Objective To investigate the loci in the STRtyper-21G kit that are prone to tolerance mismatches when compared with the GlobalFilerTM kit and the PowerPlex? 21 kit,and to analyze the underlying causes.Methods A total of 5,870 database comparison reports involving STRtyper-21G profiles and other autosomal STR kits were examined for identity alignment.Samples showing mismatched loci were re-tested using the STRtyper-21G,GlobalFilerTM,and PowerPlex? 21 kits.For loci with mismatches,primers were redesigned and sequencing was performed.Results Eight mismatched samples(8/5 870)were identified,involving the loci D18S51,D8S1179,and D2S1338.Sequencing revealed that the allele dropout at D18S51 was due to a G→A mutation at the 79th base upstream of the core sequence;at D8S1179,a C→A mutation at the 4th base upstream;and at D2S1338,a C→T mutation at the 22nd base downstream.Conclusion All mismatches were attributable to mutations in primer binding regions.These findings provide reference for interpreting mismatch results in the STRtyper-21G database.When mismatches occur at these loci and the profiles are homozygous,exclusion conclusions should be made with caution.

Objective To investigate the loci in the STRtyper-21G kit that are prone to tolerance mismatches when compared with the GlobalFilerTM kit and the PowerPlex? 21 kit,and to analyze the underlying causes.Methods A total of 5,870 database comparison reports involving STRtyper-21G profiles and other autosomal STR kits were examined for identity alignment.Samples showing mismatched loci were re-tested using the STRtyper-21G,GlobalFilerTM,and PowerPlex? 21 kits.For loci with mismatches,primers were redesigned and sequencing was performed.Results Eight mismatched samples(8/5 870)were identified,involving the loci D18S51,D8S1179,and D2S1338.Sequencing revealed that the allele dropout at D18S51 was due to a G→A mutation at the 79th base upstream of the core sequence;at D8S1179,a C→A mutation at the 4th base upstream;and at D2S1338,a C→T mutation at the 22nd base downstream.Conclusion All mismatches were attributable to mutations in primer binding regions.These findings provide reference for interpreting mismatch results in the STRtyper-21G database.When mismatches occur at these loci and the profiles are homozygous,exclusion conclusions should be made with caution.

Objective To establish a classification tree model for non-alcoholic fatty liver disease(NAFLD)among aircrews,screen for influencing factors of NAFLD,so as to provide scientific basis for prevention and intervention decisions for NAFLD.Methods Aircrews who underwent recuperation at a sanatorium from January 2019 to December 2023 were selected as the research objects.Their annual physical examination data were collected and the NAFLD detection rate was calculated.Age,body mass index(BMI),blood pressure,waist circumference,blood routine,biochemistry indexes,and thyroid function were incorporated,and a NAFLD risk model was constructed using classification regression tree method.The predictive performance of the NAFLD classification tree model was evaluated through model misclassification matrix,risk statistics,and receiver operating characteristic curve.Results A total of 4088 aircrews were included in the study,and NAFLD was detected in 380 persons(380/4088,9.30%).The NAFLD model consisted of three layers,and five explanatory variables affecting the onset of NAFLD were extracted,including BMI,triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),and total bilirubin(TBIL).BMI was located at the top of the classification tree and was the most important risk factor for NAFLD in aircrews.The area under the curve(AUC)of the model was 0.853.The predictive accuracy of NAFLD was 90.9%,indicating that the model has good accuracy and fitting effect.Conclusion In this study,the detection rate of NAFLD in aircrews was 9.30%.BMI,TG,HDL-C,ALT,and TBIL are risk factors for the onset of NAFLD.NAFLD is mainly related to weight gain and lipid metabolism disorders caused by unhealthy lifestyles.

Objective The objective of this research was to examine the cardioprotective properties of a SIRT1 agonist in mice afflicted with coronary artery disease(CAD).Methods Using the random number table method,60 male C57BL/6J mice were randomly divided into a control group,a model group,an SRT1 agonist group(Group SRT 1460,30 mg/kg),an Nrf2 inhibitor group(ML385 group,10 mg/kg),and a combined treatment group of SRT 1460+ML385,with 12 mice in each group.The control group mice were fed with normal feed,and the other groups of mice were fed with high-fat feed to create atherosclerosis mouse model.The modeling period was 12 weeks.After the successful construction of the model,ultrasonic parameters were used to detect the myocardial function of mice;two-dimensional ultrasound spot tracking technology was used to detect the strain of each layer of left ventricular myocardium.Pathological alterations in myocardial tissue were detected via HE staining,and the levels of cTnI,LDH and CK were measured using ELISA.Cardiomyocyte apoptosis was evaluated using TUNEL analysis,and levels of ROS in myocardial tissue were measured via DHE fluorescence assay.Additionally,SOD activity and MDA,GSH and Fe2+contents in myocardial tissue were determined using colorimetry.Finally,gene and protein expressions of Nrf2,GPX4,FTH1,and ACSL4 were assessed through qRT-PCR and Western blot analysis.Results A significant decrease in LVEDd and LVPWd levels was observed in the SRT 1460 group(P<0.05),whereas increases in GLSendo,GLSmid,and GCSendo levels were identified.A decrease in collagen fiber deposition was observed in the SRT 1460 group,in which the myocardium space narrowed.In comparison to the control group,the SRT 1460 group showed reductions in serum cTnI,CK,and LDH levels,cardiomyocyte apoptosis rate,ROS,MDA,and Fe2+contents,as well as ACSL4 mRNA and protein levels(P<0.05).An increase in SOD activity and GSH content as well as in Nrf2,GPX4,and FTH1 mRNA and protein levels was observed(P<0.05).By inhibiting the nuclear translocation of Nrf2,ML385 could significantly block the regulatory effect of SRT 1460(P<0.05).Conclusion It has been shown that SRT 1460 enhances GLSendo,GLSmid,and GCSmid,and improves left ventricular remodeling and systolic function in mice with CAD,in part because it regulates the Nrf2-GPX4 ferroptosis pathway.

The incidence of cardiovascular diseases(CVD)has been increasing year by year,with atherosclerosis(As)being the leading cause in terms of both incidnce and mortality for CVD in China.Traditional theories suggest that the pathogenesis of atherosclerotic CVD is associated with endothelial dysfunction and inflammatory responses caused by the accumulation of oxidized low density lipoprotein(ox-LDL).However,recent studies have demonstrated that perivascular adipose tissue(PVAT)can positively influence the occurrence and development of CVD through the vascular adventitia pathway.This article reviews the connection between PVAT and CVD,effective pathways for promoting CVD improve-ment,and the regulatory role of AMP-activated protein kinase(AMPK)on PVAT,aiming to explore effective intervention targets for CVD.

Objective To investigate the effect of the rs3765467 polymorphism of glucagon-like peptide-1 receptor(GLP-1R)gene on the efficacy of Liraglutide(Lir)in patients with type 2 diabetes mellitus(T2DM)and metabolic associated fatty liver disease(MAFLD).Methods A total of 281 patients with T2DM from May 2022 to May 2023 were selected,including 125 patients with simple T2DM(T2DM group)and 156 patients with T2DM combined with MAFLD(T2DM+MAFLD group).120 healthy individuals during the same period were selected as the control(NC)group.The related indexes of glucose and lipid metabolism were detected.The polymorphism of GLP-1R gene rs3765467 was detected.Results BMI,FPG,HbA1c,HOMA-IR and TG in each group increased in turn(P<0.05),while the distribution frequency of genotype GG and allele G decreased in turn(P<0.05).TC and LDL-C in T2DM and T2DM+MAFLD groups were higher than those in NC group(P<0.05).TC and TG levels in genotype GA/AA patients were significantly higher than those in genotype GG patients(P<0.05).Compared with before treatment,the levels of BMI,FPG,HbA1c,HOMA-IR,TC,TG and LDL-C in T2DM patients with MAFLD were significantly decreased after Lir treatment(P<0.05).There was no significant difference in BMI and related indexes of glucose and lipid metabolism in GG and GA/AA patients before and after Lir treatment(P>0.05).Conclusions The distribution frequency of GG and G allele at rs3765467 of GLP-1R gene is reduced in T2DM patients with MAFLD.The carrying of allele A was associated with increased TC and TG levels,but did not affect the efficacy of Lir in reducing weight and improving glycolipid metabolism.

AIM: To observe the characteristics of best corrected visual acuity(BCVA), microperimetry(MP), multifocal electroretinogram(mfERG), and optical coherence tomography angiography(OCTA)parameters in patients with idiopathic epiretinal membrane(IERM), and conduct a comparative study and correlation analysis on these parameters.METHODS:This was a cross-sectional study. A total of 56 patients(56 eyes)diagnosed with IERM who visited our hospital between February 2021 and November 2024 were collected as IERM group, and 33 healthy individuals(33 eyes)undergoing physical examinations were included as control group. Parameters were compared between the IERM group and the control group, as well as among IERM subgroups at different stages. Additionally, correlations among visual function parameters and between these visual function parameters and vascular structural OCTA parameters were analyzed.RESULTS: The general data of patients in the control group and IERM group were comparable. In the IERM group, BCVA, retinal sensitivity(RS), P1 wave amplitude in ring 1, superficial capillary plexus parafoveal vessel density(SCPpfvd), deep capillary plexus parafoveal vessel density(DCPpfvd), and the foveal avascular zone(FAZ)area were significantly lower than the control group(all P<0.01). In contrast, central retinal thickness(CRT), superficial capillary plexus foveal vessel density(SCPfvd), and deep capillary plexus foveal vessel density(DCPfvd)were significantly increased(all P<0.001). When comparing different stages of IERM, significant differences were observed in BCVA, CRT, RS, SCPfvd, and FAZ(all P<0.01). In eyes affected by IERM, BCVA(LogMAR)was negatively correlated with RS; P1 wave amplitude in ring 1 positively correlated with P1 wave implicit time in ring 1; SCPfvd positively correlated with BCVA(LogMAR)and negatively correlated with RS; DCPfvd negatively correlated with P1 wave implicit time in ring 1; and DCPpfvd positively correlated with RS(all P<0.05).CONCLUSION: Eyes with IERM exhibit abnormalities in visual function parameters and vascular structure, with varying degrees of alteration in BCVA, CRT, RS, SCPfvd, and FAZ across different stages. Comprehensive evaluation of BCVA, MP, mfERG, and OCTA contributes to a deeper understanding of the nature of IERM and aids in formulating appropriate diagnosis and treatment plans.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

We have isolated an intestinal probiotic strain, Pediococcus acidilactici HRQ-1. To improve its gastrointestinal fluid tolerance, transportation and storage stability, and slow-release properties, we employed the extrusion method to prepare the microcapsules with P. acidilactici HRQ-1 as the core material and sodium alginate and chitosan as the wall material. The optimal conditions for preparing the microcapsules were determined by single factor and orthogonal tests, and the optimal ratio was determined by taking the embedding rate, survival rate, storage stability, gastrointestinal fluid tolerance, and release rate as the evaluation indexes. The results showed that under the optimal embedding conditions, the embedding rate reached (89.60±0.02)%. Under the optimal formula of freeze-drying protective agent, the freeze-drying survival rate reached (76.42±0.13)%, and the average size of the microcapsules produced was (1.16±0.03) mm. The continuous gastrointestinal fluid simulation experiments confirmed that the microcapsules ensured the viable bacterial count and can slowly release bacteria in the intestinal fluid. The curve of the viable bacterial count during storage at 4 ℃ and room temperature indicated that the prepared microcapsules achieved strains' live number protection. The formula and preparation process of P. acidilactici microcapsules may provide a technological reserve for the preparation of more live bacterial drugs in the future.
Pediococcus acidilactici/chemistry* ; Probiotics/chemistry* ; Capsules/chemistry* ; Alginates/chemistry* ; Chitosan/chemistry* ; Drug Compounding/methods* ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry* ; Freeze Drying

The incidence of cardiovascular diseases(CVD)has been increasing year by year,with atherosclerosis(As)being the leading cause in terms of both incidnce and mortality for CVD in China.Traditional theories suggest that the pathogenesis of atherosclerotic CVD is associated with endothelial dysfunction and inflammatory responses caused by the accumulation of oxidized low density lipoprotein(ox-LDL).However,recent studies have demonstrated that perivascular adipose tissue(PVAT)can positively influence the occurrence and development of CVD through the vascular adventitia pathway.This article reviews the connection between PVAT and CVD,effective pathways for promoting CVD improve-ment,and the regulatory role of AMP-activated protein kinase(AMPK)on PVAT,aiming to explore effective intervention targets for CVD.