AIM:To investigate the role and mechanism of the glucagon-like peptide-1 receptor agonist lira-glutide(Lira)in regulating ferroptosis of mouse insulinoma MIN6 cells induced by high glucose and high fat.METHODS:The mouse insulinoma MIN6 cells were exposed to 30 mmol/L glucose and 500 μmol/L palmitic acid to establish an islet β cell injury model.On this basis,a ferroptosis inducer erastin,a ferroptosis inhibitor ferrostatin-1(Fer-1),and low and high concentrations of Lira were administered.Cell viability of different treatment groups were detected by CCK-8 assay.The malondialdehyde(MDA)kit was used to determine the changes in intracellular MDA content.The reactive oxygen species(ROS)kit was used to detect the changes in the ROS level of cells.The Fe2+fluorescence probe FerroOrange and mitochondrial membrane potential(JC-1)were used to detect the intracellular Fe2+levels and mitochondrial functions in different treatment groups.The mouse insulin ELISA kit was used to detect the insulin secretion of cells.RT-qPCR was used to detect the changes in the expression levels of key ferroptosis genes and insulin secretion genes in different treat-ment groups.Western blot was used to detect the expression levels of key ferroptosis proteins,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)in different treatment groups.RESULTS:Compared with the cells treated with high glucose and high fat,after treatment with Fer-1 and high-dose Lira,the cell viability,insulin secre-tion of the cells,and mitochondrial membrane potential all increased significantly,the levels of ROS,MDA and Fe2+were decreased(P<0.05).The results of RT-qPCR showed that Fer-1 and high-dose Lira significantly upregulated the expres-sion of genes promoting insulin secretion(P<0.05).The results of Western blot showed that Fer-1 and high-dose Lira sig-nificantly upregulated the expression of ferroptosis-inhibiting proteins GPX4 and SLC7A11(P<0.05).CONCLUSION:Liraglutide inhibits ferroptosis of mouse insulinoma MIN6 cells by regulating the SLC7A11/GPX4 signaling pathway,there-by improving the damage and dysfunction of MIN6 cells induced by high glucose and high fat.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Iron is one of the essential trace elements for the human body,which is crucial for the growth and development of newborns,especially premature infants.It participates in the generation of hemoglobin,affects the activity of various enzymes,and subsequently affects neurometabolism,neurochemistry,neuroanatomy,and gene/protein composition,thereby having a lasting impact on the development of the central nervous system.This article reviews the research progress on the relationship between iron metabolism and neurodevelopment in premature infants in recent years,aiming to provide scientific basis for clinical management and preventive intervention of premature infants.

AIM:To investigate the role and mechanism of the glucagon-like peptide-1 receptor agonist lira-glutide(Lira)in regulating ferroptosis of mouse insulinoma MIN6 cells induced by high glucose and high fat.METHODS:The mouse insulinoma MIN6 cells were exposed to 30 mmol/L glucose and 500 μmol/L palmitic acid to establish an islet β cell injury model.On this basis,a ferroptosis inducer erastin,a ferroptosis inhibitor ferrostatin-1(Fer-1),and low and high concentrations of Lira were administered.Cell viability of different treatment groups were detected by CCK-8 assay.The malondialdehyde(MDA)kit was used to determine the changes in intracellular MDA content.The reactive oxygen species(ROS)kit was used to detect the changes in the ROS level of cells.The Fe2+fluorescence probe FerroOrange and mitochondrial membrane potential(JC-1)were used to detect the intracellular Fe2+levels and mitochondrial functions in different treatment groups.The mouse insulin ELISA kit was used to detect the insulin secretion of cells.RT-qPCR was used to detect the changes in the expression levels of key ferroptosis genes and insulin secretion genes in different treat-ment groups.Western blot was used to detect the expression levels of key ferroptosis proteins,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)in different treatment groups.RESULTS:Compared with the cells treated with high glucose and high fat,after treatment with Fer-1 and high-dose Lira,the cell viability,insulin secre-tion of the cells,and mitochondrial membrane potential all increased significantly,the levels of ROS,MDA and Fe2+were decreased(P<0.05).The results of RT-qPCR showed that Fer-1 and high-dose Lira significantly upregulated the expres-sion of genes promoting insulin secretion(P<0.05).The results of Western blot showed that Fer-1 and high-dose Lira sig-nificantly upregulated the expression of ferroptosis-inhibiting proteins GPX4 and SLC7A11(P<0.05).CONCLUSION:Liraglutide inhibits ferroptosis of mouse insulinoma MIN6 cells by regulating the SLC7A11/GPX4 signaling pathway,there-by improving the damage and dysfunction of MIN6 cells induced by high glucose and high fat.

Iron is one of the essential trace elements for the human body,which is crucial for the growth and development of newborns,especially premature infants.It participates in the generation of hemoglobin,affects the activity of various enzymes,and subsequently affects neurometabolism,neurochemistry,neuroanatomy,and gene/protein composition,thereby having a lasting impact on the development of the central nervous system.This article reviews the research progress on the relationship between iron metabolism and neurodevelopment in premature infants in recent years,aiming to provide scientific basis for clinical management and preventive intervention of premature infants.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To establish an evaluation system of pathogen detection rate of hospitalized patients before antimicrobial treatment based on process and outcome indicators,and study its application effect.Methods Hospi-talized patients with therapeutic antimicrobial treatment in a tertiary first-class hospital from July 2022 to June 2023 were selected as the study objects.Difference in process and outcome indicators were compared between before(Ju-ly-December 2022,control group)and after(January-June 2023,intervention group)the implementation of inter-vention in the evaluation system for pathogen detection rate of hospitalized patients before antimicrobial treatment.Results 41 577 and 27 052 hospitalized patients received therapeutic antimicrobial agents were included in the inter-vention group and control group,respectively.Pathogen detection rate and the accurate pathogen detection rate in the intervention group were both higher than those in the control group(74.2％vs 62.8％and 90.3％vs 82.5％,respectively),both with statistically significant differences(both P＜0.001).The goal achievement rate and im-provement rate for pathogen detection rate were 237.5％and 18.2％respectively,the goal achievement rate and im-provement rate for accurate pathogen detection rate were 104.0％and 9.5％respectively.For the process indica-tors,the conformity rate of detection and diagnosis,accurate collection rate,timely transfer rate,acceptance rate of pathogen specimens in the intervention group were all higher than those in the control group,differences were all statistically significant(all P＜0.001).For the outcome indicators,detection rates of targeted indicators and blood culture specimens,pathogen detection rate before treatment of restricted and special grade antimicrobial agent,as well as detection rate of sterile body fluid specimens in the intervention group were all higher than those in the con-trol group,with statistical significance(all P＜0.05).In addition,the positive rate of blood culture specimens in-creased from 18.5％before intervention to 21.7％after intervention,with statistically significant difference(P＜0.05).Conclusion The establishment of indicator evaluation system can improve the detection rate and accurate detection rate of pathogens before antimicrobial treatment,as well as the management quality and connotation of indicators.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.