received routine care, while the observation group received combined MBSR on the basis of routine care. The surgical indicators, pain levels, psychological states, nursing satisfaction, and postoperative complication rates of both groups were compared. RESULTS: There was no statistically significant difference in general personal information and clinical data between the two groups（P>0.05）. The surgery duration, secondary fusion rate, and postoperative complication rate in the observation group were all lower than those in the control group (［23.54±2.07］min vs ［26.25±1.69］min, P<0.05； 8.75% vs 22.50%, P=0.017； 17% vs 29%, P=0.036), and nursing satisfaction was higher in the observation group than in the control group ( 77% vs 69%, P=0.025). The VAS scores biopsy (5.11±0.93 vs 6.27±1.32, P=0.041), discharge (0.74±0.67 vs 1.85±0.95, P=0.004), and scores of SDS (47.76±2.06 vs 50.46±2.07, P=0.009) and SAS (46.89±2.68 vs 49.75±2.83, P=0.031) in the observation group were all lower than those in the control group. CONCLUSION The application of MBSR in image fusion-guided prostate biopsy can synergistically utilize the advantages of minimally invasive technology, significantly optimize surgical indicators, and improve patients' psychological experiences, which is worthy of clinical application and promotion.
Humans ; Male ; Mindfulness ; Prostate/pathology* ; Image-Guided Biopsy ; Stress, Psychological/therapy* ; Middle Aged ; Prostatic Neoplasms/pathology* ; Aged

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Overtraining is a condition characterized by various functional disorders or pathological states caused by continuous fatigue, which occurs after a persisting imbalance between training-related load and physical function and recovery. Generally speaking, it’s a state of imbalance between training and recovery, exercise and exercise performance, and stress and stress tolerance. Overtraining can cause various phenotypic changes or pathological remodeling, such as decreased skeletal muscle strength and exhaustive exercise endurance, skeletal muscle fatigue damage and dysfunction, skeletal muscle atrophy and loss, skeletal muscle glycogen depletion, skeletal muscle soreness and stiffness, skeletal muscle glucose intolerance, inattention, memory decline, anxiety, depression, abnormal emotions and behaviors, sleep disorders, cognitive function impairment, poor appetite, weight loss, liver/heart fat deposition, compensatory increase of liver/heart insulin signaling and glycogen storage, cardiac pathological hypertrophy, exercise-induced arrhythmias, myocardial fibrosis, ectopic and visceral fat deposition, and increased risk of injury. Unfortunately, its underlying mechanism is largely unclear. Recently, the enrichment of molecular and cellular signal pathway theory offers us a new explanatory paradigm for revealing its internal mechanisms. Based on the traditional explanation mechanisms and molecular and cellular signal pathway theory, we thoroughly analyzed the key mechanisms of health damage caused by overtraining from the perspective of oxidative stress, mitochondrial quality control disorder, inflammatory response, endoplasmic reticulum stress, cell apoptosis, and so forth. Specifically, overtraining-induced excessive reactive oxygen species (ROS) leads to serious oxidative stress damage in organisms at least via depressing Kelch like ECH associated protein 1(Keap1)/nuclear factor erythroid-2-related factor (Nrf2)/antioxidant response element (ARE) antioxidant pathway and activating p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Overtraining induces mitochondrial quality control disorder and mitochondrial dysfunction, and thus triggers health impairment through inhibiting mitochondrial biogenesis and fusion, stimulating mitochondrial fission, and over-activating autophagy/mitophagy. Overtraining can also produce muscle, skeletal and joint trauma, then circulating monocytes are abundantly activated by injury-related cytokines, and in turn generate large quantities of proinflammatory IL-1β, IL-6, TNF‑α, causing systemic inflammation and inflammatory health injury. Overtraining induces excessive pathological endoplasmic reticulum stress (ERS) and severe health damage via PERK-eIF2α, IRE1α-XBP1 and ATF6 pathways which activated by proinflammatory signals. Overtraining also induces excessive apoptosis and harmful health consequences via Bax/Bcl2-Caspase 3-mediated mitoptosis which activated by oxidative stress and inflammation or even CHOP and Caspase 12-dependent ERS apoptosis. Nonetheless, it should be importantly emphasized that oxidative stress and inflammation are the central and pre-emptive mechanisms of overtraining and its health damage. Although the efficient strategies for preventing and controlling overtraining are scientifically and reasonably arranging and planning training intensity, training volume, and recovery period, as well as accurately assessing and monitoring physical function status in the early stage, yet various anti-inflammatory, anti-oxidant, anti-apoptotic, or anti-aging drugs such as curcumin, astaxanthin, oligomeric proanthocyanidins, silibinin, hibiscus sabdariffa, dasatinib, quercetin, hydroxytyrosol, complex probiotics, astragalus polysaccharides, semaglutide and fasudil also have an irreplaceable positive effect on preventing overtraining and its relevant health damage via depressing oxidative stress, mitochondrial quality control disorder, proinflammatory signals, endoplasmic reticulum stress, apoptosis and so on. We hope that this review can help us further grasp the features, mechanisms and regularity of overtraining, and provide an important reference for athletes and sports fan to conduct scientific training, improve training effectiveness, extend exercise lifespan, and promote physical and mental health.