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Abstract Background Parkinson's disease (PD) represents a growing global health challenge, with prevalence doubling from 2.5 million cases in 1990 to 6.1 million in 2016, and projections suggesting it will exceed 12 million by 2040. This exponential growth has been termed the "Parkinson's pandemic." China and the United States, which together account for nearly half of the global PD population, have developed markedly different approaches to end-of-life (EOL) care, shaped by their distinct healthcare systems and cultural contexts. Understanding these differences is crucial for developing effective global strategies. This systematic review and meta-analysis comprehensively compares advanced-stage PD care between these two nations to quantify disparities and inform evidence-based policy interventions. Methods We conducted a rigorous systematic review following PRISMA 2020 guidelines, searching six databases (PubMed, Embase, Scopus, Web of Science, CNKI, Wanfang) from January 2015 to October 2025. The timeframe was selected to capture contemporary care patterns following major healthcare reforms in both countries (Affordable Care Act implementation in the US; Healthy China 2030 initiative). Inclusion criteria encompassed peer-reviewed studies reporting on advanced PD (Hoehn-Yahr stage ≥ 3) with outcome measures including survival, quality of life (QoL), palliative care access, caregiver burden, rehabilitation utilization, or healthcare costs. The sample size threshold (n ≥ 100) balanced statistical power with inclusivity. Two independent reviewers screened 3,847 records with excellent agreement (Cohen's κ = 0.82–0.89). Quality assessment employed the Newcastle-Ottawa Scale (NOS ≥ 8 indicating high quality) and ROBINS-I for observational studies, with GRADE criteria determining evidence certainty. Meta-analyses utilized random-effects models with comprehensive heterogeneity assessment (I² statistics, meta-regression) and publication bias evaluation (Egger's test, trim-and-fill analysis). Sensitivity analyses included high-quality studies only and examined the influence of large database studies. Results Our analysis of 42 high-quality studies encompassing over 125,000 patients revealed profound and systematic cross-national disparities across multiple domains. In terms of care access, US patients demonstrated significantly higher hospice enrollment rates (28–35% vs. <1% in China, p < 0.001; HIGH certainty evidence) and greater access to specialized neuropalliative programs (15% of US centers vs. <1% in China). These differences translated into measurable quality of life disparities, with Chinese patients scoring 17.6 points worse on the PDQ-39 scale (95% CI 14.2–21.0; MODERATE certainty, I²=68%), a difference exceeding the minimal clinically important difference nearly four-fold. The burden on families showed equally striking patterns: Chinese families provided 94% of EOL care compared to 61% in the US, resulting in significantly higher caregiver depression rates (47% vs. 32%, OR = 1.89, 95% CI 1.45–2.47) and burden scores (Zarit difference: 10.2 points, 95% CI 7.8–12.6). Access to interventions revealed additional gaps, with only 9.2% of Chinese patients receiving physical therapy versus 14.4% in the US (OR = 0.61, 95% CI 0.49–0.76), and a 5.25-fold disparity in deep brain stimulation access (4.2% vs. 0.8%). Economic analysis demonstrated substantial out-of-pocket burden differences: Chinese families paid 58% of total costs ($4,200 annually) versus 12% for US families ($2,800). Meta-regression identified healthcare system characteristics as the primary driver of these disparities (R²=0.42, p < 0.001). Conclusions This comprehensive analysis reveals that systematic differences in healthcare infrastructure, insurance coverage, and cultural care models produce markedly divergent EOL experiences for PD patients in China versus the United States. These findings have immediate policy implications. For China, we recommend: (1) establishing pilot neuropalliative programs in tertiary centers with phased national expansion; (2) developing caregiver support infrastructure including respite care and training programs; (3) leveraging telemedicine platforms to address urban-rural disparities. For the United States, priorities include: (1) addressing racial disparities in rehabilitation access through culturally competent outreach; (2) expanding Medicare coverage for maintenance therapy; (3) earlier integration of neuropalliative care. Implementation science research is urgently needed to test culturally adapted interventions. As global PD prevalence accelerates, lessons from this bilateral comparison provide a framework for other nations confronting similar challenges in neurological care delivery.

Interleukin (IL)-17 is a T helper 17 cytokine implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Although IL-17A has a well-established role in murine pulmonary fibrosis models, its role in the tissue remodeling and fibrosis occurring in idiopathic pulmonary fibrosis (IPF) and RA-associated interstitial lung disease (RA-ILD) is not very well defined. To address this question, we utilized complimentary studies to determine responsiveness of human normal and pathogenic lung fibroblasts to IL-17A and used lung biopsies acquired from patients with IPF and RA-ILD to determine IL-17A receptor (IL-17RA) expression. Both normal and pathogenic IPF lung fibroblasts express functional IL-17RA and respond to IL-17A stimulation with cell proliferation, generation of extracellular matrix (ECM) proteins, and induction of myofibroblast transdifferentiation. Small interfering RNA (siRNA) silencing of IL-17RA attenuated this fibroblast response to IL-17A on ECM production. These fibroblast responses to IL-17A are dependent on NF-κB-mediated signaling. In addition, inhibiting Janus activated kinase (JAK) 2 by either siRNA or a selective pharmacological inhibitor, AZD1480—but not a JAK1/JAK3 selective inhibitor, tofacitinib—also significantly reduced this IL-17A-induced fibrogenic response. Lung biopsies of RA-ILD patients demonstrate significantly higher IL-17RA expression in areas of fibroblast accumulation and fibrosis, compared with either IPF or normal lung tissue. These observations support a direct role for IL-17A in lung fibrosis that may be particularly relevant in the context of RA-ILD.

ObjectivesTo prospectively evaluate the diagnostic performance of 3‐dimensional (3D) shear wave elastography (SWE) for assessing thyroid nodules.MethodsA total of 176 surgically or cytologically confirmed thyroid nodules (63 malignant and 113 benign) in 176 patients who had undergone conventional ultrasound (US), 2‐dimensional (2D) SWE, and 3D SWE examinations were included in this study. Quantitative elasticity values (mean elasticity, maximum elasticity, and standard deviation of elasticity of a large region of interest and mean elasticity of a 2‐mm region of interest) were measured on 2D and 3D SWE. Diagnostic performances of conventional US, 2D SWE, and 3D SWE were assessed. The role of 2D and 3D SWE in reducing unnecessary fine‐needle aspiration (FNA) for nodules with low suspicion was also evaluated.ResultsThe diagnostic performances in terms of the area under the receiver operating characteristic curve were 0.612 for conventional US, 0.836 for 2D SWE (P < .001 in comparison with conventional US), and 0.839 for 3D SWE (P < .001 in comparison with conventional US). The mean elasticity achieved the highest diagnostic performance in 2D SWE, whereas the standard deviation of elasticity achieved the highest performance in 3D SWE, although no significant difference was found between them (P > .05). Three‐dimensional SWE increased the specificity in comparison with 2D SWE (88.5% versus 82.3%; P = .039). For the 37 nodules with low suspicion on conventional US imaging, 2D SWE was able to avoid unnecessary FNA in 77.1% (27 of 35) of benign nodules, and 3D SWE further increased the number to 88.6% (31 of 35).ConclusionsThree‐dimensional SWE is a useful tool for predicting thyroid nodule malignancy and reducing unnecessary FNA procedures in thyroid nodules with low suspicion of malignancy.

Abstract The androgen receptor (AR) is the principal target for treatment of non–organ-confined prostate cancer (PCa). Androgen deprivation therapies (ADT) directed against the AR ligand–binding domain do not fully inhibit androgen-dependent signaling critical for PCa progression. Thus, information that could direct the development of more effective ADTs is desired. Systems and bioinformatics approaches suggest that considerable variation exists in the mechanisms by which AR regulates expression of effector genes, pointing to a role for secondary transcription factors. A combination of microarray and in silico analyses led us to identify a 158-gene signature that relies on AR along with the transcription factor SRF (serum response factor), representing less than 6% of androgen-dependent genes. This AR-SRF signature is sufficient to distinguish microdissected benign and malignant prostate samples, and it correlates with the presence of aggressive disease and poor outcome. The AR-SRF signature described here associates more strongly with biochemical failure than other AR target gene signatures of similar size. Furthermore, it is enriched in malignant versus benign prostate tissues, compared with other signatures. To our knowledge, this profile represents the first demonstration of a distinct mechanism of androgen action with clinical relevance in PCa, offering a possible rationale to develop novel and more effective forms of ADT. Cancer Res; 71(5); 1978–88. ©2011 AACR.

AbstractDo some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]–matched, n = 941) or HLA-identical sibling donor (n = 3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P < .001) and relapse (RR, 1.50; P < .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P < .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect.

Purpose Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.