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.

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.

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*

ObjectiveTo establish a method using ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） for the detection of six common trichothecene toxins in oats. MethodsOats were selected as the research subject in this study. Response surface design was used to optimize the QuEChERS extraction method. Additionally， a rapid and efficient strategy for sample extraction and purification was developed. Combined with UHPLC-MS/MS， six commonly co-occurring trichothecene toxins in oats were quantitatively analyzed simultaneously. ResultsThis method demonstrated good analytical performance for each analyte across the corresponding concentration ranges （r>0.99）， with accuracy ranging from 87.26% to 99.64%. The inter-day and intra-day relative standard deviations were less than 6.8% and 5.5%， respectively， indicating its potential for practical application. This method was used to detect mycotoxins in 12 oat samples from China， and it was found that one sample exceeded the standard limits for deoxynivalenol （DON）， and the co-contamination of trichothecene toxin was prevalent. ConclusionThe risk posed by these toxins has been underestimated. Ongoing， extensive monitoring is necessary to provide contamination data to assess the consumer risk.

ObjectivesTo investigate the effect of acupuncture intervention at different time during the acute phase of ischemic stroke on limb motor dysfunction 6 months after onset. MethodsThe enrolled ischemic stroke patients from four tertiary hospitals all received western basic treatment for ≥14 days； additionally， they were given the cleaning-mind and opening-orifices acupuncture method， with acupuncture at bilateral Neiguan （PC 6）， Shuigou （GV 26）， and Sanyinjiao （SP 6） of the affected side， once a day for at least 2 times. Three cohorts were formed by the timing of acupuncture intervention of the onset of the disease within 10 days， namely， the acupuncture group of 1-3 days after onset of the disease （195 cases）， the acupuncture group of 4-7 days after onset of the disease （171 cases）， and the acupuncture group of 8-10 days after onset of the disease （96 cases）. Propensity score matching was performed using R4.3.3 software， and there were 89 patients in each of the three groups after matching. Modified Rankin Scale （mRS） score， Fugl-Meyer Scale （FMA） score， EuroQoL 5-Dimension 5-Level （EQ-5D-5L） score and the proportion of good functional outcome were observed in the 3 groups of patients before treatment and 6 months after onset. A logistic regression model was constructed to analyse the effect of the timing of acupuncture intervention on the effectiveness of acupuncture treatment for limb motor dysfunction in ischaemic stroke. ResultsCompared with the pre-treatment of this group， mRS and EQ-5D-5L scores decreased and FMA increased in all three groups 6 months after onset （P＜0.01）， and all the indexes of the onset 1-3 days acupuncture group and the onset 4-7 days acupuncture group were better than those of the onset 8-10 days acupuncture group （P＜0.05）. The proportions of good functional outcome in the onset 1-3 days acupuncture group， the onset 4-7 days acupuncture group， and the onset 8-10 days acupuncture group were 76.40%， 80.90%， and 57.30%， respectively， and the proportions of good functional outcome in the onset 1-3 days acupuncture group and the onset 4-7 days acupuncture group were significantly higher than those in the onset 8-10 days acupuncture group （P＜0.05）. Multifactorial logistic analysis showed that compared with the group with 8-10 days of onset， the group with 1-3 days of onset （OR=2.796， 95%CI： 1.340~5.836， P = 0.006）， and the group with 4-7 days of onset （OR=3.482， 95%CI： 1.647~7.362， P = 0.001） increased the likelihood that patients would be nondisabled 6 months after onset. ConclusionThe intervention of cleaning-mind and opening-orifices acupuncture within 1-7 days of onset for patients with acute ischemic stroke can reduce the rate of disability 6 months after onset， improve limb motor function， and enhance the quality of life.

Objective Based on the theory of"lung governs the skin and hair"in"Yellow Emperor's Inner Classic",this paper analyzes the medication rules of whitening and freckle-removing.The aim of this study is to provide reference for the clinical practice of traditional Chinese medicine(TCM)theory and the medication in TCM cosmetics.Methods"Chinese Medical Classics"was used to search the records of whitening and freckle-related drugs.The frequency,nature,flavor,meridian tropism and compatibility laws of TCM for whitening and freckle-removal were analyzed by statistics and association rules.The network pharmacology research was used to analyze the whitening and freckle-removing effects and mechanisms of high-frequency drugs.Then,the potential active ingredients were analyzed.The whitening and anti-freckle effect was verified through cytotoxicity experiments and melanin content detection.Results A total of 171 external prescriptions were selected in eligible articles,including 261 Chinese medicinals,most of which were pungent and belong to the lung meridian.The most frequently used Chinese medicinals was"Erbai Yixin"(EBYX,Angelicae Dahuricae Radix,Typhonii Rhizoma,Asari Radix et Rhizoma).Network pharmacological analysis showed that the core targets of EBYX for whitening and removing freckles are TP53,EGFR,ALB,etc.,which are mainly involved in oxygen perception and response,skin immune regulation,skin cell growth,differentiation,stress,inflammatory response,and other biological processes.Based on the results of molecular docking,biological analysis proved that the active ingredients of EBYX are chrysophanol,gallic acid and caffeic acid,which have inhibitory effects on the proliferation of melanoma cells and melanin production.Conclusion Most of the ancient prescriptions for whitening and removing freckles are pungent and belong to the lung meridian,which embodies the theory of"lung governs the skin and hair".The high-frequency drug EBYX may play a role by regulating skin redox,immunity and inflammation.The active ingredients of EBYX have an inhibitory effect on melanin formation.This study enriches the scientific connotation of TCM whitening and freckle-removing prescriptions based on the theory of"lung governs the skin and hair",realizes interdisciplinary integration and provides support for the modernization of TCM.

Objective:To establish a menstrual prediction model after the first course of hormone replacement therapy(HRT)in premature ovarian insufficiency(POI)patients after allogeneic hematopoietic stem cell transplan-tation(allo-HSCT),and to provide certain reference value for formulating HRT plans.Methods:The retrospective analysis recruited 154 POI patients after allo-HSCT in the First Affiliated Hospital of Soochow University from Jan-uary 2017 to October 2022.They were divided into ideal menstruation group(n=116)and unideal menstruation group(n=38)according to menstruation after the first course of HRT.Basic characteristics and clinical data were compared in single-factor analysis to select predictive factors.Patients were randomly divided into training set and test set.The menstrual prediction model was developed based on random forest algorithm on the training set and the prediction efficiency was verified by the test set.Finally,we made a user interaction interface and deployed to the server for sharing.Results:The single-factor analysis suggested statistic difference of age of visit,body mass index(BMI),gravidity,parity,hematologic diseases,transplantation age,donor gender,follicle-stimulating hormone(FSH),Luteinizing Hormone(LH),lumbar bone mineral density(BMD)and HRT plan(P<0.05).According to mean decrease accuracy,the predictive factors included visit age,transplantation age,BMI,FSH,HRT plans,gravidity and parity.After the initial establishment of the random forest model,we improved it by adjusting ntree to 500,mtry to 6 and training/test set division to 80%/20% .We also used tenfold cross validation to reduce over-fitting.The area under curve(AUC)of the final constructed menstrual prediction model was 0.768,a sensitiv-ity of 0.695 and a specificity of 0.735.Conclusions:This study successfully established a menstrual prediction model for amenorrhea patients after allo-HSCT when finished the first course of HRT.The false positive rate was low,suggesting that if the prediction result of the model is non-ideal menstruation,we may consider adjusting HRT plans to promote menstruation in time.

Objective To construct a precise model for identifying traditional Chinese medicine(TCM)constitutions,thereby offering optimized guidance for clinical diagnosis and treatment plan-ning,and ultimately enhancing medical efficiency and treatment outcomes. Methods First,TCM full-body inspection data acquisition equipment was employed to col-lect full-body standing images of healthy people,from which the constitutions were labelled and defined in accordance with the Constitution in Chinese Medicine Questionnaire(CCMQ),and a dataset encompassing labelled constitutions was constructed.Second,heat-suppres-sion valve(HSV)color space and improved local binary patterns(LBP)algorithm were lever-aged for the extraction of features such as facial complexion and body shape.In addition,a dual-branch deep network was employed to collect deep features from the full-body standing images.Last,the random forest(RF)algorithm was utilized to learn the extracted multifea-tures,which were subsequently employed to establish a TCM constitution identification mod-el.Accuracy,precision,and F1 score were the three measures selected to assess the perfor-mance of the model. Results It was found that the accuracy,precision,and F1 score of the proposed model based on multifeatures for identifying TCM constitutions were 0.842,0.868,and 0.790,respectively.In comparison with the identification models that encompass a single feature,either a single facial complexion feature,a body shape feature,or deep features,the accuracy of the model that incorporating all the aforementioned features was elevated by 0.105,0.105,and 0.079,the precision increased by 0.164,0.164,and 0.211,and the F1 score rose by 0.071,0.071,and 0.084,respectively. Conclusion The research findings affirmed the viability of the proposed model,which incor-porated multifeatures,including the facial complexion feature,the body shape feature,and the deep feature.In addition,by employing the proposed model,the objectification and intel-ligence of identifying constitutions in TCM practices could be optimized.

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.