Objective To investigate the effects of 5-fluorouracil (5-FU) on the distribution, pro-portion and immunosuppressive activities of myeloid-derived suppressor cells (MDSCs) in a mouse model of liver cancer.Methods Orthotopic transplantation of H22 cell line was performed to establish the mouse model of orthotopic liver cancer.Forty mice were randomly divided into four groups (n=10) on the 7th day after transplantation.Three different doses of 5-FU (10 mg/kg, 30 mg/kg and 50mg /kg) and 0.4 ml of PBS were respectively given to the mice in each group for 10 consecutive days .A control group without canc-er cell transplantation was set up correspondingly .The distribution of MDSCs in mice liver tissues was detec-ted by immunohistochemistry .The proportions of MDSCs in spleen tissues were tested by flow cytometry . The levels of IFN-γand Arginase-I ( Arg-I) in serum samples were analyzed by enzyme-linked immunosor-bent assay.The activities of nitric oxide synthetase (NOS) in serum samples were tested by chemical colori-metry.The proliferation of T lymphocytes was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltet-razolium bromide (MTT) test.Results 5-FU reduced the tumor size and alleviated the adhesion between liver tissues and abdominal cavity in mice with liver cancer in a dose-dependent manner .The proportions of MDSCs in liver and spleen tissues from mice in four model groups were significantly higher than those in con - trol group (P<0.05).The highest proportions of MDSCs were observed in PBS treated group , followed by 10 mg/kg of 5-FU treated group , 30 mg/kg of 5-FU treated group and 50 mg/kg of 5-FU treated group .Ex-cept for comparing between PBS treated group and 10 mg/kg of 5-FU treated group, there were significant differences with the proportions of MDSCs in liver tissues among other groups (P<0.05).The levels of Arg-I and the activities of NOS in mice with liver cancer were higher than those in control group (P<0.05).The mice in PBS treated group showed the highest level of Arg-I and the strongest activities of NOS that were de-creased as concentrations of 5-FU increased( P<0.05).The levels of IFN-γin serum samples from mice with liver cancer were lower than those in control group , and the lowest level was detected in PBS treated group.IFN-γlevels were increased as concentrations of 5-FU elevated.Except for comparing between PBS treated group and 10 mg/kg of 5-FU treated group , significant differences with the levels of IFN-γin serum samples (P<0.05) were observed among other groups .No significant differences with the proliferation of T cells were observed among all groups after 24 hours of culture (P>0.05),but that were decreased in model groups than those in control group after 48 hours of culture (P<0.05).T cells from mice in PBS treated group showed the lowest level of proliferation .T cell proliferation was enhanced upon the treatment of 5-FU in a dose-dependent manner .Except for comparing between PBS treated group and 10 mg/kg of 5-FU treated group, significant differences with T cell proliferation were observed among other groups (P<0.05).The proportions of MDSCs in liver and spleen tissues were positively correlated with the levels of Arg -I and the activities of NOS, but negatively correlated with IFN-γlevel and T cell proliferation at the time point of 48 h.Conclusion To a certain extent , 5-FU could reduce the numbers of MDSCs in liver and spleen tis-sues from mice with liver cancer , inhibit immunosuppressive activities of MDSCs and restrain the growth of the tumor in a dose-dependent manner .

Adolescent ; Adult ; Child ; Child, Preschool ; Electrocoagulation ; methods ; Female ; Humans ; Hypothermia, Induced ; Male ; Middle Aged ; Prospective Studies ; Tonsillectomy ; methods ; Young Adult

A clinical data, laboratory examination, genetic test results, diagnose and treatment of a patient with 46, XY disorders of sexual development (46, XY DSD) from a family of the Asp-Glu-Ala-His-box helicase 37 ( DHX37) gene mutation were retrospectively analyzed.The child was admitted in the Department of Genetics, Endocrinology and Metabolism, Jiangxi Children′s Hospital in June 2021.The DHX37 gene mutation was confirmed as a new pathogenic gene leading to 46, XY DSD in 2019.It is featured as autosomal dominant inheritance with incomplete externality.Its clinical manifestations are abnormal external genitalia, testicular degeneration insufficiency syndrome and gonadal insufficiency.This patient is the first 46, XY DSD case caused by the heterozygous variation of DHX37 gene c. 2020C>T (p.R674W) in China.This study can provide new ideas for diagnosis and treatment of 46, XY DSD children and reliable genetic evidence for family reproduction.

Objective:To analyze the epidemiological and clinical characteristics of respiratory syncytial virus (RSV) infection in children in Jiangsu Province from 2014 to 2023.Methods:The acute respiratory infection cases in children aged 0-14 years were selected from outpatient/emergency or inpatient departments in 2 surveillance sentinel hospitals, respectively, in Nanjing, Suzhou and Taizhou of Jiangsu from 1 July 2014 to 31 December 2023, and RSV nucleic acid test was conducted and the intensity of the RSV infection was accessed by WHO influenza epidemiological threshold method, and case information and clinical data were collected. χ2 test was used to compare the differences between groups, and the Bonferroni method was used for pairwise comparisons between groups. Results:In 4 946 cases of acute respiratory infections, the RSV positive rate was 8.21% (406/4 946), and the age M( Q1, Q3) of the cases was 1 (0, 3) years. The RSV positive rate was 10.92% (258/2 362) during 2014-2019 and 6.06% (118/1 948) during 2019-2023, the difference was significant ( χ2=31.74, P<0.001). RSV infection mainly occurred from October to March during 2014-2019, with the incidence peak in December and moderate or higher intensity. The seasonality of RSV infection was not obvious during 2019-2023, with low intensity. The RSV positive rate was highest in children in age group 0- years (17.85%, 151/846), and the positive rate declined gradually with age ( χ2=184.51, P<0.001). The RSV positive rate was higher in inpatient cases (9.84%, 244/2 480) than in outpatient/emergency cases (6.57%, 162/2 466) ( χ2=17.54, P<0.001). In the 155 RSV infection cases with complete clinical data, the clinical symptoms mainly included cough (99.35%, 154/155), fever (55.48%, 86/155), and shortness of breath (45.16%, 70/155). In the cases aged <6 months, the proportion of those with fever was low, but the proportion of those with shortness of breath, transferred to intensive care units, and receiving oxygen therapy were higher (all P<0.05). Children aged <6 months and those with underlying diseases were more likely to have severe RSV infection (all P<0.05). Conclusions:RSV infection in children in Jiangsu Province showed seasonal prevalence in winter from 2014 to 2019. Since 2020, the seasonal characteristics of the epidemic have changed, the epidemic period has been dispersed and the epidemic intensity has decreased. Infants <1 year old were at high risk for RSV infection, and those <6 months old and with underlying diseases might have severe infection.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
A549 Cells ; Animals ; Apoptosis Regulatory Proteins/immunology* ; DEAD Box Protein 58/immunology* ; Dogs ; HEK293 Cells ; Humans ; Influenza A Virus, H1N1 Subtype/immunology* ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/pathology* ; Proteolysis ; RAW 264.7 Cells ; Signal Transduction/immunology* ; THP-1 Cells ; TNF Receptor-Associated Factor 3/immunology* ; Ubiquitination/immunology* ; Viral Proteins/immunology*