Mesenchymal-epithelial transition factor (MET) gene mutation is a large class of mutations commonly seen in non-small cell lung cancer (NSCLC). MET mutation includes subtypes such as MET exon 14 skipping mutation (METex14m) and MET amplification (METamp). For advanced NSCLC with METex14m, Savolitinib has a high sensitivity as a member of tyrosine kinase inhibitors (TKIs). METamp is a relatively rare genetic mutation type which can serve as a driver gene to mediate primary and later acquired drug resistance of epidermal growth factor receptor (EGFR)-TKIs. For advanced NSCLC with secondary METamp, EGFR-TKIs combined with MET-TKIs are usually used in clinical treatment, while the optimal treatment strategy for advanced NSCLC with primary METamp has not yet been determined. For locally advanced NSCLC patients with positive driver gene mutations such as EGFR, anaplastic lymphoma kinase (ALK) fusion and METex14m, there have been relevant cases reported that neoadjuvant targeted therapy could achieve a good prognosis, but there have been no cases of neoadjuvant targeted therapy for locally advanced NSCLC patients with METamp. This report describes a case of a locally advanced NSCLC patient with dual driver gene mutations (EGFR L858R combined with primary METamp), the tumor did not shrink after 1 month of Gefitinib monotherapy, but significantly subsided after 4 months of Savolitinib monotherapy. After radical surgery, the pathological results proved pathological complete response (pCR) of the tumor, and the patient had a good response to postoperative continual Savolitinib treatment, with no recurrence nor metastasis observed to date. This case reports the feasibility and effectiveness of neoadjuvant targeted therapy for locally advanced NSCLC with primary METamp, aiming to provide effective reference for perioperative treatment of locally advanced NSCLC with primary METamp.
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Humans ; Acrylamides/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Gene Amplification ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/genetics* ; Triazines

PURPOSE: The importance of long noncoding RNAs (lncRNAs) in tumorigenesis has recently been demonstrated. However, the role of lncRNAs in development of thyroid cancer remains largely unknown. MATERIALS AND METHODS: Using quantitative reverse transcription polymerase chain reaction, expression of three lncRNAs, including BRAF-activated long noncoding RNA (BANCR), papillary thyroid cancer susceptibility candidate 3 (PTCSC3), and noncoding RNA associated with mitogen-activated protein kinase pathway and growth arrest (NAMA), was investigated in the current study. RESULTS: Of the three lncRNAs (BANCR, PTCSC3, and NAMA), expression of BANCR was significantly up-regulated while PTCSC3 and NAMA were significantly down-regulated in papillary thyroid carcinoma (PTC) compared to that in normal tissue. BANCR-knockdown in a PTC-derived cell line (IHH-4) resulted in significant suppression of thyroid stimulating hormone receptor (TSHR). BANCR-knockdown also led to inhibition of cell growth and cell cycle arrest at G0/G1 phase through down-regulation of cyclin D1. In addition, BANCR was enriched by polycomb enhancer of zeste homolog 2 (EZH2), and silencing BANCR led to decreased chromatin recruitment of EZH2, which resulted significantly reduced expression of TSHR. CONCLUSION: These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.
Carcinogenesis ; Cell Cycle Checkpoints ; Cell Line ; Cell Proliferation* ; Chromatin ; Cyclin D1 ; Down-Regulation ; Polymerase Chain Reaction ; Protein Kinases ; Receptors, Thyrotropin* ; Reverse Transcription ; RNA, Long Noncoding* ; RNA, Untranslated ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyrotropin*

[ABSTRACT]OBJECTIVETo evaluate the short-term efficacy of Eustachian tube balloon dilation (ETBD) in the treatment of symptomatic Eustachian tube dysfunction (SETD) by subjective and objective analysis.METHODS Forty patients who underwent ETBD were included. Subjects’ inclusion criteria were as followed: symptoms of ETD (aural fullness predominantly, with or without otalgia, muffle hearing and tinnitus), normal tympanic membrane, type A or C tympanograms, and without a history of any middle ear diseases. Main outcomes including subjective improvement, otoscopy, pure-tone audiometry, impedance audiometry, R-value in tubomanometry (TMM) and Eustachian Tube Score (ETS) were assessed 1 week and 6 months postoperatively.RESULTSAll cases were dilated successfully. A significant effect of treatment was documented when measuring subjective improvement, impedance audiometry, R-value in TMM and ETS 1 week and 6 month postoperatively. Subjective symptoms were not relieved only in one patient. The overall success rate for all patients was 98%.CONCLUSIONETBD can provide short-term benefits to those who are diagnosed with SETD and refractory to medical management. SETD might be an optimal indication for ETBD in the treatment of ETD.

Objective To study the vestibular function in patients with sudden deafness .Methods Retrospec-tive analysis of 436 cases of patients with sudden deafness ,being divided into two groups according to whether the merger of vertigo .147 cases with vertigo group ,75 cases of which were mild to moderately severe hearing loss .In-clud the rise type of 28 cases ,26 cases of flat type ,21cases of decline type .72 cases of which were severe hearing loss .In 289 cases without vertigo ,157 cases had mild moderate and severe hearing loss .Includ the rise type of 36 cases ,57 cases of flat type ,64 cases of decline type .One hundred and thirty two cases of which were severe hearing loss .Use video electronystagmogram (VNG) to test the vestibular function .Process the data with SPSS 13 .0 soft-ware .Results One hundred and twenty three(83 .7% )cases of the vertigo group suffered from vestibular function decline ,with 51 cases of mild to moderately severe hearing loss ,72 cases of severe and above .165 (57 .1% )cases of the without vertigo group suffered from vestibular function decline .There were 45 cases of mild to moderately se-vere hearing loss ,120 cases of severe and above .35 patients with vertigo patients with BPPV ,28 cases of which happened within 1 week in sudden deafness occured and 80% of which were vestibular function decline .Conclusion Patients with sudden deafness with vertigo suffered from vestibular function damage .Patients with sudden deafness without vertigo also suffered from vestibular function damage .And the more serious the hearing loss ,the higher the vestibular function decline opportunities .

OBJECTIVE: To investigate the effect of Eustachian tube balloon dilation (ETBD) in treatment of eustachian tube related diseases. METHOD: Fifteen cases (20 ears) of otitis media with effusion and 22 cases (30 ears) of symptomatic Eustachian tube dysfunction were recruited. Technique of tubomanometry (TMM) showed obstructive Eustachian tube dysfunction in all patients. All the patients were received ETBD and followed up with VAS evaluation of ear fullness, muffled hearing, poping sound in the ear and tinnitus. And also the TMM change and middle ear effusion. RESULT: Ear fullness, muffled hearing released with 1 week (ear fullness: 8.2 ± 1.4 vs. 2.0 ± 1.2, P < 0.05, muffled hearing: 6.2 ± 1.2 vs. 3.1 ± 0.8, P < 0.05). No recurrence was seemed within 6 months. The eustachian function test turned better. Symptomatic Eustachian tube dysfunction had an effective rate of 96.6% while otitis media with effusion was 95.0%. CONCLUSION ETBD have good short-term effect in obstructive eustachian tube dysfunction related middle ear dysfunction, which might provide a good way to solve the eustachian tube related diseases.
Catheterization ; Ear Diseases ; Ear, Middle ; Eustachian Tube ; physiopathology ; Humans ; Otitis Media ; Otitis Media with Effusion ; Recurrence

OBJECTIVE: To investigate the clinical features in cochlear otosclerosis. METHOD: Three cases with cochlear otosclerosis in our hospital from March 2007 to October 2008 were reported and the relevant literatures were reviewed. All the cases were confirmed the diagnose by temporal bone high-resolution CT scan (HRCT). RESULT: The chief complaint when visited was recurrent episodic vertigo or equilibrium disturbance with progressing hearing loss in all cases. Two ears in 2 cases were simple sensorineural deafness and considered the pure cochlear otosclerosis. Others were mixed deafness with the descent of bone conduction in different extent. The characters in HRCT: the low density area could be seen in different areas of the otic capsule, the pericochlear lucency or double-ring effect were the typical signs. CONCLUSION The diagnosis of cochlear otosclerosis is considered in the insoluble sensorineural deafness and the mixed deafness with vestibular symptoms and chronic hearing loss history. Temporal bone HRCT plays an important role in the clinical diagnosis of cochlear otosclerosis.
Adult ; Aged, 80 and over ; Cochlea ; diagnostic imaging ; Female ; Humans ; Middle Aged ; Otosclerosis ; diagnosis ; diagnostic imaging ; Temporal Bone ; diagnostic imaging ; Tomography, X-Ray Computed

OBJECTIVE: To investigate the characteristic of nystagmus and treatment of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV). METHOD: The positioning nystagmic features in 43 patients with HSC-BPPV treated between April 2004 and October 2006 were recorded and analyzed with video nystagmography. After the subtype and the effect side were determined, the appropriate repositioning maneuvers were chosen. RESULT: (1) Geotropic nystagmus was recorded in 27 cases, of whom 19 cases were treated with barbecue maneuver and/or combined forced prolonged position maneuver, while the others were treated with Asprella's maneuver. (2) Apogeotropic nystagmus was recorded in 16 cases with two types, one of which could turn into geotropic nystagmus with Gufoni's maneuver or spontaneously (in 12 cases), the other type could not (in 4 cases) transform accepted barbecue maneuver and/or combined forced prolonged position maneuver. The total improvement rate was 72.1% after 1 week and 81.4% 3 months later respectively. CONCLUSION The otolith position and the pathogenesis could be distinguished according to the nystagmic characteristics and type of HSC-BPPV. It was necessary to apply the appropriate repositioning maneuvers to treat HSC-BPPV.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Nystagmus, Pathologic ; therapy ; Semicircular Canals ; Treatment Outcome ; Vertigo ; diagnosis ; therapy

AIM: To observe the effect of adrenocorticotropic hormone(ACTH) on the levels of brain-derived neurotrophic factor (BDNF), trkB and corticotropin-releasing hormone(CRH) in the hippocampus of arthritic rats.METHODS: The BDNF immunoreactivity (IR) and CRH-positive neurons were stained with immunohistochemistry and in situ hybridization methods, respectively.RESULTS: The BDNF-IR, CRH mRNA-positive neurons in the contralateral hippocampus of the arthritic rats were increased significantly, which was decreased markedly by intraperitoneal injection of ACTH. However, the effect of ACTH was attenuated after adrenalectomy (ADX).CONCLUSION: These results suggest that BDNF and CRH in the hippocampus of arthritic rats were involved in the modulation of chronic pain, ACTH produced its analgesic effect by inhibiting the increase in BDNF and CRF level. Adrenal is critical to the analgesic action of ACTH.

AIM: To observe the survive, differentiation and therapeutic effect of neural precursor cells (NPCs) differentiated from mouse embryonic stem cells (ESc) when transplanted in the frontal cortex of Alzheimer's disease (AD) rats. METHODS: NPCs were induced from mouse ESc with serum-free methods. The differentiation of transplanted NPCs was observed with immunohistochemistry methods and memory of rats was evaluated with Morris water maze test. RESULTS: About 85% of mouse ESc were differentiated into NPCs 5 days after the embryoid bodies cultured in the N2 medium. 4 and 6 weeks after transplantation, the memory impairment of AD rats was relieved, most of the grafted NPCs were kept undifferentiated and proliferated in clone shape, neuron-like long processes was observed. CONCLUSIONS: The NPCs derived from ESc survive and differentiate into neurons after grafted into the frontal cortex of AD rats, which produces therapeutic effects on AD.

Objective To study the effect of chronic low dose soman on learning and memory and long term potentiation(LTP) of hippocampal slices. Methods Rat model was established by consecutive subcutaneous injection of soman(6-10 ?g?kg 1 , s. c, sig?14) for 14 days for Morris water maze test. Long term potential of synaptic transmission was observed in CA1 region by tetanization of the Schaffer commissural pathway in rat hippocampal slices. Results In the Morris water maze, latency to find a hidden platform was longer and the times of crossing the situation of platform and the time percent of swimming in northeast obviously decreased. In the experiment on hippocampal slice of rats in vitro by microelectrode method, the generation of long term potentiation was inhibited. Conclusion Chronic low dose soman may cause an evident learning and memory disturbance and decrease hippocampal synaptic plasticity.