To Draw a Detailed Map for Maxillofacial Fast-Flow Vascular Diseases With the Combination of Color Doppler Ultrasound and Three-Dimensional Computed Tomography Angiography.

Vascular diseases, such as vascular malformations and hemangiomas, are often classified into "fast-flow" and "slow-flow" based on their internal blood velocity. Fast-flow vascular diseases of maxillofacial regions are a kind of complicated and dangerous pathological changes originating from or containing arteries, their treatment is often complex and different from disease to disease, and large amounts of intraoperative blood loss and poor operation field may cause side injury or other problems without a detailed map of the lesion. The authors use the combination of color Doppler ultrasound and three-dimensional computed tomography angiography to diagnose and classify 36 cases of maxillofacial fast-flow vascular diseases, from January 2018 to December 2022 presented in the authors' department. Three-dimensional computed tomography angiography can display the location, type, and blood supply of lesions, whereas color Doppler ultrasound has unique advantages in identifying some special lesions (such as the colorful images of orificium fistulaes and the "Yin-yang sign" of pseudoaneurysms), then projecting and marking them on the body surface, which greatly facilitate the surgical procedure. This cost-effective and noninvasive combination shows significant clinical application value.

Noninvasive Targeting System with Three-Dimensionally Printed Customized Device in Stereotactic Brain Biopsy.

OBJECTIVE: Three-dimensional (3D) printed models are used in the medical field. This study aimed to evaluate the feasibility and safety of a 3D-printed guide plate for use in brain biopsy. METHODS: Twelve patients with intracranial lesions were retrospectively reviewed to determine clinical outcomes and technical procedural operability. These patients underwent brain biopsy assisted with the 3D-printed guide plate. Postoperative computed tomography was performed to assess the accuracy and associated complications of this guide plate. RESULTS: All patients received definite diagnoses assisted by this guide plate. The deviations of the entry and target points were 3.93 ± 0.96 mm and 2.59 ± 0.11 mm, respectively. The angle drift of the puncture path was 5.12° ± 0.14°, and the deviation of the puncture depth was 2.35 ± 1.13 mm. The operation time ranged from 38.5 minutes with local anesthesia to 76.2 minutes with general anesthesia. No patient experienced complications. CONCLUSIONS: The 3D-printed guide plate was noninvasive and had acceptable accuracy and the flexibility of frameless systems. The economic and operative benefits of this device supported its status as a powerful tool for brain biopsy in medical facilities in economically disadvantaged areas or institutions without navigation systems.

Single-cell landscape of the cellular microenvironment in three different colonic polyp subtypes in children.

BACKGROUND: The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz-Jeghers syndrome (PJS) remains limited. METHODS: We conducted single-cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. RESULTS: We identified both shared and disease-specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial-mesenchymal transition (EMT)-like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon-related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber-associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption-related genes. In addition, the TNF-α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell-cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. CONCLUSION: These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.

LncRNA SNHG1 Accelerates Cell Proliferation, Migration, and Invasion of Hepatoblastoma Through Mediating miR-6838-5p/PIM3/RhoA Axis.

Hepatoblastoma (HB) is a common primary liver malignant tumor in children. Long non-coding RNAs (lncRNAs) are closely engaged in HB progression. The role and regulatory molecule mechanism of lncRNA small nucleolar RNA host gene 1 (SNHG1) in HB remain unclear. Through qRT-PCR or western blot, we found that SNHG1 and proviral integration site for moloney murine leukemia virus 3 (PIM3) were elevated but miR-6838-5p was decreased in HB cells. Cell biology experiments revealed that SNHG1 depletion or miR-6838-5p upregulation suppressed cell proliferation, migration, and invasion of HB cells. Mechanistically, luciferase activity assay validated that miR-6838-5p could interact with SNHG1 or PIM3. SNHG1 up-regulated PIM3 expression via sponging miR-6838-5p. Moreover, miR-6838-5p inhibitor abolished SNHG1 depletion-mediated suppression of malignant behaviors in HB cells. PIM3 overexpression neutralized miR-6838-5p mimics-mediated repression of malignant phenotypes in HB cells. Furthermore, miR-6838-5p overexpression suppressed RhoA activation, which was restored by PIM3 upregulation. What's more, the results at the cellular level were further verified by nude mice tumor formation experiment. In conclusion, SNHG1 regulated miR-6838-5p/PIM3/RhoA axis to promote malignant phenotypes of HB, which might provide novel therapeutic target for HB treatment.

Hugan Buzure Granule Alleviates Acute Kidney Injury in Mice by Inhibiting NLRP3/Caspase-1 Pathway and TLR4/NF-κB Pathway.

BACKGROUND: Hugan Buzure Granule (HBG) is a traditional prescription of Uygur nationality in China mainly used to treat liver cold, stomachache, spleen and rib pain, arthralgia, rheumatism and urinary system diseases. Its mechanism of action in treating acute kidney injury (AKI) continues to remain unconfirmed. This study's objective was to investigate the pharmacodynamics and mechanism of HBG in the management of AKI. METHODS: The damage to the kidney tissue was examined by using H&E (Hematoxylin-eosin) staining. The BUN (Blood Urea Nitrogen) and Cr (Creatinine) in serum were examined by biochemical kit. The content of ROS (Reactive oxygen species) in kidney tissue was determined by ROS frozen section staining, while the amount of MDA (Malondialdehyde), GSH (Glutathione), and the enzymes of CAT (Catalase) and SOD (Superoxide dismutase) were assessed by using a biochemical kit. The tissue apoptosis was seen by using the TUNEL assay. ELISA kit was utilized to assess the content of IL-6, TNF-α, and IL-1ß in serum. Immunohistochemistry and Western blot were utilized to identify the translation of proteins associated to the NLRP3/Caspase-1 pathway and the TLR4/NF-κB pathway in various tissues. RESULTS: HBG considerably improved the renal injury in mice and decreased their kidney coefficient in contrast with the Control group. Immunohistochemistry and Western blot demonstrated that the translation of NLRP3, Caspase-1, IL-18, IL-1ß, TLR4, NF-κB, IL-6, TNF-α were down-regulated in HBG groups. CONCLUSIONS: HBG may have a protective effect against AKI through anti-oxidative stress, inhibition of apoptosis and reduction of serum inflammatory factor levels. The mechanisms involved inhibiting NLRP3/Caspase-1 pathway and TLR4/NF-κB pathway.

A DFT study towards dynamic structures of iron and iron carbide and their effects on the activity of the Fischer-Tropsch process.

The Fe-based Fischer-Tropsch synthesis (FTS) catalyst shows a rich phase chemistry under pre-treatment and FTS conditions. The exact structural composition of the active site, whether iron or iron carbide (FeCx), is still controversial. Aiming to obtain an insight into the active sites and their role in affecting FTS activity, the swarm intelligence algorithm is implemented to search for the most stable Fe(100), Fe(110), Fe(210) surfaces with different carbon ratios. Then, ab initio atomistic thermodynamics and Wulffman construction were employed to evaluate the stability of these surfaces at different chemical potentials of carbon. Their FTS reactivity and selectivity were later assessed by semi-quantitative micro-kinetic equations. The results show that stability, reactivity, and selectivity of the iron are all affected by the carbonization process when the carbon ratio increases. Formation of the carbide, a rather natural process under experimental conditions, would moderately increase the turnover frequency (TOF), but both iron and iron carbide are active to the reaction.

CircFOXN2 alleviates glucocorticoid- and tacrolimus-induced dyslipidemia by reducing FASN mRNA stability by binding to PTBP1 during liver transplantation.

We aimed to examine impacts and functional mechanism of circular RNA forkhead box N2 (FOXN2) in tacrolimus (TAC)- and dexamethasone (Dex)-induced lipid metabolism disorders. RNA level and protein contents in TAC, Dex, or combined TAC- plus Dex-treated patients and Huh-7 cells were measured utilizing quantitative real-time (qRT)-PCR and western blotting assays measured the formation of lipid droplet. Total cholesterol (TC) and triglyceride (TG) levels were determined using corresponding commercial kits and Oil red O staining. RNA immunoprecipitation and RNA pull-down verified the binding relationship among circFOXN2, polypyrimidine tract binding protein 1 (PTBP1) and fatty acid synthase (FASN). Male C57BL/6 mice were used to establish a dyslipidemia mouse model to validate the discoveries at the cellular level. Dex treatment significantly promoted TAC-mediated increase of TC and TG in serum samples and Huh-7 cells. Moreover, circFOXN2 was reduced but FASN was elevated in TAC-treated Huh-7 cells, and these expression trends were markedly enhanced by Dex cotreatment. Overexpression of circFOXN2 could reverse the accumulation of TC and TG and the upregulation of FASN and sterol regulatory element binding transcription factor 2 (SREBP2) mediated by Dex and TAC cotreatment. Mechanistically, circFOXN2 reduced FASN mRNA stability by recruiting PTBP1. The protective roles of circFOXN2 overexpression on lipid metabolism disorders were weakened by FASN overexpression. In vivo finding also disclosed that circFOXN2 greatly alleviated the dysregulation of lipid metabolism triggered by TAC plus Dex. CircFOXN2 alleviated the dysregulation of lipid metabolism induced by the combination of TAC and Dex by modulating the PTBP1/FASN axis.NEW & NOTEWORTHY Collectively, our experiments revealed for the first time that circFOXN2 alleviated the Dex- and TAC-induced dysregulation of lipid metabolism by regulating the PTBP1/FASN axis. These findings suggested that circFOXN2 and FASN might be candidate targets for the treatment of Dex- and TAC-induced metabolic disorders.

"Reconstruction of large lower lip defect including vermilion using a V-Y advanced flap combined with a musculomucosal stacked flap."

SUMMARY: The reconstruction of large lower lip defect is challenging, especially to repair the vermilion at the same time. We describe a novel method for reconstruction of large lower lip defect including vermilion here. The reconstruction included 2 layers, the anterior layer was reconstructed from the V-Y advanced musculocutaneous flap of the cheek; the posterior layer was reconstructed from the musculomucosal flap from the remnant lower lip, the stacking up of the bilateral musculomucosal flaps raised the height of posterior layer and cover the top of the lower lip to form the new vermillion as well. This is a simple and reliable method with satisfactory cosmetic and functional result.

KDM1A drives hepatoblastoma progression by activating the Wnt/ß-catenin pathway through inhibition of DKK3 transcription.

This study is to explore the mechanism of KDM1A-regulated hepatoblastoma (HB) development. Cancerous and paracancer tissues of 30 HB patients were collected for detection of KDM1A and DKK3 expression. HuH-6 and HepG2 cells were subjected to assays of cellular activities after treatment with sh-KDM1A, sh-DKK3, and/or XAV-939 (an inhibitor of the Wnt/ß-catenin pathway). Chromatin immunoprecipitation was used to determine the interaction of KDM1A with DKK3. Nude mice were injected with HuH-6 cells in which KDM1A was knocked down. KDM1A was highly expressed and DKK3 was lowly expressed in HB patients. Knockdown of KDM1A reduced the proliferative and invasive capabilities of HepG2 and HuH-6 cells and accelerated the cell apoptosis; these influences were nullified by knockdown of DKK3. KDM1A inhibited DKK3 transcription by reducing H3 methylation. XAV-939 treatment inhibited the development of HepG2 and HuH-6 cells in which KDM1A and DKK3 were both knocked down. Knockdown of KDM1A reduced the tumor mass, inactivated the Wnt/ß-catenin signaling, and increased the expression of DKK3 in nude mice. KDM1A stimulates HB development by activating the Wnt/ß-catenin pathway through inhibition of DKK3 transcription.

A new macrocyclic spermidine alkaloid from the aerial part of Hyssopus cuspidatus Boriss.

Hyssopus cuspidatus Boriss. grows in Xinjiang, China. A new macrocyclic spermidine alkaloid, namely hyssopusizine (1), along with sixteen known compounds were isolated and identified from the aerial parts of H. cuspidatus. Their structures were elucidated on the basis of spectroscopic data and comparison with the literature. Among them, fifteen compounds were isolated from H. cuspidatus for the first time. The absolute configuration of compound 1 was established by comparing the calculated and experimental ECD spectroscopic data. All isolated compounds were tested for their antioxidant and antimicrobial activities. Among them, compound 10 exhibited significant effects on ABTS free-radical scavenging activity with an IC50 value of 15.6 µM. Compounds 5-7 exhibited potent antioxidant activities against ABTS and DPPH. Most compounds exhibited moderate antimicrobial activities. Hyssopusizine (1) is the first macrocyclic spermidine alkaloid discovered from the Hyssopus genus.

Screening of undernutrition in children with Hirschsprung disease using preoperative anthropometric parameters: A multicenter cross-sectional study.

BACKGROUND: The prevalence of malnutrition is unknown in patients with Hirschsprung disease. Undernutrition is associated with poor clinical outcomes. This study aims to describe the nutrition status among patients with Hirschsprung disease at admission. METHODS: We retrospectively used data from children with Hirschsprung disease admitted to three pediatric surgery centers in China from January 2016 to December 2020. The weight-for-age z scores (WAZ), height-for-age z scores (HAZ), and body mass index-for-age z scores (BAZ) were calculated as the reference for nutrition risk according to the World Health Organization child growth standards. The nutrition status of enrolled children was described and nutrition risk in each clinical characteristic was compared. The association between nutrition status and clinical outcomes was analyzed using univariate and multivariate logistic regression. RESULTS: A total of 624 patients were included in this study. The mean WAZ, HAZ, and BAZ of all patients was -0.64 ± 1.40, -0.45 ± 1.78, and -0.43 ± 1.50, respectively. Moderate to severe overall undernutrition was 16.3% (102/624). We found that WAZ and BAZ were significantly reduced with the length of aganglionic segments (P = 0.001). Children who had a definitive surgery at 3 years of age or older had significantly lower HAZ (P = 0.001). A multivariate regression model assessing postoperative Hirschsprung-associated enterocolitis showed that the WAZ was one of the independent risk factors (P = 0.001). CONCLUSION: Undernutrition is prevalent among children with Hirschsprung disease. Nutrition assessment to identify individuals at risk of undernutrition for further intervention is necessary.

miR­92a represses the viability and migration of nerve cells in Hirschsprung's disease by regulating the KLF4/PI3K/AKT pathway.

Hirschsprung's disease (HSCR) is an intestinal disease caused by defects in neural crest cell migration, proliferation, differentiation, and survival. Many reports have proposed that miRNA dysregulation is related to the occurrence of HSCR. However, the roles and mechanisms of miRNAs have not been thoroughly studied. The levels of miR­92a and KLF4 were examined using qRT­PCR and immunohistochemistry, respectively. Cell viability, migration and apoptosis were evaluated by MTT, Transwell and flow cytometry assays, respectively. A dual­luciferase reporter assay was employed to verify the binding relationship between miR­92a and KLF4. Levels of PI3K/AKT signals were further determined by western blot assay. Herein, elevated expression of miR­92a and reduced expression of KLF4 were found in HSCR tissues, and their expression patterns were negatively correlated. Overexpression of miR­92a inhibited cell viability and migration but enhanced cell apoptosis. However, overexpression of KLF4 had the opposite effects. Mechanistically, KLF4 was a target of miR­92a and it negatively affected biological functions by activating PI3K/AKT signaling. These results proved that miR­92a inhibited the proliferation and metastasis of nerve cells by regulating the KLF4/PI3K/AKT axis.

Genomic Instability in Cerebrospinal Fluid Cell-Free DNA Predicts Poor Prognosis in Solid Tumor Patients with Meningeal Metastasis.

Genomic instability (GI), which leads to the accumulation of DNA loss, gain, and rearrangement, is a hallmark of many cancers such as lung cancer, breast cancer, and colon cancer. However, the clinical significance of GI has not been systematically studied in the meningeal metastasis (MM) of solid tumors. Here, we collected both cerebrospinal fluid (CSF) and plasma samples from 56 solid tumor MM patients and isolated cell-free ctDNA to investigate the GI status using a next-generation sequencing-based comprehensive genomic profiling of 543 cancer-related genes. According to the unfiltered heterozygous mutation data-derived GI score, we found that 37 (66.1%) cases of CSF and 3 cases (6%) of plasma had a high GI status, which was further validated by low-depth whole-genome sequencing analysis. It is demonstrated that a high GI status in CSF was associated with poor prognosis, high intracranial pressure, and low Karnofsky performance status scores. More notably, a high GI status was an independent poor prognostic factor of poor MM-free survival and overall survival in lung adenocarcinoma MM patients. Furthermore, high occurrences of the co-mutation of TP53/EGFR, TP53/RB1, TP53/ERBB2, and TP53/KMT2C were found in MM patients with a high GI status. In summary, the GI status in CSF ctDNA might be a valuable prognostic indicator in solid tumor patients with MM.

Ubiquitin-Specific Protease 22 Promotes Neural Stem Cells Stemness Maintenance and Adult Hippocampal Neurogenesis, Contributing to Cognitive Recovery Following Traumatic Brain Injury.

Ubiquitin-specific protease 22 (USP22), a potential marker of cancer stem cells, significantly influences stem cell fate choices. However, its functions in neural stem cells (NSCs) and adult neurogenesis, especially following traumatic brain injury (TBI), remain only partially understood. Here, we found that aberrant USP22 expression could affect NSC proliferation and stemness maintenance, as assessed by the generation of neurospheres, cell counting kit-8 (CCK-8) and immunofluorescence staining in vitro. Moreover, USP22 depletion promotes the differentiation of NSCs, both in vitro and in vivo. In contrast, USP22 overexpression inhibits NSC differentiation into neurons. Interestingly, our data showed that USP22 promotes the proliferation but inhibits the differentiation of NSCs in the dentate gyrus (DG) of the hippocampus soon after TBI. The Morris water maze (MWM) test was adopted to evaluate neurological function, which confirmed that USP22 could improve the learning and memory capacity that was already compromised following TBI. Overall, this study uncovers a potentially novel regulatory role of USP22 in the proliferation and differentiation ability of NSCs, contributing to the hippocampus-dependent cognitive function of TBI mice and may be a novel target for future therapeutic approaches.

Mechanism of Shiliu Buxue Syrup for anemia using integrated metabolomics and network pharmacology.

For many years, Shiliu Buxue Syrup (SLBXS) has been used in the treatment of anemia in Xinjiang, China. However, the potential therapeutic mechanism of SLBXS in the treatment of anemia remains unclear. We qualitatively analyzed the ingredients of SLBXS and predicted the underlying mechanisms by network pharmacology. A mice model of anemia was established by subcutaneous injection of 1-Acetyl-2-phenylhydrazine (APH). Spleen metabolomics was performed to screen potential biomarkers and pathways related to anemia. Furthermore, core targets of crucial pathways were experimentally validated. Finally, molecular docking was used for predicting interactions between compositions and targets. Network pharmacology indicated that the 230 SLBXS ingredients may affect 141 target proteins to regulate the PI3K/AKT and HIF-1 signaling pathways. Metabolomics revealed that SLBXS could mediate 30 biomarkers, such as phosphoric acid, l-pyroglutamic acid, alpha-Tocopherol, 1-stearoyl-rac-glycerol, and dihydroxyacetone phosphate, to regulate drug metabolism-other enzymes, glutathione metabolism, glycolysis or gluconeogenesis, nicotinate and nicotinamide metabolism, nitrogen metabolism, and purine metabolism. Western blot indicated that SLBXS can regulate the protein expression levels of AKT1, Bcl2, Caspase3, HIF-1α, VEGF-A, and NOS2. The molecular docking revealed that most of the compositions had a good binding ability to the core targets. Based on these findings, we speculate that SLBXS treats anemia mainly by modulating the PI3K/AKT and HIF-1 pathways and glutathione and glycolytic metabolisms.

Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea.

Background: Biallelically mutated MYO5B is associated with microvillus inclusion disease (MVID, MIM: 251850), cholestasis, or both. This study aims at validating the splicing alteration and clinical features of an intron variant for diagnosis. Case Presentation: A homozygous variant of MYO5B, NM_001080467.2:c.2090+3A > T (NP_001073936.1:p.?) in intron 17, was identified in a patient suffering from chronic cholestasis and diarrhea. Functional validation showed that this variant caused 185 bp of intron retention in its mRNA and was predicted to present a premature translation termination site for myoVb (p.Arg697fs*47) in the head motor domain. In addition, bowel biopsy revealed decreased microvilli and local lesions of microvillus inclusion in the duodena of the patient. The patient was presented with neonatal cholestasis leading to cirrhosis, intractable diarrhea, cholelithiasis, hepatic cyst, corneal opacity, and failure to thrive. Conclusion: Our study demonstrated an intronic homozygous variant of MYO5B that affected an intron, subsequently altering splicing and leading to combined cholestasis and MVID. Our results further supported the underlying genotype-phenotype correlations and extended clinical practices toward its diagnosis and management.

Retracted: Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFκB-PUMA Signaling.

The in vitro experiments of TGF-ß1 and the results of RT-PCR could not be repeated. In order not to affect others, the authors have asked for a retraction. Reference: Qiang Yin, Shan Liu, Anbing Dong, Xiufang Mi, Fengyun Hao, Kejun Zhang. Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFkappakB-PUMA Signaling. Med Sci Monit 2016; 22: 2267-2277. DOI: 10.12659/MSM.898702.

Effectiveness of alectinib and osimertinib in a brain metastasized lung adenocarcinoma patient with concurrent EGFR mutations and DCTN1-ALK fusion.

The echinoderm microtubule associated protein-like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non-small-cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)-ALK rearrangement is extremely rare. The co-occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1-ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions after she acquired osimertinib resistance. Furthermore, we summarize 22 published cases of patients with lung adenocarcinoma with concurrent EGFR mutation and ALK rearrangement, including details of clinical characteristics, natural history, and pertinent therapy of this uncommon tumor subtype. This literature review shows that EGFR inhibition was an indispensable aspect of the treatment of patients with EGFR/ALK co-alterations in the pre-alectinib era and that ALK inhibition with crizotinib did not show more eye-catching therapeutic results. Considering the effectiveness achieved by alectinib, this case study provides a new perspective for the treatment of lung cancer brain metastasis patients with concurrent EGFR/ALK mutations.