Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the efficacy and safety of interventional therapy for bronchopleural fistula(BPF).Methods A total of 172 patients with confirmed BPF were treated with continuous negative pressure drainage(CNPD)and/or airway stent occlusion therapy.The clinical data were collected,and its effectiveness and safety were analyzed.Results In 5-7 days after interventional treatment,the pneumonia severity index(PSI)decreased significantly,and successful drainage was achieved in 166 patients(96.5％).One month after interventional therapy,the lung volume was remarkably increased.The median clinical healing time of interventional therapy was 9.0 months(95％CI=6.18-1 1.83).Multivariate analysis of the Cox proportional hazards model showed that the diagnosis time(HR=0.53,95％CI=0.38-0.74,P＜0.01)and fistula size(HR=0.74,95％CI=0.55-0.99,P=0.04)were significantly correlated with the clinical healing time.Conclusion For the treatment of BPF,CNPD and/or airway stent occlusion has several advantages such as accurate operation,minimally invasive,safe and effective.It can quickly improve the symptoms and quality of life,and prolong survival,therefore,it is worthy of clinical promotion and application.(J Intervent Radiol,2024,33:641-645)

Objective To apply PDCA(plan,do,check and action)cycle to optimize management and shorten the turnaround time(TAT)of five sex hormone tests for improving clinical efficiency and patient satisfaction.Methods A PDCA management team was established to retrospectively analyze the current status of sex hormone TAT in 2021.In 2022,PDCA tools were utilized,including fishbone diagrams for cause analysis,Pareto charts for root cause identification,formulation and implementation of corresponding im-provement measures and monitoring of TAT changes before and after PDCA.Results Through the corrective measures,such as staff personnel training,increasing testing equipment,optimization process and other improvement measures,the median TAT of sex hor-mone samples in 2022(post-PDCA improvement)was 54 minutes which was significantly lower than 61 minutes in 2021(pre-PDCA)(P＜0.05).Conclusion PDCA cycle management effectively shortened the TAT of sex hormone samples,enhanced clinical diagnostic efficiency and patient experience,improved doctor-patient relationships,while also elevated the quality management standards of labo-ratories.

Objective:To investigate the clinical efficacy and safety of programmed death protein 1 (PD-1) inhibitos combined with Fuzheng Kang'ai Decoction in patients with stage Ⅲ or Ⅳ non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis in real world.Methods:Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), total survival time (OS) and adverse events of patients with advanced or metastatic NSCLC who received PD-1 inhibitors for the first time in the Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine from August 2018 to March 2021 were retrospectively analyzed, and was prospectively followed up until September 2022. Kaplan-Meier method was used to plot survival curves and evaluate median PFS and median OS, while Cox proportional hazards regression model was used for multivariate analysis.Results:The final 66 patients were included in the study, with an ORR of 33.3% (22/66), a DCR of 86.4% (57/66), a median PFS of 9.90 months, and a median OS of 31.83 months. Univariate analysis showed that median PFS was associated with TNM stage, liver metastasis, PD-L1 expression level, lung immune prognostic index (LIPI), and traditional Chinese medicine syndrome types ( P values were 0.004, 0.033, 0.040, 0.004, and 0.001, respectively). Multivariate Cox regression analysis showed that TNM stage [ HR (95% CI)=4.179 (1.781, 9.804)], PD-L1 expression level 1%-49% [ HR (95% CI)=0.346 (0.127, 0.940)] or ≥ 50% [ HR (95% CI)=0.074 (0.019, 0.288)], LIPI [ HR (95% CI)=14.515 (2.939, 71.681)], and TCM characteristics of deficiency of yang qi [ HR (95% CI)=5.954 (2.093, 16.940)] were independent influencing factors for PFS. The overall and grade 3-5 treatment-related adverse events were 68.2% (45/66) and 9.1% (6/66), respectively. Conclusions:Fuzheng Kang'ai Decoction combined with PD-1 inhibitors is an effective and tolerable therapy for patients with advanced or metastatic NSCLC. TNM stage, liver metastasis, PD-L1 expression, LIPI and TCM characteristics are early predictors of clinical efficacy for patients with stage Ⅲ/Ⅳ NSCLC that receive traditional Chinese medicine combined with immunotherapy .

Objective To discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.

OBJECTIVE To explore the correlation between changes in intestinal toxicity and changes in component composition of the Mongolian medicine Euphorbiae pekinensis Radix(EPR)before and after processing with milk.METHODS Mice were given 95%ethanol extract of raw EPR,milk-processed EPR and water-processed EPR by gavage.The purgative effect and intestinal inflam-matory toxicity changes of EPR before and after milk processing were investigated using the fecal water content and the levels of inflam-matory factors TNF-α and IL-1β in each intestinal segment of mice as indicators;LC-MS/MS was used to analyze the composition changes of the 95%alcohol extract of EPR before and after milk processing.RESULTS Compared with the blank group,the raw and water processed products of EPR could significantly increase the water content of mouse feces and the levels of TNF-α and IL-1β in each intestinal segment(P＜0.05);compared with the raw product group,all indicators in the milk processing group were significantly reduced(P＜0.05),while there was no significant difference in the water processing group,indicating that water processing cannot at-tenuate toxicity,and the auxiliary material milk is the key auxiliary material to reduce the toxicity of EPR.Mass spectrometry analysis results showed that a total of 50 components were identified in EPR,including 38 terpenoid components,6 phenolic acid components,and 6 other components.The content of each component decreased to varying degrees after milk processing.Principal component analy-sis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were performed on the mass spectrum data of raw ma-terials and products,and it was found that the components of raw materials and products can be obviously clustered into 2 categories.13 differential components of raw materials and products were screened through t test,and 11 of which were terpene compo-nents,indicating that the composition of terpene components changed significantly after milk processing.17 components derived from EPR were detected in the residual liquid of milk excipients after processing,of which 16 were terpenoids,indicating that the terpenoid components of EPR were transferred to the excipient milk during the soaking and processing processes.CONCLUSION The toxicity of EPR is reduced and the purgative effect is alleviated after milk processing.The attenuation mechanism may be that during the milk soaking and processing processes,terpenoid components are transferred to the milk,and the content of toxic components in the decoc-tion pieces is reduced,thereby reducing the toxicity.

To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods:The methylation data of 310 cervical tissue specimens were acquired from public databases. The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer. Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub. Finally, gene-enrichment analysis, pathway analysis, immune infiltration analysis, the mutation rate and tumor mutation burden (TMB) of the genes in cervical cancer were analyzed using the cBioportal database. Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration; comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests. TMB analyses were performed using the Wilcoxon Test for statistical analyses; Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results:The methylationβvalue of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A gene) in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylationβvalue of 0.049 in normal human tissues ( P=0.008). Dihydrolipoamide S-Acetyltransferase (DLAT gene) methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08 ( P=0.002), and the methylation level β value of Lipoyltransferase 1 (LIPT1 gene) in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092 ( P=0.009). Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years, which was lower than that of patients with methylation levels<0.199 (17.56 years) ( P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type I interferon and DNA replication. The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment( P<0.05), and negatively correlated with the number ofmacrophages( P<0.05). TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants ( P=0.019). Conclusion:CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.

Chest wall tumor(CWT) is a heterogeneous tumor involving multiple systems, including primary and secondary tumors. Chest wall tumors should first be classified according to their histological origin before distinguishing between benign and malignant. Except for a very few malignant tumors, surgical resection is the first choice for the treatment of chest wall tumors. However, chest wall tumors are different from other tumors in that resection of these tumors will compromise the integrity and stability of the chest wall, which makes it necessary before surgery to evaluate not only whether the tumor can be resected, but also the necessity and feasibility of postoperative chest wall reconstruction. With the progress of medical technology, the styles and methods of surgical treatment of chest wall tumors have also made marked advancements. This article aims to briefly review the changes and developments of surgical treatment of chest wall tumors in recent years, so as to provide a reference for clinical work.