AIM: To explore the diagnostic value of 18 MHz color Doppler ultrasonography for epiretinal membrane.METHODS: A total of 44 cases(80 eyes)of patients with proposed diagnosis of cataract and vitreous opacity by fundus examination in our hospital between January 2020 and January 2022 were collected, and the affected eyes were examined by optical coherence tomography(OCT)and 18 MHz color Doppler ultrasonography, and the differences in the diagnostic sensitivity, specificity, and accuracy were compared between 18 MHz color Doppler ultrasonography and OCT for the diagnosis of epiretinal membrane.RESULTS: In the 80 eyes detected by 18 MHz color Doppler ultrasonography, 62 had epiretinal membrane and 18 had non epiretinal membrane. Totally 54 eyes were confirmed to have epiretinal membrane by OCT, 13 eyes were not diagnosed with epiretinal membrane, 5 eyes were missed diagnosis, and 8 eyes were misdiagnosed. The diagnostic consistency between 18 MHz color Doppler ultrasonography and OCT was high(Kappa=0.892, P<0.05); the 18 MHz color Doppler ultrasonography detection sensitivity of epiretinal membrane was 92%, specificity was 62%, missed diagnosis rate was 8%, misdiagnosis rate was 38%, and accuracy was 84%; compared with OCT detection, 18 MHz color Doppler ultrasonography detected a lower specificity, correct rate, positive prediction accuracy, negative prediction accuracy, and higher misdiagnosis rate(all P<0.05), and the difference in diagnostic sensitivity compared with leakage rate was not statistically significant(all P>0.05).CONCLUSION: 18 MHz color Doppler ultrasonography has some value in identifying epiretinal membrane lesions and is consistent with OCT testing.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background The widespread use of herbicides has led to environmental contamination and has implications for human health. The liver is an important organ for the detoxification of environmental pollutants; however, studies on the association between herbicide exposure and liver function are limited. Objectives To investigate the association between baseline serum herbicide levels and changes in liver enzyme levels and liver enzyme abnormalities over a 5-year period in middle-aged and older adults. Methods This study was based on a nested case-control population of type 2 diabetes established in the Dongfeng-Tongji cohort, with a total of 1388 subjects included in this study and followed up for 5 years. Epidemiological data were collected through questionnaires, and baseline serum concentrations of three herbicides (metolachlor, propham, and acetochlor) were measured by gas chromatography-triple quadrupole mass spectrometry. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were detected at baseline and follow-up visits. The associations between baseline serum herbicide levels and changes in AST and ALT over 5 years were assessed using linear regression models with herbicide levels categorized into quartiles, adjusting for age, sex, education level, smoking status, drinking status, physical activity, body mass index, and new-onset type 2 diabetes occurred during follow-up. The relationship between baseline serum herbicide levels and the risk of liver enzyme abnormalities during follow-up was further analyzed using logistic regression models. Results The positive rates of metolachlor, propham, and acetochlor were all higher than 80%, and their spiked rates of recovery ranged from 73.46% to 106.77%. The mean ± standard deviation of the age of subjects at baseline was (62.7±7.6) years, with 34.1% being male. The median serum levels of metolachlor, propham, and acetochlor at baseline were 0.05, 0.16, and 0.03 ng·mL⁻¹, respectively. There was no significant difference in baseline serum herbicide levels between the normal and abnormal liver enzyme groups at follow-up (P >0.05). The baseline liver enzyme levels and the changes in AST and ALT over 5 years in those who developed abnormal liver enzymes were significantly higher than those in the normal liver enzyme group (P <0.05). The linear regression analysis showed that the changes in AST increased progressively over 5 years in the second, third, and fourth quartiles of propham compared to the lowest quartile group (the second quartile: b=1.49, 95%CI: 0.10, 2.87; the third quartile: b=1.52, 95%CI: 0.14, 2.90; the fourth quartile: b=1.69, 95%CI: 0.31, 3.08; P <0.05). The associations of serum metolachlor and acetochlor with changes in AST were not significant. Additionally, no significant relationships were found between the three serum herbicides and the changes in ALT over 5 years or the risk of liver enzyme abnormalities. Conclusion Serum propham levels in middle-aged and older adults are positively associated with changes in liver enzyme AST, which may have an effect on liver function. More studies are needed to provide scientific evidence for the association between herbicide exposure and liver function.

Mendel established the laws and laid the foundation of modern genetics through his famous hybridization experiments on seven pairs of classic traits in the garden pea (Pisum sativum). However, the molecular bases underlying these traits have only come into sharp focus in recent years. Leveraging advances in traditional map-based cloning, TILLING, long-read resequencing, population genetics, and GWAS, this article synthesizes current knowledge of ten genes governing seven traits—plant height, seed shape, flower color, seed color, pod color, pod morphology, and flower position—by summarizing each gene’s identity, chromosomal localization, and functional pathway. For plant height, the classical Le locus corresponds to PsGA3ox1, which encodes a gibberellin 3β-hydroxylase. Mutations at Le impede the biosynthesis of the bioactive hormone GA₁, and the resulting deficiency leads to a dwarf or reduced-stature phenotype. Seed shape is determined by R, identified as PsSBEI (starch-branching enzyme I). Insertion of a transposable element into R restricts amylopectin synthesis, perturbing endosperm starch architecture and resulting in the wrinkled seeds noted by Mendel. Flower color is specified by the coordinated action of A (a bHLH transcription factor) and A2 (a WD40 scaffold). Together, they assemble the canonical MYB-bHLH-WD40 (MBW) regulatory complex, which co-activates structural genes in the anthocyanin pathway to determine pigment accumulation and floral hue. Seed color is governed by I, which encodes PsSGR (STAY-GREEN), a magnesium dechelatase that catalyzes a key step in chlorophyll catabolism. Loss-of-function alleles at I block chlorophyll degradation, yielding “stay-green” seeds in which chlorophyll persists beyond normal developmental stages. Pod coloration maps to Gp, corresponding to ChlG (chlorophyll synthase). Either direct loss of ChlG function or readthrough-fusion transcriptional interference caused by a large upstream deletion suppresses chlorophyll biosynthesis in developing pods, resulting in the yellow-pod phenotype. Pod morphology depends on two convergent regulatory pathways. The P gene, PsCLE41, signals through the P-PXY-WOX/NAC axis to promote vascular differentiation and secondary-wall programs, while V encodes PsMYB26, a transcription factor that drives secondary wall thickening in fiber cells. Acting in concert, these modules ensure robust secondary-wall deposition in the fiber layer lining the inner pod wall; disruption of either component compromises wall thickening and leads to pleated or wrinkled pods. Flower position (inflorescence determinacy at the shoot apex) is controlled by FA, identified as PsCIK, which participates in the CLAVATA-WUSCHEL (CLV-WUS) feedback circuit that maintains shoot apical meristem homeostasis. Mutations in FA destabilize this self-regulatory loop and promote terminal flowers at the apex. The expressivity of this determinacy phenotype is further modulated by a recessive modifier, Mfa, which fine-tunes the outcome in the fa background. Across these loci, convergent evidence highlights the central role of structural variation in generating the classical Mendelian phenotypes. Building on this clarified molecular landscape, we outline practical implications for quality improvement and the deliberate “design” of traits. Looking ahead, we envisage a next generation of legume genetic improvement anchored on three mutually reinforcing pillars: high-quality reference genomes to deliver contiguous, structurally faithful assemblies; comprehensive pan-genomes to capture presence/absence variation and structural polymorphism across germplasm; and precise gene editing to target coding, regulatory, and structural features alike. Together, these tools chart a path toward mechanism-based breeding, enabling purposeful, design-driven trait improvement in peas and, by extension, other legumes.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.