Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

OBJECTIVE To provide reference for medication therapy management （MTM） of diabetic patients complicated with cardiovascular disease. METHODS A 63-year-old male diabetic patient who suffered from temporary headache every morning after percutaneous coronary intervention （PCI） visited the neurology department of our hospital， and then was recommended to the pharmaceutical outpatient department. The pharmacists thought that the patient’s symptoms of headache， severe constipation and hyperuricemia were more likely induced by the medication used. The pharmacists further found that his atherosclerotic cardiovascular disease （ASCVD） influencing factors such as blood pressure， heart rate， blood glucose and blood lipids did not reach standard. The pharmacists provided MTM services for the patient through pharmacy inquiry and adverse drug reactions judgement， medication evaluation， medication reconciliation， medication education and pharmacy follow-up. RESULTS Through fifteen MTM services for thirteen weeks， the pharmacists reconciliated and optimized the medication therapy plan， discontinued the use of Isosorbide mononitrate sustained-release tablets， Nifedipine controlled-release tablets， and Indapamide tablets， which caused adverse drug reactions； the number of drugs was adjusted from fifteen to seven， and the symptom of headache disappeared； severe constipation had also been significantly improved， and hyperuricemia dropped to normal range. The ASCVD influencing factors of blood pressure， heart rate， fasting plasma glucose， glycosylated hemoglobin， low-density lipoprotein cholesterol and uric acid were reduced from ＞140/90 mmHg（1 mmHg＝0.133 kPa）， 70-80 beats per minute， 7.71 mmol/L， 7.2%， 2.13 mmol/L and 494 μmol/L before MTM services to ＜130/80 mmHg， 55-60 beats per minute， 6.22 mmol/L， 6.3%， 1.55 mmol/L and 348 μmol/L after MTM services. CONCLUSIONS The pharmacists providing MTM services to the patients can improve their quality of life and therapeutic efficacy， reduce medication risks， and enhance the level of rational drug use in hospitals and pharmaceutical service capabilities.

Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. In recent years， the clinical early diagnosis and treatment protocols of HCC have been improved， whereas the prognosis of patients is still not satisfactory， which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore， it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies， HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation， promotion， and progression stages. HCC is categorized as infantile malnutrition with accumulation， hypochondriac pain， tympan ites， and abdominal mass in traditional Chinese medicine （TCM）. In the treatment of HCC， TCM with low toxicity， multi-targets， and multi-mechanisms can inhibit tumor growth， alleviate the clinical symptoms， and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation， histone modification， and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC， and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism， with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.

Objective To compare different treatment methods for patients with gastric calculi and provide data support for clinical treatment.Methods A total of 197 patients diagnosed with gastric calculi by gastroscopy at the General Hospital of Ningxia Medical University and Cardio-Cerebrovascular Disease Hospital of General Hospital of Ningxia Medical University from July 2013 to January 2024 were enrolled.The study collected general information and other data of the patients,and divided them into groups based on the selected treatment method using a real-world research approach.The subjects were divided into four groups:drug conservative treatment group,endoscopic homemade snare treatment group,disposable snare treatment group,and stone fragmentation treatment group.Statistical analysis was performed using one-way analysis of variance.Results Gastric calculi were more common in men,with an average age of(55.45±14.21).85.3%of the patients had a history of eating persimmon,86.3%had ulcers,and 65.9%were located in the gastric angle.The self-made snare group had the lowest treatment cost,while the stone fragmentation group had the highest.There was no significant difference in the remission time of clinical symptoms among the three endoscopic treatment methods.The self-made snare had the highest patient satisfaction,but the drug combined with carbonated beverage group had the longest remission time of clinical symptoms and the lowest patient satisfaction.The frequency and duration of endoscopic treatment of dark green gastric stones were significantly higher than those of mottled and golden yellow gastric stones.Conclusion When treating patients with gastric stones,it is important to consider the size and color of the stone,as well as the patient's preferences.Patients should be fully informed about their condition and the advantages of different treatments.For patients with larger stones(about 5 cm),endoscopic snare treatment is recommended as the first choice.

Objective:To explore the curative effect of 308nm excimer laser combined with halometasone cream on vitiligo.Methods:A total of 100 patients with vitiligo who admitted to PLA Rocket Force Characteristic Medical Center from January 2022 to January 2023 were selected.They were randomly divided into control group(50 cases)which underwent treatment by halometasone cream,and observation group(50 cases)which underwent treatment by 308nm excimer laser combined with halometasone cream.The levels of T cell subpopulations(CD3+,CD4+,CD8+),inflammatory cytokines[interleukin-10(IL-10),interleukin-17(IL-17),interleukin-23(IL-23)],serum monocyte chemotactic protein-1(MCP-1)and soluble intercellular adhesion molecules-1(sICAM-1)between two groups were compared,and the effective rate of treatment and the incidence of adverse reaction between two groups were also compared.Results:The effective rate of treatment of the observation group was 96.00%(48/50),which was significantly higher than that[82.00%(41/50)]of control group,and the difference was significant(x2=5.005,P＜0.05).After treatment,the CD3+,CD4+and CD4+/CD8+levels of the observation group increased,while the CD8+level decreased,and the difference of T cell subpopulations between two groups were significant after treatment(t=6.745,2.406,3.969,3.998,P＜0.05),respectively.After treatment,the IL-10 level of observation group was higher than that of control group,while the IL-17,IL-23,MCP-1 and sICAM-1 levels of observation group were significantly lower than those of control group(t=11.607,5.892,9.140/9.920,14.682,P＜0.05),respectively.The incidence of adverse reaction of observation group and control group were respectively 14.00%(7/50)and 10.00%(5/50),and the difference of that between the two groups was no significant(P＞0.05).Conclusion:308nm excimer laser combined with halometasone cream has a favorable effect in treating vitiligo,which can improve the levels of T cell subpopulations,inflammatory cytokines,MCP-1 and sICAM-1.It does not increase adverse reactions.Therefore,it has a certain clinical value.

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and down-regulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.