Objective:To investigate the plasma level of interleukin(IL)-37 and assess its regulatory effects on monocyte activity in type 1 diabetes mellitus(T1DM) patients.Methods:This prospective study included 57 T1DM patients and 21 healthy controls who were continuously enrolled from December 2022 to January 2024 at Xinxiang Central Hospital. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble interleukin 1 receptor 8(IL-1R8) levels were measured by enzyme-linked immunosorbent assay(ELISA). Levels of IL-37 receptor subunits in monocytes were analyzed via flow cytometry. Purified monocytes were stimulated with recombinant IL-37 and co-cultured with a human pancreatic β-cell line to assess cytotoxicity, measured by target cell death and cytokine levels. Additionally, monocytes were co-cultured with autologous CD4 + T cells to evaluate antigen presentation by measuring interferon-γ(IFN-γ) and IL-17A secretion. Results:Plasma IL-37 level and IL-37 receptor subunit expression in monocytes were significantly lower in T1DM patients compared to controls(both P<0.001). However, there was no significant difference in soluble IL-1R8 levels between the groups( P=0.457). Monocytes from T1DM patients exhibited increased cytotoxicity, as indicated by higher target cell death and elevated levels of granzyme A, granzyme B, granzyme H, IL-1β, IL-6, and tumor necrosis factor-α( P<0.05). Additionally, monocyte-induced secretion of IFN-γ and IL-17A by CD4 + T cells was elevated in T1DM patients(all P<0.05). Stimulation of T1DM monocytes with recombinant IL-37 reduced target cell death and decreased granzyme B secretion compared to unstimulated monocytes(both P<0.05). However, IL-37 stimulation had no significant effect on other cytokine levels or monocyte-induced IFN-γ and IL-17A secretion( P>0.05). Conclusions:Monocytes exhibit enhanced cytotoxicity and antigen-presenting capacity in T1DM patients. IL-37 reduces monocyte cytotoxicity by inhibiting granzyme B secretion, but does not affect antigen presenting function in T1DM.

Objective:To investigate the plasma level of interleukin(IL)-37 and assess its regulatory effects on monocyte activity in type 1 diabetes mellitus(T1DM) patients.Methods:This prospective study included 57 T1DM patients and 21 healthy controls who were continuously enrolled from December 2022 to January 2024 at Xinxiang Central Hospital. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble interleukin 1 receptor 8(IL-1R8) levels were measured by enzyme-linked immunosorbent assay(ELISA). Levels of IL-37 receptor subunits in monocytes were analyzed via flow cytometry. Purified monocytes were stimulated with recombinant IL-37 and co-cultured with a human pancreatic β-cell line to assess cytotoxicity, measured by target cell death and cytokine levels. Additionally, monocytes were co-cultured with autologous CD4 + T cells to evaluate antigen presentation by measuring interferon-γ(IFN-γ) and IL-17A secretion. Results:Plasma IL-37 level and IL-37 receptor subunit expression in monocytes were significantly lower in T1DM patients compared to controls(both P<0.001). However, there was no significant difference in soluble IL-1R8 levels between the groups( P=0.457). Monocytes from T1DM patients exhibited increased cytotoxicity, as indicated by higher target cell death and elevated levels of granzyme A, granzyme B, granzyme H, IL-1β, IL-6, and tumor necrosis factor-α( P<0.05). Additionally, monocyte-induced secretion of IFN-γ and IL-17A by CD4 + T cells was elevated in T1DM patients(all P<0.05). Stimulation of T1DM monocytes with recombinant IL-37 reduced target cell death and decreased granzyme B secretion compared to unstimulated monocytes(both P<0.05). However, IL-37 stimulation had no significant effect on other cytokine levels or monocyte-induced IFN-γ and IL-17A secretion( P>0.05). Conclusions:Monocytes exhibit enhanced cytotoxicity and antigen-presenting capacity in T1DM patients. IL-37 reduces monocyte cytotoxicity by inhibiting granzyme B secretion, but does not affect antigen presenting function in T1DM.

Objective:To conduct interviews from the perspective of caregivers of children with autism spectrum disorders (ASD) and to conduct a multi-level and multi-dimensional strategy to provide help for families of children with ASD by exploring the experience of oral health care of such children.Methods:Using the purposive sampling method, a total of 11 family caregivers of children with ASD aged 12 and below who visited Outpatient Department of Pediatric Dental Prevention in Affiliated Stomatological Hospital of Nanjing Medical University from May 2020 to May 2021 were selected for semi-structured interviews. The subject was finally determined using Colaizzi's 7-step analysis method and assisted by Nvivo 12 software.Results:The current situation of oral care for children with ASD had three themes, namely, caregiver emotion, care dilemma and needs.Conclusions:More attention should be paid to the mental health of family caregivers with ASD. The oral health of children with ASD not only needs family caregivers, but also needs the common attention and support of the whole society, including multi-disciplinary and multi-department, to provide effective oral health management programs for children with ASD, so as to promote the oral health of this group of children.

Objective:To explore the effect of recombinant human syntaxin-4(STX4) on lipopolysaccharide(LPS)-induced injury in islet β-cells(INS-1).Methods:Pancreatic islet β-cells(INS-1) were divided into Control (blank control), LPS (LPS treatment), LPS+ NC (transfection of negative control vector, LPS treatment), and LPS+ STX4 (transfection of pcDNA-STX4, LPS treatment) groups. RT-qPCR and Western blot were used to detect STX4 mRNA and protein expression, flow cytometry to detect apoptosis, DCFHDA method to detect reactive oxygen species(ROS) level, xanthine oxidation method to detect superoxide orgotein dismutase(SOD) level, colorimetric method to detect glutathione peroxidase(GSH-Px) level, ammonium molybdate colorimetric method to detect catalase(CAT) level, thiobarbituric acid method to detect malonaldehyde(MDA) level, ELISA method to detect the level of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and insulin secretion levels under glucose conditions secreted by cells, Western blot method to detect Cleared Caspase-3, Bcl-2 Associated X Protein(Bax), p65 protein expression. After treatment with NF-κB signaling pathway activator, STX4 up-regulated islet β-cell INS-1 was given LPS stimulation, and the same method was used to measure apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α, insulin levels and Cleaved Caspase-3, Bax, p65 protein levels.Results:Compared with the Control group, the expression of STX4 mRNA and protein in islet β cells of the LPS group decreased, the apoptosis rate, ROS level, and MDA levels increased, and the levels of SOD, GSH-Px, and CAT decreased, the levels of IL-1β, TNF-α increased, the level of insulin secreted by the cells decreased, and the expression levels of Cleaved Caspase-3, Bax, and p65 also increased. NF-κB pathway activator treatment reversed the effect of up-regulated STX4 on islet β-cell apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α levels, and Cleaved Caspase-3 , Bax and p65 protein levels.Conclusion:Up-regulation of STX4 alleviated LPS-induced islet β cell oxidative damage, apoptosis and inflammatory factor release. The underlying mechanism might be related to the inhibition of activated NF-κB signaling pathway.

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 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 measure the distance of the lateral, inferior, and superior microfoci from a gross tumor in a pathological speci-men and to provide scientific evidence for margin extension to form the clinical target volume (CTV) in high-dose radiotherapy for rec-tal cancer. Methods: Twenty-eight surgical specimens were collected from patients with rectal cancer who underwent total mesorectal excision (TME) in Hunan Cancer Hospital between October 2016 and April 2017. The nearest distance of the farthest peripheral micro-foci from the gross tumor was measured. The in vivo-in vitro tumor retraction factor (R1) was calculated by measuring the ratio of the tumor's perpendicular depth based on magnetic resonance imaging and immediate surgical specimens. The retraction factor (R2) in the process of pathological specimen makeup was calculated by knot labeling. The distance of microfoci extension was calculated based on that measured in pathological specimens including corrections with R1 and R2 and record as microcarcinoma extension mea-sured in vivo,MEin vivo. Results: Among the 28 pathological specimens, lateral, inferior, and superior microfoci were found in 17 (60.7%), 3 (10.7%), and 0 cases, respectively. The mean R1 was 0.913 and mean R2 was 0.803. The farthest distance measured inferiorly was 28 mm in vivo after correction. The maximum, minimum, and mean measured lateral distances were 12.03 mm, 3.03 mm, and 7.50 mm after correction, respectively. The 95% frequency value was within 10 mm. Conclusions: The lateral microfoci extension was within 10 mm for 95% of the rectal cancer patients. The margin expansion to form the CTV was suggested to be 10 mm for a late-course boost of high-dose radiotherapy for rectal cancer.

Objective: To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection. Methods: A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve. Results: Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2–5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log₁₀ IU/ml and (3.95 + 0.40) log₁₀ IU/ml; t = 8.465, P < 0.001). Conclusion Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.