Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq.

BACKGROUND: The stria vascularis (SV), located in the lateral wall of the cochlea, maintains cochlear fluid homeostasis and mechanoelectrical transduction (MET) activity required for sound wave conduction. The pathogenesis of a number of human inheritable deafness syndromes, age related hearing loss, drug-induced ototoxicity and noise-induced hearing loss results from the morphological changes and functional impairments in the development of the SV. In this study, we investigate the implications of intercellular communication within the SV in the pathogenesis of sensorineural hearing loss (SNHL). We aim to identify commonly regulated signaling pathways using publicly available single-cell transcriptomic sequencing (scRNA-seq) datasets. METHODS: We analyzed scRNA-seq data, which was derived from studying the cochlear SV in mice with SNHL compared to normal adult mice. After quality control and filtering, we obtained the major cellular components of the mouse cochlear SV and integrated the data. Using Seurat's FindAllMarkers and FindMarkers packages, we searched for novel conservative genes and differential genes. We employed KEGG and GSEA to identify molecular pathways that are commonly altered among different types of SNHL. We utilized pySCENIC to discover new specific regulatory factors in SV subpopulation cells. With the help of CellChat, we identified changes in subpopulation cells showing similar trends across different SNHL types and their alterations in intercellular communication pathways. RESULTS: Through the analysis of the integrated data, we discovered new conserved genes to SV specific cells and identified common downregulated pathways in three types of SNHL. The enriched genes for these pathways showing similar trends are primarily associated with the Electron Transport Chain, related to mitochondrial energy metabolism. Using the CellChat package, we further found that there are shared pathways in the incoming signaling of specific intermediate cells in SNHL, and these pathways have common upstream regulatory transcription factor of Nfe2l2. Combining the results from pySCENIC and CellChat, we predicted the transcription factor Nfe2l2 as an upstream regulatory factor for multiple shared cellular pathways in IC. Additionally, it serves as an upstream factor for several genes within the Electron Transport Chain. CONCLUSION: Our bioinformatics analysis has revealed that downregulation of the mitochondrial electron transport chain have been observed in various conditions of SNHL. E2f1, Esrrb, Runx1, Yy1, and Gata2 could serve as novel important common TFs regulating the electron transport chain. Adm has emerged as a potential new marker gene for intermediate cells, while Itgb5 and Tesc show promise as potential new marker genes for marginal cells in the SV. These findings offer a new perspective on SV lesions in SNHL and provide additional theoretical evidence for the same drug treatment and prevention of different pathologies of SNHL.

Identification of mRNA expression profiles and their characterization in age-related hearing loss.

Age-related hearing loss (ARHL), is a pervasive health problem worldwide. ARHL seriously affects the quality of life and reportedly leads to social isolation and dementia in the elderly. ARHL is caused by the degeneration or disorders of cochlear hair cells and auditory neurons. Numerous studies have verified that genetic factors contributed to this impairment, however, the mechanism behind remains unclear. In this study, we analyzed an mRNA expression dataset (GSE49543) from the GEO database. Differentially expressed genes (DEGs) between young control mice and presbycusis mice were analyzed using limma in R and weighted gene co-expression network analysis (WGCNA) methods. Functional enrichment analyses of the DEGs were conducted with the clusterProfiler R package and the results were visualized using ggplot2 R package. The STRING database was used for the construction of the protein-protein interaction (PPI) network of the screened DEGs. Two machine learning algorithms LASSO and SVM-RFE were used to screen the hub genes. We identified 54 DEGs in presbycusis using limma and WGCNA. DEGs were associated with the synaptic vesicle cycle, distal axon, neurotransmitter transmembrane transporter activity in GO analysis, and alcoholic liver disease, pertussis, lysosome pathway according to KEGG analyses. PPI network analysis identified three significant modules. Five hub genes (CLEC4D, MS4A7, CTSS, LAPTM5, ALOX5AP) were screened by LASSO and SVM-RFE. These hub genes were highly expressed in presbycusis mice compared with young control mice. We screened DEGs and identified hub genes involved in ARHL development, which might provide novel clues to understanding the molecular basis of ARHL.

Point-wise spatial network for identifying carcinoma at the upper digestive and respiratory tract.

PROBLEM: Artificial intelligence has been widely investigated for diagnosis and treatment strategy design, with some models proposed for detecting oral pharyngeal, nasopharyngeal, or laryngeal carcinoma. However, no comprehensive model has been established for these regions. AIM: Our hypothesis was that a common pattern in the cancerous appearance of these regions could be recognized and integrated into a single model, thus improving the efficacy of deep learning models. METHODS: We utilized a point-wise spatial attention network model to perform semantic segmentation in these regions. RESULTS: Our study demonstrated an excellent outcome, with an average mIoU of 86.3%, and an average pixel accuracy of 96.3%. CONCLUSION: The research confirmed that the mucosa of oral pharyngeal, nasopharyngeal, and laryngeal regions may share a common appearance, including the appearance of tumors, which can be recognized by a single artificial intelligence model. Therefore, a deep learning model could be constructed to effectively recognize these tumors.

Distal end side-to-side anastomosis of sequential coronary bypass for size mismatched saphenous vein grafts and coronary arteries.

INTRODUCTION: The distal end anastomosis is critical to the entire sequential grafts in coronary artery bypass grafting (CABG), but caliber mismatch diminishes the quality of the anastomosis. We aimed to introduce a modified distal end side-to-side (deSTS) anastomosis to handle the size mismatch and compared with classic distal end end-to-side (deETS) anastomosis. METHODS: From January 2014 to December 2018, 185 patients who underwent off-pump CABG with size mismatched sequential vein grafts (≥3.5 mm) and target coronaries (1.0-1.5 mm) at the distal end anastomoses were included. We retrospectively reviewed the data of the patients, perioperative and follow-up outcomes were analyzed. RESULTS: The deSTS group (n = 67) showed higher anastomotic flow (19.8 ± 8.0 vs 14.9±6.8 mL/min; p < 0.001) and lower pulsatility index (2.7 ± 0.8 vs 3.2 ± 1.0; p = 0.001) than the deETS group (n = 118). Higher incidence of in-hospital myocardial infarction (MI) was found in the deETS group but without significant difference (9.0% vs. 15.3%; p = 0.220). Kaplan-Meier analysis illustrated a relatively lower MI and major adverse cardiovascular and cerebrovascular events (MACCE) incidence in the deSTS group, and the deSTS group was associated with a reduction in long-term death, MI and MACCE in the adjusted Cox regression model. In addition, relatively higher graft patency was found in the deSTS group. CONCLUSIONS: The deSTS anastomosis showed superiority in solving size mismatch in sequential CABG, including better intraoperative flow dynamics, ideal long-term graft patency and reduced the incidence of perioperative and follow-up adverse events especially in MI.

Delayed Endoscopic Management of Esophageal Sharp-Pointed Food Impaction: An Analysis of 829 Cases in China.

BACKGROUND: Esophageal foreign body impaction is the most common cause of endoscopic emergency. However, there are limited available data on delayed endoscopic management of esophageal sharp-pointed food impaction. AIMS: To investigate cases of esophageal sharp-pointed food impaction with endoscopic removal findings. METHODS: This single-center retrospective study collected medical records to identify patients with esophageal sharp-pointed food impaction who underwent endoscopic removal between April 2018 and April 2020. The patients were divided into the early (endoscopic removal <12 h) and delayed intervention (>12 h) cohorts. RESULTS: Overall, 133 and 696 patients received early and delayed intervention, respectively. The success rate of endoscopic foreign body removal was 96.45%. The most common foreign body was fish bone (66.90%), and the most common shape was "I" (56.26%). Patients from the delayed intervention cohort received general anesthesia with a higher risk for perforation, and no foreign body was identified. The duration of endoscopy, distance between the foreign body/wound and the incisor, and longest diameter of the foreign body were not different between the groups. In multivariate analysis, male sex (odds ratio = 1.792 [1.159, 2.771]; P = 0.009), longer duration of impaction (odds ratio = 2.212 [1.121, 4.365]; P = 0.022) and endoscopy (odds ratio = 1.502 [1.253, 1.800]; P < 0.001), and longest diameter of the foreign body (odds ratio = 1.632 [1.329, 2.003]; P < 0.001) were associated with a higher incidence of perforation in patients with foreign body impaction. CONCLUSIONS: Endoscopic removal is a safe and effective treatment method for sharp-pointed food impaction. Delayed endoscopic removal can increase the risk of esophageal perforation.

Effects of design and coupling parameters on the performance of electromagnetic transducers in round-window stimulation.

Many studies have investigated factors contributing to large variations in the outcomes of round-window (RW) stimulation but most have focused on the floating mass transducer (FMT). To determine whether results for the FMT hold for a fixed-type transducer (FTT), this study constructs two coupled finite element models of the transducer and the human ear that incorporate the cochlear third windows and inner structures of these two electromagnetic transducers. We use these FE models of the human ear and transducers to investigate the influence of four design parameters and coupling conditions for the transducers, i.e., the support's Young's modulus, the coupling layer's cross sectional area and Young's modulus, and the transducer's cross sectional area. The results show that an increase in the support's Young's modulus reduces the output of the FMT but increases that of the FTT. Reducing the cross sectional area and Young's modulus of the coupling layer significantly increases the low-frequency response of the FMT but slightly reduces that of the FTT. Reducing the cross sectional area of the transducer increases the output of the FMT but reduces that of the FTT. This shows that inner structures of electromagnetic transducers should be considered in the optimal design parameters and coupling conditions for RW stimulation.

A comparison of patients with neck abscesses caused by esophageal foreign body impaction vs. inflammatory disease: a retrospective study.

OBJECTIVES: During clinical practice, we have detected a few cases of neck abscesses in patients diagnosed with esophageal foreign body impaction (EFB) but without the primary inflammatory disease. However, we do not know if neck abscesses caused by an inflammatory source are more like to be associated with a more severe progression or poorer prognosis. In this study, we aimed to identify differences between these two groups of patients by comparing progression and prognosis. MATERIALS AND METHODS: We retrospectively reviewed all patients who underwent neck abscess incisions between January 2011 and March 2022 and divided these patients into two groups: an EFB group and an inflammation group. Data were described by percentages, means, and standard deviations (SDs). Fisher's precision probability test was used to compare differences between the EFB and inflammation groups. Categorical variables were analyzed by Pearson's Chi-squared test. In addition, three factors including hospital days, intensive care unit (ICU) stay, and drainage-tube removal time were used for multivariate analysis to identify independent correlations separately. RESULTS: We enrolled a total of 33 patients with neck abscesses who received surgical incisions; the EFB group included 14 (42%) cases, while the inflammatory group included 19 (58%) cases. No significant differences were identified between the two groups in terms of surgery type (with or without mediastinotomy) and postoperative management (negative pressure drainage or postoperative irrigation). There were no significant differences between the two groups in terms of hospital stay, the timing of drainage-tube removal, the risk of ICU admission, and the probability of receiving intubation and tracheotomy. The incidence rate of esophageal perforation differed significantly between the two groups (p < 0.001). However, there were no significant differences in terms of other preoperative or postoperative comorbidities. The multivariate analysis revealed that the application of mediastinotomy (HR = 0.216 [0.049, 0.963]; p = 0.044) was correlated with a longer stay in the hospital. The time from symptoms to surgery was associated with a longer drainage tube removal time (HR = 0.392 [0.159, 0.967]; P = 0.042) and longer ICU stay (OR = 79.754[1.513, 4203.182]; P = 0.03). CONCLUSION: Patients with neck abscesses associated with EFB and inflammation received the same therapeutic management, and there were no significant differences between these two groups in terms of prognosis. Furthermore, esophageal perforation was found to be irrelevant to the aggravation of neck abscesses, and there was no need for additional surgery to repair a perforated esophagus in patients with neck abscesses. LEVEL OF EVIDENCE: Retrospective cohort (2b).

[Research on computer aided diagnosis of otitis media based on faster region convolutional neural network].

Otitis media is one of the common ear diseases, and its accurate diagnosis can prevent the deterioration of conductive hearing loss and avoid the overuse of antibiotics. At present, the diagnosis of otitis media mainly relies on the doctor's visual inspection based on the images fed back by the otoscope equipment. Due to the quality of otoscope equipment pictures and the doctor's diagnosis experience, this subjective examination has a relatively high rate of misdiagnosis. In response to this problem, this paper proposes the use of faster region convolutional neural networks to analyze clinically collected digital otoscope pictures. First, through image data enhancement and preprocessing, the number of samples in the clinical otoscope dataset was expanded. Then, according to the characteristics of the otoscope picture, the convolutional neural network was selected for feature extraction, and the feature pyramid network was added for multi-scale feature extraction to enhance the detection ability. Finally, a faster region convolutional neural network with anchor size optimization and hyperparameter adjustment was used for identification, and the effectiveness of the method was tested through a randomly selected test set. The results showed that the overall recognition accuracy of otoscope pictures in the test samples reached 91.43%. The above studies show that the proposed method effectively improves the accuracy of otoscope picture classification, and is expected to assist clinical diagnosis.

[Numerical study on the effect of middle ear malformations on energy absorbance].

In order to study the effect of middle ear malformations on energy absorbance, we constructed a mechanical model that can simulate the energy absorbance of the human ear based on our previous human ear finite element model. The validation of this model was confirmed by two sets of experimental data. Based on this model, three common types of middle ear malformations, i. e. incudostapedial joint defect, incus fixation and malleus fixation, and stapes fixation, were simulated by changing the structure and material properties of the corresponding tissue. Then, the effect of these three common types of middle ear malformations on energy absorbance was investigated by comparing the corresponding energy absorbance. The results showed that the incudostapedial joint defect significantly increased the energy absorbance near 1 000 Hz. The incus fixation and malleus fixation dramatically reduced the energy absorbance in the low frequency, which made the energy absorbance less than 10% at frequencies lower than 1 000 Hz. At the same time, the peak of energy absorbance shifted to the higher frequency. These two kinds of middle ear malformations had obvious characteristics in the wideband acoustic immittance test. In contrast, the stapes fixation only reduced the energy absorbance in the low frequency and increased energy absorbance in the middle frequency slightly, which had no obvious characteristic in the wideband acoustic immittance test. These results provide a theoretical reference for the wideband acoustic immittance diagnosis of middle ear malformations in clinic.

A caffeic acid phenethyl ester analog inhibits the proliferation of nasopharyngeal carcinoma cells via targeting epidermal growth factor receptor.

A previous study reported that compound 5A, a caffeic acid phenethyl ester (CAPE) analog, exhibited obvious neuroprotective activity, in particular, compound 5A possessed higher stability and membrane permeability than CAPE. CAPE displays antitumour function; therefore, evaluating the antitumour effect of its analog with higher stability and membrane permeability is worthwhile. We first investigated the antitumour activity of compound 5A. We found that compound 5A significantly inhibited the proliferation of tumor cells and showed low cytotoxicity in normal cells. Furthermore, compound 5A was found to induce the cell cycle arrest and apoptosis of CNE2 cells. Through the prediction of SwissTargetPrediction and subsequent confirmation, epidermal growth factor receptor (EGFR) was identified as a target of compound 5A. Compound 5A also influenced the expression of genes downstream of EGFR in nasopharyngeal carcinoma (NPC) cells. Based on these findings, compound 5A inhibits the proliferation of NPC cells by targeting EGFR and may become a new candidate compound for NPC treatment.

Elevated antistreptolysin O titer is closely related to cardiac mitral insufficiency in untreated patients with Takayasu arteritis.

BACKGROUND: The etiology of Takayasu arteritis (TA) is unknown; however, a possible relationship between streptococcal infection and TA has been proposed. This study aimed to identify the clinical features and cardiac valvular involvement in untreated TA patients with an elevated antistreptolysin O (ASO) titer. METHODS: In this retrospective study, the clinical characteristics and features of valvular involvement were compared in TA patients with or without an elevated ASO titer. RESULTS: Of the 74 untreated TA patients, 13 patients were found have elevated ASO titers (17.6%). Mitral insufficiency was the most common in patients with elevated ASO (69.2%, 9/13), followed by aortic valve insufficiency (46.2%, 5/13) and tricuspid insufficiency (46.2%, 5/13), which were no significantly different than that in normal ASO group. The proportions of moderate to severe mitral (30.8% vs 1.6%, p = 0.000) and tricuspid valve (15.4% vs 1.64%, p = 0.023) insufficiency in the ASO positive group were significantly higher than those in the ASO negative group. The odds of mitral regurgitation in patients with elevated ASO titers were 3.9 times higher than those in the group with normal ASO titers (p = 0.053, OR = 3.929, 95% confidence interval [CI]: 0.983-15.694). Furthermore, the risk of moderate to severe mitral insufficiency in patients with elevated ASO titers was 41.6 times higher than that in patients with normal ASO titers (p = 0.002, OR = 41.600, 95% CI: 3.867-447.559). CONCLUSIONS: An increase in ASO titer is related to valvular involvement in TA and is closely linked to mitral insufficiency.

The role of third windows on human sound transmission of forward and reverse stimulations: A lumped-parameter approach.

The vestibular and cochlear aqueducts serve as additional sound transmission paths and produce different degrees of volume velocity shunt flow in cochlear sound transmission. To investigate its effect on forward and reverse stimulations, a lumped-parameter model of the human ear, which incorporates the third windows, was developed. The model combines a transmission-line ear-canal model, a middle-ear model, and an inner-ear model, which were developed previously by different investigators. The model is verified by comparison with experiments. The intracochlear differential-pressure transfer functions, which reflect the input force to the organ of Corti, were calculated. The results show that middle-ear gain for forward sound transmission is greater than the gain for reverse sound transmission. Changes in the cochlear aqueduct impedance have little effect on forward and reverse stimulations. The vestibular aqueduct has little effect on forward stimulation, but increasing its impedance causes deterioration on reverse stimulation below 300 Hz. Decreasing its impedance increases the excitation effect during reverse stimulation over the entire frequency, especially below 1000 Hz. Moreover, compared with the case without the third windows, the presence of the third windows has little effect on forward stimulation. Whereas, it boosts the reverse stimulation's performance below 300 Hz.

The racial disparity of nasopharyngeal carcinoma based on the database analysis.

OBJECTIVE: To investigate whether the racial/ethnical disparity of nasopharyngeal carcinoma exists among the four major ethical groups in the United States named Asians, Caucasians, African Americans and Hispanics between the years of 1973 to 2013 using the Surveillance, Epidemiology, and End Result (SEER) database. METHODS: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database from 1973 to 2013 was utilized in this study to calculate survival trends for the four main ethical groups in the United States. The cases of nasopharyngeal carcinoma were extracted based on the SEER code cs0204schema. Death due to the diagnosed nasopharyngeal cancer was considered to be the event of interest, and death due to other causes was treated as the censoring events. Kaplan-Meier model was adopted to estimate survival outcomes; the Cox proportional hazards model was employed to do the hazard ratios (HR) estimation. RESULTS: A total of 8068 eligible patients of nasopharyngeal carcinoma were identified. The cohort was composed of 40.69% Caucasians, 11.34% African Americans, 40.16% Asians and 7.81% Hispanics. According to the multivariate Cox regression analysis, Asians had a better survival prognosis against Caucasians (HR: 0.74, 95% CI: 0.65-0.84, P < 0.001). African Americans showed marginal worse survival prognosis compared with Caucasians (HR: 1.26, 95% CI: 1.07-1.49, P < 0.005). There was no significant difference between Hispanics and Caucasians (HR: 1.13, 95% CI: 0.92-1.39, P = 0.261). CONCLUSION: Asians showed a disease specific survival advantage over Caucasians, African Americans and Hispanics, which was independent of sex, age at diagnosis, grade, TNM staging and treatment strategy.

[Numerical analysis of the influence of otitis media on the hearing compensation performance of round-window stimulation].

In order to study the influence of tympanic membrane lesion and ossicular erosion caused by otitis media on the hearing compensation performance of round-window stimulation, a human ear finite element model including cochlear asymmetric structure was established by computed tomography (CT) technique and reverse engineering technique. The reliability of the model was verified by comparing with the published experimental data. Based on this model, the tympanic membrane lesion and ossicular erosion caused by otitis media were simulated by changing the corresponding tissue structure. Besides, these simulated diseases' effects on the round-window stimulation were studied by comparing the corresponding basilar-membrane's displacement at the frequency-dependent characteristic position. The results show that the thickening and the hardening of the tympanic membrane mainly deteriorated the hearing compensation performance of round-window stimulation in the low frequency; tympanic membrane perforation and the minor erosion of ossicle with ossicular chain connected slightly effected the hearing compensation performance of round-window stimulation. Whereas, different from the influence of the aforementioned lesions, the ossicular erosion involving the ossicular chain detachment increased its influence on performance of round-window stimulation at the low frequency. Therefore, the effect of otitis media on the hearing compensation performance of round-window stimulation should be considered comprehensively when designing its actuator, especially the low-frequency deterioration caused by the thickening and the hardening of the tympanic membrane; the actuator's low-frequency output should be enhanced accordingly to ensure its postoperative hearing compensation performance.

The Endoscopic Prelacrimal Recess Approach to the Pterygopalatine Fossa and Infratemporal Fossa.

PURPOSE: The authors studied the anatomic importance of the endoscopic prelacrimal recess approach (PLRA) to the pterygopalatine fossa (PPF) and infratemporal fossa (ITF). METHODS: Ten adult heads (20 sides) from cadavers fixed in formalin were dissected using the PLRA. Anatomic dissections were detailed and several crucial landmarks measured. RESULTS: Identification of the infraorbital neurovascular bundle is the crucial step for the detection of other branches of the maxillary artery. The distance from the base of columella to inferior orifice of the nasolacrimal duct, sphenopalatine foramen, pterygold canal, foramen rotundum, foramen ovale was (32.97 ±â€Š3.44), (63.93 ±â€Š4.52), (66.81 ±â€Š3.44), (68.13 ±â€Š4.43), and (85.23 ±â€Š6.25) mm, respectively. The PLRA can be used to expose the entire maxillary sinus and PPF, most parts of the ITF (lateral pterygoid muscle, foramen ovale, mandibular division of the trigeminal nerve, and its divisions), maxillary artery and its branches, and the superior part of the medial pterygoid muscle (upon the floor of the maxillary sinus). The lateral boundary can be reached to visualize the temporomandibular joint and vertically oriented temporalis muscle. CONCLUSION: Use of the PLRA to the PPF and ITF offers a clear visual field, wide range of exposure, as well as preservation of the integrity of nasal structures.

Concept and Evaluation of a New Piezoelectric Transducer for an Implantable Middle Ear Hearing Device.

Implantable middle ear hearing devices (IMEHDs) have been developed as a new technology to overcome the limitations of conventional hearing aids. The piezoelectric cantilever transducers currently used in the IMEHDs have the advantages of low power consumption and ease of fabrication, but generate less high-frequency output. To address this problem, we proposed and designed a new piezoelectric transducer based on a piezoelectric stack for the IMEHD. This new transducer, attached to the incus body with a coupling rod, stimulates the ossicular chain in response to the expansion-and-contraction of its piezoelectric stack. To test its feasibility for hearing loss compensation, a bench testing of the transducer prototype and a temporal bone experiment were conducted, respectively. Bench testing results showed that the new transducer did have a broad frequency bandwidth. Besides, the transducer was found to have a low total harmonic distortion (<0.75%) in all frequencies, and small release time (1 ms). The temporal bone experiment further proved that the transducer has the capability to produce sufficient vibrations to compensate for severe sensorineural hearing loss, especially at high frequencies. This property benefits the treatment of the most common sloping high-frequency sensorineural hearing loss. To produce a 100 dB SPL equivalent sound pressure at 1 kHz, its power consumption is 0.49 mW, which is low enough for the transducer to be utilized in the IMEHD.

Upregulation of miR-129-5p affects laryngeal cancer cell proliferation, invasiveness, and migration by affecting STAT3 expression.

microRNA-129-5p may have a relationship with laryngeal squamous cell carcinoma (LSCC), but the expression and function of miRNA-129-5p are not fully understood. This study was performed to investigate the expression and function of miRNA-129-5p in LSCC and its effects on STAT3. HBE and Hep-2 cells were cultured and analyzed by western blotting and real-time PCR. miR-129-5p expression was detected by real-time PCR. Hep-2 cells were transfected with a miR-129-5p expression vector. Cell proliferation, invasion, migration, cell cycle, and apoptosis assays were used to determine the role of miRNA-129-5p in the growth, invasion, and migration of LSCC cells and to determine the importance of STAT3 in these effects. STAT3 mRNA expression in Hep-2 cells was significantly higher than that in HBE cells (P < 0.05). miR-129-5p expression detected by real-time PCR showed that it was expressed at a lower level in Hep-2 cells than in HBE cells (P < 0.05). Compared with the control cells, the transfected cells showed lower STAT3 mRNA expression. For up to 7 days in culture, the transfected cells showed lower proliferation than the control cells (P < 0.05). After 24 h in culture, the apoptosis rate in miR-129-5p-transfected cells was 3.48 ± 0.38 %, while the rate in control cells was 0.92 ± 0.09 % (P = 0.0028), but the statistical significance was lost after 72 h in culture (P = 0.3180). The invasion and migration of the cells were inhibited after 24 and 72 h in culture when the miR-129-5p expression in Hep-2 cells was upregulated (P = 0.0037 and 0.00383, respectively), while there was no statistically significant difference at 48 h (P = 0.0712). STAT3 expression could be suppressed by the upregulation of miR-129-5p expression. Both the proliferation and migration of tumor cells were suppressed when the level of STAT3 expression was decreased. The apoptosis rate of tumor cells was also increased. Based on these data, we suggest that miR-129-5p may directly inhibit STAT3 expression and play an important role in the development of LSCC.

Thyroid carcinoma cells produce PLGF to enhance metastasis.

Cancer neovascularization is essential for metastasis of thyroid carcinoma. However, the underlying molecular mechanisms are ill-defined. Recently, placental growth factor (PLGF) has been shown to play critical roles in the pathological angiogenesis through regulating matrix metalloproteinases (MMPs); here, we were prompted to examine the role of PLGF in the metastasis of thyroid carcinoma. We found that the PLGF and MMP9 levels strongly correlated in the thyroid carcinoma specimen. Higher PLGF and MMP9 levels were detected in the thyroid carcinoma with metastasis. Using a human thyroid carcinoma cell line, TT, we found that overexpression of PLGF in TT cells increased expression of MMP9, while inhibition of PLGF in TT cells decreased expression of MMP9. However, modification of MMP9 levels in TT cells did not affect PLGF levels, suggesting that PLGF may regulate MMP9 in thyroid carcinoma cells. Moreover, application of a specific MAPK p42/p44 inhibitor, but not the application of a specific MAPK p38 inhibitor or specific Akt or JNK inhibitors, substantially abolished the effect of PLGF on MMP9 activation, suggesting that PLGF may increase expression of MMP9 via p42/p44 signaling pathway. Together, these data suggest that antagonizing PLGF in thyroid carcinoma cells may be a promising therapy to suppress cancer metastasis.

Ultra-small superparamagnetic iron oxide mediated magnetic hyperthermia in treatment of neck lymph node metastasis in rabbit pyriform sinus VX2 carcinoma.

Lymph node metastasis of rabbit VX2 pyriform sinus carcinoma can be enhanced by MR scanning after injecting ultra-small superparamagnetic iron oxide (USPIO) into the submucosa beside the tumor. The metastasis lymph node which fit in with the diagnostic criteria will be placed into the alternating magnetic field after MR scanning. Then, magnetic particles can be heated to the effective therapeutic temperature. And it evaluates the possibility of diagnosis together with therapy in cervical metastasis of pyriform sinus carcinoma. Twenty rabbits bearing VX2 tumor in pyriform sinuses were randomly divided into hyperthermia group and control group after USPIO MR scanning; each group contained 10 rabbits. The hyperthermia for the experimental group was conducted by the alternating magnetic field. After hyperthermia, the detection of apoptosis for the two groups was tested by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL), transmission electron microscopy (TEM), and the expression of Bcl-2 and Bax evaluated by immunohistochemical analysis. The apoptosis rate detected by TUNEL in hyperthermia group was 100 %, while the control group was only 20 % (p < 0.05). TEM observation showed that cell chromatin condensation and clumping, condensed cytoplasm, endoplasmic reticulum membrane fusion with loose change, and the formation of a bubble could be seen in the hyperthermia group. However, the control group showed a more complete cytoplasm and nucleus. Bcl-2 protein expression in the hyperthermia group was lower than the control group, and Bax protein expression in hyperthermia group was higher (p < 0.05). USPIO indirect lymphography could localize the metastatic lymph nodes for hyperthermia. And it could make the metastatic cervical lymph nodes apoptosis when placed into the alternating magnetic field.

[Comparison of pedicled and scheltoned endoscopic methods harvesting saphenous vein in shank].

OBJECTIVE: To compare the efficacies of endoscopic harvesting saphenous vein as sequential graft by pedicled and scheltoned technique. METHODS: From June 2013 to December 2013, a total of 93 patients undergoing coronary artery bypass with endoscopic vein harvesting in shank were recruited. Saphenous veins were harvested by pedicled method in group A (n =46) and scheltoned method in group B (n =47). Harvesting method was decided by a random number for each patient. Saphenous veins were used as sequential grafts during off-pump coronary artery bypass. Inter-group comparisons were made in time for harvesting, time for repairing, venous injuries and perioperative effect of saphenous vein. The postoperative follow-up period was 30 days. Early failure of saphenous vein graft was evaluated with coronary computed tomography (CT) angiography. RESULTS: All saphenous veins in shank were harvested successfully. No significant difference existed in vein length. In groups A and B, average time for harvesting was (21. 7 ± 5. 6) and (27. 4 ± 6. 4) min (P < 0. 05) and time for repairing (7. 2 ± 2. 7) and (10. 6± 4. 4) min respectively (P <0. 05). No severe injury resulted in non-using of saphenous in both groups. The repair rates of saphenous vein were 10. 9% and 38. 3% respectively (P < 0. 05). For each repaired saphenous vein, the average number of locations was (1. 6 ± 0. 5) and (3. 1 ± 1. 0) sites respectively (P < 0. 05). All patients were discharged uneventfully. There was no perioperative onset of myocardial infarction or malignant arrhythmia. For groups A and B, 89. 1% and 93. 6% were followed up for 1 month post-operation. No angina, myocardial infarction or heart failure occurred. For groups A and B, 32 and 37 cases were re-examined on CT coronary angiography and all saphenous vein grafts maintained patency. CONCLUSIONS: Pedicled method is more safe and reliable for endoscopic saphenous vein harvesting. It can ensure the quality of sequential graft, shorten harvesting time and reduce the risks of vein injury.