The innate immune response is the first line of defense for the host against viral infections. Targeted degradation of pathogenic microorganisms through autophagy, in conjunction with pattern recognition receptors synergistically inducing the production of interferon (IFN), constitutes an important pathway for the body to resist viral infections. Rubicon, a Run domain Beclin 1-interacting and cysteine-rich domain protein, has an inhibitory effect on autophagy and IFN production. On the one hand, Rubicon, as a component of the phosphoinositide 3-kinase (PI3K) complex, interacts with different domains of vacuolar protein sorting 34 (Vps34), ultraviolet radiation resistance associated gene (UVRAG), guanosine triphosphate (GTP) kinase, and RAS oncogene family member 7 (Rab7) to mediate the inhibition of autophagy maturation; on the other hand, Rubicon inhibits the ubiquitination of nuclear factor κB essential modulator (NEMO) and the dimerization of interferon regulatory factor 3 (IRF3), thereby blocking the signal transduction related to IFN production. Research has revealed that various viruses, such as Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), Sendai virus (SeV), and hepatitis C virus (HCV), achieve innate immune evasion by regulating the expression or function of Rubicon. Rubicon is expected to be a new target for antiviral therapy.
Humans ; Autophagy/immunology* ; Immunity, Innate ; Interferons/immunology* ; Immune Evasion ; Animals ; Virus Diseases/virology* ; Signal Transduction ; Viruses/immunology* ; Intracellular Signaling Peptides and Proteins/immunology* ; Autophagy-Related Proteins

OBJECTIVE: To analyze the significance of total vitamin D (tVD), total procollagen type I amino-terminal propeptide (tPINP) and β-CrossLaps (β-CTx) in the staging and prognosis of patients with multiple myeloma (MM). METHODS: A total of 54 patients with newly diagnosed MM admitted to the Second Affiliated Hospital of Fujian Medical University from 2020 to 2022 were selected as the observation group (MM group), and 50 healthy persons who underwent physical examinations in our hospital were selected as the control group. The expression levels of tVD, tPINP and β-CTx in the two groups were detected by chemiluminescence method. The differences in the expression levels of tVD, tPINP and β-CTx among MM patients at different ISS stages were analyzed. The expression levels of tVD, tPINP and β-CTx in MM patients with different levels of hemoglobin (Hb), serum calcium (Ca), creatinine (Crea), albumin (ALB), β₂-microglobulin (β₂-MG) and lactate dehydrogenase (LDH) were compared. The correlations between the expression levels of tVD, tPINP, β-CTx and the aforementioned clinical parameters were analyzed, respectively. The relationship between the expression levels of tVD, tPINP, β-CTx and the progression-free survival (PFS) of MM patients was analyzed. RESULTS: The expression level of tVD in the MM group was significantly lower than that in the control group (21.73±14.45 ng/ml vs 30.78±9.94 ng/ml, P =0.022). The expression level of β-CTx in the MM group was significantly higher than that in the control group (1.43±0.99 ng/ml vs 0.53±0.29 ng/ml, P =0.013). The tVD level in MM patients with ISS stage I-II was significantly higher than that of MM patients with ISS stage III (29.50±14.59 ng/ml vs 12.62±7.73 ng/ml, P =0.028), indicating that the higher the ISS stage, the lower the tVD level. The tPINP and β-CTx levels in MM patients with high Ca levels (>2.65 mmol/L) were significantly higher than those in patients with low Ca levels (≤2.65 mmol/L) (P =0.016, P =0.021). The tVD level of MM patients was positively correlated with the ALB level (r =0.570), tPINP was positively correlated with Ca and β₂-MG levels (r =0.791,r =0.673), and β-CTx was positively correlated with tPINP level (r =0.616). The PFS of the low tVD expression group was significantly lower than that of the high tVD expression group (P =0.041). CONCLUSION The expression level of tVD is decreased in MM patients, which can be used as an indicator to evaluate the disease stage and prognosis of the patients. The β-CTx expression level is increased in MM patients. tPINP and β-CTx may be correlated with clinical symptoms such as osteolytic lesions and renal function changes in MM patients.
Humans ; Multiple Myeloma/pathology* ; Procollagen/blood* ; Vitamin D/blood* ; Prognosis ; Peptide Fragments/blood* ; Collagen Type I/blood* ; Female ; Male ; Middle Aged ; Aged ; Neoplasm Staging

Objective To investigate the relationships of the expression of microRNA-487a-3p (miR-487a-3p) and A kinase-interacting protein 1 (AKIP1) mRNA in the endometrial cancer (EC) tissue with the patient survival within 5 years after surgery. Methods The EC tissue and adjacent normal tissue samples were collected from 130 EC patients who underwent surgical treatment at the Fourth Hospital of Shijiazhuang from September 2016 to April 2019.qRT-PCR was employed to determine the expression levels of miR-487a-3p and AKIP1 mRNA.The patients were followed up for 5 years after surgery to record the survival status.After removal of the patients who missed follow-up,78 surviving patients were recorded as the EC survival group,and 34 deceased patients were recorded as the EC death group.The dual luciferase reporter gene assay was conducted to verify the targeting relationship between miR-487a-3p and AKIP1 mRNA.Comparison was conducted for the expression levels of miR-487a-3p and AKIP1 mRNA between adjacent normal tissue and EC tissue,the expression levels of miR-487a-3p and AKIP1 mRNA in the EC tissue among patients with different clinical pathological parameters,and the clinical pathological parameters and the expression levels of miR-487a-3p and AKIP1 mRNA in the EC tissue between the EC survival group and the EC death group.The correlations of miR-487a-3p and AKIP1 mRNA levels in the EC tissue with the degree of tumor differentiation,International Federation of Gynecology and Obstetrics (FIGO) stage,lymph node metastasis,and depth of muscle invasion were analyzed.The relationships of miR-487a-3p and AKIP1 mRNA with patient prognosis and the risk factors affecting the survival of EC patients within 5 years after surgery were analyzed to evaluate the value of miR-487a-3p and AKIP1 mRNA levels in predicting the survival of EC patients within 5 years after survival. Results The EC tissue showed lower miR-487a-3p level (0.41±0.08 vs. 1.00±0.05;t=71.306,P<0.001) and higher AKIP1 mRNA level (2.35±0.37 vs. 1.00±0.03;t=41.465,P<0.001) than the adjacent normal tissue.The miR-487a-3p low expression group and AKIP1 mRNA high expression group had higher proportions of patients with low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,and deep invasion of muscle layer than the miR-487a-3p high expression group and AKIP1 mRNA low expression group,respectively (all P<0.05).The results of dual luciferase reporter gene assay showed that the relative activity of luciferase in the miR-487a-3p small interfering RNA (siRNA)+AKIP1 mRNA-wild type (WT) group was higher than that in the miR-487a-3p empty vector+AKIP1 mRNA-WT group (2.85±0.19 vs. 1.00±0.04;t=23.339,P<0.001).There was no significant difference in the relative activity of luciferase between the miR-487a-3p empty vector+AKIP1 mRNA-mutant type (MUT) group and the miR-487a-3p siRNA+AKIP1 mRNA-MUT group (1.04±0.05 vs. 1.05±0.03;t=0.420,P=0.683).MiR-487a-3p in the EC tissue had negative correlations with AKIP1 mRNA,FIGO stage,lymph node metastasis,and depth of muscle invasion and a positive correlation with the degree of tumor differentiation (all P<0.001).AKIP1 mRNA had positive correlations with FIGO stage,lymph node metastasis,and depth of muscle invasion and a negative correlation with the degree of tumor differentiation (all P<0.001).The 5-year overall survival rates in the miR-487a-3p high expression group and AKIP1 mRNA low expression group (89.47% and 84.91%) were higher than those in the miR-487a-3p low expression group and AKIP1 mRNA high expression group (49.09% and 55.93%),respectively (both P<0.05).The EC death group had higher proportions of patients with low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,and deep invasion of muscle layer,higher AKIP1 mRNA level in the EC tissue,and lower miR-487a-3p level than the EC survival group (all P<0.05).Low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,deep invasion of muscle layer,low miR-487a-3p level,and high AKIP1 mRNA level were independent risk factors for the survival of EC patients within 5 years after surgery (all P<0.05).The area under curve (AUC) values of miR-487a-3p and AKIP1 mRNA alone (0.785 and 0.789,respectively) were lower than that of their combination (0.908) in predicting the survival of EC patients within 5 years after surgery (both P<0.05). Conclusion The EC tissue has a low miR-487a-3p level and a high AKIP1 mRNA level,both of which are correlated with clinicopathological parameters and prognosis and can be used to predict the survival of EC patients within 5 years after surgery.
Humans ; Female ; Endometrial Neoplasms/pathology* ; MicroRNAs/genetics* ; RNA, Messenger/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Middle Aged ; Survival Rate ; Nuclear Proteins

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Objective To identify the sets of lymphocytes that could systematically evaluate immune function of colorectal cancer patients, based on the expression of colorectal cancer T cells, natural killer (NK) cells, and NKT cell surface protein receptors. Methods Peripheral blood samples from 144 patients with colorectal cancer and 87 healthy controls were collected, and the differences in surface receptors of lymphocyte subsets in peripheral blood of patients and healthy controls were analyzed by means of flow cytometry and cell culture. Results Compared with healthy control group, the percentage of peripheral blood total lymphocytes, CD16^brightCD56^dimNK cells and NKT cells decreased in patients with colorectal cancer. The percentage of T cells, CD16^brightCD56^dimNK cells and NKT cell surface inhibitory receptors T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitor motif domains (TIGIT) increased; T cells, NK cells, NKT cell surface chemokine receptor C-C motif chemokine receptor 7 (CCR7) slightly decreased. Conclusion There are differences in the proportion of NK cell subsets and the expression profile of surface receptors in peripheral blood of patients with colorectal cancer.
Humans ; Lymphocyte Subsets ; Killer Cells, Natural ; Lymphocyte Count ; Receptors, Chemokine ; Colorectal Neoplasms

OBJECTIVE: To observe the variability of hemoglobin (HB) level in patients with renal anemia, and to analyze its relationship with effect of repeated blood transfusion therapeutic in patients. METHODS: A retrospective cohort study and propensity score matching method were used, 60 patients with renal anemia who had effective treatment with repeated blood transfusion in Changzhou No.2 People's Hospital from May 2018 to May 2021 were retrospectively analyzed and set as the effective group; 153 patients with renal anemia who had ineffective treatment with repeated blood transfusion in the hospital in the same period were collected and set as the ineffective group, the propensity score matching method was used, the patients who were effective and ineffective in repeated blood transfusion were matched 1∶1 for analysis; the medical records and laboratory indexes of the two groups were checked; the Hb level of patients within 6 months (1/month) were recorded, the residual standard deviation (Res-SD) of Hb of patients was calculated according to the Hb level and evaluated the variability of Hb level; the relationship between HB variability level and therapeutic effect of repeated blood transfusion in patients with renal anemia was analyzed. RESULTS: After propensity score matching, there was no statistical significant difference between the two groups in terms of baseline data such as age, sex, dialysis age and BMI (P>0.05). The levels of serum albumin and transferrin of patients in the ineffective group were significantly lower than those of patients in the effective group (P<0.05); at 1 and 2 months of the observation period, there was no statistical significant difference in Hb levels of patients in both groups (P>0.05); the Hb level of patients in the ineffective group was significantly lower than that of patients in the effective group at 3, 5 and 6 months, and significantly higher than that of patients in the effective group at 4 months (P<0.05); the Res-SD of male patients and female patients in the ineffective group were respectively significantly higher than that of male patients and female patients in the effective group (P<0.05). Logistic regression analysis results showed that high variability of Hb level (Res-SD) was a risk factor for the ineffective treatment of repeated blood transfusion in patients with renal anemia (OR>1, P<0.05); the decision curve results showed that, when the high-risk threshold was 0.0-1.0, Res-SD predicted the net benefit rates of male and female patients with renal anemia were greater than 0, which was clinically significant, the smaller the high-risk threshold in the above range, the greater the net benefit rate. CONCLUSION The therapeutic effect of repeated blood transfusion in patients with renal anemia may be related to the variability of Hb level.
Humans ; Male ; Female ; Retrospective Studies ; Hemoglobins/therapeutic use* ; Anemia/therapy* ; Chronic Disease ; Blood Transfusion ; Kidney Diseases

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis. METHODS: 20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc. during the patient's initial diagnosis, the relationship between the patient's prognosis and CD47 was evaluated. RESULTS: The expression of CD47 in bone marrow (P=0.0115) and peripheral blood mononuclear cells (P=0.0069) in new diagnosis AML patients was significantly higher than that of controls. In bone marrow mononuclear cells, the total survival time of patients with high CD47 expression was less than that of CD47 low expression patients (P=0.036). There was statistical significance in difference stratification group (P=0.012), but there was no statistical significance between CD47 expression and survival time in peripheral blood mononuclear cells (P=0.116). There were no statistical significance between bone marrow mononuclear cell CD47 expression and gene mutation fusion genes related to leukemia , CD34⁺, CD38⁺, CD123⁺ (P>0.05). The proportion of bone marrow protocells in AML patients was >50%, the ECOG score was >2 points, MLLELL fusion gene and chromosome prognosis stratification were all risk factors affecting the survival of patients (P=0023, 0.036, 0.012, 0.001, respectively). The high expression of bone marrow CD47 in AML patients indicated a high risk of recurrence (P=0.017). CONCLUSION The high expression of bone marrow mononuclear cell CD47 in AML patients indicates poorer survival and higher risk of recurrence.
Adult ; CD47 Antigen ; China ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Leukocytes, Mononuclear/pathology* ; Prognosis

OBJECTIVE: To explore the hematopoiesis protection effect of Danggui Buxue Tang (DBT) and its main components Angelica polysaccharide (APS) and Astragalus polysaccharide (ASPS) on myelosuppression mice, and the mechanism of anti-apoptosis of Meg-01 cells. METHODS: Mice were radiated with 4 Gy of ¹³⁷Csγ ray to establish the model of radiation-induced myelosuppression. DBT, APS or ASPS (10 mg/kg) were injected into irradiated mice. Peripheral blood cell counts were performed on mice before radiation (day 0) and day 7, 14 and 21 after radiation. On the 21st day, poor plasma platelets were collected from mice to detect TPO concentration and then the mice were sacrificed. The femoral bone marrow cells were cultured for colony cell forming units (CFU). Meg-01 cells were cultured without FBS for 24 h to induce apoptosis, and then treated with DBT/APS/ASPS for 72 h. Flow cytometry (FCM) was used to detect early apoptosis (Annexin V), mitochondrial membrane potential (JC-1) and the expression of Caspase-3 to analyze the effect of DBT/APS/ASPS on cell apoptosis. RESULTS: DBT can stimulate the recovery of white blood cells (WBC), red blood cells (RBC) and platelets (PLT) of myelosuppression mice, especially for WBC and PLT (P<0.01, P<0.05). Compared with the control group, the number of BFU-E, CFU-MK and CFU-GM increased after adding DBT (BFU-E & CFU-GM: P<0.05； CFU-MK: P<0.01). The effect of DBT on blood TPO concentration in mice was not obvious (P=0.89). RBC, WBC and PLT were increased in APS group compared with control group (P<0.05). WBC increased after the treatment of ASPS (P<0.05). APS stimulated the formation of CFU-F, CFU-MK and CFU-GM (P<0.05). Only CFU-GM increased in ASPS group(P<0.05). Besides, DBT decreased the apoptosis of Meg-01 cells (P<0.05). The early apoptosis rate and total death rate in APS (100 μg/ml) group were lower than that of control group (P<0.01, P<0.05). The early apoptosis rate of ASPS (100 μg/ml) group was lower than that of control group (P<0.05). JC-1 and Caspase-3 showed that APS (100 μg/ml) significantly reduced apoptosis rate (P<0.01, P<0.05). CONCLUSION DBT has protective effect on hematopoietic system, especially WBC and PLT, and has anti-apoptotic effect on Meg-01. It was found that the above effects of DBT were mainly caused by APS, and its anti-apoptosis mechanism was carried out mainly through JC-1 and Caspase-3 pathways.
Mice ; Animals ; Caspase 3 ; Bone Marrow ; Polysaccharides

OBJECTIVE: To investigate the efficacy and safety of VDZ (Vedolizumab) in the salvage treatment of glucocorticoid resistance to gastrointestinal graft-versus-host disease (GR-GI GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: The clinical data of 5 patients with refractory GI GVHD who received allo-HSCT in Wuhan Children's Hospital from December 2020 to December 2021 were retrospectively analyzed with VDZ salvage therapy. RESULTS: Among the 5 children with refractory GI GVHD, there were 1 male and 4 female, including 2 cases of extremely severe aplastic anemia, 1 case of acute myeloid leukemia (M2, high-risk), 1 case of fanconi anemia and 1 case of myelodysplastic syndrome. The median age of transplant recipients was 54.4 (12-164) months. The median treatment time from transplantation to VDZ was 1.4 (0.6-6.8) months. On average, 3.5 (2-5) doses of VDZ were received. After receiving treatment, 2 patients achieved a complete response (CR), 2 patients achieved a very good partial response (VGPR), 1 patient was non-responsive (NR) after a short-term partial response (PR). Compared with that before VDZ treatment, the amount of diarrhea, stool color, blood and traits of the children after medication were effectively improved. The median follow-up time was 9.3 (7.23-12.83) months. No disseminated or severe bacterial/fungal infections occurred during VDZ treatment and follow-up, and 2 children died of leukemia recurrence and pulmonary bronchiolitis obliterans. CONCLUSION VDZ salvage treatment of refractory GI GVHD in children has obvious short-term efficacy and good safety.
Child ; Humans ; Female ; Male ; Child, Preschool ; Salvage Therapy ; Glucocorticoids/therapeutic use* ; Retrospective Studies ; Graft vs Host Disease