Objective:To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2).Methods:Three children who were diagnosed with ILFS2 at the Children′s Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). Results:The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c. 3596G>A and c.1181A>T in child 1, c.2617C>T and c. 2T>C in child 2, and c. 3596G>A and c. 2817_2818insT in child 3. Among these, the c. 1181A>T and c. 2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+ PM3+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:Combined with the patient′s clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c. 1181A>T and c. 2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.

OBJECTIVE: To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2). METHODS: Three children who were diagnosed with ILFS2 at the Children's Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). RESULTS: The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c.3596G>A and c.1181A>T in child 1, c.2617C>T and c.2T>C in child 2, and c.3596G>A and c.2817_2818insT in child 3. Among these, the c.1181A>T and c.2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+PM3+PP3) and pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION Combined with the patient's clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
Humans ; Exome Sequencing ; Genetic Testing/methods* ; Liver Failure, Acute/etiology* ; Mutation ; Child ; Adult ; Neoplasm Proteins

Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

Head and neck squamous cell carcinoma(HNSCC)is a highly prevalent malignancy with poor prognosis.Treatment strategies to date have achieved limited success in significantly improving overall survival rates.γδ T cells,a unique subset of immune cells in the tumor microenvironment,can link adaptive and innate immune functions.While γδ T cells can effectively recognize and eliminate HNSCC tumor cells,certain subsets of these cells can secrete interleukin-17,contributing to tumor progression.Nevertheless,due to their remarkable cyto-toxic activity,γδ T cells have been identified as promising candidates for antitumor immunotherapy.This article reviews the biological back-ground of γδ T cells,their role in tumor immunity in HNSCC,and recent advances in γδ T cell immunotherapy,aiming to provide new in-sights into HNSCC diagnosis and treatment.

Head and neck squamous cell carcinoma(HNSCC)is a highly prevalent malignancy with poor prognosis.Treatment strategies to date have achieved limited success in significantly improving overall survival rates.γδ T cells,a unique subset of immune cells in the tumor microenvironment,can link adaptive and innate immune functions.While γδ T cells can effectively recognize and eliminate HNSCC tumor cells,certain subsets of these cells can secrete interleukin-17,contributing to tumor progression.Nevertheless,due to their remarkable cyto-toxic activity,γδ T cells have been identified as promising candidates for antitumor immunotherapy.This article reviews the biological back-ground of γδ T cells,their role in tumor immunity in HNSCC,and recent advances in γδ T cell immunotherapy,aiming to provide new in-sights into HNSCC diagnosis and treatment.

Objective:To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2).Methods:Three children who were diagnosed with ILFS2 at the Children′s Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). Results:The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c. 3596G>A and c.1181A>T in child 1, c.2617C>T and c. 2T>C in child 2, and c. 3596G>A and c. 2817_2818insT in child 3. Among these, the c. 1181A>T and c. 2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+ PM3+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:Combined with the patient′s clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c. 1181A>T and c. 2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.

Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients,detect their related resistance genes,and provide reference for the clinical treatment of carbapenem resistant Enterobacteria(CRE)infections and the rational use of antibiotics.Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected.The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method.The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR.Results Among the 400 strains,51 strains were identified as CRE,accounting for 12.75%.Among these,49 strains produced carbapenemases,with 41 strains(80.39%)being CR Klebsiella pneumoniae and 10 strains(19.61%)being CR Escherichia coli.Among the CRE strains,34 strains(66.67%)carried blaKPC,13 strains(25.49%)carried blaNDM,and 2 strains(3.92%)carried blaOXA-48.Conclusion Compared with other commonly used antibiotics,colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli.In addition,there was good concordance between drug resistance phenotype testing and genotyping.Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions.

Objective To establish a method for the determination of 10 organophosphorus flame retardants in drinking water by on-line solid phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry (On-line SPE-UPLC-MS/MS). Methods After adding the internal standard, the water sample was filtered by Millipore filtration, and then concentrated and detected by Online SPE-UPLC-MS/MS. Samples were concentrated by C₈ SPE column and separated by C₁₈ column with acetonitrile-water-formic acid as the mobile phases gradient elution，and were detected by multiple reaction monitoring (MRM) acquisition under anion mode. Results The 10 organophosphorus flame retardants all displayed good linear relationships within a certain range of concentrations, with the correlation coefficients being more than 0.990. The method detection limits were 0.60-5.50 ng/L, and the spiked recoveries of low, medium and high concentrations were 64%-106% , 83%-104% and 85%-99%, respectively. Conclusion The method is simple, sensitive, rapid, accurate and reliable, so it is applicable for the determination of 10 organophosphorus flame retardants in drinking water.

Objective:To investigate the efficacy and safety of daratumumab in the treatment of systemic light chain amyloidosis.Methods:The clinical data of 24 patients with systemic light chain amyloidosis who received daratumumab-based regimens in Sichuan Provincial People's Hospital from January 2020 to November 2022 were retrospectively analyzed. The treatment process of patients was summarized and the therapeutic efficacy was evaluated. Kaplan-Meier method was used to make survival analysis and the adverse reactions were analyzed.Results:All 24 patients included 2 cases (8.33%) of Mayo 2004 stageⅠ, 2 cases (8.33%) of Mayo 2004 stage Ⅱ and 20 cases (83.33%) of Mayo 2004 stage Ⅲ. All patients were treated with daratumumab-based regimen, and 17 patients had evaluable efficacy. In the chemotherapy regimens, 15 patients received DVd (daratumumab + bortezomib + dexamethasone) regimen, 7 patients received DVCd (daratumumab + bortezomib + cyclophosphamide + dexamethasone) regimen, 1 patient received DRd (daratumumab + lenalidomide + dexamethasone) regimen, and 1 patient received DTd (daratumumab +thalidomide + dexamethasone) regimen. After 1 course of daratumumab-based regimens in 17 cases with evaluable efficacy, the strict complete remission (sCR) rate was 41.18% (7/17), the overall response rate (ORR) was 88.24% (15/17). Among 17 patients who received daratumumab-based chemotherapy regimen as the first-line treatment, sCR rate of 11 cases with evaluable efficacy was 36.36% (4/11) after 1 course of treatment ORR was 90.90% (10/11). Among 5 relapsed/refractory patients, sCR rate of 4 cases with evaluable efficacy was 50.00% (2/4) after 1 course of treatment; ORR was 75.00% (3/4). Among 24 patients, renal involvement was found in 17 patients at the initial diagnosis. After 1 course of daratumumab-based chemotherapy regimen, ORR of 7 cases with evaluable efficacy was 85.71% (6/7), among which 42.86% (3/7) patients with renal involvement had an assessed renal response of very good partial remission (VGPR) or above. At the initial diagnosis, 19 cases had cardiac involvement; ORR of 14 cases with evaluable efficacy was 85.71% (12/14), among which 42.86% (6/14) patients had cardiac response to VGPR or above. After daratumumab-based chemotherapy regimen, the main adverse reactions were infusion-related adverse reactions, myelosuppression and infection, all of which were tolerated by the patients. The median follow-up time of 24 patients was 7.0 months (0.5- 16.5 months), the median progression-free survival time was 7.0 months (0.5-16.5 months) and the median overall survival time was 7.0 months (0.5-35.0 months).Conclusions:Daratumumab-based chemotherapy regimen has good efficacy and safety in the treatment of systemic light chain amyloidosis.

Objective To analyze the epidemiological characteristics of norovirus infectious diarrhea in the active monitoring of foodborne diseases in Jiangsu Province from 2015 to 2020, so as to provide reference for the prevention and control of foodborne diseases caused by norovirus. Methods Norovirus positive diarrhea cases were collected from sentinel hospitals in 13 districts and cities of Jiangsu Province, and their epidemiological and clinical characteristics were analyzed. Results Atotal of 3 620 norovirus positive cases were detected and isolated from 61 489 samples. The main serotype was GII (71.97%), the onset season was winter and spring, and the onset age was 1-3 years old and 14-34 years old. There was no significant difference in norovirus positive rate between different sexes, and the main symptom was diarrhea (incidence rate was 92.10%), Meat and meat products (20.20%) were the main types of suspected exposed foods. Conclusion Norovirus infection has obvious seasonal characteristics, and the population is generally susceptible. It is high in children and young people, and meat food was the main suspicious exposure food. We should continue to improve the ability of active monitoring, identification, early warning and control of foodborne diseases, so as to reduce the occurrence of foodborne diseases.