Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Trace elements and vitamins are essential micronutrients for metabolism.Micronutrients deficiency results in adverse effects on human body,and brings huge challenge to clinical nutrition therapy.To normalize micronutrients application in clinical practice,European Society for Clinical Nutrition and Metabolism(ESPEN)published ESPENpractical short micronutrient guideline on January 2024.Based on previous version published in 2022,current guideline shortens the interpretation of biochemical and physical mechanisms,focuses on micronutrients deficiency and inflammation,recommends the methods of micronutrients assessment and supplementation in different statuses during clinical practices.This paper summarizes specific recommendations and comments for domestic peers to communicate,and provides reference for the management of micronutrient therapy in China.

Objective To explore the clinical features,treatment and prognosis of glioblastomas(GBM)in adults.Methods A retrospective cohort study was performed on 176 adult GBM patients admitted to our department from January 2015 to December 2021.Chi-square test was used to investigate the clinical differences between isocitrate dehydrogenase(IDH)mutant and wild-type GBM.Kaplan-Meier and Log-Rank tests were employed to plot survival curve and compute the survival analysis.Multivariate Cox regression model was applied to identify the independent prognostic factors.Results IDH wild-type GBM account for 89.2％and had significantly differences from the IDH-mutant GBM in terms of age of onset,Karnofsky(KPS)score at admission,symptoms of neurological deficit,and methylation status of O6-methylguanine-DNA-methyltransferase(MGMT)promoter(P＜0.05).For the IDH wild-type GBM patients receiving conventional therapy,univariate Cox hazard analysis showed gross total resection,methylation of MGMT promoter,initiation of radiation within the 5th to 6th week after surgery,and adjuvant temozolomide(TMZ)chemotherapy ≥6 cycles were favorable prognostic factors for overall survival(OS);GBMs in the left hemisphere,involvement of single lobe,methylation of MGMT promoter,and initiation of radiation within the 5th to 6th week after surgery were favorable prognostic factors for progression free survival(PFS)(all P＜0.05).Moreover,multivariate Cox hazard regression analysis indicated that methylation of MGMT promoter,and initiation of radiation within the 5th to 6th week after surgery,and adjuvant TMZ chemotherapy ≥6 cycles were independent protective factors for OS,and GBMs in the left hemisphere,involvement of single lobe and methylation of MGMT promoter were independent protective factors for PFS in the GBM patients(all P＜0.05).Conclusion The clinical and prognostic features are totally different between IDH mutant and wild-type GBM,and molecular detections are needed for the further pathological classification.Methylation of MGMT promoter is a primary marker of favorite prognosis for IDH wild-type GBM,and slightly delay in radiotherapy(the 5th to 6th week after surgery)can effectively improve the survival prognosis of IDH wild-type GBM.

Objective:To explore the role of c-Jun N-terminal kinase (JNK) /c-Jun signaling pathway mediated by endoplasmic reticulum stress in triptolide-induced apoptosis of melanoma A375 cells.Methods:Nude mice were subcutaneously inoculated with melanoma A375 cells on the back to establish the animal model of melanoma. Tumor formation could be observed at approximately 3 weeks after inoculation, and then the mice were divided into 4 groups (4 mice in each group) : control group (injected with sodium chloride physiological solution via the tail vein), 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (injected with 0.1, 0.2, and 0.4 mg/kg triptolide via the tail vein, respectively). Injections were performed twice a week. After 3 weeks of injections, tumors were resected, and their size and weight were measured. The apoptosis levels of tumor xenografts were detected by the terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. qPCR was conducted to determine the mRNA expression of inositol-requiring enzyme 1 (IRE1), JNK, and c-Jun, and Western blot analysis to determine the protein expression of IRE1, JNK, c-Jun, phosphorylated-JNK (p-JNK), and phosphorylated-c-Jun (p-c-Jun). Comparisons among multiple groups were performed using one-way analysis of variance, and multiple comparisons were performed using Dunnett's test.Results:Significant differences were observed in the tumor mass, volume and tumor suppression rate among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (all P < 0.05) ; all the triptolide groups showed significantly decreased tumor masses and volumes (all P < 0.05), but significantly increased tumor suppression rates compared with the control group (all P < 0.05). The tumor apoptosis index significantly differed among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (7.67% ± 1.15%, 9.67% ± 3.21%, 62.00% ± 6.08%, and 85.67% ± 5.51%, respectively; F = 305.91, P < 0.001), and the 0.2- and 0.4-mg/kg triptolide groups showed significantly increased tumor apoptosis indices compared with the control group ( t = 17.56, 27.72, respectively, both P < 0.05). qPCR and Western blot analysis revealed significant differences in the mRNA expression of IRE1, JNK, and c-Jun among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups ( F = 112.23, 27.51, 112.37, respectively, all P < 0.05), as well as in the relative protein expression levels of IRE1, JNK, c-Jun, p-JNK, and p-c-Jun among the above 4 groups (all P < 0.05). Additionally, the 0.4-mg/kg triptolide group showed significantly increased mRNA and protein expression of IRE1, JNK and c-Jun (including p-JNK, p-c-Jun) compared with the control group (all P < 0.05). The mRNA and protein expression levels of IRE1, JNK, and c-Jun in the tumor tissues tended to increase with the rise in drug concentrations, and the protein expression levels of p-JNK and p-c-Jun showed the same trend. Conclusion:Triptolide could activate the JNK/c-Jun signaling pathway mediated by the endoplasmic reticulum stress, and then induce apoptosis of melanoma A375 cells in mice.

Objective:To investigate the influence of nutritional therapy on short-term efficacy of gastric cancer patients with malnutrition after radical gastrectomy.Methods:The prospec-tive randomized control study was conducted. The clinicopathological data of patients with malnutri-tion after radical resection of gastric cancer who were admitted to the Zhongshan Hospital of Fudan University from December 2020 to December 2022 were selected. Based on random number table, all patients were allocated into the nutritional therapy group and the control group. Patients in the nutritional therapy group were given dietary guidance and daily oral nutrition supplements for 90 days after discharge, while patients in the control group were only given the same dietary guidance. Observation indicators: (1) grouping situations of the enrolled patients; (2) follow-up; (3) comparison of nutritional indicators at 90 days after discharge; (4) comparison of inflammation and physical function indicators at 90 days after discharge; (5) comparison of clinical outcome indicators at 90 days after discharge. Measurement data with normal distribution were expressed as Mean± SD, and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(IQR), and non-parameter rank sum test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and chi-square test was used for comparison between groups. Comparison of ordinal data was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 187 patients were selected for eligibility. There were 131 males and 56 females, aged (65±12)years. Of the 187 patients, there were 95 patients in the nutritional therapy group and 92 patients in the control group, respectively. The gender (male, female), age, cases with cardiovascular complications, cases with respiratory complications, cases with diabetes, surgical methods (partial gastrectomy, total gastrectomy), tumor staging (Ⅰ stage, Ⅱ stage, Ⅲ stage), body mass, body mass index (BMI), skeletal muscle index, albumin (Alb), hemoglobin (Hb), neutrophil-to-lymphocyte ratio (NLR), 6-minutes walking distance, grip strength were 68, 27, (64±12)years, 21, 4, 7, 59, 36, 17, 27, 51, (59±11)kg, (21.5±3.1)kg/m 2, (42±7)cm 2/m 2, (39±5)g/L, (112±25)g/L, 2.3(8.0), (456±97)m, (29±8)kg in patients of the nutritional therapy group, versus 63, 29, (66±13)years, 22, 3, 9, 56, 36, 14, 24, 54, (58±11)kg, (21.1±2.9)kg/m 2, (42±7)cm 2/m 2, (39±4)g/L, (111±26)g/L, 2.2(8.4), (459±98)m, (29±8)kg in patients of the control group, showing no significant difference in the above indicators between the two groups ( χ2=0.21, t=-1.29, χ2=0.09, 0, 0.35, 0.03, 0.51, t=0.80, 0.85, 0.19, 0.14, 0.16, Z=-0.28, t=-0.17, 0.43, P>0.05). (2) Follow-up. All 187 patients were followed up for 90 days after surgery. During the follow-up period, all patients had good compliance and were able to follow the dietary guidance. Five patients in the nutrition therapy group experienced diarrhea and nausea adverse reactions, which were relieved after symptomatic treatment. No adverse reactions were found in the control group. (3) Comparison of nutritional indicators at 90 days after discharge. The body mass, body mass loss, BMI, skeletal muscle index, Alb, Hb were (58±10)kg, 2(6)kg, (21.0±2.9)kg/m 2, (41±7)cm 2/m 2, (41±4)g/L, (125±18)g/L in patients of the nutritional therapy group, versus (56±10)kg, 3(6)kg, (20.4±2.7)kg/m 2, (39±7)cm 2/m 2, (41±4)g/L, (121±21)g/L in patients of the control group. There were significant differences in body mass loss and skeletal muscle index between the two groups ( Z=-4.70, t=2.39, P<0.05), and there was no significant difference in body mass, BMI, Alb, and Hb ( t=1.30, 1.51, 0.80, 1.32, P>0.05). (4) Comparison of inflammation and body function indicators at 90 days after discharge. The NLR, 6-minutes walking distance, grip strength were 2.1(5.1), (478±99)m, and (33±9)kg in patients of the nutritional therapy group, versus 2.2(5.7), (465±96)m, (30±8)kg in patients of the control group. There was a significant difference in grip strength between the two groups ( t=2.08, P<0.05), and there were no significant difference in NLR and 6-minutes walking distance ( Z=-1.28, t=0.91, P>0.05). (5) Comparison of clinical outcome indicators at 90 days after discharge. The quality of life score and readmission rate were (79±14)points, 4.2%(4/95) in patients of the nutritional therapy group, versus (78±16)points, 6.5%(6/92) in patients of the control group, showing no significant difference in the above indicators between the two groups ( t=0.58, χ2=0.14, P>0.05). Conclusion:Nutritional therapy with daily oral nutrition supplements can improve the short-term nutritional status and body function of patients with malnutrition after radical gastrectomy for gastric cancer.

Malnutrition and dehydration are prevalent in the elderly poplulation, and obesity is also a growing problem, which pose a serious challenge to the nutritional management in geriatrics. In order to better guide clinical practice, the European Society for Clinical Nutrition and Metabolism (ESPEN) published the practical guideline on clinical nutrition and hydration in geria-trics on March 5, 2022. This guideline provides 82 recommendations on clinical nutrition and hydration in geriatrics based on clinical practicability, covering basic problems and general prin-ciples, prevention and treatment of malnutrition/nutri-tional risk, prevention and treatment of specific diseases, as well as prevention and treatment of obesity, along with flow-charts, hoping to be convenient for doctors, nutritionists and nurses to use in clinical practice.

Objective:To analyze the key genes and mechanisms of sepsis secondary to multiple trauma based on bioinformatics methods.Methods:Data set GSE70311 was downloaded from Gene Expression Omnibus database.After data set pretreatment, differentially expressed genes (DEGs) in peripheral blood of patients with sepsis secondary to multiple injuries were screened using Limma R package.ClusterProfiler R package was used for gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis of DEGs.Finally, the protein-protein interaction network was constructed by using the STRING online database and Cytoscape, and the hub genes of sepsis secondary to multiple injuries were identified based on Cytohubba.Results:In the GSE70311 dataset, 328 DEGs were obtained.The results of GO enrichment analysis showed that the biological processes involved in DEGs in sepsis secondary to multiple trauma mainly included T cell differentiation, positive regulation of cytokine production, defense response to bacteria, response to virus and defense response to virus, etc.The results of KEGG pathway enrichment analysis showed that DEGs were significantly enriched in hematopoietic cell lineage, Staphylococcus aureus infection, asthma, Th1 and Th2 cell differentiation, and antigen processing and presentation etc.signaling pathways in sepsis secondary to multiple trauma.Five hub genes were further screened by protein-protein interaction analysis, including STAT1, IFIT3, ISG15, IFIT1 and MX1. Conclusions:STAT1, IFIT3, ISG15, IFIT1 and MX1 are potential hub genes of sepsis secondary to multiple trauma, involved in T cell differentiation, positive regulation of cytokine production and defense response to pathogenic microorganisms, and enriched in Th1 and Th2 cell differentiation and antigen processing and presentation etc.signaling pathways.

Objective:To explore and evaluate the accuracy, conformity, and clinical application value of digital surgical techniques in guiding 125I seed implantation in the brachytherapy of deep head and neck tumors. Methods:Twelve patients with deep head and neck tumors who received brachytherapy of radioactive 125I seed implantation were selected for the study.The locations of the implantation needles and seeds were designed based on CT images before the operation.A digital positioning model was built according to the treatment plan to accurately import the planned locations of implantation needles into the surgical navigation system.Meanwhile, an individualized puncture guidance template was designed and printed according to the patients′ facial profiles as well as the locations and directions of the implantation needles.During the operation, the template was put in place under the guidance of the navigation system and meanwhile, the implantation needle puncture and radioactive seed implantation were conducted under the joint guidance of the visual needle path and real-time implantation needle locations in the navigation system and template guidance holes.The locations of the implantation needle and the seeds were validated by CT scan and the dose distribution in target areas was calculated.Adverse reactions such as hematoma, pain, infection, nonunion of puncture sites, and tumor cell implantation were observed during and after the operation. Results:All 12 patients successfully received implantation needle puncture and radioactive seed implantation under the guidance of the digital surgical techniques, achieving excellent effects of real-time visualization guidance.Meanwhile, the locations and number of the implantation needles and seeds were consistent with the treatment plan and were distributed evenly.Furthermore, according to postoperative verification, D90 ranged from 83.7 Gy to 131.0 Gy, with an average of 107.5 Gy; V100 was 89.6%-99.3%, with an average of 94.6%, and V150 ranged from 40.2% to 58.9%, averaging 47.8%.No serious adverse reactions were observed during and after the operation. Conclusions:With digital surgical techniques, the surgical navigation system and 3D-printed individualized puncture guidance template jointly guided the implantation needle puncture and 125I seed implantation, improving the accuracy and conformity of the brachytherapy.Therefore, they have clinical application value in head and neck brachytherapy, especially in deep areas with complex anatomical structures.

The American Society for Parenteral and Enteral Nutrition (ASPEN) held the annual academic conference online from March 20 to 23,2021. The current hot topics of clinical nutrition were widely discussed on the conference. The authors briefly report and analyze the hot topics of the conference in order to share and exchange with surgical colleagues.

The European Society for Clinical Nutrition and Metabolism held the 43 rd annual academic conference online from September 9 to 14,2021. Based on reports from the con-ference, the authors launched a review on the current hot topics in clinical nutrition.