Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system. Liquid-liquid phase separation (LLPS) is a physiological process that facilitates the reversible and dynamic assembly of biomolecular condensates. Increasing evidence suggests that LLPS plays a significant role in the pathogenesis of hereditary hearing loss. Nevertheless, there is a conspicuous lack of systematic investigations exploring the impact of LLPS abnormalities on the etiology of hereditary hearing loss. In this review, we examine the mechanisms by which dysfunctions in LLPS contribute to hereditary hearing loss, specifically focusing on its effects on mechanoelectrical transduction in hair bundles, transcriptional regulation, post-transcriptional modifications, the actin cytoskeleton, ion homeostasis within the inner ear, and energy and redox homeostasis. Furthermore, we evaluate the considerable potential of targeting LLPS as a therapeutic approach for hearing loss and propose innovative perspectives on LLPS that may guide future research initiatives in the field of auditory disorders.
Humans ; Animals ; Hearing Loss/physiopathology* ; Phase Separation

OBJECTIVE To investigate the effects and mechanism of galangin （GAL） on hepatocyte apoptosis in rats with obstructive jaundice （OJ） based on the Janus kinase 2 （JAK2）/signal transduction and activator of transcription 3 （STAT3） signaling pathway. METHODS Taking male SD rats as the object， the OJ model was established by double ligation of common bile duct， and 48 rats with successful modeling were randomly separated into OJ model group （model group）， low-dose GAL group （GAL-L group）， high-dose GAL group （GAL-H group） and high-dose GAL+JAK2 activator colivelin group （GAL-H+ colivelin group）， with 12 rats in each group； another 12 SD rats with laparotomy/abdominal closure without ligation were selected as sham operation group （sham group）. Each administration group was given relevant medicine intragastrically and/or intraperitoneally， once a day， for 7 consecutive days. After the last medication， the morphology of liver tissue in rats was observed； the serum levels of total bilirubin （TBIL）， direct bilirubin （DBIL）， alanine transaminase （ALT） and γ -glutamyltransferase （GGT）， as well as the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in mail：guoweishengjcy@126.com liver tissue were detected. The apoptotic rate of liver tissue cells， the expression levels of signaling pathway-related proteins （phosphorylated JAK2， JAK2， phosphorylated STAT3， STAT3） and apoptosis-related proteins [B cell lymphoma 2 （Bcl-2）， Bcl-2 related X protein （Bax）] were determined. RESULTS Compared with sham group， congestion of liver sinusoids， damage to liver lobules， disordered arrangement and swollen morphology of liver cells， the disappearance of nucleoli， and significant infiltration of inflammatory cells and fibrous tissue proliferation were observed in model group； the serum levels of TBIL， DBIL， ALT and GGT， the level of MDA in liver tissue， the apoptosis rate of liver cells， the protein expression of Bax， and the protein phosphorylation levels of JAK2 and STAT3 in liver tissue of model group were increased significantly （P＜0.05）； the level of SOD and the protein expression of Bcl-2 in liver tissue were decreased significantly （P＜0.05）. Compared with the model group， the pathological injuries of liver tissue were relieved in GAL-L group and GAL-H group， all quantitative indicators had significantly improved， and the effect of GAL-H group was more significant （P＜ 0.05）. Colivelin could significantly reverse the improvement effects of GAL on liver injury and related indicators of OJ rats （P＜ 0.05）. CONCLUSIONS GAL may inhibit liver cell apoptosis in OJ rats， improve liver function and alleviate oxidant stress， the mechanism of which may be associated with inhibiting JAK2/STAT3 signaling pathway.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Objective:To study the application of 3D printing technology in multi-center fenestrated/branched endovascular repair (F/B-EVAR) for endovascular repair of abdominal aortic diseases.Methods:From Feb 2018 to Mar 2023, The clinical and followup data of 316 cases of abdominal aortic lesions undergoing repair with F/B-EVAR at 69 medical centers nationwide using 3D printing technology to guide physician-modified stent graft were retrospectively analyzed.Results:The mean follow-up time of the patients was 23 months (2-60 months), and 24 cases were lost to follow up, the follow-up rate was 92.4% (292/316), the mean postoperative hospitalization time was (8.2±4.9) days. A total of 944 main abdominal branch arteries were reconstructed. Intraoperative reconstruction of 11 branches failed, with a success rate of 98.8% (933/944). Within 30 days after surgery, 8 patients died (2.5%), and 6 patients died during follow-up, a total of 14 patients died (4.4%). There were 11 cases (3.5%) of spinal cord ischemia and no patient suffered from permanent paraplegia. There were 19 patients (6.0%) with postoperative renal function injury. Internal leakage was found in 26 patients, and the rate of internal leakage was 8.2%.Conclusion:3D printing technology can accurately locate the location of branch arteries, simplifing the surgical process, shortening the learning curve , and improving clinical efficacy.

Objective:To review the risk factors for early and medium-term complications of fenestration-branch endovascular thoracic aortic repair (F/B-TEVAR) in patients with complex aortic arch disease.Methods:The clinical and follow-up data of 202 patients undergoing F/B-TEVAR treatment from Feb 2019 to Sep 2023 in these centers were retrospectively analyzed .Results:There were 46 cases suffering from postoperative complications (22.8%). The risk factors with statistical significance included aortic atherosclerotic plaque [ OR=2.843; 95% CI (1.4-5.6); P<0.01], aortic intramural thrombosis [ OR=2.358; 95% CI (1.2-4.6), P=0.011], the aortic dilatation [ OR=4.219; 95% CI (1.6-11.3), P<0.01], the history of stroke [ OR=2.088; 95% CI (1.1-4.1), P=0.032], smoking history [ OR=2.680; 95% CI: (1.3-5.5); P<0.01], duration of surgery [ OR=1.9; 95% CI: (1.2-2.9); P=0.042].While the application of 3D printing assistive technology [ OR=0.392; 95% CI: (0.2-0.9); P=0.048] was in a negative correlation with postoperative complication. Conclusions:The independent risk factors for complications after F/B-TVAR included aortic atherosclerotic plaque, aortic intramural thrombosis, the aortic dilatation, the history of stroke, smoking history,duration of surgery.The application of 3D printing technology can effectively reduce the complication rate.

Objective: To investigate the correlation between serum lysosomal-associated membrane protein 2 (LAMP-2), LAMP-2 antibody levels and the progression of renal function in patients with chronic kidney disease (CKD). Methods: A total of 80 patients with CKD 3 to 5 stage (CKD group) and 50 healthy controls (control group) from August 2016 to August 2017 in Affiliated Dongfeng Hospital, Hubei University of Medicine were enrolled. The levels of hemoglobin, creatinine, urea, albumin, LAMP-2 and LAMP-2 antibody in fasting elbow venous blood of 2 groups were detected, and the estimate glomerular filtration rate (eGFR) was calculated. The CKD patients were followed up for 1 year, and renal function deterioration was defined as eGFR declined more than average value; the follow-up was over when the patients started dialysis or died, and those patients also defined as renal function deterioration. The patients were divided into high level group and low level group according to the serum LAMP-2 and LAMP-2 antibody levels. Results: The eGFR, hemoglobin and albumin in CKD group were significantly lower than those in control group: (24.60 ± 5.79) ml/min vs. (119.20 ± 9.52) ml/min, (111.36 ± 24.41) g/L vs. (144.60 ± 17.85) g/L and (36.83 ± 3.84) g/L vs. (45.92 ± 6.37) g/L, the creatinine, urea, LAMP-2 and LAMP-2 antibody were significantly higher than those in control group: (306.17 ± 49.24) μmol/L vs. (83.24 ± 5.55) μmol/L, (15.17 ± 3.39) mmol/L vs. (5.57 ± 1.33) mmol/L, (24.76 ± 5.47) μg/L vs. (12.93 ± 4.43) μg/L and (20.33 ± 4.89) μg/L vs. (9.98 ± 2.20) μg/L, and there were statistical differences (P<0.01). All 80 patients with CKD patients completed follow-up, and the follow-up time was 3 to 12 (8.14 ± 1.95) months. The eGFR at the end of followed-up was significantly lower than that at enrolment: (19.38 ± 7.30) ml/min vs. (24.60 ± 5.79) ml/min, the creatinine and LAMP-2 antibody at the end of followed-up were significantly higher than those at enrolment: (397.56 ± 52.32) μmol/L vs. (306.17 ± 49.24) μmol/L and (22.35 ± 4.74) μg/L vs. (20.33 ± 4.89) μg/L, and there were statistical differences (P<0.01); there were no statistical differences in hemoglobin, albumin, urea and LAMP-2 between the end of follow-up and enrollment (P>0.05). Among the 80 patients with CKD, renal function deterioration was in 42 cases, and renal function stability was in 38 cases. In renal function deterioration patients, the eGFR and urea at the end of followed up were significantly lower than those at enrolment: (18.28 ± 6.92) ml/min vs. (24.46 ± 5.76) ml/min and (13.51 ± 1.92) mmol/L vs. (14.81 ± 3.32) mmol/L, the creatinine, LAMP-2 and LAMP-2 antibody at the end of followed up were significantly higher than those at enrolment: (412.47 ± 53.21) μmol/L vs. (303.16 ± 47.87) μmol/L, (29.07 ± 5.42) μg/L vs. (25.89 ± 5.39) μg/L and (25.03 ± 3.30) μg/L vs. (20.95 ± 4.86) μg/L, and there were statistical differences (P<0.01 or <0.05); there were no statistical differences in hemoglobin and albumin between the end of follow-up and enrolment (P>0.05). In renal function stability patients, the eGFR at the end of follow-up was significantly lower than that at enrolment: (20.38 ± 7.58) ml/min vs. (24.73 ± 5.89) ml/min, the creatinine at the end of follow-up was significantly higher than that at enrolment: (381.07 ± 46.64) μmol/L vs. (309.49 ± 51.15) μmol/L, and there were statistical differences (P<0.01); there were no statistical differences in hemoglobin, albumin urea, LAMP-2 and LAMP-2 antibody between the end of follow-up and enrolment (P>0.05). In CKD patients, 38 cases were in LAMP-2 high level group (≥ 24.75 μg/L), and 42 cases were in LAMP-2 low level group (<24.75 μg/L); 38 cases were in LAMP-2 antibody high level group (≥ 20.33 μg/L), and 42 cases were in LAMP-2 antibody low level group (<20.33 μg/L). Kaplan-Meier curve analysis result showed that the renal function deterioration risk in LAMP-2 high level group was significantly higher than that in LAMP-2 low level group, LAMP-2 antibody high level group was significantly higher than that in LAMP-2 antibody low level group, and there were statistical differences (P<0.01). Conclusions Serum LAMP-2, LAMP-2 antibody levels are increased in patients with CKD, and higher serum LAMP-2 and LAMP-2 antibody levels may be associated with high risk of adverse kidney outcomes and become a promising marker to predict CKD progression.

Objective: To evaluate the immunogenicity of high-dose inactivated quadrivalent influenza serial vaccines (split virion) for elderly people. Methods: Immunogenicity assays on mouse as research animal model with inactivated quadrivalent influenza serial vaccines (split virion) were carried out. Then rates of seroconversion and geometric mean hemagglutination inhibition titers (GMTs) at day 21 after the last vaccination among those who received high-dose (HD) A+ B influenza vaccine, were compared with those who received other vaccines by hemagglutination inhibition (HAI) test. Results: The result of HAI test showed in HD serial vaccine groups, GMTs for all kinds of HA in the two HD serial vaccine groups were significantly different from that of the two SD serial vaccine groups, respectively (P<0.0001), but not the titers for A3 in one B dose first group. Further- more, GMTs for strain A in one B dose first groups were significantly higher than that of one B dose first groups in both HD and SD groups, and vice versa in the GMTs for strain B. The result of the assay of the impact of different immunization intervals of HD serial influenza vaccine on immunogenicity indicated that the immunity responses in 7 or 10 d groups were higher than that in 3 d group. Conclusions It is a new method to prevent the flu for elderly by HD A+ B serial influenza vaccine, whose HA dose per immunization was reduced into two injections, worked best when the immunization interval was 7-10 d. The protective immunity can be improved by selecting immune procedure of the serial vaccine according to the epidemic type surveillance of influenza virus A and B strains.

Objective: Quadrivalent influenza vaccines contain two lineages of type B virus, this study aimed to assess whether the result of single radial immunodiffusion (SRID) are accurate. The cross-interference of two type B hemagglutinins remains unknown. Methods: We detected the vaccine samples developed by Jiangsu GDK Biological Technology Co., ltd by SRID. Results: There was no significant difference between the HA content of antigen reagent, bulk sample and mixed sample of two B bulk within 10 to 40 μg/ml (P>0.05). Then each hemagglutinin B was diluted respectively by other three HA, 30 μg/ml, the other hemagglutinin B or phosphate buffer solution were measured within 10-160 μg/ml. Within 10-40 μg/ml, the HA content was proportional to the diameters of immunodiffusion (R²=0.998), while within the higher content range, a ternary linear regression equation fitted best (R²=0.999). Conclusions No cross-interference between B/Brisbane and B/Phuket was found in SRID within both detection ranges.

Objective To analyze the cases of anaphylactic death cases and explore the standards of judi-cial expertise of anaphylactic death for providing evidence for judicial expertise. Methods Fifty-nine cas-es death due to allergic reaction in Shanghai were collected. And details of medical history, clinical manifestation of anaphylactic reaction and postm ortem exam ination findings were review ed for all cases. Results In the 59 cases, there were 58 cases died from drug allergy, including 77.6% of them were an-tibiotics. The rates of treating in standard hospital and illegal clinic were 37.3% and 61.0%, respectively. The allergic sym ptom s were dyspnea and facial cyanosis. The time from contacting allergens to death ranged from 1 m in to 3 d. The concentration of total serum IgE ranged from 50 to 576.92 IU/m L . The results of clinical manifestation and pathological anatomy had obviously changes. Conclusion B ased on the exclusion of all other cause of death and synthetically analysis of details of cases, medical history, clinical manifestation and anatomy, the conclusion of anaphylactic death can reached. The details of cas-es including clinical history, exposure to allergens, and clinical manifestation play an im portant role in diagnosis of anaphylactic death.

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus with pathogenic mechanisms that may be driven by innate immune pathways. The goal of this study is to characterize the expression of the structural (S, E, M, N) and accessory (ORF 3, ORF 4a, ORF 4b, ORF 5) proteins of MERS-CoV and to determine whether any of these proteins acts as an interferon antagonist. Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells, and their native expression and subcellular localization were assessed using Wes tern blotting and indirect immunofluorescence. While ORF 4b demonstrated majorly nuclear localization, all of the other proteins demonstrated cytoplasmic localization. In addition, for the first time, our experiments revealed that the M, ORF 4a, ORF 4b, and ORF 5 proteins are potent interferon antagonists. Further examination revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production (IFN-β promoter activity, IRF-3/7 and NF-κB activation) and ISRE promoter element signaling pathways. Together, our results provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.
Cell Line ; Coronavirus ; genetics ; pathogenicity ; Genes, Viral ; Humans ; Interferons ; antagonists & inhibitors ; Open Reading Frames ; Recombinant Proteins ; genetics ; metabolism ; Viral Matrix Proteins ; genetics ; metabolism ; Viral Regulatory and Accessory Proteins ; genetics ; metabolism ; Viral Structural Proteins ; genetics ; metabolism