The output of cataract surgery performed by trained non-ophthalmologist physicians in rural areas: study of cataract outcomes and up-take of services report 7.

BACKGROUND: Cataract is the leading cause of blindness worldwide and surgery can restore vision in most patients. Some patients have little access to surgical services due to lack of cataract surgeons and the unaffordable costs. In 2005 we built a service model that trained rural non-ophthalmologist physicians to perform cataract surgeries in rural China. This study evaluates the long-term impacts of this model. METHODS: We conducted a retrospective cohort study to analyze patients' hand-written medical records and electronic outpatient record between January 2005 and December 2019 at two rural health clinics in Southern China. RESULTS: In total, 34,601 patients (49,942 eyes) underwent cataract surgery by non-ophthalmologist physicians from 2005 to 2019.Visual acuity was clearly documented in 38,251 eyes. Before surgery, the unaided distance visual acuity (UDVA) of 60.7% (23,205/38,251) eyes was less than 0.05 decimal. On the first day after surgery, the percentage of UDVA < 0.05 eyes was reduced to 6.0%, and 96.7% (36,980/38,251) of the eyes achieved a better UDVA compared to pre-operation. Surgical-related complications occurred in 218 eyes. The most common complication was posterior capsule rupture (114, 0.23%). 44.3% (15,341/34,601) of the patients chose to have a second eye cataract surgery (SECS) in the same clinic. At one of the outpatient clinics, 21,595 patients received basic eye care apart from cataract surgery between 2018 and 2020. CONCLUSIONS: Non-ophthalmologist physicians trained for cataract surgeries in rural clinics can improve cataract related visual acuity and basic eye care to the local population.

Therapeutically Fine-Tuning Autonomic Nervous System to Treat Sepsis: A New Perspective on the Immunomodulatory Effects of Acupuncture.

Recent studies have highlighted the immunomodulatory effects of acupuncture on sepsis and proposed novel non-pharmacological or bioelectronic approaches to managing inflammatory illnesses. Establishing rules for selectively activating sympathetic or vagal nerve-mediated anti-inflammatory pathways using acupuncture has valuable clinical applications. Over the years, studies have revealed the segmental modulatory role of acupuncture in regulating visceral function by targeting the autonomic nervous system (ANS). In this review, we aim to summarize recent findings on acupuncture in treating sepsis, focusing on the underlying ANS mechanism, as well as the rules of acupoint specificity, intensity, frequency, and other parameters utilized in these studies. Mechanistically, the immunomodulatory properties of the sympathetic nervous system have been highlighted. Furthermore, we explore the immunotherapeutic benefits of acupuncture in treating sepsis. A better understanding of the immunoregulatory mechanism of sympathetic nervous system may offer novel approaches for the development of therapeutics to treat or prevent a variety of inflammatory diseases.

Overcoming Cancer Persister Cells by Stabilizing the ATF4 Promoter G-quadruplex.

Persister cells (PS) selected for anticancer therapy have been recognized as a significant contributor to the development of treatment-resistant malignancies. It is found that imposing glutamine restriction induces the generation of PS, which paradoxically bestows heightened resistance to glutamine restriction treatment by activating the integrated stress response and initiating the general control nonderepressible 2-activating transcription factor 4-alanine, serine, cysteine-preferring transporter 2 (GCN2-ATF4-ASCT2) axis. Central to this phenomenon is the stress-induced ATF4 translational reprogramming. Unfortunately, directly targeting ATF4 protein has proven to be a formidable challenge because of its flat surface. Nonetheless, a G-quadruplex structure located within the promoter region of ATF4 (ATF4-G4) is uncovered and resolved, which functions as a transcriptional regulator and can be targeted by small molecules. The investigation identifies the natural compound coptisine (COP) as a potent binder that interacts with and stabilizes ATF4-G4. For the first time, the high-resolution structure of the COP-ATF4-G4 complex is determined. The formation of this stable complex disrupts the interaction between transcription factor AP-2 alpha (TFAP2A) and ATF4-G4, resulting in a substantial reduction in intracellular ATF4 levels and the eventual death of cancer cells. These seminal findings underscore the potential of targeting the ATF4-G4 structure to yield significant therapeutic advantages within the realm of persister cancer cells induced by glutamine-restricted therapy.

Extracellular vesicle-packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models.

Perineural invasion (PNI) is a biological characteristic commonly observed in pancreatic cancer. Although PNI plays a key role in pancreatic cancer metastasis, recurrence, and poor postoperative survival, its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) were closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles (EVs) were involved in PNI in dorsal root ganglion coculture and mouse sciatic nerve models. Next, we demonstrated that CAFs promoted PNI through extracellular vesicle transmission of PNI-associated transcript (PIAT). Mechanistically, PIAT specifically bound to YBX1 and blocked the YBX1-Nedd4l interaction to inhibit YBX1 ubiquitination and degradation. Furthermore, PIAT enhanced the binding of YBX1 and PNI-associated mRNAs in a 5-methylcytosine (m5C)-dependent manner. Mutation of m5C recognition motifs in YBX1 or m5C sites in downstream target genes reversed PIAT-mediated PNI. Consistent with these findings, analyses using a KPC mouse model demonstrated that the PIAT/YBX1 axis enhanced PNI through m5C modification. Clinical data suggested that the PIAT expression in the serum EVs of patients with pancreatic cancer was associated with the degree of neural invasion and prognosis. Our study revealed the important role of the PIAT/YBX1 signaling axis in the tumor microenvironment (TME) in promoting tumor cell PNI and provided a new target for precise interference with CAFs and RNA methylation in the TME to suppress PNI in pancreatic cancer.

Targeted quantitative metabolomic and flavor objective quantification technique reveal the impact mechanism of shaking on black tea quality and non-volatile metabolites.

Shaking constitutes a pivotal technique for enhancing black tea quality; nevertheless, its impact on the transformation mechanism of non-volatile metabolites (NVMs) in black tea remains obscure. The present study aimed to investigate the impact of shaking-withering methods (SWM) and traditional-withering methods (TWM) on black tea quality and NVMs conversion. A total of 57 NVMs and 14 objective quantitative indicators were obtained. SWM enhanced sweetness and umami taste, as well as appearance and liquor color brightness of black tea. Eight key differential NVMs were identified by multivariate statistical and dose over threshold value analysis. Metabolic pathway and evolution law analysis revealed that SWM enhanced the oxidation of catechins and flavonol glycosides, promoted the decarboxylation of glutamic acid, then facilitated the formation of theaflavin-3,3'-digallate, finally enhanced the taste and color quality of black tea. This study offers theoretical guidance and technical support for the targeted processing of high-quality black tea.

Empathy in undergraduate medical students: a multi-center cross-sectional study in China.

BACKGROUND: Fostering empathy has been continuously emphasized in the global medical education. Empathy is crucial to enhance patient-physician relationships, and is associated with medical students' academic and clinical performance. However, empathy level of medical students in China and related influencing factors are not clear. METHODS: This was a cross-sectional study among medical students in 11 universities. We used the Jefferson Scale of Empathy Student-version of Chinese version to measure empathy level of medical students. Factors associated with empathy were identified by the univariate and multivariate logistic regression analyses. Based on the variables identified above, the nomogram was established to predict high empathy probability of medical students. Receiver operating characteristic curve, calibration plot and decision curve analysis were used to evaluate the discrimination, calibration and educational utility of the model. RESULTS: We received 10,901 samples, but a total of 10,576 samples could be used for further analysis (effective response rate of 97.02%). The mean empathy score of undergraduate medical students was 67.38 (standard deviation = 9.39). Six variables including gender, university category, only child or not, self-perception doctor-patient relationship in hospitals, interest of medicine, Kolb learning style showed statistical significance with empathy of medical students (P < 0.05). Then, the nomogram was established based on six variables. The validation suggested the nomogram model was well calibrated and had good utility in education, as well as area under the curve of model prediction was 0.65. CONCLUSIONS: We identify factors influencing empathy of undergraduate medical students. Moreover, increasing manifest and hidden curriculums on cultivating empathy of medical students may be needed among medical universities or schools in China.

Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain.

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain and unravel the underlying mechanisms.

Leukoaraiosis: Epidemiology, Imaging, Risk Factors, and Management of Age-Related Cerebral White Matter Hyperintensities.

Leukoaraiosis (LA) manifests as cerebral white matter hyperintensities on T2-weighted magnetic resonance imaging scans and corresponds to white matter lesions or abnormalities in brain tissue. Clinically, it is generally detected in the early 40s and is highly prevalent globally in individuals aged >60 years. From the imaging perspective, LA can present as several heterogeneous forms, including punctate and patchy lesions in deep or subcortical white matter; lesions with periventricular caps, a pencil-thin lining, and smooth halo; as well as irregular lesions, which are not always benign. Given its potential of having deleterious effects on normal brain function and the resulting increase in public health burden, considerable effort has been focused on investigating the associations between various risk factors and LA risk, and developing its associated clinical interventions. However, study results have been inconsistent, most likely due to potential differences in study designs, neuroimaging methods, and sample sizes as well as the inherent neuroimaging heterogeneity and multi-factorial nature of LA. In this article, we provided an overview of LA and summarized the current knowledge regarding its epidemiology, neuroimaging classification, pathological characteristics, risk factors, and potential intervention strategies.

Design and Application of pH-Responsive Liposomes for Site-Specific Delivery of Cytotoxin from Cobra Venom.

Background: Current immunotherapies with unexpected severe side effects and treatment resistance have not resulted in the desired outcomes for patients with melanoma, and there is a need to discover more effective medications. Cytotoxin (CTX) from Cobra Venom has been established to have favorable cytolytic activity and antitumor efficacy and is regarded as a promising novel anticancer agent. However, amphiphilic CTX with excellent anionic phosphatidylserine lipid-binding ability may also damage normal cells. Methods: We developed pH-responsive liposomes with a high CTX load (CTX@PSL) for targeted acidic-stimuli release of drugs in the tumor microenvironment. The morphology, size, zeta potential, drug-release kinetics, and preservation stability were characterized. Cell uptake, apoptosis-promoting effects, and cytotoxicity were assessed using MTT assay and flow cytometry. Finally, the tissue distribution and antitumor effects of CTX@PSL were systematically assessed using an in vivo imaging system. Results: CTX@PSL exhibited high drug entrapment efficiency, drug loading, stability, and a rapid release profile under acidic conditions. These nanoparticles, irregularly spherical in shape and small in size, can effectively accumulate at tumor sites (six times higher than free CTX) and are rapidly internalized into cancer cells (2.5-fold higher cell uptake efficiency). CTX@PSL displayed significantly stronger cytotoxicity (IC50 0.25 µg/mL) and increased apoptosis in than the other formulations (apoptosis rate 71.78±1.70%). CTX@PSL showed considerably better tumor inhibition efficacy than free CTX or conventional liposomes (tumor inhibition rate 79.78±5.93%). Conclusion: Our results suggest that CTX@PSL improves tumor-site accumulation and intracellular uptake for sustained and targeted CTX release. By combining the advantages of CTX and stimuli-responsive nanotechnology, the novel CTX@PSL nanoformulation is a promising therapeutic candidate for cancer treatment.

Basement membrane-associated gene expression as a predictor of survival in oral cancer.

BACKGROUND: This study sought to investigate the prognostic value of basement membrane (BM)-associated gene expressions in oral cancer. METHODS: We harvested and integrated data on BM-associated genes (BMGs), the oral cancer transcriptome, and clinical information from public repositories. After identifying differentially expressed BMGs, we used Cox and Lasso regression analyses to create a BMG-based risk score for overall survival at various intervals. We then validated this score using the GSE42743 cohort as a validation set. The prognostic potential of the risk scores and their relations to clinical features were assessed. Further, we conducted functional pathway enrichment, immune cell infiltration, and immune checkpoint analyses to elucidate the immunological implications and therapeutic potential of the BMG-based risk score and constituent genes. To confirm the expression levels of the BMG LAMA3 in clinical samples of oral cancer tissue, we performed quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. RESULTS: The BMGs LAMA3, MMP14, and GPC2 demonstrated notable prognostic significance, facilitating the construction of a BMG-based risk score. A higher risk score derived from BMGs correlated with a poorer survival prognosis for oral cancer patients. Moreover, the risk-associated BMGs exhibited a significant relationship with immune function variability (P < 0.05), discrepancies in infiltrating immune cell fractions, and immune checkpoint expressions (P < 0.05). The upregulated expression levels of LAMA3 in oral cancer tissues were substantiated through qRT-PCR and immunohistochemical staining. CONCLUSION: The BMG-based risk score emerged as a reliable prognostic tool for oral cancer, meriting further research for validation and potential clinical application.

Genome-wide identification of G-protein coupled receptors (GPCRs) and their expression profile in response to ß-cypermethrin stress in Zeugodacus cucurbitae.

G-protein coupled receptors (GPCRs) are the largest and most diverse transmembrane receptor family in the cell. They are involved in regulating a wide range of biological processes, including behavior, reproduction, and development. However, GPCRs have not yet been identified in Zeugodacus cucurbitae. The current study focuses on the GPCRs identification, classification, distribution, and their expression analysis under ß-cypermethrin stress to uncover novel targets for pest management and assist in the development of effective strategies for controlling the melon fly population. We identified 80 GPCRs genes including 50 GPCRs identified in family A, 17 GPCRs identified in family B, 8 identified in family C, and 5 identified in family F. Z. cucurbitae GPCRs showed significant differences in both the number of genes in families or subfamilies, as well as the sequencing of the genes. Interestingly, newly identified GPCRs genes are expressed differently at various developmental stages of Z. cucurbitae. Further, we evaluated these 80 GPCRs using Realtime quantitative PCR to confirm their expression between ß-cypermethrin-resistant (RS) strain and susceptible strain (SS) of Z. cucurbitae. We identified 50 GPCR genes were highly overexpressed in a RS. Among these genes, eight genes were strongly induced by the 30% lethal concentration (LC) while two genes were significantly increased by the 50% LC of ß-cypermethrin. This first genome-wide profiling and characterization of GPCRs could lay foundation for unraveling detoxification mechanism and target site modifications which may improve the insect resistance and could be effective insecticide targets for Z. cucurbitae management.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. METHODS: Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. RESULTS: Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27-5.33; P < .0087). Comparisons of ML-derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62-0.79) for PAH. CONCLUSIONS: This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.

The prevalence and genotype distribution of human papillomavirus in central Fujian Province during the COVID-19 pandemic.

BACKGROUND: Global human activities were significantly impacted by the emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by the 2019 novel coronavirus. This study aimed to investigate the prevalence and genotype distribution of HPV infection in Central Fujian Province during the pandemic. METHODS: Cervical samples were collected from 21,612 outpatients and 12,664 females who underwent physical examinations and HPV screening at the People's Hospital of Fujian Province in Fuzhou from April 2020 to April 2023. HPV detection and genotyping were conducted using PCR hybridization. RESULTS: The overall HPV infection rate was 16.1% during the COVID-19 pandemic, with the outpatient group exhibiting a greater infection rate (19.0%) than did the healthy group (12.3%). The top five high-risk HPV (HR-HPV) genotypes in both groups were HPV52, HPV53, HPV58, HPV16, and HPV51. Additionally, HPV81 and HPV43 were the two most common low-risk HPV (LR-HPV) genotypes in the patient group, while HPV81 and HPV42 were the two most common LR-HPV genotypes in the healthy group. The highest prevalence of HPV infection was observed in individuals aged ≤ 24 years (28.4%, 95% CI 25.9-30.9), followed by those aged ≥ 55 years (23.6%, 95% CI 21.6-24.7) and other age groups. The prevalence decreased from 23.0% (95% CI 22.4-23.7) in 2018-2019 to 13.8% (95% CI 12.0-15.5) in 2023. CONCLUSION: This study provides valuable insights into the prevalence and genotypes of HPV infection in the female population of Central Fujian Province from 2020 to 2023. The findings indicate that the prevalence of HPV infection in Central Fujian Province remains relatively low compared to the national average. Furthermore, the prevalence of HPV decreased during the COVID-19 pandemic; however, as the pandemic waned, there was potential for an increase in HPV infection rates. Therefore, it is crucial to strengthen HPV screening and vaccination strategies to prevent the potential spread of HPV.

Mapping and functional characterization of structural variation in 1060 pig genomes.

BACKGROUND: Structural variations (SVs) have significant impacts on complex phenotypes by rearranging large amounts of DNA sequence. RESULTS: We present a comprehensive SV catalog based on the whole-genome sequence of 1060 pigs (Sus scrofa) representing 101 breeds, covering 9.6% of the pig genome. This catalog includes 42,487 deletions, 37,913 mobile element insertions, 3308 duplications, 1664 inversions, and 45,184 break ends. Estimates of breed ancestry and hybridization using genotyped SVs align well with those from single nucleotide polymorphisms. Geographically stratified deletions are observed, along with known duplications of the KIT gene, responsible for white coat color in European pigs. Additionally, we identify a recent SINE element insertion in MYO5A transcripts of European pigs, potentially influencing alternative splicing patterns and coat color alterations. Furthermore, a Yorkshire-specific copy number gain within ABCG2 is found, impacting chromatin interactions and gene expression across multiple tissues over a stretch of genomic region of ~200 kb. Preliminary investigations into SV's impact on gene expression and traits using the Pig Genotype-Tissue Expression (PigGTEx) data reveal SV associations with regulatory variants and gene-trait pairs. For instance, a 51-bp deletion is linked to the lead eQTL of the lipid metabolism regulating gene FADS3, whose expression in embryo may affect loin muscle area, as revealed by our transcriptome-wide association studies. CONCLUSIONS: This SV catalog serves as a valuable resource for studying diversity, evolutionary history, and functional shaping of the pig genome by processes like domestication, trait-based breeding, and adaptive evolution.

Somatic PDGFRB activating variants promote smooth muscle cell phenotype modulation in intracranial fusiform aneurysm.

BACKGROUND: The fusiform aneurysm is a nonsaccular dilatation affecting the entire vessel wall over a short distance. Although PDGFRB somatic variants have been identified in fusiform intracranial aneurysms, the molecular and cellular mechanisms driving fusiform intracranial aneurysms due to PDGFRB somatic variants remain poorly understood. METHODS: In this study, single-cell sequencing and immunofluorescence were employed to investigate the phenotypic changes in smooth muscle cells within fusiform intracranial aneurysms. Whole-exome sequencing revealed the presence of PDGFRB gene mutations in fusiform intracranial aneurysms. Subsequent immunoprecipitation experiments further explored the functional alterations of these mutated PDGFRB proteins. For the common c.1684 mutation site of PDGFRß, we established mutant smooth muscle cell lines and zebrafish models. These models allowed us to simulate the effects of PDGFRB mutations. We explored the major downstream cellular pathways affected by PDGFRBY562D mutations and evaluated the potential therapeutic effects of Ruxolitinib. RESULTS: Single-cell sequencing of two fusiform intracranial aneurysms sample revealed downregulated smooth muscle cell markers and overexpression of inflammation-related markers in vascular smooth muscle cells, which was validated by immunofluorescence staining, indicating smooth muscle cell phenotype modulation is involved in fusiform aneurysm. Whole-exome sequencing was performed on seven intracranial aneurysms (six fusiform and one saccular) and PDGFRB somatic mutations were detected in four fusiform aneurysms. Laser microdissection and Sanger sequencing results indicated that the PDGFRB mutations were present in smooth muscle layer. For the c.1684 (chr5: 149505131) site mutation reported many times, further cell experiments showed that PDGFRBY562D mutations promoted inflammatory-related vascular smooth muscle cell phenotype and JAK-STAT pathway played a crucial role in the process. Notably, transfection of PDGFRBY562D in zebrafish embryos resulted in cerebral vascular anomalies. Ruxolitinib, the JAK inhibitor, could reversed the smooth muscle cells phenotype modulation in vitro and inhibit the vascular anomalies in zebrafish induced by PDGFRB mutation. CONCLUSION: Our findings suggested that PDGFRB somatic variants played a role in regulating smooth muscle cells phenotype modulation in fusiform aneurysms and offered a potential therapeutic option for fusiform aneurysms.