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*

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

A case of secondary pulmonary infection in a patient with acute exacerbation of chronic obstructive pulmonary disease was admitted.The patient was initially giren piperacillin-tazobactam combined with levofloxacin for anti-infective treatment before the pathogen was identified.lafer,the HRZE anti-tuberculosis regimen was added,but the patient continued to experience high fever,yellow purulent sputum,and dyspnea.Subsequent,bronchoalveolar lavage fluid pathogen metagenomic sequencing revealed Nocardia terpenica.Clinical pharmacists,based on the patient's condition changes and in accordance with relevant guidelines and literature,suggested using various antimicrobial agents,including compound sulfamethoxazole tablets,linezolid glucose injection,amikacin injection combined with imipenem-cilastatin,to manage the patient's intolerance to sulfonamides and the bone marrow suppression induced by linezolid and to provide medication suggestions.The clinician adopted all the suggestions.Through the collaborative efforts of physicians and clinical pharmacists,the patient's condition improved,allowing for discharge with medication.Post-discharge,medication education and follow-up were conducted,leading to successful recovery.In this case,the clinical pharmacist reviewed domestic and international literature on Nocardia terpenica and the characteristics of antimicrobial drugs,and utilized their expertise to assist clinicians in treating rare infection cases,realizing their professional value.

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 down-regulated metabolites in sera of RIPS 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[13Cs]-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 expression and prognostic value of microRNA-29b-2-5p(miR-29b-2-5p)and syntaxin 16(STX16)in hepatocellular carcinoma(HCC).Methods The cancer tissues and adjacent tissues of 88 HCC patients diagnosed in Nantong Tumor Hospital from January 2013 to September 2020 were collected.The expressions of miR-29b-2-5p and STX16 in cancer tissues and adjacent tissues were analyzed by real-time fluorescent quantitative PCR.The expression of STX16 protein in cancer tissues and adjacent tissues were analyzed by immunohistochemistry.Pearson correlation analysis was used to analyze the correlation be-tween miR-29b-2-5p and STX16.Non-parametric χ2 test was used to analyze the relationship between the ex-pression of the two proteins and clinicopathological parameters,and Kaplan-Meier survival curve was used to analyze the relationship between the expression of the two proteins and prognosis.Results The relative ex-pression level of miR-29b-2-5p was 0.780(0.351,1.708)in cancer tissues and 1.014(0.458,3.124)in adja-cent tissues in 88 HCC patients.The relative expression level of miR-29b-2-5p in cancer tissues was signifi-cantly lower than that in adjacent tissues(P=0.012).The relative expression level of STX16 mRNA was 0.775(0.406,0.946)in cancer tissues and 0.368(0.080,1.301)in adjacent tissues in 88 HCC patients.The relative expression level of STX16 mRNA in cancer tissues was significantly higer than that in adjacent tissues(P<0.01).Immunohistochemical results showed that STX16 was expressed in the cytoplasm,and the expres-sion of STX16 in cancer tissues was higher than that in adjacent tissues(P<0.05).The expression of miR-29b-2-5p in cancer tissues was related to cancer stage(P<0.05),and the expression of STX16 was related to cancer stage and alpha-fetoprotein(P<0.05).Patients with low miR-29b-2-5p expression had a shorter over-all survival(OS)than those with high miR-29b-2-5p expression,and patients with high STX16 expression had a shorter OS than those with low STX16 expression(P<0.05).Conclusion The expression of miR-29b-2-5p is low and STX16 is high in HCC tissues.The combined detection of miR-29b-2-5p and STX16 can effectively evaluate the prognosis of HCC patients.

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 develop an intelligent recognition and precise segmentation technique using ultrasonic images，and to enhance diagnostic efficiency and accuracy.Methods:A total of 1，430 patients diagnosed with uterine fibroids through transvaginal ultrasonography at the Maternal and Child Health Hospital of Guangming from November 2020 to October 2024 were retrospectively included. Ultrasonic images were manually annotated by two experienced physicians and reviewed by a senior expert. The Mask DINO deep learning model was used for lesion segmentation，and the segmentation results were optimized using ellipse fitting technology. Model performance was evaluated using the Dice coefficient，intraclass correlation coefficient（ICC），mean absolute error（MAE），and measurement accuracy.Results:In the test set of 286 cases，the average Dice coefficient of model prediction was 0.992，indicating extremely high segmentation accuracy. The average accuracy of lesion identification by the model was 0.909，with 241 correctly identified samples，19 basically correct samples，and 26 incorrect samples. In terms of long and short axis measurements，the ICC of the model's direct predictions were 0.871（short axis）and 0.784（long axis），with MAE of 0.436 cm（short axis）and 0.508 cm（long axis）. After optimization with ellipse fitting，the ICC increased to 0.893（short axis）and 0.866（long axis），and the MAE decreased to 0.191 cm（short axis）and 0.274 cm（long axis），the measurement accuracy improved significantly.Conclusions:The intelligent recognition and precise segmentation technique for uterine fibroids based on ultrasonic images constructed in this study performed excellently in lesion segmentation and measurement，it can significantly improve the efficiency and accuracy of diagnosis.

OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.

Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86％,95.16％,and 95.10％,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90％.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59％,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24％,53.39％,and 62.37％for junior technicians,and to 92.06％,83.24％,and 83.12％for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46％,10.61％,and 3.71％for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13％)of red blood cell diseases,5 cases(0.16％)of platelet diseases,2 343 cases(76.90％)of infection-related disea-ses,and 28 cases(0.92％)of malignant hematological diseases.In addition,332 cases(10.90％)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.