Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H₂O₂), which is then used in the Cu⁺-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Objective:To investigate the correlation of the emm genotypes and virulence genes with the isolation sites of Group A Streptococcus (GAS). Methods:It was a retrospective study.The specimens were collected from children with impetigo in Beijing Children′s Hospital, Capital Medical University from 2006 to 2008 for GAS isolation and identification.A total of 24 GAS strains were isolated from 16 children with impetigo, among which 7 pairs of strains were isolated from the throat and skin of 7 children, and 1 pair of strains was isolated from the vulva and skin of one child, and the remaining 8 GAS strains were isolated from the skin pus samples of 8 children.Polymerase chain reaction was applied to detect the emm genotypes and 13 virulence genes ( speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa). The correlation of the emm genotypes and virulence genes with the isolation sites of GAS strains was analyzed. Results:In this study, four emm genotypes were detected, including emm1.0 (15/24), emm12.0 (4/24), emm22.0 (2/24) and emm160.0 (1/24), and one subtype emm12.19 (2/24) was detected as well.The carrying rates of 13 virulence genes speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were 58.3%, 100%, 91.7%, 100%, 50.0%, 12.5%, 54.2%, 66.7%, 16.7%, 25.0%, 12.5%, 100% and 91.7%, respectively.All strains carried 5 to 11 virulence genes and they all carried speB, speF and smeZ.There were significant differences in the carrying rate of speA and speJ among the strains with different emm genotypes (all P<0.05). There was no significant difference in the distribution of virulence genes between skin isolates and pharyngeal isolates, including the 5 pairs of strains carrying the emm1.0 genotype (all P>0.05). Conclusions:The distribution of virulence gene of GAS in children with impetigo is significantly correlated with the emm genotype, rather than the isolation site.

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

As a new type of immunosuppressant，iguratimod can mediate the anti-inflammatory signaling pathway by inhibiting the proliferation of inflammatory cells and reducing the release of inflammatory cytokines， and play the role of anti-inflammatory. It can affect the proliferation of immune cells and the expression of immune factors，reduce the production and deposition of immune complexes in the body，and play the role of immune regulation. It can regulate bone metabolism by mediating signaling pathways such as Wnt/β-catenin，Toll-like receptor 4/nuclear factor-κB and osteoprotegerin/nuclear factor-κB receptor activating factor ligand， and play a role in bone protection. It can inhibit pulmonary fibrosis by inhibiting the expression of transforming growth factor β1/ Smad2/3 signaling pathway，tumor necrosis factor-α，interleukin-1，interleukin-6，matrix metalloproteinase-9 and other inflammatory cytokines in lung tissue，and inhibiting the expression of collagen and fibronectin. Its efficacy and safety have been confirmed in the clinical application of rheumatoid arthritis and primary Sjogren syndrome and included in the diagnosis and treatment of the disease. It has also shown good efficacy in the clinical application of other connective tissue diseases such as systemic lupus erythematosus and ankylosing spondylitis，and no obvious safety risks have been found.

Objective To systematically review the incidence and influencing factors of refeeding syndrome(RFS)in critically ill patients,and provide references for early identification of RFS and formulation of preventive measures.Methods Computerized searches were conducted for studies on RFS in critically ill patients in the databases of China National Knowledge Infrastructure(CNKI),Wanfang,VIP,CBM,PubMed,Embase,Web of Science,CINAHL,Cochrane Library from inception to May 29th,2024.Data analysis was performed using Stata 16.0 software.Results A total of 29 articles with 5 720 participants were included.The Meta-analysis showed that the incidence of RFS in critically ill patients was 33.68％.The subgroup analysis showed that the incidence of RFS in critically ill patients was higher in studies conducted in 2020 or later(38.22％),in the Americas(36.39％),and with only electrolyte changes as the diagnostic basis(37.51％).Risk factors for RFS in critically ill patients included higher acute physiological and chronic health evaluation Ⅱ scores(OR=1.41),higher sequential organ failure assessment scores(OR=1.29),initiation of feeding within 48 h of ICU admission(OR=3.36),age ≥60 years(OR＝2.82),diabetes mellitus(OR=3.53),pre-albumin concentration＜150 g/L(OR=5.53),albumin concentration＜30 g/L(OR=3.26),caloric intake＞25％standard calories(OR=2.86),enteral solution temperature of 36～38 ℃(OR=2.32),feeding rate＞50 ml/h(OR=3.76),fasting time ≥2 d before feeding(OR=2.46),history of alcoholism(OR=2.64).Conclusion The incidence of RFS in critically ill patients is high and there are many influencing factors.Nurses should improve their awareness and attention to RFS,accurately identify high-risk groups and risk factors,and adopt a multidisciplinary collaborative model to develop whole-course,detailed and personalized intervention measures to prevent RFS.

ObjectiveTo explore the possible mechanism of Bushen Huoxue Formula （补肾活血方， BHF） in the treatment of Parkinson's disease （PD） from the the perspective of intestinal flora. MethodsSeventy-two male C57/BL6J mice were randomly divided into blank group， model group， Madopar group and low-， medium- and high-dose BHF groups， with 12 mice in each group. The mice in the blank group were intraperitoneally injected with 10 ml/kg of normal saline， and those in the other groups were intraperitoneally injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 3 mg/ml to induce PD mice model， both once a day for 7 consecutive days. After successful modeling， the low-， medium-， and high-dose BHF groups were given 7.5， 15， and 30 g/（kg·d） of BHF by gavage， respectively， while the Madopar group was given 112.5 mg/（kg ·d） of Domedopar tablets by gavage， and the blank group and the model group were given 15 ml/（kg·d） of distilled water， all once a day for 14 consecutive days. The rod climbing test， rotating rod test， grip strength test and weight-bearing swimming test were used to evaluate the behavioral indicators of mice. Western blotting was used to measure the protein expression levels of Toll-like receptor （TLR）/nuclear factor kappa B （NF-κB） pathway inflammatory factors in the mouse ileum， including Toll-like receptor 2 （TLR2）， Toll-like receptor 4 （TLR4）， NF-κB， tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6）， and interleukin 17 （IL- 17）. 16S rRNA high-throughput sequencing was used to analyze changes in mouse intestinal flora. ResultsCompared to those in the blank group， the mice in the model group had longer bottoming time when climbing the pole， reduced grip strength， shortened rotary pole duration and swimming duration， and increased protein expression levels of TLR2， TLR4， NF-κB， TNF-α， and IL-6 in the ileal tissue （P＜0.01）. Compared to the model group， the Madopar group and the low-， medium- and high-dose BHF groups had shortened bottoming time of the climbing pole and increased grip strength； the Madopar group and the high-dose BHF group had prolonged rotary pole duration， and reduced protein expressions of TLR2， TLR4， NF-κB， TNF-α， IL-6， and IL-17 levels； and only the high-dose BHF group had prolonged swimming duration （P＜0.05 or P＜0.01）. Compared to those in the low-dose BHF group， the bottoming time of the climbing pole were shorter in the moderate- and high-dose groups （P＜0.05 or P＜0.01）， and the grip strength increased while the protein expression levels of TLR2， TLR4 and IL-17 decreased in the high-dose group （P＜0.05 or P＜0.01）. The intestinal flora results showed significant differences between the blank group and the model group in the Dominance index， Pielou_e index， Shannon index， and Simpson index （P＜0.05 or P＜0.01）. Compared to those of the model group， the Shannon index， Chao1 index， and Observed_otus index of the Madopar group， as well as the Chao1 index， Observed_otus index， Dominance index， Pielou_e index， Shannon index， and Simpson index of the high-dose BHF group all showed significantly statistical differences （P＜0.05 or P＜0.01）. At the phylum level， the relative abundance categories of bacterial phyla with statistically significant differences in each group included Proteobacteria， Bacteroidetes， and Firmicutes （P＜0.05 or P＜0.01）. At the genus level， the relative abundance categories of bacterial genera with statistically significant diffe-rences among each group included Muribaculaceae， Akkermansia， and Helicobacter pylori （P＜0.05 or P＜0.01）. ConclusionThe possible mechanism of BHF in treating PD may be to reconstruct the disordered intestinal flora structure and improve the inflammatory response.

Objective: To establish an optimized method for isolation and purification of microglia from aged rat brain tissue, and the phenotype of microglia was detected by flow cytometry. Methods: With young rats(3 months old) as control, the brain tissues of aged rats were immediately processed into single cell suspensions by mechanical dissociation and enzymatic digestion using type IV collagenase. Microglia were isolated on Percoll gradients(30%-37%-70%). The cells were stained with fluorescence-labeled antibodies and the phenotype of microglia was detected by flow cytometry. Results: This study developed a method that enzymatic digestion and mechanical dissociation combined with density gradient centrifugation. More single cells could be obtained by using this method. And the survival rate of cells was more than 90%. The flow cytometric analysis showed that the expression of M1 microglia marker CD86 and MHC Ⅱ increased(P<0.01), and the expression of M2 microglia marker CD200R increased(P<0.01) in aged rats compared with that in young rats. Conclusion The use of type IV collagenase and mechanical digestion combined with density gradient centrifugation is good for isolating and purifying microglia from adult and aged rat brain tissue.

The clinical data of a child with WAGR syndrome combined with end-stage renal disease admitted to the Department of Nephrology, Beijing Children′s Hospital, Capital Medical University in April 2023 was retrospectively analyzed.After a review of domestic and foreign literatures, the long-term renal function of children with WAGR syndrome was summarized.A boy, aged 11 years and 11 months, presented with a poor appetite as the initial symptom, and had markedly elevated creatinine and an estimated glomerular filtration rate of 14.96 mL/(min·1.73m 2).The inquiry about the medical history showed that the child was born with aniridia, had a history of nephroblastoma, and was mentally retarded.Gene sequencing revealed a copy number deletion of approximately 5.38 Mb in the short arm of chromosome 11, 11p14.2p13, which led to the diagnosis of WAGR syndrome.There is currently no cure for WAGR syndrome, while the detection rate of the disease has further increased with an improved understanding of the disease and extensive use of genetic testing.However, there is a lack of data on long-term renal function in children with WAGR syndrome in China.This report is the first instance of a child with WAGR syndrome progressing to end-stage renal failure in China, highlighting the significance of early identification and prompt molecular diagnosis of suspected WAGR syndrome in infancy and childhood and the importance of monitoring renal function and metabolism index of the diagnosed child from prepuberty to adulthood.In addition, the life-cycle management of children with WAGR syndrome is suggested.

Purpose To evaluate the value of shear wave elastic imaging of liver and spleen in predicting high risk esophageal and gastric varices in cirrhosis.Materials and Methods Sixty-four patients with cirrhosis in the First Hospital of Lanzhou University from November 2019 to April 2022 were enrolled prospectively,and underwent gastroscopy,elastography and serological examination.According to gastroscopy,patients were divided into high-risk varices(HRV,30 cases)and non-HRV group(34 cases),the differences of each clinical index and shear wave elastic imaging parameter between the groups were compared.The diagnostic efficacy of liver and spleen stiffness measurement for HRV was analyzed.And the diagnostic models were established for exploring the diagnostic effectiveness of different models with respect to excluding HRV in compensated liver cirrhosis.Results There were significant differences in platelet[(74±24)×109/L vs.(124±50)×109/L],liver stiffness[(16.1±5.6)kPa vs.(13.6±5.5)kPa]and spleen stiffness[(41.7±8.9)kPa vs.(28.1±8.6)kPa]between HRV and non-HRV groups(t/Z/χ2=5.136,-1.832,-6.206,all P<0.05).The areas under the curve of liver stiffness and spleen stiffness for predicting HRV were 0.660 and 0.858,respectively.The Baveno Ⅵ combined with the spleen stiffness model had the best performance(30.0％)for excluding HRV.Conclusion The measurement of liver and spleen stiffness by shear wave elastography has great diagnostic value for predicting HRV in cirrhosis,and spleen stiffness is better than liver stiffness.

Objective:To analyze the expression level of hepcidin in urine of patients with type 2 diabetic kidney disease (DKD) in different stages and its relationship with DKD and related indicators.Methods:From June 2022 to December 2023, 139 inpatients with type 2 diabetes mellitus in the Department of Endocrinology, Zhoupu Hospital Affiliated to Shanghai Health Medical College were selected as the research objects. The stage of DKD was judged by urinary albumin/creatinine ratio (UACR): UACR <30 mg/g in stage A1, UACR ≥30 mg/g~≤300 mg/g in stage A2. DKD in stage A3 was UACR >300 mg/g. According to the stage of DKD, there were 50 patients with stage A1 (group A1), 47 patients with stage A2 (group A2), and 42 patients with stage A3 (group A3). Urinary hepcidin was determined by enzyme-linked immunosorbent assay, and fasting blood glucose, total cholesterol, triglyceride, alanine aminotransferase (ALT), serum creatinine and hemoglobin A1c (HbA1c) were measured and compared. The correlation between urinary hepcidin and other markers, the risk factors of DKD and the evaluation of diagnostic value were analyzed. Measurement data with normal distribution were expressed as xˉ± s, mean comparison among the three groups, if the variance was homogeneous, the analysis of variance test was used; if the variance was not homogeneous, the Welch test was used; the proportion or rate of enumeration data among the groups was tested by χ2 test; Pearson correlation analysis was used for correlation analysis; binary Logistic regression model was used for multivariate analysis; The value of urinary hepcidin in the diagnosis of DKD was analyzed by receiver operating characteristic curve. Results:Urinary hepcidin was (5.3±1.0) μg/L in group A1, (7.7±2.5) μg/L in group A2, and (10.1±2.7) μg/L in group A3. There was significant difference among the three groups ( F=58.92， P<0.001), and urinary hepcidin increased with the severity of DKD; Urinary Hepcidin was related to UACR ( R=0.684, P<0.001), serum creatinine ( R=0.590, P<0.001), course of disease ( R=0.485, P<0.001), triglyceride ( R=0.264, P=0.002), age ( R=0.235, P<0.001), P=0.005), total cholesterol ( R=0.224, P=0.008), systolic pressure ( R=0.194, P=0.022), glomerular filtration rate ( R=-0.540, P<0.001) and BMI ( R=-0.175, P=0.040); There was no correlation with fasting blood glucose, HbA1c, ALT and diastolic blood pressure (all P>0.05). Secondly, the increase of urinary hepcidin level was a risk factor for DKD by binary Logistic regression analysis ( OR=4.147,95% CI: 2.154-7.984, P<0.001). Finally, receiver operating characteristic curve analysis showed that the optimal cut-off point of urinary hepcidin was 6.35 μg/L, with a sensitivity of 0.831 and a specificity of 0.880. Conclusion:Urinary hepcidin increases with the severity of DKD, which may be a biomarker for early diagnosis of DKD.