Objective To analyze the seroepidemiology characteristics of Epstein-Barr virus(EBV)infection in children in Shenyang.Methods From June 2022 to May 2023,serum was collected from 12 083 children at Shengjing hospital of China Medical University.Serum capsid antigen(VCA)-IgM,VCA-IgG,EBV nuclear antigen-IgG(EBNA-IgG),and early antigen-IgG(EA-IgG)antibodies were detected using the LIAISION chemiluminescence immunoassay.EBV-DNA was detected using real-time PCR.Differences in antibody positivity rates between sexes,ages,and seasons of onset were compared.Results In 12 083 patients,the positive rates of VCA-IgM,VCA-IgG,EBNA-IgG,and EA-IgG were 9.95％(1 202/12 083),50.57％(6 110/12 083),46.03％(5 562/12 083)and 4.93％(596/12 083).The positive rates of VCA-IgM and EA-IgG were lower in male patients(9.09％and 4.44％,respectively)than in female patients(11.10％,5.60％;all P＜0.05).The differences in the positive rates for VCA-IgM,VCA-IgG,EBNA-IgG,and EA-IgG antibodies in children of different ages were statistically significant(all P＜0.05).Differences in the positive rates of VCA-IgG,EBNA-IgG,and EA-IgG antibodies were statistically significant when compared between seasons(all P＜0.05).Fourteen EBV antibody-positive combinations were detected,of which the main combination was VCA-IgG and EBNA-IgG double-positive,with a total of 4 741 cases(39.24％).Of the 3 712 children who underwent EBV-DNA detection testing,3 034(81.73％)were EBV-DNA-negative and 678(18.27％)were EBV-DNA-posi-tive.VCA-IgG and EBNA-IgG double positivity was the most common in EBV-DNA-negative and EBV-DNA-positive children,accounting for 983(26.48％)and 194 cases(5.23％),respectively.Conclusion Both VCA-IgG and EBNA-IgG antibodies are main positive in children with EBV infection in Shenyang.The positive rate of EBV antibodies is lower in boys than in girls.The positive rates of EBV anti-bodies differ in children of different ages and seasons of onset.

To revise GBZ 188 Technical Specification for Occupational Health Surveillance based on national laws, regulations, standards, specifications and legal documents of occupational disease, and combination with the actual situation in China. The main modifications are as follows: the occupational health surveillance for workers exposed to toluene (xylene may implement by reference), bromopropane, methyl iodide, ethylene oxide, chloroacetic acid, indium and its compounds, coal tar, coal tarasphalt, asphalt, β-naphthylamine, dust of metal and its compounds(tin, iron, antimony, barium and its compounds), hard metal dust, erionite dust, low temperature, laser, tick-borne encephalitis virus, Borrelia burgdorferi, and human immunodeficiency virus, for scraper or grind operators, and underground workers using squatting or kneeling position, crawling position, side-lying position, or shoulder position for a long period of time are included. The emergency health screening for workers exposed to arsenic, fluorine and its inorganic compounds, and acrylamide are included. The occupational medical examination (OME) for workers exposed to amino and nitro compounds of benzene, phosgene, monomethylamine, organic fluorine and dimethyl sulfate has been adjusted and made mandatory, with corresponding assessments required upon leaving the job. The special occupational health surveillance for workers exposed to mycobacterium tuberculosis and hepatitis virus is removed. The OME conclusion of reexamination is removed, and standardize recheck/additional inspection requirements. The optional items in OME performed before, during and after leaving post are removed, but the optional items in emergency medical examination are retained. Additional OME items are added. The Guideline for OME Summary Reports is added as informative appendix, and so on. The revised GBZ 188 Technical Specification for Occupational Health Surveillance is more scientific and practical.

Objective:To investigate the clinical features, therapy and prognosis of human cytomegalovirus(HCMV)pneumonia in pediatric patients, and to analyze the diagnosis value of detecting HCMV DNA in bronchoalveolar lavage fluid(BALF)by real-time PCR.Methods:The clinical characteristics of 58 pediatric inpatients who were HCMV DNA positive in BALF were retrospectively reviewed.All the patients were from Shengjing Hospital of China Medical University from January 2015 to December 2019.Clinical, radiologic, laboratory and microbiologic data was collected for each patient.The study cohort was divided into HCMV productive infection and latent infection consisting of 22 and 36 patients respectively, based on the HCMV active infection in lung or not.Receiver operating characteristic(ROC)curve was used to assess utility of detecting HCMV DNA in BALF and establish a threshold for diagnosis.Results:(1)Compared with patients in latent infection group, the children in productive infection group had a lower age of onset( P<0.05), a higher proportion of male( P<0.05), and more prolonged hospitalization stay( P<0.05). Pulmonary rales, hypoxemia and higher AST, CK, LDH in serum were easier to detect in productive infection group( P<0.05). Higher HCMV DNA copies in BALF was also detected( P<0.01). Patients in productive infection group had significantly more exposure to additional oxygen treatment or mechanical ventilation and systemic hormone therapy( P<0.05), while with poorer outcomes( P<0.05). (2) ROC curve analysis showed that the AUC for HCMV DNA in BALF in diagnosis of HCMV pneumonia was 0.708 with a threshold of 8.83×10 3 copies/mL, a sensitivity of 77.27%, and a specificity of 58.33%. Conclusion:Those who are diagnosed HCMV pneumonia have a lower age of onset with higher male proportion.These children suffered severer clinical signs.The patients with HCMV DNA copies higher than 8.83×10 3 copies/mL in BALF would be more likely to be diagnosed as HCMV pneumonia.

Objective:To compare the effects of different intraocular infusion solutions on histology and function of retina.Methods:Human corneal endothelial cells (HCEC), human retinal pigment epithelium (HRPE) cells and rat retinal ganglion cells (RGC) were divided into normal control group, balanced saline solution (BSS) group and compound electrolyte intraocular irrigating solution (CEIIS) group, and the cells were cultured in 10% DMEM/F12 medium, BSS and CEIIS for 12, 24 and 48 hours, respectively, according to grouping.The proliferation absorbance value of cultured cells was measured by cell counting kit-8 (CCK8) method.The expression of apoptosis related proteins in cultured cells was detected by cellular immunofluorescence staining.The cell apoptosis rate and cell cycle were measured by flow cytometry.The mitochondrial damage was detected by lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) quantitative detection kit.Fifteen New Zealand white rabbits were randomly divided into control group ( n=3), BSS group ( n=6) and CEIIS group ( n=6). The left eyes were taken for vitrectomy and different intraocular perfusion fluids were used during vitrectomy according to grouping.The retinal function of operative eyes was measured by flash electroretinogram (ERG) before operation and 24 hours after operation, and the structural changes of each layer of retina were detected by optical coherence tomography (OCT). The early apoptosis of retinal cells was detected by TUNEL staining.The expressions of cytochrome C and bax protein in retina were detected by immunohistochemical staining.The ultrastructural changes of retina were observed under a transmission electron microscope.The use and care of animals complied with the ARVO statement.This study protocol was approved by an Ethics Committee of Peking University People's Hospital (No.2019PHE059). Results:The three kinds of cultured cells in BSS and CEIIS groups were damaged in various degrees.With the extension of culture time, proliferated cells were decreased and the number of apoptotic cells was increased.Compared with the BSS group, cultured cells in the CEIIS group were dense and in orderly arrangement with uniform morphology and size.The apoptosis rates of HRPE cells and RGC in the BSS group were (37.157±6.918)% and (29.993±12.330)%, respectively, which were significantly higher than (4.163±1.310)% and (6.337±1.903)% in the CEIIS group ( P=0.003, 0.045). There was no significant difference in G0/G1+ S phase ratio of HCEC and HRPE cells among the normal control group, BSS group and CEIIS group (HCEC: F=2.226, P=0.189; HRPE: F=2.634, P=0.151), and the proportion of G2/M division arrest phase of RGC in the BSS group was significantly higher than that in the normal control group and CEIIS group ( P=0.047, 0.024). The proliferation absorbance values of HCEC, HRPE cells and RGC in the CEIIS group were significantly higher than those in the BSS group at each culture time point (all at P<0.05). The fluorescence intensity of cytochrome C, bax, caspase-3 and caspase-9 proteins in the BSS group was stronger than that in the normal control group and CEIIS group, and the fluorescence intensity of bcl-2 was weaker than that in the CEIIS group, and the fluorescence intensity of zonula occluden-1 (ZO-1) was weaker than that in the normal control group and CEIIS group.The release level of LDH in the BSS group was significantly higher than that in the CEIIS group at different time points (all at P<0.001). After 48 hours of culture, the release level of SDH in the BSS group was significantly higher than that in the CEIIS group ( P<0.05). No retinal histological abnormalities was found through OCT examination of rabbit eyes after vitrectomy in the two groups, but transmission electron microscopy showed that there were different degrees of loose arrangement of retinal photoreceptor cells, a large number of photoreceptor outer membrane discs falling off and vacuolar degeneration in the two groups, especially in the BSS group.TUNEL staining showed that the apoptotic cells were mainly located in the inner nuclear layer and RGC layer.The number of apoptotic retinal cells was (135.2±22.8)/high-power field of vision in the BSS group, which was significantly higher than (81.3±17.7)/high-power field of vision in the CEIIS group ( t=4.175, P=0.002). Full field flash ERG showed that the amplitudes of scotopic 3.0 ERG a- and b-wave in the CEIIS group after operation were significantly lower than those before operation, but the differences were not statistically significant (all at P>0.05). The amplitudes of scotopic 3.0 ERG a- and b-wave in the BSS group after operation were significantly lower than those before operation ( P=0.026, 0.010). Conclusions:In vivo and in vitro research results show that compared with BSS, there were few apoptotic cells in retinal tissue after vitrectomy perfused by CEIIS.

Animals ; Antigens, Surface/genetics* ; Cell Communication/genetics* ; Copulation/physiology* ; Fallopian Tubes/metabolism* ; Female ; Fertilization/genetics* ; GPI-Linked Proteins/genetics* ; Gene Expression Regulation ; Genes, Reporter ; Green Fluorescent Proteins/metabolism* ; Litter Size ; Luminescent Proteins/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism* ; Reproduction/genetics* ; Signal Transduction ; Sperm Count ; Sperm Motility/genetics* ; Spermatozoa/metabolism* ; Uterus/metabolism*

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.

ABSTRACT OBJECTIVE：To evaluate the in vitro and in vivo genotoxicity of emodin-8-O-β-D-glucoside（EG），and to compare the difference of in vitro cell test and in vivo test of rats. METHODS：2D and 3D hepatocyte models were established by in vitro two-dimensional（2D）and three-dimensional（3D）cell culture. After modeling，2D and 3D hepatocyte were divided into blank control group（0.5％ DMSO），mitomycin C group（positive control，0.1 μg/mL），EG low-dose，medium-dose and high-dose groups（10，50，200 μg/mL），respectively. The micronucleus ratio and tail DNA％ of HepaRG cells were detected. SD rats were divided into blank control group（0.5％ sodium carboxymethyl cellulose），ethyl methanesulfonate group（positive control，200 mg/kg），EG low-dose，medium-dose and high-dose groups（100，300，1 000 mg/kg），with 6 rats in each group. They were given medicine intragastrically for consecutive 15 d，once a day. 15 days later，the micronucleus formation rate of bone marrow polychromatic erythrocytes and hepatocytes，the tail DNA％ and tail distance of peripheral blood lymphocytes and hepatocytes were measured. RESULTS：In the in vitro 2D HepaRG hepatocyte model，compared with blank control group，the micronucleus formation rate and tail DNA％ of HepaRG cell were increased significantly in mitomycin C group （P＜0.01）. There was no statistical significance in micronucleus formation rate and tail DNA％ of HepaRG cell among EG groups（P＞0.05）. In 3D HepaRG cell model， compared with blank control group， micronucleus formation rate and tail DNA％ of HepaRG cell were increased significantly in mitomycin C group （P＜0.01 or P＜0.001）， while tail DNA％ of HepaRG cell wasincreased significantly in EG high-dose group（P＜0.01）. In the in vivo test，compared with blank control group，the micronucleus formation rate of bone marrow polychromatic erythrocytes and hepatocytes，the tail DNA％ and tail distance of peripheral blood lymphocytes and hepatocytes were all increased significantly in ethyl methanesulfonate group（P＜0.01）. Tail DNA％ of peripheral blood lymphocytes was increased significantly in EG high-dose group （P＜0.01）. There was no statistical significance in the micronucleus formation rate of bone marrow polychromatic erythrocytes and hepatocytes，the tail DNA％ and tail distance of hepatocytes among EG groups（P＞0.05）；with the increase of dose，there was an increasing trend. CONCLUSIONS：The results of this study suggest that in 2D cell model，EG not lead to chromosome breakage and DNA damage，but the long-term administration and repeated administration in vivo of 3D cell model show that EG has a certain risk of DNA damage，so the evaluation results of 3D HepaRG cell model are more similar to those of rats in vivo. KEYWORDS Emodin-8-O-β-D-glucoside；Genotoxicity；Two-dimensional culture；Three-dimensional culture；Rat；Micronucleus test