BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Heat shock protein 70 (HSP70), an evolutionarily conserved molecular chaperone, serves as a central regulator within tumor immune networks. This review summarizes the multiple immune regulatory mechanisms mediated by HSP70 through its specific domains: promoting antigen presentation and cross-presentation processes; prolonging immune response duration; regulating innate and adaptive immune responses; and interacting with immune checkpoint molecules like programmed death-1 ligand 1 (PD-L1). In translation of clinical research, HSP70 can serve as a vaccine adjuvant to enhance immunogenicity, while its inhibitors can overcome resistance to immunotherapy. Additionally, membrane-bound HSP70 represents a potential immunotherapeutic target, and its targeting strategies show significant synergistic effects when combined with immune checkpoint inhibitors. However, due to the functional redundancy of the molecular chaperone network, the clinical efficacy of single-agent HSP70 inhibition is limited. In-depth elucidation of HSP70's synergistic regulatory mechanisms within the chaperone interaction network has important implications for developing novel tumor immunotherapy strategies.
HSP70 Heat-Shock Proteins/metabolism* ; Humans ; Immunotherapy/methods* ; Neoplasms/immunology* ; Animals ; B7-H1 Antigen/metabolism*

Tumor immune microenvironment is an important microecology for tumor development, where tumor-associated macrophages are the most abundant immune cells in the tumor immune microenvironment, with high plasticity and heterogeneity. Under the regulation of various environmental factors, tumor-associated macrophages can differentiate into different subgroups. Though complex and variable, all these environmental factors ultimately regulate tumor-associated macrophages by influencing the temporal and spatial heterogeneity of these cells’ internal components, structure, and functions. Mitochondrion are important organelles, responsible for energy production, metabolism, and centers of multiple signal transduction. More and more studies have found that mitochondria can regulate cell functions through various mechanisms such as morphological change, metabolic reprogramming, intermediate metabolites or mitochondrial genetic material. Mitochondrial disorders are involved in many diseases and pathological processes. Here, we review the mechanisms by which mitochondria regulate the polarization of macrophages and thus reshape the tumor immune microenvironment. Further, we discuss and prospect the current status of macrophage mitochondria-related tumor immunotherapy.

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on the intracranial pressure in patients undergoing laparoscopic hysterectomy by measuring the optic nerve sheath diameter (ONSD) via ultrasound.Methods:Forty-two American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-60 yr, with a body mass index of 18-28 kg/m 2, scheduled for elective laparoscopic hysterectomy, were divided into 2 groups ( n=21 each) using a random number table method: control group (group C) and TEAS group (group T). In group T, TEAS was applied to the Yintang (EX-HN3) and Taiyang (EX-HN5) acupoints at 30 min before anesthesia, the stimulation used alternating dense-disperse waves at a frequency of 2/100 Hz, with the current intensity starting at 1 mA and increasing to the maximum tolerable level just below the pain threshold, and stimulation was maintained at the Hegu (LI4), Quanliao (SI18), and Fengchi (GB20) acupoints during surgery until the procedure was completed. Patients had electrode pads applied to the corresponding acupoints without electrical stimulation in group C. The ONSD was measured upon entry into the operating room (T 0), 3 min after anesthesia induction (T 1), 5 min after trendelenburg position (T 2), 30 min after trendelenburg position (T 3), 60 min after trendelenburg position (T 4), and immediately after the end of operation (T 5). Results:Compared to the baseline at T 0, the ONSD was significantly increased at T 3-5 in group C and at T 4, 5 in group T ( P<0.05). The ONSD was significantly lower at T 4, 5 in group T than in group C ( P<0.05). Conclusions:TEAS can reduce the intracranial pressure to some extent in patients undergoing laparoscopic hysterectomy.

OBJECTIVE: To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. METHODS: Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay. RESULTS: The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ［ (5.78±2.69) pg/ ml］ and CXCL-13 ［(0.83±0.59) pg/ml］ in protein elevated group were significantly higher than those in the protein normal group ［IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/ml］ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant. CONCLUSION The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.
Humans ; Central Nervous System ; Cytokines ; Interleukin-10 ; Interleukin-6 ; Lymphoma

Objective:To evaluate the influence of depression and anxiety on sleep quality, and to provide a basis for preventing sleep disorders in community-dwelling older adults.Methods:Cluster sampling was used.A self-designed questionnaire, the Pittsburgh Sleep Quality Index(PSQI), the Patient Health Questionnaire-9(PHQ-9), and the Generalized Anxiety Disorder Questionnaire-7(GAD-7)were used for the survey.The sleep quality and the influence of depression and anxiety on sleep quality of 955 community-dwelling older adults aged 60 and above were investigated.Results:The detection rate of sleep disorders, depression and anxiety were 24.5%, 19.1% and 14.3%, respectively.There was a positive correlation between sleep quality scores(including the total score and the scores of each dimension)and the anxiety and depression scores( rs: 0.115-0.558, P<0.01 for all). After adjusting for possible confounding effects of gender, age, food intake or tea drinking before bed, Logistic regression analysis showed that the presence of depression( OR=3.555, 95% CI: 2.235-5.653, P<0.05)and anxiety( OR=1.812, 95% CI: 1.070-3.070, P<0.05)were significantly related to sleep disorders in the elderly.The multivariate adjusted population attributable risk of depression and anxiety for sleep disorders in the elderly was 32.56% and 16.09%, respectively.The presence of depression and anxiety were associated with 38.87% of the population attributable risk for sleep disorders. Conclusions:Depression and anxiety are important risk factors for sleep disorders in the elderly.Strengthening the identification and intervention of depression and anxiety is beneficial to improve the sleep quality of elderly living in the community.

OBJECTIVE: To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies. METHODS: The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated. RESULTS: A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027). CONCLUSION The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/complications* ; Leukemia, Plasma Cell ; Retrospective Studies ; Esophageal Neoplasms/complications* ; Esophageal Squamous Cell Carcinoma/complications* ; Prognosis ; Neoplasms, Second Primary

OBJECTIVE: To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft. RESULTS: There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3⁺ cells, CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells, NK cells and CD14⁺ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4⁺CD25⁺ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078). CONCLUSION High number of CD34⁺ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3⁺ cells, CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells, NK cells and CD14⁺ cells tend to increase the occurrence of aGVHD, but high number of CD4⁺CD25⁺ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; CD4-Positive T-Lymphocytes ; Leukemia, Myeloid, Acute/complications* ; Graft vs Host Disease

OBJECTIVE: To compare the clinical characteristics of children with hemophagocytic lymphocytosis (HLH) associated with primary Epstein-Barr virus (EBV) infection and EBV reactivation, and explore the effects of different EBV infection status on the clinical indexes and prognosis of HLH. METHODS: The clinical data of 51 children with EBV associated HLH treated in Henan Children's Hospital from June 2016 to June 2021 were collected. According to the detection results of plasma EBV antibody spectrum, they were divided into EBV primary infection-associated HLH group (18 cases) and EBV reactivation-associated HLH group (33 cases). The clinical features, laboratory indexes and prognosis of the two groups were analyzed and compared. RESULTS: There were no significant differences in age, gender, hepatomegaly, splenomegaly, lymphadenopathy, neutrophil count in peripheral blood, hemoglobin content, platelet count, plasma EBV-DNA load, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, albumin, fibrinogen, triglyceride, ferritin, hemophagocytosis in bone marrow, NK cell activity and sCD25 between the two groups(P>0.05). The central nervous system involvement and CD4/CD8 in EBV reactivation-associated HLH group were significantly higher than those in primary infection-associated HLH group, but the total bilirubin was significantly lower than that in primary infection-associated HLH group (P<0.05). After treatment according to HLH-2004 protocol, the remission rate, 5-year OS rate and 5-year EFS rate of patients in EBV reactivation-associated HLH group were significantly lower than those in EBV primary infection-associated HLH group (P<0.05). CONCLUSION EBV reactivation-associated HLH is more likely to cause central nervous system involvement and the prognosis is worser than EBV primary infection-associated HLH, which requires intensive treatment.
Child ; Humans ; Epstein-Barr Virus Infections/complications* ; Lymphohistiocytosis, Hemophagocytic/complications* ; Herpesvirus 4, Human ; Retrospective Studies ; Prognosis

OBJECTIVE: To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML). METHODS: The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed. RESULTS: Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified). CONCLUSION D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.
Aged ; Male ; Female ; Humans ; Aged, 80 and over ; Decitabine/therapeutic use* ; Retrospective Studies ; Cytarabine/therapeutic use* ; Prognosis ; Mutation ; Leukemia, Myeloid, Acute/genetics*