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.

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.

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.

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 identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.