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.

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.

Objective:To investigate the characteristics of cortical morphology in children with attention defi-cit hyperactivity disorder(ADHD)and those with oppositional defiant disorder(ODD)from both categorical and dimensional analyses.Methods:A total of 72 children were enrolled,including 16 children with ADHD and ODD,20 children with ADHD without ODD,and 36 age-gender-matched normal children.The diagnoses were made ac-cording to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)criteria.The Chi-nese Wechsler Intelligence Scale for Children(C-WISC)was used to access intelligence quotient.All subjects par-ticipated in the magnetic resonance imaging(MRI)scan.The features of cortical morphology were determined using FreeSurfer software.Results:Children with ADHD and ODD[(6 528.1±857.5)mm3 vs.(7 591.2±657.3)]and children with ADHD only[(6 867.2±41.3)mm3 vs.(7 591.2±657.3)mm3]had smaller volume in the left later-al superior temporal gyrus(P＜0.05)than controls.No difference was found between ADHD with ODD group and ADHD without ODD group.There was no correlation between the cortical volume of left lateral superior temporal gyrus and ODD symptoms.Conclusion:The reduced cortical volume of left lateral superior temporal gyrus may be an important indication of the abnormal brain structure of ADHD in children.And comorbid status of ODD dose not change this structural variation.

Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library. Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated. Ⅱ-1 (IC₅₀ = 6.40 ± 0.34 μmol·L^-1) and Ⅱ-2 (IC₅₀ = 7.15 ± 0.51 μmol·L^-1) exhibited outstanding activity. Subsequently, the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay, Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability. Using molecular docking technology and molecular dynamics simulation technology, the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A (DYRK1A). By enzyme activity testing, the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48% and 32%, respectively.

Objective To observe the clinical efficacy of compound Wufengcao liquid combined with negative pressure wound therapy with instillation(NPWTi)for the treatment of stage Ⅲ-Ⅳ pressure injury(PI),and to preliminarily explore its action mechanism.Methods(1)Clinical research:from January 2019 to October 2022,60 PI patients who were admitted to the Scrofula Department and Wound Care Clinic at Nanjing Municipal Hospital of Traditional Chinese and Western Medicine were randomly divided into normal saline NPWTi group and compound Wufengcao liquid NPWTi group,with 30 cases in each group.Both groups underwent NPWTi under the premise of systemic basic treatment,before treatment,after removing the negative pressure device in the 1st,2nd and 3rd weeks of treatment,the pressure ulcer scale for healing(PUSH)score,the wound bacterial culture detection rate and the wound healing time were counted,and the vascular endothelial growth factor(VEGF)content of wound tissue was detected by ELISA method.(2)Animal experiments:24 SD rats were randomly divided into blank group,model group,normal saline NPWTi group and compound Wufengcao liquid NPWTi group,6 rats in each group.PI rat model was established by local tissue ischemia/reperfusion injury method,and the negative pressure device was removed at the end of each day of treatment.Before treatment and 3,7 and 10 days after treatment,the wound morphology of each group of rats was observed,the wound histopathology was observed by HE staining,the CD34 positive cells rate of wound tissue was detected by immunohistochemistry,and the expressions of p38 mitogen-activated protein kinase(p38 MAPK),nuclear factor-κB p65(NF-κB p65),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),arginase-1(Arg-1)and transforming growth factor-β(TGF-β)in rat blood and wound tissue were detected by ELISA and RT-qPCR.Results(1)Clinical research:Both groups could effectively reduce the PUSH score and the wound bacterial culture detection rate,shorten the wound healing time,and promote the expression of VEGF in wound tissue,the compound Wufengcao liquid NPWTi group was better than the normal saline NPWTi group(P<0.05).(2)Animal experiments:Compared with blank group,the rats in the model group showed obvious wound inflammatory response and tissue damage,and the CD34 positive cells rate,blood and wound tissue p38 MAPK,NF-κB p65,iNOS and TNF-α levels were significantly increased,Arg-1 and TGF-β level was significantly reduced(P<0.05);Compared with model group,after 7 days of treatment,the normal saline NPWTi group and the compound Wufengcao liquid NPWTi group significantly decreased the wound morphology score,the histopathological morphology was significantly improved,the CD34 positive cells rate was significantly increased(P<0.05),the levels of blood and wound tissue p38 MAPK,NF-κB p65,iNOS,and TNF-α were significantly reduced,and the levels of Arg-1 and TGF-β were significantly increased(P<0.05),and the compound Wufengcao liquid NPWTi group was better than that of the normal saline NPWTi group(P<0.05).Conclusion Compound Wufengcao liquid combined with NPWTi can effectively promote the healing of PI wounds,and its mechanism of action may be by inhibiting the activation and expression of p38 MAPK/NF-κB signaling pathway,thereby regulating the polarization balance of M1/M2 macrophages.

Objective:To summarize the relevant evidence of exercise intervention for patients with multiple myeloma at home and abroad, and provide evidence-based basis for medical staff to formulate exercise intervention programs.Methods:Through the method of evidence-based nursing, the literatures related to exercise intervention for patients with multiple myeloma were systematically retrieved from relevant guideline websites, professional association websites and databases at home and abroad, including best practices, recommended practices, guidelines, expert consensus, evidence summary, systematic reviews and so on. The search time limit was established until April 16, 2024. Two researchers evaluated the quality of the literature and extracted the data. JBI pre-classification of evidence and level of Recommendation system (2014 version) was used to determine the level of evidence items and recommendation level.Results:A total of 15 articles were included, including 1 clinical decision, 4 guidelines, 8 systematic reviews, 1 expert consensus and 1 evidence summary. A total of 26 pieces of evidence were summarized, including 5 aspects, including applicable population, exercise evaluation, exercise plan, exercise precautions and exercise management.Conclusions:The best evidence summarized in this study provides a basis for the development and management of exercise intervention in patients with multiple myeloma. It is suggested that clinical staff should fully consider the clinical context when applying the evidence, and develop personalized exercise intervention programs based on the patient′s status and preferences.

Purpose To detect the expression of PP1A and GSDME and the abundance of CD8+T lymphocytes in colorectal cancer,and to explore the correlation and clinical significance of PP1A and GSDME mediated pyroptosis.Methods GEPIA da-tabase was applied to analyze the mRNA expression of PP1A and GSDME in colorectal cancer and normal tissues.Western blot assay was used to detect the expression of PP1A in colorectal cancer and the corresponding normal mucosa.Immunohisto-chemistry was applied to detect the expression of PP1A and GS-DME and CD8+T lymphocytes abundance in 107 colorectal car-cinomas and normal mucosa adjacent to the carcinomas.Spearman rank correlation was used to analyze the correlation between PP1A,GSDME and CD8+T cells abundance.Results The GEPIA database search showed that mRNA expression of PP1A and GSDME in colorectal cancer differed compared to normal tissues(P＜0.05).Western blot analysis showed that the relative expression of PP1A in colorectal cancer tissue was significantly higher than that in para-cancerous tissues(0.937 vs 0.643,P＜0.001).Immunohistochemical results showed that the expression of PP1A in colorectal cancer tissues was signifi-cantly higher than that in normal mucosa(P＜0.05).The ex-pression of GSDME in cancer tissue was closely correlated with patients'age,clinical stage and mismatch repair proteins(P＜0.05),and the distribution of CD8+T cells in the cancer infil-tration front was significantly higher than that in the normal mu-cosa,and the distribution of CD8+T cells in the cancer was cor-related with pT stage,clinical stage and lymph node metastasis.Spearman correlation analysis showed that PP1A was negatively correlated with GSDME expression(r=-0.196,P＜0.05).The overall survival PP1A-positive colorectal cancer patients was worse than that of PP1A-negative patients(P＜0.05),and the prognosis of patients was correlated with the degree of differentia-tion,lymph node metastasis,pT stage and clinical stage.Posi-tive expression of PP1A,degree of differentiation,clinical stage,pT stage and lymph node metastasis are independent risk factors affecting the prognosis of colorectal cancer patients.Conclusion PP1A is highly expressed in colorectal cancer and negatively correlated with GSDME-mediated cell pyroptosis,and the differ-ential expression of both is closely related to the progression and prognosis of colorectal cancer,which can be used as a potential indicator for judgment of the prognosis of colorectal cancer pa-tients.The differential distribution of CD8+T cells may be asso-ciated with GSDME-mediated cell pyroptosis and tumor develop-ment.

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.