Acute vestibular syndrome（AVS） accounts for about 5% of walk clinic, and 20% of neurology consultations in the emergency department. A central acute vestibular syndrome is of high-risk vertigo disorders or potentially life-threaten disorders. Some of the central vestibular vertigo, especially brainstem or cerebellar ischemic infarction, can be misdiagnosed due to the absence of focal neurological symptoms and signs. In the past decade, the diagnosis mode and diagnosis pathway of vestibular syndrome have been made great progress. The HINTS examination battery reported by Kattah et al. （2009）, the STANDING examination battery reported by Vanni et al. （2014） as well as the "Big five" step examination procedure reported by Brandt et al. （2017） have been used widely to identify stroke in clinic. The TiTrATE proposed by Newman Toker and Edlow（2015） as well as the ATTEST proposed by Gurley and Edlow（2019） have promoted the accuracy for AVS diagnosis. However, only about 50% of patients with cerebellar ischemic infarction have spontaneous nystagmus. The sensitivity of direction-changing nystagmus in diagnostic predicting stroke in acute vestibular syndrome was only 38%. The diagnostic predictive sensitivity of AICA stroke was only 62% when the horizontal head pulse test were normal. Therefore, the bed-side test battery for differentiating acute isolated vertigo as well as the diagnosis approach of AVS need to be further improved. Based on the SCD diagnosis strategy and the differentiating pathway for vestibular disorders proposed by the author, I propose further in this paper the step-rised SCD strategy for the acute vestibular syndrome, and the ABC mode for differentiating central vestibular vertigo[A: Associated neurological deficit（or: with headache=HAND）; B: Eye（E³） GAP examination battery; C: Combined warning battery of A³B²C²D²E³], as well as the differential diagnosis pathway of acute vestibular diseases. The history questioning of associated neurological deficit and the examining batteries for acute central vestibular disorders can be summarized as an illogical English phrase "HAND-Eye（E³） GAP" for memory.
Humans ; Vestibular Diseases/diagnosis* ; Vertigo/diagnosis* ; Diagnosis, Differential ; Nystagmus, Pathologic/diagnosis* ; Acute Disease

Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

[Purpose]To analyze the incidence and changing trends of elderly breast cancer(de-fined as diagnosis at age ≥ 60 years old)in China and globally from 1990 to 2021,and to predict its trends from 2022 to 2035.[Methods]Data on the number of new cases and crude incidence rate of elderly breast cancer in China and globally were extracted from the 2021 Global Burden of Disease Study(GBD)database.The age-standardized incidence rate(ASIR)was calculated by sex and age group.The Joinpoint regression model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC),to describe the incidence trend of elderly breast cancer from 1990 to 2021.The Bayesian age-period-cohort(BAPC)model was applied to predict the incidence of elderly breast cancer from 2022 to 2035.[Results]From 1990 to 2021,the number of new breast cancer cases among elderly individuals globally increased from 416 444 to 1 023 776,while in China,the number rose from 26 371 to 158 085.The ASIR increased from 89.04/105 to 94.73/105 globally and from 27.24/105 to 58.40/105 in China.By sex,the ASIR of el-derly females increased from 155.19/105 to 170.54/105 globally and from 49.13/105 to 106.00/105 in China;the ASIR of elderly males increased from 2.78/105 to 4.72/105 globally and from 1.69/105 to 6.81/105 in China.By age group,from 1990 to 2021,the incidence rates of breast cancer in elderly female and male both peaked in the age group of 85～89 years old globally.In China,the most significant increases in incidence rates were observed in the age group of 60～64 years old for elderly females and the age group of 70～74 years old for elderly males;these two age groups had the highest incidence rates in their respective sexes in 2021.Joinpoint analysis showed that the ASIR of elderly breast cancer in China presented a continuous upward trend from 1990 to 2021(AAPC=2.51％),with the fastest growth during 2016-2019(APC=5.14％).The global ASIR showed only a slight fluctuating upward trend(AAPC=0.20％),with significant increases only during 1990-1995 and 2003-2010.Predictions from the BAPC model indicated that by 2035,the global ASIR of elderly breast cancer would reach 107.84/105(192.26/105 for females and 6.02/105 for males),while the ASIR in China would reach 104.35/105(188.08/105 for females and 13.32/105 for males).[Conclusion]From 1990 to 2021,the incidence of elderly breast cancer showed an upward trend both in China and globally,with a particularly pronounced increase in elderly male.The disease burden of elderly breast cancer in China is expected to continue increasing in the future,necessi-tating strengthened primary and secondary prevention measures,as well as optimized screening programs for the elderly population to reduce disease risks and improve prognosis.

Objective:Primary sclerosing cholangitis (PSC) is a rare autoimmune disease. This study aims to describe the baseline characteristics and clinical outcomes of Chinese PSC patients and explore risk factors associated with prognosis, addressing the lack of long-term prognostic analysis in China.Methods:Clinical data of PSC patients were retrospectively collected from May 2009 to June 2023 in Beijing Friendship Hospital Affiliated to Capital Medical University, and patient follow-up was conducted through outpatient visits, telephone calls, and medical record reviews. The Cox proportional hazards model and the Kaplan-Meier method were employed to identify risk factors and estimate transplant-free survival.Results:A total of 65 PSC patients were enrolled, with male patients accounting for 50.8% and an average age of onset of 44 years. The disease types primarily included large duct PSC (57.9%) and whole duct PSC (22.8%). Most patients (78.5%) sought medical attention due to symptoms, with common clinical manifestations including jaundice (32.3%), fatigue (23.1%), abdominal discomfort (21.5%), pruritus (16.9%), and fever (10.8%). A total of 19 patients (29.2%) had concomitant ulcerative colitis. Compared to large duct PSC or whole duct PSC, small duct PSC showed a lower proportion of concomitant ulcerative colitis ( P<0.001) and milder baseline disease severity. After a median follow-up of 29 months (interquartile range: 11,53), 19 patients experienced liver transplantations and/or liver disease-related deaths. The overall 2-year and 5-year transplant-free survival rates for PSC patients were 76.0% and 59.5%, respectively. Elevated bile acid levels were identified as an independent risk factor for poor outcomes in PSC patients. Conclusion:The study population of Chinese PSC patients predominantly consisted of middle-aged males, characterized by a low ratio of asymptomatic cases, a low incidence of associated inflammatory bowel disease, and a low rate of transplant-free survival. Elevated bile acid level was identified as an independent risk factor for poor outcomes in PSC patients.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

[Purpose]To analyze the incidence and changing trends of elderly breast cancer(de-fined as diagnosis at age ≥ 60 years old)in China and globally from 1990 to 2021,and to predict its trends from 2022 to 2035.[Methods]Data on the number of new cases and crude incidence rate of elderly breast cancer in China and globally were extracted from the 2021 Global Burden of Disease Study(GBD)database.The age-standardized incidence rate(ASIR)was calculated by sex and age group.The Joinpoint regression model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC),to describe the incidence trend of elderly breast cancer from 1990 to 2021.The Bayesian age-period-cohort(BAPC)model was applied to predict the incidence of elderly breast cancer from 2022 to 2035.[Results]From 1990 to 2021,the number of new breast cancer cases among elderly individuals globally increased from 416 444 to 1 023 776,while in China,the number rose from 26 371 to 158 085.The ASIR increased from 89.04/105 to 94.73/105 globally and from 27.24/105 to 58.40/105 in China.By sex,the ASIR of el-derly females increased from 155.19/105 to 170.54/105 globally and from 49.13/105 to 106.00/105 in China;the ASIR of elderly males increased from 2.78/105 to 4.72/105 globally and from 1.69/105 to 6.81/105 in China.By age group,from 1990 to 2021,the incidence rates of breast cancer in elderly female and male both peaked in the age group of 85～89 years old globally.In China,the most significant increases in incidence rates were observed in the age group of 60～64 years old for elderly females and the age group of 70～74 years old for elderly males;these two age groups had the highest incidence rates in their respective sexes in 2021.Joinpoint analysis showed that the ASIR of elderly breast cancer in China presented a continuous upward trend from 1990 to 2021(AAPC=2.51％),with the fastest growth during 2016-2019(APC=5.14％).The global ASIR showed only a slight fluctuating upward trend(AAPC=0.20％),with significant increases only during 1990-1995 and 2003-2010.Predictions from the BAPC model indicated that by 2035,the global ASIR of elderly breast cancer would reach 107.84/105(192.26/105 for females and 6.02/105 for males),while the ASIR in China would reach 104.35/105(188.08/105 for females and 13.32/105 for males).[Conclusion]From 1990 to 2021,the incidence of elderly breast cancer showed an upward trend both in China and globally,with a particularly pronounced increase in elderly male.The disease burden of elderly breast cancer in China is expected to continue increasing in the future,necessi-tating strengthened primary and secondary prevention measures,as well as optimized screening programs for the elderly population to reduce disease risks and improve prognosis.

Objective:Primary sclerosing cholangitis (PSC) is a rare autoimmune disease. This study aims to describe the baseline characteristics and clinical outcomes of Chinese PSC patients and explore risk factors associated with prognosis, addressing the lack of long-term prognostic analysis in China.Methods:Clinical data of PSC patients were retrospectively collected from May 2009 to June 2023 in Beijing Friendship Hospital Affiliated to Capital Medical University, and patient follow-up was conducted through outpatient visits, telephone calls, and medical record reviews. The Cox proportional hazards model and the Kaplan-Meier method were employed to identify risk factors and estimate transplant-free survival.Results:A total of 65 PSC patients were enrolled, with male patients accounting for 50.8% and an average age of onset of 44 years. The disease types primarily included large duct PSC (57.9%) and whole duct PSC (22.8%). Most patients (78.5%) sought medical attention due to symptoms, with common clinical manifestations including jaundice (32.3%), fatigue (23.1%), abdominal discomfort (21.5%), pruritus (16.9%), and fever (10.8%). A total of 19 patients (29.2%) had concomitant ulcerative colitis. Compared to large duct PSC or whole duct PSC, small duct PSC showed a lower proportion of concomitant ulcerative colitis ( P<0.001) and milder baseline disease severity. After a median follow-up of 29 months (interquartile range: 11,53), 19 patients experienced liver transplantations and/or liver disease-related deaths. The overall 2-year and 5-year transplant-free survival rates for PSC patients were 76.0% and 59.5%, respectively. Elevated bile acid levels were identified as an independent risk factor for poor outcomes in PSC patients. Conclusion:The study population of Chinese PSC patients predominantly consisted of middle-aged males, characterized by a low ratio of asymptomatic cases, a low incidence of associated inflammatory bowel disease, and a low rate of transplant-free survival. Elevated bile acid level was identified as an independent risk factor for poor outcomes in PSC patients.

Vertigo （or dizziness） is one of the most common symptoms in clinical practice. The misdiagnosis rate of vertigo diseases is high due to the factors that vertigo disorders involve multiple systems and organs throughout the body with a wide range of pathogenesis, and different kind of vertigo diseases often present with overlapping clinical presentation. In recent years, scholars have conducted many explorations in the diagnosis model of vertigo disorders, the identification model of high-risk central vertigo, or the combination of diagnostic tests such as the TiTrATE diagnostic model for vertigo disorders （Newman-Toker and Edlow, 2015）, the ATTEST differential diagnosis model for acute vertigo （Gurley and Edlow, 2019）; the application of the ABCD2 score to assess the risk of high-risk vertigo （Navi et al, 2012）, and the "TriAGe+" score to assess the risk of stroke in vertigo patients （Kuroda et al, 2017）; HINTS battery （Kattah et al, 2009）, HINTS+ battery （Newman-Toker et al, 2013）, and STANDING battery （Vanni et al, 2014） for acute serious vestibular disorders. These diagnostic approaches are immensely beneficial in enhancing the accuracy of vertigo diagnosis, as well as for identifying high-risk central vertigo with reducing the misdiagnosis of vertigo. Based on clinical experience, with referring to the diagnostic approaches mentioned above, the author propose the SCD programmatic diagnostic strategy for vertigo disorders[Strategy 1: Classification of vertigo syndromes （syndromes, S）; Strategy 2: Identify/diagnose high-risk central vertigo （central, C）; Strategy 3: differential diagnosis of peripheral vertigo （disease, D） ] and the A·E³GAP·AT differentiation battery and A²B²C²D²E³ alarm battery for dangerous central vertigo as well as targeted identifying and examining of E³GAP battery for central vertigo in five steps.The SCD programmatic diagnostic strategy for vertigo disorders is beneficial for clinicians to grasp diagnostic approach and pay special attention to dangerous central vertigo, while mastering the differential diagnosis model of dangerous central vertigo as well as the rapid diagnostic approach of peripheral vertigo.
Humans ; Vertigo/diagnosis* ; Diagnosis, Differential ; Dizziness/etiology*