Relationship Between Air Pollutants and the Incidence of Epistaxis in Yangzhou.

Objectives: This project aims to explore the relationship between the air quality index (AQI), the concentration of 6 air pollutants, and the incidence of epistaxis in Yangzhou. Also, to provide reference information for the prevention and treatment of epistaxis. Methods: Data of patients with epistaxis admitted to the Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2017 to December 2021 were collected. In addition, the local AQI and the concentrations of 6 air pollutants, namely particulate matter (PM2.5, PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3), were analyzed at the time of onset. Furthermore, the correlation with the incidence of epistaxis has been analyzed. Results: From 2017 to 2021, there were 24,721 patients with epistaxis aged from 0 to 17 years old while male patients were more than females. The incidence was higher in April, May, and June. There was a statistically significant difference in the number of daily epistaxis in different months and under AQI conditions (P < .05). Spearman's correlation analysis showed that there was a positive correlation between the number of daily epistaxis and the concentrations of AQI, CO, NO2, O3, PM2.5, PM10, and SO2 in Yangzhou, in which O3, PM10, and SO2 were highly correlated with the average number of daily epistaxis, and there was no obvious time lag effect of air pollutants on epistaxis. Conclusion: Epistaxis in the Yangzhou area is more common in males, mostly occurs in 0 to 17 years old, with seasonal. There was also a positive correlation between the incidence of epistaxis and air pollutants in Yangzhou. Therefore, by reducing the AQI index in daily life, and reducing the concentration of environmental pollutants in the air, the occurrence of epistaxis could be prevented and reduced to a certain extent.

lncRNAs regulate cell stemness in physiology and pathology during differentiation and development.

Long non-coding RNA (lncRNA) are an important class of ubiquitous genes involved in diverse biological functions. lncRNAs, defined as noncoding RNAs with a length exceeding 200 nucleotides, are abundantly expressed throughout cells; however, their precise functions remain largely elusive. From embryonic stem cell proliferation and differentiation to cancer cell proliferation and invasion, lncRNAs play multifaceted regulatory roles across various cellular stages. Moreover, lncRNAs participate in the regulation of differentiation and regeneration during cellular development processes while also playing a pivotal role in maintaining and regulating cell stemness. In this article, we comprehensively review the current knowledge regarding lncRNAs in this field, discussing their biological functions and mechanisms underlying stemness regulation along with the factors implicated in these processes. We emphasize the growing evidence supporting the significance of lncRNAs in governing cell stemness while indicating that disruptions or mutations within them may serve as fundamental causes for certain developmental disorders.

Study on the correlation of C-reactive protein/albumin ratio with sudden sensorineural hearing loss complicated by hypertension: a prospective study.

BACKGROUND: Understanding the pathophysiology of sudden sensorineural hearing loss (SSNHL) and identifying its clinical symptoms and associated risk factors are crucial for doctors in order to create effective prevention and therapeutic methods for this prevalent otolaryngologic emergency. METHODS: This study focuses on investigating the correlation between the C-reactive protein/albumin ratio (CAR) and SSNHL complicated by hypertension. In this study, 120 patients diagnosed with SSNHL were divided into groups with and without hypertension, and propensity score matching was used to compare and analyze the severity, type, prognosis, and CAR levels in SSNHL. RESULTS: The results showed that the SSNHL group with hypertension had significantly higher CAR levels, age, hearing curve abnormalities, and more severe hearing loss compared to the control group with isolated SSNHL. These differences were statistically significant (p < 0.001). Among different subtypes of SSNHL, CAR levels increased progressively with the advancement of the condition, and these differences were also statistically significant (p < 0.001). CONCLUSION: In summary, in patients with SSNHL, those with hypertension had higher CAR levels than those without a history of hypertension, and they experienced more severe hearing loss. Moreover, there was a clear correlation between CAR levels and the extent of SSNHL, indicating that greater CAR levels in patients with SSNHL are connected to more severe hearing loss in various hearing patterns and perhaps indicative of a poorer prognosis.

[A study of mismatched negative in normal hearing patients of different ages].

Objective:To study the characteristics of Mismatch negativity（MMN） in normal hearing patients of different ages, and to compare the MMN of normal hearing subjects at different ages to explore the differences in MMN between different ages. Methods:MMN test was performed on both ears using the classic Oddball mode. A frequency of 1 000 Hz（standard stimuli） and 2 000 Hz（deviant stimuli） was used to evoked the MMN. According to different age groups: the juvenile group（7-17 years old）, the youth group（18-44 years old）, the middle-aged group（45-59 years old）, and the elderly group（60-75 years old）, with 25 cases in each group. The MMN characteristics of normal hearing subjects in different age groups were analyzed statistically and the differences between groups were compared. All subjects underwent pure tone threshold test, tympanic reactance test and ABR test before MMN test. Results:MMN waveform could be elicited from both ears of 100 subjects. Among them, the average latency of the juvenile group was（159.70±20.34） ms while the average amplitude was（4.34±2.26） µV, For the youth group, the average latency was（166.01±28.67） ms and the average amplitude was（3.70±2.28） µV. Then in the middle-aged group, the average latency was（175.16±37.24） ms, meanwhile, the average amplitude was（2.69±0.84） µV. Finally, the elderly group has an average latency of（178.03±14.37） ms and an average amplitude of（2.11±0.70） µV. Therefore, there was no statistical difference in latency and amplitude between all groups（P>0.05）, and there was no statistical difference in latency and amplitude between left and right ears among all subjects as a whole（P>0.05）. However, when the left and right ears of all groups were compared, it was found that the latency between the left and right ears of the Juvenile group had statistical significance（P<0.05）, and the amplitude difference was not statistically significant（P>0.05）, while the latency and amplitude differences between the left and right ears of other groups had no statistical significance（P>0.05）. There were also no significant differences in latency and amplitude between men and women（P>0.05）. Conclusion:There was no statistically significant difference in the latency and amplitude of mismatched negative among normal hearing subjects of different ages, and no statistically significant difference in the MMN latency and amplitude between the left and right ears of subjects and between men and women. Therefore, the study inferred that the auditory cerebral cortex of subjects aged 7-75 years old maintained a stable state for a long time after maturity, and the latency and amplitude of mismatched negative waves were relatively stable. It is not affected by age, gender and ear side, and can stably reflect the auditory cortex function of the subjects. It has broad application prospects in clinical practice, and provides a reliable detection means for future research on the changes of the auditory cerebral cortex of patients, which is worthy of our further research and clinical promotion.

Topological disruption of low- and high-order functional networks in presbycusis.

Prior efforts have manifested that functional connectivity (FC) network disruptions are concerned with cognitive disorder in presbycusis. The present research was designed to investigate the topological reorganization and classification performance of low-order functional connectivity (LOFC) and high-order functional connectivity (HOFC) networks in patients with presbycusis. Resting-state functional magnetic resonance imaging (Rs-fMRI) data were obtained in 60 patients with presbycusis and 50 matched healthy control subjects (HCs). LOFC and HOFC networks were then constructed, and the topological metrics obtained from the constructed networks were compared to evaluate topological differences in global, nodal network metrics, modularity and rich-club organization between patients with presbycusis and HCs. The use of HOFC profiles boosted presbycusis classification accuracy, sensitivity and specificity compared to that using LOFC profiles. The brain networks in both patients with presbycusis and HCs exhibited small-world properties within the given threshold range, and striking differences between groups in topological metrics were discovered in the constructed networks (LOFC and HOFC). NBS analysis identified a subnetwork involving 26 nodes and 23 signally altered internodal connections in patients with presbycusis in comparison to HCs in HOFC networks. This study highlighted the topological differences between LOFC and HOFC networks in patients with presbycusis, suggesting that HOFC profiles may help to further identify brain network abnormalities in presbycusis.

Inflammatory cytokines and risk of allergic rhinitis: A Mendelian randomization study.

BACKGROUND: Epidemiological and experimental evidences have implicated chronic inflammation in the association with allergic rhinitis (AR). However, it remains unclear whether specific circulating cytokines are the cause of AR or the consequence of bias. To examine whether genetic-predicted changes in circulating cytokine concentrations are related to the occurrence of AR, we conducted a two-sample Mendelian randomization (MR) analysis. METHODS: We investigated the causal effects of 26 circulating inflammatory cytokines on AR through MR analysis. The primary method employed in this study was the inverse variance-weighted (IVW) method. Sensitivity analyses were conducted using simple median, weighted median, penalized weighted median, and MR-Egger regression. RESULTS: Our study revealed suggestive evidence that higher levels of circulating IL-18 (OR per one standard deviation [SD] increase: 1.006; 95 % CI, 1.002 to 1.011; P = 0.006, PFDR = 0.067, random-effects IVW method) and Macrophage inflammatory protein-1α (MIP-1α) (OR per one SD increase: 1.015; 95 % CI, 1.004 to 1.026; P = 0.009, PFDR = 0.048, random-effects IVW method) were associated with an increased risk of AR. Conversely, higher levels of circulating TRAIL were associated with a decreased risk of AR (OR per one SD increase: 0.993; 95 % CI, 0.989 to 0.997; P = 4.58E-4, PFDR = 0.004, random-effects IVW method). Only the results of TRAIL exist after Bonferroni-correction (the p-value < 0.0019). Sensitivity analysis yielded directionally consistent results. No significant associations were observed between other circulating inflammatory cytokines and AR. CONCLUSION: Genetically predicted levels of IL-18, and MIP-1α are likely to associated with an increased risk of AR occurrence. Genetically predicted levels of TRAIL are statistically significant in reducing the risk of AR occurrence. However, the current research evidence does not support an impact of other inflammatory cytokines on the risk of AR. Future studies are needed to provide additional evidence to support the current conclusions.

AAV-mediated Gpm6b expression supports hair cell reprogramming.

Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV-ie-mediated Gpm6b overexpression promoted SC-derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re-entry cell cycle and facilitating the SC-to-HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans-differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV.

Structural connectome combining DTI features predicts postoperative language decline and its recovery in glioma patients.

OBJECTIVES: A decline in language function is a common complication after glioma surgery, affecting patients' quality of life and survival. This study predicts the postoperative decline in language function and whether it can be recovered based on the preoperative white matter structural network. MATERIALS AND METHODS: Eighty-one right-handed patients with glioma involving the left hemisphere were retrospectively included. Their language function was assessed using the Western Aphasia Battery before and 1 week and 3 months after surgery. Structural connectome combining DTI features was selected to predict postoperative language decline and recovery. Nested cross-validation was used to optimize the models, evaluate the prediction performance of the models, and identify the most predictive features. RESULTS: Five, seven, and seven features were finally selected as the predictive features in each model and used to establish predictive models for postoperative language decline (1 week after surgery), long-term language decline (3 months after surgery), and language recovery, respectively. The overall accuracy of the three models in nested cross-validation and overall area under the receiver operating characteristic curve were 0.840, 0.790, and 0.867, and 0.841, 0.778, and 0.901, respectively. CONCLUSION: We used machine learning algorithms to establish models to predict whether the language function of glioma patients will decline after surgery and whether postoperative language deficit can recover, which may help improve the development of treatment strategies. The difference in features in the non-language decline or the language recovery group may reflect the structural basis for the protection and compensation of language function in gliomas. CLINICAL RELEVANCE STATEMENT: Models can predict the postoperative language decline and whether it can recover in glioma patients, possibly improving the development of treatment strategies. The difference in selected features may reflect the structural basis for the protection and compensation of language function. KEY POINTS: • Structural connectome combining diffusion tensor imaging features predicted glioma patients' language decline after surgery. • Structural connectome combining diffusion tensor imaging features predicted language recovery of glioma patients with postoperative language disorder. • Diffusion tensor imaging and connectome features related to language function changes imply plastic brain regions and connections.

Numerical Simulation Investigation on Natural Gas Leakage under Different Kitchen Layouts in China.

The safety of an open kitchen is a controversial topic in China. In this study, natural gas leakage and ventilation processes under an open kitchen layout and closed kitchen layout are simulated by CFD. The evolution of a hazardous gas cloud and the triggering behaviors of alarms are analyzed and discussed. For closing all windows in the leakage process, the state of the partition door is a major factor. A closed kitchen layout with a closing partition door performs best in confining a hazardous gas cloud. At this point, it is difficult for a hazardous gas cloud to appear in the living area. With the partition door open, the gas cloud develops rapidly. For opening windows in the leakage process, a large scale hazardous gas cloud is not able to form under all layouts. For alarm-triggering behaviors, a closed kitchen layout when closing the partition door also performs best. When opening the partition door, alarms cannot trigger stably under all layouts. For the ventilation process, hazardous gas cloud dissipation under an open kitchen layout is slightly faster than the closed kitchen layout. Under a weak convection effect, there is a transition stage which delays the time point for exhausting leaked gas. Based on the analysis, some recommendations for accident prevention are proposed. Residents should try to use closed kitchens and close partition doors when not cooking. If open kitchens are used, multiple alarms with lower trigger values should be installed. It is better to choose a ceiling type for gas alarms. The windows of the house are recommended to select two layers type. Higher layers can open during the ventilation process to accelerate the exhaust of leaked gas. These recommendations provide a reference for preventing fires and explosions.

Numerical Simulation Analysis of the Hydrogen-Blended Natural Gas Leakage and Ventilation Processes in a Domestic House.

The blending of hydrogen in natural gas may have effects on the safety of its usage in a domestic house. In this work, the leakage accident of hydrogen-blended natural gas (HBNG) in the kitchen of a domestic house is analyzed by CFD with a hydrogen blending ratio (HBR) ≤ 30%. The whole process is divided into the gas accumulation process and the ventilation process. In the initial leakage stage, the influence of heights and the HBR on the gas distribution is analyzed. HBNG concentration increases with increasing height. Based on the exit Froude number, the formation of a gas cloud in the kitchen is significantly influenced by the initial momentum and buoyancy, while it is more driven by the concentration gradient beyond the kitchen. In contrast to height, the variation of HBR on the HBNG distribution is not significant. In the ventilation process, the evolution of the hazardous gas cloud volume is analyzed. With windows and doors closed, the hazardous gas cloud fills the house in approximately 3600 s after the leakage occurs. When windows and doors are open for ventilation, the volume of the hazardous gas cloud first declines rapidly and then slowly. The reasons for the variation rate of hazardous gas cloud volume are analyzed according to ventilation conditions. The difference during the decline stage for different HBRs is analyzed according to the gas layering properties. Under a lack of convection condition, the ventilation process finally reaches a stagnant stage. In addition, another ventilation process has been investigated after extending the gas accumulation time. After extending the gas accumulation time, the effect of different HBRs on the ventilation process remains the same as before. However, it postpones the time point to enter the stagnation stage. As gas accumulation time extends from 3600 to 5400 and 7200 s, the ventilation time into the stagnation stage increases from about 4800 to 5400 and 6000 s, respectively. This study has implications for the establishment of a risk assessment system based on hazardous gas cloud volume.

Clinical utility of inflammatory biomarkers in COVID-19-related sudden sensorineural hearing loss.

BACKGROUND: The etiology and pathophysiological mechanisms of sudden sensorineural hearing loss (SSNHL) remain unclear, but it is generally believed to be associated with viral infections, vascular diseases, and autoimmune disorders. Considering that coronavirus disease 2019 (COVID-19) is promising candidates for SSNHL, we studied the immune cells changes by COVID-19 in patients with SSNHL. METHODS: We collected data from 47 patients with SSNHL and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Patients were divided into ineffective or effective groups based on the degree of hearing recovery at discharge. Clinical information was collected and processed for both groups. Logistic regression models were used to determine the risk factors for an unfavorable prognosis in COVID-19-related SSNHL. Receiver operating characteristic (ROC) curves were used to estimate the predictive value. RESULTS: There was statistically significant difference in C-reactive protein (CRP), auditory curve, degree decline, pretreatment hearing, posttreatment hearing, systolic blood pressure, diastolic blood pressure, total bilirubin, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), indirect-bilirubin and platelet count between groups (p < 0.05). In the logistic regression model, high levels of SII and NLR were associated with treatment ineffectiveness, pre- and postcorrectively (both, p < 0.05). And ROC curve analysis showed higher AUC of 0.765 for SII, 0.697 for NLR,0.681 for CRP, and 0.553 for platelet-to-lymphocyte ratio (PLR) in predicting treatment outcomes. CONCLUSION: The prognosis of COVID-19-related SSNHL was associated with inflammation. SII, NLR and CRP could serve as predictive markers of unfavorable outcomes in COVID-19-related SSNHL. SII may be considered an independent risk factor for poor prognosis in COVID-19-related SSNHL.

PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas.

BACKGROUND: Glioma is the most common intracranial malignancy. Immune-infiltration and tumour stemness are associated with the prognosis of glioma. Although pleckstrin homology containing family A, number 4 (PLEKHA4) is widely expressed in various human cancers, its role in glioma remains unclear. METHODS: We examined the features and clinical significance of PLEKHA4 in gliomas by analysing relevant data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Gene set enrichment analysis (GSEA) was performed to determine the possible functions and pathways involving PLEKHA4 in glioma. The relationship between PLEKHA4 expression and the degree of oncogenic dedifferentiation was analysed using stemness scores (ss) calculated from epigenetic and transcriptomic features. We also explored the relationship between PLEKHA4 expression and immune cell infiltration in gliomas using the CIBERSORT databases. Furthermore, drug sensitivity analysis was performed using datasets from the GDSC and GTRP databases. In addition, we performed relevant in vitro experimental studies. RESULTS: PLEKHA4 DNA hypomethylation status was associated with its high expression in glioma tissues as well as poor prognoses. Univariate and multivariate Cox analyses indicated that PLEKHA4 expression may be considered as an independent prognostic factor in patients with glioma. GSEA indicated that high PLEKHA4 expression was associated with Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Wingless-Type MMTV Integration Site Family (Wnt), JUN N-terminal kinase (JNK) signalling pathways and involved in apoptotic, cytoskeletal, and cell adhesion biological processes (BPs). In addition, increased PLEKHA4 expression was associated with higher glioma stemness scores than lower PLEKHA4 expression levels. Furthermore, the expression of PLEKHA4 was shown to be associated with glioma infiltration by CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. Drug sensitivity analysis also showed that PLEKHA4 expression was negatively correlated with the sensitivity of several small molecule kinase inhibitors. Furthermore, in vitro experiments confirmed that PLEKHA4 knockdown inhibited the proliferation of glioma cells. CONCLUSIONS: PLEKHA4 is highly expressed in glioma tissues and correlated with tumour stemness, immune cell infiltration and proliferation, suggesting its potential as a novel prognostic biomarker and therapeutic target in glioma.

Prognostic Correlation of Immune-Inflammatory Markers in Sudden Sensorineural Hearing Loss: A Retrospective Study.

BACKGROUND: The mechanism of sudden sensorineural hearing loss (SSNHL) remains incompletely understood, but immune cell infiltration has been identified as a crucial component in the sickness. The patients with SSNHL may benefit from investigating markers related to inflammation. METHODS: From April 2022 to 2023, 80 patients who were diagnosed with SSNHL in the Department of Otolaryngology at Yangzhou University's Clinical Medical College were enrolled in the SSNHL group. And patients were separated into effective and ineffective groups based on the degree to which their hearing had recovered prior to discharge. As the control group, 80 healthy volunteers were chosen from hospital's physical examination center. Neutrophils, lymphocytes, platelets, and white blood cells were counted. Additionally, quantified and statistically examined were the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII). The risk variables for prognosis were identified using logistic regression models, and the prediction accuracy of the model was calculated using the receiver operating characteristic (ROC) curves. RESULTS: The SSNHL group had higher levels of white blood cells, neutrophils, platelets, NLR, PLR, and SII than the control group. While the PLR lacked statistical significance, the NLR and SII of the patients in the ineffective group were noticeably higher than those in the effective group. CONCLUSION: Patients with SSNHL exhibit inflammatory immune responses. Patients with SSNHL can have their prognosis determined by the simple peripheral blood indicators NLR and SII, particularly SII, which is significant for predicting prognosis and directing treatment.

Clinical Analysis of Supraclavicular Flaps for the Repair of the Pharyngeal Fistula.

Objectives: We explored the value of supraclavicular flaps in repairing pharyngeal fistula. Methods: Patients treated with supraclavicular flaps were included. Data on preoperative radiotherapy, surgical modality, flap size, postoperative healing, and other clinical outcomes were collected. Techniques, indications, and postoperative complications after repairing with supraclavicular flaps were described. A total of 16 male patients aged 58 to 79 years were involved, including 10 cases of postoperative pharyngeal fistula after hypopharyngeal cancer, 5 cases of postoperative pharyngeal fistula after laryngeal cancer, and 1 case of postoperative pharyngeal fistula after laryngeal and esophageal cancer. In 12 patients, the pharyngeal fistula was repaired by double island folding of the supraclavicular flap; in the remaining 4 patients, the pharyngeal fistula was repaired by the supraclavicular flaps combined with the pectoralis major flaps. The supraclavicular flap was 6 to 8 cm in width and 6 to 15 cm in length. Results: One patient developed partial necrosis at the distal end of the flap, which was successfully treated with debridement and dressing. The flaps grew well in the remaining 15 patients. Among them, a patient with a postoperative pharyngeal fistula after hypopharyngeal carcinoma was implanted with radioactive particles for tumor recurrence at the esophageal entrance, and died in the 11th month after surgery. Conclusions: The supraclavicular flap can achieve excellent results in the repair of pharyngeal fistula.

Resection of high-grade glioma involving language areas assisted by multimodal techniques under general anesthesia: a retrospective study.

BACKGROUND: Multimodal techniques-assisted resection of glioma under general anesthesia (GA) has been shown to achieve similar clinical outcomes as awake craniotomy (AC) in some studies. In this study, we aim to validate the use of multimodal techniques can achieve the maximal safe resection of high-grade glioma involving language areas (HGILAs) under GA. METHODS: HGILAs cases were reviewed and collected between January 2009 and December 2020 in our center. Patients were separated into multimodal group (using neuronavigation, intraoperative MRI combined with direct electrical stimulation [DES] and neuromonitoring [IONM]) and conventional group (neuronavigation alone) and clinical outcomes were compared between groups. Studies of HGILAs were reviewed systematically and the meta-analysis results of previous (GA or AC) studies were compared with our results. RESULTS: Finally, there were 263 patients in multimodal group and 137 patients in conventional group. Compared to the conventional group, the multimodal group achieved the higher median EOR (100% versus 94.32%, P < 0.001) and rate of gross total resection (GTR) (73.8% versus 36.5%, P < 0.001) and the lower incidence of permanent language deficit (PLD) (9.5% versus 19.7%, P = 0.004). The multimodal group achieved the longer median PFS (16.8 versus 10.3 months, P < 0.001) and OS (23.7 versus 15.7 months, P < 0.001) than the conventional group. The multimodal group achieved a higher rate of GTR than the cohorts in previous multimodal studies under GA and AC (73.8% versus 55.7% [95%CI 32.0-79.3%] versus 53.4% [35.5-71.2%]). The multimodal group had a lower incidence of PLD than the cohorts in previous multimodal studies under GA (9.5% versus 14.0% [5.8-22.1%]) and our incidence of PLD was a little higher than that of previous multimodal studies under AC (9.5% versus 7.5% [3.7-11.2%]). Our multimodal group also achieved a relative longer survival than previous studies. CONCLUSIONS: Surgery assisted by multimodal techniques can achieve maximal safe resection for HGILAs under GA. Further prospective studies are needed to compare GA with AC for HGILAs.

The Study on Prognosis in Patients with Adenoid Cystic Carcinoma of the External Auditory Canal.

BACKGROUND: Adenoid cystic carcinoma of the external auditory canal is a rare primary malignancy, and surgery is the primary management strategy. This study aims to optimize management strategies and improve prognosis of adenoid cystic carcinoma of the external auditory canal. METHODS: Seventeen patients with adenoid cystic carcinoma of external auditory canal who had been admitted to a single institution from January 2008 to March 2019 were recruited and retrospectively reviewed. Among patients with T1 tumors, 2 underwent local external auditory canal resection, 1 received lateral temporal bone resection+superficial parotidectomy. Among patients with T2 tumors, all 5 patients underwent lateral temporal bone resection+superficial parotidectomy. Among patients with T3 tumors, 3 underwent subtotal temporal bone resection+superficial parotidectomy, 2 underwent subtotal temporal bone resection+superficial parotidectomy+radiotherapy, and 1 underwent extended temporal bone resection+superficial parotidectomy+radiotherapy. Among patients with T4 tumors, 2 underwent subtotal temporal bone resection+superficial parotidectomy and 1 underwent extended temporal bone resection+total parotidectomy+radiotherapy. RESULTS: The common manifestations included otalgia (82.4%), hearing loss (23.5%), external auditory canal mass (23.5%), otorrhea (17.6%), and aural fullness (5.9%). In the study, 5/17 (29.4%) patients had been misdiagnosed preoperatively, 5/17 (29.4%) patients revealed local recurrence, and 3/17 patients (17.6%) were identified with distant metastasis postoperatively. The 3- and 5-year overall survival rates were 88.2% and 82.3%, respectively. There was no significant difference in overall survival (P=.746) and disease-free survival (P=.933) between patients receiving different surgical approaches. Three out of 17 patients (17.6%) died of T2, T3, and T4 diseases, respectively. CONCLUSION: Otalgia is the most common manifestation of adenoid cystic carcinoma of the external auditory canal, and misdiagnosis is frequently encountered. Surgery is the preferred therapy, and local resection is associated with relapse, lateral temporal bone resection is strongly recommended in patients with early-stage tumor. Regular follow-up should be routinely conducted postoperatively to early identify local recurrence.

Trace analysis of dimethoxytrityl alcohol (DMT-OH) in oligonucleotide matrices using liquid chromatography coupled with tandem mass spectrometry.

A liquid chromatography (LC) method with ultraviolet (UV) and tandem mass spectrometry (MS/MS) detection was developed to quantify dimethoxytrityl alcohol (DMT-OH), a small molecule byproduct generated during the detritylation reaction in oligonucleotide synthesis. The pros and cons of quantification via multiple analytical methods including LC coupled with UV, selected ion monitoring (SIM), and multiple reaction monitoring (MRM) were evaluated. The MRM method was ultimately selected for further qualification and exhibited good linearity (R2 = 0.997 from 0.5 to 64 ng mL-1), accuracy (recoveries ranging 75-90% with ≤ 2% RSD), repeatability (<5% RSD), and sensitivity (LOQ of 1.6 ng mL-1). The MRM method was further applied to analyze DMT-OH in various oligonucleotide intermediates and drug substances. Similar MRM methods for six other small molecule impurities (aniline, benzamide, isobutyramide, 2-phenylacetamide, succinamide, and uny-CTP) as well as their application are also presented.

Discovery of structural diverse reversible BTK inhibitors utilized to develop a novel in vivo CD69 and CD86 PK/PD mouse model.

For the past two decades, BTK a tyrosine kinase and member of the Tec family has been a drug target of significant interest due to its potential to selectively treat various B cell-mediated diseases such as CLL, MCL, RA, and MS. Owning to the challenges encountered in identifying drug candidates exhibiting the potency block B cell activation via BTK inhibition, the pharmaceutical industry has relied on the use of covalent/irreversible inhibitors to address this unmet medical need. Herein, we describe a medicinal chemistry campaign to identify structurally diverse reversible BTK inhibitors originating from HITS identified using a fragment base screen. The leads were optimized to improve the potency and in vivo ADME properties resulting in a structurally distinct chemical series used to develop and validate a novel in vivo CD69 and CD86 PD assay in rodents.

Distance-Triggered Distinct Aryl Migrations on Azidodiboranes.

Derived from structurally similar precursors, two different azidodiboranes went through distinct aryl migration reactions triggered by different boron-boron separation distances. Biphenylene based diborane with a shorter boron-boron distance underwent heterolateral aryl migration to form a seven-membered azadiborepin, while xanthrene based diborane with a longer boron-boron distance afforded a stable bis-azidoborane scaffold. The pyrolysis of such a bis-azidoborane led to eight-membered oxazadiborocine through homolateral aryl migration and subsequent [3+2] cycloaddition. Density functional theory (DFT) calculations unveiled that the boron-boron separation distances were the intrinsic factors for the distinct migrations.

The value of inflammatory biomarkers in the occurrence and prognosis of sudden sensorineural hearing loss: a meta-analysis.

OBJECTIVES: Sudden sensorineural hearing loss (SSNHL) is one of the common emergencies in otorhinolaryngology. Several studies have shown that chronic inflammation is associated with its onset and prognosis. However, the association between some inflammatory biomarkers and SSNHL is still unclear. Therefore, we conducted this meta-analysis to explore the value of inflammatory biomarkers in the occurrence and prognosis of SSNHL. METHODS: Pubmed, Embase, Cochrane and Web of Science databases were searched comprehensively, the eligible literatures were screened out by formulating the inclusion criteria and exclusion criteria. After extracting sample size, mean and standard deviation, we performed meta-analysis with standardized mean deviation (SMD) and 95% confidence interval (CI) as effect sizes. RESULTS: A total of 17 articles were included in this meta-analysis, including 2852 subjects, 1423 patients and 1429 healthy controls. The results of meta-analysis showed that the neutrophil-to-lymphocyte ratio (NLR) of the experimental group was significantly higher than the control group (SMD = 1.05, 95% CI 0.87-1.24, P < 0.001), the NLR of the recovery group was significantly lower than the unrecovered group (SMD = 0.68, 95% CI 0.27-1.08, P < 0.05); The platelet-to-lymphocyte ratio (PLR) of the experimental group was significantly higher than the control group (SMD = 0.55, 95% CI 0.34-0.76, P < 0.05), the PLR of the recovery group was significantly lower than the unrecovered group (SMD = 0.44, 95% CI 0.05-0.82, P < 0.05); The C-reactive protein-to-serum albumin ratio (CRP/Alb) of the experimental group was significantly higher than the control group (SMD = 0.39, 95% CI 0.04-0.74, P < 0.05). CONCLUSIONS: The results showed that high NLR, PLR, and CRP/Alb indicated the occurrence of SSNHL, NLR and PLR could predict prognosis of SSNHL.