Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.

Objectives:This study aimed to explore the association between perceived mental stress (MS), lymphocyte subset variations, and coronary lesion severity in patients with coronary artery disease (CAD).Methods:Patients with CAD were enrolled in this study from September 2023 to May 2024. Perceived Stress Scale-14 (PSS-14) was used to evaluate MS during the last 1 month. Lymphocyte subsets were analyzed, including the percentage and absolute counts of CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD3 -CD19 +, CD3 -CD56 +16 +, and the Th/Ts ratio. Statistical analysis was conducted using SPSS 24.0. Results:This study recruited patients with 323 CAD, with an average age of 61 (56, 68) years, including 203 males and 120 females. According to the PSS-14, a score of 14-42 and 43-70 were categorized as normal and increased MS, respectively. Patients with CAD with increased MS had significantly higher Gensini scores than those with normal MS [37(19,64) vs. 28(12,50), Z=-2.19, P=0.029]. Male CAD patients with increased MS exhibited significantly higher Gensini scores [39(20, 58) vs. 26(12, 45), Z=-2.37, P=0.018], levels of CD3 +CD8 +%[28.3%(23.6%,36.6%) vs. 25.9%(21.0%,32.4%), Z=-2.05, P=0.041], and CD3 +CD8 +absolute value [485 (346, 675) vs. 396 (309, 510) cells/μl, Z=-2.55, P=0.011] than those with normal MS. In male patients with CAD, a positive correlation was observed between Gensini scores (correlation coefficient: 0.181, P=0.011), PSS-14 scores, and CD3 +CD8 +absolute value (correlation coefficient: 0.162, P=0.038). Conclusion:This study reveals a positive correlation between MS and coronary stenosis severity, with notable sex differences. In male patients with CAD, higher levels of MS are associated with more severe coronary stenosis. The potential underlying mechanism may involve the regulation of lymphocyte subsets .

Objective:To explore the characteristics and evolutionary features of cognitive impairment and clinical transformation in early-stage Parkinson′s disease (PD) patients.Methods:Based on the cohort of patients with primary unmedicated PD admitted to the Parkinson′s Specialized Outpatient Clinic of Affiliated Brain Hospital of Nanjing Medical University from November 2018 to July 2022, follow-up was conducted for PD patients who completed the baseline assessment and had a follow-up time of 1.5 years or more, and a total of 87 patients finally completed the follow-up and were included in the study. At follow-up, the 87 patients were divided into a cognitively impaired group ( n=36) and a cognitively normal group ( n=51) according to the norm proposed by Professor Jia Jianping and colleagues in 2011 for the Chinese elderly population. Differences in baseline clinical characteristics between the 2 groups were compared, and binary Logistic regression analysis was used to explore risk factors for cognitive impairment in PD patients. In addition, transformed grouping according to cognitive assessment results at baseline and follow-up was used to compare differences in patients′ baseline clinical characteristics among the 3 groups: a reversal group [Parkinson′s disease-mild cognitive impairment (PD-MCI), reverting to Parkinson′s disease-cognitively normal (PD-CN); n=15], a non-reversal group (persistent PD-MCI; n=24), and a stable group (stable PD-CN; n=36). Results:Cognitive reversal occurred at follow-up in 36.6% (15/41) of patients with cognitive impairment at baseline, and 21.7% (10/46) of patients with normal cognition at baseline had cognitive impairment at follow-up. At the end of the follow-up, the 87 patients with PD had higher Unified Parkinson′s Disease Rating Scale Ⅱ (UPDRS-II) scores [8 (6, 11)], Unified Parkinson′s Disease Rating Scale Ⅲ (UPDRS-Ⅲ) scores [23 (16, 30)], and Hoehn-Yahr stages [2.0 (1.5, 2.5)] than those at baseline [7(4, 10), 19(14, 25), 1.5(1.0, 2.0)]. The differences were statistically significant ( Z=-2.498, P=0.012; Z=-3.039, P=0.002; Z=-4.436, P<0.001). The cognitively impaired group had lower Montreal Cognitive Assessment scores [22.00(19.00, 23.75)] and fewer years of education [9.00(8.00, 11.75) years] but higher Parkinson′s Disease Non-Motor Symptoms Questionnaire (PD-NMSQ) scores [8.00(5.25, 12.00)] than the cognitively normal group [25.00(24.00, 27.00), 12.00(9.00, 15.00) years, 6.00(3.00, 8.00)], and the differences were statistically significant ( Z=-4.764, P<0.001; Z=-3.016, P=0.003; Z=-3.281, P=0.001). Multivariate Logistic regression showed that years of education ( OR=0.829, 95%CI 0.715-0.960, P=0.012) and PD-NMSQ scores ( OR=1.200, 95%CI 1.040-1.384, P=0.012) were independent predictors of cognitive impairment in patients with PD. There were statistically significant differences among the reversal, non-reversal, and stable groups in years of education ( F=5.366, P=0.010), PD-NMSQ scores ( H=10.795, P=0.005), and UPDRS-Ⅱ scores ( H=6.957, P=0.031). Pairwise comparisons showed lower PD-NMSQ scores [4.00(3.00, 7.00) vs 8.00(6.25, 12.75); Z=-2.989, P=0.003] and lower UPDRS-Ⅱ scores [6.00(3.00, 6.00) vs 7.00(6.00, 10.00); Z=-2.756, P=0.006] in the reversal group than in the non-reversal group, indicating better baseline quality of life in cognitive reversal patients. Conclusions:Low educational level and severe non-motor symptoms were risk factors predicting cognitive impairment in PD patients. Conversely, mild non-motor symptoms with high quality of life (lower UPDRS-Ⅱ scores) were important factors for cognitive reversal.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.

Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.

Objectives:This study aimed to explore the association between perceived mental stress (MS), lymphocyte subset variations, and coronary lesion severity in patients with coronary artery disease (CAD).Methods:Patients with CAD were enrolled in this study from September 2023 to May 2024. Perceived Stress Scale-14 (PSS-14) was used to evaluate MS during the last 1 month. Lymphocyte subsets were analyzed, including the percentage and absolute counts of CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD3 -CD19 +, CD3 -CD56 +16 +, and the Th/Ts ratio. Statistical analysis was conducted using SPSS 24.0. Results:This study recruited patients with 323 CAD, with an average age of 61 (56, 68) years, including 203 males and 120 females. According to the PSS-14, a score of 14-42 and 43-70 were categorized as normal and increased MS, respectively. Patients with CAD with increased MS had significantly higher Gensini scores than those with normal MS [37(19,64) vs. 28(12,50), Z=-2.19, P=0.029]. Male CAD patients with increased MS exhibited significantly higher Gensini scores [39(20, 58) vs. 26(12, 45), Z=-2.37, P=0.018], levels of CD3 +CD8 +%[28.3%(23.6%,36.6%) vs. 25.9%(21.0%,32.4%), Z=-2.05, P=0.041], and CD3 +CD8 +absolute value [485 (346, 675) vs. 396 (309, 510) cells/μl, Z=-2.55, P=0.011] than those with normal MS. In male patients with CAD, a positive correlation was observed between Gensini scores (correlation coefficient: 0.181, P=0.011), PSS-14 scores, and CD3 +CD8 +absolute value (correlation coefficient: 0.162, P=0.038). Conclusion:This study reveals a positive correlation between MS and coronary stenosis severity, with notable sex differences. In male patients with CAD, higher levels of MS are associated with more severe coronary stenosis. The potential underlying mechanism may involve the regulation of lymphocyte subsets .

Objective:To explore the characteristics and evolutionary features of cognitive impairment and clinical transformation in early-stage Parkinson′s disease (PD) patients.Methods:Based on the cohort of patients with primary unmedicated PD admitted to the Parkinson′s Specialized Outpatient Clinic of Affiliated Brain Hospital of Nanjing Medical University from November 2018 to July 2022, follow-up was conducted for PD patients who completed the baseline assessment and had a follow-up time of 1.5 years or more, and a total of 87 patients finally completed the follow-up and were included in the study. At follow-up, the 87 patients were divided into a cognitively impaired group ( n=36) and a cognitively normal group ( n=51) according to the norm proposed by Professor Jia Jianping and colleagues in 2011 for the Chinese elderly population. Differences in baseline clinical characteristics between the 2 groups were compared, and binary Logistic regression analysis was used to explore risk factors for cognitive impairment in PD patients. In addition, transformed grouping according to cognitive assessment results at baseline and follow-up was used to compare differences in patients′ baseline clinical characteristics among the 3 groups: a reversal group [Parkinson′s disease-mild cognitive impairment (PD-MCI), reverting to Parkinson′s disease-cognitively normal (PD-CN); n=15], a non-reversal group (persistent PD-MCI; n=24), and a stable group (stable PD-CN; n=36). Results:Cognitive reversal occurred at follow-up in 36.6% (15/41) of patients with cognitive impairment at baseline, and 21.7% (10/46) of patients with normal cognition at baseline had cognitive impairment at follow-up. At the end of the follow-up, the 87 patients with PD had higher Unified Parkinson′s Disease Rating Scale Ⅱ (UPDRS-II) scores [8 (6, 11)], Unified Parkinson′s Disease Rating Scale Ⅲ (UPDRS-Ⅲ) scores [23 (16, 30)], and Hoehn-Yahr stages [2.0 (1.5, 2.5)] than those at baseline [7(4, 10), 19(14, 25), 1.5(1.0, 2.0)]. The differences were statistically significant ( Z=-2.498, P=0.012; Z=-3.039, P=0.002; Z=-4.436, P<0.001). The cognitively impaired group had lower Montreal Cognitive Assessment scores [22.00(19.00, 23.75)] and fewer years of education [9.00(8.00, 11.75) years] but higher Parkinson′s Disease Non-Motor Symptoms Questionnaire (PD-NMSQ) scores [8.00(5.25, 12.00)] than the cognitively normal group [25.00(24.00, 27.00), 12.00(9.00, 15.00) years, 6.00(3.00, 8.00)], and the differences were statistically significant ( Z=-4.764, P<0.001; Z=-3.016, P=0.003; Z=-3.281, P=0.001). Multivariate Logistic regression showed that years of education ( OR=0.829, 95%CI 0.715-0.960, P=0.012) and PD-NMSQ scores ( OR=1.200, 95%CI 1.040-1.384, P=0.012) were independent predictors of cognitive impairment in patients with PD. There were statistically significant differences among the reversal, non-reversal, and stable groups in years of education ( F=5.366, P=0.010), PD-NMSQ scores ( H=10.795, P=0.005), and UPDRS-Ⅱ scores ( H=6.957, P=0.031). Pairwise comparisons showed lower PD-NMSQ scores [4.00(3.00, 7.00) vs 8.00(6.25, 12.75); Z=-2.989, P=0.003] and lower UPDRS-Ⅱ scores [6.00(3.00, 6.00) vs 7.00(6.00, 10.00); Z=-2.756, P=0.006] in the reversal group than in the non-reversal group, indicating better baseline quality of life in cognitive reversal patients. Conclusions:Low educational level and severe non-motor symptoms were risk factors predicting cognitive impairment in PD patients. Conversely, mild non-motor symptoms with high quality of life (lower UPDRS-Ⅱ scores) were important factors for cognitive reversal.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.