OBJECTIVE To establish a full-cycle management model for type 2 diabetes mellitus （T2DM） patients led by clinical pharmacists. METHODS Based on literature research， a basic framework and items of full-cycle management model led by clinical pharmacists were initially formulated. The Delphi method was adopted to conduct questionnaire inquiries among 26 experts to determine the specific implementation items of the model. The analytic hierarchy process （AHP） method was used to determine the weight values of items at all levels， and the reliability and validity of the model items were analyzed. RESULTS The recovery rates of the two rounds of expert consultation questionnaires were 86.67% and 100%， respectively， and the expert authority coefficient was 0.88. Kendall’s concordance coefficients of the tertiary-level items were 0.064 and 0.084， respectively， and the P values from the χ 2 tests were all less than 0.05； the consistent ratios of the judgment matrices for all levels of AHP model were all less than 0.1. The established full-cycle management led by clinical pharmacists comprised three primary-level items （pharmacy service pathway for T2DM patients during hospitalization， pharmacy management pathway for hypoglycemia in T2DM inpatients， and the pharmacy follow-up pathway for T2DM discharged patients， with weights of 0.098， 0.568 and 0.334， respectively）， twelve secondary-level items （e.g. pharmaceutical care during hospitalization for 1 to 2 days， admission assessment and education， with weights ranging from 0.143 to 0.333） and thirty-seven tertiary-level items （e.g. assessment of medication compliance， verification of the medication plan for discharge， with weights ranging from 0.068 to 0.750）. Cronbach’s α coefficients for primary-level items and the overall questionnaire were 0.762， 0.879， 0.928 and 0.951， respectively. The item-level and scale-level content validity indexes were 0.967 and 0.808， respectively. CONCLUSIONS A full-cycle management model for T2DM patients led by clinical pharmacists has been constructed successfully， demonstrating high scientificity and reliability.

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

In response to the current problems in the traditional methods used for teaching the course of "maternal, child, and adolescent health", including the monotony of teaching modes, poor learning outcomes, limited use of information technology-based teaching, and the need for improved faculty professionalism, this study explored the reform and practice of teaching modes for this course. Teaching reform centered on a task-driven pre-class learning guide, supported by the development of a resource platform. This platform was used to assign pre-class and post-class tasks. An information technology-based platform facilitated teaching implementation during class. Systematical analysis and evaluation were performed on the teaching process and implementation effects. By continuously optimizing course design, adjusting teaching strategies, and improving the autonomy and learning efficiency of students, the system can be used to improve teaching effectiveness and quality. This system provides a reference for information technology-based teaching reform in similar courses.

In response to the current problems in the traditional methods used for teaching the course of "maternal, child, and adolescent health", including the monotony of teaching modes, poor learning outcomes, limited use of information technology-based teaching, and the need for improved faculty professionalism, this study explored the reform and practice of teaching modes for this course. Teaching reform centered on a task-driven pre-class learning guide, supported by the development of a resource platform. This platform was used to assign pre-class and post-class tasks. An information technology-based platform facilitated teaching implementation during class. Systematical analysis and evaluation were performed on the teaching process and implementation effects. By continuously optimizing course design, adjusting teaching strategies, and improving the autonomy and learning efficiency of students, the system can be used to improve teaching effectiveness and quality. This system provides a reference for information technology-based teaching reform in similar courses.

Objective:To investigate the effects of matrix metalloproteinase 10(MMP10)on the proliferation,migration,invasion,and lymph node metastasis of oral squamous cell carcinoma(OSCC)cells,and to explore the underlying mechanisms.Methods:Gene expression profile data and survival data of head and neck squamous cell carcinoma(HNSCC)tissues and adjacent non-cancerous tissues were downloaded from The Cancer Genome Atlas(TCGA).Protein expression profile data of HNSCC tissues and adjacent non-cancerous tissues were downloaded from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)database,and select the data of OSCC from HNSCC.The data from public database were used to analyze the differences in MMP10 expression at the mRNA and protein level between HNSCC/OSCC tissues and adjacent non-cancerous tissues,and to analyze the impact of MMP10 expression level on the survival rate of HNSCC patients,as well as the impact of human papillomavirus(HPV)on MMP10 gene expression in HNSCC patients.MMP10 expression level in 52 pairs of OSCC tissue samples and adjacent non-cancerous tissue samples(from the First Affiliated Hospital of Fujian Medical University)was measured by real-time quantitative PCR.After silencing MMP10 expression using siRNA(siMMP10-1291 and siMMP10-1336),the effect of MMP10 on the proliferation ability of OSCC cells was detected by CCK-8 assay and colony formation assay.The effects of MMP10 on the migration and invasion abilities of OSCC cells was assessed by wound-healing assay and transwell assay,respectively.To verify the effect of MMP10 knocking down on lymph node metastasis of OSCC cells in vivo,we constructed a nude mouse tongue cancer orthotopic model by shRNA(shMMP10-1291 and shMMP10-1336).Differential expression genes associated with MMP10 were screened from the gene expression profile data of OSCC patients in the TCGA database,and pathway enrichment analysis was performed using the GSEA software to further analyze the correlation between MMP10 and genes from the significantly enriched pathway.Results:Compared with adjacent non-cancerous tissues,the expression level of MMP10 in HNSCC and OSCC tissues was significantly increased(P<0.000 1),and HNSCC patients with high MMP10 expression had a lower survival rate(HR=1.32,P=0.04).HNSCC patients in the HPV-group had higher MMP10 gene expression levels(P<0.000 1),but their survival rate was significantly lower than that of HNSCC patients in the HPV+group(HR=0.48,P=0.004).Downregulating MMP10 expression could inhibit the migration,invasion and lymph node metastasis in vivo of OSCC cells.In OSCC patients,differentially expressed genes associated with MMP10 were significantly enriched in the Wnt signaling pathway(NES=1.505,P=0.029),and multiple genes in the Wnt signaling pathway,including WNT3,WNT3A,WNT5A,and WNT5B,were positively correlated with the expression level of MMP10.Conclusion:MMP10 promotes the invasion,metastasis and lymph node metastasis in vivo of OSCC cells by regulating the Wnt signaling pathway.

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck ; Carcinogenesis/genetics* ; Cell Transformation, Neoplastic ; Wnt Signaling Pathway ; Disease Models, Animal ; Head and Neck Neoplasms/genetics* ; Wnt Proteins ; Frizzled Receptors/genetics* ; Janus Kinase 1 ; STAT3 Transcription Factor

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.