Brain responses to self- and other- unfairness under resource distribution context: meta-analysis of fMRI studies.

Under resource distribution context, individuals have a strong aversion to unfair treatment not only toward themselves but also toward others. However, there is no clear consensus regarding the commonality and distinction between these two types of unfairness. Moreover, many neuroimaging studies have investigated how people evaluate and respond to unfairness in the abovementioned two contexts, but the consistency of the results remains to be investigated. To resolve these two issues, we sought to summarize existing findings regarding unfairness to self and others and to further elucidate the neural underpinnings related to distinguishing evaluation and response processes through meta-analyses of previous neuroimaging studies. Our results indicated that both types of unfairness consistently activate the affective and conflict-related anterior insula (AI) and dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA), but the activations related to unfairness to self appeared stronger than those related to others, suggesting that individuals had negative reactions to both unfairness and a greater aversive response toward unfairness to self. During the evaluation process, unfairness to self activated the bilateral AI, dACC, and right dorsolateral prefrontal cortex (DLPFC), regions associated with unfairness aversion, conflict, and cognitive control, indicating reactive, emotional and automatic responses. In contrast, unfairness to others activated areas associated with theory of mind, the inferior parietal lobule and temporoparietal junction (IPL-TPJ), suggesting that making rational judgments from the perspective of others was needed. During the response, unfairness to self activated the affective-related left AI and striatum, whereas unfairness to others activated cognitive control areas, the left DLPFC and the thalamus. This indicated that the former maintained the traits of automaticity and emotionality, whereas the latter necessitated cognitive control. These findings provide a fine-grained description of the common and distinct neurocognitive mechanisms underlying unfairness to self and unfairness to others. Overall, this study not only validates the inequity aversion model but also provides direct evidence of neural mechanisms for neurobiological models of fairness.

Moiré Engineering of Spin-Orbit Torque by Twisted WS2 Homobilayers.

Artificial moiré superlattices created by stacking 2D crystals have emerged as a powerful platform with unprecedented material-engineering capabilities. While moiré superlattices are reported to host a number of novel quantum states, their potential for spintronic applications remains largely unexplored. Here, the effective manipulation of spin-orbit torque (SOT) is demonstrated using moiré superlattices in ferromagnetic devices comprised of twisted WS2/WS2 homobilayer (t-WS2) and CoFe/Pt thin films by altering twisting angle (θ) and gate voltage. Notably, a substantial enhancement of up to 44.5% is observed in SOT conductivity at θ ≈ 8.3°. Furthermore, compared to the WS2 monolayer and untwisted WS2/WS2 bilayers, the moiré superlattices in t-WS2 enable a greater gate-voltage tunability of SOT conductivity. These results are related to the generation of the interfacial moiré magnetic field by the real-space Berry phase in moiré superlattices, which modulates the absorption of the spin-Hall current arising from Pt through the magnetic proximity effect. This study highlights the moiré physics as a new building block for designing enhanced spintronic devices.

Exploring publications in 3 major orthodontic journals: A comparative bibliometric analysis of two 10-year periods (2002-2011 and 2012-2021).

INTRODUCTION: This study aimed to perform a bibliometric analysis examining contributing countries and collaborative networks, authors and collaborative relationships, the performance of the institutions, and cocited journals and references in 3 major orthodontic journals (American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, and Angle Orthodontist) over two 10-year periods (2002-2011 and 2012-2021). METHODS: In this study, 4432 publications in the first decade and 4012 publications in the second decade were quantitatively analyzed and visualized using visualization software such as VOSviewer (Leiden University, Leiden, Netherlands), CiteSpace (Drexel University, Philadelphia, Pa), and Scimago Graphica (SCImago Lab, Spain). RESULTS: Institutions in the United States had the highest number of publications through the 2 decades, whereas Brazil, South Korea, and China achieved significant improvements in performance in the second decade compared with the first. Closer collaborative networks among scholars were revealed in the second decade. The cocitation analysis of the journals showed that highly cited journals included more professional orthodontic journals in the second decade than in the first decade. CONCLUSIONS: Bibliometric analysis of publications in 3 major orthodontic journals over two 10-year periods revealed a trend of diversification in countries and institutions participating in publishing, international collaborations, and collaboration networks among authors in the field of orthodontics during the 2 decades.

P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together.

Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children's Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.

Biological signatures of the International Prognostic Index in diffuse large B-cell lymphoma.

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma with clinical and biological heterogeneity. The International Prognostic Index (IPI) shows great prognostic capability in the era of rituximab, but the biological signatures of IPI remain to be discovered. In this study, we analyzed the clinical data in a large cohort of 2592 patients with newly diagnosed DLBCL. Among them, 1233 underwent DNA sequencing for oncogenic mutations, and 487 patients underwent RNA sequencing for lymphoma microenvironment (LME) alterations. Based on IPI scores, patients were categorized into 4 distinct groups, with 5-year overall survival of 41.6%, 55.3%, 71.7%, and 89.7%, respectively. MCD-like subtype was associated with age of >60 years, multiple extranodal involvement, elevated serum lactate dehydrogenase (LDH), and IPI scores ranging from 2 to 5, whereas ST2-like subtype showed an opposite trend. Patients with EZB-like MYC+ and TP53Mut subtypes exhibited poor clinical outcome independent of the IPI; integrating TP53Mut into IPI could better distinguish patients with dismal survival. The EZB-like MYC-, BN2-like, N1-like, and MCD-like subtypes had inferior prognosis in patients with IPI scores of ≥2, indicating necessity for enhanced treatment. Regarding LME categories, the germinal center-like LME was more prevalent in patients with normal LDH and IPI scores of 0 to 1. The mesenchymal LME served as an independent protective factor, whereas the germinal center-like, inflammatory, and depleted LME categories correlated with inferior prognosis for IPI scores of 2 to 5. In summary, our work explored the biological signatures of IPI, thus providing useful rationale for future optimization of the IPI-based treatment strategies with multi-omics information in DLBCL.

Bibliometric and visualized analysis of randomized controlled trials in orthodontics between 1991 and 2022.

INTRODUCTION: In many evidence-based approaches to orthodontic research, randomized controlled trials (RCTs) represent authoritative evidence to identify rational therapeutics. This study aimed to perform mappings of bibliometric networks on orthodontic RCTs and summarize visual characteristics between 1991 and 2022. METHODS: The articles were retrieved from the Web of Science Core Collection in October 2022 without an initial time limit. Only orthodontic RCTs were eligible. Some bibliometric tools (HistCite, VOSviewer, SCImago Graphica, and CiteSpace) were applied for visualized analysis. Data such as geography, productive institutions, hot articles, journals, authors, references, and keywords were extracted and summarized for analysis. RESULTS: A total of 1122 orthodontic RCTs were searched. A total of 3841 authors from 1157 institutions in 65 countries published orthodontic RCTs. The United States (149) was the most prolific country, and the University of Sao Paulo (35) was the most productive institution. The American Journal of Orthodontics and Dentofacial Orthopedics (206) was the most popular journal for scholars. The visualization results of keyword co-occurrence identified 5 clusters: (1) tooth movement and auxiliary measures, (2) appliances and oral health, (3) orthodontic discomfort and symptomatic therapy, (4) periodontal disease in orthodontics and health maintenance, and (5) retention and relapse. CONCLUSIONS: Over the past 31 years, publications and citations on orthodontic RCTs from the Web of Science Core Collection have increased notably across many countries, authors, and institutions. Recently, there has been a significant increase in the attention to orthodontic RCTs that focus on accelerating tooth movement.

A Population-Based and Clinical Cohort Validation of the Novel Consensus Definition of Metabolic Hyperferritinemia.

CONTEXT: There is limited data on the clinical significance of metabolic hyperferritinemia (MHF) based on the most recent consensus. OBJECTIVE: We aimed to validate the clinical outcomes of MHF in the general population and patients with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: The NHANES database and PERSONS cohort were included. MHF was defined as elevated serum ferritin with metabolic dysfunction (MD) and stratified into different grades according to ferritin (grade 1: 200 [females]/300 [males]-550 ng/mL; grade 2: 550-1000 ng/mL; grade 3: >1000 ng/mL). The clinical outcomes, including all-cause death, comorbidities, and liver histology, were compared between non-MHF and MHF in adjusted models. RESULTS: In NHANES, compared with non-MHF with MD, MHF was related to higher risks of advanced fibrosis (P = .036), elevated albumin-creatinine ratio (UACR, P = .001), and sarcopenia (P = .013). Although the association between all grades of MHF and mortality was insignificant (P = .122), grades 2/3 was associated with increased mortality (P = .029). When comparing with non-MHF without MD, the harmful effects of MHF were more significant in mortality (P < .001), elevated UACR (P < .001), cardiovascular disease (P = .028), and sarcopenia (P < .001). In the PERSONS cohort, MHF was associated with more advanced grades of steatosis (P < .001), lobular inflammation (P < .001), advanced fibrosis (P = .017), and more severe hepatocellular iron deposition (P < .001). CONCLUSION: Both in the general population and in at-risk individuals with MAFLD, MHF was related with poorer clinical outcomes.

Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: The randomized GUIDANCE-01 trial.

We report the results of GUIDANCE-01 (NCT04025593), a randomized, phase II trial of R-CHOP alone or combined with targeted agents (R-CHOP-X) guided by genetic subtyping of newly diagnosed, intermediate-risk, or high-risk diffuse large B cell lymphoma (DLBCL). A total of 128 patients were randomized 1:1 to receive R-CHOP-X or R-CHOP. The study achieved the primary endpoint, showing significantly higher complete response rate with R-CHOP-X than R-CHOP (88% vs. 66%, p = 0.003), with overall response rate of 92% vs. 73% (p = 0.005). Two-year progression-free survival rates were 88% vs. 63% (p < 0.001), and 2-year overall survival rates were 94% vs. 77% (p = 0.001). Meanwhile, post hoc RNA-sequencing validated our simplified genetic subtyping algorithm and previously established lymphoma microenvironment subtypes. Our findings highlight the efficacy and safety of R-CHOP-X, a mechanism-based tailored therapy, which dually targeted genetic and microenvironmental alterations in patients with newly diagnosed DLBCL.

Positron emission tomography-adapted therapy in low-risk diffuse large B-cell lymphoma: results of a randomized, phase III, non-inferiority trial.

BACKGROUND: The current standard of care for non-bulky diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) of 0 is four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) but whether the same efficacy can be achieved with reduced chemotherapy regimen of four cycles for non-bulky DLBCL patients with an IPI of 1 remains unclear. This study compared four cycles versus six cycles of chemotherapy in non-bulky low-risk DLBCL patients with negative interim positron emission tomography with computed tomography (PET-CT, Deauville 1-3), irrespective of age and other IPI risk factors (IPI 0-1). METHODS: This was an open-label, randomized, phase III, non-inferiority trial. Patients aged 14-75 years with newly diagnosed low-risk DLBCL, according to IPI, achieving PET-CT confirmed complete response (CR) after four cycles of R-CHOP were randomized (1:1) between four cycles of rituximab (4R-CHOP+4R arm) or two cycles of R-CHOP plus two cycles of rituximab (6R-CHOP+2R arm). The primary endpoint was 2-year progression-free survival (PFS), conducted in the intention-to-treat population. Safety was assessed in patients with at least one cycle of assigned treatment. The non-inferiority margin was -8%. RESULTS: A total of 287 patients were included in the intention-to-treat analysis, the median follow-up was 47.3 months, and the 2-year PFS rate was 95% (95% confidence interval [CI], 92% to 99%) and 94% (95% CI, 91% to 98%) for the 4R-CHOP+4R and 6R-CHOP+2R arm. The absolute difference in 2-year PFS between the two arms was 1% (95% CI, -5% to 7%), supporting the non-inferiority of 4R-CHOP+4R. Grade 3-4 neutropenia was lower in the last four cycles of rituximab alone in the 4R-CHOP+4R arm (16.7% versus 76.9%), with decreased risk of febrile neutropenia (0.0% versus 8.4%) and infection (2.1% versus 14.0%). CONCLUSIONS: For newly diagnosed low-risk DLBCL patients, interim PET-CT after four cycles of R-CHOP was effective in identifying patients with Deauville 1-3 who would have a good response and Deauville 4-5 patients who might have high-risk biological features or develop resistance. Reducing the standard six cycles to four cycles of chemotherapy had comparable clinical efficacy and fewer adverse events in low-risk, non-bulky DLBCL with interim PET-CT confirmed CR.

Identification of a novel splicing-altering LAMP2 variant in a Chinese family with Danon disease.

AIMS: This study aimed to identify a novel splicing-altering LAMP2 variant associated with Danon disease. METHODS AND RESULTS: To identify the potential genetic mutation in a Chinese pedigree, whole-exome sequencing was conducted in the proband, and Sanger sequencing was performed on the proband's parents. To verify the impact of the splice-site variant, a minigene splicing assay was applied. The AlphaFold2 analysis was used to analyse the mutant protein structure. A splice-site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified as a potential pathogenic variant. The minigene splicing revealed that this variant causes exon 6 to be skipped, resulting in a truncated protein. The AlphaFold2 analysis showed that the mutation caused a protein twist direction change, leading to conformational abnormality. CONCLUSIONS: A novel splice-site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified. This discovery may enlarge the LAMP2 variant spectrum, promote accurate genetic counselling, and contribute to the diagnosis of Danon disease.

A Trained Humanoid Robot can Perform Human-Like Crossmodal Social Attention and Conflict Resolution.

To enhance human-robot social interaction, it is essential for robots to process multiple social cues in a complex real-world environment. However, incongruency of input information across modalities is inevitable and could be challenging for robots to process. To tackle this challenge, our study adopted the neurorobotic paradigm of crossmodal conflict resolution to make a robot express human-like social attention. A behavioural experiment was conducted on 37 participants for the human study. We designed a round-table meeting scenario with three animated avatars to improve ecological validity. Each avatar wore a medical mask to obscure the facial cues of the nose, mouth, and jaw. The central avatar shifted its eye gaze while the peripheral avatars generated sound. Gaze direction and sound locations were either spatially congruent or incongruent. We observed that the central avatar's dynamic gaze could trigger crossmodal social attention responses. In particular, human performance was better under the congruent audio-visual condition than the incongruent condition. Our saliency prediction model was trained to detect social cues, predict audio-visual saliency, and attend selectively for the robot study. After mounting the trained model on the iCub, the robot was exposed to laboratory conditions similar to the human experiment. While the human performance was overall superior, our trained model demonstrated that it could replicate attention responses similar to humans.

Effectiveness of COVID-19 Vaccination Against SARS-CoV-2 Omicron Variant Infection and Symptoms - China, December 2022-February 2023.

What is already known about this topic?: A considerable percentage of the population has received both primary and booster vaccinations, which could potentially provide protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infections and related symptoms. What is added by this report?: The self-reported infection rate, as determined from an online survey, reached its peak (15.5%) between December 19 and 21, 2022, with an estimated 82.4% of individuals in China being infected as of February 7, 2023. During the epidemic, the effectiveness of booster vaccinations against SARS-CoV-2 Omicron infection was found to be 49.0% within three months of vaccination and 37.9% between 3 and 6 months following vaccination. Furthermore, the vaccine effectiveness of the booster vaccination in relation to symptom prevention varied from 48.7% to 83.2% within three months and from 25.9% to 69.0% between 3 and 6 months post-booster vaccination. What are the implications for public health practice?: The development and production of efficacious vaccines, together with prompt vaccinations or emergency vaccinations, have the potential to mitigate the epidemic's impact and safeguard public health.

Serum pro-surfactant protein B is correlated with clinical properties in osteosarcoma patients.

It is critical to find efficient non-invasive prognostic factor for osteosarcoma. In this study, we demonstrated that serum protein of pro-surfactant protein B (pro-SFTPB) may be a potential diagnostic indicator in osteosarcoma. We found that serum pro-SFTPB was highly expressed in osteosarcoma patients and presented good diagnostic value to discern osteosarcoma patients from non-osteosarcoma control subjects. Serum pro-SFTPB was also significantly correlated with advanced clinical stage, distant metastasis, and shorter overall survival. In addition, serum pro-SFTPB was demonstrated to be an independent prognostic factor for osteosarcoma. Overall, our study demonstrated that serum pro-SFTPB may be a useful diagnostic factor for osteosarcoma.

Change in global burden of unintentional drowning from 1990 to 2019 and its association with social determinants of health: findings from the Global Burden of Disease Study 2019.

OBJECTIVE: To systematically analyse global, regional and national burden change of unintentional drowning from 1990 to 2019, and to further quantify the contribution of social determinants of health (SDH) on the change. DESIGN: Data from the Global Burden of Disease Study 2019 were used in this study. SETTING AND PARTICIPANTS: Individuals of all ages and genders from 204 countries and territories. MAIN OUTCOME MEASURES: The main outcomes were the age-standardised rates (ASRs) of mortality and disability-adjusted life-years (DALYs) of unintentional drowning. The percentage change in the ASRs were used to estimate the joint effect of SDH on trends in global burden of drowning. RESULTS: We observed that the global burden of unintentional drowning declined markedly from 1990 to 2019, with age-standardised mortality rate and DALYs rate decreasing by 61.5% and 68.2%, respectively. Women, children, middle Socio-Demographic Index (SDI) countries, South-East Asia and Western Pacific region had higher reduction. At national level, greater reductions were observed in Armenia and Republic of Korea, but significant increases in Cabo Verde and Vanuatu. We found that every one percentile increase in six SDHs (Gross Domestic Product (GDP) per person, SDI, educational attainment, health spending, health workers and urbanisation) was associated with a decrease of 0.15% and 0.16% in drowning age-standardised mortality rate and DALYs rate globally, respectively. Health spending and GDP per capita were the main contributors to the reduction of drowning globally. CONCLUSIONS: The global burden of unintentional drowning significantly declined in the past three decades, and the improvement of SDHs such as GDP per capita and health spending mainly contributed to the decrease. Our findings indicate that improvement of SDHs is critical for drowning prevention and control.

A nuclear NKRF interacting long noncoding RNA controls EBV eradication and suppresses tumor progression in natural killer/T-cell lymphoma.

Long intergenic noncoding RNAs (lincRNAs) are differentially expressed in EBV-infected cells and play an essential role in tumor progression. Molecular pathogenesis of lincRNAs in EBV-driven natural killer T cell lymphoma (NKTCL) remains unclear. Here we investigated the ncRNA profile using high-throughput RNA sequencing data of 439 lymphoma samples and screened out LINC00486, whose downregulation was further validated by quantitative real-time polymerase chain reaction in EBV-encoded RNA (EBER)-positive lymphoma, particularly NKTCL. Both in vitro and in vivo studies revealed the tumor suppressive function of LINC00486 through inhibiting tumor cell growth and inducing G0/G1 cell cycle arrest. As mechanism of action, LINC00486 specifically interacted with NKRF to abrogate its binding with phosphorylated p65, activated NF-κB/TNF-α signaling and subsequently enhanced EBV eradication. Solute carrier family 1 member 1 (SLC1A1), upregulated and mediated the glutamine-addiction and tumor progression in NKTCL, was negatively correlated with the expression of NKRF. NKRF specifically bound to the promoter and transcriptionally downregulated the expression of SLC1A1, as evidenced by Chromatin Immunoprecipitation (ChIP) and luciferase assay. Collectively, LINC00486 functioned as a tumor suppressor and counteracted EBV infection in NKTCL. Our study improved the knowledge of EBV-driven oncogenesis in NKTCL and provided the clinical rationale of EBV eradication in anti-cancer treatment.

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor T therapy.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.