Mannosylated Fluoropolypeptide Nanovaccines Remodeling Tumor Immunosuppressive Microenvironment to Achieve Highly Potent Cancer Immunotherapy.

It is challenging for nanovaccines (NVs) to effectively deliver antigens/neoantigens to prime specifically potent immunities and remodel immunosuppressive tumor microenvironment (TME) for combating immune "cold" cancers. Herein, a novel kind of mannosylated fluoropolypeptide NVs of MFPCOFG (i.e., mannosylated fluoropoly(D,L-cysteine) ovalbumin-loaded Fe2+-gallic acid) is designed that synergistically integrates triple antigen-metal-thermoimmunity to remodel immunosuppressive TME and achieve highly potent immunities. MFPCOFG plus near-infrared irradiation (NIR) effectively facilitated antigen uptake and escape, induced the maturation and antigen cross-presentations of dendritic cells and macrophages, polarized anti-inflammatory macrophage phenotype M2 into tumoricial M1, primed potent CD4+/CD8+T cells responses, proinflammatory cytokines secretion and immune memory effects, showcasing triple antigen-metal-thermoimmunity outperforming combo/mono-immunity. Importantly, both MFPCOFG + NIR and personalized NVs can remarkably enhance the tumor infiltration of CD4+/CD8+T and NK cells to boost potent immunities and long-lasting memory effects, reduce regulatory T (Tregs) and M2 to remodel immunosuppressive TME in B16-OVA and 4T1 models, achieving superior tumor prevention, ablation, and tumor relapse and metastasis inhibition, as further orchestrated with anti-PD-1. Consequently, this work opens up a new avenue to design biocompatible polypeptide nanovaccines with potent immune-priming and TME-remodeling capabilities, holding great potentials to combat immune "cold" cancers with clinic-used anti-PD-1 for cancer immunotherapy and personalized immunotherapy.

Inequalities in health care use among patients with arthritis in China: using Andersen's Behavioral Model.

BACKGROUND: This study sought to assess socioeconomic-related inequalities in health care use among arthritis patients in China and to analyze factors associated with this disparity. METHODS: This study used data from the 2018 China Health and Retirement Longitudinal Study. 3255 arthritis patients were included. The annual per capita household expenditure was used to divide individuals into five categories. We calculated actual, need-predicted, and need-standardized distributions of health care use by socioeconomic groups among people with arthritis. The concentration index (Cl) was used to assess inequalities in health service use. Influencing factors of inequalities were measured with the decomposition method. RESULTS: The outpatient and inpatient service use rates among 3255 arthritis patients were 23.13% and 21.41%, respectively. The CIs for actual outpatient and inpatient services use were 0.0449 and 0.0985, respectively. The standardized CIs for both outpatient and inpatient services use increase (CI for outpatient services use = 0.0537; CI for inpatient services use = 0.1260), indicating the emergence of a significant pro-rich inequity. Annual per capita household expenditure was the chief positive contributor to inequity for both outpatient (104.45%) and inpatient services use (105.74%), followed by infrequently social interaction (22.60% for outpatient services use) and Urban Employee Basic Medical Insurance (UEBMI) (11.90% for inpatient services use). By contrast, UEBMI also provided a high negative contribution to outpatient services use (-15.99%). CONCLUSIONS: There are significant pro-rich inequalities in outpatient and inpatient services use among patients with arthritis, which are exacerbated by widening economic gaps. Interventions to address inequalities should start by improving the economic situation of lower socioeconomic households.

The costs, health and economic impact of air pollution control strategies: a systematic review.

BACKGROUND: Air pollution poses a significant threat to global public health. While broad mitigation policies exist, an understanding of the economic consequences, both in terms of health benefits and mitigation costs, remains lacking. This study systematically reviewed the existing economic implications of air pollution control strategies worldwide. METHODS: A predefined search strategy, without limitations on region or study design, was employed to search the PubMed, Scopus, Cochrane Library, Embase, Web of Science, and CEA registry databases for studies from their inception to November 2023 using keywords such as "cost-benefit analyses", "air pollution", and "particulate matter". Focus was placed on studies that specifically considered the health benefits of air pollution control strategies. The evidence was summarized by pollution control strategy and reported using principle economic evaluation measurements such as net benefits and benefit-cost ratios. RESULTS: The search yielded 104 studies that met the inclusion criteria. A total of 75, 21, and 8 studies assessed the costs and benefits of outdoor, indoor, and mixed control strategies, respectively, of which 54, 15, and 3 reported that the benefits of the control strategy exceeded the mitigation costs. Source reduction (n = 42) and end-of-pipe treatments (n = 15) were the most commonly employed pollution control methodologies. The association between particulate matter (PM) and mortality was the most widely assessed exposure-effect relationship and had the largest health gains (n = 42). A total of 32 studies employed a broader benefits framework, examining the impacts of air pollution control strategies on the environment, ecology, and society. Of these, 31 studies reported partially or entirely positive economic evidence. However, despite overwhelming evidence in support of these strategies, the studies also highlighted some policy flaws concerning equity, optimization, and uncertainty characterization. CONCLUSIONS: Nearly 70% of the reviewed studies reported that the economic benefits of implementing air pollution control strategies outweighed the relative costs. This was primarily due to the improved mortality and morbidity rates associated with lowering PM levels. In addition to health benefits, air pollution control strategies were also associated with other environmental and social benefits, strengthening the economic case for implementation. However, future air pollution control strategy designs will need to address some of the existing policy limitations.

The cost-effectiveness of a co-managed care model for elderly hip fracture patients in China: a modelling study.

Background: The clinical effectiveness of multidisciplinary co-managed care for hip fracture patients in China has been demonstrated in a multicenter non-randomized controlled study. This study aims to estimate the cost-effectiveness of the co-managed care. Methods: The study is based on a multicenter clinical trial (n = 2071) in China. We developed a state transition microsimulation model to estimate the cost-effectiveness of the co-managed care compared with usual care for hip fracture patients from healthcare system perspective. The costs incorporated into the model included hospitalization costs, post-discharge expenses, and secondary fracture therapy costs. Effectiveness was measured using quality-adjusted life years (QALYs). Costs and effects were discounted at 5% annually. A simulation cycle length of 1-year and a lifetime horizon were employed. The cost-effectiveness threshold was established at USD 37,118. To address uncertainties, one-way deterministic sensitivity analysis and probabilistic sensitivity analysis were conducted. Findings: In the base case analysis, the co-managed care group had a lifetime cost of USD 31,571 and achieved an effectiveness of 3.22 QALYs, whereas the usual care group incurred a cost of USD 27,878 and gained 2.85 QALYs. The incremental cost-effectiveness ratio was USD 9981 per QALY gained; thus the co-managed care model was cost-effective. The cost-effectiveness was sensitive to the age of having hip fractures and hospitalization costs in the intervention group. Interpretation: The co-managed care in hip fracture patients represents value for money, and should be scaled up and prioritized for funding in China. Funding: The study is supported by Capital's Funds for Health Improvement and Research (2022-1-2071, 2018-1-2071).

A nomogram to predict intracranial hypertension in moderate traumatic brain injury patients.

OBJECTIVE: Patients with moderate traumatic brain injury (TBI) are under the threat of intracranial hypertension (IHT). However, it is unclear which moderate TBI patient will develop IHT and should receive intracranial pressure (ICP)-lowering treatment or invasive ICP monitoring after admission. The purpose of the present study was to develop and validate a prediction model that estimates the risk of IHT in moderate TBI patients. METHODS: Baseline data collected on admission of 296 moderate TBI patients with Glasgow Coma Scale (GCS) score of 9-11 was collected and analyzed. Multi-variable logistic regression modeling with backward stepwise elimination was used to develop a prediction model for IHT. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated. Finally, the prediction model was validated in a separate cohort of 122 patients from 3 hospitals. RESULTS: Four independent prognostic factors for IHT were identified: GCS score, Marshall head computed tomography score, injury severity score and location of contusion. The C-statistic of the prediction model in internal validation was 84.30% (95% confidence interval [CI]: 0.794-0.892). The area under the curve for the prediction model in external validation was 82.80% (95% CI: 0.747∼0.909). CONCLUSIONS: A prediction model based on baseline parameters was found to be highly sensitive in distinguishing moderate TBI patients with GCS score of 9-11 who would suffer IHT. The high discriminative ability of the prediction model supports its use in identifying moderate TBI patients with GCS score of 9-11 who need ICP-lowering therapy or invasive ICP monitoring.

[Magnetic induced phase shift detection system based on a novel sensor for cerebral hemorrhage].

The main magnetic field, generated by the excitation coil of the magnetic induction phase shift technology detection system, is mostly dispersed field with small field strength, and the offset effect needs to be further improved, which makes the detection signal weak and the detection system difficult to achieve quantitative detection, thus the technology is rarely used in vivo experiments and clinical trials. In order to improve problems mentioned above, a new Helmholtz birdcage sensor was designed. Stimulation experiment was carried out to analyze the main magnetic field in aspects of intensity and magnetic distribution, then different bleeding volume and bleeding rates experiments were conducted to compared with traditional sensors. The results showed that magnetic field intensity in detection region was 2.5 times than that of traditional sensors, cancellation effect of the main magnetic field was achieved, the mean value of phase difference of 10 mL rabbit blood was (-3.34 ± 0.21)°, and exponential fitting adjusted R 2 between phase difference and bleeding volumes and bleeding rates were both 0.99. The proposed Helmholtz birdcage sensor has a uniform magnetic field with a higher field strength, enable more accurate quantification of hemorrhage and monitored change of bleeding rates, providing significance in magnetic induced technology research for cerebral hemorrhage detection.

Sociodemographic and health system factors associated with variations in hospitalization costs for rheumatic diseases in adults aged 45 years and older: A cross-sectional study of provincial health accounts in Jiangsu Province, China.

AIM: To report the cost of hospitalization and the associated risk factors for rheumatic diseases in middle-aged and elderly patients in China. METHODS: The study participants included inpatients from hospitals of various levels in the Jiangsu Province Health Account database in 2016. Participants were selected by using a multistage sampling method. Patients <45 years of age were excluded, and patients hospitalized for rheumatic diseases were identified according to the 10th edition of the International Classification of Diseases. Generalized linear models were used to analyze the sociodemographic characteristics related to the hospitalization costs of patients with rheumatic diseases. RESULTS: The study included 3696 patients. The average cost of hospitalization for patients with rheumatic diseases was USD 4038.63. Female sex, a long length of stay, age between 65 and 74 years, free medical care, not being covered by the Urban-Rural Residents Basic Medical Insurance, and a high hospital level were associated with high hospitalization costs. CONCLUSION: This study examined hospitalization costs and relevant influencing factors in middle-aged and elderly patients with rheumatic disease in China. Our findings are useful for further research on costs of disease and the economic evaluation of strategies to prevent rheumatic disease.

Robust 3D phase retrieval via compressed support detection from snapshot diffraction pattern.

Traditional multislice iterative phase retrieval (MIPR) from snapshot two-dimensional measurements suffers from the two limitations of pre-defined support and iterative stagnation. To eliminate the requirements for priori knowledge of support masks, this paper proposes a multislice iterative phase retrieval algorithm based on compressed support detection and hybrid input-output algorithm (CSD-MIPR-HIO). The CSD-MIPR-HIO algorithm firstly uses compressed support detection to adaptively detect the support masks of each plane from single 2D diffraction intensity, and then uses a hybrid input-output (HIO) iterative algorithm for MIPR. The proposed method breaks the limitations of traditional MIPR algorithms on priori knowledge of support masks and achieve high-quality reconstruction in noisy environments. Numerical and optical experiments confirm the feasibility, superiority, and robustness of our proposed CSD-MIPR-HIO method.

A CNN-SVR model for NO2 profile prediction based on MAX-DOAS observations: The influence of Chinese New Year overlapping the 2020 COVID-19 lockdown on vertical distributions of tropospheric NO2 in Nanjing, China.

In this study, a hybrid model, the convolutional neural network-support vector regression model, was adopted to achieve prediction of the NO2 profile in Nanjing from January 2019 to March 2021. Given the sudden decline in NO2 in February 2020, the contribution of the Coronavirus Disease-19 (COVID-19) lockdown, Chinese New Year (CNY), and meteorological conditions to the reduction of NO2 was evaluated. NO2 vertical column densities (VCDs) from January to March 2020 decreased by 59.05% and 32.81%, relative to the same period in 2019 and 2021, respectively. During the period of 2020 COVID-19, the average NO2 VCDs were 50.50% and 29.96% lower than those during the pre-lockdown and post-lockdown periods, respectively. The NO2 volume mixing ratios (VMRs) during the 2020 COVID-19 lockdown significantly decreased below 400 m. The NO2 VMRs under the different wind fields were significantly lower during the lockdown period than during the pre-lockdown period. This phenomenon could be attributed to the 2020 COVID-19 lockdown. The NO2 VMRs before and after the CNY were significantly lower in 2020 than in 2019 and 2021 in the same period, which further proves that the decrease in NO2 in February 2020 was attributed to the COVID-19 lockdown. Pollution source analysis of an NO2 pollution episode during the lockdown period showed that the polluted air mass in the Beijing-Tianjin-Hebei was transported southwards under the action of the north wind, and the subsequent unfavorable meteorological conditions (local wind speed of < 2.0 m/sec) resulted in the accumulation of pollutants.

Establishing cost-effectiveness threshold in China: a community survey of willingness to pay for a healthylife year.

INTRODUCTION: The willingness to pay per quality-adjusted life year gained (WTP/Q) is commonly used to determine whether an intervention is cost-effective in health technology assessment. This study aimed to evaluate the WTP/Q for different disease scenarios in a Chinese population. METHODS: The study employed a quadruple-bounded dichotomous choice contingent valuation method to estimate the WTP/Q in the general public. The estimation was conducted across chronic, terminal and rare disease scenarios. Face-to-face interviews were conducted in a Chinese general population recruited from Jiangsu province using a convenience sampling method. Interval regression analysis was performed to determine the relationship between respondents' demographic and socioeconomic conditions and WTP/Q. Sensitivity analyses of removing protest responses and open question analyses were conducted. RESULTS: A total of 896 individuals participated in the study. The WTP/Q thresholds were 128 000 Chinese renminbi (RMB) ($36 364) for chronic diseases, 149 500 RMB ($42 472) for rare diseases and 140 800 RMB ($40 000) for terminal diseases, equivalent to 1.76, 2.06 and 1.94 times the gross domestic product per capita in China, respectively. The starting bid value had a positive influence on participants' WTP/Q. Additionally, residing in an urban area (p<0.01), and higher household expenditure (p<0.01), educational attainment (p<0.02) and quality of life (p<0.02) were significantly associated with higher WTP/Q. Sensitivity analyses demonstrated the robustness of the results. CONCLUSION: This study implies that tailored or varied rather than a single cost-effectiveness threshold could better reflect community preferences for the value of a healthy year. Our estimates hold significance in informing reimbursement decision-making in health technology assessment in China.

Atmospheric plasma treatment: an alternative of HF etching in lithium disilicate glass-ceramic cementation.

Objectives: This study aimed to investigate whether the atmospheric pressure plasma jet (APPJ) could modify the surface of lithium disilicate glass ceramics (LDC) instead of hydrofluoric acid (HF) in LDC resin cementation. Methods: Two hundred and thirty-two LDC blocks were randomly divided into seven groups: Group 1 (16 specimens) was the blank control group (without HF or APPJ treatment); Group 2 (36 specimens) was etched by HF; Groups 3-7 (36 specimens each) were treated with APPJ, and the relative air humidity (RAH) of the discharge was 22.8%, 43.6%, 59.4%, 75.2%, and 94.0%, respectively. Three LDC blocks in each group were characterized via X-ray photoemission spectroscopy (XPS) analyses, 3 blocks via contact angle measurements, and other 10 blocks via surface roughness measurements. The residual LDC blocks in groups 2-7 were cemented to composite cylinders. Testing the cemented specimens' shear bond strength (SBS) before and after thermocycling (6,500 cycles of 5°C and 55°C) revealed fracture patterns. Data were analyzed by ANOVA (post hoc: Bonferroni) (α = 0.05). Results: After APPJ treatment, the water contact angle values of APPJ treated blocks dropped from 31.37° to 5.66°, while that of HF etched ones dropped to 18.33°. The O/C ratio increased after HF etching or APPJ treatment according to the calculated results, except for the APPJ-treated samples at a RAH of 22.8%. The surface roughness of LDC blocks showed no statistic difference before and after APPJ treatment, but experienced significant difference after HF etching. The O/Si and O/C ratios varied after HF etching or APPJ treatment. No significant difference in SBS values could be found among groups 2-7 before or after artificial aging (p > 0.05). All specimens showed mixed failure patterns. Conclusion: The APPJ treatment method reported in this study is a promising novel strategy for surface modification of the LDC. With acceptable bonding strength, it might be an alternative to HF in LDC-resin cementation.

Phycicoccus sonneraticus sp. nov., a Novel Endophytic Actinobacterium Isolated from the Bark of Sonneratia apetala.

A novel endophytic actinobacterial strain, designated MQZ13P-5T, was isolated from a piece of bark of Sonneratia apetala, collected from Guangxi Zhuang Autonomous Region, China. This strain was Gram-stain positive, aerobic, non-spore-forming, non-motile and rod-shaped. Comparative 16S rRNA gene sequence analysis showed that strain MQZ13P-5T was related to the genus Phycicoccus with exhibiting the highest similarity (98.0%) to Phycicoccus endophyticus IP6SC6T. The phylogenetic trees based on 16S rRNA gene sequences and core genes indicated that strain MQZ13P-5T belonged to the genus Phycicoccus and could not be assigned to any described species. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain MQZ13P-5T and type strains of Phycicoccus species were less than 84% and 27%, respectively, below the thresholds for species delineation. This strain showed chemotaxonomic and phenotypic properties consistent with its classification in the genus Phycicoccus. Based on the taxonomic data, strain MQZ13P-5T should represent a novel species of the genus Phycicoccus, for which the name Phycicoccus sonneraticus sp. nov. is proposed, with the type strain MQZ13P-5T (= CGMCC 1.18744T = JCM 34337T).

Knowledge domain and emerging trends in multimorbidity and frailty research from 2003 to 2023: a scientometric study using citespace and VOSviewer.

BACKGROUND: Multimorbidity and frailty represent emerging global health burdens that have garnered increased attention from researchers over the past two decades. We conducted a scientometric analysis of the scientific literature on the coexistence of multimorbidity and frailty to assess major research domains, trends, and inform future lines of research. METHODS: We systematically retrieved scientific publications on multimorbidity and frailty from the Web of Science Core Collection, spanning from 2003 to 2023. Scientometric analysis was performed using CiteSpace and VOSviewer, enabling the visualization and evaluation of networks comprising co-citation references, co-occurring keywords, countries, institutions, authors, and journals. RESULTS: A total of 584 eligible publications were included in the analysis. An exponential rise in research interest in multimorbidity and frailty was observed, with an average annual growth rate of 47.92% in publications between 2003 and 2022. Three major research trends were identified: standardized definition and measurement of multimorbidity and frailty, comprehensive geriatric assessment utilizing multimorbidity and frailty instruments for older adults, and the multifaceted associations between these two conditions. The United States of America, Johns Hopkins University, Fried LP, and the Journal of the American Geriatrics Society were identified as the most influential entities within this field, representing the leading country, institution, author, and journal, respectively. CONCLUSIONS: Scientometric analysis provides invaluable insights to clinicians and researchers involved in multimorbidity and frailty research by identifying intellectual bases and research trends. While the instruments and assessments of multimorbidity and frailty with scientific validity and reliability are of undeniable importance, further investigations are also warranted to unravel the underlying biological mechanisms of interactions between multimorbidity and frailty, explore the mental health aspects among older individuals with multimorbidity and frailty, and refine strategies to reduce prescriptions in this specific population.

Effects of edaravone dexborneol on neurological function and serum inflammatory factor levels in patients with acute anterior circulation large vessel occlusion stroke.

The goal of this study is to evaluate and analyze the effects of edaravone (EDV) dexborneol on neurological function and serum inflammatory factor levels among patients with acute anterior circulation big artery blockage stroke. A total of 142 patients with acute anterior circulation large vessel occlusion (LVO) were randomly allocated to the study group (69 patients) or the control group (73 patients). In the study group, patients were treated with 37.5 mg EDV dexborneol twice a day for 10-14 days, based on the control group. The primary efficacy outcome was the National Institutes of Health Stroke Scale score change from baseline to 90 days and the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days after randomization. The secondary outcome included the decrease in inflammatory factors at 14 days. The primary safety outcome was the incidence of hemorrhagic transformation assessed according to Heidelberg bleeding classification within 7 days. A higher percentage of patients with HIHSS score ≤5 at 90 days in the EDV dexcamphorol group was observed than in the control group (75.36% vs 64.38%; P = 0.015). A higher percentage of patients with mRS score ≤1 at 90 days in the EDV dexcamphorol group was observed than in the control group (63.77% vs 50.68%; P = 0.012). After treatment, the levels of IL-6 and hs-CRP were significantly lower following treatment and compared to the control group (P < 0.05). In patients receiving the EDV dexborneol group, a significantly decreased risk of radiographic intracranial hemorrhage was found compared with the control group (20.29% vs 39.73%; P = 0.0006). In conclusion, EDV dexborneol can improve the clinical outcomes of patients with acute anterior circulation LVO stroke, which can be used as an effective supplement to thrombectomy therapy.

Study of the Immediately Detection of Mild Traumatic Brain Injury by Feature Engineering on Electroencephalography.

The electroencephalographic (EEG) diagnosis of mild traumatic brain injury (mTBI) is not usually timely, and the detection is often performed several hours or days after the trauma, leading to a decrease in the accuracy of its detection. In this study, EEG signals are recorded immediately after mTBI by connecting a bipolar single lead to injured animals. And three types of EEG features, namely time domain, frequency domain, and nonlinear dynamics, are screened for optimal feature subset in mTBI detection. First, EEG signals of animals are recorded before and after establishing the animal model of mTBI. Second, signal preprocessing, feature extraction, and feature preprocessing are performed to obtain the full-feature dataset, and 1442 feature subsets are obtained by 15 feature reduction algorithms extracted from combinations of 47 features. Ultimately, the support vector machines and K-nearest neighbor algorithms are trained and tested respectively, and their performance is comprehensively compared to determine the optimal feature subset for mTBI detection. In the EEG dataset collected in this study, a total of eight feature subsets extracted from combinations of original 47 features and classification models with 100% accuracy are obtained. This study shows the perspective of immediately detecting mTBI based on a bipolar single-lead EEG.

Temporal trends in inequalities of the burden of cardiovascular disease across 186 countries and territories.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. The extent to which CVD affects the population's health varies across countries. Moreover, quantitative estimates of the trend of inequalities in CVD burden remain unclear. The objective of our study was to assess the socioeconomic inequalities and temporal trends of CVD burden across 186 countries and territories from 2000 to 2019. METHODS: We extracted data from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019, and conducted a cross-national time-series analysis. Age-standardized disability-adjusted life-year (DALY) rates were used to measure the burden of CVDs, and gross national income (GNI) per capita was used to approximate the socioeconomic development. Concentration curves and concentration indexes (CIs) were generated to evaluate the cross-national socioeconomic inequality of CVD burden. A joinpoint regression analysis was used to quantify the changes in trends in socioeconomic inequality of CVD burden from 2000 to 2019. RESULTS: The age-standardized DALY rates of CVDs decreased in 170 (91%) of 186 countries from 2000 to 2019. The concentration curves of the age-standardized DALY rates of CVDs were above the equality line from 2000 to 2019, indicating a disproportional distribution of CVD burden in low-income countries. The CIs declined from - 0.091 (95% CI: -0.128 to - 0.054) in 2000 to - 0.151 (95% CI: -0.190 to - 0.112) in 2019, indicating worsened pro-poor inequality distributions of CVD burden worldwide. A four-phase trend of changes in the CIs of age-standardized DALY rates for CVD was observed from 2000 to 2019, with an average annual percentage change (AAPC) of - 2.7% (95% CI: -3.0 to - 2.4). Decreasing trends in CIs were observed in all CVD subcategories but endocarditis, with AAPC ranging from - 6.6% (95% CI: -7.3 to - 5.9) for ischemic heart disease to - 0.2% (95% CI: -0.4 to - 0.1) for hypertensive heart disease. CONCLUSIONS: Globally, the burden of CVD has decreased in more than 90% of countries over the past two decades, accompanied by an increasing trend of cross-country inequalities. Moreover, the overall burden of CVD continues to fall primarily on low-income countries.

Conductivity reactivity index for monitoring of cerebrovascular autoregulation in early cerebral ischemic rabbits.

BACKGROUND: Cerebrovascular autoregulation (CVAR) is the mechanism that maintains constant cerebral blood flow by adjusting the caliber of the cerebral vessels. It is important to have an effective, contactless way to monitor and assess CVAR in patients with ischemia. METHODS: The adjustment of cerebral blood flow leads to changes in the conductivity of the whole brain. Here, whole-brain conductivity measured by the magnetic induction phase shift method is a valuable alternative to cerebral blood volume for non-contact assessment of CVAR. Therefore, we proposed the correlation coefficient between spontaneous slow oscillations in arterial blood pressure and the corresponding magnetic induction phase shift as a novel index called the conductivity reactivity index (CRx). In comparison with the intracranial pressure reactivity index (PRx), the feasibility of the conductivity reactivity index to assess CVAR in the early phase of cerebral ischemia has been preliminarily confirmed in animal experiments. RESULTS: There was a significant difference in the CRx between the cerebral ischemia group and the control group (p = 0.002). At the same time, there was a significant negative correlation between the CRx and the PRx (r = - 0.642, p = 0.002) after 40 min after ischemia. The Bland-Altman consistency analysis showed that the two indices were linearly related, with a minimal difference and high consistency in the early ischemic period. The sensitivity and specificity of CRx for cerebral ischemia identification were 75% and 20%, respectively, and the area under the ROC curve of CRx was 0.835 (SE = 0.084). CONCLUSION: The animal experimental results preliminarily demonstrated that the CRx can be used to monitor CVAR and identify CVAR injury in early ischemic conditions. The CRx has the potential to be used for contactless, global, bedside, and real-time assessment of CVAR of patients with ischemic stroke.

Biocompatible Polymer-Modified Nanoplatform for Ferroptosis-Enhanced Combination Cancer Therapy.

Ferroptosis is a novel type of iron-dependent non-apoptotic pathway that regulates cell death and shows unique mechanisms including causing lipid peroxide accumulation, sensitizing drug-resistant cancers, priming immunity by immunogenic cell death, and cooperatively acting with other anticancer modalities for eradicating aggressive malignancies and tumor relapse. Recently, there has been a great deal of effort to design and develop anticancer biocompatible polymeric nanoplatforms including polypeptide and PEGylated ones to achieve effective ferroptosis therapy (FT) and synergistic combination therapies including chemotherapy (CT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), gas therapy (GT) including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S), and immunotherapy (IT). To be noted, the combo therapies such as FT-CT, FT-PTT, FT-GT, and FT-IT are attracting much efforts to fight against intractable and metastatic tumors as they can generate synergistic antitumor effects and immunogenic cell death (ICD) effects or modulate immunosuppressive tumor microenvironments to initiate strong antitumor immunity and memory effects. The polymeric Fenton nano-agents with good biosafety and high anticancer efficacy will provide a guarantee for their applications. In this review, various biocompatible polymer-modified nanoplatforms designed for FT and combo treatments are summarized for anticancer therapies and discussed for potential clinical transitions.

Temporal trends in inequalities of the burden of HIV/AIDS across 186 countries and territories.

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) has reported that HIV/AIDS continues to take a disproportionate toll on global health. However, the trends in global inequality of HIV/AIDS burden have remained ambiguous over the past two decades. The objectives of our study were to assess the socioeconomic inequalities, and temporal trends of HIV/AIDS across 186 countries and territories from 2000 to 2019. METHODS: We extracted data from the GBD 2019, and conducted a cross-national time-series analysis. Age-standardized disability-adjusted life-year (DALY) rates were used to measure the global burden of HIV/AIDS. Gross national income (GNI) per capita was used to approximate the national socioeconomic status. Linear regression analysis was conducted to investigate the relationship between age-standardized DALY rates due to HIV/AIDS and GNI per capita. The concentration curve and concentration index (CI) were generated to evaluate the cross-national socioeconomic inequality of HIV/AIDS burden. A joinpoint regression analysis was used to quantify the changes in trends in socioeconomic inequality of HIV/AIDS burden from 2000 to 2019. RESULTS: A decrease in age-standardized DALY rates for HIV/AIDS occurred in 132 (71%) of 186 countries/territories from 2000 to 2019, of which 52 (39%) countries/territories achieved a decrease in DALYs of more than 50%, and 27 (52%) of the 52 were from sub-Saharan Africa. The concentration curves of the age-standardized DALY rates of HIV/AIDS were above the equality line from 2000 to 2019. The CI rose from - 0.4625 (95% confidence interval - 0.6220 to -0.2629) in 2000 to -0.4122 (95% confidence interval - 0.6008 to -0.2235) in 2019. A four-phase trend of changes in the CIs of age-standardized DALY rates for HIV/AIDS was observed across 2000 to 2019, with an average increase of 0.6% (95% confidence interval 0.4 to 0.8, P < 0.001). CONCLUSIONS: Globally, the burden of HIV/AIDS has decreased over the past two decades, accompanied by a trend of narrowing cross-country inequalities of HIV/AIDS burden. Moreover, the burden of HIV/AIDS continues to fall primarily in low-income countries.

Ancylobacter mangrovi sp. nov., a novel endophytic bacterium isolated from mangrove plant.

Two novel strains GSK1Z-4-2T and MQZ15Z-1 were isolated from branches of mangrove plants collected from Guangxi Zhuang Autonomous Region, China. Both strains were Gram-negative, aerobic, non-flagellated and non-spore-forming bacteria. The comparison of 16S rRNA gene sequences initially indicated that the two strains were assigned to the genus Ancylobacter with sharing the highest similarity to Ancylobacter pratisalsi DSM 102029T (97.3%). The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strains GSK1Z-4-2T and MQZ15Z-1 were 99.9%, 97.4% and 77.4%, respectively, which revealed that the two strains belonged to the same species. Phylogenetic analyses based on 16S rRNA gene sequences and the core proteome showed that the two strains formed a well-supported cluster with A. pratisalsi DSM 102029T. Moreover, the ANI and isDDH values between strain GSK1Z-4-2T and A. pratisalsi DSM 102029T were 83.0% and 25.8%, respectively, demonstrating that strain GSK1Z-4-2T was a previously undescribed species. Meanwhile, strains GSK1Z-4-2T and MQZ15Z-1 exhibited most of chemotaxonomic and phenotypic features consistent with the description of the genus Ancylobacter. Based on the polyphasic data, strains GSK1Z-4-2T and MQZ15Z-1 should represent a novel species of the genus Ancylobacter, for which the name Ancylobacter mangrovi sp. nov. is proposed. The type strain is GSK1Z-4-2T (=MCCC 1K07181T = JCM 34924T).