Background: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominant, inherited, systemic, vascular disorder primarily involving the small arteries. It is characterized by migraine, recurrent ischemic strokes, cognitive decline, and dementia. Mutations in the Notch receptor 3 gene (NOTCH3) and the HtrA serine peptidase 1 gene (HTRA1) are 2 genetic causes for CADASIL. The NOTCH3 gene, located on chromosome 19p13.12, is the most common disease-causing gene in CADASIL. Objective: To investigate genetic causes in 2 unrelated Han-Chinese patients with presentations strongly suggestive of CADASIL. Methods: Exome sequencing was performed on both patients and potential pathogenic mutations were validated by Sanger sequencing. Results: This study reports on 2 unrelated Han-Chinese patients with presentations strongly suggestive of CADASIL, identifying that NOTCH3 mutations were the genetic cause. A common mutation, c.268C>T (p.Arg90Cys), and a novel mutation, c.331G>T (p.Gly111Cys) in the NOTCH3 gene, were detected and confirmed in the patients, respectively, and were predicted to be deleterious based on bioinformation analyses. Conclusions: We identified 2 NOTCH3 mutations as likely genetic causes for CADASIL in these 2 patients. Our findings broaden the mutational spectrum of the NOTCH3 gene accountable for CADASIL. Clinical manifestations supplemented with molecular genetic analyses are critical for accurate diagnosis, the provision of genetic counseling, and the development of therapies for CADASIL.

Background: Polydactyly, characterized by supernumerary digits in the upper or lower extremities, is the most common congenital digital abnormalities. It derives from the defective patterning of anteroposterior axis of the developing limb, with various etiology and clinical heterogeneity. The patients with post-axial polydactyly type A (PAPA) have the typical symptom of a well-formed supernumerary digit outside the fifth digit.Objective: The aim of present study was to identify the causative mutations of two unrelated Han Chinese patients with non-syndromic PAPA.Methods: Two unrelated Han Chinese patients and 100 ethnicity-matched, unrelated normal controls were recruited for this study. BGISEQ-500 exome sequencing was performed in the two patients, followed by validation in the patients and 100 controls by using Sanger sequencing.Results: Two mutations in the GLI family zinc finger 3 gene (GLI3), including a frameshift mutation c.3437_3453delTCGAGCAGCCCTGCCCC (p.L1146RfsX95) and a nonsense mutation c.3997C>T (p.Q1333X), were identified in two patients but were absent in the 100 healthy controls.Conclusion: The two GLI3 mutations, p.L1146RfsX95 and p.Q1333X, may account for non-syndromic PAPA in the two patients, respectively. The findings of this study may expand the mutational spectrum of GLI3-PAPA and provide novel insights into the genetic basis of polydactyly.

Purpose: The study was aimed at identifying that cytochrome b (CYTB) expression regulation by trimethylamine N‐oxide (TMAO) can induce mitochondria reactive oxygen species (ROS) and promote vascular endothelial cells (VECs) pyroptosis. Methods: VECs were transfected with TET methylcytosine dioxygenase 2 (TET2)/CYTB overexpression lentivirus, CYTB siRNA, TET2 shRNA, or NC. ROS levels were measured using MitoSOX Red fluorescence, and pyroptosis was evaluated via Hoechst 33342/PI staining. Western blot was used to measure TET2, the NOD-like receptor thermal protein domain associated protein 3 (NLRP3), proteolytic cleavage of gasdermin D (GSDMD), CYTB, and Caspase-1 expression. Interleukin (IL)-1β was quantified by ELISA. The mRNA expression of IL-1β, CYTB, ND2, and TET2 was measured by qRT-PCR. Cellular ultrastructure was examined by electron microscope, and calcium flux was monitored with Fluo-4AM. CYTB methylation was detected using Targeted Bisulfite Sequencing. Results: This study showed that TMAO can down-regulate the expression of CYTB inVECs, cause VECs pyroptosis and mitochondrial dysfunction (MDF). CYTB overexpression antagonized the effect of TMAO. Further, silencing CYTB promoted mtROS production, and MitoTEMPO, a ROS scavenger, inhibited VECs pyroptosis caused by CYTB silencing. In addition, TET2 had demethylation activity. The expression of CYTB was positively regulated by TET2. TMAO was able to inhibit the expression of TET2 and promote the methylation level of the CYTB gene promoter. Conclusion: TMAO promotes the methylation level of the CYTB gene promoter and down-regulates the expression of CYTB by inhibiting the expression of TET2. The decreased expression level of CYTB induces ROS, promoting VECs pyroptosis.

Acupuncture has potential in the treatment of female sexual dysfunction (FSD), but its effectiveness needs to be verified. A meta-analysis to provide a summary of studies that had investigated the efficacy of acupuncture as a treatment for FSD. A systematic screening was conducted on electronic databases such as Pubmed, Embase, Cochrane Library, CNKI, and CBM to select studies that met the criteria before April 2023. We only included those studies assessing women's sexual functioning by the Female Sexual Function Index (FSFI). By calculating the relative risk (RR) using the standardized mean difference (SMD) and 95% confidence interval (CI), these data were combined to generate a summary of the findings. The pooled results were calculated using a random-effects model. A total of 4 studies involving 178 participants were included, and the comprehensive results indicated a significant difference in FSFI scores between the acupuncture group and the control group. In the desire and arousal scale, there was a statistically significant difference between the acupuncture group and the control group. But in the scale of lubrication, orgasm, satisfaction, and pain, there was no statistically significant difference between the two groups. A comparison of overall FSFI scores, sexual desire, and sexual arousal revealed that acupuncture treatment can improve female sexual dysfunction to some extent. However, in terms of vaginal lubrication, orgasm, sexual satisfaction, and sexual pain, acupuncture treatment did not significantly improve female sexual dysfunction. In the future, it is necessary to include more RCT trials and expand the number of patients analyzed to make the conclusions more reliable.

Female breast cancer is the most common and the fifth deadliest cancer worldwide. It is influenced by a combination of genetic, hormonal, and environmental factors. The excision repair cross‐complementation group 3 gene (ERCC3) has recently been identified as a breast cancer susceptibility gene in various cohorts of different geographical and ethnic origin. To explore the role of ERCC3 mutations in breast cancer development and pathological diagnosis, genetic analysis was conducted in 291 patients and 291 controls from mainland China. Bioinformatic analysis and immunohistochemistry (IHC) were performed. A novel ERCC3 mutation p.Y116X was identified in a breast cancer family, while no frequency bias for the genotype and allele of rs754010782 and rs371627165 was observed (all P > 0.05). Bioinformatic analysis revealed that ERCC3 expression was negatively associated with estrogen receptor (ER), progesterone receptor (PR), nontriple‐negative status, and nodal status of breast cancers. ERCC3 amplifications and deep deletions primarily occurred in breast invasive cancer not otherwise specified (NOS) and metaplastic breast cancer, respectively. The decreased ERCC3 expression in tumor tissues of patient with p.Y116X mutation was found by IHC. The ERCC3 mutation p.Y116X may increase breast cancer risk in the Han‐Chinese population. ERCC3 exhibits potential as a biomarker for the pathological diagnosis of breast cancer.

Cancer stem cells (CSCs) are a small but highly plastic subpopulation of tumor cells that play essential roles in tumor initiation, heterogeneity, metastasis, therapeutic resistance, and recurrence. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of CSC biology through diverse molecular mechanisms. They can modulate chromatin architecture, epigenetic modifications, transcriptional activity, RNA stability, alternative splicing, protein function, signaling pathway activation, intercellular communication, and even micropeptide production. Through these regulatory modes, lncRNAs influence key CSC properties, including self-renewal, proliferation, survival, differentiation, metabolic plasticity, epithelial–mesenchymal transition, immune evasion, and drug resistance. Increasing evidence indicates that lncRNAs regulate major stemness-associated pathways, such as Wnt/β-catenin, Notch, Hedgehog, Hippo/YAP, TGF-β, and PI3K/AKT signaling, thereby sustaining CSC phenotypes and promoting tumor progression. In addition, CSC-associated lncRNAs may serve as promising biomarkers for diagnosis, prognosis prediction, recurrence monitoring, and therapeutic response evaluation. Therapeutic strategies targeting lncRNAs, including antisense oligonucleotides, small interfering RNAs, CRISPR/Cas-based approaches, and nanoparticle-mediated delivery systems, offer potential opportunities to eliminate CSCs and overcome treatment resistance. However, the clinical translation of lncRNA-targeted therapies remains limited by tumor heterogeneity, context-dependent lncRNA functions, delivery efficiency, off-target effects, and safety concerns. In this review, we summarize the molecular mechanisms of lncRNA action, discuss the functional roles of lncRNAs in CSC regulation, and highlight their clinical implications as biomarkers and therapeutic targets. A deeper understanding of lncRNA-mediated CSC regulation may provide new insights into cancer progression and support the development of more precise strategies to prevent tumor relapse and improve therapeutic outcomes .