Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Cross-border teaching provides new opportunities for college students to gain diverse insights amid the globalization and internationalized education, In July 2024, guided by the Chinese Association for Science and Technology, the Chinese Nutrition Society and the Hong Kong Nutrition Association collaborated to host a three-week clinical nutrition internship at Peking Union Medical College Hospital for five college students from Hong Kong SAR, China. This program included participating in outpatient rounds, attending in inpatient nutrition management, and attending lectures, aiming to enhance students' professional skills and clinical experience. Cultural exchange and value-based education also enriched students' social responsibility and cultural understanding. The Hong Kong students also brought diverse cultural backgrounds and inputs, enabling multidimensional communication during the training. Post-internship feedback survey showed that the students found the inernship valuable for their career development and hoped for more learning opportunities. This cross-border high-quality internship program fostered skill enhancement, cultural exchange between young students in Beijing and Hong Kong and contributed to advancement of clinical nutrition.

Objective:To evaluate the impact of a high-energy-density, high-protein, immune-modulating, cancer-specific foods for special medical purposes (FSMP) on nutritional adequacy, safety, and efficacy in postoperative cancer patients.Methods:This multicenter randomized controlled trial enrolled patients with gastrointestinal or head and neck cancer scheduled for surgery and at nutritional risk. Participants were randomized 1∶1 to receive either the investigational cancer-specific FSMP (FSMP group) or a commercially available tumor-specific enteral nutrition (EN) formula (control group). The "nutritional transition phase" (postoperative days 0-3) provided the assigned EN, with energy deficits supplemented by parenteral nutrition (PN). This was followed by the "full EN phase" (intervention period: 10±3 days), with a target energy intake of 105-146 kJ/kg/day. Nutritional adequacy was considered achieved if the actual intake reached ≥80% of the target in both phases. The primary outcomes were the body weight and prealbumin improvement rates after intervention , and the secondary outcomes were the improvement rates of handgrip strength, gait speed, serum albumin, and hemoglobin. Non-inferiority was tested using the confidence intervals, with the least squares mean difference and its 95% CI derived from a Logistic regression model (non-inferiority margin: -0.12).Results:A total of 220 patients from 17 centers completed the study (FSMP group: n=109; control group: n=111). After the nutrition support, the weight loss was (-0.9±2.1) kg and (-1.3±1.8) kg in the FSMP and control groups ( P=0.162), whereas prealbumin increased in both groups (59.0±69.0 mg/L vs. 50.0±62.0 mg/L, P=0.418). The lower bounds of the 95% CIs were -0.08 for both weight and prealbumin improvement rates, exceeding the predefined non-inferiority margin (-0.12). No significant differences were observed in the improvements in albumin, hemoglobin, handgrip strength, or gait speed (all P>0.05). No serious adverse events related to the formulas occurred. The FSMP group had a higher incidence of diarrhea (31.9% vs. 17.8%) and lower compliance rate (<80% intake: 13.4% vs. 5.9%), but the percentages of total energy intake over the estimated energy requirements (% of target) were comparable (89.9%±24.5% vs. 94.0%±22.3%, P=0.310). Conclusions:The cancer-specific FSMP can improve postoperative nutritional status in cancer patients, demonstrating non-inferiority to existing tumor-specific EN formulas in terms of nutritional adequacy, safety, and efficacy.

Objective:To construct a mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases based on the Liverpool mindfulness model, providing practical guidance for improving their physical and mental symptoms.Methods:The system searched for relevant literature on the application of mindfulness intervention in patients with malignant hematological diseases retrieved from Cochrane Library, PubMed, CINAHL, PsycInfo, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. The search period was from January 1, 1982 to December 26, 2023. Using the Liverpool mindfulness model as the theoretical framework, based on the literature review, group meetings and semi-structured interviews, a preliminary draft of a mindfulness cancer rehabilitation training program for patients with malignant hematologic diseases was developed. After 2 rounds of Delphi expert consultation, the final version of the intervention plan was determined.Results:Among the 19 experts, there were 4 males and 15 females, aged 30-61 (47.11 ± 7.64) years old. The effective recovery rates of the two rounds of expert inquiry questionnaires were both 19/19, and the expert authority coefficients were both 0.88. The Kendall coordination coefficients for the two rounds of inquiry were 0.214 and 0.220, respectively ( χ2=77.37, 108.66, both P<0.01).A mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases was ultimately developed, including intervention subjects, intervention personnel, intervention sites and forms, intervention timing, intervention intensity, intervention process and training theme content. Conclusions:The mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases constructed based on the Liverpool mindfulness model is necessary, scientific, and clinically suitable, and can provide a basis for clinical psychological nursing practice for patients with malignant hematologic diseases.

Objective:To evaluate the impact of a high-energy-density, high-protein, immune-modulating, cancer-specific foods for special medical purposes (FSMP) on nutritional adequacy, safety, and efficacy in postoperative cancer patients.Methods:This multicenter randomized controlled trial enrolled patients with gastrointestinal or head and neck cancer scheduled for surgery and at nutritional risk. Participants were randomized 1∶1 to receive either the investigational cancer-specific FSMP (FSMP group) or a commercially available tumor-specific enteral nutrition (EN) formula (control group). The "nutritional transition phase" (postoperative days 0-3) provided the assigned EN, with energy deficits supplemented by parenteral nutrition (PN). This was followed by the "full EN phase" (intervention period: 10±3 days), with a target energy intake of 105-146 kJ/kg/day. Nutritional adequacy was considered achieved if the actual intake reached ≥80% of the target in both phases. The primary outcomes were the body weight and prealbumin improvement rates after intervention , and the secondary outcomes were the improvement rates of handgrip strength, gait speed, serum albumin, and hemoglobin. Non-inferiority was tested using the confidence intervals, with the least squares mean difference and its 95% CI derived from a Logistic regression model (non-inferiority margin: -0.12).Results:A total of 220 patients from 17 centers completed the study (FSMP group: n=109; control group: n=111). After the nutrition support, the weight loss was (-0.9±2.1) kg and (-1.3±1.8) kg in the FSMP and control groups ( P=0.162), whereas prealbumin increased in both groups (59.0±69.0 mg/L vs. 50.0±62.0 mg/L, P=0.418). The lower bounds of the 95% CIs were -0.08 for both weight and prealbumin improvement rates, exceeding the predefined non-inferiority margin (-0.12). No significant differences were observed in the improvements in albumin, hemoglobin, handgrip strength, or gait speed (all P>0.05). No serious adverse events related to the formulas occurred. The FSMP group had a higher incidence of diarrhea (31.9% vs. 17.8%) and lower compliance rate (<80% intake: 13.4% vs. 5.9%), but the percentages of total energy intake over the estimated energy requirements (% of target) were comparable (89.9%±24.5% vs. 94.0%±22.3%, P=0.310). Conclusions:The cancer-specific FSMP can improve postoperative nutritional status in cancer patients, demonstrating non-inferiority to existing tumor-specific EN formulas in terms of nutritional adequacy, safety, and efficacy.

Objective:To construct a mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases based on the Liverpool mindfulness model, providing practical guidance for improving their physical and mental symptoms.Methods:The system searched for relevant literature on the application of mindfulness intervention in patients with malignant hematological diseases retrieved from Cochrane Library, PubMed, CINAHL, PsycInfo, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. The search period was from January 1, 1982 to December 26, 2023. Using the Liverpool mindfulness model as the theoretical framework, based on the literature review, group meetings and semi-structured interviews, a preliminary draft of a mindfulness cancer rehabilitation training program for patients with malignant hematologic diseases was developed. After 2 rounds of Delphi expert consultation, the final version of the intervention plan was determined.Results:Among the 19 experts, there were 4 males and 15 females, aged 30-61 (47.11 ± 7.64) years old. The effective recovery rates of the two rounds of expert inquiry questionnaires were both 19/19, and the expert authority coefficients were both 0.88. The Kendall coordination coefficients for the two rounds of inquiry were 0.214 and 0.220, respectively ( χ2=77.37, 108.66, both P<0.01).A mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases was ultimately developed, including intervention subjects, intervention personnel, intervention sites and forms, intervention timing, intervention intensity, intervention process and training theme content. Conclusions:The mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases constructed based on the Liverpool mindfulness model is necessary, scientific, and clinically suitable, and can provide a basis for clinical psychological nursing practice for patients with malignant hematologic diseases.

Cross-border teaching provides new opportunities for college students to gain diverse insights amid the globalization and internationalized education, In July 2024, guided by the Chinese Association for Science and Technology, the Chinese Nutrition Society and the Hong Kong Nutrition Association collaborated to host a three-week clinical nutrition internship at Peking Union Medical College Hospital for five college students from Hong Kong SAR, China. This program included participating in outpatient rounds, attending in inpatient nutrition management, and attending lectures, aiming to enhance students' professional skills and clinical experience. Cultural exchange and value-based education also enriched students' social responsibility and cultural understanding. The Hong Kong students also brought diverse cultural backgrounds and inputs, enabling multidimensional communication during the training. Post-internship feedback survey showed that the students found the inernship valuable for their career development and hoped for more learning opportunities. This cross-border high-quality internship program fostered skill enhancement, cultural exchange between young students in Beijing and Hong Kong and contributed to advancement of clinical nutrition.

OBJECTIVE To evaluate the comprehensive value of four first-line combination immunotherapy for unresectable hepatocellular carcinoma， and provide a reference for determining the optimal clinical treatment decision for unresectable hepatocellular carcinoma. METHODS R4.2 software was used for network meta-analysis to obtain the effect values of the efficacy and safety indicators of four combination therapies [atezolizumab combined with bevacizumab （AB）， sintilimab combined with bevacizumab biosimilars （SB）， camrelizumab combined with apatinib （CA）， durvalumab combined with tremelimumab （DT）]. Combined with the efficacy， safety and economic indicators， the categorical based evaluation technique （M-MACBETH） was used to establish the value tree. At the same time， the comprehensive value scores of four therapies were calculated， and sensitivity analysis was performed to evaluate the robustness. RESULTS In terms of prolonging median overall survival， the advantage order of the four therapies was ranked as SB， CA， AB and DT. In terms of extending median progression-free survival， the advantage order of the four therapies was CA， SB， AB and DT. In terms of safety， the order of advantages was DT， AB， SB and CA. In terms of economy， the order of advantages was CA， SB， AB and DT. The comprehensive scores of SB， CA， AB and DT were 67.11， 57.77， 52.53 and 42.59 points， respectively. The results of the sensitivity analysis showed that the ranking results of comprehensive value for four regimens were robust. CONCLUSIONS Among the four first-line immune combination therapies for unresectable hepatocellular carcinoma， SB is the optimal treatment regimen， followed by CA， AB and DT.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).