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 explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Objective:To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction

ObjectiveTo investigate an outbreak of norovirus diarrhea in a welfare home for the elderly in Shanghai， and to analyze the epidemiology and virus genotype characteristics of the epidemic， thus providing a scientific basis for the prevention and control of norovirus epidemic. MethodsCase definition was clarified. After case definition， a standardized questionnaire was used to carry out case investigation to make comprehensive analysis in combination with field epidemiological investigation and laboratory tests results. ResultsThe epidemic lasted for 14 days， and 23 cases were reported with an incidence rate of 12.37% （23/186）， including 3 males and 20 females. There were more cases on the 1st， 4th and 6th floor of the main building in the welfare home， accounting for 52.17% （12/23） of total cases. 19 cases were reported in the main building， with an incidence rate of 11.59% （19/164）； 4 cases were reported in the auxiliary building， with an incidence rate of 18.18% （4/22）. There was no significant difference in the morbidity between the main building and the auxiliary building （χ²=0.779，P>0.05）. The main clinical manifestations were vomiting and diarrhea. There was a significant difference in the incidence of vomiting symptoms among the elderly， nursing staff and other staff in the welfare home （χ²=10.216， P<0.05）. But there was no significant difference in the incidence of diarrhea among the elderly， nursing staff and other staff （χ²=1.218， P>0.05）. Fecal samples were collected from 23 cases， 1 case family member， 68 risk personnel and 14 environmental surface swab samples. Norovirus GⅡ was detected in stool samples of 19 cases， 1 family member and 36 risk personnel. ConclusionOutbreak of norovirus infection is reported in a welfare home in Shanghai. The close contact between the elderly and health workers might lead to the outbreak.

Urinary retention is a common complication of bedridden patients in traumatic orthopedics. The severe condition can even cause permanent bladder injury and renal failure, which brings great pain and psychological pressure to patients and seriously hinders their rehabilitation. The traditional Chinese medicine appropriate technologies have the characteristics of safety, effectiveness, low cost, simplicity and easy learning and achieve good clinical effects in the prevention and treatment of bedridden patients with urinary retention in traumatic orthopaedics, including Chinese herbal medicine, acupuncture and moxibustion, massage, etc. The authors summarize the research progress in appropriate technologies of traditional Chinese medicine in the prevention and treatment of bedridden patients with urinary retention in traumatic orthopedics from aspects of action principles, operation methods and effects of acupuncture points, moxibustion therapy, manipulation therapy, external treatment of traditional Chinese medicine and acupoint injection, so as to provide a reference for further nursing research and clinical application.

Objective:To investigate the clinical characteristics and prognosis of Epstein-Barr virus-related diseases in adults.Methods:The clinical data of 59 patients with Epstein-Barr virus-related diseases in Huashan Hospital, Fudan University, Shanghai from January 2017 to August 2019 were analyzed retrospectively. The clinical manifestations of patients with infectious mononucleosis (IM), chronic active Epstein-Barr virus infection (CAEBV) and lymphoma in patients were compared. Patients were divided into acute course group (IM) and chronic course group (CAEBV+ lymphoma), and the results of labratory indications (blood rontine, liver function, imflammatory indications, Epstein-Barr virus DNA, Epstein-Barr virus antibody and T lymphocyte) were compared between two groups. Statistical analysis was performed by Mann-Whitney U test, chi-square test or Fisher exact probability test. Results:Among the 59 patients, 23 cases (39.0%) were diagnosed with IM, 23 cases (39.0%) were lymphoma and 13 cases (22.0%) were CAEBV. The clinical manifestations of patients with Epstein-Barr virus-related diseases were fever (57/59, 96.6%), lymphadenopathy (37/59, 62.7%) and splenomegaly (36/59, 61.0%). There were 17 patients in the chronic course group experienced hemophagocytic lymphohistiocytosis (HLH). The white blood cell counts, hemoglobin levels and platelet counts of patients in the chronic course group (4.07(1.94, 8.35)×10 9/L, 89.5(74.5, 108.0) g/L and 100(37, 161)×10 9/L, respectively) were all lower than those in the acute course group (9.91(6.75, 17.38)×10 9/L, 132.5(118.2, 152.0) g/L and 197(129, 233)×10 9/L, respectively), with statistically significant differences ( U=3.69, 5.22 and 3.61, respectively, all P<0.01). The levels of procalcitonin, C-reactive protein and serum ferritin in the chronic course group (0.45(0.15, 1.13) μg/L, 47.75(17.57, 84.67) mg/L and 2 000(682, 2 002) μg/L, respectively) were all higher than those in the acute course group (0.12(0.07, 0.28) μg/L, 6.39(3.13, 11.38) mg/L and 482(159, 1 271) μg/L, respectively), with statistically significant differences ( U=-2.95, -3.77 and -4.16, respectively, all P<0.01). The counts of CD4 + T lymphocytes, CD8 + T lymphocytes, CD19 + B lymphocytes and natural killer cells in the chronic course group (259.15(101.98, 509.26), 214.69(119.31, 529.47), 46.14(4.44, 135.87) and 81.09(41.53, 118.46)/μL, respectively) were all lower than those in the acute course group (738.88(592.20, 893.94), 1 609.17(920.88, 3 952.34), 144.52(83.65, 215.14) and 309.82(123.78, 590.68)/μL, respectively), with statistically significant differences ( U=3.66, 3.80, 2.90 and 3.40, respectively, all P<0.01), while the CD4 + /CD8 + T lymphocytes ratio in the chronic course group was higher (0.90(0.60, 1.70) vs 0.45(0.10, 1.28))( U=-2.29, P=0.02). Twenty-three patients with IM were all cured, while 10 patients with lymphoma died and 13 received chemotherapy. Seven patients with CAEBV died and six improved. Conclusions:The clinical characteristics of Epstein-Barr virus-related diseases in adults are fever, lymphadenectasis, splenomegaly.Chronic Epstein-Barr virus infection may be associated with HLH. The prognosis of adults with acute Epstein-Barr virus infection is good, while that of long-term chronic Epstein-Barr virus infection is poor.

Objective To assess the quantitative impact of the application of high-throughput sequencing worldwide on clinical virology.Methods The following records from 2000 to 2018 were collected from National Center for Biotechnology Information:The number of complete genome of virus records per year;the number of virus discovery articles per year;the number of virus quasi-species articles per year;the number of viral infection gene signature articles per year.The method of interrupted time series was applied to analyze the trends of those records.Results Since the sequencing centers worldwide began to transit from the Sanger sequencing to the high-throughput sequencing technology in 2008,the annual value of records mentioned above increased by 3.755,2.760,6.195 and 3.885 times respectively.The long-term trends of change of each record are as follows:the number of complete genome of virus records increased by 1639.991 per year (P＜0.001);the number of virus discovery articles increased by 83.091 per year (P＜0.001);the number of virus quasi-species articles increased by 2.509 per year (P＜ 0.001);the number of viral infection gene signature articles increased by 30.836 per year (P＜ 0.001).Conclusions In 2008,the sequencing centers worldwide began to apply high-throughput sequencing technology which led to continuous decrease of the cost for sequencing.It result ed in not only increasingly enriched applications in clinical virology but also a long-term positive impact on the advance of clinical virology.

Objective To investigate the outcome and affecting factors of patients with osteosarcoma after recurrence.Methods Retrospective analysis was used to analyze the achieved data and prognosis-related factors of 72 patients with extremity osteosarcoma after recurrence from June 2000 to September 2012 through multicenter joint treatment.37 males and 35 females were included.The overall age was 7 to 61 years old (average age22.2 years old).Classification based on the tumor recurrent parts:42 cases (58.3％) on femur,18 cases (25％) on tibia,7 cases (9.7％) on humerus and 5 cases (6.9％) on fibula.Classification based on metastases:14 cases of simple recurrence (19.4％),58 cases (80.6％) of recurrence with metastasis:29 cases (40.3％) of recurrence occurred first,9 cases (12.5％) of metastasis occurred firstly,20 cases (27.8％) of simultaneous recurrence with metastasis;12/14 patients (16.7％) of simple recurrence had long-term survival,but 2 died (2.8％).Six of 58 patients (8.3％) of recurrence with metastasis had long-term survival but 52 died (72.2％).Results The overall 10-year postrelapse survival rate of the 72 patients was 25％.Kaplan-Meier univariate analysis revealed that postrelapse survival was significantly influenced by the continued treatment after recurrence and the number of postoperative chemotherapy,but it was not significantlyinfluenced by age,gender and the number of preoperative chemotherapy.Multivariate analysis revealed that the continued treatment after recurrence and the number of postoperative chemotherapy were independent prognostic factors (P=0.002,P=0.007).At the same time,according to the survival curve grouped by different indicators,the number of chemotherapy after recurrence has no significant effect on TFS.However,the continued treatment after recurrence has obvious statistical significance on improving TFS and OS of patients (P=0.026,P=0.002).Conclusion Resection and standard postoperative chemotherapy had significant effects on the postrelapse survival in patients with osteosarcoma.There are good prospects for further multimodal therapy and multicenter cooperation for osteosarcoma after recurrence.

Objective To investigate the clinical and epidemiological characteristics of osteosarcoma in China and analyze the incidence and clinical treatment of osteosarcoma.Methods The clinical data of 1 593 patients with osteosarcoma in 7 bone cancer treatment centers from January 2000 to February 2017 were analyzed.We retrieved large samples of documents in the database,extracted the relevant data and compared the data with this study.SPSS 13 software was used for statistical analysis and each factor was tested by x2.Results Of 1 593 patients,984 were males and 609 were females.The ratio of male to female was 1.62∶ 1.The average age was 23.2 years (range from 3-80 years).The peak age of onset was 11-20 years (52.4％).There were 217 elderly patients (＞ 40 years old).The tumors occurred in 1 524 limbs and 69 in axial bone.The most common sites of disease were distal femur 706 cases,proximal tibia 375 cases,distal humerus 117 cases and others 395 cases.There were 1 154 cases (71％) around the knee joint.The axial bone included 18 cases of spine,49 cases of pelvis and 2 cases of rib.Preoperative biopsy was performed in 1 111 cases and incisional biopsy in 280 cases.Preoperative diagnosis could be made in 1 345 cases (84.4％ of all patients,accounting for 96.7％ of biopsy patients).There were 79 cases with metastasis at first visit,accounting for 5％.Preoperative chemotherapy was performed in 1 185 cases (74.4％).With the DIA preoperative chemotherapy 271 cases,DIA+MTX 251 cases,AP 149 cases.220 cases of tumor cell necrosis rate was evaluated after operationaccording to the Huvos classification.There were78 cases of grade Ⅰ,105 cases of Ⅱ grade,35 cases of Ⅲ and 2 cases of grade Ⅳ.There were 1 299 cases undergoingpostoperative chemotherapy (81.5％),1 306 patients undergoinglimb salvage surgery (82％).Thespecific operation with prosthetic replacement is the most common (911 cases,69.8％).The postoperative chemotherapy included DIA+MTX regimen 471 cases,DIA regimen 266 cases and AP regimen 98 cases.Before and after the operation,379 cases were treated with the same chemotherapy regimen and 666 cases were changed.A total of 18 large sample documents were retrieved in Chinese data base (5 684 cases).The sex ratio,age range,peak incidence and location of the disease were similar to those of this study.The average age was 1-2 years old younger.The percentage of lung metastases associated with initial visits washigher.The rate of preoperative and postoperative chemotherapy and limb salvage waslowand the rate of tumor necrosis wasbetter after chemotherapy.A total of 22 large sample literatures were searched in foreign database (12 850 cases).The ratio of men and women is 1.30∶1 and the proportion of women is higher than the domestic data.The average age was 1-2 years older.The ratio of the knee joint was lower.The percentage of lung metastases associated with initial visits washigher.The rate of preoperative and postoperative chemotherapy and limb salvage were similar to that of this study and the rate of tumor necrosis was better after chemotherapy.Conclusion The general situation of the incidence of osteosarcoma (sex,age,location of the disease) is not significantly different from the previous reports both at home and abroad.In the treatment,preoperative and postoperative chemotherapy rate and limb salvage surgery rate have improved significantly compared with the past.The chemotherapy program from the coexistence of various programs,gradually to the DIA+MTX and DIA program as the mainstream program.

Objective To explore the factors associated with the quality of life (QOL) in patients after liver and kidney transplantation.Methods A multicenter cross-sectional survey was carried out in 5 Level Ⅲ Class A hospitals.153 liver transplant recipients and 301 kidney transplant recipients of outpatient clinic follow-up from March to December in 2015 were selected and investigated with a self-designed general state questionnaire,and Quality of Life Scale for Liver and Kidney Transplant Recipients which developed by our research group.Results There were significant differences in QOL total score in liver and kidney transplant recipients among groups of marital status and occupation.Divorced,unemployed and low-educated patients showed lower QOL total score than married,employed and high-educated ones (P ＜ 0.05).As compared with non-living-related transplantation group,patients undergoing living-related transplantation presented a better status in QOL total scores (P＜0.05).The QOL total score was obviously lower in patients suffering from complications and rejection than in those without occurrence of complications and rejection (P＜ 0.01).Postoperative time was correlated positively and significantly with QOL scores,and variances existed among different stages postoperation (P ＜ 0.01).Multivariable regression analysis demonstrated that education,marital status,postoperative time,type of donor and chemotherapy were the factors influencing liver transplant recipients' QOL,while marital status,postoperative time,type of donor,medical care assurance,complications and rejection after operation had effect on kidney transplant recipients.Conclusion Attaching importance to QOF among liver and kidney transplant recipients,and implementing scientific and effective nursing intervention based on the characteristics of them are necessary.