CD8+T cell-based immune-therapeutics,including immune checkpoint inhibitors and adoptive cell therapies(tumor-infiltrating lymphocytes(TILs),T cell receptor-engineered T cells(TCR-T),chimeric antigen receptor T cells(CAR-T)),have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases.However,immunotherapy resistance and tumor insusceptibility frequently occur,leading to treatment failure.Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites,immune-inhibitory cytokines,and alteration of gene expression,which suppress the activity of immune cells,particularly CD8+T cells to evade immune surveillance.Therefore,targeting tumor cell metabolic adaptations to reshape the immune microenvi-ronment holds promise as an immunomodulatory strategy to facilitate immunotherapy.Here,we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming,focusing on the regulatory mechanisms underlying tumor cell glucose metabolism,amino acid meta-bolism,and lipid metabolism in influencing CD8+T cells to provide promising metabolic targets or combinational strategies for immunotherapy.

Objective To explore the current status of minor children parenting concerns among young and middle-aged breast cancer patients and investigate the influencing factors based on a random forest model so as to provide references for clinical interventions.Methods A convenience sampling method was used to select breast cancer patients undergoing treatment in our hospital between April and December 2023.A self-designed general information questionnaire,the Chinese version of parenting concerns questionnaire(PCQ),perceived social support scale(PSSS),concern about recurrence scale(CARS),and the brief illness perception questionnaire(BIPQ)were used for the study.A random forest model and the least absolute shrinkage and selection operator(LASSO)were employed to prioritise variables and filtered by significance.The selected variables were then incorporated into the multiple linear regression analysis.Results A total of 260 patients completed the study.The score of minor children parenting concerns of young and middle-aged breast cancer patients was 51.1±6.4.The multiple linear regression analysis,which included variables determined by random forest and LASSO regression(and sorted by the importance of influencing factors),showed that higher disease perception,lower perceived social support,greater concern about cancer recurrence,stage IV tumors,being divorced/widowed,and having more minor children were associated with higher parenting concerns among young and middle-aged breast cancer patients(all P<0.05),accounting for 57.0%of the total variance.Conclusion The minor children parenting concerns in young and middle-aged breast cancer patients are at a moderately high level and are influenced by a variety of factors.Healthcare professionals should develop targeted measures and interventions to reduce the parenting concerns among the patients.

Objective:To explore the effects of vitamin D supplementation combined with suspended lumbar abdominal muscle training on rehabilitation and bone metabolism indexes of patients after OVCF.Methods:A total of 140 patients with osteoporotic vertebral compression fractures (OVCF) treated at Yantaishan Hospital from Jun. 2021 to Jun. 2024 were included in this study. Patients were randomly assigned to a control group and an observation group using a random number table, with 70 patients in each group. The control group received suspension lumbar and abdominal muscle training, while the observation group received vitamin D supplementation combined with suspension lumbar and abdominal muscle training. Outcomes evaluated included VAS scores, Oswestry Disability Index (ODI) , Cobb Angle, lumboabdominal muscle strength, and serum levels of 25-hydroxyvitamin D [25 (OH) D], bone mineral density T value, and bone metabolism markers [serum osteocalcin (OC) , calcitonin (CT) , total type I collagen amino-terminal propeptide (tPINP) , type I collagen carboxy-terminal peptide β special sequence (β-CTX) , intact parathyroid hormone (iPTH) , and bone-specific alkaline phosphatase (BALP) ] measured by chemiluminescence.Results:In comparison with the control group, the VAS and ODI scores in the observation group were lower after treatment ( t=13.66, t=9.87, P < 0.05) . Compared to the control group, the lumbar muscle strength score of the observation group, the 25 (OH) D level and bone mineral density T value was higher after treatment ( t=57.63, t=6.64, t=5.01, P < 0.05) , and the Cobb Angle was smaller ( t=9.21, P < 0.05) .Compared with the control group, the bone metabolism indexes OC, CT, tPINP, and BALP were higher in the observation group after treatment ( t=4.21, t=3.05, t=2.66, t=3.16, P < 0.05) , while the iPTH and β-CTX were lower ( t=7.28, t=3.50, P < 0.05) . Conclusions:Vitamin D supplementation combined with suspended lumbar and abdominal muscle training can promote postoperative rehabilitation of OVCF patients and improve the level of bone metabolism indexes after surgery.

OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
Humans ; Cell Movement ; Transcription Factors/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Cycle Proteins ; Azepines/pharmacology* ; Epithelial-Mesenchymal Transition ; Carcinoma, Squamous Cell/metabolism* ; Esophageal Squamous Cell Carcinoma ; Triazoles/pharmacology* ; Nuclear Proteins/genetics* ; Cell Proliferation ; Acetyl-CoA Carboxylase/genetics* ; Transfection ; Autophagy ; Bromodomain Containing Proteins

Objective To investigate the role of mitochondrial antiviral signaling protein(MAVS)in viral infection-triggered generalized pustular psoriasis(GPP)in children.Methods This retrospective case-control study enrolled 80 GPP patients aged 0～18 years from Children's Hospital of Chongqing Medical University(from October 2013 to April 2019).Whole-exome sequencing identified rare MAVS variants associated with GPP.Pathogenicity of variants was predicted using Mutation Taster,Disease Association,SIFT,and CADD bioinformatics tools.Sanger sequencing validated variants,followed by construction of wild-type(WT)and mutant MAVS expression plasmids transfected into HEK 293 cells.Protein expression was assessed by Western blot.Dual-luciferase reporter gene assays measured IFNB1 and NF-κB transcriptional activity.Genotype distribution of the MAVS c.171dupT/p.H57fs variant was analyzed using Fisher's exact test.Results This study enrolled 80 pediatric GPP patients(aged 0～18 years).Whole-exome sequencing identified five rare MAVS variants,with bioinformatics analyses predicting deleterious effects on protein stability and function.Western blot demonstrated that the c.171dupT mutation in GPP patients significantly reduced full-length MAVS expression(P<0.001);dual-luciferase assays further revealed this variant impaired MAVS-mediated IFNB1 transcriptional activation by 85%(P<0.001),abrogated NF-κB signaling pathway activation(P<0.001),but exhibited no dominant-negative effect on wild-type MAVS function(P>0.05).Conclusion The MAVS c.171dupT frameshift variant may contribute to infection-triggered GPP in children,suggesting its potential as a genetic biomarker for GPP susceptibility.

Objective To explore the current status of minor children parenting concerns among young and middle-aged breast cancer patients and investigate the influencing factors based on a random forest model so as to provide references for clinical interventions.Methods A convenience sampling method was used to select breast cancer patients undergoing treatment in our hospital between April and December 2023.A self-designed general information questionnaire,the Chinese version of parenting concerns questionnaire(PCQ),perceived social support scale(PSSS),concern about recurrence scale(CARS),and the brief illness perception questionnaire(BIPQ)were used for the study.A random forest model and the least absolute shrinkage and selection operator(LASSO)were employed to prioritise variables and filtered by significance.The selected variables were then incorporated into the multiple linear regression analysis.Results A total of 260 patients completed the study.The score of minor children parenting concerns of young and middle-aged breast cancer patients was 51.1±6.4.The multiple linear regression analysis,which included variables determined by random forest and LASSO regression(and sorted by the importance of influencing factors),showed that higher disease perception,lower perceived social support,greater concern about cancer recurrence,stage IV tumors,being divorced/widowed,and having more minor children were associated with higher parenting concerns among young and middle-aged breast cancer patients(all P<0.05),accounting for 57.0%of the total variance.Conclusion The minor children parenting concerns in young and middle-aged breast cancer patients are at a moderately high level and are influenced by a variety of factors.Healthcare professionals should develop targeted measures and interventions to reduce the parenting concerns among the patients.

Objective:To explore the effects of vitamin D supplementation combined with suspended lumbar abdominal muscle training on rehabilitation and bone metabolism indexes of patients after OVCF.Methods:A total of 140 patients with osteoporotic vertebral compression fractures (OVCF) treated at Yantaishan Hospital from Jun. 2021 to Jun. 2024 were included in this study. Patients were randomly assigned to a control group and an observation group using a random number table, with 70 patients in each group. The control group received suspension lumbar and abdominal muscle training, while the observation group received vitamin D supplementation combined with suspension lumbar and abdominal muscle training. Outcomes evaluated included VAS scores, Oswestry Disability Index (ODI) , Cobb Angle, lumboabdominal muscle strength, and serum levels of 25-hydroxyvitamin D [25 (OH) D], bone mineral density T value, and bone metabolism markers [serum osteocalcin (OC) , calcitonin (CT) , total type I collagen amino-terminal propeptide (tPINP) , type I collagen carboxy-terminal peptide β special sequence (β-CTX) , intact parathyroid hormone (iPTH) , and bone-specific alkaline phosphatase (BALP) ] measured by chemiluminescence.Results:In comparison with the control group, the VAS and ODI scores in the observation group were lower after treatment ( t=13.66, t=9.87, P < 0.05) . Compared to the control group, the lumbar muscle strength score of the observation group, the 25 (OH) D level and bone mineral density T value was higher after treatment ( t=57.63, t=6.64, t=5.01, P < 0.05) , and the Cobb Angle was smaller ( t=9.21, P < 0.05) .Compared with the control group, the bone metabolism indexes OC, CT, tPINP, and BALP were higher in the observation group after treatment ( t=4.21, t=3.05, t=2.66, t=3.16, P < 0.05) , while the iPTH and β-CTX were lower ( t=7.28, t=3.50, P < 0.05) . Conclusions:Vitamin D supplementation combined with suspended lumbar and abdominal muscle training can promote postoperative rehabilitation of OVCF patients and improve the level of bone metabolism indexes after surgery.

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

The aim of the present study was to explore the role of group II and III metabotropic glutamate receptors (mGluRs) in carotid body plasticity induced by chronic intermittent hypoxia (CIH) in rats. Sprague Dawley (SD) rats were treated with CIH in Oxycycler A84 hypoxic chamber for 4 weeks, and the tail artery blood pressure was measured at the end of model preparation. RT-qPCR was performed to examine the mRNA expression levels of mGluR2/3/8 in rat carotid body. Carotid sinus nerve activity was detected by ex vivo carotid sinus nerve discharge recording technique, and acute intermittent hypoxia (AIH) was administered to induce carotid body sensory long-term facilitation (sLTF), in order to observe the role of group II and group III mGluRs in carotid body plasticity induced by CIH. The results showed that: 1) After 4 weeks of CIH exposure, the blood pressure of rats increased significantly; 2) CIH down-regulated the mRNA levels of mGluR2/3, and up-regulated the mRNA level of mGluR8 in the carotid body; 3) AIH induced sLTF in carotid body of CIH group. In the CIH group, activation of group II mGluRs had no effect on sLTF of carotid body, while activation of group III mGluRs completely inhibited sLTF. These results suggest that CIH increases blood pressure in rats, and group III mGluRs play an inhibitory role in CIH-induced carotid body plasticity in rats.
Rats ; Animals ; Carotid Body/metabolism* ; Rats, Sprague-Dawley ; Hypoxia ; Receptors, Metabotropic Glutamate/metabolism* ; RNA, Messenger/metabolism*

The purpose of this study was to investigate the effect of glutamate and its ionotropic receptor agonists on the response to acute hypoxia in rat carotid body in vitro. Briefly, after SD rats were anesthetized and decapitated, the bilateral carotid bifurcations were rapidly isolated. Then bifurcation was placed into a recording chamber perfused with 95% O₂-5% CO₂ saturated Kreb's solution. The carotid body-sinus nerve complex was dissected, and the carotid sinus nerve discharge was recorded using a suction electrode. To detect the response of carotid body to acute hypoxia, the chamber was perfused with 5% O₂-5% CO₂-90% N₂ saturated Kreb's solution for a period of 100 s at an interval of 15 min. To observe the effect of glutamate, ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonist AMPA or N-methyl-D-aspartate (NMDA) receptor agonist NMDA on the response to acute hypoxia in rat carotid body, the chamber was perfused with 5% O₂-5% CO₂-90% N₂ saturated Kreb's solution containing the corresponding reagent. The results showed that glutamate (20 μmol/L), AMPA (5 μmol/L) or NMDA (10 μmol/L) inhibited the acute hypoxia-induced enhancement of carotid sinus nerve activity, and these inhibitory effects were dose-dependent. In summary, the activation of glutamate ionotropic receptors appears to exert an inhibitory effect on the response to acute hypoxia in carotid body of rats.
Rats ; Animals ; Glutamic Acid/pharmacology* ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology* ; N-Methylaspartate/pharmacology* ; Carotid Body ; Rats, Sprague-Dawley ; Carbon Dioxide ; Receptors, N-Methyl-D-Aspartate ; Receptors, AMPA ; Hypoxia