Ulcerative colitis(UC) is a recurrent, chronic, nonspecific inflammatory bowel disease. The longer the course of the disease, the higher the risk of cancerization. In recent years, the incidence and mortality rates of colon cancer in China have been increasing year by year, seriously threatening the life and health of patients. Therefore, studying the mechanism of "inflammation cancer transformation" in UC and conducting early intervention is crucial. The "Kenang" theory is an important component of traditional Chinese medicine(TCM) theory of phlegm and blood stasis. It is based on the coexistence of phlegm and blood stasis in the body and deeply explores the pathogenic syndromes and characteristics of phlegm and blood stasis. Kenang is a pathological product formed when long-term Qi stagnation leads to the internal formation of phlegm and blood stasis, which is hidden deep within the body. It is characterized by being hidden, progressive, and difficult to treat. The etiology and pathogenesis of "inflammation cancer transformation" in UC are consistent with the connotation of the "Kenang" theory. The internal condition for the development of UC "inflammation cancer transformation" is the deficiency of healthy Qi, with Qi stagnation being the key pathological mechanism. Phlegm and blood stasis are the main pathogenic factors. Phlegm and blood stasis accumulate in the body over time and can produce cancer toxins. Due to the depletion of healthy Qi and a weakened constitution, the body is unable to limit the proliferation and invasion of cancer toxins, eventually leading to cancer transformation in UC. In clinical treatment, the focus should be on removing phlegm and blood stasis, with syndrome differentiation and treatment based on three basic principles: supporting healthy Qi to strengthen the body's foundation, resolving phlegm and blood stasis to break up the Kenang, and regulating Qi and blood to smooth the flow of energy and resolve stagnation. This approach helps to dismantle the Kenang, delay, block, or even reverse the cancerization process of UC, reduce the risk of "inflammation cancer transformation", improve the patient's quality of life, and provide new perspectives and strategies for early intervention in the development of colon cancer.
Humans ; Colitis, Ulcerative/immunology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Cell Transformation, Neoplastic

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

As an indispensable trace element in the human body,copper plays an important role in various physiological and biochemical reactions.The dyshomeostasis of copper leads to the disorder of copper metabolism and the occurrence of related diseases.Cuproptosis,a newly proposed regulatory cell death mode,is different from the known apoptosis,pyroptosis,necroptosis,and ferroptosis.Recent studies have found that the dyshomeostasis of copper has been observed in a variety of cancers.Therefore,targeting copper for disease treatment may become a new strategy and a new idea.This article systematically summarizes the fundamental properties of copper,copper dyshomeostasis-related diseases (Menkes syndrome,Wilson's disease,and cancer) and their treatment,and reviews the research progress in cuproptosis.
Humans ; Copper/metabolism* ; Homeostasis ; Neoplasms/metabolism* ; Hepatolenticular Degeneration/metabolism* ; Menkes Kinky Hair Syndrome/metabolism*

Objective To investigate the mechanism of Guizhi Fuling Pills in the treatment of polycystic ovary syndrome(PCOS)and endometriosis(EMT).Methods TCMSP was utilized to obtain the active ingredients and related targets of the constituent Chinese medicines of Guizhi Fuling Pills.GeneCards,PharmGKB,and TTD databases were used to screen PCOS and EMT disease targets,respectively.The Venn R diagram was drawn after obtaining the intersecting targets of drugs and diseases using the Venn R package in R software,the drug-active ingredient-potential target interactions network diagram was made in Cytoscape,the intersecting target protein-protein interactions(PPI)network diagram was drawn in the STRING platform,and Cytoscape was used to optimize the PPI network and screen the core targets.R language was applied for Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and AutoDockTools was for molecular docking.Results A total of 85 active ingredients and 191 corresponding targets of Guizhi Fuling Pills were obtained,and 77 potential targets of Guizhi Fuling Pills for the treatment of PCOS and EMT.The core active ingredients of Guizhi Fuling Pills for PCOS and EMT were quercetin,β-sitosterol,kaempferol,hederagenin,baicalein,and the core targets were AKT1,EGFR,IL-6,TNF,and TP53.GO functional analysis yielded 2 020 biological process,34 cellular components,126 molecular functions,and KEGG enrichment analysis yielded 165 signaling pathways.Molecular docking showed that the core components in the formula docked well with the targets.Conclusion Guizhi Fuling Pills may regulate the signaling pathways of lipid and atherosclerosis,AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,and chemical carcinogenesis-receptor activation through quercetin,β-sitosterol,kaempferol,hederagenin,and baicalein,and act on AKT1,EGFR,IL-6,TNF,and TP53,thus treating PCOS and EMT with homotherapy for heteropathy.

By consulting ancient herbal books and modern literature， this paper systematically sorted out and researched the processing history， relevant processing norms in recent years， modern processing technology， chemical composition changes of processed products and their pharmacological mechanism of Scutellariae Radix， in order to provide a basis for the further development of Scutellariae Radix decoction pieces. According to the textual research of ancient books， there were many kinds of processing auxiliary materials of Scutellariae Radix， such as wine， vinegar， salt， honey， pig bile and so on， among which the wine processing was the most diverse and detailed， and the processed products such as raw products， stir-fried products， wine-processed products， fried charcoal products were still in use. The modern processing techniques of Scutellariae Radix mainly focus on the processing aspects of softening and slicing， wine processing and charcoal frying， and the research methods are relatively unified. At present， it is found that the changed chemical constituents of Scutellariae Radix after processing are flavonoids， polysaccharides， volatile oils and trace elements， etc. Pharmacological effects of processed products are hemostasis， antibacterial， anti-inflammatory， antioxidant， analgesic and antipyretic， treatment of lung diseases， treatment of colitis， etc. However， in the studies of Scutellariae Radix processing， there is a lack of research on the structural changes of chemical components caused by processing and a comprehensive comparative study on the pharmacological effects of various processed products. Based on this， it is suggested to carry out systematic research on the processing technology to processing mechanism， further explore the relationship between the change rule of material basis and pharmacological action before and after processing of Scutellariae Radix， and deepen the exploration of molecular mechanism and clinical application of processed products of Scutellariae Radix， in order to clarify the scientific connotation of the processing mechanism of Scutellariae Radix， and lay a foundation for the subsequent expansion of the application of Scutellariae Radix decoction pieces and the formulation of processing standards.

Objective:To investigate the diagnostic value of machine learning model based on 18F-FDG PET/CT for polymyalgia rheumatica (PMR). Methods:From November 2014 to December 2022, 177 patients (119 males, 58 females; age: 67.0 ( 61.0, 72.0) years) admitted to the Department of Rheumatology and Immunology, the First People′s Hospital of Changzhou, with suspected PMR and undergoing 18F-FDG PET/CT examination were retrospectively analyzed. Patients were randomly divided into training set and validation set at the ratio of 7∶3. Three machine learning models, including classification and regression tree (CART), the least absolute shrinkage and selection operator (LASSO) algorithm, and logistic regression, were established based on the PET/CT imaging features to aid in the diagnosis of PMR. The diagnostic efficacy of each model was evaluated by ROC curve analysis and differences among AUCs were analyzed by Delong test. Results:There were 78(44.1%, 78/177) PMR patients and 99(55.9%, 99/177) non-PMR patients, and 124 patients in the training set and 53 patients in the validation set. The logistic regression model (training set: AUC=0.961; validation set: AUC=0.930) was superior to the CART (training set: AUC=0.902, z=2.96, P=0.003; validation set: AUC=0.844, z=2.46, P=0.014) in diagnosing PMR, and was similar to LASSO algorithm (training set: AUC=0.957, z=0.95, P=0.340; validation set: AUC=0.930, z=0.00, P=1.000), but with fewer sites evaluated. The simplified PMR-Logit score had the AUC of 0.951 in the overall population, with the sensitivity of 89.74%(70/78) and the specificity of 90.91%(90/99). Conclusion:Machine learning models based on 18F-FDG PET/CT imaging features are expected to be an effective diagnostic tool for PMR.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Pharmaceutical cocrystals are one of the effective strategies to improve the solubility and bioavailability of poorly water-soluble drugs. However, the phase transformation of cocrystals during dissolution can lead to the recrystallization of the parent drugs, and thus negating the solubility advantage of cocrystals. The introduction of suitable excipients into the cocrystal formulation may inhibit the phase transformation during dissolution, resulting in the enhanced dissolution and bioavailability of poorly soluble drugs. In addition, the complex gastrointestinal environment and absorption behavior of drugs can have significant impacts on the oral bioavailability of cocrystals. This review summarizes the recent studies of the dissolution and absorption of pharmaceutical cocrystals, and aims to provide guidance for the rational design of pharmaceutical cocrystal formulations.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.