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.

In recent years， data mining algorithms have been widely employed in scientific research within the field of traditional Chinese medicine （TCM）. The data mining algorithms are used to effectively handle and analyze the complex data in TCM formulas， providing a rational explanation for the mechanism of action. This method has proven particularly useful in uncovering patterns of compatibility and frequent combinations of herbs in TCM， thereby enhancing the reliability and accuracy of clinical diagnosis， target screening， and the study of new drugs. This paper reviews and analyzes 147 papers on TCM formula research that utilize data mining algorithms. The results indicate that data mining algorithms play a unique advantage in six sub- areas， including the study on the mechanism of action in TCM formula， the dose-efficacy of TCM formulas， the identification of core drugs pairs/groups， mining the relationships among “formulas-drug-symptom”， the discovery of new formulas， and mining the compatibility law. Notably， association rules and clustering algorithms are the most representative.

BackgroundThe guardianship ability of guardians of patients with severe mental disorders plays an important role in supporting the patients' recovery and reintegration into society. It is necessary to develop a scientific tool since there is a lack of tools to quantitatively assess the guardianship ability. ObjectiveTo explore and develop an assessment scale for the guardianship ability of guardians of patients with severe mental disorders， so as to provide references for the construction of scientific and reasonable guardianship ability evaluation tools. MethodsA pool of scale items was constructed through a literature review and interviews， followed by two rounds of expert consultation with 15 specialists. 364 guardians of patients with severe mental disorders in Guangzhou were investigated. The scale items were screened and optimized using item analysis and exploratory factor analysis， and the structural validity of the scale was further verified through confirmatory factor analysis. The content validity of the scale was evaluated by item-level content validity index （I-CVI） the average scale-level content validity index （S-CVI/Ave）. The reliability of the scale was tested by Cronbach's α coefficient and split-half reliability. ResultsThe guardianship ability scale for guardians of patients with severe mental disorders consists of 25 items， including three dimensions of guardianship willingness， guardianship knowledge and behavior and guardianship self-efficacy. The results of the item analysis showed that all items met the corresponding criteria and were retained. Validity test： the I-CVI ranged from 0.800 to 1.000， and the S-CVI/Ave was 0.964. Factor load of each item on the corresponding factors ranged from 0.596 to 0.976， and the model demonstrated good fit： chi-square degree of freedom ratio （χ²/df） was 2.444， Tucker-Lewis index （TLI） was 0.908， comparative goodness of fit index （CFI） was 0.917， standardized root mean square residual （SRMR） was 0.049， and root mean square residual （RMSEA） was 0.089. Reliability test showed that the total scale had a Cronbach's α coefficient of 0.966， and the split half reliability coefficient was 0.915. ConclusionThe guardianship ability scale for patients with severe mental disorders developed in this study has good reliability and validity， and has certain application value for the assessment of guardianship ability for patients with severe mental disorders. ［Funded by Health Science and Technology Project of Guangzhou （number， 20221A011049）］

Purpose To observation the relationship be-tween the β-catenin/Slug signal specific inhibitor FH535 and EMT,and to explore the role of LPCAT1 in regulating the inva-sion,metastasis,and growth of cervical cancer cells.Methods Hela cells were transfected with sh-NC and sh-LPCAT1,and SiHa cells were transfected with Vector group and LPCAT1 over-expression plasmid.SiHa cells were divided into control group(Con),LPCAT1 group,LPCAT1+FH535 group and FH535 group.The proliferation of cervical cancer cells was detected by CCK-8 analysis and colony formation test.The metastasis and invasion ability of cervical cancer cells were detected by wound healing test and Transwell test.Western blot was used to analyze the expression of LPCAT1,β-catenin/Slug signaling pathway and EMT-related proteins in cells.Results Compared with Vector group,the cell viability,colony number,migration and invasion number of SiHa cells in LPCAT1 group increased signif-icantly(P＜0.05).Compared with sh-NC group,the cell via-bility,colony number,migration and invasion number of Hela cells in sh-LPCAT1 group decreased significantly(P＜0.05).Compared with LPCAT1 group,the levels of Wnt4(1.18±0.05 vs 0.80±0.06),β-catenin(1.05±0.08 vs 0.77±0.05),Slug(1.13±0.06 vs 0.28±0.02),Cyclin D1(0.99±0.06 vs 0.44±0.02),N-cadherin(0.91±0.07 vs 0.46±0.03)and vimentin(0.95±0.06 vs 0.49±0.03)in SiHa cells in LPCAT1+FH535 group decreased significantly(P＜0.05),and the level of E-cadherin(0.44±0.03 vs 0.58±0.03)in-creased significantly(P＜0.05).In addition,compared with LPCAT1 group,the number of colonies(224±15 vs 146±11),migration(85±3vs51±4)and invasive(166±10 vs 90±5)cells of SiHa cells in LPCAT1+FH535 group decreased signifi-cantly(P＜0.05).Conclusion The increase of LPCAT1 ex-pression may promote the metastasis and progress of CC by acti-vating β-catenin/Slug signaling pathway,and LPCAT1 may be a potential marker for predicting CC metastasis.

BACKGROUND:Frog active peptides have rich activities,such as antibacterial and anti-tumor,and are expected to solve the problem of antibiotic resistance. OBJECTIVE:The active peptide QUB2984 was discovered in the skin secretions of Agalychnis callidryas.Its structure and properties were simulated by bioinformatics.The peptide was synthesized,purified,and identified and its biological functions were investigated. METHODS:Agalychnis callidryas skin secretions were collected by electrostimulation.The sequence of QUB2984 was obtained through constructing a cDNA library with isolated mRNA.BLAST was used for peptide sequence alignment.Besides that,Iterative Threading ASSEmbly Refinement(I-TASSER)and HeliQuest tools were used for protein secondary structure simulation.It was synthesized by solid-phase peptide synthesis,purified by reverse-phase high-performance liquid chromatography,and structurally confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.The purified peptide was used to evaluate its biological activity.Its antibacterial effect was evaluated by the minimum inhibitory concentration method.Its cytotoxic effect was detected by MTT assay.Its safety was investigated by a hemolysis test. RESULTS AND CONCLUSION:(1)Peptide QUB2984 had basically α-spiral structure,with a relatively intact hydrophobic surface,and a certain destructive ability to biofilm.The third amino acid position of QUB2984 was composed of W and had a G-X-G structure.(2)The minimum inhibitory concentration of QUB2984 against gram-positive Staphylococcus aureus was 2 μmol/L,the minimum inhibitory concentration against gram-negative Escherichia coli was 2 μmol/L,and the minimum inhibitory concentration against the fungus Candida albicans was 8 μmol/L.(3)The active peptide QUB2984 had obvious inhibitory effect on human non-small cell lung cancer cells NCI-H838 at 10-5 mol/L concentration,and the hemolytic effect on horse red cells at 64 μmol/L concentration was 50%.(4)The results showed that QUB2984 had anti-bacterial and anti-cancer activity,and it had a positive charge of +3,which was conducive to contact with bacteria or cells.

Objective:To investigate the alteration of m6A demethylase AlkB homolog 5 (ALKBH5) expression and its impact on form-deprivation myopia (FDM) retina in guinea pigs.Methods:Thirty normal SPF grade 3-week-old tricolor guinea pigs were randomly divided into normal control group and experimental group, with 15 in each group.In the experimental group, the right eyes were covered as FDM group and the left eyes uncovered were set as self-control group.Ocular biometry was performed at one-week intervals from baseline to week 4 of the experiment.Spherical equivalent was detected by streak retinoscopy and axial length was measured by A-scan ultrasonography.Animals were sacrificed after 4 weeks of modeling.The distribution and expression of ALKBH5 protein in the guinea pig retina was detected by immunohistochemical and immunofluorescence staining.Expression of ALKBH5 mRNA and protein in guinea pig retina was detected by real-time fluorescence quantitative PCR and Western blot, respectively.The use of animals in ophthalmic and vision research followed the tenets of Animal Research in Vision and Ophthalmology, and the study was approved by the Ethics Committee of North Sichuan Medical College (No.2023087).Results:At weeks 2, 3, and 4 after myopia induction, diopters and axial lengths were significantly higher in the FDM group than in the normal control group and the self-control group (all at P<0.001). Immunohistochemistry and immunofluorescence assays showed that ALKBH5 protein was expressed in the retinal nerve fiber layer, rod/cone photoreceptor cells, and retinal pigment epithelium (RPE) layer, and was highly expressed in the retinal nerve fiber layer and RPE layer.The relative ALKBH5 immunofluorescence intensity in the normal control group, self-control group and FDM group was 1.000±0.204, 0.874±0.076 and 0.571±0.053, respectively, which was lower in the FDM group than in the normal control and self-control groups, showing statistically significant differences ( t=4.069, P=0.006; t=5.176, P=0.014). After 4 weeks of modeling, ALKBH5 mRNA and protein expressions were significantly lower in FDM group than in normal control and self-control groups (both at P<0.01). Conclusions:The expression of m6A demethylase ALKBH5 is decreased in the retina of FDM guinea pigs, suggesting that ALKBH5 and related m6A methylation modification may be involved in the development and progression of myopia.

Objective To investigate the incidence and causes of medication errors(MEs)related to aspirin in the eld-erly(≥60 years old)of China,to provide data for targeted precautions,and to promote medication safety in the elderly.Methods Reports about aspirin-related MEs in the elderly were extracted from the National Monitoring Network for Clinical Safe Drug Medication from September 22,2012 to September 22,2022.The severity of errors,content of errors,where errors were made,the personnel who made these errors,and causes of errors were analyzed retrospectively and statistically.Results A total of 386 MEs reports were extracted,235 males and 151 females,with a median age of 70(60-98)years old.Regarding the severity of MEs,errors of class B were dominating(314 cases,81.35%).As for the severe MEs(9 cases,2.33%),5 cases of ME were as-sociated with bleeding.There are four patients suffering from gastrointestinal bleeding:one patient took aspirin three times a day,one patient broke off enteric-coated tablets,one patient took aspirin as acarbose mistakenly,one patient took aspirin with Xuesai-tong for long time.One patient had urinary urgency,but did not seek medical attention in time,then developed into visible hema-turia.Two patients missed taking aspirin led to stent thrombosis.One patient suffered from diarrhea after overdosing on 29 pills of aspirin by mistake.One patient with hyperuricemia had gout after taking aspirin.Among these 386 MEs,224(58.03%)cases were triggered by physicians,the first three error factors were frequency(multiple times a day),dosage(the dosage of enteric-coated tablets is not the whole tablet),and variety.Most of these MEs were due to a lack of knowledge or training,and fatigue.Regarding the MEs caused by pharmacists(87 cases,22.54%).Pharmacists identified 274 cases(70.98%)of errors.Conclusion When it comes to aspirin-related MEs,it ought to be noticed that the drug usage and dosage,drug interaction,and selection of drug varieties when combining with other diseases(such as atrial fibrillation and hyperuricemia).It is recommended that information construction be fortified to decrease the ME of the prescription link,and the clinicians be better informed of rational drug use.At the same time,patient medication education should be improved.