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.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective To evaluate the application efficacy of low-dose test method combined with variable helical pitch(VHP)technology in computed tomography angiography(CTA)of lower extremity arteries.Methods Eighty patients with CTA imaging of bilateral lower extremity arteries were selected and divided into group A and group B on average.VHP technology was used in group A,and conventional fixed pitch scanning was used in group B.The objective and subjective image quality of the two groups were compared,and the radiation dose and contrast agent dosage of the two groups were recorded and compared.Results The subjective image quality evaluation of group A was significantly better than that of group B,and the difference was statistically significant(Kappa test,P<0.05).In the objective image quality evaluation,the CT value and signal-to-noise ratio(SNR)value of the common iliac artery,popliteal artery and anterior tibial artery in group A were higher than those in group B at the same level,and the differences were statistically significant(P<0.05);The effective dose(ED)value in group A was(6.74±1.20)mSv,and that in group B was(7.93±1.78)mSv(P<0.05).The dosage of contrast agent in group A was significantly lower than that in group B[(73.97±12.15)mL in group A,(82.50±2.61)mL in group B](P<0.05).Conclusion Low-dose test method combined with VHP technology not only can reduce the radiation dose and contrast agent dosage,but also can effectively improve the success rate and image quality of lower extremity arteries examination,which is worthy of clinical application.

Objective:To explore the clinical manifestations and genetic etiology of a Chinese pedigree affected with Familial focal epilepsy with variable foci (FFEVF).Methods:A FFEVF pedigree presented at the Department of Medical Genetics of Linyi Maternal and Child Health Care Hospital on March 14, 2023 was selected as the study subject. The proband was subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of the proband and other affected members and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Linyi Maternal and Child Health Care Hospital (Ethics No. QTL-YXLL-2023048).Results:WES revealed that the proband has harbored a heterozygous c. 1642C>T (p.Arg548Cys) missense variant in exon 15 of the NPRL3 gene. Sanger sequencing confirmed that the variant was inherited from the proband′s father, and multiple members of the pedigree had also harbored the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of unknown significance (PM2_supporting + PP3). Conclusion:The clinical phenotype of FFEVF patients caused by variants of NPRL3 gene is extensive, and the patients may present with neurological abnormality of autism spectrum disorder in addition to seizures.

Objective To investigate the diagnostic potential of low-dose computed tomography angiography(CTA)and global biomimetic three-dimensional model reconstruction technology in patients with arterial erectile dysfunction(ED).Methods A total of 136 patients with ED were selected.Digital subtraction angiography(DSA)was performed on all patients as per their treatment requirements and conditions,following ultrasound and CTA examination,and 75 patients finally completed DSA examination.All patients with International Index for Erectile Function(IIEF5)score ranged from 1 to 20.All patients received immediate ultrasound monitoring after injection of alprostadil 10 μg and underwent CTA examination.DSA was conducted at a minimum interval of 72 h.The global biomimetic three-dimensional model tool was used to reconstruct the CTA data and evaluate the stenosis of the pudendal vessels.The diagnostic efficacy of CTA examination,ultrasound and DSA examination were compared and calculated.Results A total of 1 632 vessels were evaluated in 136 patients,including 155 stenoses.DSA was performed in 75 patients.A total of 900 vessels were evaluated,of which 88 were stenoses.Compared with the results of CTA,ultrasound and DSA,the average stenosis scores of all measured vessels were not statistically significant(P＜0.05).The correlation between CTA and ultrasound(r2=0.939 9,P＜0.000 1)and DSA(r2=0.944 0,P＜0.000 1)in the evaluation of vascular stenosis were good,and the diagnostic consistency was consistent.Conclusion Low-dose CTA and global biomimetic three-dimensional model reconstruction technology can effectively diagnose pudendal artery stenosis,and can perform all-round reconstruction observation,which is worthy of further clinical application.

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.

Objective:To investigate the effects of overexpression of Nkx2.5 gene on the anti apoptotic ability of bone marrow mesenchymal stem cells (BMSCs) and cardiac function after myocardial infarction.Methods:A cell ischemia model was established by culturing cells under oxygen glucose deprivation/reoxygenat (OGD/R) conditions. The experiment was divided into four groups: bone marrow mesenchymal stem cells cultured under normal conditions (BMSC group), BMSC group cultured under glucose and oxygen deprivation (BMSC+OGD/R group), overexpressed empty vector BMSC group cultured under glucose and oxygen deprivation(BMSC NC+OGD/R group), and overexpressed Nkx2.5 BMSC group cultured under glucose and oxygen deprivation (BMSC Nkx2.5+OGD/R group). The apoptosis rate of BMSCs in each group was detected via flow cytometry, and BMSC protein was extracted. The expression of caspase-3 and pro-caspase-3, caspase-8 and pro-caspase-8, caspase-9, and cytochrome C protein and expression of Nkx2.5 in the BMSCs of each group were detected by Western blot to determine the anti-apoptotic pathway in vitro. The model of myocardial infarction in mice was established by ligating the left anterior descending branch of coronary artery. The experiment was divided into five groups: sham surgery group, myocardial infarction untreated group, myocardial infarction tail vein injection of BMSC group, myocardial infarction tail vein injection of BMSC empty body group, myocardial infarction tail vein injection of BMSC overexpression Nkx2.5 group. The changes of cardiac function in mice were evaluated by echocardiography. Normal distribution econometric data were compared between groups using convenient analysis, and pairwise comparisons were conducted using LSD-t test. Results:The apoptosis rate of the BMSC+OGD/R group (12.98±1.24)% was higher than that of the BMSC group (7.82±0.42)%, and the difference was statistically significant ( P<0.001). The apoptosis rate of the BMSC NKx2.5+OGD/R group (11.26±0.22)% was lower than that of the BMSC+OGD/R group (12.98±1.24)% and the BMSC NC+OGD/R group (13.14±0.70)%, with statistically significant differences ( P<0.05). Compared to BMSC group ((0.36±0.08), (1.13±0.04), (0.36±0.06), (1.12±0.13), (1.23±0.08), (0.60±0.05), (0.67±0.14)), BMSC+OGD/R group ((1.05±0.10), (0.62±0.04), (1.07±0.09), (0.57±0.07), (0.55±0.08), (1.25±0.09), (0.71±0.04)) and BMSC NC+OGD/R group ((1.16±0.16), (0.64±0.06), (1.19±0.16), (0.56±0.06), (0.50±0.06), (1.28±0.06), (0.73±0.04)), the expression of Caspase-3 (0.72±0.08) and pro-caspase-3(0.89±0.09), Caspase-8 (0.63±0.08) and pro-caspase-8(0.85±0.12), Caspase-9 (0.87±0.09), cytochrome C (0.91±0.10), and Nkx2.5 (1.54±0.16) in BMSC Nkx2.5+OGD/R group was statistically significant (all P<0.05). In vivo experiments showed that the heart ejection fraction (29.05±7.07)% of mice treated with BMSC Nkx2.5 after myocardial infarction was significantly improved compared to the BMSC group (16.57±2.09)% and BMSC NC group (18.08±3.27)% (all P<0.05). Conclusion:BMSC Nkx2.5 may enhance the anti-apoptosis ability of BMSCs and improve cardiac function after myocardial infarction by inhibiting the death receptor pathway and the mitochondrial signal pathway .