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

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl₄） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl₄ was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg^-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G₀/G₁ phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G₀/G₁ phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G₀/G₁ phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Objective:To test the feasibility, efficacy and safety of percutaneous patent foramen ovale(PFO) closure utilizing the Pansy biodegradable occluder(PBO) at 1-, 3-, 6-, 12-, 24-, and 36-month follow-up.Methods:In this single-center prospective clinical study, we enrolled 15 patients with PFO eligible for closure, all treated with the PBO, with device sizes ranging 24-34 mm. All clinical data were recorded in a 36-month follow-up period. Patients were summoned to the hospital in the 1, 3, 6, 12, 24, and 36 months after closure for transthoracic echocardiography(TTE), or transesophageal echocardiography(TEE), contrast transcranial doppler(cTCD) or contrast transthoracic echocardiography(cTTE), and a routine fasting blood sample.Results:The mean age was 27-68(44.0±16.4) years old. Indications for closure were cryptogenic stroke in 6 patients and migraine in 9 patients. Procedures were technically successful in 100%(15/15), in which course TTE showed that the position and shape of occluders were satisfactory. Small residual shunt was found by TTE in 2 patients with ASA in 1 month and 6 months after closure, respectively. 1 patient with cryptogenic stroke had another recurrent stroke 8 months after closure. At 12-month follow-up, 11 cases were closure. At 36-month follow-up, 13 cases were closure. 12 patients without atrial septal aneurysm(ASA) were closure. 1 patients with ASA was complete closure. No device-related complications occurred during the follow-up.Conclusion:PBO has good biocompatibility and suitable degradation time. A high technical success rate and closure rate can be achieved in those patients without ASA. Percutaneous closure of PFO using PBO is feasible, effective, and safe.

Passing the hospital grading evaluation, establishing a tertiary-A specialized hospital for occupational diseases, enhancing hospital's internal quality and sustainable development, and continuously improving medical service quality are important measures to promote the high-quality development of hospitals. The evaluation standards for occupational disease specialized tertiary-A hospital require standardized, scientific, and sustainable management of medical equipment. Guangdong Province Hospital for Occupational Disease Prevention and Treatment is the first tertiary-A hospital for occupational diseases specialized in Guangdong Province. Relative regulation on medical equipment management was systematically reviewed based on the requirement of tertiary-A specialized hospital for occupational diseases during hospital grading evaluation process. Building and completing the medical equipment management system, standardizing and strengthening government procurement management, completing the configuration management and safety management of large-scale medical equipment, strengthening the effectiveness analysis and evaluation of large equipment, enhancing training on medical equipment usage, establishing emergency allocation systems for first-aid and life support medical equipment, and forming a medical equipment quality and safety management team is the measure to systematically improve and implement each item in various regulation for the full lifecycle management of medical equipment. It provides vital support in passing the tertiary-A hospital evaluation for hospitals. During the hospital grading evaluation process, each issue identified in medical equipment management was addressed and improved. This process continuously enhanced the hospital's medical equipment management level, ensured the safe and effective use of medical equipment, and improved the quality of medical services, laying a solid foundation for the hospital to become a high level specialized medical institution for occupational diseases.

Objective:To establish UPLC fingerprint method and 2 contents determination methods of Buddleja officinalis; To provide a reference for improving the quality control standard and evaluation of Buddleja officinalis from different habitats.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddleja officinalis. The similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to compare the quality differences of Buddleja officinalis from different habitats. The contents of acteoside and linarin in Buddleja officinalis were determined.Results:There were 12 common peaks in UPLC fingerprints of Buddleja officinalis, six of which were identified as echinacoside, acteoside, cynaroside, isoacteoside, linarin, and apigenin. The fingerprint similarity of 17 batches of Buddleja officinalis was more than 0.9; Buddleja officinalis from different habitats were classified into 2 groups. Five differential markers were determined by OPLS-DA analysis. The order of significance was acteoside > peak 3 > echinacoside > isoacteoside > linarin. Edgeworthia chrysantha was identified by the method of fingerprint as counterfeit. The results of content determination showed that the content of Buddleja officinalis in Hubei and Sichuan was the high and stable.Conclusion:The method can effectively analyze the differences of Buddleja officinalis from different habitats, and provide reference for the quality control of Buddleja officinalis.

Objective:To explore the changes of dynamic cerebral autoregulation ability in pilots exposed to acute positive acceleration(+ Gz) by transcranial Doppler combined with beat-to-beat blood pressure.Methods:A total of 26 pilots enrolled in the + 8Gz manned centrifuge trial at the Air Force Medical Center, Air Force Medical University from June to October 2022 were prospectively included. Blood pressure and heart rate were monitored in the resting state before the trial and within 5 min after centrifugation. Transcranial Doppler combined with noninvasive continuous beat-to-beat blood pressure monitor were used to detect bilateral middle cerebral artery blood flow velocity and beat-to-beat pulse pressure respectively. The transfer function analysis was applied to derive the parameters of cerebral blood flow autoregulation in each frequency band from 0.02 to 0.50 Hz, and the phase, gain and coherence were calculated. The above parameters were compared between resting state and after acute + 8Gz positive acceleration exposure.Results:Compared with the resting state, in all of the 26 pilots after acute + 8Gz positive acceleration exposure, the systolic and diastolic blood pressure and heart rate increased significantly ( P<0.001), the phase significantly increased and the gain significantly decreased in the ultra-low frequency band (0.02-0.07 Hz) ( P<0.05); whereas there were no statistical differences of gain and phase in the low frequency band (0.07-0.20 Hz) and the high frequency band (0.20-0.50 Hz) (all P>0.05). Conclusions:Transcranial Doppler combined with beat-to-beat pulse pressure can be used for the assessment of changes in immediate dynamic cerebral autoregulation after acute + Gz exposure, and transfer function analysis of ultra-low frequency band parameters is suitable for this type of evaluation.

Objective To explore the feasibility of peritoneal dialysis catheter placement assisted by flexible ureteroscope.Methods A retrospective analysis was conducted on clinical data of 54 cases of end-stage renal disease receiving peritoneal dialysis catheter placement from May 2019 to March 2023.The placement method was chosen by the patient.In the conventional group,23 cases were guided by a metal guide wire for insertion of the peritoneal dialysis catheter,while in the flexible ureteroscope group,31 cases were guided by flexible ureteroscope instead of guide wire for insertion of the peritoneal dialysis catheter.The success rate of catheterization,surgical time,use of postoperative analgesic,complications related to peritoneal dialysis catheter,and postoperative creatinine decrease were compared between the two groups.Results The catheter placement was successfully performed in both groups.The total incidence of complications related to peritoneal dialysis catheter in the flexible ureteroscope group was lower than that in the conventional group[6.5%(2/31)vs.30.4%(7/23),χ2 =3.878,P =0.049].Between the conventional group and the flexible ureteroscope group,there were no statistically significant differences in the surgical time,postoperative analgesic usage,and the decrease of creatinine at 2 weeks after surgery(P>0.05).The median postoperative follow-up period was10 months(range,3-24 months)in the two groups,and there were no complications such as peritoneal leakage,intestinal perforation,or intraperitoneal bleeding.Conclusion The placement of peritoneal dialysis catheter guided by the flexible ureteroscope instead of metal guide wire is a safe,visible,and accurate method,which can reduce complications related to peritoneal dialysis catheter,and detect and manage comorbidities in the abdominal cavity.

Clinical data of 15 patients diagnosed with acute renal infarction (ARI) in Affiliated Zhongshan Hospital of Dalian University from Jan 2011 to Dec 2021 were retrospectively analyzed. Of the included 15 patients, there were 14 cases of cardiac origin and 1 case of antiphospholipid syndrome. We found that there were 12 cases of atrial fibrillation, 2 cases of atrial premature beats, 12 cases of elevated level of D-dimer, 15 cases of elevated level of LDH, 11 cases of positive urine occult blood and positive urine protein. Among the 15 patients, catheter-directed thrombolysis was performed in 4 cases, of which 3 cases were revascularized successfully, intravenous thrombolysis in 2 cases and alone anticoagulation therapy in 9 cases. It is suggested that CECT or CTA can assist the early diagnosis of ARI especially in patients with acute onset and persistent abdominal pain with high risk factors of thromboembolism, high levels of LDH, microscopic hematuria and/or proteinuria. Despite prolonged embolic ischemia, try to reconstruct blood flow to save the kidney as much as possible. Late standardized anticoagulant therapy is of critical importance to prevent recurrent embolic episodes.

【Objective】 To investigate the predictive value of high preoperative neutrophile-lymphocyte ratio (NLR) for the prognosis of nonurothelial carcinoma of the bladder (NUBC) after radical cystectomy (RC). 【Methods】 Clinical and follow-up data of NUBC patients undergoing RC during Jan.2005 and Dec.2020 were collected. The optimal cut-off value of NLR was determined with the receiver operating characteristic (ROC) curve. The survival curve was drawn with Kaplan-Meier method to compare the differences in cancer specific survival (CSS) and overall survival (OS) between the high-NLR and low-NLR groups. The independent risk factors of CSS and OS were screened with Cox proportional hazard regression model. 【Results】 Of the 62 eligible cases,34 (54.8%) were diagnosed with adenocarcinoma,17 (27.4%) with squamous cell carcinoma, 6 (9.7%) with small cell carcinoma and 5 (8.1%) with sarcoma. Kaplan-Meier analysis results showed high NLR was associated with poor CSS (P=0.001) and OS (P<0.001). Cox regression results indicated that high NLR (HR=2.42, 95%CI: 1.12-5.23, P=0.025) and advanced pathologic tumor stage (HR=3.21, 95%CI:1.53-6.74,P=0.002) were independent risk factors of unfavorable CSS. Similarly, high NLR (HR=2.75, 95%CI: 1.35-5.56, P=0.005) and advanced pathologic tumor stage (HR=2.81, 95%CI:1.43-5.57, P=0.003) were independent risk factors of unfavorable OS. 【Conclusion】 As an independent risk factor of unfavorable CSS and OS in NUBC patients undergoing RC, high preoperative NLR is of great value in the prediction of long-term prognosis and may help to optimize individualized treatment.

This article analyzed the clinical data of a patient with occupational chemical poisoning in a fabric processing workshop in August 2020, and carried out occupational hygiene investigation and testing. The patient went to the doctor because of painless progressive vision loss in both eyes, and was clinically diagnosed with methanol poisoning optic neuropathy in both eyes. The glue, solvent, washing machine water, and curing agent used in the workshop were used for qualitative analysis of volatile organic components, and methyl acetate was all detected. Esters, the relative percentages were 42.56%, 66.67%, 46.43%, and 41.63%, respectively. Therefore, it was judged that the patient was occupational acute methyl acetate poisoning, the enterprise should strengthen the awareness of safe production and enhance the occupational hygiene knowledge and self-protection awareness of workers.