Qinghua Ma

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.

We aimed to assess the association of cognitive dysfunction with health-related quality of life (HRQOL) among older adults in China. We analyzed community-based cross-sectional data of 5,557 Chinese individuals aged 60 years and above in the Weitang Geriatric Diseases Study. Cognitive dysfunction and HRQOL were assessed using the Abbreviated Mental Test (AMT) and the European Quality of Life-5 dimensions (EQ-5D), respectively. We estimated the impacts of cognitive dysfunction on the EQ-5D index and visual analogue scale (VAS) scores using linear regression models, and the association between cognitive dysfunction and self-reported EQ-5D health problems using logistic regression models. The EQ-5D index and VAS scores were significantly lower for individuals with cognitive dysfunction than their counterparts. After controlling for covariates, the differences in EQ-5D index and VAS scores between individuals with and without cognitive dysfunction were -0.016 (95% confidence interval [CI]: -0.024, -0.008), and -3.4 (95% CI: -4.5, -2.4), respectively. Cognitive dysfunction was associated with reporting of problems in pain/discomfort (odds ration [OR]: 1.37; 95% CI: 1.12, 1.69), and anxiety/depression (OR: 2.13; 95% CI: 1.41, 3.23). The negative impact on HRQOL increased with the severity of cognitive dysfunction. The results indicate cognitive dysfunction was associated with worse HRQOL in older adults.

OBJECTIVE: To determine health-state utility (HSU) values for type 2 diabetes (T2D) patients with various clinical conditions in China, and to examine how these conditions are correlated with HSU values. METHODS: A consecutive sample of T2D patients was recruited from a tertiary hospital in Suzhou, China. HSU values of T2D patients were measured using the EQ-5D-5L, a new version of the EQ-5D. T2D patients' clinical data were collected from the survey and the clinical examination; sociodemographic data were obtained from the survey. Ordinary least square (OLS) models were employed to estimate the impact of clinical conditions on HSU values controlling for sociodemographic conditions. Nonparametric biased-corrected and accelerated (BCA) bootstrap was used to calculate the 95% confidence intervals (CIs). RESULTS: A total of 289 T2D patients provided data. The mean HSU value of the sample was 0.876 (standard deviation: 0.14), with a median of 0.895 (range: -0.063 to 1). Using the OLS model and BCA bootstrap, the impact of significant conditions on HSU values and 95% CIs are as follows: neuropathy (-0.057, [-0.093, -0.017]), heart disease (-0.074, [-0.122, -0.018]), cerebrovascular disease (-0.160, [-0.287, -0.030]), and increasing diabetes duration (-0.004, [-0.007, -0.001]). CONCLUSION: The HSU values estimated can be used to assess the cost-effectiveness of health care interventions for T2D patients in China.

BACKGROUND: Prevalence estimates of heterotopic ossification (HO) following cervical artificial disc replacement (ADR) varied widely in previous studies. We conducted a systematic review and meta-analysis to summarize its point prevalence. METHODS: Electronic searches of PubMed, Web of Science, Embase, and Cochrane Library databases were conducted to identify studies that reported prevalence of HO. Definitions of HO and severe HO were based on McAfee grading system. Random-effects model was used to estimate the pooled prevalence. We conducted subgroup analyses according to the different length of follow-up time, and performed univariate metaregression analyses to explore the effects of potential variables on the overall prevalence. RESULTS: A total of 38 studies were included in this study. The pooled data showed that the prevalence of HO after cervical ADR within the 1 to 2 years, 2 to 5 years, and 5 to10 years of follow-up was 38.0% (95% confidence interval [CI], 30.2%-46.5%), 52.6% (95% CI, 43.1%-61.9%), and 53.6% (95% CI, 40.0%-66.7%), respectively, while the prevalence of severe HO was 10.9% (95% CI, 9.0%-13.2%), 22.2% (95% CI, 15.5%-30.7%), and 47.5% (95% CI, 30.0%-65.8%), respectively. Follow-up time was positively associated with the prevalence of severe HO (P < .01), and the 1-month growth of mean follow-up went with 0.63% increase of severe HO. CONCLUSION: This meta-analysis reported data on the prevalence of HO and severe HO after cervical ADR, and provided information on its process of development. These should be useful to enable surgeons and patients to gain a better understanding of HO after cervical ADR.