BACKGROUND: Parkinson's disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data. METHODS: Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes. RESULTS: GBD 2021 estimated 508,378 (95% UI: 430,499-592,748) incident cases of PD, 92,035 (95% UI: 75,908-108,133) deaths, and 2,159,514 (95% UI: 1,826,196-2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004-2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. CONCLUSIONS The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.
Humans ; Parkinson Disease/mortality* ; China/epidemiology* ; Global Burden of Disease ; Male ; Incidence ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Quality-Adjusted Life Years ; Aged, 80 and over ; Cost of Illness ; Adolescent ; Pattern Analysis, Machine

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective: To explore the mediating effect of parental hostile attribution bias on depression and anxiety between parents and children, so as to provide the reference for the promotion of children's mental health. Methods: Students of grades 2-6 in two public primary schools in Linping District, Hangzhou City and their parents were investigated using stratified sampling method in November 2022. Emotions of children were surveyed using Depression Self-Rating Scale for Child (DSRSC) and Screen for Child Anxiety Related Emotional Disorders (SCARED), while emotions and hostile attribution bias of parents were surveyed using Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS) and Social Cognitive Screening Questionnaire (SCSQ). Mediating effect of parental hostile attribution bias on depression and anxiety between parents and children was analyzed using a structural equation model. Results: Totally 300 questionnaires were allocated, and 263 valid questionnaires were recovered, with an effective rate of 87.67%. There were 137 boys (52.09%), and 126 girls (47.91%), with a mean age of (9.95±1.44) years. There were 69 fathers and 194 mothers investigated. The prevalence of depression among parents was 27.00%, the prevalence of anxiety among parents was 4.18%, and the median score of hostile attribution bias was 1.00 (interquartile range, 2.00). The prevalence of depression among children was 11.03%, and the prevalence of anxiety among children was 29.66%. Parents' depression and anxiety affected children's depression and anxiety directly (effect value=0.270, 95%CI: 0.131-0.436), and also indirectly affected children's depression and anxiety by increasing their hostile attribution bias (effect value=0.028, 95%CI: 0.004-0.082), with the mediating effect contributed 9.40% of the total effect. Conclusion Parents' depression and anxiety affect children's depression and anxiety directly or indirectly through hostile attribution bias.

Objective:To analyze the effect and main gaps of each stage in the AIDS prevention cascade for men who have sex with men (MSM) provided in intervention projects supported by the China AIDS Fund for non-governmental organizations (CAFNGO) and provide suggestions to improve the quality of cascade services and project management.Methods:Data were collected through the CAFNGO management information system and field interviews to analyze the differences in the number of MSM receiving HIV testing and confirming tests, the newly reported patients, and the number of antiviral treatment (ART) referrals of newly established reported patients among different social organization service areas. A service chain chart was also drawn.Results:Between 2016 and 2020, 1 508 MSM intervention projects were funded by CAFNGO, including 1 183 234 MSM being mobilized to receive HIV testing. However, only 68.8% (1 183 234/1 719 139) of the testing capacity of social organizations was covered by these projects. As a result, 55 783 HIV-positive MSM were detected in preliminary screening, and only 86.6% (48 327/55 783) received confirming tests. The proportion of newly reported infections was 3.8% (45 347/1 183 234). The ratio of antiviral treatment (ART) referrals for newly reported patients between 2017 and 2020 was 89.8% (32 719/36 444). 75.8%(1 143/1 508) of total MSM intervention projects were implemented by community-based organizations (Non-registered civil affairs departments). In comparison, organizations registered in civil affairs departments took up 24.2% (365/1 508) of the total MSM intervention projects. No significant difference was noticed in the proportion of newly reported infected (3.8% and 3.8%) and the ratio of ART referrals (89.7% and 89.9%) between community-based organizations and registered organizations' projects. But these two proportions are significantly different between these two types of organizations in some areas in China.Conclusions:The AIDS prevention cascade established in CAFNGO has effectively promoted the early detection and treatment of infected MSM. However, CAFNGO needs more financial support to extend testing coverage for MSM. Meanwhile, confirmation testing for positives in preliminary screening and ART referrals needs to be improved for newly reported patients. In addition, various capacity building needs to be provided for different social organizations.

Objective To evaluate the narrow-band imaging (NBI) in differential diagnosis of colo-rectal proliferative lesions. Methods Suspected lesions in colon were examined with white light and NBI colonoscopy, respectively. The ensitivity and specificity in diagnosing colorectal inflammatory hyperplasia, adenoma, early cancer and advanced cancer were compared between NBI and conventional colonoscopy with reference to pathology as gold standard. The pit patterns and the surface microvessels of the lesions were also determined and scored with NBI combined with magnifying endoscopy, and were compared with pathological diagnosis. Results (1) A total of 368 lesions were detected in 280 patients with conventional colonoscopy and NBI. The sensitivity and specificity of NBI in differential diagnosis of colorectal lesions were superior to those of conventional colonoscopy. (2) The pit patterns of colorectal inflammatory hyperplasia were mainly type Ⅰ and Ⅱ , while in adenomas were mainly type Ⅱ and Ⅲ (94. 2%). The pit patterns of early cancer were type Ⅲ (18. 8%), Ⅳ (56. 3%) and Ⅴ (25.0%), and those of advanced cancer were mainly type Ⅴ (94. 0%). (3) The average scores of surface microvesseis of colorectal inflammatory hyperplasia, ade-noma, early cancer and advanced cancer were 1.35 ± 0. 72, 3. 86 ±1.07, 6. 52±2. 59 and 11.42 ± 3.59, respectively. Scores over 6. 5 was a strong indicator of malignant lesions. Conclusion NBI is superior to conventional eolonoscopy in differential diagnosis of colorectal lesions. Observing pit patterns and microves-sels of the lesion with combination of NBI and magnifying endoscopy is helpful in diagnosis.