Refractory inner ear disease refers to a spectrum of inner ear diseases that fail to achieve good therapeutic effects even after standardized treatment recommended by existing clinical practice guidelines. This disease spectrum is characterized by diverse etiological factors, high phenotypic heterogeneity, unclear subtype characteristics, unknown pathogenic mechanisms, and variable prognosis, making it difficult to define precisely. Refractory inner ear disease accounts for a significant proportion of the total population with inner ear diseases and has not been systematically summarized, refined, and deeply studied to date. This article, for the first time, clearly proposes the concept, definition, and scope of refractory inner ear disease, and elaborates on the current research status, challenges, and coping strategies for refractory inner ear disease. With the development and progress of science and technology, we believe that in the future we will witness more innovative technologies and new drugs applied to the treatment of refractory inner ear disease, bringing hope of cure to patients.
Humans ; Labyrinth Diseases/therapy*

Objective To explore the prescription and preparation technology of compound Bupleurum suppository and draft its quality standard.Methods The volatile oil of Bupleurum was extracted by steam distillation,and the compound Bupleurum-based suppository was prepared by mixing the volatile oil with taurine using the melting method.The quality standard of the preparation was formulated according to the quality inspection items of the general rule 0107 of the Pharmacopoeia of the People's Republic of China(2020 Edition,Volume IV);The contents of n-hexanoic acid and n-heptanoic acid in the preparation were determined by gas chromatography-mass spectrometry(GC-MS).The content of taurine in the preparation was determined by high-performance liquid chromatography(HPLC).Results The optimized distillation time of the volatile oil was 1.5 h,The linear ranges of n-hexanoic acid,n-heptanoic acid and taurine are 23.175 0-115.875 0 μg·mL-1(R2=0.999 4),4.590 0-68.850 0 μg·mL-1(R2=0.998 9)and 15-125 μg·mL-1(R2=0.999 6),respectively.The average recoveries are 99.83%,101.96%,98.89%with RSDs of 2.84%,1.36%,2.88%,respectively.The RSDs of precision,stability,and repeatability tests are less than 5%.The properties,mass difference,melting time,microbial limit,and stability assessment of the preparationwere all in accordance with the Pharmacopoeia of the People's Republic of China.Conclusion Compound Bupleurum suppository preparation technology is reasonable and feasible,which meets the quality standard.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

BACKGROUND:Synovitis is involved in all stages of osteoarthritis and is a key factor contributing to the development of osteoarthritis.Studies have shown that circular RNA(circRNA)plays an important role in the proliferation,apoptosis and extracellular matrix degradation of synovial cells and chondrocytes.OBJECTIVE:To observe the effects of circRNA SEC24A on the interleukin-1β-induced proliferation,apoptosis,and expression of inflammatory factors in human synovial fibroblasts.METHODS:Human synovial fibroblasts were divided into four groups,including control group,interleukin-1β group,empty vector group,and sh-circSEC24A group.Except for the control group,the other three groups were induced with 10 ng/mL interleukin-1β for 24 hours to establish inflammatory cell models;the empty vector group and sh-circSEC24A group were infected with empty vector virus and lentiviral vector knocking down circSEC24A.CCK-8 assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.ELISA was used to detect the levels of matrix metalloproteinase-9,matrix metalloproteinase-13,interleukin-6,and tumor necrosis factor-α in cell supernatant.Western blot assay was used to detect the relative expression levels of Bax,Bcl-2,matrix metalloproteinase-9,matrix metalloproteinase-13,casepase3,cleaved-casepase3,casepase8,and cleaved-casepase8 proteins in cells.RESULTS AND CONCLUSION:(1)qRT-PCR results showed that compared with the normal group,the expression of circSEC24A in human synovial fibroblasts induced by interleukin 1β was significantly up-regulated.(2)The absorbance value of cells in the sh-circSEC24A group detected by CCK-8 assay was significantly higher than that of interleukin 1β group and empty vector group(P＜0.05).The apoptosis rate of sh-circSEC24A group detected by flow cytometry was significantly lower than that of interleukin 1β group and empty vector group(P＜0.05).(3)The levels of tumor necrosis factor α and interleukin 6 in the supernatant of human synovial fibroblasts in the sh-circSEC24A group detected by ELISA were significantly lower than those in the interleukin 1β group and the empty vector group(P＜0.01,P＜0.001).(4)Western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the expression of the pro-apoptotic factor Bax protein in the sh-circSEC24A group significantly decreased,and the expression of the anti-apoptotic factor Bcl-2 protein increased significantly(P＜0.05);apoptosis and related activating factors cleaved-casepase3 and cleaved-casepase8 protein expressions were both reduced(P＜0.05).(5)ELISA and western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the sh-circSEC24A group had lower levels of matrix metalloproteinase 9 and matrix metalloproteinase 13 protein(P＜0.05).These findings indicated that the expression of circSEC24A was abnormally increased in human synovial fibroblasts induced by interleukin 1β.Knocking down circSEC24A expression could promote the proliferation of human synovial fibroblasts and inhibit apoptosis,inflammatory factor release,and extracellular matrix degradation,suggesting that circSEC24A may be an important intervention target for early osteoarthritis.

Objective To explore the prescription and preparation technology of compound Bupleurum suppository and draft its quality standard.Methods The volatile oil of Bupleurum was extracted by steam distillation,and the compound Bupleurum-based suppository was prepared by mixing the volatile oil with taurine using the melting method.The quality standard of the preparation was formulated according to the quality inspection items of the general rule 0107 of the Pharmacopoeia of the People's Republic of China(2020 Edition,Volume IV);The contents of n-hexanoic acid and n-heptanoic acid in the preparation were determined by gas chromatography-mass spectrometry(GC-MS).The content of taurine in the preparation was determined by high-performance liquid chromatography(HPLC).Results The optimized distillation time of the volatile oil was 1.5 h,The linear ranges of n-hexanoic acid,n-heptanoic acid and taurine are 23.175 0-115.875 0 μg·mL-1(R2=0.999 4),4.590 0-68.850 0 μg·mL-1(R2=0.998 9)and 15-125 μg·mL-1(R2=0.999 6),respectively.The average recoveries are 99.83%,101.96%,98.89%with RSDs of 2.84%,1.36%,2.88%,respectively.The RSDs of precision,stability,and repeatability tests are less than 5%.The properties,mass difference,melting time,microbial limit,and stability assessment of the preparationwere all in accordance with the Pharmacopoeia of the People's Republic of China.Conclusion Compound Bupleurum suppository preparation technology is reasonable and feasible,which meets the quality standard.

BACKGROUND:Synovitis is involved in all stages of osteoarthritis and is a key factor contributing to the development of osteoarthritis.Studies have shown that circular RNA(circRNA)plays an important role in the proliferation,apoptosis and extracellular matrix degradation of synovial cells and chondrocytes.OBJECTIVE:To observe the effects of circRNA SEC24A on the interleukin-1β-induced proliferation,apoptosis,and expression of inflammatory factors in human synovial fibroblasts.METHODS:Human synovial fibroblasts were divided into four groups,including control group,interleukin-1β group,empty vector group,and sh-circSEC24A group.Except for the control group,the other three groups were induced with 10 ng/mL interleukin-1β for 24 hours to establish inflammatory cell models;the empty vector group and sh-circSEC24A group were infected with empty vector virus and lentiviral vector knocking down circSEC24A.CCK-8 assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.ELISA was used to detect the levels of matrix metalloproteinase-9,matrix metalloproteinase-13,interleukin-6,and tumor necrosis factor-α in cell supernatant.Western blot assay was used to detect the relative expression levels of Bax,Bcl-2,matrix metalloproteinase-9,matrix metalloproteinase-13,casepase3,cleaved-casepase3,casepase8,and cleaved-casepase8 proteins in cells.RESULTS AND CONCLUSION:(1)qRT-PCR results showed that compared with the normal group,the expression of circSEC24A in human synovial fibroblasts induced by interleukin 1β was significantly up-regulated.(2)The absorbance value of cells in the sh-circSEC24A group detected by CCK-8 assay was significantly higher than that of interleukin 1β group and empty vector group(P＜0.05).The apoptosis rate of sh-circSEC24A group detected by flow cytometry was significantly lower than that of interleukin 1β group and empty vector group(P＜0.05).(3)The levels of tumor necrosis factor α and interleukin 6 in the supernatant of human synovial fibroblasts in the sh-circSEC24A group detected by ELISA were significantly lower than those in the interleukin 1β group and the empty vector group(P＜0.01,P＜0.001).(4)Western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the expression of the pro-apoptotic factor Bax protein in the sh-circSEC24A group significantly decreased,and the expression of the anti-apoptotic factor Bcl-2 protein increased significantly(P＜0.05);apoptosis and related activating factors cleaved-casepase3 and cleaved-casepase8 protein expressions were both reduced(P＜0.05).(5)ELISA and western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the sh-circSEC24A group had lower levels of matrix metalloproteinase 9 and matrix metalloproteinase 13 protein(P＜0.05).These findings indicated that the expression of circSEC24A was abnormally increased in human synovial fibroblasts induced by interleukin 1β.Knocking down circSEC24A expression could promote the proliferation of human synovial fibroblasts and inhibit apoptosis,inflammatory factor release,and extracellular matrix degradation,suggesting that circSEC24A may be an important intervention target for early osteoarthritis.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To study the clinical efficacy of percutaneous transhepatic cholangial drainage (PTCD) and primary closure of common bile duct after laparoscopic common bile duct exploration (LCBDE) in treatment of choledocholithiasis complicated with moderate and severe cholangitis.Methods:The clinical data of 127 patients with choledocholithiasis complicated with acute cholangitis admitted to Yantai Affiliated Hospital of Binzhou Medical University from January 2021 to August 2023 were retrospectively analyzed. Finally, 45 patients were enrolled, including 20 males and 25 females, aged (71.3±8.2) years. All 45 patients were treated with sequential PTCD and primary closure of common bile duct after LCBDE. The interval from PTCD to primary closure, white blood cell count, total bilirubin, alanine transaminase before and after PTCD, operation time of primary closure, intraoperative blood loss, postoperative retention time of abdominal drainage tube, postoperative hospitalization time, postoperative complications (bile leakage, bleeding, etc.) were analyzed.Results:The serum total bilirubin, alanine transaminase and white blood cell count of 45 patients were (143.2±32.1) μmol/L, (173.6±23.4) U/L, (16.3±2.9)×10 9/L at admission, and (100.5±21.4) μmol/L, (103.5±12.7) U/L, (8.6±1.7) ×10 9/L after PTCD, respectively. The interval between PTCD and primary closure of common bile duct after LCBDE was (4.3±1.1) d, the operative time of primary closure was (123.4±20.5) min, the amount of intraoperative blood loss was (32.6±8.7) ml. The postoperative hospitalization time was (6.8±1.6) d, and the postoperative retention time of abdominal drainage tube was (4.5±1.3) d, and postoperative complications occurred in 7 cases (15.6%), including biliary leakage in 4 cases (8.9%), subxiphoid incision infection in 1 case (2.2%), and effusion in gallbladder fossa with infection in 2 cases (4.4%). Conclusion:The sequential application of PTCD and primary closure of common bile duct after LCBDE in treatment of choledocholithiasis complicated with moderate and severe cholangitis is a safe, effective and minimally invasive method, and primary closure of common bile duct after LCBDE is safe and reliable within 1 week after PTCD.

AIM: To evaluate the combining ability of prostate-specific membrane antigen (PSMA) targeted radioactive drug

Objective:To evaluate the feasibility and efficacy of 68Ga-PSMA PET/CT-guided targeted prostate biopsy for the diagnosis of clinically significant prostate cancer(csPCa). Methods:This retrospective analysis allocated 89 patients with elevated PSA levels between 4.0-20.0 ng/ml to PET group(n=48) or TRUS group(n=41) between September 2017 and June 2019. Patients with PSMA-avid lesions (SUV max≥8.0) underwent PET-TB via a single-puncture percutaneous transgluteal approach (n=19), while patients with negative PSMA-PET underwent systematic TRUS-GB (n=29). Patients in the TRUS group who did not get 68Ga-PSMA PET/CT examination underwent TRUS-GB directly (n=41). The mean age, prostate volume, PSA value of PET group and TURS group were (71.2±9.1) years vs. (68.0±12.0) years, (62.9±29.1)ml vs. (65.4±38.9)ml , 8.8(6.6, 13.6) ng/ml vs. 9.8(7.1, 13.1)ng/ml, respectively (all P>0.05). The diagnostic efficacy and difference of PCa and csPCa between the two groups were compared. PET-TB adopts a new mode of percutaneous gluteus approach and carries out precise image fusion of PSMA-PET/CT and pelvic CT in the same machine and in the same position (prone position). Under the direct guidance of CT, the biopsy is performed with only one precise puncture. Results:PCa and csPCa were detected in 27/89(30.3%)and 20/89(22.5%)in all patients. PET group detected significantly more cases of PCa and csPCa than those of TRUS group [PCa: 41.7%(20/48) vs. 17.1%(7/41), χ2=6.328; csPCa: 33.3%(16/48) vs. 9.8%(4/41), χ2=7.055, P<0.01]. Of 19 patients with PSMA-PET positive, PET-TB detected 16 cases of PCa(84.2%) by a single needle puncture, and the proportions of cancer tissues were ≥80% in 2, 50%-79% in 8, and <50% in 6 cases. Among these, Gleason score was underestimated by biopsy histopathology in 2 patients. Of 3 patients with PET-TB negative, 1 case of low-risk PCa(Gleason 3+ 3) was detected by complementary TRUS-GB. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy of 68Ga-PSMA PET/CT(SUV max≥8.0) for the diagnosis of csPCa were 73.9%(14/19), 93.1%(27/29), 87.5%(14/16), 81.3%(26/32)and 85.4%(41/48), respectively. For PET-TB, only one patient had slight symptoms of haematuria after the puncture, no cases of hematochezia, hemospermia, urinary retention or pelvic infection were observed. Conclusions:68Ga-PSMA PET/CT is a feasible novel puncture technique that may serve as a triage tool for prostate biopsy, and PET-TB may improve the detection rate of csPCa compared with TURS-GB, especially in patients with serum PSA 4.0-20.0 ng/ml.