BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

Objective To investigate the effects of governor vessel pushing manipulation on behavioral outcomes in valproic acid(VPA)-induced autism spectrum disorder(ASD)rats and explore its underlying mechanisms using prefrontal RNA sequencing(RNA-Seq).Methods Nine Sprague-Dawley pregnant rats at gestational day 12.5 were divided into two groups,six received intraperitoneal VPA injection(600 mg/kg)for modeling,and three received saline.Male offspring at postnatal day 21 were evaluated using the three-chamber social test and open field test to validate the ASD model.VPA-induced male offspring were randomly assigned to the model group(n=5)or tuina group(n=5),while saline offspring formed the blank group(n=5).The blank group and model group received no intervention,while the tuina group underwent governor vessel pushing manipulation stimulation along the governor vessel using a custom device,twice a day for 14 days,totaling 28 times.Post-intervention,behavioral assessments included social index(SI)and social preference index(SPI)in the three-chamber test,total distance traveled and central zone time in the open field test,marble-burying test for stereotyped behaviors,and Nissl staining for prefrontal cortical neuron survival.RNA-Seq identified differentially expressed genes(DEGs)in the prefrontal cortex,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Real time fluorogenic quantitative PCR(RT-qPCR)validated DEGs,and Western blotting analyzed proteins in enriched pathways.Results Pre-intervention,both model and tuina groups showed reduced SI,SPI,total distance,and central zone time compared to the blank group(P<0.05),confirming successful modeling.Post-intervention,the model group exhibited lower SI,SPI,total distance,central zone time,increased marble-burying(P<0.05),and fewer Nissl bodies(P<0.01)versus the blank group.Compared to the model group,the tuina group displayed improved SI,SPI,total distance,central zone time(P<0.05),reduced marble-burying(P<0.05),and increased Nissl bodies(P<0.01).RNA-Seq revealed 213 prefrontal DEGs(181 upregulated,32 downregulated)in the tuina group.GO analysis highlighted cellular components,while KEGG identified 181 pathways,with 67 significantly enriched(P<0.05),notably the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.RT-qPCR confirmed decreased collagen type Ⅰ alpha 2(Col1α2),transforming growth factor-α(TGF-α),epidermal growth factor receptor 3(ErbB3),and serum/glucocorticoid regulated kinase 2(Sgk2)(P<0.05),and increased hepatic growth factor(Hgf)(P<0.01)in the model group,reversed by governor vessel pushing manipulation.Western blotting showed reduced prefrontal NRG1,ErbB3,nNOS,PI3K,AKT,p-nNOS,p-PI3K,and p-AKT in the model group(P<0.05),which were upregulated by tuina.Conclusion Governor vessel pushing manipulation ameliorates social deficits,anxiety,stereotyped behaviors,and neuronal loss in ASD rats,potentially via activation of the PI3K/AKT signaling pathway.

Objective To investigate the effects of governor vessel pushing manipulation on behavioral outcomes in valproic acid(VPA)-induced autism spectrum disorder(ASD)rats and explore its underlying mechanisms using prefrontal RNA sequencing(RNA-Seq).Methods Nine Sprague-Dawley pregnant rats at gestational day 12.5 were divided into two groups,six received intraperitoneal VPA injection(600 mg/kg)for modeling,and three received saline.Male offspring at postnatal day 21 were evaluated using the three-chamber social test and open field test to validate the ASD model.VPA-induced male offspring were randomly assigned to the model group(n=5)or tuina group(n=5),while saline offspring formed the blank group(n=5).The blank group and model group received no intervention,while the tuina group underwent governor vessel pushing manipulation stimulation along the governor vessel using a custom device,twice a day for 14 days,totaling 28 times.Post-intervention,behavioral assessments included social index(SI)and social preference index(SPI)in the three-chamber test,total distance traveled and central zone time in the open field test,marble-burying test for stereotyped behaviors,and Nissl staining for prefrontal cortical neuron survival.RNA-Seq identified differentially expressed genes(DEGs)in the prefrontal cortex,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Real time fluorogenic quantitative PCR(RT-qPCR)validated DEGs,and Western blotting analyzed proteins in enriched pathways.Results Pre-intervention,both model and tuina groups showed reduced SI,SPI,total distance,and central zone time compared to the blank group(P<0.05),confirming successful modeling.Post-intervention,the model group exhibited lower SI,SPI,total distance,central zone time,increased marble-burying(P<0.05),and fewer Nissl bodies(P<0.01)versus the blank group.Compared to the model group,the tuina group displayed improved SI,SPI,total distance,central zone time(P<0.05),reduced marble-burying(P<0.05),and increased Nissl bodies(P<0.01).RNA-Seq revealed 213 prefrontal DEGs(181 upregulated,32 downregulated)in the tuina group.GO analysis highlighted cellular components,while KEGG identified 181 pathways,with 67 significantly enriched(P<0.05),notably the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.RT-qPCR confirmed decreased collagen type Ⅰ alpha 2(Col1α2),transforming growth factor-α(TGF-α),epidermal growth factor receptor 3(ErbB3),and serum/glucocorticoid regulated kinase 2(Sgk2)(P<0.05),and increased hepatic growth factor(Hgf)(P<0.01)in the model group,reversed by governor vessel pushing manipulation.Western blotting showed reduced prefrontal NRG1,ErbB3,nNOS,PI3K,AKT,p-nNOS,p-PI3K,and p-AKT in the model group(P<0.05),which were upregulated by tuina.Conclusion Governor vessel pushing manipulation ameliorates social deficits,anxiety,stereotyped behaviors,and neuronal loss in ASD rats,potentially via activation of the PI3K/AKT signaling pathway.

Surgery is an important treatment for the anterior mediastinal disease. With the rapid development of minimally invasive techniques, complete resection of the lesion in most patients with thymic disease can be achieved through thoracoscopic surgery. Practice has proved that the three-port resection of anterior mediastinal thymus disease via the subxiphoid approach is an ideal surgical method for the treatment of anterior mediastinal thymic tumors at present, which has strong popularization and popularity and can benefit the patients. The procedure focuses primarily on the anterior and upper mediastinum and can thoroughly expose the anatomy of the mediastinum and both sides, with minimal intraoperative bleeding, high safety, minimal trauma and postoperative pain, and a short hospital stay. It has clear advantages over conventional thoracic open-heart surgery and transversal resection. However, the surgical approach and field of view, and intraoperative precautions of this procedure are completely different from those of previous thoracoscopic procedures, and from the subxiphoid single-port approach adopted by other centers. Based on 10 years of surgical experience at our center, a modular mode of surgical operation has been developed and its procedure has been standardized. This paper will share and discuss relevant operational points and experiences.

Objective:To investigate the application prospect of 3D virtual reconstruction and printing technology based on thin-slice CT images in network cloud+dual-track teaching.Methods:A total of 120 medical students who were on probation in The Second Affiliated Hospital of Air Force Medical University from April 2021 to April 2022 were selected as subjects and were randomly divided into experimental group and control group, with 60 students in each group. The students in the experimental group received 3D virtual reconstruction and printing technology combined with network cloud+dual-track teaching, and those in the control group received network cloud+dual-track teaching alone. After 6 months of learning, the teaching effect was compared by closed-book examination, skill operation, speech defense, and questionnaire survey. SPSS 23.0 was used for the t-test and the chi-square test. Results:Compared with the control group in terms of department examination, the experimental group had significantly better scores of theoretical knowledge [(84.25±5.53) vs. (79.43±6.69), P<0.001] and operational skills [(87.68±5.72) vs. (82.97±5.32), P<0.001]. The experimental group had significantly higher scores than the control group in speech [(44.90±2.56) vs. (41.88±2.71), P<0.001] and defense [(45.83±2.62) vs. (43.85±2.56), P<0.001]. The questionnaire survey showed that compared with the control group, the experimental group had significantly higher scores of practical ability, active learning ability, expression ability, practice enthusiasm, and information acquisition ability ( P<0.001). Conclusion:The network cloud+dual-track teaching model assisted by 3D virtual reconstruction and printing technology can significantly improve the objective learning effect and subjective learning initiative of students and has a relatively high value of teaching application and promotion.

National Comprehensive Cancer Network (NCCN) has updated and released the latest content of NCCN guidelines version 1. 2023 thymomas and thymic carcinomas (known as "guidelines"). The guideline sets standards for the diagnosis and treatment of thymoma and thymic carcinoma based on high quality clinical evidence and the latest advances in research. There have been some updates and revisions in the latest two versions of the guidelines, mainly focusing on the principles of radiotherapy, the principles of systematic therapy, multidisciplinary participation and the improvement of some footnotes, compared with the first version of the guidelines in 2022. In this paper, the contents of the new guideline will be interpreted in order to provide reference for the work of thymoma and thymic carcinoma in our country at the present stage.

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

Objective:To summarize the experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula.Methods:The surgical methods without repairing the fistula were performed through VATS, small incision assisted with VATS or thoracotomy. The focus of the surgery was to promote lung expansion, eliminate the residual cavity of chest cavity and keep effective drainage. After entering the chest cavity from the affected side, wash chest cavity with a large amount of warm normal saline and sterilize intermittently with iodophor to ensure the sterile environment in the pus cavity. Then completely remove the pleural cellulose or fiberboard on visceral pleura to promote lung expansion, eliminate the residual cavity of the chest cavity. The fistula was covered tightly and supported firmly by the visceral pleura on the lung. Multiple T-tubes were placed in thoracic cavity and fistula to keep effective postoperative drainage.Results:Among 92 cases, 85 cases were cured and the cure rate was 92.4% (85/92).7 cases died and the mortality rate was 7.61% (7/92). The 7 dead cases include 5 cases with esophagogastric anastomotic fistula (the death of 3 cases was cause by aortic esophagogastric fistula, the death of 1 case was cause by thoracic gastric tracheal fistula and 1 case was dead because of pulmonary infection and respiratory failure), 1 case with esophageal rupture (the cause of death was septic shock ), and 1 case with esophageal perforation(the cause of death was pulmonary infection and respiratory failure).Conclusion:Most of the surgeries without repairing gastrointestinal intrathoracic fistula are conducted simply through VATS or small incision assisted with VATS., which is safe and effective.

Single-cell RNA-seq (scRNA-seq) can describe the changes of gene expression in a single tumor cell. And it can reveal the status and function of tumor cells, and capture the extensive transcriptome heterogeneity in the cell population. The application of scRNA-seq can monitor the specific highly expressed genes in esophageal squamous cell carcinoma (ESCC) , and it can also monitor genes related to radio chemotherapy resistance in tumor cells, which is helpful to provide more accurate auxiliary diagnosis for ESCC. Besides, scRNA-seq can evaluate the recurrence risk and survival time of patients. An in-depth study of the relationship between tumor cells and tumor microenvironment in ESCC will provide a theoretical basis for developing a new immunotherapy scheme for ESCC.