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Background: Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating type 2 diabetes mellitus (T2DM) in clinical studies. Accumulating evidence has suggested that the therapeutic effects of MSCs are not due to their direct differentiation into functional β-cells but are instead mediated by their paracrine functions. Among them, exosomes, nano-sized extracellular vesicles, are important substances that exert paracrine functions. However, the underlying mechanisms of exosomes in ameliorating T2DM remain largely unknown. Methods: Bone marrow mesenchymal stem cell (bmMSC)-derived exosomes (bmMDEs) were administrated to T2DM rats and high-glucose-treated primary islets in order to detect their effects on β-cell dedifferentiation. Differential miRNAs were then screened via miRNA sequencing, and miR-146a was isolated after functional verification. TargetScan, reporter gene detection, insulin secretion assays, and qPCR validation were used to predict downstream target genes and involved signaling pathways of miR-146a. Results: Our results showed that bmMDEs reversed diabetic β-cell dedifferentiation and improved β-cell insulin secretion both in vitro and in vivo. Results of miRNA sequencing in bmMDEs and subsequent functional screening demonstrated that miR-146a, a highly conserved miRNA, improved β-cell function. We further found that miR-146a directly targeted Numb, a membrane-bound protein involved in cell fate determination, leading to activation of β-catenin signaling in β-cells. Exosomes derived from miR-146a-knockdown bmMSCs lost the ability to improve β-cell function. Conclusions: These findings demonstrate that bmMSC-derived exosomal miR-146a protects against diabetic β-cell dysfunction by acting on the NUMB/β-catenin signaling pathway, which may represent a novel therapeutic strategy for T2DM. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). Methods: HucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta [MAP 1LC3B]), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting. Results: HucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism. Conclusions: These findings demonstrate that HucMDEs improved hepatic glucose and lipid metabolism in T2DM rats by activating autophagy via the AMPK pathway, which provides novel evidence suggesting the potential for HucMDEs in clinically treating T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Motor imagery (MI) induced EEG patterns are widely used as control signals for brain-computer interfaces (BCIs). Kinetic and kinematic factors have been proved to be able to change EEG patterns during motor execution and motor imagery. However, to our knowledge, there is still no literature reporting an effective online MI-BCI using kinetic factor regulated EEG oscillations. This study proposed a novel MI-BCI paradigm in which users can online output multiple commands by imagining clenching their right hand with different force loads.Methods: Eleven subjects participated in this study. During the experiment, they were asked to imagine clenching their right hands with two different force loads (30% maximum voluntary contraction (MVC) and 10% MVC). Multi-Common spatial patterns (Multi-CSPs) and support vector machines (SVMs) were used to build the classifier for recognizing three commands corresponding to high load MI, low load MI and relaxed status respectively. EMG were monitored to avoid voluntary muscle activities during the BCI operation. The event-related spectral perturbation (ERSP) method was used to analyse EEG variation during multiple load MI tasks.Results: All subjects were able to drive BCI systems using motor imagery of different force loads in online experiments. We achieved an average online accuracy of 70.9%, with the highest accuracy of 83.3%, which was much higher than the chance level (33%). The event-related desynchronization (ERD) phenomenon during high load tasks was significantly higher than it was during low load tasks both in terms of intensity at electrode positions C3 (p < 0.05) and spatial distribution.Conclusions: This paper demonstrated the feasibility of the proposed MI-BCI paradigm based on multi-force loads on the same limb through online studies. This paradigm could not only enlarge the command set of MI-BCI, but also provide a promising approach to rehabilitate patients with motor disabilities. [ABSTRACT FROM AUTHOR]

Background: Over the past few decades, there have been many studies of aspects of brain-computer interface (BCI). Of particular interests are event-related potential (ERP)-based BCI spellers that aim at helping mental typewriting. Nowadays, audiovisual unimodal stimuli based BCI systems have attracted much attention from researchers, and most of the existing studies of audiovisual BCIs were based on semantic incongruent stimuli paradigm. However, no related studies had reported that whether there is difference of system performance or participant comfort between BCI based on semantic congruent paradigm and that based on semantic incongruent paradigm.Methods: The goal of this study was to investigate the effects of semantic congruency in system performance and participant comfort in audiovisual BCI. Two audiovisual paradigms (semantic congruent and incongruent) were adopted, and 11 healthy subjects participated in the experiment. High-density electrical mapping of ERPs and behavioral data were measured for the two stimuli paradigms.Results: The behavioral data indicated no significant difference between congruent and incongruent paradigms for offline classification accuracy. Nevertheless, eight of the 11 participants reported their priority to semantic congruent experiment, two reported no difference between the two conditions, and only one preferred the semantic incongruent paradigm. Besides, the result indicted that higher amplitude of ERP was found in incongruent stimuli based paradigm.Conclusions: In a word, semantic congruent paradigm had a better participant comfort, and maintained the same recognition rate as incongruent paradigm. Furthermore, our study suggested that the paradigm design of spellers must take both system performance and user experience into consideration rather than merely pursuing a larger ERP response. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that turning is associated with more instability than straight walking and instability increases with turning angles. However, the precise relationship of changes in stability with the curvature and step length of turning is not clear. The traditional center of mass (COM)-center of pressure (COP) inclination angle requires the use of force plates. A COM-foot contact point (FCP) inclination angle derived from kinematic data is proposed in this study as a measure of the stability of turning.Methods: In order to generate different degrees of stability, we designed an experiment of walking with different curvatures and step lengths. Simultaneously, a novel method was proposed to calculate the COM-FCP inclination angles of different walking trajectories with different step lengths for 10 healthy subjects. The COM-FCP inclination angle, the COM acceleration, the step width and the COM-ankle inclination angles were statistically analyzed.Results: The statistical results showed that the mediolateral (ML) COM-FCP inclination angles increased significantly as the curvature of the walking trajectories or the step length in circular walking increased. Changes in the ML COM acceleration, the step width and the ML COM-ankle inclination angle verified the feasibility and reliability of the proposed method. Additionally, the ML COM-FCP inclination angle was more sensitive to the ML stability than the ML COM-ankle inclination angle.Conclusions: The work suggests that it is more difficult to keep balance when walking in a circular trajectory with a larger curvature or in a larger step length. Essentially, turning with a larger angle in one step leads to a lower ML stability. A novel COM-FCP inclination angle was validated to indicate ML stability. This method can be applied to complicated walking tasks, where the force plate is not applicable, and it accounts for the variability of the base of support (BOS) compared to the COM-ankle inclination angle. [ABSTRACT FROM AUTHOR]

Background: A number of studies have been done on movement imagination of motor sequences with a single limb. However, brain oscillatory patterns induced by movement imagination of motor sequences involving multiple limbs have not been reported in recent years. The goal of the present study was to verify the feasibility of application of motor sequences involving multiple limbs to brain-computer interface (BCI) systems based on motor imagery (MI). The changes of EEG patterns and the inter-influence between movements associated with the imagination of motor sequences were also investigated.Methods: The experiment, where 12 healthy subjects participated, involved one motor sequence with a single limb and three kinds of motor sequences with two or three limbs. The activity involved mental simulation, imagining playing drums with two conditions (60 and 30 beats per minute for the first and second conditions, respectively).Results: Movement imagination of different limbs in the sequence contributed to time-variant event-related desynchronization (ERD) patterns within both mu and beta rhythms, which was more obvious for the second condition compared with the first condition. The ERD values of left/right hand imagery with prior hand imagery were significantly larger than those with prior foot imagery, while the phase locking values (PLVs) between central electrodes and the mesial frontocentral electrode of non-initial movement were significantly larger than those of the initial movement during imagination of motor sequences for both conditions. Classification results showed that the power spectral density (PSD) based method outperformed the multi-class common spatial patterns (multi-CSP) based method: The highest accuracies were 82.86 % and 91.43 %, and the mean values were 65 % and 74.14 % for the first and second conditions, respectively.Conclusions: This work implies that motor sequences involving multiple limbs can be utilized to build a multimodal classification paradigm in MI-based BCI systems, and that prior movement imagination can result in the changes of neural activities in motor areas during subsequent movement imagination in the process of limb switching. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the minimally invasive cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) approach in the management of renal cell carcinoma (RCC) with level III or IV inferior vena cava (IVC) thrombus and evaluate the survival outcomes. Methods: We performed a retrospective analysis on 32 RCC patients with IVC thrombus that underwent nephrectomy and thrombectomy via the minimally invasive CPB/DHCA approach between January 2007 and December 2013. Perioperative variables (for example, operative time, CPB duration, and circulatory arrest duration), estimated blood loss, hospital stay, perioperative complications, and survival data were recorded and analyzed. Results: Thirty-two patients (median age: 56 years) were treated surgically using the CPB and DHCA approach for RCC with a level III (n = 25) or level IV (n = 7) tumor thrombus. The median operation time was 360 min (interquartile range (IQR): 300 to 435 min) with median CPB and DHCA durations of 149 min and 23 min, respectively. The median estimated blood loss was 2,500 ml. Four complications were observed but no deaths occurred perioperatively. The median follow-up was 25 months (range: 4 to 64 months). The mean overall survival (OS) was 28.2 ± 4.6 months while the disease-free survival (DFS) was 19.5 ± 11.6 months. In patients with M0 disease, ten patients developed metastases and were treated with sorafenib as an adjuvant therapy. The mean OS and DFS of this subgroup were 25.4 ± 12.8 months and 16.0 ± 14.2 months, respectively. Conclusions: Radical nephrectomy and thrombectomy using CPB and DHCA to treat RCC is a relatively safe approach associated with low morbidity and mortality. This minimally invasive procedure may help minimize surgical trauma and improve perioperative outcomes. [ABSTRACT FROM AUTHOR]

Background: There are different opinions about the relationship of two disjunctively distributed varieties Adiantum reniforme L. var. sinense Y.X.Lin and Adiantum reniforme L. Adiantum reniforme var. sinense is an endangered fern only distributed in a narrowed region of Chongqing city in China, while Adiantum reniforme var. reniforme just distributed in Canary Islands and Madeira off the north-western African coast. To verify the relationship of these two taxa, relative phylogenetic analyses, karyotype analyses, microscopic spore observations and morphological studies were performed in this study. Besides, divergence time between A. reniforme var. sinense and A. reniforme var. reniforme was estimated using GTR model according to a phylogeny tree constructed with the three cpDNA markers atpA, atpB, and rbcL. Results: Phylogenetic results and divergence time analyses-all individuals of A. reniforme var. sinense from 4 different populations (representing all biogeographic distributions) were clustered into one clade and all individuals of A. reniforme var. reniforme from 7 different populations (all biogeographic distributions are included) were clustered into another clade. The divergence between A. reniforme var. reniforme and A. reniforme var. sinense was estimated to be 4.94 (2.26-8.66) Myr. Based on karyotype analyses, A. reniforme var. reniforme was deduced to be hexaploidy with 2n = 180, X = 30, while A. reniforme var. sinense was known as tetraploidy. Microscopic spore observations suggested that surface ornamentation of A. reniforme var. reniforme is psilate, but that of A. reniforme var. sinense is rugate. Leaf blades of A. reniforme var. sinense are membranous and reniform and with several obvious concentric rings, and leaves of A. reniforme var. reniforme are pachyphyllous and coriaceous and are much rounder and similar to palm. Conclusion: Adiantum reniforme var. sinense is an independent species rather than the variety of Adiantum reniforme var. reniforme. As a result, we approve Adiantum nelumboides X. C. Zhang, nom. & stat. nov. as a legal name instead of the former Adiantum reniforme var. sinense. China was determined to be the most probable evolution centre based on the results of phylogenetic analyses, divergence estimation, relative palaeogeography and palaeoclimate materials. [ABSTRACT FROM AUTHOR]

Background: Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving the oncogenic role of CRT in PC. Methods: We investigated the potential role and mechanism of CRT in regulating intracellular free Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo. Results: Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK). TG-promoted cell invasion and migration was also rescued by CRT silencing but enhanced by IRE1α silencing (one of the key stressors in unfolded protein response). Meanwhile, CRT was co-immunoprecipitated and co-localized with IRE1α in vitro and its silencing led to the chronic ERS via upregulating IRE1α independent of IRE1-XBP1 axis. Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In vivo, CRT silencing decreased subcutaneous tumor size and distant liver metastasis following with the increase of IRE1α expression. A negative relationship between CRT and IRE1α was also observed in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients. Conclusions: CRT promotes EMT in PC via mediating intracellular free Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling. [ABSTRACT FROM AUTHOR]

Background: In recent years, hyperthermia has been widely applied as a novel strategy for cancer treatment due to its multiple antitumour effects. In particular, the potential influences of hyperthermia on the tumour immune microenvironment may improve the efficacy of immunotherapies. However, the effect of hyperthermia on renal cell carcinoma (RCC) has not been well characterized until now., Methods: In the present study, we primarily evaluated the effects of hyperthermia on cellular function via cellular proliferation, migration, invasion and apoptosis assays. In addition, the influence of hyperthermia on the immunogenicity of RCC cells was analysed using flow cytometry analysis, enzyme-linked immunosorbent assays, and immunofluorescent (IF) staining., Results: Our results demonstrate that hyperthermia significantly inhibits RCC cell proliferation, migration, and invasion and promotes cell apoptosis. In addition, we verified that hyperthermia improves the immunogenicity of RCC cells by inducing immunogenic cell death., Conclusion: Our findings suggest that hyperthermia is a promising therapeutic strategy for RCC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists., Methods: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021., Results: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study., Conclusions: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Although headache disorders are common, the current diagnostic approach is unsatisfactory. Previously, we designed a guideline-based clinical decision support system (CDSS 1.0) for diagnosing headache disorders. However, the system requires doctors to enter electronic information, which may limit widespread use., Methods: In this study, we developed the updated CDSS 2.0, which handles clinical information acquisition via human-computer conversations conducted on personal mobile devices in an outpatient setting. We tested CDSS 2.0 at headache clinics in 16 hospitals in 14 provinces of China., Results: Of the 653 patients recruited, 18.68% (122/652) were suspected by specialists to have secondary headaches. According to "red-flag" responses, all these participants were warned of potential secondary risks by CDSS 2.0. For the remaining 531 patients, we compared the diagnostic accuracy of assessments made using only electronic data firstly. In Comparison A, the system correctly recognized 115/129 (89.15%) cases of migraine without aura (MO), 32/32 (100%) cases of migraine with aura (MA), 10/10 (100%) cases of chronic migraine (CM), 77/95 (81.05%) cases of probable migraine (PM), 11/11 (100%) cases of infrequent episodic tension-type headache (iETTH), 36/45 (80.00%) cases of frequent episodic tension-type headache (fETTH), 23/25 (92.00%) cases of chronic tension-type headache (CTTH), 53/60 (88.33%) cases of probable tension-type headache (PTTH), 8/9 (88.89%) cases of cluster headache (CH), 5/5 (100%) cases of new daily persistent headache (NDPH), and 28/29 (96.55%) cases of medication overuse headache (MOH). In Comparison B, after combining outpatient medical records, the correct recognition rates of MO (76.03%), MA (96.15%), CM (90%), PM (75.29%), iETTH (88.89%), fETTH (72.73%), CTTH (95.65%), PTTH (79.66%), CH (77.78%), NDPH (80%), and MOH (84.85%) were still satisfactory. A patient satisfaction survey indicated that the conversational questionnaire was very well accepted, with high levels of satisfaction reported by 852 patients., Conclusions: The CDSS 2.0 achieved high diagnostic accuracy for most primary and some secondary headaches. Human-computer conversation data were well integrated into the diagnostic process, and the system was well accepted by patients. The follow-up process and doctor-client interactions will be future areas of research for the development of CDSS for headaches., (© 2023. The Author(s).)

Background: To determine whether transrectal ultrasound and urologist&#95;dually guided pelvic floor muscle exercise is associated with immediate, early and long-term urinary continence after radical prostatectomy., Materials and Methods: Data from 114 patients with localized prostate cancer (PC) who underwent RP at Henan Cancer Hospital from November 2018 to April 2021 were included in the retrospective study. Of the 114 patients, 50 patients in the observation group underwent transrectal ultrasound and urologist&#95;dually guided PFME, and 64 patients in the control group underwent verbally&#95;guided PFME. Contractile function of the external urinary sphincter was in the observation group was evaluated. The immediate, early and long-term urinary continence rates were assessed in both groups, and the factors affecting urinary continence were analyzed., Results: The urinary continence rate at 2 weeks and 1, 3, 6 and 12 months in the observation group after RP was significantly higher than that in the control group (52.0% vs. 29.7%, 70.0% vs. 39.1%, 82% vs. 57.8, 88% vs. 70.3%, 98.0 vs. 84.4%, p < 0.05). The contractile function of the external urinary sphincter was obviously correlated with urinary continence at multiple visits after RP, except for the 12-month visit. Transrectal ultrasound and urologist-dually guided PFME was verified to be an independent positive factor for urinary continence at 2 weeks and 1, 3, 6 and 12 months using logistic regression analysis. However, TURP was a negative factor for postoperative urinary continence at different times., Conclusions: Transrectal ultrasound and urologist&#95;dually guided PFME had a significant role in improving immediate, early and long-term urinary continence after RP and acted as an independent prognostic factor., (© 2023. The Author(s).)

Purpose: This study aimed to explore the feasibility and safety of the tunnel approach in laparoscopic radical right hemicolectomy for colon cancer., Methods: From July 2016 to October 2018, a total of 106 consecutive patients with colon cancer who underwent laparoscopic radical right hemicolectomy at the Affiliated Cancer Hospital of Zhengzhou University were enrolled. The patients were stratified into either a tunnel approach (TA) (n = 56) group or traditional medial approach (MA) (n = 50) group according to the surgical technique performed. The baseline demographics, perioperative outcomes and oncologic outcomes were compared between the two groups., Results: The baseline characteristics did not differ between groups. The TA group had significantly less blood loss [20.0 (10.0-40.0) vs. 100 (100.0-150.0) ml, p < 0.001] and a shorter operation time [128.4 ± 16.7 vs. 145.6 ± 20.3 min, p < 0.001] than the MA group. The time to first flatus and postoperative hospital stay were similar [3.0 (2.0-4.0) vs. 3.0 (3-4.0) days, p = 0.329; 10.4 ± 2.6 vs. 10.7 ± 3.0 days, p = 0.506] between the two groups. The conversion to laparotomy and complication rates were similar between groups (0 vs. 6.0%, p = 0.203; 14.3% vs. 18.0%, p = 0.603, respectively). No treatment-related deaths occurred in either group. The TA group did not have significantly better survival outcomes than the MA group (p = 0.372)., Conclusions: The TA seems to allow for more favourable results in terms of blood loss and operative time than the MA, with similar results regarding time to first flatus, hospital stay, postoperative complication rate, conversion rate and oncologic outcomes; moreover, the TA is easier for beginners to master., (© 2022. The Author(s).)

BRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations in both KRAS and BRAF genes have been identified in non-small cell lung cancer (NSCLC). They lead to the proliferation, differentiation, and apoptosis of tumor cells by activating the RAS/RAF/MEK/ERK signaling pathway. To date, agents that target RAS/RAF/MEK/ERK signaling pathway have been investigated in NSCLC patients harboring BRAF mutations. BRAF and MEK inhibitors have gained approval for the treatment of patients with NSCLC. According to the reported findings, the combination of MEK inhibitors with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor-tyrosine kinase inhibitors or BRAF inhibitors is highly significant for improving clinical efficacy and causing delay in the occurrence of drug resistance. This review summarized the existing experimental results and presented ongoing clinical studies as well. However, further researches need to be conducted to indicate how we can combine other drugs with MEK inhibitors to significantly increase therapeutic effects on patients with lung cancer.