OBJECTIVE To investigate the clinical characteristics of euglycemic diabetic ketoacidosis （euDKA） induced by empagliflozin， and provide references for safe medication. METHODS Case reports of euDKA induced by empagliflozin were retrieved and analyzed from PubMed， Web of Science， CNKI， and Wanfang Data. The Naranjo’s scale was adopted to assess the causal relationship between empagliflozin and euDKA. RESULTS A total of 29 patients were enrolled， including 16 males and 13 females，with a median age of 58 years. All patients were diagnosed with type 2 diabetes mellitus； 22 patients had at least one comorbidity. The median time to euDKA onset was 60 days after administration， and 7 cases occurred within 2 weeks of treatment. Perioperative periods，fasting，and low-carbohydrate or ketogenic diets were the main predisposing factors. Common presentations included nausea，vomiting， fatigue， tachypnea，and tachycardia. The causal relationship between empagliflozin and euDKA was assessed as “probable” in all cases. According to adverse reaction severity grading， 13 cases were grade 3 （severe） and 16 cases were grade 4 （life-threatening）. All patients discontinued empagliflozin and recovered after corresponding treatment. CONCLUSIONS euDKA is a serious adverse reaction to empagliflozin， which mostly occurs early in treatment. Perioperative periods， fasting， and ketogenic diets are prone to induce euDKA. Elderly patients and those with comorbidities are at higher risk. Risk assessment should be conducted before clinical administration； blood ketones and acid-base monitoring should be strengthened in the early medication period； withhold the drug before elective surgery， avoid prolonged fasting；upon diagnosis， discontinue empagliflozin and initiate intravenous insulin， provide fluid resuscitation promptly， and use other treatments to improve patient prognosis.

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

Objective:To describe the hotspots and application trends of artificial intelligence (AI) in epidemiology in the past decade and analyze its advantages and challenges.Methods:The literatures with AI and epidemiology related keywords were systematically retrieved from Web of Science and China National Knowledge Infrastructure from 2014 to 2024. CiteSpace was used for bibliometric analysis of publication volume, keyword co-occurrence, clustering, emergence and cited literature co-occurrence analysis.Results:A total of 5 389 English papers and 1 659 Chinese papers were included, showing an increasing publication trend. High-frequency Chinese keywords included prediction, influencing factor, and machine learning, while English keywords frequently used were machine learning, prediction, and artificial intelligence. The Chinese keywords formed 14 clusters such as epidemiological characteristic, dietary pattern, and elderly individual, and the English keywords formed 21 clusters including prediction model, risk factor, and adult. In international studies, health policy, COVID-19, and digital health were the emerging frontier keywords. Eleven core papers were selected, covering key areas like traffic accident risk assessment, public health big data application, and deep learning in medical diagnosis.Conclusions:This study systematically summarized the research hotspots and development trends of AI applications in epidemiology over the past decade by using bibliometric methods, which indicated that current AI-based epidemiological studies are still in the exploratory phase, with the coexisting of both advantages and challenges. Continued attention should be paid to the future development of this field.

AIM:To observe the effect of continuous light on the structure and differential metabolites of gut microbiota in mice.METHODS:The mice were randomly divided into normal light(light/dark,LD)group and 24-hour continuous light(light/light,LL)group.The body weight,fasting blood glucose,serum free fatty acids,serum triacylglycerol and serum total cholesterol levels of each group of mice were measured after 10 weeks.Fresh feces were collected,and 16S rRNA sequencing technology was used to study the effect of continuous light on the diversity,structure,and species composition of gut microbiota in mice.Additionally,liquid chromatography-mass spectrometry(LC-MS)analysis was per-formed to observe the effect of continuous light on the metabolites in mice.RESULTS:Compared with the LD group,the body weight,fasting blood glucose and lipid levels of the LL group were increased(P＜0.05).At the phylum level,the proportion of Firmicutes in the LL group increased,while the proportion of Bacteroidetes decreased.At the class level,the abundance of norank_f_Muribaculaceae and Prevotellaceae_UCG-001 in the LL group decreased significantly,while the abundance of Lactobacillus,Turicibacter and Odoribacter increased significantly.Non-targeted metabolomics analysis iden-tified 65 and 73 differential metabolites under positive and negative modes,involving six major metabolic pathways,in-cluding ABC transporters,purine metabolism,pyrimidine metabolism,secondary bile acid biosynthesis,protein digestion and absorption,and choline metabolism in cancer.CONCLUSION:The structure and metabolites of gut microbiota in mice exposed to continuous light are relatively specific,and inosine may be a key biomarker and potential therapeutic tar-get for biological clock disorders.

Objective:To describe the hotspots and application trends of artificial intelligence (AI) in epidemiology in the past decade and analyze its advantages and challenges.Methods:The literatures with AI and epidemiology related keywords were systematically retrieved from Web of Science and China National Knowledge Infrastructure from 2014 to 2024. CiteSpace was used for bibliometric analysis of publication volume, keyword co-occurrence, clustering, emergence and cited literature co-occurrence analysis.Results:A total of 5 389 English papers and 1 659 Chinese papers were included, showing an increasing publication trend. High-frequency Chinese keywords included prediction, influencing factor, and machine learning, while English keywords frequently used were machine learning, prediction, and artificial intelligence. The Chinese keywords formed 14 clusters such as epidemiological characteristic, dietary pattern, and elderly individual, and the English keywords formed 21 clusters including prediction model, risk factor, and adult. In international studies, health policy, COVID-19, and digital health were the emerging frontier keywords. Eleven core papers were selected, covering key areas like traffic accident risk assessment, public health big data application, and deep learning in medical diagnosis.Conclusions:This study systematically summarized the research hotspots and development trends of AI applications in epidemiology over the past decade by using bibliometric methods, which indicated that current AI-based epidemiological studies are still in the exploratory phase, with the coexisting of both advantages and challenges. Continued attention should be paid to the future development of this field.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

AIM:To observe the effect of continuous light on the structure and differential metabolites of gut microbiota in mice.METHODS:The mice were randomly divided into normal light(light/dark,LD)group and 24-hour continuous light(light/light,LL)group.The body weight,fasting blood glucose,serum free fatty acids,serum triacylglycerol and serum total cholesterol levels of each group of mice were measured after 10 weeks.Fresh feces were collected,and 16S rRNA sequencing technology was used to study the effect of continuous light on the diversity,structure,and species composition of gut microbiota in mice.Additionally,liquid chromatography-mass spectrometry(LC-MS)analysis was per-formed to observe the effect of continuous light on the metabolites in mice.RESULTS:Compared with the LD group,the body weight,fasting blood glucose and lipid levels of the LL group were increased(P＜0.05).At the phylum level,the proportion of Firmicutes in the LL group increased,while the proportion of Bacteroidetes decreased.At the class level,the abundance of norank_f_Muribaculaceae and Prevotellaceae_UCG-001 in the LL group decreased significantly,while the abundance of Lactobacillus,Turicibacter and Odoribacter increased significantly.Non-targeted metabolomics analysis iden-tified 65 and 73 differential metabolites under positive and negative modes,involving six major metabolic pathways,in-cluding ABC transporters,purine metabolism,pyrimidine metabolism,secondary bile acid biosynthesis,protein digestion and absorption,and choline metabolism in cancer.CONCLUSION:The structure and metabolites of gut microbiota in mice exposed to continuous light are relatively specific,and inosine may be a key biomarker and potential therapeutic tar-get for biological clock disorders.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.