BACKGROUND: Gout is a chronic disease primarily caused by elevated urate levels, severely affecting joint health. Its global distribution varies, and updated data for China are lacking. This study aimed to analyze the current burden and trends of gout globally and in China, examining the burden by gender, age, and risk factors while providing future predictions. METHODS: This descriptive epidemiological secondary analysis utilized data from the Global Burden of Disease, Injuries, and Risk Factors (GBD) 2021 study. Age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life years (DALYs) rates (ASDR) were used to assess the gout burden. Trends from 1990 to 2021 were analyzed across global regions, genders, and sociodemographic index (SDI) levels. The burden in China was further examined by gender, age, and associated risk factors. The Bayesian age-period-cohort (BAPC) model was used to predict future trends. Gout burden in China and the United States was compared. RESULTS: In 2021, gout affected 57 million people globally, with 9.4 million new cases and 1.75 million DALYs. From 1990 to 2021, the ASIR, ASPR, and ASDR increased by 17.2%, 21.9%, and 21.3%, respectively. Males experienced a significantly higher burden, with greater ASIR, ASPR, and ASDR increasing with higher SDI levels. In China, male ASIR, ASPR, and ASDR were over 2.8 times those of females, and the burden increased with age. In 2021, 31.4% of gout-related DALYs in China were attributed to high body mass index and 7.6% to kidney dysfunction. Between 1990 and 2021, the high body mass index-related burden of gout rose annually for both genders, while the kidney dysfunction-related gout burden remained stable. By 2050, the burden of gout in China is expected to continue increasing, with a slower rise in females and a decline in males after an initial increase. However, the overall burden will remain substantial. In comparison, the gout burden will be higher in the United States than in China. CONCLUSIONS Gout is becoming a significant health burden globally and in China, particularly among Chinese males and older individuals. With the aging population and lifestyle changes exacerbating the issue, effective strategies and measures are essential to prevent or reduce gout-related health issues.
Humans ; Gout/epidemiology* ; Male ; Female ; Incidence ; Middle Aged ; Prevalence ; China/epidemiology* ; Adult ; Risk Factors ; Aged ; Global Burden of Disease ; Disability-Adjusted Life Years ; Young Adult ; Adolescent ; Quality-Adjusted Life Years

Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

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Objective:To evaluate cerebrospinal fluid (CSF) flow dynamics and volume changes of pulsatile tinnitus (PT) patients induced by sigmoid sinus wall dehiscence (SSWD) using MRI.Methods:This was a cross-sectional study. Totally 55 SSWD-PT patients, and 35 age- and sex-matched healthy controls were prospectively enrolled at Beijing Tongren Hospital, Capital Medical University from October 2019 to September 2023. The CSF at the midbrain aqueduct level was analyzed based on phase-contrast MRI to obtain the flow dynamics information. Based on T 1-weighted turbo field echo sequence, the CSF was segmented and the volume of CSF was calculated using ITK-SNAP software. The Mann-Whitney U test was used to compare the differences of each parameter between the two groups. Binary logistic regression was used to analyze the parameters with statistically significant differences to obtain the independent influencing factors of SSWD-PT and establish the combined parameters. Receiver operating characteristic curve analysis was used to evaluate the efficacy of diagnosing SSWD-PT. Results:Compared with controls, the SSWD-PT group showed significantly decreased mean flux (MF), mean velocity, peak velocity( P<0.05), and significantly increased regurgitant fraction (RF), CSF volume ( P<0.05). No significant differences were observed in forward flow volume, backward flow volume, and stroke volume ( P>0.05). The logistic regression results showed that MF ( OR=0.497, 95% CI 0.305-0.808, P=0.005) and RF ( OR=1.809, 95% CI 1.040-3.147, P=0.036) were independent influencing factors of SSWD-PT. The area under the curve (AUC) of MF and RF for diagnosing SSWD-PT were 0.641 (95% CI 0.517-0.766) and 0.675 (95% CI 0.564-0.786), respectively. The AUC of the combination of MF and RF was 0.724 (95% CI 0.614-0.833). Conclusions:SSWD-PT patients have abnormal changes in CSF flow dynamics and volume. The MF and RF demonstrate moderate diagnostic value for diagnosing SSWD-PT.

Objective:To investigate the clinical features of patients with congenital atresia of the oval window (CAOW).Methods:A retrospective analysis was conducted on 7 cases (8 ears) of surgically confirmed CAOW treated at our department from July 2018 to July 2024. Among the cases, 1 patient had bilateral CAOW, and 4 patients had unilateral CAOW combined with other types of ossicular chain malformations in the contralateral ear. We collected and analyzed the clinical data, audiological features, and temporal bone HRCT results of all patients.Results:The 7 patients were diagnosed at ages ranging from 8 to 19 years, with a mean age of (13.2±6.9) years. None of the patients exhibited significant auricular deformities. All presented with conductive hearing loss or mixed hearing loss predominantly of the conductive type, with an intact tympanic membrane. The diagnosis of CAOW was confirmed via endoscopic tympanotomy, revealing a concave oval window area on the medial wall of the tympanic cavity, sealed by a bony plate. All 8 ears exhibited additional ossicular chain deformities. Stapes absence was present in all 8 ears. Partial absence of the incus long process was observed in 3 ears, while, abnormal bony connections between the incus long process and the promontory were seen in 4 ears, 1 ear had a short malleolar handle, 1 ear had a smaller than normal malleus volume. In addition, facial nerve deformities were found in 6 ears, with 4 ears showing bifurcation of the facial nerve and 2 ears showing facial nerve obscuration of the oval window. Pure-tone audiometry revealed that 62.5% (5/8 ears) of patients had air conduction (AC) thresholds≥60 dB preoperatively, with a mean pure-tone average (PTA) of (69.0±11.8) dB HL and a mean air-bone gap (ABG) of (52.0±7.0) dB. The mean AC threshold and ABG were higher in the low-frequency (125-1 000 Hz) range compared to the high-frequency (2 000-8 000 Hz) range (both P<0.05). Preoperative HRCT showed abnormalities in all patients, with 7 ears being diagnosable as CAOW. Although the remaining 1 ear could not be diagnosed as CAOW, stapes and incus long process absence were detected. Conclusion:CAOW is rare in clinical, as the patients with non-progressive conductive hearing loss (AC≥60 dB, ABG≥50 dB) since childhood, intact tympanic membrane without malformations of auricle and external auditory canal, and thick bony plate covered the oval window of the HRCT imaging, CAOW should be highly suspected, which could be confirmed by the exploratory tympanotomy.