Objective To evaluate the value of an optimized three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with a longer repetition time (TR, 16 000 ms) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in the endolymphatic hydrops (EH) imaging after intratympanic gadolinium (Gd) administration, and to compare it with a conventional 3D-real IR based on the turbo spin echo (TSE) sequence. Methods From July 2021 to November 2022, twenty-seven patients received both the conventional and optimized 3D-real IR sequences after bilateral intratympanic Gd administration. Images of the two sequences were qualitativly evaluated and compared. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and area ratio of endolymph against the total lymphatic space from the two sequences were measured and compared. Results 14(25.9%) ears with insufficient contrast for the EH diagnosis on the conventional sequence were clearly displayed on the optimized sequence. Image score, CNR and SNR of the optimized sequence were significantly higher than those of the conventional sequence (P ＜ 0.001). The scanning time of two sequences was similar. The area ratio of endolymph against the total lymphatic space in the cochlear was significantly higher on the conventional 3D-real IR than that on the optimized 3D-real IR (P ＜ 0.001); there was no statistical difference in the vestibule between the two sequences. Conclusions Compared with conventional sequence, optimized 3D-real IR sequence with a longer TR may be better for evaluation of EH after intratympanic Gd administration.

Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P＜0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P＜0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.

Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome， whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress， the nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine （TCM） to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients （including five types of compounds： flavonoids， terpenes， alkaloids， saponins， phenols） and 6 kinds of compound preparations （including three types of formulas： heat-clearing and detoxifying formulas， purgative formulas for promoting bowel movement， and formulas for reinforcing vital qi and consolidating the constitution） can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1， heme oxygenase-1， antioxidant response element and AMP-activated protein kinase， thereby alleviating sepsis-induced lung injury.

Astaxanthine (AST) has important biological activities including antioxidant and anti-inflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss (CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2 (NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathway using quantitative PCR and Western blotting. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction. Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL.

Objective:To explore the sex-based heterogeneity in demographic and pathological trends of lung cancer during the past 30 years.Methods:Patients with primary lung cancer who received surgical treatment in the Department of thoracic surgery, Shanghai Pulmonary Hospital Tongji University from 1989 to 2018 were retrospectively analyzed. The differences between male and female patients in age, smoking history, pathological stage and type were compared. Mann- Kendall trend test was performed for trend analysis. Results:A total of 58 433 patients were included in this study, encompassing 30 729(52.6%) men and 27 , 704(47.4%) women. Compared with male patients, female patients were younger(56.0 years old vs. 59.7 years old), and had a higher proportion of non-smokers(98.3% vs. 52.3%), stage Ⅰ lung cancers(60.6% vs. 49.3%), and adenocarcinoma(93.7% vs. 56.1%, all P-values <0.001). Trend analyses revealed that the proportion of female patients increased year by year, and surpassed males in 2015, with the current ratio of male to female being 1∶1.5. After 2013, the age of onset in females was getting younger, and the average age decreased from 58.7 years old to 54.7 years old( P=0.02). The decrease in the proportion of smoking patients was mainly reflected by male patients(from 68.5% to 31.1%, P<0.01). Stage Ⅰ lung cancers in male and females outnumbered advanced stage in 2012 and 2010, respectively, with a much higher proportion in female patients. Among male patients, adenocarcinoma has replaced squamous cell carcinoma as the most common pathological type since 2012, while in female patients adenocarcinoma remained the most common pathological type of lung cancer, and its proportion continued to increase reaching over 98%. Conclusion:A dramatic change in gender distribution was noticed during the past 30 years. Female patients became the primary population in surgically-treated lung cancers, with a trend of getting younger. The proportion of smokers and squamous cell carcinoma decreased significantly in male patients, and adenocarcinoma has become the most common pathological type of lung cancer. The proportion of stage Ⅰ lung cancers was on a dramatic rise, with the popularization of CT screening for lung cancer.

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,
Ear Ossicles ; Humans ; Incus ; Malleus

A chemical investigation on

Objective To investigate the relationship between preoperative albumin-to-alkaline phosphatase ratio and overall survival (OS) after radical cystectomy of bladder cancer.Methods The clinical date of patients with bladder cancer who underwent radical cystectomy and urinary diversion and confirmed by pathology from Jan 2007 to Dec 2015 were analyzed retrospectively,with 140 cases undergoing laparoscopic surgery and 26 cases undergoing open surgery.There were 148 males and 18 females,aged was 33-85 years,with an ayerage ageof (65.1 ± 9.4) years.There were 55 cases of cutaneous ureterostomy,96 cases of Brick diversior with ileum,and 15 cases of ileal neobladder.The AAPR range 0.03-1.67,with an average 0.62 ± 0.23,and body mass index (BMI) was 16.79-32.65 kg/m2,with an average of (24.00 ± 3.32) kg/m2.There were 33 cases with hydronephrosis and 133 no hydronephrosis,31 cases with hypertension and 135 cases no hypertension,and 14 cases with diabetes and 152 cases no diabetes.Four cases were classified as grade0,65 cases as grade 1,86 cases as grade 2,and 11 cases as grade 3.Based on the preoperative AAPR(0.62 ±0.23),they were divided into three groups,with 55 cases in the low AAPR (0.42 ± 0.09) group,55 cases in the middle AAPR (0.58 ± 0.05) group,and 56 cases in the high AAPR (0.86 ± 0.21)group.Cox proportional hazards regression methodology were used to evaluate the relationship between preoperative AAPR and overall survival.Survival analysis was conducted using the Kaplan-Meier method and compared with the log-rank test.Results 166 patients were followed up for 1-144 months,with a median of 63 months,and 71 cases died and 95 survived.The median serum AAPR level in all cases was 0.59 (range 0.03-1.67).Results of univariate Cox regression model revealed that AAPR(HR =0.09,95％ CI 0.022-0.391,P =0.001),high AAPR (HR=0.40,95％CI0.216-0.742,P=0.003),age (HR =2.42,95％ CI 1.294-4.531,P =0.006),tumor size (HR =2.11,95％ CI 1.112-4.014,P =0.023),pT3 stage (HR=8.93,95％CI3.173-25.114,P＜0.001),pT4 stnge(HR =10.39,95％ CI 3.110-34.707,P ＜0.001),pN1 stage(HR =2.80,95％ CI 1.422-5.531,P =0.003),pN3 stage (HR =17.06,95％ CI2.192-132.863,P =0.007),pathological grade (HR =0.30,95％ CI 0.113-0.817,P =0.019),hydronephrosis (HR =2.36,95 ％ CI 1.406-3.939,P =0.001),adjuvant chemotherapy (HR =2.66,95％ CI 1.674-4.247,P ＜ 0.001)were associated with OS.Compared with patients in the lowest of AAPR,the risk for death in the highest AAPR group decreased about 59％ (HR =0.406,95％ CI 0.200-0.822,P =0.012)after adjustment for age,BMI,tumor size,number of tumor,T category,N category,pathological grade,hydronephrosis,ASA level,adjuvant chemotherapy in multiple Cox regression models.Each unit increase in the AAPR was associated with about 80％ decreased risk of death (HR =0.199,95％ CI 0.051-0.779,P =0.020) after adjusting for the confounding variables.After adjusting for age,BMI,tumor size,number of tumor,T category,N category,pathological grade,hydronephrosis,ASA level,adjuvant chemotherapy,the curve fitting results showed that with the increase of AAPR,the risk of death decreased and the overall survival prolonged.Consistent with the linear trend test results,the relationship between AAPR and OS is linear.Conclusions AAPR was associated with overall survival of patients who underwent radical cystectomy of bladder cancer.

Objective:To investigate the chronic restraint stress induced expressions of acid sensitive receptors and its role in the esophageal inflammation and oxidative stress.Methods:Twenty male specific pathogen free (SPF) Kunming mice were randomly divided into two groups: stress group and control group (each group, n=10). Stress mice were restrained in self-made restraint device for 2 hours per day and lasted for total 14 days. The histopathological changes of esophageal mucosa were observed by hematoxylin eosin (HE) staining under light microscope. The expression of nicotinamide adenine dinucleotide phosphate (Nox-4) was detected by immunohistochemistry, real time fluorescent quantitative polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbent assay (ELISA). The mRNA expressions of acid sensitive receptors were detected by qRT-PCR. Results:HE staining showed that stress mice had obvious infiltrations of neutrophils and eosinophils, and also showed inflammatory change in esophgus, while no significant abnormality was found in the esophagus of control mice. The inflammotory scores in stress group were significantly higher than that in control group ( P<0.001). Immunohistochemistry showed that Nox-4 was mainly expressed in the lamina propria, mucosa and submucosa of esophagus. The mRNA expression levels of Nox-4 in stress group was (2.67±0.62) times higher than control group, with statistically significant difference ( P<0.001). In addition, the plasma concentration of Nox-4 in stress group was significantly higher than that of control group [(0.42±0.01)ng/ml vs (2.13±0.35)ng/ml, P<0.001]. The transcription levels of acid sensitive receptors in stressed mice, such as transient receptor potential vanilloid-1 (TRPV-1), TRPV-4, acid-sensing ion channel-1 (ASIC-1), ASIC-2 and ASIC-3 were significantly higher than those in the control group, with statistically significant difference ( P<0.001). Pearson correlation analysis showed that there was a positive correlation between Nox-4 mRNA expression and TRPV-1, TRPV-4, ASIC-1, ASIC-2, ASIC-3 mRNA expression in stress group ( r=0.97, 0.94, 0.98, 0.95 and 0.99, P<0.01). Conclusions:Stress may increases the expression of acid sensitive receptors and result in an esophageal inflammation and oxidative stress, which may contribute to the formation of esophageal hypersensitivity.

Objective To investigate the expression of NADPH oxidase Nox-4 induced by stress in gastric mucosa and its role in inflammation.Methods Twenty male SPF Kunming mice were randomly divided into chronic restraint stress group(stress group) and control group.Stress mice were restrained in selfmade restraint device for 2 hours each day.The rest of the time,the mice in the two groups had free access to food and water normally,experiment lasted 14 days.The histopathological changes of gastric mucosa were assessed by HE staining under light microscope.The expression of Nox-4 in gastric mucosa of mice was carried out by immunohistochemical method.The relative expression levels of Nox-4,antioxidant protein (Mn-SOD,GSH,Catalase) and inflammatory factors(IL-8,IL-1β,TNF-α) in gastric mucosa were detected by real-time quantitative RT-PCR and ELISA.Results Basal cell proliferation,neutrophil,eosinophil and plasma cell infiltration and inflammatory changes were observed in the lamina propria and glandular epithelium of stress mice,while no obvious abnormalities were found in control mice.The expression of Nox-4 in stress group was deeper and more abundant than that in control group,mainly expressed in lamina propria and glandular epithelium.The mRNA expression levels of Nox-4 in gastric mucosa of stress group was(2.42±0.51) times higher than that of control group,and blood concentration of stress group was(2.23±0.67) times higher than that of control group(t=-46.32,P＜0.001).The RT-PCR of antioxidant proteins in gastric mucosa showed that the transcription levels of Mn SOD,GSH and Catalase in stress group were significantly lower than that of control group (Mn-SOD:0.59± 0.10,GSH:0.58± 0.11,Catalase:0.57± 0.09),and there were significant differences between the two groups(t=13.57,11.67,15.01,P＜0.01).RT-PCR results showed that the transcription levels of IL-8,IL-1β,TNF-α in stress group were significantly higher than those in control group (IL-8:1.47±0.34,IL-1β:1.48 ± 0.42,TNF-α:1.51 ± 0.37),and there were significant differences in two groups(t=-18.45,-19.14,-20.85,P＜0.01).ELISA results showed that the serum levels of inflammatory factors in stress group were significantly higher than those in control group(2.25±0.37,3.59±0.45,3.41±0.34),and the differences were statistically significant(t=-47.11,-79.36,-96.32,P＜0.01).Pearson correlation analysis showed that there was a positive correlation between serum concentration of Nox-4 and inflammatory factors(IL-8,IL-1β,TNF-αt) in stress group(r=0.97,0.99,0.98,P＜0.01).Spearman rank correlation analysis showed that the grade of gastric mucosal inflammation was positively correted with serum levels of Nox-4 and inflammatory factors (IL-8,IL-1β,TNF-α) (r =0.96,0.92,0.91,0.94,all P＜ 0.01)Conclusion Stress may lead to gastric mucosal lesion by overexpression of proinflammatory factors through destroying the balance of oxidation/antioxidant system in gastric mucosa.