Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective This study aimed to investigate the effect of stage Ⅰ comprehensive cardiac rehabili-tation in patients with acute ST elevation myocardial infarction(STEMI)after emergency percutaneous coronary intervention(PCI).Methods A total of 72 patients with acute ST-segment elevation myocardial infarction combined with PCI admitted to the Department of Cardiovascular Medicine of Beijing Electric Power Hospital of State Grid Corporation from June 2021 to June 2022,which were selected as the research objectsand divided into control group and observation group randomly(36 cases in each group).The control group was treated with routine nursing and health education,and the observation group with stage Ⅰ comprehensive cardiac rehabilitation,including initial assessment(cardiovascular comprehensive assessment),exercise training(exercise training and breathing train-ing),daily activity suggestions and health education,discharge assessment(six-minute walking test and Barthel index assessment).The score of Barthel index(BI)at discharge,the 6-minute walking test distance(6MWD)at discharge,the incidence of major adverse cardiovascular event(MACE)during hospitalization and within one month of discharge,and the length of stay were compared between the two groups.Results After intervention,the six-minute walking test distance(6MWD)and Barthel index(BI)score in the observation group were better than those in the control group,the difference was statistically significant(P<0.05).The incidence of major adverse cardiovascular events(MACE)during hospitalization and one month after discharge was lower in the observation group than in the control group,and the difference was statistically significant(P<0.05).The length of hospital-ization in observation group was lower than that in control groupbut there was no statistical difference(P>0.05).Conclusion The application of phase Ⅰ comprehensive cardiac rehabilitation training in patients with acute ST-segment elevation myocardial infarction combined with emergency PCI could improve the patients'exercise ability,improve their ability of daily activity,reduce the incidence of major adverse cardiovascular events(MACE)in the early stage of the disease,facilitate the patients to return to their families and society as soon as possible,and improve their quality of life.It has high clinical application value.

Background and objective Transcription factor(TF)can bind specific sequences that either promotes or represses the transcription of target genes,and exerts important effects on tumorigenesis,migration,invasion.Staphylococcal nuclease-containing structural domain 1(SND1),which is a transcriptional co-activator,is considered as a promising target for tumor therapy.However,its role in lung adenocarcinoma(LUAD)remains unclear.This study aims to explore the role of SND1 in LUAD.Methods Data from The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),Clinical Pro-teomic Tumor Analysis Consortium(CPTAC),and Human Protein Atlas(HPA)database was obtained to explore the associa-tion between SND1 and the prognosis,as well as the immune cell infiltration,and subcellular localization in LUAD tissues.Furthermore,the functional role of SND1 in LUAD was verified in vitro.EdU assay,CCK-8 assay,flow cytometry,scratch assay,Transwell assay and Western blot were performed.Results SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients.In addition,SND1 was predominantly present in the cytoplasm of LUAD cells.Enrichment analysis showed that SND1 was closely associated with the cell cycle,as well as DNA replication,and chro-mosome segregation.Immune infiltration analysis showed that SND1 was closely associated with various immune cell popula-tions,including T cells,B cells,cytotoxic cells and dendritic cells.In vitro studies demonstrated that silencing of SND1 inhib-ited cell proliferation,invasion and migration of LUAD cells.Besides,cell cycle was blocked at G,phase by down-regulating SND1.Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

Objective:To explore the clinical efficacy of targeted interventional embolization therapy by a multidisciplinary team for the hemorrhagic shock caused by acute pelvic fracture or/and acetabular fracture.Methods:A retrospective study was conducted to analyze the data of 63 patients with hemorrhagic shock caused by pelvic fracture or/and acetabular fracture who had been admitted to Department of Orthopaedics, The Second Hospital of Shanxi Medical University from January 2015 to July 2022. There were 44 males and 19 females with an age of (39.6±15.6) years, and 23 pelvic fractures, 35 acetabular fractures, and 5 pelvic and acetabular fractures. The time from injury to targeted interventional embolization therapy was 2.67 (2.00, 3.33) hours. All the patients were treated with targeted interventional embolization therapy by a multidisciplinary team involving orthopedics, interventional medicine, general surgery, and urology. The shock index and lactate level within 12 hours after therapy, 24-hour urine output, and incidence of complications 3 weeks after therapy were recorded.Results:No bleeding was found again in the 63 patients after embolization. Within 12 hours after therapy, the shock index was ≤1.0, indicating the shock was corrected. Within 12 hours after targeted interventional embolization therapy, the shock index (0.70±0.46) and lactate value [(2.03±1.35) mmol/L] in the 63 patients were significantly lower than those before therapy [(1.76±0.56) and (4.53±1.74) mmol/L] ( P<0.05). The 24-hour urine output [(50.26±20.38) mL/h] was significantly higher than that before therapy [(21.56±1.27) mL/h] ( P<0.05). Two patients experienced poor blood circulation in the distal skin of the great toe, which was relieved after treatment with blood circulation promotion and anticoagulation. Three patients developed necrosis of the hip soft tissue, which was cured after multiple times of debridement and anti-infection treatments. One patient with severe injury died from multiple organ dysfunction. Conclusions:The targeted interventional embolization therapy can not only diagnose the bleeding location in patients with hemorrhagic shock caused by pelvic fracture or/and acetabular fracture, but also timely and accurately carry out hemostatic treatment to correct shock. Moreover, a multidisciplinary team can help patients avoid multiple surgeries and decrease their pain and financial loss.

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

Objective : To investigate the expression , clinical significance , progression , and prognosis of miR⁃381 ⁃3p in acute myeloid leukemia (AML) , as well as its impact on AML cell proliferation and apoptosis , in order to provide theoretical basis for the treatment of AML. Methods : Bioinformatics analysis was used to identify differentially expressed miRNAs , clinical data and blood samples of AML patients were collected , and the expression levels of miRNAs in the bone marrow fluid of the included patients were measured to further elucidate the relationship between miRNAs and AML. The included patients were followed up to calculate overall survival (OS) and disease⁃free survival (DFS) ; AML cells were cultured in vitro , miR⁃381 ⁃3p plasmids were constructed , miR⁃381 ⁃3p was overexpressed and miR⁃381 ⁃3p was knocked down in AML , and they were divided into five groups : control , miR⁃381 mimics , mimics NC , miR⁃381 inhibitor , inhibitor NC . The proliferation and apoptosis of AML cells were detected using CCK⁃8 and flow cytometry . Results : Differentially expressed miRNAs were identified using bioinforDifferentially expressed miRNAs were identified using bioinfor included . The expression level of miR⁃381 in AML patients was lower than that in the control group , and all FAB subtypes were lower than those in the normal group . The expression level of miR⁃381 was not related to the age , gender , peripheral blood leukocytes , lymphocytes , and FAB typing of AML patients , and the OS and DFS of miR⁃381 patients with high expression were significantly prolonged , with statistically significant differences . In vitro experiments had shown that knocking down miR⁃381 could inhibit apoptosis and promote proliferation of AML cells . Overexpression of miR⁃381 could promote apoptosis and inhibit proliferation of AML cells . Conclusion MiR⁃381 ⁃ 3p is low expressed in AML patients , and its overexpression can significantly prolong OS and DFS . miR⁃381 ⁃3p can promote apoptosis of AML cells , inhibit proliferation , and may become a targeted molecule for the treatment of AML.

Three children with Skene duct cyst were presented in this article. By reviewing literature, in pediatric population, Skene duct cycts mostly occur in newborns and conservative therapy is the first choice in this group.In contrast, it is extremely rare between the ages of 1 and 12, and surgical excised is the preferred therapy because of having a similar pathogenesis to adults.

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

Objective: To study the miR-1285 through Yes-associated protein 1(YAP1) on the proliferation, apoptosis and mechanism of chronic myelogenous leukemia K562 cells. Methods: The plasmid of miR-1285 was constructed to make K562 cells overexpress miR-1285 and knock down miR-1285. They were divided into four groups: miR-1285 mimics, mimics control, miR-1285 inhibitor, and inhibitor control; qRT-PCR was used to quantitatively analyze the expression of miR-1285 of these four groups. The expression level of miR-1285 in the group was used to verify the transfection efficiency. The apoptosis and proliferation of the four groups were detected by CCK-8 and Annexin V-FITC; the changes of YAP and its downstream molecule epidermal growth factor receptor(EGFR) were detected by Western blot, and apoptosis related molecules BAX, Bcl-2 protein expression was detected. Results: After knock down miR-1285, it can promote the proliferation of K562 cells and inhibit apoptosis. The expression of YAP increased, the expression of downstream molecule EGFR increased correspondingly, the expression of apoptosis-related molecule BAX decreased, and the expression of Bcl-2 increased; After expressing miR-1285, K562 cell proliferation decreased, apoptosis increased, YAP expression decreased, downstream molecule P-EGFR expression decreased, apoptosis molecule BAX expression increased, and Bcl-2 expression decreased. Conclusion miR-1285 can inhibit the proliferation and promote apoptosis of K562 cells of chronic myelogenous leukemia by inhibiting the expression of YAP. It is expected to become a targeted molecule for the treatment of chronic myelogenous leukemia.