Ulcerative colitis （UC）， a chronic relapsing inflammatory bowel disease， involves multifaceted pathological mechanisms such as intestinal barrier dysfunction， immune dysregulation， and oxidative stress. Current therapeutic strategies remain limited in efficacy and safety. In recent years， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway has emerged as a pivotal therapeutic target for UC due to its central role in energy metabolism， inflammatory regulation， and intestinal homeostasis. This article systematically reviewed the mechanisms by which traditional Chinese medicine （TCM） prevented and treated UC through the regulation of the AMPK signaling pathway， with a focus on elucidating AMPK's multidimensional regulatory network in inflammatory signaling crosstalk， alleviating oxidative stress， restoring intestinal immune balance， repairing the intestinal barrier， and modulating gut microbiota. Leveraging its unique advantages of multi-target engagement and low toxicity， TCM demonstrates promising potential in UC treatment and has become a focal area of research. By systematically summarizing and synthesizing the existing literature on TCM-mediated AMPK pathway modulation in UC， this review aims to provide a theoretical foundation for advancing mechanistic research and clinical interventions in UC.

Objective To compare the contents of malonyl-ginsenosides Rb3 （MG-Rb3） in different parts, including roots, stems, leaves and flowers, of Panax ginseng, P. quinquefolium and P. notoginseng and explore the effects of two drying methods, constant temperature drying and vacuum freeze drying on their contents. Methods The contents of MG-Rb3 in P. ginseng, P. quinquefolium and P. notoginseng were compared based on HPLC analysis, using enzymatically synthesized MG-Rb3 as the reference standard. Results The buds of P. ginseng and P. quinquefolium exhibited relatively high levels of MG-Rb3, which were approximately 7.3-18.1 times and 2.8-4.3 times higher than those found in the roots, respectively, and the lowest contents were detected in the stems. The content of MG-Rb3 in P. notoginseng flower buds was about 31.2 times higher than that in leaves. The content of MG-Rb3 in the buds treated by constant temperature drying was about 1-1.1 times that of using vacuum freeze drying. Conclusion The highest content of MG-Rb3 was detected in the flower buds of P. ginseng and P. notoginseng, and the content of MG-Rb3 in leaves of P. quinquefolium was the highest. Content of MG-Rb3 in the buds after constant temperature drying was slightly higher than that of using vacuum freeze drying.

Pancreatic cancer （PC）， a highly malignant tumor of the digestive system， is characterized by extremely high incidence and mortality rates， imposing a severe burden on the healthcare system. Despite significant advancements in comprehensive therapeutic strategies for PC， clinical benefits for patients remain limited due to the high heterogeneity and unique microenvironment of the tumor. Therefore， further elucidating the molecular mechanisms underlying PC progression and developing novel， effective therapeutic strategies have become an urgent necessity in the current research. Programmed cell death （PCD） is a genetically orchestrated process of autonomous cell demise that is crucial for maintaining cellular homeostasis. Recent studies have demonstrated that tumor cells can remodel the tumor microenvironment by modulating various PCD pathways—including apoptosis， autophagy， pyroptosis， and ferroptosis—thereby driving tumor proliferation， invasion， and drug resistance. Traditional Chinese medicine （TCM） possesses unique advantages in anti-tumor therapy， characterized by multi-component， multi-target， and multi-pathway regulation. Accumulating evidence suggests that TCM formulas and their natural active compounds can effectively delay the malignant progression of PC by modulating PCD in tumor cells. This article systematically summarizes the molecular mechanisms of PCD in PC progression and reviews the mechanisms by which TCM formulas and natural active compounds intervene in PC through PCD modulation. This review aims to provide theoretical support and future research directions for the prevention and treatment of PC with TCM.

Objective:To understand the evolution and variation characteristics of the H1N1 influenza virus in Wuxi City from 2018 to 2023.Methods:Real time PCR was used to perform nucleic acid testing on throat swab samples of influenza like cases sent to sentinel hospitals for testing. The influenza A (H1N1) pdm09 positive samples were subjected to cell culture, and nucleic acid was extracted from strains with a red blood cell agglutination test (HA) ≥1∶8. The whole genome sequence was amplified, and a library was constructed. The MiSeq sequencer was used for sequencing on the machine. Using NC_026431.1 as a reference strain, we analyzed the offline data using CLC Genomics Workbench (Version 23) software. MEGA 7.0 software was used to construct a phylogenetic tree, and NetNGlyc 1.0 Server software was used to predict N-glycosylation sites.Results:The nucleotide and amino acid homology between 38 strains of A (H1N1) pdm09 influenza virus from 2018 to 2023 were 96.06%-100% and 96.12%-100%, respectively. From February to May 2023, all 12 strains of A (H1N1) pdm09 had two amino acid mutation sites occurring in the HA antigenic determinant cluster, namely the Ca region (A203T) and the Cb region (K71Q). No mutations were found in the HA receptor binding site and NA resistance site. The strains from January to June 2018 belong to the 6B. 1A evolutionary branch, the strains from December 2018 to January 2020 belong to three evolutionary branches: 6B. 1A. 1, 6B. 1A. 5a, and 6B. 1A. 7, and the strains from February to May 2023 belong to the 6B. 1A. 5a. 2a evolutionary branch. 38 strains of A (H1N1) pdm09 HA gene all have 7 potential N-glycosylation sites, while NA gene has 7-8 potential N-glycosylation sites.Conclusions:There are characteristic amino acid mutation sites of H1N1 influenza A in Wuxi City from 2018 to 2023. The emergence of these mutation sites may affect the virus′s transmission and antigenic changes.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Breast cancer is one of the most common and fatal malignancies among women worldwide, and its treatment efficacy is often limited by drug resistance and the presence of undruggable targets. Traditional small-molecule drugs have difficulty effectively modulating certain critical targets such as transcription factors and non-coding RNAs, necessitating new therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) function by recruiting pathogenic proteins to the cellular ubiquitin-proteasome system, thereby inducing their specific degradation. In contrast, ribonuclease-targeting chimeras (RIBOTACs) utilize small-molecule ligands but bind to RNA and direct endogenous RNases to selectively degrade pathogenic RNA molecules. By employing a "degradation rather than inhibition" mechanism, targeting chimera technology broadens the druggable landscape and offers a novel precision therapeutic strategy for breast cancer, particularly for refractory and drug-resistant cases. This approach not only overcomes the limitations of traditional drugs, such as the absence of suitable binding sites or poor selectivity, but also reduces required dosages and potential adverse effects. Recent studies have preliminarily demonstrated the therapeutic potential of PROTACs and RIBOTACs in breast cancer, encompassing target design, mechanistic investigation, and preclinical as well as early clinical applications. Research into these technologies reveals their ability to tackle previously undruggable targets, thereby providing theoretical support for the development of safer and more effective precision therapies for breast cancer. In the future, with advances in drug delivery systems and clinical trials, PROTACs and RIBOTACs are expected to be used synergistically with immunotherapy and chemotherapy, offering breast cancer patients more promising comprehensive treatment options and potentially driving oncology toward broader intervention of undruggable targets.
Humans ; Breast Neoplasms/drug therapy* ; Female ; Proteolysis ; Ribonucleases/metabolism* ; Molecular Targeted Therapy/methods* ; Antineoplastic Agents/therapeutic use*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To assess the intervention effect of nicotinamide mononucleotide (NMN) on the mouse model of hematotoxicity induced by subacute benzene exposure. Methods Benzene exposure and NMN intervention were adopted in a 2×2 factorial design, as benzene exposure and non-exposure, and NMN intervention and non-intervention. Male specific pathogen-free C57BL/6J mice were randomly assigned to negative control group, NMN control group, simple benzene exposure group and NMN intervention group, with 12 mice in each group. Benzene exposure of mice in simple benzene exposure group and NMN intervention group was conducted by dynamic inhalation of benzene at a concentration of 325 mg/m³ for six hours per day, five days per week for four weeks (28 days). Mice in the negative control and NMN control group inhaled clean air. During benzene exposure, mice in the NMN control group and NMN intervention group received NMN in drinking water at a dose of 300 mg/kg body weight. Peripheral blood samples of mice were collected for complete blood count analysis and calculation of composite inflammatory indices after 28 days. Results Interaction analysis showed that the counts of peripheral white blood cell, neutrophil, lymphocyte, and platelet of mice in the simple benzene exposure group were lower than those in the negative control group (all P<0.05). Neutrophil and platelet counts in the NMN intervention group were higher than those in the simple benzene exposure group (all P<0.05). The results of main effect analysis showed that the monocyte count of peripheral blood, systemic inflammatory index, systemic inflammatory response index, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio of mice in the benzene exposure group increased (all P<0.05), and the basophil count and lymphocyte/monocyte ratio decreased (all P<0.05), compared with the control group. Conclusion Oral NMN alleviates subacute benzene-induced decreases in peripheral neutrophil and platelet counts in mice. This protective effect may be related to the targeted intervention of NMN on mitochondrial energy metabolism disorder and oxidative damage induced by benzene exposure in male mice.

Objective To observe the therapeutic effect of Suoquan Runchang Prescription for senile mice with constipation and its mechanism of action.Methods Senile Kunming mice were randomly divided into constipation group,Suoquan Runchang Prescription group,ISCK03[stem cell factor(SCF),receptor tyrosine kinase(c-Kit)signaling pathway inhibitor]group,Suoquan Runchang Prescription+ISCK03 group,and normal group,with 12 mice in each group.Except for the normal group,a constipation model was constructed by gavage of 150 mg/kg Compound Diphenoxylate Suspension in all groups of senile Kunming mice.After successful modeling,each group was treated for two weeks.At the end of the intervention,the fecal particles count and fecal water content were detected,the serum levels of interleukin(IL)-1β,IL-6,motilin,gastrin,5-hydroxytryptamine(5-HT),and vasoactive intestinal peptide(VIP)were detected by enzyme-linked immunosorbent assay(ELISA),and the changes in gastric emptying rate and small intestine propulsion rate were determined,the pathologic changes of colonic tissues were detected by hematoxylin-eosin(HE)staining,and protein expressions of SCF and c-Kit in the colonic tissues was detected by Western Blot.Results Compared with the normal group,the disrupted cellular structure,thinner muscle layer,damaged mucosal epithelium were seen in the constipation group,and the fecal particle count,fecal water content,serum motilin,gastrin and 5-HT levels,gastric emptying rate,small intestine propulsion rate,the protein expression levels of SCF and c-Kit in colonic tissues were decreased,and the serum IL-1 β,IL-6 and VIP levels were increased,the differences being statistically significant(P＜0.05).Compared with the constipation group,the colonic tissues damage were improved in Suoquan Runchang Prescription group,the fecal particle count,fecal water content,serum motilin,gastrin and 5-HT levels,gastric emptying rate,small intestine propulsion rate,protein expression levels of SCF and c-Kit in colonic tissues were elevated,the serum IL-1β,IL-6 and VIP levels were decreased,the difference being statistically significant(P＜0.05).The indexes mentioned above in mice of ISCK03 group versus to the results of Suoquan Runchang Prescription group(P＜0.05).Compared with Suoquan Runchang Prescription group,the colonic tissues damage showed aggravated in Suoquan Runchang Prescription+ISCK03 group,and the fecal particle count,fecal water content,serum motilin,gastrin and 5-HT levels,gastric emptying rate,small intestine propulsion rate,protein expression levels of SCF and c-Kit in colonic tissues were decreased,the serum IL-1β,IL-6 and VIP levels were increased,the difference being statistically significant(P＜0.05).Conclusion Suoquan Runchang Prescription can effectively improve constipation in senile mice,and its therapeutic effect maybe related to the up-regulation of SCF,c-Kit expression,thus promoting intestinal peristalsis.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.