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 establish a method for determining the content of bear bile powder in Longze Xiongdan capsules with taursodeoxycholic acid（TUDCA） and taurchenodeoxycholic acid（TCDCA） as indexes.
Methods: HPLC series evaporation photodetector was adopted on Chrom Core AQ C₁₈ column(4.6 mm×250 mm, 5 μm), with the mobile phase comprising of acetonitrile ( A ) and 5 mmol·L^-1 ammonium acetate solution (B) in a gradient elution (0-40 min, 25%A; 40-50 min, 25%A→29%A; 50-80 min, 29%A; 80-100 min, 29%A→40%A) at the flow rate of 1.0 mL·min^-1. The column temperature was 30 ℃. The ELSD was used, of which the drift tube temperature was 110 ℃ and the flow rate of carrier gas（N₂） was 2.5 L·min^-1.
Results: In the ranges of 1.069-9.57 μg and 0.740 46-7.404 64 μg, logarithms of the injected amount of TUDCA and TCDCA presented good linear relationships with logarithms of the peak area, respectively. The RSDs of precision, repeatability and stability tests were all lower than 2.0%. At three concentration levels the recoveries of TUDCA and TCDCA were 95.2%-97.7% and 91.9%-95.9%, respectively. Samples of 42 batches showed that the contents of TUDCA and TCDCA were 0.18-0.43 and 0.10-0.44 mg·granule^-1, respectively.
Conclusion: This method can be used for the quality control of bear bile powder in Longze Xiongdan capsules, thus provides a scientific basis for improving its quality standard.

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.

Diabetic nephropathy is a common microvascular complication of diabetes mellitus and one of the main causes of death in patients with diabetes mellitus. Ferroptosis is a newly discovered iron-dependent regulated cell death, which may contribute to the pathogenesis and development of diabetic nephropathy. Adenosine monophosphate-activated protein kinase (AMPK)-mediated ferroptosis-related signaling pathways can slow down the progression of diabetic nephropathy, but excessive activation of AMPK signaling pathway may induce cells to undergo autophagic death. Activation of the signaling pathway mediated by nuclear factor-erythroid 2-related factor (Nrf) 2 and heme oxygenase (HO)-1 can inhibit ferroptosis of cells and alleviate diabetic nephropathy. However, the regulatory effect of HO-1 on ferroptosis is bidirectional, and activation of HIF-1α/HO-1 pathway may lead to intracellular iron overload and ultimately promote ferroptosis. Transforming growth factor (TGF)-β1 mediated signaling pathways can accelerate lipid peroxidation by down-regulating the levels of SLC7A11/GSH/GPX4. The ferroptosis-related signaling pathways mediated by exosome lncRNAs/circRNAs/miRNAs are also involved in the pathogenesis and development of diabetic nephropathy. In addition, signaling pathways mediated by stimulator of interferon gene (STING) and the novel ferroptosis promoter acyl-CoA synthetase long-chain family (ACSL) 1 can induce ferroptosis to promote the progression of diabetic nephropathy. In this review, we focus on the roles of ferroptosis in diabetic nephropathy through the signaling pathways mediated by AMPK, Nrf2/HO-1, TGF-β and exosomes, to elaborate the pathogenesis and development of diabetic nephropathy, and the potential therapeutic target for diabetic nephropathy.
Diabetic Nephropathies/etiology* ; Ferroptosis ; Humans ; Signal Transduction ; Heme Oxygenase-1/genetics* ; NF-E2-Related Factor 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Transforming Growth Factor beta1/metabolism* ; MicroRNAs/metabolism* ; RNA, Long Noncoding/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Lipid Peroxidation ; Animals

Objective To analyze the influencing factors of post-operative delirium (POD) in middle-aged and elderly patients in intensive care unit (ICU) and construct risk prediction model for it.Methods A total of 112 middle-aged and elderly postoperative patients in the ICU of Lu'an Hospital of Anhui Medical University from January, 2018 to February, 2021 were selected. On the second day after the operation, they were transferred to ICU, and assessed with the Confusion AssessmentMethod for Intensive Care Unit (CAM-ICU). The patients were divided into delirium group (n = 52) and non-delirium group (n = 60) according to assessment. Univariate analysis was used to compare the differences in clinical data between the two groups, and multivariate Logistic regression analysis was used to screen the independent influencing factors to construct risk prediction model. Receiver operating characteristic (ROC) curve was used to evaluate prediction performance. Results Multivariate logistic regression analysis showed Acute Physiology and Chronic Health Evaluation II score (APACHE II score) (OR = 1.424, 95%CI 1.204 to 1.685, P < 0.001), ICU sleep quality score (OR = 1.432, 95%CI 1.159 to 1.770, P < 0.001), and postoperative oxygenation index ≤ 300 (OR = 4.485, 95%CI 1.644 to 12.240, P = 0.001) were independent influencing factors of postoperative delirium in ICU. The prediction model was: logit(P) = -11.381+0.354X1 (APACHE II score, cut-off value 16)+0.359X2 (ICU sleep quality score, cut-off value 13)+1.501X3 (postoperative oxygenation index ≤ 300), with the sensitivity and specificity of 79.2% and 79.7% respectively. The area under the ROC curve was 0.866 (95%CI 0.801 to 0.930), more than those of the factors alone (P < 0.05). Conclusion The prediction model based on Logistic regression can predict the occurrence of postoperative delirium in middle-aged and elderly patients in ICU.

Objective:To understand the incentive effect and influencing factors of the current economic incentive policy for medical alliances in Longhua District of Shenzhen(the alliance for short) on doctors′ willingness to work at primary medical institutions(the primary for short) from the perspective of mental account, and to explore the economic incentive effect of different economic incentive distribution methods on doctors′ willingness to work at the primary.Methods:The questionnaire was designed based on mental account theory. Random sampling was made in November 2019 for a questionnaire survey among doctors in two district-level medical institutions of the alliance in Longhua District of Shenzhen. The purpose was to analyze their inclination to work at the primary and their selection preferences for economic incentive distribution methods under the current economic incentive policy. The data were analyzed by descriptive analysis, and the influencing factors of doctors′ willingness to work at the primary were analyzed by χ2 test and binary logistic regression. Results:A total of 254 valid questionnaires were collected with an effective recovery rate of 90.7%. Among the respondents, 189(74.4%) were willing to work at the primary, 168(66.1%) chose to receive the economic incentives specifically for working at the primary, and 148 people(58.3%) hoped to receive such economic incentives immediately. Education background, self-rated economic income level of doctors and different payment methods of economic incentive for working at the primary had significant effects on their willingness to work at the primary( P<0.05). Conclusions:The current economic incentive policy of the alliance can meet the demands for economic incentives in terms of doctors′ material accounts, and doctors′ overall inclination to work at the primary was strong. If the amount of economic incentives is constant, doctors preferred to receive the economic incentives specifically, mainly affected by income accounts and additional income accounts. In addition, education and self-assessment of economic income level were important factors affecting the willingness of doctors to work at the primary, which may be affected by mental accounts other than material accounts.

Luohu District of Shenzhen has implemented the global budget management mode as " surplus reward, no compensation for overspending and reasonable sharing" in the hospital group, which continued to strengthen cooperation, optimize services, reduce costs, and improve health outcomes. The authors employed the game theory to build a game model of medical alliance under Luohu global budget management mode, discussing the reasons of medical and health institution′s stronger cooperation and what could be improved in Luohu′s case. Based on the experience of Luohu total budget management, it is suggested that when implementing total budget, all localities should improve closed-loop management, expand coverage, adopt compound medical insurance payment method, promote outpatient coordination, strengthen assessment and incentives, so as to give full play to the incentive role of total budget.

Objective:To explore the risk factors affecting the occurrence of lower extremity deep venous thrombosis in patients with acute cerebral hemorrhage during intensive care unit (ICU) period.Methods:One hundred and thirty-five patients with acute cerebral hemorrhage who were transferred to ICU of our hospital from December 2016 to August 2019 were enrolled. The clinical data were collected, including gender, age, Glasgow coma scale (GCS) scores, hematoma volume, body mass index (BMI), systolic pressure, D-dimer, activated partial thromboplastin time, surgery before transfer, unplanned surgery during ICU period, and so on. According to occurrence of lower extremity deep venous thrombosis, these patients were divided into thrombosis group and non-thrombosis group; univariate analysis was used to compare the differences in clinical data between the two groups, and multivariate Logistic regression analysis was used to screen the independent risk factors for lower limb deep vein thrombosis, and the predictive efficacy was evaluated using receiver operating characteristic (ROC) curve.Results:Thirteen patients (9.63%) were diagnosed as having lower extremity deep venous thrombosis. There were statistical differences between two groups in GCS scores at admission, hematoma volume, BMI, D-dimer, platelet count, surgery before admission, unplanned surgery during ICU period, and hemostasis treatment ( P<0.05). Results of multivariate Logistic regression analysis showed that BMI, D-dimer, and unplanned surgery during ICU period were independent risk factors for lower extremity deep venous thrombosis ( OR=1.868, 95%CI: 1.147-3.043, P=0.012; OR=1.004, 95%CI: 1.000-1.008, P=0.037; OR=0.019, 95%CI: 0.001-0.446, P=0.014). ROC curve showed the area under the curve by combining these three factors was 0.982 ( P=0.000), with sensitivity of 92.31% and specificity of 96.72%. Conclusion:Acute cerebral hemorrhage patients with high BMI, high D-dimer level, and unplanned surgery during ICU period are more likely to have low extremity deep venous thrombosis during ICU period; these patients should be alerted in clinical process.

Germany has introduced the " point method" of fee-for-service at the outpatient departments under a global budget system, in an effort to curb medical expenditure growth. The authors employed the game theory to build a physician′s game model under Germany′s point method, illustrating the causes of " increasing points" behaviors of physicians, the negative effects caused by the increase of points as well as the prevention and control measures employed by Germany and its mechanism. Point method payment has been introduced in several areas in China at their inpatient departments, which is delivered to medical service providers via the performance-based distribution model, with the providers affected in their behaviors. As a result, some areas will tend to appear such " increasing points" behaviors as competing for patients, lowering admission criteria, and raising point value. In view of Germany′s experiences, China should adopt such measures as dynamic monitoring system, disclosure of " increasing points " behaviors, perfection of hierarchical medical system, and strengthening the self-governance via medical sector′s associations.