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Objective:To investigate the clinical efficacy of totally laparoscopic pylorus-preserving gastrectomy (TLPPG) with preservation of the first branch of the right gastroepiploic vein in early gastric cancer (EGC).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 38 EGC patients who were admitted to the Subei Hospital Affiliated to Yangzhou University from July 2018 to May 2021 were collected. There were 18 males and 20 females, aged 60 (range, 39?73) years. All patients underwent TLPPG with preservation of the first branch of the right gastroepiploic vein.Observation indicators: (1) surgical and postoperative condi-tions; (2) postoperative histopathological examination. (3) follow-up. Follow-up was conducted using outpatient examination, WeChat interview and medical record review to detect the nutritional status, residual stomach function, cholecystolithiasis, tumor recurrence and metastasis and death of patients. Follow-up was up to July 2022. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical and postoperative conditions. All 38 patients underwent TLPPG with preservation of the first branch of the right gastroepiploic vein successfully, without laparotomy conversion. The operation time, volume of intraoperative blood loss, time to postoperative first flatus, time to postoperative first liquid food intake and duration of postoperative hospital stay of the 38 patients were (180±28)minutes, (58±38)mL, (2.7±0.6)days, (3.4±0.7)days and (10.3±2.8)days, respectively. Of the 38 patients, there were 6 cases with postoperative complications ≥grade Ⅱ of Clavien-Dindo classification. (2) Postoperative histopatho-logical examination. The tumor diameter, distance from proximal resection margin to tumor and distance from distal resection margin to tumor of the 38 patients were (1.8±0.5)cm, (3.4±0.2)cm and (4.3±0.4)cm, respectively. Both of proximal and distal resection margin was negative. Numbers of lymph node examined and numbers of lymph node examined in the No.6 lymph node of the 38 patients were 23.3±3.9 and 3.4±1.1, respectively. There were 38 cases with pathological T1 stage including 23 cases of T1a stage and 15 cases of T1b stage. There were 36 cases with pathological N0 stage and 2 cases with pathological N1 stage. There were 36 cases with pathological ⅠA stage and 2 cases with pathological ⅠB stage of TNM staging. (3) Follow-up. All 38 patients were followed up for 18(range, 12?48)months. The hemoglobin, serum albumin and total serum protein of the 38 patients were (125.4±5.8)g/L, (42.4±2.3)g/L and (71.6±2.1)g/L, respectively, at postoperative 6 month. Endo-scopy was used to evaluate the function of residual stomach of patients at postoperative 12 month. There were 4 patients with moderate amount of food remaining in the residual stomach. No patient suffered reflux esophagitis, reflux gastritis and bile reflux. None of the 38 patients received post-operative chemotherapy, and there was no tumor recurrence and metastasis or death occured in patient.Conclusion:TLPPG with preservation of the first branch of the right gastroepiploic vein is safe and feasible for the treatment of EGC patients with tumor located at 1/3 of the middle segment of stomach.
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Objective: To summarize clinical features and our experience of the diagnosis and treatment of laryngocele. Methods: Clinical data of 11 laryngocele patients in department of Otorhinolaryngology Head and Neck Surgery of the Second Affiliated Hospital of Shanxi Medical University from January 2012 to December 2021 were retrospectively reviewed, including 9 men and 2 women, aged from 12 to 75 years, with median age of 56 years. Electronic laryngoscope was performed in 10 of all patients, laryngeal CT in 10 and cervical color ultrasound in 5 before operation.All the operations were performed under general anesthesia, and the external cervical approach was used for external and combined laryngocele. The internal laryngocele was resected by low temperature plasma through transoral endoscopy. Patients were followed up regularly after operation to evaluate the effect. Clinical feature, types of lesions, imaging findings, surgical approaches and follow-up results were analyzed through descriptive statistical method. Results: Eleven laryngocele patients were divided into mixed type (n=6), internal type (n=4) and external type (n=1).Nine patients presented with hoarseness or dysphonia, 7 with cervical mass and 1 with airway obstruction. Surgical resections were done through external cervical approach (n=7)or transoral endoscopic approach (n=4). All the operations were successful and no complication occurred. All cases were followed up from 17 to 110 months. No recurrence was encountered. Conclusions: Laryngocele is a rare lesion with atypical clinical presentation. Preoperative imaging including CT scan and electronic laryngoscope is essential to evaluate the location, and extent of the lesion, and to make the surgical plan.Complete surgical excision is required. Surgical resection is the only effective method for the treatment of laryngocele.
Subject(s)
Male , Humans , Female , Middle Aged , Child , Adolescent , Young Adult , Adult , Aged , Laryngocele/pathology , Retrospective Studies , Larynx/pathology , Laryngoscopy/methods , HoarsenessABSTRACT
Objective: To analyze the flow field characteristics of the upper airway in patients with different adenoid hypertrophy using computational fluid dynamics (CFD). Methods: From November 2020 to November 2021, the cone-beam CT (CBCT) data of 4 patients [2 males and 2 females,age range 5-7 years, mean (6.0±1.2) years] with adenoid hypertrophy who were hospitalized in the Department of Orthodontics and the Department of Otolaryngology at Hebei Eye Hospital were selected. The degree of adenoid hypertrophy in the 4 patients was divided into normal S1 (A/N<0.6), mild hypertrophy S2 (0.6≤A/N<0.7), moderate hypertrophy S3 (0.7≤A/N<0.9) and severe hypertrophy S4 (A/N≥0.9) according to the ratio of adenoid thickness to the width of nasopharyngeal cavity (A/N). The CFD model of the upper airway was established using ANSYS 2019 R1 software, and the internal flow field of the CFD model was numerically simulated. Eight sections were selected as observation and measurement planes for flow field information. Relevant flow field information includes airflow distribution, velocity variation, and pressure variation. Results: In the S1 model, the maximum pressure difference occurred in the 4th and 5th observation planes (ΔP=27.98). The lowest pressures and the maximum flow rates of S2 and S3 were located in the 6th observation plane. The airflow in S1 and S2 models completely passed through the nasal cavity. In the S3 model, the mouth-to-nasal airflow ratio was close to 2∶1. In S4 model, the airflow completely passed through the mouth; in the S1 and S2 models, hard palates were subjected to a downward positive pressure with a pressure difference of 38.34 and 23.31 Pa, respectively. The hard palates in S3 and S4 models were subjected to a downward negative pressure with a pressure difference of -2.95 and -21.81 Pa, respectively. Conclusions: The CFD model can objectively and quantitatively describe the upper airway airflow field information in patients with adenoid hypertrophy. With the increasing degree of adenoid hypertrophy, the nasal ventilation volume gradually decreased, whereas the oral space ventilation volume gradually increased, and the pressure difference between the upper and lower surfaces of the palate gradually decreased until the pressure became negative.
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Objective:To evaluate the role of permanent sigmoid colostomy created through the extraperitoneal route combined with pelvic floor peritoneal reconstruction after laparoscopic Miles surgery for lower rectal cancer.Methods:A total of 88 patients undergoing laparoscopic Miles surgery at Gastrointestinal Center of Northern Jiangsu People's Hospital from Apr 2016 to Apr 2020 were divided into extraperitoneal ostomy group(40 cases) and transperitoneal ostomy group (48 cases).Results:There were no significant differences in operating time, stoma-forming time, intraoperative blood loss, first exhausting time, first defecation time and hospital stay between the two groups (all P>0.05). There were 17 cases of complications in observation group vs. 16 cases in control group ( χ2=0.782， P=0.376). After 12 months, the complications in observation group were significantly less than control group ( χ2=8.601， P=0.003). There was no parastoma hernia in observation group vs.7 in control group ( χ2=4.502， P=0.034). The satisfaction rate of ostomy control defecation in observation group (70%) was significantly higher than that in control group (38%) after 12 months ( P=0.001). Conclusion:A permanent sigmoid colostomy created through the extraperitoneal route combined with pelvic floor peritoneal reconstruction during laparoscopic Miles surgery is safe and feasible, with fewer complications and better defecation function than that of the stoma through transperitoneal approach.
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OBJECTIVE@#To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft.@*METHODS@#We examined the effects of treatment with different concentrations of PNS on H22 cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H22 cells. Mouse models bearing H22 cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate.@*RESULTS@#Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H22 cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05).@*CONCLUSION@#PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H22 tumor-bearing mice.
Subject(s)
Animals , Humans , Mice , Carcinoma, Hepatocellular/pathology , Cyclophosphamide/therapeutic use , Hemolysin Proteins , Heterografts , Interleukin-2 , Liver Neoplasms/pathology , Panax notoginseng , Saponins/therapeutic use , Tumor Necrosis Factor-alphaABSTRACT
Objectives@#No studies have yet assessed vibration characteristics according to endodontic file length. Accordingly, the objective of the present study was to examine the vibration characteristics according to nickel-titanium file length and to compare these characteristics between different file systems. @*Materials and Methods@#A total of 45 root canal models were divided into 3 experimental groups (n = 15 each) based on the file system used (ProTaper Gold [PTG], ProTaper Next, or WaveOne Gold [WOG]). Each experimental group was further divided into 3 subgroups according to file length (21, 25, or 31 mm). An electric motor (X-SMART PLUS) was used in the experiment. For each file system, vibrations generated when using a size 25 file were measured and used to calculate the average vibration acceleration. The differences in vibrations were analyzed using 1-way analysis of variance and the Scheffé post hoc test with a confidence interval of 95%. @*Results@#In the PTG file system, significantly lower vibration acceleration was observed when using a 21-mm file than when using a 31-mm file. In the WOG file system, significantly stronger vibration acceleration was observed when using a 31-mm file than when using 21- or 25-mm files. Regardless of the file length, the WOG group exhibited significantly stronger vibration acceleration than the other 2 experimental groups. @*Conclusions@#In clinical practice, choosing a file with the shortest length possible could help reduce vibrations. Additionally, consideration should be given to vibrations that could be generated when using WOG files with reciprocating motion.
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Exosomes are membranous vesicles secreted by a variety of cells, including tumor cells, with stable characters, which can reflect the physiological/pathological state of the source cells, indicating good sources of biomarkers for early diagnosis and prognosis of tumors. Urine exosomes are directly derived from the urinary system and play a more direct role in the diagnosis and prognosis of urinary system tumors. This paper reviews the recent advances in urinary exosomes as molecular markers for the early diagnosis of genitourinary tumors.
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Exosomes are membranous vesicles secreted by a variety of cells,including tumor cells,with stable characters,which can reflect the physiological/pathological state of the source cells,indicating good sources of biomarkers for early diagnosis and prognosis of tumors.Urine exosomes are directly derived from the urinary system and play a more direct role in the diagnosis and prognosis of urinary system tumors.This paper reviews the recent advances in urinary exosomes as molecular markers for the early diagnosis of genitourinary tumors.
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Membrane-associated guanylate kinase (MAGUK) family protein MAGUK invert 2 (MAGI-2) has been demonstrated to be involved in the tumorigenic mechanism of prostate cancer. The objective of this study was to investigate the expression of MAGI-2 at mRNA and protein levels. The prognostic value of MAGI-2 in Han Chinese patients with prostate cancer was also investigated. The expression data of MAGI-2 were assessed through database retrieval, analysis of sequencing data from our group, and tissue immunohistochemistry using digital scoring system (H-score). The clinical, pathological, and follow-up data were collected. The expression of MAGI-2 in prostate tumor tissues and prostate normal tissues was evaluated and compared. MAGI-2 expression was associated with clinical parameters including tumor stage, lymph node status, Gleason score, PSA level, and biochemical recurrence of prostate cancer. The relative expression of MAGI-2 mRNA was lower in the tumor tissue in The Cancer Genome Atlas (TCGA) database and sequencing data (P < 0.001). There was no difference in MAGI-2 protein expression between tumor and normal tissues in tissue microarray (TMA) results. MAGI-2 expression was associated with pathological tumor stage (P = 0.02), Gleason score (P = 0.05), and preoperation prostate-specific antigen (PSA; P = 0.04). A positive correlation was identified between MAGI-2 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expressions through the analysis of TCGA and TMA data (P < 0.0001). Patients with higher MAGI-2 expression had longer biochemical recurrence-free survival in the univariate analysis (P = 0.005), which indicates an optimal prognostic value of MAGI-2 in Han Chinese patients with prostate cancer. In conclusion, MAGI-2 expression gradually decreases with tumor progression, and can be used as a predictor of tumor recurrence in Chinese patients.
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Objectives@#No studies have yet assessed vibration characteristics according to endodontic file length. Accordingly, the objective of the present study was to examine the vibration characteristics according to nickel-titanium file length and to compare these characteristics between different file systems. @*Materials and Methods@#A total of 45 root canal models were divided into 3 experimental groups (n = 15 each) based on the file system used (ProTaper Gold [PTG], ProTaper Next, or WaveOne Gold [WOG]). Each experimental group was further divided into 3 subgroups according to file length (21, 25, or 31 mm). An electric motor (X-SMART PLUS) was used in the experiment. For each file system, vibrations generated when using a size 25 file were measured and used to calculate the average vibration acceleration. The differences in vibrations were analyzed using 1-way analysis of variance and the Scheffé post hoc test with a confidence interval of 95%. @*Results@#In the PTG file system, significantly lower vibration acceleration was observed when using a 21-mm file than when using a 31-mm file. In the WOG file system, significantly stronger vibration acceleration was observed when using a 31-mm file than when using 21- or 25-mm files. Regardless of the file length, the WOG group exhibited significantly stronger vibration acceleration than the other 2 experimental groups. @*Conclusions@#In clinical practice, choosing a file with the shortest length possible could help reduce vibrations. Additionally, consideration should be given to vibrations that could be generated when using WOG files with reciprocating motion.
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Abdominoplasty procedures have dramatically increased over the past decade or more. The American Society for Aesthetic Plastic Surgery (ASAPS) Cosmetic Surgery National Data Bank reported in 2005 an increase of 344%[1]. Saldanha introduced Lipoabdominoplasty in the early 2000[2]. Over the past two decades, Abdominoplasty, a common procedure performed by plastic surgeons worldwide has undergone progressive gradual changes with the inclusion of liposuction contouring of the trunk. The author discusses his experience and technical preferences in the performance and management of complete/full abdominoplasty patients, including the floating umbilicus technique, with simultaneous liposuction obtained over the past 40 years in private practice.
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Rhabditis axei is a free-living nematode, which can occasionally invade into humans through drinking and contacting wastewater. It is usually parasitic in the digestive and urinary systems, causing the disease of rhabditelliasis axei. This paper reports a case of R. axei infection found in the urine routine examination.
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Rhabditis axei is a free-living nematode, which can occasionally invade into humans through drinking and contacting wastewater. It is usually parasitic in the digestive and urinary systems, causing the disease of rhabditelliasis axei. This paper reports a case of R. axei infection found in the urine routine examination.
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Objective MicroRNA-145 (miR-145) is underexpressed in breast cancer. The study aimed to explore the regulatory effect of miR-145 on breast cancer MCF-7 cells by investigating the association of miR-145 with ADAM17 and EGFR. Methods The MCF-7 breast cancer cells were divided into three groups: the transfection group (transfected with microRNA-145 mimics), the control group (without transfection) and the nonsense sequence group (transfected with nonsense microRNA). MTT, transwell and real-time quantitative fluorescence polymerase chain reaction(qPCR) were respectively used to detect the proliferative capacity, invasive ability and expression of MCF-7 breast cancer cells after the transfection of miR-145 in three groups. ADAM17 and EGFR mRNA and protein levels in three groups of breast cancer MCF-7 cells were detected by qPCR and western blot. Results The results of qPCR showed that the relative expression of miR-145 was significantly higher in transfection group (13964.33±1265.30) than those in control group (1.00±0.05) and nonsense sequence group (1.03±0.15) and the difference was statistically significant (P<0.01); the expression of ADAM17 mRNA in transfection group (1.71±0.08) was significantly higher than that in control group (1.00±0.07) and the difference was statistically significant (P<0.01). Compared with the nonsense sequences at 24 h, 48 h, and 72 h, the inhibition rate of MCF-7 in transfection group was significantly increased (P<0.01). The results of transwell invasion showed that the number of transmembrane cells in transfection group [(56.20±2.17)/field] was significantly lower than those in control group [(92.80±3.90)/field] and nonsense sequence group [(91.80±4.97)/field of view ] (P < 0.01). Western blot results showed that the protein content of ADAM17 and EGFR in transfection group was significantly lower than those in the control group and the nonsense sequence group (P<0.01). Conclusion MiR-145 inhibits the proliferation and invasion of breast cancer MCF-7 cell line by acting on the ADAM17-EGFR signaling pathway.
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The ventral pallidum (VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion. Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamic-derived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.
Subject(s)
Animals , Female , Male , Rats , Action Potentials , Basal Forebrain , Cell Biology , Dimaprit , Pharmacology , Dose-Response Relationship, Drug , Electric Stimulation , GABAergic Neurons , Histamine , Pharmacology , Histamine Agonists , Pharmacology , Lysine , Metabolism , Patch-Clamp Techniques , Pyridines , Pharmacology , Rats, Sprague-Dawley , Receptors, Histamine H1 , Metabolism , Receptors, Histamine H2 , Metabolism , Sodium Channel Blockers , Pharmacology , Tetrodotoxin , Pharmacology , gamma-Aminobutyric Acid , MetabolismABSTRACT
Exosomes actively secreted by prostate cancer cells are mediators of signal transduction between prostate tumor cells and mesenchymal cells, and they can promote the progress of prostate cancer by altering the microenvironment of primary tumors and metastasis tumors. In particular, exosomes participate in various molecular events related to prostate cancer progress by carrying bioactive molecules, such as RNAs and proteins. Therefore, exosomes and their carrying molecules are expected to be novel biomarkers for predicting the progress of prostate cancer and therapeutic targets of prostate cancer. In recent years, there are many researches in the field of prostate cancer-derived exosomes which have shown great values in predicting and preventing the progress of prostate cancer, and this review sums up the current advances.
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Objective: To compare the efficiency of two-dimensional speckle tracking echocardiography (2D-STE) and late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for detecting cardiac amyloidosis. Methods: Systolic longitudinal peak strain by 2D-STE and LGE by CMR were retrospectively analyzed in 10 patients with cardiac amyloidosis. Results: CMR showed 10 patients with LGE and 2D-STE showed 9 patients with ventricular systolic longitudinal peak strain decreasing, the diagnostic consistency of CMR and 2D-STE was 90％. There were 4 patients having both strain abnormality and LGE at meanwhile, 4 patients without CMR presented right ventricular involvement while with 2D-STE indicated abnormal right ventricular systolic longitudinal peak strain, 1 patient with CMR presented LGE in ventricular sepatum while 2D-STE indicated systolic longitudinal peak strain decreasing in both ventricles. Conclusion: 2D-STE and CMR had good consistency for diagnosing left ventricular involvement in patients with cardiac amyloidosis; 2D-STE may have better sensitivity for diagnosing right ventricular amyloidosis.
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BACKGROUND: Adiponectin is an adipokine that regulates lipid and glucose metabolism and has been shown to have anti-inflammatory and anti-atherogenic effects. It also plays an important role in the development of cardiovascular disease (CVD). METHODS: This study evaluated the association between adiponectin 45T/G polymorphism and cardiovascular complication in type 2 diabetes in Koreans. RESULTS: The present study included 758 patients with type 2 diabetes. The distribution of the adiponectin 45T/G polymorphism was 3.56% (n = 27) for GG, 42.35% (n = 321) for TG, and 54.09% (n = 410) for TT in patients with type 2 diabetes. The prevalence of CVD was significantly higher in subjects with the GG + TG genotype compared to those with the TT genotype (17.5% vs. 9.8%, P = 0.002). The G allele was associated with a higher risk of CVD (P = 0.002). CONCLUSION: Our findings suggest that the adiponectin 45T/G polymorphism is associated with diabetic cardiovascular complication in type 2 diabetes.
Subject(s)
Humans , Adipokines , Adiponectin , Alleles , Cardiovascular Diseases , Genotype , Glucose , Metabolism , PrevalenceABSTRACT
Objective To detect NF1 gene mutations in a patient with neurofibromatosis type 1 (NF1).Methods Polymerase chain reaction (PCR) and DNA sequencing were performed to detect mutations of the NF1 gene in a patient with NF1,his parents and 100 unrelated healthy controls.Results A novel frameshift mutation (c.3822delC) was identified in the patient,but not found in his parents or the unrelated healthy controls.Conclusion The novel frameshift mutation (c.3822delC) found in the patient is not a rare single nucleotide polymorphism (SNP),and may be a causative mutation for NF1 by affecting the function of the NF1 gene.
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<p><b>BACKGROUND</b>Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform.</p><p><b>METHODS</b>A review of the literature revealed 60 mutation hotspots in seven target genes (EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM) that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCarta™ kit in ten lung cancer specimens. EGFR, KRAS, and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility.</p><p><b>RESULTS</b>Our data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCarta™ kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform.</p><p><b>CONCLUSIONS</b>We established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.</p>