Clpf encodes pentatricopeptide repeat protein (PPR5) and regulates pink flesh color in watermelon (Citrullus lanatus L.).

KEY MESSAGE: The gene controlling pink flesh in watermelon was finely mapped to a 55.26-kb region on chromosome 6. The prime candidate gene, Cla97C06G122120 (ClPPR5), was identified through forward genetics. Carotenoids offer numerous health benefits; while, they cannot be synthesized by the human body. Watermelon stands out as one of the richest sources of carotenoids. In this study, genetic generations derived from parental lines W15-059 (red flesh) and JQ13-3 (pink flesh) revealed the presence of the recessive gene Clpf responsible for the pink flesh (pf) trait in watermelon. Comparative analysis of pigment components and microstructure indicated that the disparity in flesh color between the parental lines primarily stemmed from variations in lycopene content, as well as differences in chromoplast number and size. Subsequent bulk segregant analysis (BSA-seq) and genetic mapping successfully narrowed down the Clpf locus to a 55.26-kb region on chromosome 6, harboring two candidate genes. Through sequence comparison and gene expression analysis, Cla97C06G122120 (annotated as a pentatricopeptide repeat, PPR) was predicted as the prime candidate gene related to pink flesh trait. To further investigate the role of the PPR gene, its homologous gene in tomato was silenced using a virus-induced system. The resulting silenced fruit lines displayed diminished carotenoid accumulation compared with the wild-type, indicating the potential regulatory function of the PPR gene in pigment accumulation. This study significantly contributes to our understanding of the forward genetics underlying watermelon flesh traits, particularly in relation to carotenoid accumulation. The findings lay essential groundwork for elucidating mechanisms governing pigment synthesis and deposition in watermelon flesh, thereby providing valuable insights for future breeding strategies aimed at enhancing fruit quality and nutritional value.

Identification of Chromosomal Regions and Candidate Genes for Round leaf Locus in Cucumis melo L.

Leaf morphology plays a crucial role in plant classification and provides a significant model for studying plant diversity while directly impacting photosynthetic efficiency. In the case of melons, leaf shape not only influences production and classification but also represents a key genetic trait that requires further exploration. In this study, we utilized forward genetics to pinpoint a recessive locus, dubbed Cmrl (Round leaf), which is responsible for regulating melon leaf shape. Through bulked segregant analysis sequencing and extensive evaluation of a two-year F2 population, we successfully mapped the Cmrl locus to a 537.07 kb region on chromosome 8 of the melon genome. Subsequent genetic fine-mapping efforts, leveraging a larger F2 population encompassing 1322 plants and incorporating F2:3 phenotypic data, further refined the locus to an 80.27 kb interval housing five candidate genes. Promoter analysis and coding sequence cloning confirmed that one of these candidates, MELO3C019152.2 (Cmppr encoding a pentatricopeptide repeat-containing family protein, Cmppr), stands out as a strong candidate gene for the Cmrl locus. Notably, comparisons of Cmrl expressions across various stages of leaf development and different leaf regions suggest a pivotal role of Cmrl in the morphogenesis of melon leaves.

Clinical efficacy and safety analysis of aumolertinib in real-world treatment of EGFR-mutated advanced non-small-cell lung cancer.

Background: This study aims to determine the efficacy and safety profile of aumolertinib in the real-word treatment setting for advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations. Methods: We retrospectively analyzed the clinical data of 173 EGFR-mutated advanced NSCLC patients who received aumolertinib treatment at Henan Cancer Hospital from April 2020 to December 2022. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves, while a Cox regression model was used for multifactorial analysis and prognostic factor assessment. Results: Among patients administered first-line aumolertinib (n = 77), the objective remission rate (ORR) of 77.92% was observed, along with a disease control rate (DCR) of 100%. The median progression-free survival (mPFS) was 24.97 months, which did not reach the median overall survival (mOS). The patients treated with aumolertinib after progression on prior EGFR-tyrosine kinase inhibitor (TKI) therapy (n = 96) exhibited an ORR of 46.88%, a DCR of 89.58%, an mPFS of 15.17 months, and an mOS of 21.27 months. First-line treatment multivariate Cox regression analysis demonstrated a statistically significant impact of elevated creatine kinase on PFS (p = 0.016) and a similar significant influence of co-mutation on OS (p = 0.034). Furthermore, subsequent-line treatment multivariate Cox regression analysis showed a statistically significant impact of elevated creatine kinase on median PFS (p = 0.026) and a significant effect on the number of metastatic organs (p = 0.017), co-mutation (p = 0.035), and elevated creatine kinase (p = 0.014) on median OS. Conclusion: Aumolertinib has shown clinical significance and can safely be used in the real-world setting for patients with EGFR mutation-positive NSCLC.

Evolution of Microstructure and Mechanical Properties of Ti-6Al-4V Alloy under Heat Treatment and Multi-Axial Forging.

The mechanical properties of various Ti-6Al-4V alloys are influenced by their respective microstructures. This study generated an ultrafine-grain (UFG) Ti-6Al-4V alloy featuring bimodal grain distribution characteristics achieved through initial heat treatment, multi-axial forging (MF), and annealing. The study also extensively examined the evolution process of the alloy's microstructure. By subjecting the materials to heat treatments at 900 °C with air cooling and 950 °C with air cooling, both materials were found to be consisted of primary α (αp) and transformed ß (αs+ß) regions with different proportions. Following MF, the sample treated at 900 °C displays a microstructure featuring UFGs of α+ß surrounding larger micron-sized αp grains. On the other hand, the sample treated at 950 °C displays a microstructure distinguished by twisted αs lamellar and fragmented ß grains surrounding larger micron-sized αp grains. Following annealing, no significant grain growth was observed in the sample. The geometrically necessary dislocations (GNDs) within the UFGs were eliminated, though some GNDs persisted within the αp grains. The samples undergoing the 900 °C heat treatment, MF, and subsequent annealing exhibited elevated strength (1280 MPa) and total elongation (10.7%). This investigation introduces a novel method for designing the microstructure of the Ti-6Al-4V alloy to achieve superior performance.

Genome-Wide Identification and Expression Analysis of Chitinase Genes in Watermelon under Abiotic Stimuli and Fusarium oxysporum Infection.

Chitinases, which catalyze the hydrolysis of chitin, the primary components of fungal cell walls, play key roles in defense responses, symbiotic associations, plant growth, and stress tolerance. In this study, 23 chitinase genes were identified in watermelon (Citrullus lanatus [Thunb.]) and classified into five classes through homology search and phylogenetic analysis. The genes with similar exon-intron structures and conserved domains were clustered into the same class. The putative cis-elements involved in the responses to phytohormone, stress, and plant development were identified in their promoter regions. A tissue-specific expression analysis showed that the ClChi genes were primarily expressed in the roots (52.17%), leaves (26.09%), and flowers (34.78%). Moreover, qRT-PCR results indicate that ClChis play multifaceted roles in the interaction between plant/environment. More ClChi members were induced by Race 2 of Fusarium oxysporum f. sp. niveum, and eight genes were expressed at higher levels on the seventh day after inoculation with Races 1 and 2, suggesting that these genes play a key role in the resistance of watermelon to Fusarium wilt. Collectively, these results improve knowledge of the chitinase gene family in watermelon species and help to elucidate the roles played by chitinases in the responses of watermelon to various stresses.

Multi-Omics Analysis Reveals Intricate Gene Networks Involved in Female Development in Melon.

Sexual differentiation is an important developmental phenomenon in cucurbits that directly affects fruit yield. The natural existence of multiple flower types in melon offers an inclusive structure for studying the molecular basis of sexual differentiation. The current study aimed to identify and characterize the molecular network involved in sex determination and female development in melon. Male and female pools separated by the F2 segregated generation were used for sequencing. The comparative multi-omics data revealed 551 DAPs and 594 DEGs involved in multiple pathways of melon growth and development, and based on functional annotation and enrichment analysis, we summarized four biological process modules, including ethylene biosynthesis, flower organ development, plant hormone signaling, and ubiquitinated protein metabolism, that are related to female development. Furthermore, the detailed analysis of the female developmental regulatory pathway model of ethylene biosynthesis, signal transduction, and target gene regulation identified some important candidates that might have a crucial role in female development. Two CMTs ((cytosine-5)-methyltransferase), one AdoHS (adenosylhomocysteinase), four ACSs (1-aminocyclopropane-1-carboxylic acid synthase), three ACOs (ACC oxidase), two ARFs (auxin response factor), four ARPs (auxin-responsive protein), and six ERFs (Ethylene responsive factor) were identified based on various female developmental regulatory models. Our data offer new and valuable insights into female development and hold the potential to offer a deeper comprehension of sex differentiation mechanisms in melon.

Microstructures and Mechanical Properties of Al-Zn-Mg-Cu Alloys under Multi-Directional Severe Strain and Aging.

Microstructure is a significant factor that influences the mechanical properties of alloys. The effect of multiaxial forging (MAF) and subsequent aging treatment on the precipitated phases of Al-Zn-Mg-Cu alloy remains unclear. Therefore, an Al-Zn-Mg-Cu alloy was processed by means of solid solution and aging treatment, and MAF and aging treatment in this work, and the composition and distribution of precipitated phases were characterized in detail. The MAF results for dislocation multiplication and grain refinement were found. The high density of dislocation greatly accelerates the nucleation and growth of precipitated phases. Thus, the GP-zones almost transform into precipitated phases during subsequent aging. The MAF and aging alloy has more precipitated phases than the solid solution and aging treated alloy. The precipitates on the grain boundary are coarse and discontinuously distributed due to dislocation and grain boundary promoting the nucleation, growth and coarsening of the precipitates. The hardness, strength, ductility and microstructures of the alloy have been studied. Without compromising the ductility much, the MAF and aging alloy has higher hardness and strength, with values of 202 HV and 606 MPa, respectively, and an appreciable ductility of 16.2%.

Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study.

Goals: To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action. Methods: Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding. Results: 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment. Conclusion: W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.

Case report: Epithelioid inflammatory myofibroblastic sarcoma treated with an ALK TKI ensartinib.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive variant of inflammatory myofibroblastic tumor (IMT) and has a poor prognosis. EIMS is characterized by epithelioid morphology, neutrophilic infiltrate and specific fusion partners of anaplastic lymphoma kinase (ALK). Despite no standard therapy for EIMS, ALK tyrosine kinase inhibitors (TKIs) are recommended for these tumors. The present case describes an abdominal mass that presented in a 31-year-old male. The patient suffered from recurrence and multiple metastases 2 months after surgery. Ensartinib was administered and RANBP2-ALK fusion was detected. A partial response has been observed for 4 months and there has been no recurrence. This study provided a successful case with sustained response of targeted therapy.

Whole-transcriptome analyses identify key differentially expressed mRNAs, lncRNAs, and miRNAs associated with male sterility in watermelon.

Male sterility is a valuable trait for watermelon breeding, as watermelon hybrids exhibit obvious heterosis. However, the underlying regulatory mechanism is still largely unknown, especially regarding the related non-coding genes. In the present study, approximately 1035 differentially expressed genes (DEGs), as well as 80 DE-lncRNAs and 10 DE-miRNAs, were identified, with the overwhelming majority down-regulated in male-sterile floral buds. Enrichment analyses revealed that the general phenylpropanoid pathway as well as its related metabolisms was predicted to be altered in a mutant compared to its fertile progenitor. Meanwhile, the conserved genetic pathway DYT1-TDF1-AMS-MS188-MS1, as well as the causal gene ClAMT1 for the male-sterile mutant Se18, was substantially disrupted during male reproductive development. In addition, some targets of the key regulators AMS and MS188 in tapetum development were also down-regulated at a transcriptional level, such as ABCG26 (Cla004479), ACOS5 (Cla022956), CYP703A2 (Cla021151), PKSA (Cla021099), and TKPR1 (Cla002563). Considering lncRNAs may act as functional endogenous target mimics of miRNAs, competitive endogenous RNA networks were subsequently constructed, with the most complex one containing three DE-miRNAs, two DE-lncRNAs, and 21 DEGs. Collectively, these findings not only contribute to a better understanding of genetic regulatory networks underlying male sterility in watermelon, but also provide valuable candidates for future research.

Clinical efficacy and prognosis analysis of treatment regimens for EGFR mutant non-small cell lung cancer and brain metastasis: a retrospective study.

BACKGROUND: The aims of the study were to evaluate potential differences among first-line treatment for EGFR mutant (m+) non-small cell lung cancer (NSCLC) patients with brain metastasis in China and to identify the factors influencing survival outcomes. METHODS: In this retrospective study, 172 EGFRm + patients with advanced NSCLC who received a 1st generation EGFR tyrosine kinase inhibitor (TKI) were divided into 4 groups: A, EGFR-TKI (n = 84); B, EGFR-TKI + pemetrexed + cisplatin/carboplatin chemotherapy (CT) (n = 55); C, EGFR-TKI + bevacizumab (n = 15); and D, EGFR-TKI + pemetrexed + cisplatin/carboplatin CT + bevacizumab (n = 18). Intracranial and extracranial progression-free survival (PFS), the overall survival (OS), objective remission rates (ORRs) and adverse events were analyzed. RESULTS: Intracranial PFS of groups C + D was longer than for groups A + B (18.9 m vs. 11.0 m, P = 0.027). Extracranial PFS were longer in group B in comparison with group A (13.0 m vs. 11.5 m, P = 0.039) and in groups C + D compared to groups A + B (18.9 m vs. 11.9 m, P = 0.008). Median OS in groups A and B were 27.9 m and 24.4 m, respectively, while groups C and D have not yet achieved median OS. Significant difference was found in intracranial ORR between groups A + B vs. C + D (31.0% vs. 65.2%, P = 0.002). Most patients suffered grade 1-2 treatment-related adverse events, which were relieved soon after symptomatic treatment. CONCLUSIONS: First-generation EGFR-TKI + bevacizumab treatment outperformed other regimens in EGFRm + NSCLC patients with brain metastasis. The therapy improved the control and delayed progression of intracranial lesions and prolonged survival times.

Melatonin delays ABA-induced leaf senescence via H2 O2 -dependent calcium signalling.

Precocious leaf senescence can reduce crop yield and quality by limiting the growth stage. Melatonin has been shown to delay leaf senescence; however, the underlying mechanism remains obscure. Here, we show that melatonin offsets abscisic acid (ABA) to protect photosystem II and delay the senescence of attached old leaves under the light. Melatonin induced H2 O2 accumulation accompanied by an upregulation of melon respiratory burst oxidase homolog D (CmRBOHD) under ABA-induced stress. Both melatonin and H2 O2 induced the accumulation of cytoplasmic-free Ca2+ ([Ca2+ ]cyt ) in response to ABA, while blocking of Ca2+ influx channels attenuated melatonin- and H2 O2 -induced ABA tolerance. CmRBOHD overexpression induced [Ca2+ ]cyt accumulation and delayed leaf senescence, whereas deletion of Arabidopsis AtRBOHD, a homologous gene of CmRBOHD, compromised the melatonin-induced [Ca2+ ]cyt accumulation and delay of leaf senescence in Arabidopsis under ABA stress. Furthermore, melatonin, H2 O2  and Ca2+ attenuated ABA-induced K+ efflux and subsequent cell death. CmRBOHD overexpression and AtRBOHD deletion alleviated and aggravated the ABA-induced K+ efflux, respectively. Taken together, our study unveils a new mechanism by which melatonin offsets ABA action to delay leaf senescence via RBOHD-dependent H2 O2 production that triggers [Ca2+ ]cyt accumulation and subsequently inhibits K+ efflux and delays cell death/leaf senescence in response to ABA.

Rhinitis symptom in patients with self-reported allergic rhinitis is influenced by sensitization pattern: A cross-sectional study of China.

BACKGROUND: Allergic rhinitis (AR) is characterized by distinct clinical heterogeneity and allergic sensitization patterns. We aimed to quantify rhinitis symptoms in patients with self-reported allergic rhinitis according to the potential sensitization patterns for relevant allergens in China. METHODS: We used latent class analysis (LCA; a subset of structural equation modeling) to independently cluster patients into different patterns of atopic sensitization in an unsupervised manner, based on specific immunoglobulin E tests. AR symptom severity was assessed by the visual analogue scale. We evaluated the association between the severity of AR and the allergen sensitization patterns. RESULTS: LCA revealed four phenotypes of atopic sensitization among 967 patients with self-report AR. We labeled latent classes as: Class 1, weed pollens and indoor sensitization (n = 74 [7.7%]); Class 2, weed pollen with low indoor sensitization (n = 275 [28.4%]); Class 3, low or no sensitization (n = 350 [36.2%]); and Class 4, house dust mite-dominated sensitization (n = 268 [27.7%]). AR was more severe in Class 2 compared to the other 3 classes, indicating that upper respiratory symptoms are more severe among patients with isolated seasonal rhinitis. CONCLUSION: We have identified four sensitization patterns in patients with self-reported AR, which were associated with different clinical symptoms and comorbidities.

The HD-ZIP Gene Family in Watermelon: Genome-Wide Identification and Expression Analysis under Abiotic Stresses.

Homeodomain-leucine zipper (HD-ZIP) transcription factors are one of the plant-specific gene families involved in plant growth and response to adverse environmental conditions. However, little information is available on the HD-ZIP gene family in watermelon. In this study, forty ClHDZs were systemically identified in the watermelon genome, which were subsequently divided into four distinctive subfamilies (I-IV) based on the phylogenetic topology. HD-ZIP members in the same subfamily generally shared similar gene structures and conserved motifs. Syntenic analyses revealed that segmental duplications mainly contributed to the expansion of the watermelon HD-ZIP family, especially in subfamilies I and IV. HD-ZIP III was considered the most conserved subfamily during the evolutionary history. Moreover, expression profiling together with stress-related cis-elements in the promoter region unfolded the divergent transcriptional accumulation patterns under abiotic stresses. The majority (13/23) of ClHDZs in subfamilies I and II were downregulated under the drought condition, e.g., ClHDZ4, ClHDZ13, ClHDZ18, ClHDZ19, ClHDZ20, and ClHDZ35. On the contrary, most HD-ZIP genes were induced by cold and salt stimuli with few exceptions, such as ClHDZ3 and ClHDZ23 under cold stress and ClHDZ14 and ClHDZ15 under the salt condition. Notably, the gene ClHDZ14 was predominantly downregulated by three stresses whereas ClHDZ1 was upregulated, suggesting their possible core roles in response to these abiotic stimuli. Collectively, our findings provide promising candidates for the further genetic improvement of abiotic stress tolerance in watermelon.

Molecular Characteristics and Pathogenicity of a Novel Recombinant Porcine Reproductive and Respiratory Syndrome Virus Strain from NADC30-, NADC34-, and JXA1-Like Strains That Emerged in China.

Recently, the emergence of a NADC34-like porcine reproductive and respiratory syndrome virus (PRRSV), which causes a large number of abortions in swine herds, has raised great concern in China. In this study, a PRRSV variant strain, PRRSV/CN/FJGD01/2021, evolved from recombination between NADC30-like, NADC34-like, and JXA1-like viruses was isolated in Fujian province in 2021, and its pathogenicity in piglets was examined. Animal experiments demonstrated that PRRSV/CN/FJGD01/2021 infection could induce 100% morbidity and cause higher viremia, a persistently higher fever (>40°C for 14 consecutive days), significant weight loss, and severe histopathological lung lesions compared to the NADC30-like FJZ03 strain and NADC34-like FJ0908 strain in piglets. The PRRSV/CN/FJGD01/2021 strain displayed higher pathogenicity than the FJZ03 and FJ0908 strains, but lower pathogenicity than the Chinese highly pathogenic (HP)-PRRSVs in piglets. Moreover, the Ingelvac PRRS modified live vaccine (MLV) provides incomplete cross-protection against heterologous PRRSV/CN/FJGD01/2021 in piglets. Our findings contribute to the understanding of the current epidemic situation of NADC34-like PRRSV in China. IMPORTANCE The pathogenicity of NADC34-like PRRSV has broad variations in virulence. Importantly, NADC34-like PRRSV has undergone complex recombination with local strains since it first emerged in 2017 in China. However, the pathogenicity of the recombinant NADC34-like virus was rarely experimentally evaluated in pigs. In this study, a novel PRRSV strain, PRRSV/CN/FJGD01/2021, was isolated from sows enduring a high-abortion-rate (20%) period in China in 2021. Notably, phylogenetic and recombination analyses revealed that PRRSV/CN/FJGD01/2021 is a recombinant virus from NADC30-, NADC34-, and JXA1-like isolates. PRRSV/CN/FJGD01/2021 was shown to cause higher virus load, persistent fever, significant weight loss, moderate respiratory clinical signs, and severe histopathological lung lesions in piglets. PRRSV/CN/FJGD01/2021 exhibited higher pathogenicity than NADC30-like FJZ03 and NADC34-like FJ0908, but lower than Chinese HP-PRRSVs for piglets. These data indicated that PRRSV/CN/FJGD01/2021 has intermediate virulence for piglets. Furthermore, the Ingelvac PRRS MLV could partly provide protective efficacy against PRRSV/CN/FJGD01/2021 challenge in piglets.

Novel Bisexual Flower Control Gene Regulates Sex Differentiation in Melon (Cucumis melo L.).

The sex-control system involves several mechanisms in melon. The present study identified a novel bisexual flower control gene from the hermaphroditic melon germplasm, different from the previously recognized one. Genetic analysis showed that a single recessive gene in the newly identified locus b controlled the bisexual flower phenotype in melons. We generated 1431 F2 segregating individuals for genetic mapping of locus b, which was delimited to a 47.94 kb region. Six candidate genes were identified in the delimited interval, and candidate No. 4 encoding melon CPR5 protein was selected as the suitable one for locus b and was denoted CmCPR5. CPR5 reportedly interacted with ethylene receptor ETR1 to regulate ethylene signal transduction. Moreover, the ethephon assays showed that the parental lines (unisexual line and bisexual line) had contrasting expression patterns of CmCPR5. The BiFC and LCI assays also confirmed that CmCPR5 interacted with CmETR1 in 0426 but not in Y101. However, crossover tests showed that CmETR1 functioned normally in both parental lines, suggesting CPR5 malfunction in Y101. This study proposed a corollary mechanism of bisexual flower regulation during stamen primordium development in which the inhibition of stamen primordia development was prevented by the malfunctioning CmCPR5, resulting in bisexual flowers.

Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.