Dual-channel intrinsic and nonlinear chirality for an all-optical logic operation.

Chiral metasurfaces hold excellent performance in enhancing spin-dependent light-matter interaction, showing broad application prospects in areas such as chiral imaging, chiral light sources, and chiral sensing. However, utilizing resonant metasurfaces to achieve all-optical logic gates has not been reported yet. In this work, dual-channel intrinsic and nonlinear chiroptical responses are achieved on lithium niobate metasurfaces. The combination of bound states in the continuum (BICs) resonant modes with chiral metasurfaces has revealed its linear and nonlinear chirality. The metasurface achieves linear circular dichroism above 0.9 and nonlinear circular dichroism close to 0.9 on the dual-band. Based on the second-order nonlinear chiroptical response, multiple all-optical logic gates (including NOT, OR, NAND, AND, and NOR) can be realized on the chiral metasurfaces. Our results confirm the operability of resonant metasurfaces in realizing all-optical logic gates, offering a potentially promising approach for the development of new, to the best of our knowledge, all-optical logic devices.

Morphological phenotype of right ventricular outflow tract is associated with cardiovascular outcomes and premature death.

Morphology of right ventricular outflow tract (RVOT) is potentially related to cardiovascular outcomes. However, this relationship still remains to be verified with direct evidence. We retrospectively reviewed cases from the autopsy specimen library in the Center of Forensic Medicine in Sun Yat-sen University from 2017 to 2023. Six RVOT morphological characteristics were measured and their association with cardiovascular diseases (CVDs), sudden cardiac death (SCD) and age at death was evaluated. Relationship between myocardial fibrosis in RVOT and CVDs was investigated. RVOT characteristics were recruited by machine learning algorithms for diagnosing CVDs. A total of 2370 cases were finally recruited. Perimeter of sub-valve plane (pSBV) in RVOT was positively associated with risk of CVDs and SCD (OR: 1.21, 95%CI: 1.07-1.37, p = 0.003; OR: 1.33, 95%CI: 1.16-1.52, p < 0.001). Compared with thickness of septum (tS) < 3.0 mm, tS ≥ 3.0 mm was associated with premature death in disease-dominant death (ß=-0.16, 95%CI: -0.20 to -0.11, p < 0.001) and SCD (ß=-0.15, 95%CI: -0.21 to -0.10, p < 0.001). Degree of myocardial fibrosis in the posterior septum was increased in coronary atherosclerosis (6.86%±2.48% vs. 4.91%±2.14%, p = 0.011) and cardiomyopathies (8.11%±3.24% vs. 4.88%±3.11%, p = 0.005). A logistic regression model, recruiting age, left and right ventricular wall thickness, pSBV, circumference of pulmonary annulus and aortic annulus, was elected as an optimal diagnostic model of CVDs, yielding AUC of 0.734 (95%CI: 0.705-0.763), 0.781 (0.740-0.821) and 0.763 (0.725-0.800) in training, validation and test sets. Increased pSBV significantly correlates with higher risk of CVDs and SCD. And tS ≥ 3.0 mm is an independent risk factor of premature death regardless of diseases.

Salvage chemotherapy regimens with arsenic trioxide for relapsed or refractory neuroblastoma: a promising approach.

In patients with relapsed or refractory neuroblastoma (NB), the limited efficacy of conventional chemotherapies necessitates the exploration of new treatment options. Previous studies have highlighted the anti-tumor properties of arsenic trioxide (ATO) in high-risk NB (HR-NB). This study aims to assess the effectiveness and safety of ATO combined with salvage chemotherapy regimens, featuring cyclophosphamide and topotecan, as a foundational treatment for children with relapsed or refractory NB. Eleven patients (four relapsed, seven refractory NB) were retrospectively analyzed for efficacy and treatment relevance. Salvage treatments, incorporating ATO (0.18 mg/kg daily for 8 h intravenously on days 1 to 10), were administered upon disease progression or relapse, with assessments conducted every two cycles. Treatments had 63.6% efficacy, with six cases of partial response, one case of stable disease, and four cases of disease progression. The overall response rate was 54.5%, and the disease control rate was 63.6%. Importantly, the systemic toxicity experienced by patients following salvage chemotherapy with ATO was mild. Salvage chemotherapy regimens featuring ATO demonstrated potential for prolonging disease stabilization for relapsed or refractory HR-NB patients, exhibiting both favorable efficacy and safety profiles. This suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.

Point 1. The inadequate effectiveness of traditional chemotherapy in individuals with recurrent or resistant neuroblastoma (NB) necessitates the investigation of novel therapeutic approaches. Point 2. Arsenic trioxide (ATO)-based salvage treatments are both effective and less toxic in relapsed or refractory NB. Point 3. Salvage chemotherapy regimens incorporating ATO have shown promise in extending disease stabilization in relapsed or refractory high-risk NB patients, with favorable efficacy and safety profiles, which suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.

Nonreciprocal polarized transmission via bound states in the continuum.

We realize the observation of near-unity nonreciprocal polarized transmission via the bound states in the continuum (BICs) in a double-layer grating structure. By introducing out-of-plane perturbations and topological defects that break the mirror symmetry between the upper and lower layers, the far-field polarization states in momentum space are inverted vertically and horizontally, showing mirrored polarization characteristics for incident channels from different upper and lower ports. During the process of introducing mirror perturbations in the upper and lower layers, a π/2 phase inversion occurs in the Г-M direction, making chirality possible. Utilizing this bidirectionally tunable nonreciprocal spatiotemporal phase transition enables multiple modulations of polarization states and opens up more possibilities for asymmetric light manipulation in chiral optical effects.

Characterization of a novel SCN5A mutation associated with long QT syndrome and arrhythmogenic right ventricular cardiomyopathy in a family.

Sudden cardiac death represents a significant diagnostic challenge for forensic pathologists, particularly in inherited arrhythmia syndromes or cardiomyopathies resulting from genetic defects. Molecular autopsies can reveal the underlying molecular etiology in such cases. In this study, we investigated a family with a history of sudden cardiac death to elucidate the molecular basis responsible for sudden cardiac death. The proband underwent a comprehensive forensic examination. Family members received thorough clinical evaluations, including electrocardiogram, Holter monitoring, echocardiography, and cardiac magnetic imaging. Whole exome sequencing and genetic analysis were performed on the deceased and her parents. In addition, Western blotting and patch-clamp recordings were employed to evaluate the expression and function of the mutant protein in vitro. Forensic examination diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) as the cause of sudden death. Genetic analysis identified a novel missense mutation in SCN5A (p.V1323L), which was assessed as likely pathogenic by the ACMG guideline. Another family member carrying the mutation manifested long QT syndrome and mild cardiac fibrosis. The cellular electrophysiological study demonstrated that the mutation resulted in an enhanced late sodium current, suggesting it was a gain-of-function mutation. This study characterizes a novel SCN5A mutation that putatively causes long QT syndrome and may contribute to the development of ARVC. Our work expands the pathogenic spectrum of SCN5A variants and underscores the importance of molecular autopsy in sudden death cases, especially in those with suspected genetic disorders.

Strong coupling of double excitons with guided mode resonances and quasi-bound states in the continuum in heterogeneous metamaterials.

Heterogeneous metamaterials containing excitonic materials provide an ideal platform for strong exciton-photon coupling. In this Letter, we theoretically demonstrate four strong couplings in a heterogeneous metamaterial consisting of a TiO2 grating standing on a perovskite-WS2-perovskite waveguide layer by tuning the structural sizes. The quasi-bound state in the continuum (qBIC) and the guided mode resonance (GMR) both strongly coupled with the excitons of both perovskite and WS2 under oblique incident illumination, resulting in four large Rabi splittings of 177.32, 187.53, 406.25, and 435.09 meV via a reasonable combination of oscillator strengths of perovskite and WS2. Double strong coupling behaviors are also achieved when the grating period equals 222 nm with an incident light angle of 19.3°. Moreover, double ultrastrong coupling can even be realized by the GMR and qBIC respectively interacting with the exciton of WS2 when its oscillator strength reaches a certain value. Our work paves an effective avenue to realizing strong coupling and even ultrastrong coupling between multiple excitons and multiple optical modes.

Ultra-slow-light and dynamically quantitative optical storage modulation via quasi-BICs.

We achieve dynamically tunable dual quasi-bound states in the continuum (quasi-BICs) by implementing them in a silicon-graphene multilayer composite structure and utilize the quasi-BIC modes to achieve ultra-large group delays (velocity of light slows down 105 times), showing 2-3 orders of magnitude higher than the group delays of previous electromagnetically induced transparency modes. The double-layer graphene holds great tuning capability and leads to the dramatically reduced group delay from 1929.82 to 1.58 ps with only 100 meV. In addition, the log-linear variation rule of group delay with Fermi level (Ef) in the range of 0-10 meV is analyzed in detail, and the double-logarithmic function relationship between the group delay and quality factor (Q-factor) is theoretically verified. Finally, the quantitative modulation of the optical storage is further realized in this basis. Our research provides ideas for the reform and upgrading of slow optical devices.

lncRNA Gm20257 alleviates pathological cardiac hypertrophy by modulating the PGC-1α-mitochondrial complex IV axis.

Pathological cardiac hypertrophy, a major contributor to heart failure, is closely linked to mitochondrial function. The roles of long noncoding RNAs (lncRNAs), which regulate mitochondrial function, remain largely unexplored in this context. Herein, a previously unknown lncRNA, Gm20257, was identified. It markedly increased under hypertrophic stress in vivo and in vitro. The suppression of Gm20257 by using small interfering RNAs significantly induced cardiomyocyte hypertrophy. Conversely, the overexpression of Gm20257 through plasmid transfection or adeno-associated viral vector-9 mitigated angiotensin II-induced hypertrophic phenotypes in neonatal mouse ventricular cells or alleviated cardiac hypertrophy in a mouse TAC model respectively, thus restoring cardiac function. Importantly, Gm20257 restored mitochondrial complex IV level and enhanced mitochondrial function. Bioinformatics prediction showed that Gm20257 had a high binding score with peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), which could increase mitochondrial complex IV. Subsequently, Western blot analysis results revealed that Gm20257 substantially affected the expression of PGC-1α. Further analyses through RNA immunoprecipitation and immunoblotting following RNA pull-down indicated that PGC-1α was a direct downstream target of Gm20257. This interaction was demonstrated to rescue the reduction of mitochondrial complex IV induced by hypertrophic stress and promote the generation of mitochondrial ATP. These findings suggest that Gm20257 improves mitochondrial function through the PGC-1α-mitochondrial complex IV axis, offering a novel approach for attenuating pathological cardiac hypertrophy.

Prenatal triphenyl phosphate exposure impairs placentation and induces preeclampsia-like symptoms in mice.

Triphenyl phosphate (TPhP) is an organophosphate flame retardant that is widely used in many commercial products. The United States Environmental Protection Agency has listed TPhP as a priority compound that requires health risk assessment. We previously found that TPhP could accumulate in the placentae of mice and impair birth outcomes by activating peroxisome proliferator-activated receptor gamma (PPARγ) in the placental trophoblast. However, the underlying mechanism remains unknown. In this study, we used a mouse intrauterine exposure model and found that TPhP induced preeclampsia (PE)-like symptoms, including new on-set gestational hypertension and proteinuria. Immunofluorescence analysis showed that during placentation, PPARγ was mainly expressed in the labyrinth layer and decidua of the placenta. TPhP significantly decreased placental implantation depth and impeded uterine spiral artery remodeling by activating PPARγ. The results of the in vitro experiments confirmed that TPhP inhibited extravillous trophoblast (EVT) cell migration and invasion by activating PPARγ and inhibiting the PI3K-AKT signaling pathway. Overall, our data demonstrated that TPhP could activate PPARγ in EVT cells, inhibit cell migration and invasion, impede placental implantation and uterine spiral artery remodeling, then induce PE-like symptom and impair birth outcomes. Although the exposure doses used in this study was several orders of magnitude higher than human daily intake, our study highlights the placenta as a potential target organ of TPhP worthy of further research.

MicroRNA-26a in respiratory diseases: mechanisms and therapeutic potential.

MicroRNAs (miRNAs) are short, non-coding single-stranded RNA molecules approximately 22 nucleotides in length, intricately involved in post-transcriptional gene expression regulation. Over recent years, researchers have focused keenly on miRNAs, delving into their mechanisms in various diseases such as cancers. Among these, miR-26a emerges as a pivotal player in respiratory ailments such as pneumonia, idiopathic pulmonary fibrosis, lung cancer, asthma, and chronic obstructive pulmonary disease. Studies have underscored the significance of miR-26a in the pathogenesis and progression of respiratory diseases, positioning it as a promising therapeutic target. Nevertheless, several challenges persist in devising medical strategies for clinical trials involving miR-26a. In this review, we summarize the regulatory role and significance of miR-26a in respiratory diseases, and we analyze and elucidate the challenges related to miR-26a druggability, encompassing issues such as the efficiency of miR-26a, delivery, RNA modification, off-target effects, and the envisioned therapeutic potential of miR-26a in clinical settings.

A blueprint for tumor-infiltrating B cells across human cancers.

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.

Deep learning-based inverse design of multi-functional metasurface absorbers.

A novel approach-integrating a simulated annealing (SA) algorithm with deep learning (DL) acceleration-is presented for the rapid and accurate development of terahertz perfect absorbers through forward prediction and backward design. The forward neural network (FNN) effectively deduces the absorption spectrum based on metasurface geometry, resulting in an 80,000-fold increase in computational speed compared to a full-wave solver. Furthermore, the absorber's structure can be precisely and promptly derived from the desired response. The incorporation of the SA algorithm significantly enhances design efficiency. We successfully designed low-frequency, high-frequency, and broadband absorbers spanning the 4 to 16 THz range with an error margin below 0.02 and a remarkably short design time of only 10 min. Additionally, the proposed model in this Letter introduces a novel, to our knowledge, method for metasurface design at terahertz frequencies such as the design of metamaterials across optical, thermal, and mechanical domains.

Arrhythmia onsets triggered by acute myocardial ischemia are not mediated by lysophosphoglycerides accumulation in ventricular myocardium.

Lysophosphoglycerides (LPLs) have been reported to accumulate in myocardium and serve as a cause of arrhythmias in acute myocardial ischemia. However, in this study we found that LPLs level in the ventricular myocardium was decreased by the onset of acute myocardial ischemia in vivo in rats. Decreasing of LPLs level in left ventricular myocardium, but not right, was observed within 26 min of left myocardial ischemia, regardless of whether arrhythmias were triggered. Lower LPLs level in the ventricular myocardium was also observed in aconitine-simulated ventricular fibrillation (P < 0.0001) and ouabain-simulated III° atrioventricular block (P < 0.0001). Shot-lasting electric shock, e.g., ≤ 40 s, decreased LPLs level, while long-lasting, e.g., 5 min, increased it (fold change = 2.27, P = 0.0008). LPLs accumulation was observed in long-lasting myocardial ischemia, e.g., 4 h (fold change = 1.20, P = 0.0012), when caspase3 activity was elevated (P = 0.0012), indicating increased cell death, but not coincided with higher frequent arrhythmias. In postmortem human ventricular myocardium, differences of LPLs level in left ventricular myocardium was not observed among coronary artery disease- and other heart diseases-caused sudden death and non-heart disease caused death. LPLs level manifested a remarkable increasing from postmortem 12 h on in rats, thus abolishing the potential for serving as biomarkers of sudden cardiac death. Token together, in this study we found that LPLs in ventricular myocardium were initially decreased by the onset of ischemia, LPLs accumulation do not confer arrhythmogenesis during acute myocardial ischemia. It is necessary to reassess the roles of LPLs in myocardial infarction.

Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation.

Neutralizing antibodies (nAbs) play an important role against SARS-CoV-2 infections. Previously, we have reported one potent receptor binding domain (RBD)-binding nAb Ab08 against the SARS-CoV-2 prototype and a panel of variants, but Ab08 showed much less efficacy against the variants harboring the L452R mutation. To overcome the antibody escape caused by the L452R mutation, we generated several structure-based Ab08 derivatives. One derivative, Ab08-K99E, displayed the mostly enhanced neutralizing potency against the Delta pseudovirus bearing the L452R mutation compared to the Ab08 and other derivatives. Ab08-K99E also showed improved neutralizing effects against the prototype, Omicron BA.1, and Omicron BA.4/5 pseudoviruses. In addition, compared to the original Ab08, Ab08-K99E exhibited high binding properties and affinities to the RBDs of the prototype, Delta, and Omicron BA.4/5 variants. Altogether, our findings report an optimized nAb, Ab08-K99E, against SARS-CoV-2 variants and demonstrate structure-based optimization as an effective way for antibody development against pathogens.

High-intensity focused ultrasound for endometrial ablation in adenomyosis: a clinical study.

Objective: The present study aimed to investigate the clinical efficacy of endometrial ablation with high-intensity focused ultrasound (HIFU) for symptom relief in women with adenomyosis. Methods: Between July 2014 and July 2020, 167 patients with adenomyosis treated at the Zhongshan City People's Hospital were enrolled in this study. Patients were divided into two groups according to patient aspirations: the control group, including patients who only underwent ablation of adenomyosis lesions (group A) and the treatment group, including patients who underwent removal of adenomyosis lesions and endometrial ablation (group B). Results: The reduced dysmenorrhea scores (visual analog scale) and menstrual volume scores (pictorial blood assessment chart) were measured before and after treatment. The scores were obtained by subtracting the postoperative scores from the preoperative scores and were compared to determine whether the symptoms had alleviated. Compared with the menstrual volume of group A, that in group B showed significant improvements. The average relief rates of dysmenorrhea in the two groups also showed significant improvement. However, the scores in group B showed a more significant improvement than those in group A. Conclusion: Therefore, our findings suggest that endometrial ablation using HIFU may be superior to conventional therapy with regard to alleviating the symptoms of increased menstruation in women with adenomyosis.

Study on the interaction protein of transcription factor Smad3 based on TurboID proximity labeling technology.

TurboID is a highly efficient biotin-labelling enzyme, which can be used to explore a number of new intercalating proteins due to the very transient binding and catalytic functions of many proteins. TGF-ß/Smad3 signaling pathway is involved in many diseases, especially in diabetic nephropathy and inflammation. In this paper, a stably cell line transfected with Smad3 were constructed by using lentiviral infection. To further investigate the function of TGF-ß/Smad3, the protein labeling experiment was conducted to find the interacting protein with Smad3 gene. Label-free mass spectrometry analysis was performed to obtain 491 interacting proteins, and the interacting protein hnRNPM was selected for IP and immunofluorescence verification, and it was verified that the Smad3 gene had a certain promoting effect on the expression of hnRNPM gene, and then had an inhibitory effect on IL-6. It lays a foundation for further study of the function of Smad3 gene and its involved regulatory network.

Triphenyl phosphate interferes with the synthesis of steroid hormones through the PPARγ/CD36 pathway in human trophoblast JEG-3 cells.

Triphenyl phosphate (TPhP), a chemical commonly found in human placenta and breast milk, has been shown to disturb the endocrine system. Our previous study confirmed that TPhP could accumulate in the placenta and interference with placental lipid metabolism and steroid hormone synthesis, as well as induce endoplasmic reticulum (ER) stress through PPARγ in human placental trophoblast JEG-3 cells. However, the molecular mechanism underlying this disruption remains unknown. Our study aimed to identify the role of the PPARγ/CD36 pathway in TPhP-induced steroid hormone disruption. We found that TPhP increased lipid accumulation, total cholesterol, low- and high-density protein cholesterol, progesterone, estradiol, glucocorticoid, and aldosterone levels, and genes related to steroid hormones synthesis, including 3ßHSD1, 17ßHSD1, CYP11A, CYP19, and CYP21. These effects were largely blocked by co-exposure with either a PPARγ antagonist GW9662 or knockdown of CD36 using siRNA (siCD36). Furthermore, an ER stress inhibitor 4-PBA attenuated the effect of TPhP on progesterone and glucocorticoid levels, and siCD36 reduced ER stress-related protein levels induced by TPhP, including BiP, PERK, and CHOP. These findings suggest that ER stress may also play a role in the disruption of steroid hormone synthesis by TPhP. As our study has shed light on the PPARγ/CD36 pathway's involvement in the disturbance of steroid hormone biosynthesis by TPhP in the JEG-3 cells, further investigations of the potential impacts on the placental function and following birth outcome are warranted.

Tunability-selective lithium niobate light modulators via high-Q resonant metasurface.

Herein, we propose and demonstrate an efficient light modulator by intercalating the nonlinear thin film into the optical resonator cavities, which introduce the ultra-sharp resonances and simultaneously lead to the spatially overlapped optical field between the nonlinear material and the resonators. Differential field intensity distributions in the geometrical perturbation-assisted optical resonator make the high quality-factor resonant modes and strong field confinement. Multiple channel light modulation is achieved in such layered system, which enables the capability for tunability-selective modulation. The maximal modulation tunability is up to 1.968 nm/V, and the figure of merit (FOM) reaches 65.6 V-1, showing orders of magnitude larger than that of the previous state-of-the-art modulators. The electrical switch voltage is down to 0.015 V, the maximal switching ratio is 833%, and the extinction ratio is also up to 9.70 dB. These features confirm the realization of high-performance modulation and hold potential for applications in switches, communication and information, augmented and virtual reality, etc.

Arsenic trioxide induces ferroptosis in neuroblastoma by mediating GPX4 transcriptional inhibition.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood, significantly contributes to cancer-related mortality, presenting a dearth of efficacious treatment strategies. Previously, our studies have substantiated the potent cytotoxicity of arsenic trioxide (ATO) against NB cells, however, the specific underlying mechanism remains elusive. Here, we first identified ATO as a novel GPX4 inhibitor, which could trigger the ferroptosis in NB cells. In vitro, ATO significantly inhibited the proliferation and migration ability of NB cells SK-N-AS and SH-SY5Y, and induced ferroptosis. Furthermore, the iron chelator deferoxamine reversed ATO-mediated intracellular reactive oxygen species accumulation and hindered the generation of the lipid peroxidation product malondialdehyde. Conversely, ferric ammonium citrate notably intensified its cytotoxic effects, especially on retinoic acid (RA)-resistant SK-N-AS cells. Subsequently, the quantitative real-time polymerase chain reaction results showed ATO significantly inhibited the transcription of GPX4 in NB cells. Remarkably, immunoblotting analysis revealed that MG132 exhibited a notable effect on elevating GPX4 levels in NB cells. Nevertheless, pretreatment with MG132 failed to reverse the ATO-mediated decrease in GPX4 levels. These findings suggested that ATO reduced the GPX4 expression level in NB cells by mediating GPX4 transcriptional repression rather than facilitating ubiquitinated degradation. In conclusion, our research has successfully indicated that ATO could induce ferroptosis and initiate lipid peroxidation by regulating the transcriptional repression of GPX4, and ATO holds promise as a potential anti-tumor agent in NB, specifically for patients with RA-resistant HR-NB.

Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a myeloid neoplasia with potentially fatal consequences, and about 2/3 of cases involve the BRAFV600E kinase-activated mutation. Vemurafenib, a BRAF inhibitor, has demonstrated significant clinical improvements in LCH. However, the high relapse rate of LCH following cessation of vemurafenib therapy remains a major challenge, and alternative treatment strategies require further investigation. METHODS: In this retrospective multi-center study, we evaluated the efficacy and safety of vemurafenib combined with conventional chemotherapy in patients with severe or refractory LCH. RESULTS: Seventeen patients were enrolled in the study, with eleven classified as risk organ involvement (RO +). Six received the combination therapy as the primary treatment, and eleven after being refractory to prior chemotherapy. The overall response rate was 94.1%. Progression-free survival among all 17 patients was 70.6% (12/17) at a median follow-up of 32 months, and relapse-free survival among the 15 patients with discontinuation after a response was 73.3%(11/15) at a median follow-up of 34 months. Five of six patients (83.3%) with myeloid BRAFV600E mutations demonstrated molecular remission. The overall survival rate was 100%. Adverse events were mostly classified as grades 1 or 2. CONCLUSION: Our data suggest that the combination of vemurafenib and chemotherapy can achieve sustained clinical and molecular level relief in children with LCH, and side effects are tolerable.