In this study, we employ the homotopy renormalization (HTR) method to analytically investigate Rasmussen’s problem, which characterizes the viscous fluid motion between a pair of infinitely large, coaxially rotating disks. The original set of nonlinear ordinary differential equations is reformulated within a homotopy-based framework, allowing us to construct global asymptotic approximations with closed-form expressions. The HTR method overcomes the limitations of traditional perturbation and renormalization techniques, and avoids the need for asymptotic matching. In addition, the analytic expressions allow for direct estimation of flow parameters such as boundary layer thickness. These results demonstrate the effectiveness of the HTR method in asymptotic analysis and highlight its potential for broader applications in nonlinear fluid dynamics.

Assessing the failure of urban gas pipelines is crucial for identifying risk factors and preventing gas accidents that result in economic losses and casualties. Most previous studies on gas pipeline failure assessment are based on the basic Bayesian network (BN). However, the conditional probability table (CPT) determined by expert experience is often affected by subjective factors, leading to inaccurate evaluation results. This paper proposes a novel gas pipeline failure risk assessment model based on Bayesian network optimized by machine learning. Firstly, the pipeline fault tree model is constructed according to the accident data that leads to pipeline failure, and the fault tree model is mapped to the Bayesian network. Secondly, by establishing a neural network model, the value of the CPT of the Bayesian network is determined. Aiming at the problem that the true probability of a Bayesian network child node cannot be obtained, the Noisy-OR gate model is introduced to determine the CPT of the node.The advantage of the novel Bayesian network model is that the value of CPT is determined based on data-driven, which effectively reduces the subjective impact of expert experience. Subsequently, the pipeline risk analysis is conducted based on statistical data from the Pipeline and Hazardous Materials Safety Administration (PHMSA). The two-way inference function of Bayesian network is used to obtain the failure probability of gas pipeline and the posterior probability of root node. By comparing with the results of traditional methods, the rationality of the results obtained by the model is verified. Finally, the sensitivity analysis identified Other (Other external damage), third-party excavation damage, incorrect operation and fire or explosion as key influences on gas pipeline failure. The Bayesian network model established in this study is based on data-driven. It effectively reduces the effect of subjectivity brought by expert experience and helps to improve the accuracy of failure assessment. This study reflects that machine learning technology will be an important research direction in the field of gas pipeline risk assessment in the future.

The safety of hydrogen-blended natural gas (HBNG) in a confined space is an issue, especially for ventilation processes. In this study, leakage and ventilation processes of low-pressure HBNG with different hydrogen-blended ratio (HBR) in a confined space are simulated and validated by experiment based on similarity criteria. For the leakage process, the leak direction and HBR do not significantly affect gas accumulation behaviour. The required time for a gas cloud to fill space decreases slightly with HBR rising and they generally show a linear relationship. For the ventilation process, the main influences on the leakage process are the total leakage mass and the ventilation conditions. The required time for hazardous gas cloud dissipation increases with total leakage mass and decreases with HBR. For different ventilation conditions, the ranking of required time to exhaust leaked gas is low > centre > high > mix. Through the analysis of pressure distribution, it is found time difference is produced by different airflow patterns. With the asymmetric layout, outside air rushes into the confined space from the high side and then flows out from the low side carrying the leaked HBNG. These findings inform the design of ventilation for HBNG utilization scenarios like restaurant facing the street.

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.

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.

The layout optimization design of a natural gas gathering pipeline network is a multi-objective optimization problem because the extant theories are unable to meet the different decision preferences in scheme design, which restricts the intelligentization of gas gathering pipeline layout optimization. Currently, there are no generic design studies on the loop-star pipeline network. Therefore, this paper proposes a generic layout optimization model containing a large number of discrete and continuous variables, such as pipe connection relationships, pipe sizes, pipe length, and pipe specifications. In the solution section, drawing inspiration from the hormone regulation mechanism and local foraging rule in bionics, an improved particle swarm optimization algorithm based on hormone regulation (HRPSO) is proposed, and it obtains the favorable parameters range of the HRPSO algorithm. The results illustrate that the HRPSO algorithm exhibits convergence to the global optimum with a probability of 1. In comparison to manual design, the comprehensive costs of the optimized scheme are saved by 22.71% with the HRPSO algorithm. Compared to the four PSO variants in the paper, it can save costs by 5.38%, 4.95%, 4.09%, and 3.65%, respectively.

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.

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. 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. 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). 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.

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.

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.

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.

Neurodegenerative diseases (NDs) have become a serious global health problem as the population ages. Traditionally, treatment strategies for NDs have included oral and intravenous administration; however, the blood–brain barrier (BBB) can prevent drugs from reaching the brain, rendering the treatment incomplete and the effect unsatisfactory. Additionally, the prolonged or excessive use of drugs that can cross the BBB can damage liver and kidney function. Recent studies have shown that nose-to-brain drug delivery can noninvasively bypass the BBB, allowing drugs to enter the brain through the olfactory or trigeminal nerve pathways; additionally, nanoparticle carriers can enhance drug delivery. This review introduces drug carrier nanoparticles for nose-to-brain delivery systems, compares the advantages and disadvantages of different nanoparticles, and discusses the factors influencing nose-to-brain nanomedicine delivery and enhancement strategies. We also summarize nose-to-brain delivery and nanomedicines for treating NDs, the current challenges of this approach, and the future promise of nanomedicine-based ND treatment.

It is of great significance to explore the physical properties of optical propagation, thus the scholars are keen on the physical essence represented by classical mathematical physics equations. In this paper, a higher order nonlinear Schro center dot dinger equation describing the behavior of polarization mode in optical fibers is firstly analyzed qualitatively, and the existence of periodic and soliton solutions is proved by using bifurcation method. Secondly, all chirped wave patterns with special form for the equation are obtained by using the complete discrimination system for polynomial method and direct integral method, the chirped rational functions and some elliptic functions wave patterns are initially found. As a result, the parameter stability of these patterns is given for the first time, which shows the variant of patterns as the parameters change, and the graphs of several typical patterns are drawn.

1临床资料 患者,女,58岁,因"咽痛3 h"就诊于苏北人民医院耳鼻咽喉科门诊.患者3 h前出现咽部疼痛,伴下颌疼痛,无意识不清,无头晕,无恶心呕吐,体温正常,无其他不适.患者既往高血压病史十年余,未进行正规治疗及定期监测血压,否认冠心病、糖尿病等慢性疾病史,否认手术史、外伤史,否认吸烟酗酒等其他不良嗜好.门诊查体:咽部色红,扁桃体Ⅰ度、不伴充血肿胀,间接喉镜下会厌正常.电子喉镜示双侧声带肥厚,黏膜慢性充血,双侧前中1/3处边缘结节样小隆起.颈内动脉超声检查发现左侧颈总动脉内见絮状回声,范围较大,大部分充填血管管腔,内血流部分充盈,提示左侧颈总动脉内急性栓子,范围较大(图1),考虑可能为导致咽痛的主要原因,遂转诊于血管外科.头颈CT血管造影(CTA)检查示左侧颈动脉夹层,予以抗凝溶栓等对症治疗,随即患者咽痛症状消失.3个月后随访,未见异常.

目的 探讨内镜耳道入路手术和显微镜耳后入路开放手术治疗中耳胆脂瘤的疗效.方法 回顾性分析2019年1月～2021年6月在江苏省苏北人民医院接受手术的49例(49耳)中耳胆脂瘤患者的临床资料,采用传统显微镜耳后入路开放手术(开放手术组)25例,采用耳内镜外耳道入路手术(内镜手术组)24例,评估内镜耳道入路手术和显微镜耳后入路开放手术与治疗相关的手术时间、并发症和复发之间的关系.结果 开放手术组和内镜手术组的人口统计学、疾病特征、并发症、复发率间均无显著差异(P均＞0.05).开放手术组和内镜手术组手术时间有显著差异,内镜手术组用时更少,更具优势(t=7.15,P＜0.05).结论 内镜下耳道入路是治疗中耳胆脂瘤的有效方法,由经验丰富的外科医师进行操作,其疗效与传统的显微镜耳后切开入路相似,用时更少.

目的 探讨外耳及中耳恶性肿瘤的临床类型、分期、治疗及预后.方法 回顾性分析2008年1月-2020年3月在我院接受手术的23例外耳及中耳恶性肿瘤患者的临床资料.其病理类型分为鳞状细胞癌14例,腺样囊性癌8例,Merkel细胞癌1例,临床分期T1期2例,T2期7例,T3期10例,T4期4例.5例单独行手术治疗,13例行手术治疗及术后放疗,4例行手术治疗及术后放化疗,1例行放化疗.结果 全组病人3年生存率69.6％,5年生存率52.2％,Ⅰ、Ⅱ期病人3年、5年生存率均高于Ⅲ、Ⅳ期,p＜0.05,差异具有统计学意义,按病理类型比较3年、5年生存率p＞0.05,无显著差异.结论 对于外耳及中耳恶性肿瘤,早期诊断、早期治疗是提高生存率的关键,以手术为主的综合治疗是本病最佳治疗手段.预后与患者就诊时的临床分期、手术方式密切相关.

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.

目的 探讨儿童听力筛查未通过原因及耳聋基因筛查的意义.方法 扬州市就诊我院门诊的 14 岁及以下入学儿童听力筛查未通过 245 人,所有儿童均行声导抗及耳声发射检查,5 周岁及以上儿童进行纯音测听检查,5 周岁以下儿童进行行为测听检查,不能配合者行ABR检查.基因筛查采用 4 个基因(GJB2、SLC26A4、12SrRNA和GJB3)20 个位点的高通量测序.结果 复测通过 64 人(26.12%),耵聍栓塞及外耳道疾病 31 人(12.65%),分泌性中耳炎 132 人(53.88%),急慢性中耳炎 12 人(4.90%),先天性中耳胆脂瘤 2 人(0.82%),小儿听神经病 1 人(0.41%),感音神经性聋 1 人(0.41%),大前庭水管综合征 2 人(0.82%).GJB2 基因杂合突变 9 人(3.67%),未筛查出纯合突变或复合杂合突变;SLC26A4 基因杂合突变 1 人(0.41%),纯合突变 1 人(0.41%);线粒体 12SrRNA基因突变携带 1 人(0.41%),未发现GJB3 基因突变携带者.结论 听力和耳聋易感基因联合筛查对发现耳聋和迟发性耳聋具有协同作用,解除病因和给予正确指导可降低耳聋的发生率.

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.

The European Medicines Agency, the U.S. Food and Drug Administration, and other regulatory agencies expect that all pharmaceutical products be assessed for the potential presence of N-nitrosoamine (nitrosamine) impurities. This white paper addresses general considerations for nitrosamine risk assessments of oligonucleotide products. The authors propose a general risk assessment platform which should facilitate safe, consistent development of new treatments and alignment with regulatory expectations.