AIM:To investigate the effects of saponin from Panax japonicus IVa(SPJ IVa)on acute lung inju-ry in rats and to explore its possible protective mechanism.METHODS:Sixty SD rats were randomly divided into four groups,15 rats in each group:the control group,model group,low-dose SPJ IVa group,and high-dose SPJ IVa group.A rat model of ALI was established via intratracheal instillation of lipopolysaccharide(LPS,2 mg/kg).Rats in the low-and high-dose SPJ IVa groups were intraperitoneally injected with 15 and 45 mg/kg SPJ IVa,respectively,30 min after model-ing.Serum,bronchoalveolar lavage fluid(BALF),and lungs were collected 24 h after modeling.Pathomorphological changes in lung tissues were assessed using HE staining.The wet weight/dry weight ratio of lung tissues was measured us-ing the weighing method,whereas ELISA was used to measure the levels of interleukin-1β(IL-1β),IL-6,and tumor ne-crosis factor-α(TNF-α)in the serum and BALF.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)were assessed using the kit method.Cell apoptosis in lung tissues was evaluated by immunohisto-chemical staining of cleaved caspase-3 and TUNEL.Western blot was used to measure the expression of nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),nuclear factor-κB(NF-κB)p65,and Toll-like receptor 4(TLR4)in lung tissues.RESULTS:Compared with control group,the lung tissues of the model group were significantly damaged,and the lung injury scores(0.21±0.22 vs 2.98±0.46)and lung wet/dry weight ratios(3.09±0.41 vs 6.36±0.61)were significantly increased(P<0.01).Compared with model group,the lung injury scores(1.80±0.31 and 1.05±0.25 vs 2.98±0.46)and lung wet/dry weight ratios(5.25±0.44 and 3.89±0.35 vs 6.36±0.61)in low-and high-dose SPJ IVa groups were significantly reduced(P<0.01).The administration of LPS resulted in elevated levels of pro-inflammatory cy-tokines(IL-1β,IL-6,and TNF-α)as well as the oxidative marker MDA in both serum and BALF(P<0.01).Additional-ly,it led to a decrease in antioxidant markers SOD and GSH(P<0.01).However,treatment with both low and high doses of SPJ IVa effectively attenuated the LPS-induced production of pro-inflammatory factors and oxidative markers MDA(P<0.01),while also increasing SOD and GSH levels(P<0.05 or P<0.01).In the model group,evident apoptosis was ob-served in lung tissues,whereas treatment with low and high doses of SPJ IVa significantly suppressed TUNEL-positive cells and the expression of cleaved caspase-3(P<0.01).The expression levels of Nrf2,HO-1,NF-κB p65,and TLR4 in lung tissues were significantly higher in the model group than in the control group(P<0.01);in turn,after treatment with low and high doses of SPJ IVa,Nrf2 and HO-1 were further upregulated(P<0.01),whereas NF-κB p65 and TLR4 were downregulated(P<0.01).CONCLUSION:The inhibitory effect of SPJ IVa on LPS-induced ALI in rats may be attribut-ed to its ability to suppress the TLR4/NF-κB-and Nrf2/HO-1-mediated inflammatory response and oxidative stress.

Background The threshold limit values (TLVs) established and regularly updated by the American Conference of Governmental Industrial Hygienists (ACGIH) are widely adopted and referenced globally, serving as a crucial reference for China's occupational exposure limits (OELs). It is necessary to track it regularly and compare it with China's OELs. Objective To compare the OELs stipulated in Occupational exposure limits for hazardous agents in the workplace—Part 1: Chemical hazardous agents (GBZ 2.1—2019) and the ACGIH TLVs (2024) and to provide references for subsequent formulation and revision of OELs in China. Methods The OELs specified in GBZ 2.1—2019 and the TLVs issued by ACGIH were used to establish a database using Microsoft Excel 2019 software. Cross verification was conducted through matching Chemical Abstracts Service Registry Numbers (CAS Rn) and both Chinese and English names to ensure accuracy. Then, comparisons and analyses were carried out based on the type of limit values, which were matched as follows: permissible concentration-time weighted average (PC-TWA) with threshold limit value-time weighted average (TLV-TWA), permissible concentration-short term exposure limit (PC-STEL) with threshold limit value-short term exposure limit (TLV-STEL), and maximum allowable concentration (MAC) with threshold limit value-ceiling (TLV-C). Comparisons included types, quantities, and sizes of limits. Results The GBZ 2.1—2019 OELs and the ACGIH TLVs (2024) were generally consistent in terms of types and definitions, but there were differences in the number and size of the limits. In terms of the number of limits, GBZ 2.1—2019 specified 365 OELs for 358 chemical hazardous agents, while ACGIH TLVs (2024) included 316 corresponding limits. Among these, 148 (46.9%) limits were consistent, 38 (12.0%) were basically consistent, and 130 (41.1%) were inconsistent. In terms of the size of the limits, out of the 130 inconsistent limits, 51 OELs were lower than the corresponding TLVs, 67 OELs were higher than the corresponding TLVs, and 12 were under different limit types. For some chemical hazardous agents, their OELs were significantly lower or higher than their TLVs. Conclusion Some of the OELs for chemical hazardous agents specified in GBZ 2.1—2019 are significantly lower or higher than the TLVs. For these chemical hazardous factors, it is recommended to prioritize their inclusion in research projects and to complete the revisions as soon as possible based on the latest scientific evidence.

Objective:To explore the genetic etiology for a child with Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 (PEOA6).Methods:A child who had attended the Women and Children′s Hospital Affiliated to Ningbo University on 7 August, 2023 was selected as the study subject. Clinical data of the child were analyzed retrospectively. The child and her parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Women and Children′s Hospital Affiliated to Ningbo University (Ethics No. EC2020-048).Results:The child, a 7-year-old female, had presented with limb muscle pain, amyosthenia, significantly increased creatine kinase, congenital diaphragmatic hernia and recurrent respiratory tract infections. WES revealed that she has harbored a heterozygous c. 1590G>C (p.L530F) variant of the DNA2 gene, which was verified to have a de novo origin by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1590G>C was rated as a likely pathogenic variant (PS2+ PM2_Supporting+ PP3). Conclusion:The c.1590G>C (p.L530F) variant of the DNA2 gene probably underlay the PEOA6 in this child.

Objective:To explore the values of fat saturation sequence in MRI for juvenile arthritis.Methods:A total of 1 131 cases with juvenile arthritis and 1 601 with symptomatic arthritis were examined by MRI normal T1 weighted imaging (T1WI) and T2 weighted imaging (T2WI)sequence and spectral presaturation attenuatedinversion recovery (SPAIR) T2 fat saturation sequence.All the images were independently evaluated by two senior doctors from the Department of Radiology and the Department of Pediatric Rheumatology and Immunology respectively to confirm the types and degree of pathological changes of joint tissues.Results:Among the subjects,847 patients demonstrated positive in MRI,accounting for 52.9％;409 patients showed positive in normal sequence,accounting for 48.3％;816 patients showed positive in fat saturation sequence,accounting for 96.3％.Joint hydrops accounted for 59.5％.Bone marrow edema accounted for 39.7％.The relevant ratio of bone marrow edema,joint hydrops,thickening of synovium and cartilage injuries in fat saturation sequence were higher than that in normal sequence (P＜0.05).The relevant ratio of bone erosion in normal sequence was higher than that in fat saturation sequence (P＜0.05).However,no significant difference of joint cysts was found between the fat saturation sequence and normal sequence (P＜0.05).Conclusion:Application of fat saturation sequence by MRI to check juvenile arthritis could obviously improve the positive MRI relevant ratio.In addition,the relevant ratio of the early pathological changes of juvenile arthritis (such as bone marrow edema and joint hydrops) was high,which might provide references for the early diagnosis of juvenile arthritis.

Objective To explore the significance of interleukin (IL)-1β and IL-6 in serum of children with hyperuricemia (HUA). Methods 142 children including 71 children with HUA (HUA group) and 71 control children (control group), healthy and inguinal hernia children were selected as control group. 71 HUA children were subdivided into GA (gout attacks) group (n=28) and NGA (non-gout attacks) group (n=43) according to whether they had a history of acute gout attacks, including sudden monoarthritis of rapid onset with intense pain and swelling or without. Enzyme-linked immunosorbent assay was used to measure the level of IL-1β and IL-6 in serum. Results Serum IL-1β and IL-6 levels of HUA children were significantly higher than those of control group (all P<0.05). Serum IL-1β and IL-6 levels of HUA children in GA group were significantly higher than those of NGA group (P<0.05). Serum IL-1β and IL-6 levels of GA group in acute phase was significantly higher than those of HUA children in remission stage、NGA group and control group (P<0.05). Serum IL-1β and IL-6 levels of GA group in remission stage and NGA group was significantly higher than those of control group (P<0.05). There were no significant differences between HUA children in remission stage and NGA group (P>0.05). The serum IL-1β and IL-6 levels of HUA children were positively correlated with WBC, neutrophils, monocytes, uric acid, ESR, CRP, BUN and Cr (all P<0.05), while not correlated with triglyceride, total cholesterol, LDL-C and HDL-C(all P<0.05). Conclusion IL-1β and IL-6 play an important role in the pathogenesis of HUA in children.

The aim of the study was to investigate the effect of oleic acid(OA)and isosorbide mononitrate(ISMN)on the phase diagrams of glyceryl monooleate(GMO)liquid crystalline systems and release of ISMN from them. Liquid crystalline systems of GMO/H2O, GMO/H2O/ISMN and GMO/H2O/OA were prepared and their phase diagrams were plotted. Investigation of water absorption of GMO and ISMN release profiles shown that the release mechanism of ISMN was diffusion-controlled. Increased drug loading accelerated the release rate. However, the increased loading of OA decreased ISMN release. The result could offer practical basis for drug loading and the selection of additives in GMO liquid crystalline system.

Objective To observe the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP),high density lipoprotein cholesterol (HDL-C) in predicting cardiovascular damage in Kawasaki disease (KD).Methods Enzyme-linked fluorescence analysis (ELFA) technique was used to measure serum NT-proBNP levels in 406 KD patients [including 104 cases of incomplete Kawasaki disease (IKD)] at the acute phase,the convalescent stage,at the same time,the blood HDL-C,Albumin,globulin,alanine aminotransferase (ALT),C-reactive protein (CRP),red blood cell sedimentation rate (ESR),blood white cell count (WBC),hemoglobin (Hb),blood platelet count (PLT) level were tested.According to the results of echocardiography,electrocardiogram,myocardial enzymes in KD,patients were divided into two groups:two hundred and twenty-two with cardiovascular damage and 184 without cardiovascular damage group.The age,gender,fever,the first application of the intravenous gamma globulin,laboratory markers of clinical features observed above the detection levels were compared,and these parameters for each group were compared using t test or analysis of variance,the single factor which was statistically significant were received operating characteristic curve (ROC) analysis.Then the cardiovascular damage group was divided into echocardiography abnormal group and echocardiography normal group,and t test was adopted to compare the clinical parameters of the two groups.Results ① The age,lip and oral changes,the first application of intravenous gamma globulin,blood NT-proBNP,HDL-C,albumn and ALT was significantly different between the cardiovascular damage group and non cardiovascular damage group (t/x22=4.989,4.721,6.212,18.834,12.788,4.851,4.541,All P＜0.05).② When the blood NT-pro-BNP was higher than 786.5 ng/L,its sensitivity and specificity for differentiating KD with cardiovascular damage was 86.5％ and 84.8％,respectively.When the blood HDL-C was lower than 0.655 mmol/L,its sensitivity and specificity for differentiating KD with cardiovascular damage was 80.4％ and 69.4％ respectively.When the blood NT-proBNP was higher than 786.5 ng/L in addition to HDL-C lower than 0.655 mmol/L,the specificity for differentiating KD with cardiovascular damage was 91.8％.③ For the 222 cases with cardiovascular dam-age,their blood NT-proBNP,HDL-C levels were statistically significantly different between the echocardiogra-phy abnormal group and echocardiography normal group (t=3.354,4.084,All P＜0.05).④ The serum NT-proBNP,ALT levels of the 406 acute and convalescent KD patients were significantly higher than the recovery phase.The blood HDL-C,albumin level of acute patients were significantly lower than those at the recovery phase,the difference was statistically significant (t=22.335,4.951,20.334,15.073,All P＜0.05).⑤ One hundred and four children with IKD were divided into patients with cardiovascular damage (74 cases) and without cardiovascu-lar damage (30 cases),the age,lip and oral changes,the first application of intravenous gamma globulin,blood NT-proBNP,HDL-C,albumin and ALT were significantly differentbetween these two groups (t=3.083,2.157,6.423,6.409,3.649,8.658,All P＜0.05).Conclusion Blood NT-proBNP and HDL-C are good pre-dictive parameters in children with cardiovascular damage of KD,IKD.

Objective To explore the effect of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein injection (rhTNFR:FC) on the expression of cartilage oligomeric matrix protein (COMP) in the synovial fluid and peripheral blood of juvenile idiopathic arthritis (JIA); and to explore the clinical significance of COMP for JIA and the relationship between rhTNFR:FC and COMP in JIA.Methods Thirty-five patients with JIA (JIA group),30 patients with traumatic arthritis (trauma group) and 30 patients with indirect inguinal hernia hernioplasty (normal group) were included.Peripheral blood from all enrolled patients and synovial fluid from 15 JIA and 10 trauma arthritis were obtained for COMP detection before the treatment.Fifteen JIA (group A) patients were treated with combined rhTNFR:FC,diseasemodifying antirheumatic drugs (DMARDs) and non-steroid anti-inflammatory drugs (NSAIDs),20 JIA (group B) were treated with combined DMARDs and NSAIDs.After three to six months' treatment and when the disease were in remission,peripheral blood from group A and B were drawn for COMP detection.In group A,the synovial fluid from 5 patients were obtained for COMP detection after treatment.At the same time,such as tender joint count (TJC),swollen joint count (SJC),time for morning stiffness,blood routine,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) and other parameters before and after treatment were measured.The level of COMP was tested by double antibody sandwich enzyme-linked immunosorbent assay.The measurement data were tested for variance and independent sample t-test; and the enumeration data were tested by chi-squared or Fisher's exact test.Pearson's correlation analysis was adopted to analyze the association among the variables.Results ① The blood COMP level before treatment was (0.77±0.29) ng/ml in the JIA group,(1.00±0.28) ng/ml in the traumatic arthritis group,and (1.33±0.37) ng/ml in the normal control group.The level in the former two groups was obviously lower than that in the normal control group.The variation was statistically significant (F=25.345,P＜0.05).The comparison between any two groups was statistically significant (P＜0.05).② The COMP level in the synovial fluid before treatment were (14.8±1.6) ng/ml in the JIA group,(15.1±1.0) ng/ml in the traumatic arthritis group.The variation was not stati-stically significant (t=0.523,P=0.606).③ The serum COMP level of the systemic JIA group was obviously lower than that of the oligoarticular JIA patients,and patients with enthesitis-related arthritis and polyarticular JIA (0.26± 0.03 vs.0.87±0.17,0.89±0.22 and 0.70±0.35 ng/ml,respectively; F=9.244,P＜0.05).④ The serum COMP level of JIA at the acute phase was negatively correlated with white blood cells count (WBC),CRP and ESR (r=-0.556,-0.582 and-0.684,respectively; P all＜0.05).By contrast,no correlation was detected between the serum COMP level and joint tenderness index,joint swelling index,morning stiffness duration,hemoglobin level and platelet count(r=0.06,-0.206,-0.107,0.15 and-0.185,respectively; P all ＞0.05).⑤ The serum COMP level was obviously lower in the JIA with joint destruction than that without joint destruction (0.52±0.22 vs.0.92±0.22 ng/ml; t=5.207,P＜0.05).⑥After treatment,the blood COMP level in group A was (1.33±0.21) ng/ml and (0.96±0.22) ng/ml in group B,which was obviously higher than that in the JIA group before treatment (0.77±0.29) ng/ml.In addition,the level in group A was higher than that in group B.The variation was statistically significant (F=24.681,P＜0.05).⑦ After treatment,the COMP level in the synovial fluid (18.4± 1.1) ng/ml (n=5) was higher than that before the treatment was (14.8± 1.6) ng/ml (n =15).The variation was of statistical significant (t=4.565,P＜0.05).Conclusion The COMP level in blood and synovial fluid declines before treatment and increases after treatment.The increase is more obvious after combined with rhTNFR:FC treatment.The serum COMP level is remarkably decreased in JIA at the acute phase,systemic JIA,and the JIA with destruction of joint,and showes a negative correlation with WBC,CRP and ESR.Serum COMP may be a useful marker of active disease,destruction of joint and growth inhibition for patients with JIA.rhTNFR:FC treatment for JIA can facilitate the recovery of COMP.

Objective To explore the correlation between the distribution of uric acid (UA) level and the biochemical indicators which reflect the degree of organ lesions among hospitalized children.Methods Patients who were hospitalized to the Department of Pediatrics and received the blood UA test from June 2012 to October 2013 were included,23 217 cases in total.The biochemical analyzer-Japan's Olympus AU 2700 was used to detect blood biochemistry; and uricase-peroxidase coupling method was used to detect blood UA.Among these patients,2 099 cases whose UA level exceeded the normal level.Then the patients' gender,age,primary diagnosis and UA level were recorded; and the distribution of their UA level was described.The Chi-square or Fisher test was used to assess the incidence rate.At the same time,each blood biochemical indicators of the patients with high UA level were recorded ; and the relationships between the blood UA of the 1 650 patients with complete records and each blood biochemical indicator were analyzed with Pearson correlation analysis.Results The incidence rate of hyperuricemia among the hospitalized children was 9.04％(2 099/23 217).In particular,the incidence rate among boys and girls was 6.5t％(890/13 657) and 12.65％ (1 209/9 560) respectively (x2 =256.9,P＜0.05).The incidence rate of hyperuricemiin different diseases was as follows:in the critical illness 36.93％ (113/306),neonatal disease 20.34％ (922/4 533),urinary system diseases 12.08％ (47/389),circulatory system diseases 11.67％ (21/180),nervous system diseases 11.05％(112/1 014),digestive diseases 10.50％(190/1 810),infectious diseases 10.18％(120/1 179),blood diseases 7.58％ (55/726),endocrine system diseases 5.74％ (17/296),autoimmune diseases 4.24％ (48/1 131),respiratory diseases 3.90％ (454/11 653) respectively (x2=1423.0,P＜0.05).The incidence of hyperuricemia at younger than one month was 18.31％(929/5 075),younger than one year old was 4.22％ (359/8 501),younger than six years old was 10.68％(600/5 618),younger than 15 years old was 5.24％ (211/4 023) respectively (x2=858.5,P＜0.05).Blood UA was positively correlated to urea nitrogen,creatinine,lacticdehydrogenase,α-hydroxy-butyrate dehydrogenase,creatine kinase and creatine kinase-MB (r=0.426,0.44,0.324,0.367,0.413,0.431,P＜0.05).Blood UA was not correlated to fructosamine,blood glucose,triglycerides,total cholesterol,low-density lipoprotein and high density lipoprotein.Conclusion The incidence of hyper-uricemia among hospitalized children is high; and the incidence among children with severe diseases and newborn babies is high; followed by in children with urinary system and circulatory system diseases.The blood UA level is closely related to the blood biochemical indicators which reflect the lesions of heart and kidney.

Objective To observe the changing levels of serum sFas before and after intravenous i mmunoglobulin (IVIG) treatment of incomplete Kawasaki disease (IKD),to explore the roles of sFas in the pathogenesis of IKD and IVIG treatment mechanism.Methods Thirty eight cases of IKD children were selected as experimental group and 20 examples of the same age of children as the control group.The IKD children were treated by IVIG in combination with aspirin (ASP) ; and blood test was performed before treatment,3 days after treatment,and 14 days after treatment,respectively.Dual-resistant sandwich enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum sFas,plasma Fibrinogen (PT-D),d-dimer (D-D),and c-reactive protein (CRP).Results The levels of serum sFas,PT-D,D-D,and CRP were significantly higher than the control group for IKD children before treatment[(0.55 ± 0.14)ng/L vs (0.24 ±0.04) ng/L,(552.3 ± 147.2) mg/dl vs (277.3 ±82.5)mg/dl,(649.0 ±201.6) μg/L vs (315.4 ±91.8)μg/L,and(72.2 ±28.7)mg/L vs (7.2 ±2.9)mg/L; t' =12.41,9.11,8.64,13.82;All P ＜ 0.05] ;3 days after treatment,compared with those before treatment and control group,the sFas level of IKD children at the third day after treatment was significantly decreased compared to that before treatment and control groups,respectively [(0.43 ± 0.09) ng/L vs (0.55 ± 0.14) ng/L,(0.24 ± 0.04) ng/L,F =47.624,All P ＜0.05] ;For the level of sFas at the 14th day after treatment,no statistical significance was found between IKD children and the control group[(0.24 ±0.05) ng/L vs (0.24 ±0.04) ng/L,t =0.596,P ＞ 0.05].Conclusions The abnormally increased serum sFas level before IVIG treatment suggests that dysfunction of apoptosis be involved in the pathogenesis of the IKD.Intravenous immunoglobulin treatment may be involved in the apoptosis process.