The pathogenesis of Acute-on-chronic liver failure (ACLF) involves several forms of cell death, such as pyroptosis, apoptosis, and necroptosis, which consist of PANoptosis. To explore PANoptosis as a regulated cell death pathway in ACLF. Firstly, a bioinformatic strategy was used to observe the role of the PANoptosis pathway in ACLF and identify differentially expressed genes related to PANoptosis. Enrichment analysis showed that PANoptosis-related pathways were up-regulated in ACLF. We screened out BAX from the intersection of pyroptosis, apoptosis, necroptosis, and DEGs. Secondly, we screened articles from literature databases related to PANoptosis and liver failure, and specific forms of PANoptosis were reported in different experimental models in vitro and in vivo. Secondly, we established a model of ACLF using carbon tetrachloride-induced liver fibrosis, followed by D-galactosamine and lipopolysaccharide joint acute attacks. A substantial release of inflammatory factors(IL-6, IL-18, TNFα, and IFNγ) and the key proteins of PANoptosis (NLRP3, CASP1, GSDMD, BAX, CASP8, CASP3, CASP7, and MLKL) were detected independently in the ACLF rats. Finally, we found that combining TNF-α/INF-γ inflammatory cytokines could induce L02 cells PANoptosis. Our study highlighted the potential role of ACLF and helps drug discovery targeting PANoptosis in the future.

BackgroundAcute-on-chronic liver failure (ACLF) is a refractory disease with high mortality, which is characterized by a pathophysiological process of inflammation-related dysfunction of energy metabolism. Jieduan-Niwan formula (JDNWF) is a eutherapeutic Chinese medicine formula for ACLF. However, the intrinsic mechanism of its anti-ACLF effect still need to be studied systematically.PurposeThis study aimed to investigate the mechanism of JDNWF against ACLF based on altered substance metabolic profile in ACLF the expression levels of related molecules.Materials and methodsThe chemical characteristics of JDNWF were characterized using ultra performance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry. Wistar rats subjected to a long-term CCL4 stimulation followed by a combination of an acute attack with LPS/D-GalN were used to establish the ACLF model. Liver metabolites were analyzed by LC-MS/MS and multivariate analysis. Liver function, coagulation function, histopathology, mitochondrial metabolic enzyme activity and mitochondrial damage markers were evaluated. The protein expression of mitochondrial quality control (MQC) was investigated by western blot.ResultsLiver function, coagulation function, inflammation, oxidative stress and mitochondrial enzyme activity were significantly improved by JDNWF. 108 metabolites are considered as biomarkers of JDNWF in treating ACLF, which were closely related to TCA cycle. It was further suggested that JDNWF alleviated mitochondrial damage and MQC may be potential mechanism of JDNWF improving mitochondrial function.ConclusionsMetabolomics revealed that TCA cycle was impaired in ACLF rats, and JDNWF had a regulatory effect on it. The potential mechanism may be improving the mitochondrial function through MQC pathway, thus restoring energy metabolism.

Abstract ACLF (Acute on chronic liver failure) is a systemic inflammatory disease. PANoptosis is a newly discovered regulated cell death (RCD) that occurs in the infectious and inflammatory diseases. The purpose of this study is to investigate the presence of PANoptosis in liver failure. We selected articles from PubMed and Web of Science databases to collect data from these articles through bibliometrics, data mining, and other methods, and then integrated and analyzed these data. Then, we used the public dataset (GSE139602) to obtain central differentially expressed genes (DEGs) to perform various bioinformatics analyses to predict the potential biological mechanism of ACLF. Finally, we conducted experiment validation in a model of ACLF with rats. We found that in the same cell model or animal disease model of liver failure, three types of RDC can occur simultaneously. Enrichment analysis showed that RDC and immune signaling pathways are important pathways in ACLF, and DEGs are mainly involved in immune and inflammatory responses, biosynthesis, and metabolic pathways. The vivo experiments in rats have shown that a large release of inflammatory factors and the key proteins of PANoptosis were all detected separately in the ACLF rats. Those data support the existence of PANoptosis in ACLF.

目的 分析内耳道(internal auditory canal,IAC)和桥小脑角区(cerebellopontine angle,CPA)脂肪瘤的临床表现、影像学特点和治疗.方法 回顾性分析首都医科大学附属北京同仁医院2005～2019年经影像学检查确诊的10例IAC和CPA脂肪瘤患者.结果 10例患者中,5例病变位于IAC,4例位于CPA,1例位于IAC及CPA.所有病例均为单侧发病,其中2例合并内耳畸形.听力下降是主要的临床表现,部分患者可出现耳鸣、眩晕.结论 脂肪瘤是I AC和C PA的罕见肿瘤.影像学检查特别是核磁的压脂序列可以清楚明确的进行诊断.对于无症状或症状不严重的患者,随诊观察并且定期复查影像学检查是主要的治疗选择.如果患者症状严重保守且治疗无效,在充分权衡手术获益的情况下可以考虑手术切除.

Acute-on-chronic liver failure (ACLF) is a critical and refractory disease and a hepatic disorder accompanied by immune dysfunction. Thus, it is essential to explore key immune-related genes of ACLF and investigate its mechanisms. We used two public datasets (GSE142255 and GSE168048) to perform various bioinformatics analyses, including WGCNA, CIBERSORT, and GSEA. We also constructed an ACLF immune-related protein-protein interaction (PPI) network to obtain hub differentially expressed genes (DEGs) and predict corresponding miRNAs. Finally, an ACLF rat model was established to verify the results. A total of 388 DEGs were identified in ACLF, including 162 upregulated and 226 downregulated genes. The enrichment analyses revealed that these DEGs were mainly involved in inflammatory-immune responses and biosynthetic metabolic pathways. Twenty-eight gene modules were obtained using WGCNA and the coral1 and darkseagreen4 modules were highly correlated with M1 macrophage polarization. As a result, 10 hub genes and 2 miRNAs were identified to be significantly altered in ACLF. The bioinformatics analyses of the two datasets presented valuable insights into the pathogenesis and screening of hub genes of ACLF. These results might contribute to a better understanding of the potential molecular mechanisms of ACLF. Finally, further studies are required to validate our current findings.

Objective:To explore the clinical application value of each sequence by analyzing the characteristics of labyrinthine signal on MRI in patients with unilateral sudden deafness.Methods:Totally 52 patients of unilateral sudden deafness with inner ear MRI were analyzed retrospectively at Beijing Tongren Hospital, Capital Medical University from January 2016 to July 2019, all of which could find abnormalities in the labyrinth, including 17 cases of plain scan and 35 cases of enhanced scan, with sequences including plain T 1WI, enhanced T 1WI, plain and enhanced delayed 3D fluid attenuation inversion recovery (3D-FLAIR). The affected labyrinthine signal characteristics of each sequence were analyzed and the involvement sites were judged. The ability of each sequence to show labyrinthine abnormal signal was evaluated and scored. The Friedman test and Wilcoxon signed rank sum test were used to compare the subjective scores of the ability to show labyrinthine high signal in different sequences in plain and enhanced patients, respectively. Fisher′s exact probability method was used to analyze the relationship between the affected sites and the recovery of hearing, tinnitus and vertigo symptoms. Results:Fifty-two patients (100%, 52/52) showed labyrinthine high signal on T 1WI, 8 (15.4%, 8/52) showed higher signal and 3 (5.8%, 3/52) showed low signal on T 2WI. Thirty-five (100%, 35/35) showed high signal on enhanced T 1WI, among which 27 had enhancement (77.1%, 27/35). Fifty-two (100%, 52/52) showed significant high signal of the affected labyrinth on 3D-FLAIR (17 plain scan, 35 enhanced scan). The scores were 2 (2, 2), 3 (2, 3), 3 (3, 4) and 4 (4, 4) of T 1WI, enhanced T 1WI, plain and enhanced 3D-FLAIR respectively. The overall difference in subjective scores of plain T 1WI, enhanced T 1WI and enhanced 3D-FLAIR in enhanced patients was statistically significant (χ2=64.528, P<0.001), and the comparison between the two was statistically different (all corrected P<0.05). The plain 3D-FLAIR score was higher than the plain T 1WI in patients with a statistically significant difference ( Z=-3.729, P<0.001). Twenty-seven cases (51.9%, 27/52) exhibited high signal at the ampulla of semicircular canals, with a statistically significant difference in the distribution of hearing recovery or not ( P=0.001). Conclusions:Both T 1WI and 3D-FLAIR sequences can effectively identify the labyrinthine high signal, but the latter was better than the former of its ability to display, especially delayed enhanced 3D-FLAIR. The high signal at the ampulla of semicircular canals was a characteristic predictor of non-recovery of hearing.

Objective: To explore the value of speculating etiology of the magnetic resonance imaging (MRI) T1 weighted imaging (T1WI) labyrinthine high signal ratio in patients with unilateral sudden deafness accompanied by vertigo and tinnitus and its relationship with hearing prognosis. Methods: Fifty-two patients with unilateral sudden deafness accompanied by vertigo and tinnitus who were admitted to Beijing Tongren Hospital Affiliated to Capital Medical University from January 2016 to July 2019 were collected, including 27 males and 25 females, aged (47.7±15.1) years. The inner ear MRI data of 52 patients (17 plain scan, 35 enhanced scan) with unilateral sudden deafness were retrospectively analyzed. Two radiologists independently measured the labyrinthine high signal intensity of the affected side and the contralateral normal side on T1WI and enhanced T1WI and calculated the signal ratio (the normal labyrinth signal was subtracted from the affected signal and then divided by the normal signal). The etiology of the enhanced group was judged based on two methods, including whether the abnormal high signal was enhanced or not (unenhancement indicated hemorrhage and enhancement indicated inflammation), and the locations of labyrinthine involvement on enhanced three-dimensional fluid attenuated inversion recovery (3D-FLAIR) (inflammation usually involved the perilymph spaces, while hemorrhage involved the perilymph and endolymph spaces). In the plain group, the locations of labyrinthine involvement on 3D-FLAIR was applied to infer the potential etiology. Results: The two methods presumed that 8 cases might be hemorrhage (22.9%, 8/35) and 27 be inflammation (77.1%, 27/35) in the enhanced group, which had a high consistency, while it was speculated that 7 patients might be hemorrhage (7/17) and 10 patients be inflammation (10/17) in the plain group. The measurement results of the two radiologists were highly consistent within and between the groups [the intraclass correlation coefficient (ICC) values were greater than 0.800]. The area under the receiver operating characteristic (ROC) curve (AUC) of the T1WI high signal ratio in the enhanced group for speculating etiology was 0.949 (P<0.01), when the predictive threshold value was 0.467, with a sensitivity of 96.3% and a specificity of 87.5%. It might be hemorrhage when the ratio was higher than the threshold value, otherwise it was inflammation. The T1WI labyrinthine high signal ratio was higher in the hemorrhage group than that of the inflammation group, and the hearing prognosis was worse (all P<0.05). The T1WI labyrinthine high signal ratio of the unrecovered group was higher than that of the recovered group (P=0.034). Conclusions: The etiology of labyrinthine high signal formation can be inferred by quantitative values combined with the involved sites. The high signal in the labyrinth indicates poor hearing prognosis, the higher the signal intensity, the greater the possibility of hemorrhage and the worse the hearing prognosis.

Objective: To investigate the visualization of endolymph in patients with otogenic vertigo by intravenous administration of single dose of gadolinium contrast agents and magnetic resonance three-dimensional fluid-attenuated inversion recovery sequence (3D-FLAIR MRI), and further assess the extent of endolymphatic hydrops. Methods: From Beijing Tongren Hospital of Capital Medical University between October 2017 and June 2018, 30 patients (16 males, 14 females) with unilateral otogenic vertigo were involved in this study, with the age of 30 to 68 years, mean age of (53±10) years. Eight hours after intravenous administration of single dose (0.1 mmol/kg, body weight) of gadopentetate (Gd-DTPA), 3D-FLAIR sequence was performed in 30 patients. The location of endolymphatic hydrops was observed and then the degree of hydrops was quantitatively elevated by two radiologists. The consistency test was used to analyze the location and degree of endolymphatic hydrops in the two radiologists and the paired t-test was used to compare the difference between the affected and healthy side of endolymphatic spaces of the patients with otogenic vertigo. Results: In 30 patients, the gadolinium distributed in all parts of the perilymph inside the inner ear, and can accurately outline the boundaries of the peri-and endolymph. Twenty-six patients (26/30, 86.7%) were found to have unilateral endolymphatic hydrops, including 18 mild hydrops, 8 significant hydrops. The two radiologists had a very good agreement on the assessment of endolymphatic hydrops(kappa=0.864, ICC=0.959). In the 3D-FLAIR MR images of 26 patients with endolymphatic hydrops, the saccule (26/26, 100%) had a higher rate of hydrops than the cochlea and utricle(16/26, 61.5%; 14/26, 53.8%), and two radiologists had a very good agreement on the location of endolymphatic hydrops(kappa=0.820). Moreover, there was a significantly statistical difference between the affected and healthy area of the endolymphatic space in this study (P<0.01). Conclusion: The technique of 3D-FLAIR MR imaging through single dose intravenous gadolinium injection is feasible, which can estimate endolymphatic hydrops in patients with otogenic vertigo, and accurately classify the degree of hydrops.

OBJECTIVE To summarize surgical treatment effects and to discuss surgical strategy for Small acoustic neuroma.METHODS The clinical data of 26 patients with small acoustic neuroma treated with surgery in our department were analyzed retrospectively.25 patients with preoperative hearing grading of C and D received the labyrinthine approach acoustic neuroma resection,and 1 patient with preoperative hearing grading of B received middle fossa approach acoustic neuroma resection.The preoperative and postoperative hearing level,incidence of tinnitus,balance disturbance and weakness of facial muscles were analyzed retrospectively.The control and recurrence of the tumor,the incidence of complications were recorded.RESULTS Total resection was achieved in 25 cases (96％),and in 1 cases achieved sub total resection due to the fact that the tumor was too adhesive to the facial nerve The follow-up time ranged from 6 months to 7 years with 7 cases lost contact.No deaths nor intracranial infection were encountered.Cerebrospinal fluid rhinorrhea was found in 1 cases after the operation and eustachian tube blockage was performed.All patients(100％) had their facial nerve reserved and 16 patients (88％) had their cochlea nerve reserved.17patients(89.5％) had intact facial nerve function and 2 patients suffered from level Ⅲ facial nerve paralysis (House-Brackmann grade) post operatively.6 patients suffered from vertigo pre-operatively and 5 of them reported disappearance of vertigo after the surgery.Of the 13 patients who did not have vertigo before the surgery,1 patient complained sense of dizziness and unsteady walking post-operatively.5 patients (33.3％) reported disappeared or alleviated tinnitus,8 patients (53％) had the same degree of tinnitus and 2 patients reported worsened tinnitus post-operatively.For patients who did not have tinnitus before the surgery,no tinnitus was reported post-operatively.CONCLUSION treatment strategy for small acoustic neuroma requires personalized setting based on the age of the patient,the combined systemic disease,the severity of the symptoms and the growth rate of the tumor.For patients without practical hearing,the tumor could be removed with labyrinthine approach,and the integrity of the cochlear nerve should be preserved as far as possible,for further reconstruction of hearing ability and cochlear implantation.

Objective:To review the clinical features,diagnosis and the treatment of fibrobascular polyp(FVP).Method:Four patients diagnosed as FVP underwent surgery.One polyp was removed with open approach while the other three polyps were excised with laryngoscope.Result:The pathology shows polypoid lesion covered by squamous epithelium.The underlying stroma consisted of a mixture of fibrous connective tissue with fatty cells(adipose tissue),part of the tumor was mucoid degenerated.No complications happened.The patients have been followed up for three months without reoccurrence.Conclusion:FVP is a benign tumor,surgical excision is recommended.Local excision is curative and reoccurrence is rare.

目的 观察针灸及推拿治疗肌紧张性发音障碍的临床疗效.方法 将35例肌紧张性发音障碍患者随机分成治疗组和声休组.治疗组18例,选择针刺疗法治疗,并配合颈周穴位推拿,共治疗3周.声休组17例,患者休息,无特殊治疗.观察3周后2组声道不适指数(VTD)评分、嗓音障碍指数(VHI)评分和嗓音主观评分(GRABS)等变化.结果 治疗组治疗后VTD程度和频率评分较治疗前比较差异有统计学意义(P<0.05);对照组治疗前后VTD程度评分无显著差异,频率评分治疗前后比较差异有统计学意义(P<0.05);治疗组VHI分值治疗前后比较,差异有统计学意义(P<0.01),对照组治疗前后无显著差异.治疗组GRBAS评分治疗前后比较差异有统计学意义(P<0.01),对照组治疗前后无显著差异.结论 针灸及推拿治疗肌紧张性发音障碍疗效优于声音休息方法.

Objective To evaluate the effect of treating epistaxis with radiofrequency and laser via endoscopies.Methods 343 epistaxis patients with similar symptoms and signs were enrolled and randomly divided into two groups to be treated either with radiofrequency or laser via endoscopy.Primary healing rate,surgery duration and halt frequencies were compared as well as the patients discomfort and surgeons' metal pressure stree level were measured with VAS Visual Analogue Scales(VAS).Results The primary healing rates between the radiofrequency group and the laser group were 96.4% (186 cases/ 193 sides)and 94.7%(179 cases /189 sides),the difference was not statistically significant(P>0.05).The surgery duration in radiofrequency group 2.54±0.93 was shorter than that in the laser group 4.65±1.47(P<0.05);the halt frequencies in the radiofrequency group was 1.21 ±0.31 during surgery and the need of stanching was less than that in the laser group 2.87±1.47(P<0.05);the surgeons' stree level in the radiofrequency group was 2.84±0.72 which was lower than that in the laser group 5.07±1.26(P<0.05);all the above results showed statistical significante difference.There was no statistical significance in patients' discomfort grade between the radiofrequency group 6.73±2.06 and the laser group 6.91±1.78(P>0.05).Conclusions Strictly follow the rules of the procedure,satisfactory outcome can be achieved with these two methods.There is no significant difference in the treating effects and patient discomfort level between the two methods if carefully handled.Radiofrequency has more advantages in treating epistaxis in surgery duration,halt frequency and surgeons' stress level.

Highly effective teams are composed of talented members,who have the skill and ability to realize the teams aim and can play their team roles well.Besides,they must trust each other,work together and can fulfill the task excellently.This paper conducted research on employees of different kinds of enterprises.By studying the data,a general rule on team roles was abtained,which will help corporations to reserve and choose talented employees.