Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

The protein kinase A/protein kinase G/protein kinase C-family (AGC kinase family) of eukaryotes is involved in regulating numerous biological processes. The 3-phosphoinositide- dependent protein kinase 1 (PDK1), is a conserved serine/threonine kinase in eukaryotes. To understand the roles of PDK1 homologous genes in cell death and immunity in tetraploid Nicotiana tabacum, the previuosly generated transgenic CRISPR/Cas9 lines, in which 5-7 alleles of the 4 homologous PDK1 genes (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out, were used in this study. Our results showed that the hypersensitive response (HR) triggered by transient overexpression of active Pto (Pto^Y207D) or soybean GmMEKK1 was significantly delayed, whereas the resistance to Pseudomonas syrangae pv. tomato DC3000 (Pst DC3000) and tobacco mosaic virus (TMV) was significantly elevated in these partial knockout lines. The elevated resistance to Pst DC3000 and TMV was correlated with the elevated activation of NtMPK6, NtMPK3, and NtMPK4. Taken together, our results indicated that NtPDK1s play a positive role in cell death but a positive role in disease resistance, likely through negative regulation of the MAPK signaling cascade.
Nicotiana/virology* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plants, Genetically Modified/genetics* ; Gene Knockout Techniques ; Plant Proteins/genetics* ; CRISPR-Cas Systems ; Protein Serine-Threonine Kinases/genetics* ; 3-Phosphoinositide-Dependent Protein Kinases/genetics* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Tobacco Mosaic Virus/pathogenicity*

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

AIM:The aim of this study was to explore the effects of Yiqi-Yangyin-Quyu prescription(YP)on skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome(SS),and to clarify the role of hy-droxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta(Hadhb)in mediating the effect of YP on skeletal muscle in SS.METHODS:The SS mice underwent YP treatment for 8 weeks.The morphological changes of the submandibular gland and muscle tissue were examined using hematoxylin-eosin staining.The mitochondrial status in mus-cle tissue was assessed through transmission electron microscopy.Additionally,combined transcriptome and proteome se-quencing was conducted on skeletal muscle samples.The omics sequencing results were validated by RT-qPCR.Immuno-fluorescence was used to confirm the levels of key proteins involved in the P53/peroxisome proliferator-activated receptor gamma(PPARG)signaling pathway.Immunohistochemistry and Western blot were employed to determine the levels of Hadhb key targets.RESULTS:Combined transcriptome and proteome analysis identified 1 523 differentially expressed genes(DEGs)and 182 differentially expressed proteins(DEPs)between the muscle tissue of SS mice(model group)and that of control animals(ICR group),12 of which showed co-differential expression at both transcriptomic and proteomic levels.Compared with model group,1 232 genes and 432 proteins were found to be differentially expressed in the muscle tissue of the mice in YP group.Among these,23 exhibited co-differential expression at both mRNA and protein levels.Gene Ontology(GO)analysis showed that the DEGs and DEPs between ICR and model groups were mainly involved in ener-gy metabolism and fatty acid oxidation,while the DEGs and DEPs between YP and model groups were primarily associated with sarcomere tissue and actin structure.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indi-cated that the DEGs and DEPs between ICR and model groups and between model and YP groups were enriched in the com-plement and coagulation cascade and lipid and pyruvate metabolism.The RT-qPCR validation results were consistent with those of the transcriptome analysis.Furthermore,the protein expression of the tumor suppressor P53 was significantly de-creased in YP group compared with model group,whereas that of PPARG was significantly increased.Western blot analy-sis showed that compared with ICR group,Hadhb protein expression was significantly decreased in model group,whereas the opposite trend was detected in YP group.CONCLUSION:The SS-related skeletal muscle damage is closely related to amino acid metabolism disorder and fatty acid degradation.Treatment with YP modulates innate immune defenses,lipid metabolism and energy metabolism in SS,and Hadhb is the key target of YP in SS-related skeletal muscle.

Objective To establish a rapid on-site detection method for methamphetamine(MA)based on surface-enhanced Raman spectroscopy(SERS).Methods Laboratory-synthesized colloidal silver nanoparticles(AgNPs)were employed as SERS substrates to rapidly detect methamphetamine in typical crime scene matrices,including beer,cigarette ash,and plastic containers.Results The method requires no sample pretreatment,is simple to operate,and offers high sensitivity with fast detection speed.The limit of detection(LOD)reached 10 ppb(signal-to-noise ratio,S/N＞3).The qualitative results of methamphetamine analysis from forensic case samples were highly consistent with gas chromatography-mass spectrometry(GC-MS)findings.Conclusion Methamphetamine is frequently encountered in illicit settings and criminal activities.This study achieved rapid detection of methamphetamine in complex matrices(beer,cigarette ash,and plastic containers),demonstrating good application prospects in practice and providing important value for law enforcement,public safety,and criminal investigation.

Objective:To analyze the incidence and risk factors of malignant tumors among HIV-infected patients in Taizhou, Zhejiang Province.Methods:The data were collected from the China Information System for Disease Control and Prevention and the Taizhou Chronic Disease Information Management System. A retrospective cohort study design was used. The subjects were HIV-infected patients who had their household registration in Taizhou from 2005 to 2023 and participated in the follow-up. The observation period was until December 31, 2024. The standardized incidence ratios (SIR) of malignant tumors among HIV-infected patients were analyzed. Cox proportional hazards regression model was used to analyze the influencing factors of malignant tumor incidence.Results:A total of 3 593 HIV-infected patients were included, of whom 292 had malignant tumors. The proportions of AIDS-defining malignancies and non-AIDS-defining malignancies were 12.33% (36/292) and 87.67% (256/292), respectively. The proportion of malignant tumors before and after AIDS confirmation was 43.49% (127/292) and 56.51% (165/292), respectively. 3 466 HIV-infected patients were included in the follow-up cohort, with a total follow-up of 24 968.59 person-years. The incidence rate of malignant tumors in patients with HIV infection was 658.46 per 100 000 (SIR=1.89, 95% CI: 1.61-2.20). The SIR of malignant tumors showed an upward trend with the increase of time. The results of Cox proportional hazards regression model analysis showed that HIV-infected patients in the age groups of 45-59 and ≥60 years (a HR=2.58, 95% CI: 1.26-5.28; a HR=5.00, 95% CI: 2.38-10.51) were more likely to develop malignant tumors. HIV-infected patients with an educational level of senior high school or above (a HR=0.52, 95% CI: 0.29-0.95) and those in the first CD4 +T lymphocyte/CD8 +T lymphocyte count ratio ≥0.5 (a HR=0.52, 95% CI: 0.28-0.97) were less likely to develop malignant tumors. Conclusions:From 2005 to 2023, the incidence of malignant tumors among HIV-infected people in Taizhou was higher than that of the general population, and most of them were non-AIDS-defining malignancies. It is necessary to strengthen the early screening and diagnosis of malignant tumors among HIV-infected patients.

Objective This study aims to improve the evaluation index system for the operation of department levels in tertiary public hospitals,strengthen process management,and promote the comprehensive reform and high-quality development of public hospitals.Methods Through literature retrieval and theoretical analysis,a framework for the evaluation index system of department-level operation in tertiary general public hospitals was constructed,and evaluation indicators were initially proposed.Based on the Delphi method,a systematic sorting and adjustment of the evaluation indicators for department-level operation in public hospitals were carried out,and the evaluation index system was finally established.Results The response rates and effec-tive rates of the two rounds of questionnaires using the Delphi method were 90.00％and 83.33％,respectively.The authority co-efficient was 0.8,and the differences in coordination coefficients were statistically significant.The indicators passed the consis-tency test,and the final evaluation index system was composed of 5 first-level indicators,14 second-level indicators,and 43 third-level indicators.Conclusion The evaluation indicators for the operation of department levels in tertiary general public hos-pitals are conducive to guiding hospitals to improve their internal management level and providing support for the implementation of the high-quality development strategy of public hospitals.

Objective:To analyze the incidence and risk factors of malignant tumors among HIV-infected patients in Taizhou, Zhejiang Province.Methods:The data were collected from the China Information System for Disease Control and Prevention and the Taizhou Chronic Disease Information Management System. A retrospective cohort study design was used. The subjects were HIV-infected patients who had their household registration in Taizhou from 2005 to 2023 and participated in the follow-up. The observation period was until December 31, 2024. The standardized incidence ratios (SIR) of malignant tumors among HIV-infected patients were analyzed. Cox proportional hazards regression model was used to analyze the influencing factors of malignant tumor incidence.Results:A total of 3 593 HIV-infected patients were included, of whom 292 had malignant tumors. The proportions of AIDS-defining malignancies and non-AIDS-defining malignancies were 12.33% (36/292) and 87.67% (256/292), respectively. The proportion of malignant tumors before and after AIDS confirmation was 43.49% (127/292) and 56.51% (165/292), respectively. 3 466 HIV-infected patients were included in the follow-up cohort, with a total follow-up of 24 968.59 person-years. The incidence rate of malignant tumors in patients with HIV infection was 658.46 per 100 000 (SIR=1.89, 95% CI: 1.61-2.20). The SIR of malignant tumors showed an upward trend with the increase of time. The results of Cox proportional hazards regression model analysis showed that HIV-infected patients in the age groups of 45-59 and ≥60 years (a HR=2.58, 95% CI: 1.26-5.28; a HR=5.00, 95% CI: 2.38-10.51) were more likely to develop malignant tumors. HIV-infected patients with an educational level of senior high school or above (a HR=0.52, 95% CI: 0.29-0.95) and those in the first CD4 +T lymphocyte/CD8 +T lymphocyte count ratio ≥0.5 (a HR=0.52, 95% CI: 0.28-0.97) were less likely to develop malignant tumors. Conclusions:From 2005 to 2023, the incidence of malignant tumors among HIV-infected people in Taizhou was higher than that of the general population, and most of them were non-AIDS-defining malignancies. It is necessary to strengthen the early screening and diagnosis of malignant tumors among HIV-infected patients.