OBJECTIVE: To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP). METHODS: The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test. RESULTS: A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR＝0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR＝0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR＝0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group. CONCLUSION The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.
Humans ; Middle Aged ; Blast Crisis/drug therapy* ; Homoharringtonine/therapeutic use* ; Decitabine/therapeutic use* ; Interferons/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Treatment Outcome

Objective: To evaluate the clinical characteristics, treatment response, and outcomes in patients with classical hairy cell leukemia (cHCL) and HCL variant (HCL-V). Methods: This is a retrospective case series study. Between January 2011 and December 2021, clinical data of 30 patients newly with diagnosed HCL at Peking Union Medical College Hospital were analyzed. The main outcome measures include clinical characteristics, treatment efficacy and survival. The Kaplan-Meier method was used for survival analysis. Results: Twenty-one cases of cHCL and 9 cases of HCL-v were included. The median age at diagnosis was 55.5 (range, 30-86) years, with the ratio of male to female 2.75∶1. The main clinical manifestations included fatigue in 11 cases (36.7%), abdominal distension in 7 cases (23.3%), and infection in 4 cases, while 8 cases were asymptomatic. Splenomegaly was reported in 24 cases (80.0%), including 7 (23.3%) with megalosplenia. The white blood cell count, lymphocyte count, and the proportion of peripheral hairy cells in HCL-v group were significantly higher than those in cHCL group, whereas the development of anemia, thrombocytopenia, and monocytopenia in cHCL group was more remarkable than that in HCL-v group (all P<0.05). The BRAF-V600E gene mutation was detected only in cHCL patients (11/14 vs. 0/9, P<0.001). In terms of immunophenotype, the expression of CD25, CD103, CD123 and CD200 in cHCL group (20/20, 20/20, 4/7, 7/17) were all stronger than those in HCL-v group (3/9, 7/9, 0/4, 2/8). Twenty-two patients were treated, of which 13 cases (12 cases of cHCL and 1 case of HCL-v) with cladribine, and 9 cases (4 cHCL and 5 HCL-v) with interferon. Complete remission rate and overall response rate were comparable between cladribine and interferon treatment groups (both P<0.05). The median follow-up time was 31 (range, 1-125) months, and the median overall survival (OS) of the entire group was 125 months. The 5-year OS rate in HCL-v patients represented a trend of inferior (50.0% vs. 95.0%, P=0.207). Conclusions: The clinical features of HCL are unspecific, which includes fatigue, splenomegaly and recurrent infection. The clinical features, immunophenotype, treatment response and prognosis of HCL-v are different from those of cHCL. BRAF-V600E gene mutation is suggested as a key marker for differential diagnosis. Cladribine is recommended as front-line regimen of cHCL patients with satisfactory efficacy and prognosis. Conversely, response and clinical outcome in HCL-v patients still need to be improved.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Leukemia, Hairy Cell/drug therapy* ; Cladribine/therapeutic use* ; Splenomegaly/drug therapy* ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/therapeutic use* ; Prognosis ; Interferons/therapeutic use* ; Antineoplastic Agents/therapeutic use*

OBJECTIVE: To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival. METHODS: Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated. RESULTS: Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05). CONCLUSION IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Herpesvirus 4, Human ; Cytokines/metabolism* ; Epstein-Barr Virus Infections/complications* ; Interleukin-6 ; Clinical Relevance ; Interleukin-7 ; Interleukin-8 ; Interleukin-9 ; Chemokines ; Interferons

Human bocavirus is a novel pathogen first detected in respiratory tract samples in 2005. People of different ages can be infected by human bocavirus. Children are the susceptible population, especially the infants aged from 6-24 months old. The epidemic season varies in different regions due to the differences in climate and geographical location, and it mainly occurs in autumn and winter. It's demonstrated that human bocavirus-1 is closely related to respiratory system diseases and even causes life-threatening critical illness. Also, the severity of symptom is positively correlated with viral load. Co-infections between human bocavirus-1 and other viruses often present high frequency occurrence. Human bocavirus-1 interferes immune function of host by inhibiting interferon secrete pathway. Currently, it remains limited knowledge and understanding of the roles of human bocavirus 2-4 in diseases, but the gastrointestinal diseases should be paid more attention. Detection of human bocavirus DNA by traditional polymerase chain reaction (PCR) assay shouldn't be regarded as conclusive diagnostic basis. Instead, combined with mRNA and specific antigen detection, it is beneficial to improve the accuracy of diagnosis. Till now, the knowledge of human bocavirus remains poorly studied, which is deserved to further progress.
Infant ; Humans ; Child ; Child, Preschool ; Human bocavirus ; Climate ; Coinfection ; Epidemics ; Interferons

This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT ² profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 ( t = 10.58, P < 0.001), 5.59 ( t = 3.37, P = 0.028) and 10.83 ( t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
Humans ; Healthy Volunteers ; Hepatitis B, Chronic/genetics* ; Immunotherapy ; Interleukin-15 ; Leukocytes, Mononuclear ; Nuclear Proteins ; Oligonucleotide Array Sequence Analysis/methods* ; Interferons/therapeutic use* ; Treatment Outcome

OBJECTIVE: This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats. METHODS: The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA. RESULTS: APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05). CONCLUSION EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.
Rats ; Animals ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Electroacupuncture ; Pain, Postoperative ; Interferons

As a DNA receptor in the cytoplasm,cyclic GMP-AMP synthase (cGAS) can recognize abnormal DNA in the cytoplasm and activate stimulator of interferon genes (STING) to regulate the immune response. The recent studies have demonstrated that this pathway plays a role in non-infectious inflammatory diseases by promoting the expression of type Ⅰ interferon and interferon-stimulated gene.This article reviews the activation and regulation of cGAS-STING pathway in multiple systems and the effect of this pathway on the occurrence and progression of non-infectious inflammatory diseases,providing theoretical reference for future application of cGAS-STING pathway-related drugs in non-infectious inflammatory diseases.
Humans ; Interferons ; Membrane Proteins/metabolism* ; Noncommunicable Diseases ; Nucleotides, Cyclic ; Nucleotidyltransferases/metabolism* ; Signal Transduction

The inhibition of the host's natural immune response by tumor cells was widely reported in the early phases of the development of oncology therapy, and the concept of employing the host's immune system to treat cancer, i.e. tumor immunotherapy, is not new. However, as a result of early theoretical constraints, clinical application of immunotherapy did not go smoothly and lagged significantly behind radiation and chemotherapy. The path has been winding, but the future now seems promising. Immunotherapy research has advanced enormously as a result of the maturing of immuno-editing theory and the creation of numerous technologies, despite a number of unsuccessful endeavors and clinical studies. Since around 1998, the US Food and Drug Administration (FDA) has approved a variety of tumor immunotherapies, including cytokines (interleukin-2, interferons), cancer vaccines (Provenge), immune checkpoint inhibitors (ipilimumab), and cellular therapies (chimeric antigen receptor-T (CAR-T)), signaling a boom in the field.
Cancer Vaccines/therapeutic use* ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Interferons ; Interleukin-2/therapeutic use* ; Ipilimumab ; Neoplasms/pathology* ; Receptors, Chimeric Antigen

Objective: To analyze the clinical features and prognosis of patients with cutaneous melanoma. Methods: The clinical data and follow-up data of 125 patients with cutaneous malignant melanoma (CMM) treated in the Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology between February 2008 and August 2019 were collected. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox proportional risk regression model was used for impact factor analysis. Results: Among the 125 patients, 12 were stage Ⅰ, 62 were stage Ⅱ, 30 were stage Ⅲ, and 21 were stage Ⅳ; 76 were acral and 49 were non-acral. The median survival time was 44 months, and the 1-, 2-, and 5-year survival rates were 85.4%, 63.2% and 38.7%, respectively. Kaplan-Meier univariate survival analysis showed that Karnofsky performance status score, tumor stage, primary site, vascular infiltration, Ki-67, BRAF, lactate dehydrogenase (LDH), and surgical treatment were related to the prognosis of patients (P<0.05). The median overall survival (OS) time of patients receiving interferon treatment was 53 months, which was better than 40 months of patients not receiving interferon treatment, but the difference was not statistically significant (P=0.448). Among stage Ⅲ patients, the median OS time of patients receiving interferon therapy was 40 months, which was better than 17 months of patients not receiving interferon therapy (P=0.012). Among stage Ⅱ patients, the 1-, 2-, and 5-year survival rates of acral patients were 97.1%, 84.7%, and 65.8%, and the 1-, 2-, and 5-year survival rates of non-acral patients were 93.3%, 70.0% and 17.0%. The prognosis of patients with stage Ⅱ acral type was better than that of non-acral type (P=0.043). The median survival time of stage Ⅲ patients with acral type was 32 months, better than 17 months of non-acral type, but the difference was not statistical significance (P=0.164). The median survival time of acral type and non-acral type was 8 months and 11 months respectively (P=0.458). Cox multivariate analysis showed that tumor stage and preoperative LDH level were independent prognostic risk factors for cutaneous melanoma. Conclusions: Interferon treatment can improve the prognosis of patients with stage Ⅲ, and stage Ⅱ acral type patients have better prognosis than that of non-acral type patients. Tumor stage and preoperative LDH level were independent prognostic risk factors for cutaneous melanoma.
Humans ; Melanoma/surgery* ; Skin Neoplasms/pathology* ; Prognosis ; Interferons ; Retrospective Studies

Objective: To report the clinical features and genetic variations of monogenic lupus caused by DNASE1L3 deficiency and to introduce preliminary experience on diagnosis and treatment for this disease. Methods: Clinical data of 3 children from the same pedigree were collected who were diagnosed with DNASE1L3 defect-associated monogenic lupus in August 2020 by Department of Pediatrics, Peking Union Medical College Hospital referred from Department of Pediatrics, Boai Hospital of Zhongshan. DNA was extracted from the peripheral blood of the patients and their parients to perform genetic analysis and confirmation. Six interferon-stimulated genes were relatively quantified to examine the activation of the type I interferon signaling. "DNASE1L3" "systemic lupus erythematosus" and "SLE" were searched in PubMed, Wangfang Data, CNKI databases for related reports from database established date to June 2022. Spectrum of genetic variations and clinical phenotypes were analyzed in combination with this pedigree. Results: Case 1, a 14-year-old girl with edema, hematuria, and heavy proteinuria, presented with membranous nephropathy. Case 2, the 12-year-old younger brother of case 1 with hematologic, cardiac, pulmonary, renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody and low complement C3, manifested with systemic lupus erythematosus. Case 3, the 8-year-old younger sister of case 1 with hematologic, cardiac, pulmonary and renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody, and low complement C3 and C4, manifested with systemic lupus erythematosus. Genetic testing revealed that all 3 patients carried homozygous deletions in exons 3 and 4 on DNASE1L3 gene. Interferon scores were elevated in case 1, 2 and their parents but normal in case 3. All 3 patients were diagnosed with monogenic lupus caused by DNASE1L3 defects. Literature searching identified 10 relevant publications in English and 0 publication in Chinese, involving 42 patients from 18 pedigrees (including the 3 cases from this pedigree). Nine variants were found: c.289_290delAC (p.T97Ifs*2), c.643delT (p.W215Gfs*2), c.320+4delAGTA, c.321-1G>A, Ex5 del, c.433G>A, c.581G>A (p.C194Y), c.537G>A (p.W179X), and Ex3-4 del. The hotspot variants were c.643delT (43% (36/84)) and c.289_290delAC (36% (30/84)). Kidney was affected in 31 cases (74%) of the 42 cases. Among the 25 patients, joints were affected in 16 cases (64%), fever were reported in 13 cases (52%) hematologic system was involved 13 cases (52%), rash was present in 10 cases (40%), intestinal tract was involved in 8 cases (32%), lungs were involved in 6 cases (24%), eyes were involved in 4 cases (16%), and the heart was involved in 4 cases (16%). The 2 cardiopulmonary affected patients from literature showed poor prognosis, with 1 died, and 1 right heart failure. Conclusions: The clinical manifestations of monogenic lupus caused by DNASE1L3 defect are highly heterogenous, primarily with renal, blood, joint, intestinal, and cardiopulmonary involvement. There is no correlation between the genotype and the phenotype. DNASE1L3 defects were predominantly mediated by null varations including nonsense, splicing, frameshift and exon deletions. The hotspot variants are c.643delT and c.289_290delAC. DNASE1L3 defects should be cautioned in early-onset lupus-like patients with renal, joint and hematologic involvement. Cardiopulmonary involved patients require close monitoring for poor prognosis. Copy number variations should be carefully analyzed after negative whole exome sequencing.
Male ; Child ; Humans ; Homozygote ; Complement C3 ; Antibodies, Antinuclear ; DNA Copy Number Variations ; Sequence Deletion ; Interferons ; Lupus Erythematosus, Systemic/genetics* ; Antiviral Agents ; Endodeoxyribonucleases