The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective:To discuss their effects of PLA(polylactic acid)/PTMC(polytrimethylene carbonate)and PLA/PTMC-calcium phosphate[Ca3(PO4)2]composite porous scaffolds prepared by 3D printing technology on bone marrow mesenchymal stem cells(BMSCs)of the rabbits,and to clarify their application values in bone defect repairment.Methods:After mixing the materials,PLA/PTMC and PLA/PTMC-Ca3(PO4)2 filaments were prepared by desktop filament extruder.The scaffolds were designed by CATIA V5-6R2019 modeling software and fabricated using CreatBot F430 3D printer.The chemical structure of the PLA/PTMC-Ca3(PO4)2 scaffold was detected by infrared spectroscopy.In vitro degradation experiments were used to detect the degradation weight loss rates and pH values of the two scaffolds.A contact angle measuring instrument was used to detect the hydrophilicities of the two scaffolds.The BMSCs were extracted from three newborn New Zealand white rabbits(2-5-day-old);CCK-8 method was used to detect the proliferation activities of the cells co-cultured with two scaffolds,and Alizarin red staining was used to observe the osteogenic differentiation of the cells co-cultured with two scaffolds.Results:Infrared spectroscopy confirmed the successful preparation of composite scaffolds containing PLA,PTMC,and β-Ca3(PO4)2.During degradation for 6-14 weeks,compared with PLA/PTMC scaffold,the degradation rates of the PLA/PTMC-Ca3(PO4)2 scaffold in lipase solution and phosphate-buffered saline(PBS)were significantly increased(P<0.05 or P<0.01).During degradation for 8-14 weeks,compared with PLA/PTMC scaffold,the pH value of the PLA/PTMC-Ca3(PO4)2scaffold in lipase solution was significantly increased(P<0.01).Compared with PLA/PTMC scaffold,the contact angle of the PLA/PTMC-Ca3(PO4)2 scaffold was significantly decreased(P<0.01).On days 5 and 7 of cell co-culture,compared with PLA/PTMC scaffold,the proliferation activity of the cells co-cultured with PLA/PTMC-Ca3(PO4)2 scaffold was significantly increased(P<0.05 or P<0.01).After 21 d of co-culture,both scaffolds overlapped with BMSCs and locally formed calcified nodules,which were stained orange by Alizarin red.Compared with PLA/PTMC scaffold,the number of mineralized calcium nodules in the cells co-cultured with PLA/PTMC-Ca3(PO4)2 scaffold was increased,with greater density and deeper color.Conclusion:The PLA/PTMC-Ca3(PO4)2 composite porous scaffolds containing PLA,PTMC,and β-Ca3(PO4)2 are successfully prepared by 3D printing technology.These scaffolds exhibit good degradation properties and show advantages in biocompatibility,hydrophilicity,and osteogenic induction;they are excellent materials for the bone defect repairment.

AIM:To investigate the effects of γ-synuclein on autophagy and apoptosis of colon cancer cells in-duced by endoplasmic reticulum stress,as well as the protective effect on the cells.METHODS:Gene expression profile chip analysis was performed to compare the cDNA expression profiles between human colon cancer HCT116 cells with γ-synu-clein knockdown and HCT116 cells with control siRNA,and to identify potential molecules related to autophagy and apop-tosis.In colon cancer cell lines,the functional effects of γ-synuclein on autophagy and apoptosis induced by thapsigargin(TG),an endoplasmic reticulum stress-inducing agent,were systematically explored by conducting immunofluorescence staining,Western blot,CCK-8 assay,flow cytometry,and transmission electron microscopy.Western blot was used to de-tect the expression of γ-synuclein protein,autophagy-related proteins[microtubule-associated protein 1 light chain 3(LC3),beclin-1,autophagy-related protein 5(ATG5)and ATG7],and apoptosis-related proteins[poly(ADP-ribose)polymerase(PARP),pro-caspase-3,and pro-caspase-9].To further analyze the mechanism of γ-synuclein in regulating autophagy and apoptosis,extracellular signal-regulated kinase(ERK)inhibitor PD98059,ERK inhibitor SP600125 and c-Jun N-terminal kinase(JNK)activator anisomycin were applied separately to test HCT116 cells transfected with γ-synu-clein siRNA.Subsequently,autophagy proteins,apoptosis proteins,and ERK and JNK pathway-related proteins were de-tected by Western blot.RESULTS:The TG-induced autophagy of colon cancer cells mainly occurred at the early stage(0～24 h),and apoptosis mainly occurred at the late stage(36～48 h).Endoplasmic reticulum stress up-regulated the ex-pression of γ-synuclein in colon cancer cells,which was associated with enhanced autophagy.γ-Synuclein promoted au-tophagy by activating ERK and JNK pathways at the early stage(0～24 h),and inhibited apoptosis by blocking JNK path-ways at the late stage(24～48 h)to protect HCT116 cells.In our model,γ-synuclein was observed to play a critical role in the transition from endoplasmic reticulum stress-induced autophagy to apoptosis.CONCLUSION:In the context of endo-plasmic reticulum stress,γ-synuclein promotes autophagy and inhibits apoptosis by regulating ERK and JNK signaling pathways,thus protecting colon cancer cells.This provides a potential idea for anti-tumor therapy.

Objective To investigate the research status and the research hotspots on male nurses at home and abroad in last decade,so as to provide references for further research in male nurses.Methods Literature between 2013 and 2024 on male nurses were retrieved from the Web of Science(WOS)and CNKI.CiteSpace 6.2.6 R7 software was used to analyse the volume of publication,keyword co-occurrence,keyword clustering and emergence.Results A total of 736 articles were included in the study.From 2013 to 2023,the number of published papers of male nurses in CNKI and WOS showed an increasing trend.The research was primarily affiliated with 263 institutions across 62 countries.The country with the highest volume of publication is China,followed by the United States,although there was a need to enhance collaboration with other nations.The institution with the most publications is the Hong Kong Polytechnic University.A comprehensive analysis of keyword co-occurrence,clustering,and emerging trends revealed that the research hotspots in the field of male nursing in CNKI mainly includes the advantages of male nurses,psychological capital,humanistic care,development,needs,professional identification.Whereas WOS focuses on the topics such as gender bias against male nurses,mental health,workplace violence,ambivalent sexism,motivational barriers,individual differences,societal prejudice and knowledge and attitucle.Both domestic and international research on male nurses primarily consist of cross-sectional surveys and qualitative studies,with fewer intervention studies.Currently,the researches regarding male nursing focus on the qualitative study of mental health of male nurses.Conclusion Focusing on the mental health and professional status of male nurses,domestic scholars need to increase the formulation and implementation of interventions in this field in order to address the practical issues faced by male nurses,therefore to promote the comprehensive development of the nursing profession,enhance the overall quality and service quality of the nursing team,and provide patients with higher quality in nursing services.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

Glioma is the most common primary intracranial tumor, and most patients present as glioblastoma, with high morbidity and mortality. The prognosis of patients with glioblastoma remains poor after surgical resection combined with standardized treatment of radiotherapy and chemotherapy. In recent years, although the breakthrough of immunotherapy have been achieved in the treatment of a variety of solid tumors, the existing data show that immunotherapy is not effective in improving the survival of patients with glioblastoma. However, studies have shown that immunotherapy can have a synergistic effect with radiotherapy which can increase antigen presentation and promote the formation of pro-inflammatory tumor microenvironment, providing more relevant targets for immunotherapy. The purpose of this paper is to discuss the effect of radiotherapy on tumor immune microenvironment and the role of radiotherapy combined with immune checkpoint inhibitors in the treatment of glioblastoma.

Mycoplasma pneumoniae pneumonia (MPP) complicated with cerebral venous sinus thrombosis (CVST) is rare.We retrospectively analyzed the clinical data of two patients with refractory mycoplasma pneumoniae pneumonia (RMPP) complicated with CVST who were hospitalized in Xi′an children′s Hospital from December 2018 to April 2019, inquired the relevant literature, analyzed the clinical diagnosis and treatment characteristics, and discussed the diagnosis and treatment measures of RMPP complicated with CVST.Two cases were 6-year-old girls with fever and cough as the main symptoms.After physical examination, the respiratory sounds of the affected lung decreased, and the sounds of phlegm and dampness could be heard in both lungs.Mycoplasma pneumoniae (MP) antibody and RNA were positive.Chest CT showed lobar pneumonia with a large number of pleural effusion.The effect of macrolide antibiotics anti infection treatment was not good.Headache symptoms occurred during the course of the disease, and serum D-dimer increased significantly.Brain MRI showed CVST, including 1 case with lower extremity pain, and B-ultrasound showed right lower extremity arterial embolism.After anti infection, thrombectomy, anticoagulation and symptomatic treatment, 2 cases were discharged.When children with MPP, especially those with RMPP, have extracranial thrombosis and/or neurological symptoms, accompanied by elevated serum D-dimer, the possibility of CVST should be considered, and brain MRI examination should be performed in time to confirm and actively treat, which can reduce or avoid the occurrence of sequelae.Thrombosis may be related to excessive inflammatory reaction and vascular endothelial injury caused by MP infection.

Objective: To compare relevant dosimetric parameters of non-coplanar volumetric modulated arc therapy (VMAT) in treating brain tumors in conventional flattening filter (FF) or flattening filter-free (FFF) delivery mode, aiming to explore the appropriate evaluation method of accelerator for stereotactic radiosurgery (SRS). Methods: Clinical data of 10 patients with single cranial tumor were retrospectively analyzed. All patients received non-coplanar VMAT at a prescription dose of 25 Gy in 1 fraction. Dosimetric parameters including conformity index (CI), heterogeneity index (HI), gradient index (GI₅₀, GI₂₅), gradient, volume of the brain tissue receiving larger than 10 Gy and 12 Gy(V₁₀ and V₁₂) and beam-on time were statistically compared between two treatment plans by paired sample t-test. Results: When FFF-VMAT was compared with FF-VMAT in SRS for intracranial tumors, Paddick gradient index GI₅₀ was 2.91±0.34 vs.3.07±0.35, 6.91±0.28 vs.7.35±0.27 for GI₂₅, (0.57±0.07) cm vs.(0.61±0.08) cm for gradient, respectively (all P<0.05), whereas CI did not significantly differ (P>0.05). For the normal brain tissues, the average dose was (160.64±43.64) cGy vs.(174.27±53.98) cGy, (45.35±30.32)% vs.(48.37±30.88)% for V₁₀ and (36.69±25.15)% vs.(39.48±25.37)% for V₁₂, respectively (all P<0.05). Conclusions Non-coplanar VMAT in FFF delivery mode can improve dose distribution and normal brain tissue sparing in the treatment of intracranial single tumors. Meanwhile, supplement of GI index and gradient index can implement comprehensive evaluation of the SRS planning.

Objective To analyze the dosimetric and delivery efficiency differences between IMRT plans based on Halcyon and Trilogy Accelerator for left side breast cancer.Methods A total of 10 patients with left side breast cancer based on the Trilogy platform were retrospectively analyzed.For each patient,plan based on Halcyon was redesigned using Eclipse Version 15.1 TPS.In order to evaluate plan quality,dose coverage of target and dose to organs at risk,monitor unit efficiency,segment size and delivery time were compared.Results Halcyon treatment platform could meet the clinical objective.Dose distribution of the target volume had no significant difference with the Trilogy plans (P＞0.05).Volumes receiving 10 Gy,20 Gy and D of the left lung were significantly reduced(Z=-2.22--1.78,P＜0.05).V5 of heart for Halcyon and Trilogy was(27.80±7.66)％ and (23.18±8.19)％,respectively(Z=-0.71,P＜0.05),while D was (7.03± 1.8)Gy and(7.11±2.40)Gy,respectively(P＞0.05).Halcyon increased the monitor unit from 1 526.2±227.7 by Trilogy to 1 770.5±383.9(Z=-0.71,P＜0.05),but decreased the delivery time from (12.38± 1.49) min by Trilogy to (3.01 ±0.28) min (Z =-3.42,P＜ 0.05).Conclusion Halcyon treatment platform can meet the clinical requirements,reduce dose to normal tissue with high delivery efficiency.

Objective To evaluate the role of hippocampal CD200 receptor 1(CD200R1)in peri-operative neurocognitive disorders(PND)in mice.Methods Sixty clean-grade male C57BL/6 mice,aged 9-10 months,weighing 32-38 g,were used in the study.The experiment was performed in two parts.Ex-periment Ⅰ Thirty-six mice were divided into 2 groups(n＝18 each)using a random number table meth-od: control group(group C)and PND group.Group C only received isoflurane anesthesia.Partial left lo-bectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1,3 and 7 days after surgery,and the freezing time was recorded.The mice were then sacrificed,and the hippocampus was isolated for determination of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)contents(by enzyme-linked immunosorbent assay)and CD200 and CD200R1 expression(by Western blot).ExperimentⅡ Twenty-four mice were divided into 2 groups(n＝12 each)using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group,respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery,and the freezing time was recorded.Re-sults Experiment Ⅰ Compared with group C,the freezing time in the contextual fear conditioning test was significantly shortened,and the contents of IL-1β were increased at 1 and 3 days after surgery,the contents of TNF-α were increased at 3 and 7 days after surgery,and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND(P＜0.05).ExperimentⅡ Compared with IgG1-Fc group,the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group(P＜0.05).Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.