Objective To investigate whether the activation of secretory prophospholipase A2 (sPLA2) plays the role in the pathophysiological mechanism of acute aristolochic acid nephropathy (AAN) in rats. Methods Wistar rats were randomly divided into two groups. Model group received decocted Aristolochia Manshuriensis Kom 30 g·kg-1d-1 by gavage for 7 days following tap water in same way for additional 7 days. Control group received only tap water by garage at parallel time. The renal pathological changes were observed at the 4th, 8th and 14th day. The injury of renal tubules and interstitium was observed under light microscope following a semi-quantity grade. The level of Scr was measured to evaluate glomerular function. Urinary N-acetyl-beta-glucosaminidase (NAG) was tested as renal tubular injury marker. The activity of sPLA2 in serum was detected by manifesting the color of thiols in the substrate. The protein expression of renal cortex and medulla COX-2 was analyzed by Western blot. The metabolic products of pretaglandins (PC, s) including 6-kcto-PGF1α and TXB2 in the plasma and urine were assayed by radioimmunoassay. The ratio of 6-keto-PGF1α/TXB2 was calculated. Results After Aristolochia administration, the tubulointerstitial injury and Scr increased in AA rats and reached the peak at the 8th day, the tubulointerstitial injury index(8.14±2.55 vs 1.50±0.71, P<0.05) and Scr[(0.24±0.10) vs (0.19±0.02) μmol/g, P<0.05] increased significantly in AA rats compared with control group. The activity of sPLA2 (μmol ·min-1·mg-1) in AA group elevated by 1.3-fold compared to control group at 8th day (133.15±17.05 vs 101.3±16.07, P<0.05), while theexpression of COX-2 in renal cortex increased (1.16±0.36 vs 0.69±0.28, P<0.05) with no change in renal medulla. Even though the levels of serum 6-keto-PGF1α and TXB2 did not change obviously in both AA and control group, but urinary levels of 6-keto-PGF1α and TXB2 increased by 2-fold and 3-fold in AA group compared to control group, respectively (all P<0.05), while the ratio of 6-keto-PGF1α/TXB2 decreased significantly (207.53±17.52 vs 296.64±51.31, P<0.05). All of above changes recovered to the control level at the 14th day except the tubulointerstitial injury index. Conclusion Serum sPLA2 is activated in the rots with acute kidney injury induced by aristolochic acid, which accompanied by up-regulated expression of COX-2 in renal cotex and increased the metabolic products of vasoconstrictive PG s in urine. These changes may participate the mechanism of renal peritubular ischemia in AAN.

AIM: To investigate the effect of injection stauntoniae ( IS) on inflammatory pain responses in mice.METHODS:The carrageenan test was used to determine the anti-inflammatory and analgesic effects of IS .Except for control group, the mice in other groups received an injection of λ-carrageenan solution (1%, 50 μL) into the plantar region of the left hind paws , followed by a subcutaneous injection of IS at doses of 12.5%, 50%and 100%or equal vol-ume of 0.9%NaCl.Both paw edema and hyperalgesia to thermal stimulation were measured 4 h, 12 h, 24 h and 48 h after the injection of λ-carrageenan solution.The lumbar-5 (L5) dorsal root ganglions (DRGs) of the mice were taken to inves-tigate the cyclooxygenase 2 ( COX-2) expression by immunohistochemical staining .RESULTS:Subcutaneous injection of IS potently inhibited paw edema and hyperalgesia induced by λ-carrageenan in the mice accompanied with the inhibition of COX-2 protein expression in L 5 DRGs.CONCLUSION:IS exerts the anti-inflammatory and analgesic effects on the in-flammatory responses by inhibiting the protein expression of COX-2 in DRGs.

Objectives To investigate the correlation between single nucleotide polymorphisms (SNP) in interleu-kin-15 (IL-15) and treatment response in childhood acute lymphoblastic leukemia (ALL). Methods Genomic DNA samples extracted from remission bone marrow cells of ALL patients were genotyped by MassArray. Five SNPs (rs10519612, rs10519613, rs17007695, rs17015014 and rs35964658) in IL-15 and their association to minimal residual disease (MRD) status in the end of induction therapy were studied. Results SNP rs17007695 was associated with the early response in children with ALL(P=0.049) and the incidence of positive MRD after induction therapy in CC genotype carriers was 1.8 times more than that in TT genotype carriers. Haplotype analysis of these five SNPs showed that the frequency of haplotype CACGG in MRD positive group was 2.1 times higher than that in MRD negative group (P=0.035). Conclusions IL-15 gene polymorphism was associated with the early treatment response in Han Chinese children with acute lymphoblastic leuke-mia.

Objectives To evaluate the long-term outcomes of childhood low-or intermediate-risk neuroblastoma (NB) and their relevant prognostic factors. Methods A total of 70 new cases of low-or intermediate-risk NB diagnosed and treated by NB-99 protocol between 1999 and 2008 were analyzed retrospectively. Results Of these 70 NB patients, fourteen patients were in low-risk group and 56 were in intermediate-risk group. Sixty-seven patients reached complete remission (CR) or very good partial remission and 3 (5%) achieved partial remission. Ten patients relapsed. One patient occured second malignant neo-plasm. No patients died of chemotherapy-related adverse events or infections. The 5 year overall survival rate was 85.9%, event-free survival rate was 81.0%. Bone marrow infiltration, age at diagnosis, stage, lactate dehydrogenase level had a significant effect on prognosis. Conclusion Develop cytogenetic and molecular biology tests and pretreatment risk stratification are im-portant for further improvement of treatment protocol.

Objectives To evaluate the clinical features, treatment scheme and long-term outcomes of stage 1、2 childhood neuroblastoma (NB). Methods The retrospective study included 49 newly diagnosed NB stage 1、2 patients from June 1998 to December 2010. Clinical data and long-term outcomes were analyzed. Results Twenty-four patients with stage 1 NB and twenty patients with stage 2 NB were found among all 237 patients with NB enrolled in this study. The median age at diagnosis was 25 months( 2 week to 9 year old),29 males and 20 females. Thirty-one patients (63.6%) without symptoms were discovered with tumor by physical or imaging examination. Thorax and abdomen were the most common sites of primary tumor (21 and 22 cases, accounting for 42.9% and 44.9% of all patients, respectively). Forty (81.6%) NB patients had favorable pathology classification. One patient was of MYCN amplification status. Urine vanilla mandelic acid was normal in 32 (91.4%) patients, and serum lactate dehydrogenase was less than five times of the normal value in all patients. Ten NB patients were treated ac-cording to the low-risk protocol who received surgery alone.Thirty-nine patients were treated according to intermediate-risk protocol who received both surgery and chemotherapy. All the patients achieved very good partial remission (100%).The medi-an follow-up period was 60 months(22 months to148months). Nine patients were lost after a follow up of 3 months in medi-an. The 2-、3-、5-year event free survival and overall survial of all 49 patients was 100%. Conclusions The prognosis for neu-roblastoma of stage 1、2 in this study was with 100%survival, which provides opportunity for further reduction of dosage and/or duration of episodes in chemotherapy.

Chimeric antigen receptor T cell (CAR-T) therapy is becoming the most promising treatment method in children and adolescent with refractory and relapse malignancies.While CAR-T cells exhibit powerful antitumour activity, this therapy has been associated with unique and significant toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) by triggering immune effector cells, even develop rapid and life-threatening cardiovascular, respiratory and/or neurological dysfunction.The assessment and grading of these adverse events vary widely in different clinical trials and institutions.For integrating the definitions and grading systems for toxicities from immune effector responses, in 2018, the American Bone Marrow Transplantation Society proposed consensus definitions and grading which is objective and easy to apply for CRS and ICANS.It helps clinicians and nurses make early critical care assessment and guide critical care interventions, thereby improving the efficacy and safety of CAR-T therapy.

Objective To investigate the microstructural changes of temporal lobe epilepsy(TLE)in patients with sleep disorders based on diffusion kurtosis imaging(DKI).Methods This research prospectively included 38 TLE patients(case group)and 20 healthy controls(HC)(HC group).Participants used sleep questionnaires to evaluate their sleep status.All TLE patients were divided into groups with and without sleep disorders according to the diagnostic criteria and scale scores of sleep disorders.The mean kurtosis(MK),mean diffusivity(MD),and fractional anisotropy(FA)of the relevant region of interest(ROI)were measured by DKI sequence.The differences of sleep quality scores and DKI parameters between groups were further compared via independent samples t-test and one-way analysis of variance.Results The Epworth sleepiness scale(ESS),Athens insomnia scale(AIS),and Pittsburgh sleep qual-ity index(PSQI)scores of TLE patients with sleep disorders were significantly higher than those of HC group(P＜0.05).The FA and MK values in TLE patients were significantly lower than those in HC group,while the MD value of TLE patients were substan-tially higher than that of HC group(P＜0.05).The values of MK and FA in left TLE patients with sleep disorders were significantly lower than those of without sleep disorders(P＜0.05),while there was no significant difference in MD value between the two groups(P＞0.05).MK value of right TLE patients with sleep disor-ders was significantly lower than that of without sleep disorders(P＜0.05),however,there were no significant differences in MD and FA values between the two groups(P＞0.05).Conclusion Quantitative DKI analysis revealed differences in DKI parameters in TLE patients combined with sleep disorders,inferring a specific white matter fiber damage in this group and providing imaging data to support the personalized treatment and prognostic assessment of these patients.

Objective Based on meteorological factors, the prediction of the risk of cardiovascular and cerebrovascular diseases(CVD) and the analysis of its correlation with the incidence rate. Methods The research utilizes six years of data on CVD incidence from Xingyi, from 2017 to 2022, as the subject of study. The incidence risk levels are categorized based on the 25%, 50%, 75%, and 95% quantiles of the cumulative probability of the number of cases. The study is conducted based on the relationship between meteorological factors and the risk of incidence of CVD. Results The incidence of CVD shows a significant correlation with temperature, vapor pressure, atmospheric pressure, and relative humidity. It is negatively correlated with temperature and vapor pressure, among which the correlation with the daily minimum temperature is the highest at -0.504 (P < 0.05), and positively correlated with atmospheric pressure and relative humidity. Meteorological factors that have a significant correlation with the incidence rate are selected as input factors for the machine prediction model. It was found that the random forest model performs best in predicting the risk of incidence of CVD, with a comprehensive score of 0.851. Analysis of Relative Risk (RR) values found that there is a lagged association between exposure levels to meteorological factors and the incidence of cardiovascular and cerebrovascular diseases. A temperature drop of more than 11°C and an increase in atmospheric pressure of more than 8 hPa can significantly increase the risk of incidence. Conclusion The study revealed significant correlations between the incidence of CVD and meteorological parameters including temperature, water vapor pressure, atmospheric pressure, and relative humidity. Utilizing machine learning models, the research effectively predicted the risk of these diseases, uncovering that extreme weather conditions significantly elevate the risk of incidence. These findings provide a basis for meteorological risk assessment in public health interventions, emphasizing the importance of taking preventative measures in the context of extreme climate changes.

Homoharringtonine (HHT), a plant alkaloid from Cephalotaxus harringtonia, exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s. Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens. Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C), whereas patients in arm B were treated with HHT-containing regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT. From February 2009 to November 2015, 59 patients less than 2 years old with de novo AML (other than acute promyelocytic leukemia) were recruited. A total of 42 patients achieved a morphologic complete remission (CR) after the first course, with similar rates in both arms (70.6% vs.72.0%). At the end of the follow-up period, 40 patients remained in CR and 5 patients underwent hematopoietic stem cell transplantation in CR, which could not be considered as events but censors. The 5-year event-free survival (EFS) was 60.2%±9.6% for arm A and 88.0%±6.5% for arm B (P= 0.024). Patients in arm B experienced shorter durations of leukopenia, neutropenia, and thrombocytopenia and had a lower risk of infection during consolidation chemotherapy with high-dosage Ara-C. Consequently, the homoharringtonine-based regimen achieved excellent EFS and alleviated hematologic toxicity for children aged younger than 2 years with de novo AML compared with the anthracycline-based regimen.