[Objective]To investigate the clinical features and high risk of very preterm infants with late-onset bacteri-al sepsis,so as to propose feasible prevention and treatment suggestions.[Methods]Totally 94 very preterm infants with late-onset bacterial sepsis from the Neonatology Department of Women's Hospital of Jiangnan University were recruited from February,2012 to January,2024.Their clinical data,including the perinatal situation,clinical symptoms,patho-gens,risk factors and treatment,were collected and analyzed.[Results]The incidence rate of very preterm infants with late-onset bacterial sepsis were 8.40 for 100 live birth babies.The major pathogens of the infections among these very pre-mature infants included gram-positive bacteria(71.1%).Logistic regression analysis showed that long term(≥7 d)use of antibiotics,invasive mechanical ventilation,indwelling central venous catheter(≥7 d),and vaginal delivery were high risk factors of very preterm infants with late-onset bacterial sepsis,the relative risk(OR)values were 2.787,4.243,3.033 and 2.174,respectively.[Conclusion]The gram-positive bacteria are the main pathogens of late-onset bacterial sepsis in very preterm infants.Long term(≥7 d)use of antibiotics,invasive mechanical ventilation,indwelling central ve-nous catheter(≥7 d)and vaginal delivery are high risk factors of very preterm infants with late-onset bacterial sepsis.The incidence of late-onset bacterial sepsis in very preterm infants can be reduced by strengthening perinatal management,shortening the time of antibiotic application and reducing invasive operations.

Background and Objectives: Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction ofarticular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation. Methods: and Results: Real-time reverse transcription–polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3’-untranscribed region. Conclusions These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Brain science accelerates the study of intelligence and behavior, contributes fundamental insights into human cognition, and offers prospective treatments for brain disease. Faced with the challenges posed by imaging technologies and deep learning computational models, big data and high-performance computing (HPC) play essential roles in studying brain function, brain diseases, and large-scale brain models or connectomes. We review the driving forces behind big data and HPC methods applied to brain science, including deep learning, powerful data analysis capabilities, and computational performance solutions, each of which can be used to improve diagnostic accuracy and research output. This work reinforces predictions that big data and HPC will continue to improve brain science by making ultrahigh-performance analysis possible, by improving data standardization and sharing, and by providing new neuromorphic insights.

Objective To investigate the change of CD35 expression on neutrophils in the peripheral blood and the relationship between the change and disease activity in patient with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV).Methods Forty untreated patients with active MPO-AAV(patient group)and forty healthy volunteers (control group) were enrolled into this study,and Bermingham vasculitis activity score (BVAS) for every patient was recorded.Flow cytometry (FCM) was employed to detect the CD35 and MPO expression on the neurtrophil,and enzyme linked immunosorbent assay (ELISA) was taken to test the levels of autoantibody against MPO-Antineutrophil cytoplasmic antibody (MPO-ANCA),fragment a from the activated complement factor B (Ba) and MPO in peripheral blood from both group.All test results were compared between the 2 groups by t test,Non-parametric test,Spearman correlation analysis.In addition,the relations among the laboratory results and the relationship between BVAS and the laboratory results were analyzed respectively.Results Compared with the control group,the expression level,which was represented as mean flourscence indensity (MFI),of CD35 and neutrophil membrane MPO on peripheral blood neutrophils was significantly increased [(2 014±968) vs (1 454±511),t=3.024,P=0.002 and (709±244) vs (580±158),t=2.806,P＜0.01,respectively],and the MPO expression level in neutrophils was significantly lower [(1 525±1 033) vs (3 196±2 126),t=-4.468,P＜0.01].Ba and MPO levels in serum of the patient group was significantly higher than that in the control group [37.89(26.17,63.14) μg/L vs 27.99(18.64,46.52) μg/L,Z=-2.521,P=0.012 and 546.16(450.55,729.96) U/L vs 327.93(279.02,365.10) U/L,Z=7.121,P＜0.01,respectively].In patient group,the expression level of CD35 had a significant positive relationship with peripheral blood neutrophil count (r=0.573,P＜0.01),serum Ba (r=0.433,P=0.005) and BVAS (r=0.368,P=0.020),respectively,whereas,there was a negative correlation between the MPO expressed on the neutrophils and that in the neutrophils (r=-0.458,P=0.003),and a positive relationship between MPO-ANCA and BVAS (r=0.351,P=0.026).Conclusion There is significant increased expression of CD35 on the neutrophil of patient with MPO-AAV,which might protect the neutrophil from destruction by the activated complement alternative pathway,and more neutrophils consequently contribute to the MPO-AAV pathogenesis.Inhibition of CD35 expression might become one of the potential new pathways for the treatment of MPO-AAV.

OBJECTIVE: To analyze the epidemiological characteristics and predict epidemiological trends of occupational chemical poisoning,based on directly reported data during 2006-2015 in Guangdong Province. METHODS: The data of patients with occupational chemical poisoning reported from National Information Surveillance System for Occupational Disease and Occupational Health from 2006 to 2015 in Guangdong Province were collected. The epidemiological characteristics were retrospectively analyzed. The autoregressive integral moving average model( ARIMA model) was established and validated based on the number of the new onset cases and was used to predict the trends of occupational chemical poisoning from 2017 to 2020 in Guangdong Province. RESULTS: From 2006 to 2015,1 288 new cases of occupational chemical poisoning were reported in Guangdong Province,which accounted for 24. 4% of the total number of new cases of occupational diseases in the province( 5 283 cases). Among the new cases,the percentage of acute and chronic poisoning was 21. 7%( 279/1 288) and 78. 3%( 1 009/1 288). There was 74. 7%( 962/1 288) of organic solvent poisoning. Five kinds of new occupational chemical poisoning were found. Most of the new cases were male,accounting for 56. 7%( 729/1 288). They were mainly distributed and concentrated in Pearl River Delta Region,accounting for 95. 9%(1 235/1 288). Shenzhen,Dongguan and Guangzhou were the most three cities which had 425,325 and 209 cases respectively,all of them accounted for 74. 4%( 959/1 288). The new cases of poisoning mainly distributed in medium and small enterprises( 72. 0%),private economic enterprises( 50. 9%) and manufacturing industries(70. 5%). The number of occupational chemical poisoning diseases decreased first,and increased,and the proportion to the total number of occupational diseases in Guangdong Province showed a straight downward trend(P < 0. 01). The median age at diagnosis was 35 years old and the median work year at diagnosis was 2. 0 years,and both of them showed an increasing trend( P < 0. 01). CONCLUSION: Occupational chemical poisoning in Guangdong Province has certain characteristic of crowd aggregation and epidemic trends.

OBJECTIVE: To analyze the distribution of network reported suspected occupational diseases( SOD),and the follow-up of confirmed diagnosis of occupational diseases in Guangdong Province from 2014 to 2017. METHODS: In July2018,the SOD cases reported from 2014 to 2017 in the direct network of Guangdong Province were collected as study subjects through the Suspected Occupational Diseases Report Card,Occupational Disease Report Card and Pneumoconiosis Report Card from the subsystem of National Information Surveillance System for Occupational Disease and Occupational Health. And the institutions for occupational disease diagnosis were asked to collect related data of applying for diagnosis and to investigate the final confirmed diagnostic status through the report cards of occupational diseases and pneumoconiosis. RESULTS: A total of 10 155 SOD cases were reported in Guangdong Province from 2014 to 2017,with an average annual growth rate of 62. 2% and an increasing trend year by year. The top three SOD were: suspected occupational otorhinolaryngological oral diseases( 58. 9%), particularly the suspected occupational noise deafness( 99. 9%); suspected occupational chronic chemical poisoning( 24. 6%),particularly suspected occupational chronic benzene poisoning( 88. 4%); and suspected occupational pneumoconiosis( 12. 8%). In total,there were 3 514 SOD cases applying for occupational diseases diagnosis,and the appication rate was 34. 6%. The final confirmed diagnosis rate was 59. 5%( 2 090/3 514). The application rate of occupational otorhinolaryngological oral diseases,occupational chronic chemical poisoning,occupational pneumoconiosis was 33. 8%,31. 3% and 35. 7%,while the final confirmed diagnosis rate was 54. 0%,49. 9% and 89. 5%. The application rate and the final confirmed diagnosis rate were the highest in the occupational disease prevention and treatment institutions, with the rate of 58. 1% and 70. 2% respectively. The application rate and the final confirmed diagnosis rate from occupational health examination were lower than those from occupational disease diagnosis institution,outpatient department and hospitalization( P < 0. 005). CONCLUSION: There is a rapid increasing trend of SOD in Guangdong Province from 2014 to 2017,but the confirmed diagnosis rate is low.

OBJECTIVE: To analyze the effects of long term exposure to power frequency electromagnetic fields( PFEMF) on apoptotic rates of peripheral blood T and B lymphocytes in workers of transformer substation. METHODS: A random number table method was used to select 73 workers with long-term exposure to PFEMF as exposure group and 70 non-exposure workers( administrative and logistics staffs) were selected as control group from 10 transformer substations in a province.The peripheral venous blood of workers in these two groups was collected,and the apoptosis of T and B lymphocytes were detected and analyzed by flow cytometry. RESULTS: The apoptosis rates of T and B lymphocyte between the exposure and non-exposure groups showed no statistical difference( median: 1. 555% vs 0. 790%,0. 020% vs 0. 030%,P > 0. 05).The multivariate linear regression analysis showed that both the PFEMF exposure and length of service had no significant effects on the apoptosis rates of T lymphocyte and B lymphocyte after adjusting confounding factors such as gender,age,alcohol drinking,smoking,medication history,medical radiation exposure and stressful events( P > 0. 05). CONCLUSION: Long-term exposure to PFEMF has no effects on apoptosis of peripheral blood T and B lymphocytes in workers of transformer substation.

Objective To explore preliminarily the role of the E2 subunit of pymvate dehydrogenase (PDC-E2) modified by xenobiotics (e.g.2-octynic acid,2-OA) in the pathogenesis of primary biliary cirrhosis (PBC).Methods Patients of PBC (102 cases),primary sclerosing cholangitis (PSC,34 cases) and healthy controls (HC,50 cases) were selected.The anti-PDC-E2,anti-2-OA and anti-lipoic acid (LA) antibody in the peripheral blood of the 3 groups were tested by enzyme linked immunosorbent assay (ELISA).By inhibitive ELISA (iELISA),30 of the 102 PBC patients with anti-PDC-E2 antibody but without anti-2-OA antibody were selected to detect whether there was any new epitope on the PEC-E2 conjugated with 2-OA.The chi-square test and Fisher exact test were taken to analyze the enumeration data.The two-tailed unpaired t test with Welch's correction was used to compare the measurement data.Spearman rank correlation analysis was also employed for proper test.Results The positive rate of anti-PDC-E2,anti-LA and anti-2-OA antibody in PBC patients was 94.1％(96/102),73.5％(73/102) and 53.9％(55/102) respectively,all of which were statistically significantly higher than those in healthy controls group but were of no significant difference between PSC and healthy controls group.There was no significant relevance between the levels of Anti-LA and anti-2-OA antibody in the PBC group (r=-0.065,P=0.520).The iELISA results showed that the antibody,which only identified the epitopes on 2-OA-PDC-E2 induced by the 2-OA conjugation with PDC-E2,existed in 40％(12/30) of the PBC patients,and more interestingly,this antibody was predominantly appeared in PBC patients at their early clinical stage.Conclusion There are anti-LA antibody and anti-2-OA antibody in PBC patients,which have shown no significant association with each other.It is very likely that new antigenic conformational epitopes on PDC-E2 modified by 2-OA would emerge,which might led to the immune response in the individuals who are susceptible to PBC,and thus contribute for the breaking of PDC-E2 immune tolerance,and PBC occurrence finally.

Objective To determine the levels and significance of Krebs von den lungen-6(KL-6), pulmonary surfactant protein A (SP-A), SP-D and interleukin (IL)-6 in patients with connective tissue disease interstitial lung disease (CTD-ILD). Methods The serum KL-6, SP-A, SP-D and IL-6 in all subjects were detected and the imaging and pulmonary function were recorded t test, χ2 test, non-parametric test, ANOVA and correlation analysis were used for data analysis. Results ① The levels of serum KL-6, SP-A, SP-D, IL-6 in the CTD-ILD group [551.4 (428.2, 883.5) U/ml, 938.4(435.2, 2324.7) pg/ml, 90.7 (80.7, 100.3) ng/ml and 30.4 (22.9, 41.7) pg/ml; P all<0.05] was significantly higher than that in the CTD group [192.9 (139.2, 266.2) U/ml; 458.0 (372.6, 529.0) pg/ml; 80.0 (71.2, 98.3) ng/ml; 18.6 (4.9, 31.0) pg/ml, Z=-5.383, -3.76, -2.123,-3.903, P all <0.05]; and higher than healthy controls (n=30) [183.2(141.9, 216.6) U/ml; 229.0(162.0, 248.0) pg/ml;50.8(26.1, 96.4) ng/ml;7.1(3.7, 8.7) pg/ml, Z=-5.801,-8.13, 2.272, 3.266;P all<0.05].②The levels of KL-6 in pulmonary HRCT for active ILD group was significantly higher than the non-active ILD group [998.5 (640.3, 1293.3) U/ml vs 565.0(434.0, 799.5) U/ml, Z=2.182, P=0.023], there was no statistical difference in the levels of SP-A, SP-D, IL-6 between the 2 groups. ③ Spearman correlation analysis showed that KL-6 was negatively correlated with forced vital capacity (FVC%);SP-D, IL-6 and diffusing capacity of carbon monoxide (DLCO %). ④ Logistic multiple regression analysis showed that KL-6 [OR=1.017, P=0.002, 95%CI (1.006, 1.028)], SP-A [OR=1.023, P=0.009, 95%CI (1.006, 1.041)], SP-D [OR=1.175, P=0.009, 95%CI (1.075, 1.264)], IL-6[OR=1.213, P=0.001, 95%CI(1.088, 1.354)] were the risk factors for ILD. Conclusion Serum KL-6, SP-A, SP-D and IL-6 are significantly increased and correlate with CTD-ILD. KL-6 is related to the pulmonary inflammatory disease and vital capacity, while SP-D and IL-6 are related to diffusion function.