Objective To investigate the therapeutic effect of dental pulp stem cells(DPSCs)on autoimmune hepatitis in in vivo and in vitro experiments and the related mechanism.Methods An in vitro co-culture system was used to evaluate the immunoregulatory effect of DPSCs,and 32 mice were randomly divided into healthy control group,model group,positive drug group,and DPSCs treatment group,with 8 mice in each group.The serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and inflammatory factors were measured,and HE staining was used to assess liver pathological injury.An analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results The in vitro experiment showed that the positive rates of CD105,CD73,and CD90 in DPSCs were 99.97%,100%,and 99.53%,respectively,while the positive rates of CD34,HLA-DR,and CD45 were 0.56%,0.17%,and 0,respectively.DPSCs significantly inhibited the proliferation of Th1 and Th17 subsets,with inhibition rates of 31.32%and 45.76%,respectively;DPSCs promoted the proliferation of Treg(CD4+CD25+FoxP3+),with a promoting rate of 52.29%.DPSCs had an inhibition rate of 93.70%on the proliferation of lymphocytes.In the mouse model of autoimmune hepatitis,compared with the model group,the DPSCs treatment group had significant reductions in the serum levels of ALT and AST,with reduction rates of 66.8%and 60.0%,respectively(t=3.321 and 2.907,P=0.007 5 and 0.017 5)and significant reductions in the inflammatory factors tumor necrosis factor-α and interleukin-1β,with reduction rates of 57.5%and 71.3%,respectively(t=2.484 and 2.796,P=0.039 8 and 0.020 6),and histopathological examination showed no significant improvement in periportal bridging necrosis(t=1.969,P=0.098).Conclusion DPSCs effectively alleviate immune-mediated liver injury through immunoregulation,which provides an experimental basis for clinical translation.

Objective To investigate the therapeutic effect of dental pulp stem cells(DPSCs)on autoimmune hepatitis in in vivo and in vitro experiments and the related mechanism.Methods An in vitro co-culture system was used to evaluate the immunoregulatory effect of DPSCs,and 32 mice were randomly divided into healthy control group,model group,positive drug group,and DPSCs treatment group,with 8 mice in each group.The serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and inflammatory factors were measured,and HE staining was used to assess liver pathological injury.An analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results The in vitro experiment showed that the positive rates of CD105,CD73,and CD90 in DPSCs were 99.97%,100%,and 99.53%,respectively,while the positive rates of CD34,HLA-DR,and CD45 were 0.56%,0.17%,and 0,respectively.DPSCs significantly inhibited the proliferation of Th1 and Th17 subsets,with inhibition rates of 31.32%and 45.76%,respectively;DPSCs promoted the proliferation of Treg(CD4+CD25+FoxP3+),with a promoting rate of 52.29%.DPSCs had an inhibition rate of 93.70%on the proliferation of lymphocytes.In the mouse model of autoimmune hepatitis,compared with the model group,the DPSCs treatment group had significant reductions in the serum levels of ALT and AST,with reduction rates of 66.8%and 60.0%,respectively(t=3.321 and 2.907,P=0.007 5 and 0.017 5)and significant reductions in the inflammatory factors tumor necrosis factor-α and interleukin-1β,with reduction rates of 57.5%and 71.3%,respectively(t=2.484 and 2.796,P=0.039 8 and 0.020 6),and histopathological examination showed no significant improvement in periportal bridging necrosis(t=1.969,P=0.098).Conclusion DPSCs effectively alleviate immune-mediated liver injury through immunoregulation,which provides an experimental basis for clinical translation.

Objective: To investigate the seroprevalence and influencing factors of serum neutralizing antibodies among SARS-CoV-2 infected individuals, so as to provide the evidence for developing the health management and COVID-19 vaccination strategy among SARS-CoV-2 infected individuals. Methods: Recovered SARS-CoV-2 infected individuals from January 1st, 2020 to February 10th, 2021 in Zhejiang Province were recruited in March 2021. Participants' demographics, underlying diseases, date of definitive diagnosis and severity of clinical symptoms were collected using questionnaire surveys, and serum neutralizing antibody against SARS-CoV-2 was detected using a fluorescent immunoassay. In addition, factors affecting the seropositivity of neutralizing antibody against SARS-CoV-2 were identified using a multivariable logistic regression model. Results: A total of 559 SARS-CoV-2 infected individuals were enrolled, including 480 confirmed cases and 79 asymptomatic carriers, with an median (interquartile range) age of 47.00 (22.00) years, and all participants had never received COVID-19 vaccination. The median (interquartile range) duration from diagnosis to serum sampling was 387.00 (11.00) days, and the seroprevalence of neutralizing antibody against SARS-CoV-2 was 83.90%. The serum neutralizing antibody against SARS-CoV-2 was all positive 9 months after diagnosis, and the seroprevalence of neutralizing antibody against SARS-CoV-2 appeared no tendency towards a decline with time within 14 months after diagnosis (P>0.05). Multivariable logistic regression analysis showed that women were 1.892 times (95%CI: 1.169-3.064) more likely to produce serum neutralizing antibodies against SARS-CoV-2 than men, and mild, common and severe/critically ill SARS-CoV-2 infected cases were 2.438 (95%CI: 1.305-4.557), 4.481 (95%CI: 2.318-8.663), and 23.525 (95%CI: 2.990-185.068) times more likely to produce serum neutralizing antibodies against SARS-CoV-2 than asymptomatic carrier, respectively. Conclusions The seroprevalence of neutralizing antibody was 100.00% among SARS-CoV-2 infected individuals within 9 months after diagnosis. Individuals' gender and severity of clinical symptoms correlate with the seroprevalence of neutralizing antibody against SARS-CoV-2.

Objective:To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors.Methods:Ninety-one cases of Wilms tumor diagnosed at Shanghai Children′s Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016."Results:The specimens were obtained by core biopsy ( n=21), primary nephrectomy ( n=41), post-chemotherapy nephrectomy/resection ( n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) ( n=11). The specimens of core biopsy and primary nephrectomy ( n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk ( n=0), intermediate risk ( n=10) and high risk ( n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk ( n=0), intermediate risk ( n=5) and high risk ( n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions:The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.

Objective To investigate the effect of sub-anesthesia dose of isoflurane in 60％ oxygen on acute lung injury in aged rats with sepsis.Methods Ninety male Sprague-Dawley rats,aged 12-14 months,weighing 500-800 g,were divided into 3 groups (n=30 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis plus isoflurane plus oxygen treatment group (S+I+O group).Sepsis was induced by cecal ligation and puncture in S and S+I+O groups.In group S+I+O,0.7％ isoflurane in 60％ oxygen was inhaled for 1 h starting from 1 and 6 h after operation.Eighteen rats were selected in each group and observed for 7 days after operation,and the survival rate was recorded.Six rats were selected in each group at 24 h after operation,and bronchoalveolar lavage fluid (BALF) was collected to determine the protein concentrations (by BCA protein assay),blood samples were collected from the femoral artery for blood gas analysis,PaO2 was recorded,and the oxygenation index was calculated.Six rats in each group were sacrificed at 24 h after operation,the left lung specimens were obtained and stained with hematoxylin and eosin for examination of pathological changes,the right lung specimens were obtained for determination of wet to dry weight ratio (W/D ratio),and blood samples were collected from the right atrium for measurement of the concentrations of interleukin-1β (IL-1β),IL-6,tumor necrosis factor-α (TNF-α),high-mobility group box 1 protein (HMGB1) and IL-10 in serum (by enzyme-linked immunosorbent assay).Results Compared with group Sham,the survival rate was significantly decreased,and the concentrations of IL-1β,IL-6,TNF-α,HMGB1 and IL-10 in serum were increased in S and S+I+O groups,and W/D ratio and protein concentrations in BALF were significantly increased,and the oxygenation index was decreased in group S (P＜0.05).Compared with group S,the survival rate was significantly increased,W/D ratio and protein concentrations in BALF were decreased,the oxygenation index was increased,the concentrations of IL-1β,IL-6,TNF-α and HMGB1 in serum were decreased,and the concentration of serum IL-10 was increased (P＜0.05),and the pathological changes were significantly attenuated in group S+I+O.Conclusion Sub-anesthesia dose of isoflurane in 60％ oxygen can reduce acute lung injury in aged rats with sepsis,and the mechanism may be ralated to inhibiting systemic inflammatory responses.