Intervalley Scattering Induced Terahertz Field Enhancement in Graphene Metasurface.

Terahertz (THz) field enhancement has significant applications in high-resolution imaging, next-generation wireless communications, and networking. In this work, we experimentally demonstrate a graphene metasurface for THz field enhancement that is based on the intervalley scattering theory. Each meta-atom of the metasurface is composed of one split-ring resonator (SRR) embedded in one graphene patch. The experimental results show that, by electrically adjusting the conductivity of the graphene patch, the THz field through the entire sample is enhanced by 23 times and the transmission amplitude at 0.47 THz decreases 8.4 dB. Moreover, the maximum phase difference at 0.43 THz reaches 88°. The experiment shows good agreement with simulation. This study paves a way for exploring THz-matter interactions and nonlinear optics.

Tunable slow light device based on a graphene metasurface.

Slow light devices have significant applications in memory, switching, and quantum optics. However, the design and fabrication of slow light devices with large tunable group delay are still challenging. Here, a graphene-based slow light device that can electrically modulate the group delay of terahertz (THz) waves is proposed and experimentally demonstrated. The unit cell of the device consists of a U-shaped metal resonator and an Ω-shaped metal resonator, with three graphene ribbons embedded between the two resonators. Under electrical stimuli, a relatively high amplitude modulation depth of 74% is achieved and the maximum transmission amplitude is as high as 0.7 at the transmission peak of 0.6 THz. Most importantly, the maximum group delay variation reaches 5 ps at 0.76 THz and the maximum group delay amplitude is as high as 8.8 ps. The experiment shows good agreement with simulation. This study paves a new way for developing novel switchable nanophotonic devices and slow light devices.

Polarization insensitive flexible ultra-broadband terahertz metamaterial absorber.

We propose a polarization insensitive, flexible ultra-broadband terahertz (THz) metamaterial absorber. It consists of a chromium composite resonator on the top, a polyimide (PI) dielectric layer in the middle, and a chromium substrate. The simulation results show that the absorption achieves more than 90% ultra-wideband absorption in the range of 1.92-4.34 THz. The broadband absorption is produced by the combination of electric dipole resonance and magnetic resonance, as well as impedance matching with free space. Due to the rotational symmetry of the unit structure, the absorber is insensitive to polarization of the THz wave and has a larger range of incident angles. The total thickness of the absorber is only 13.4 µm, showing highly flexible and excellent high-temperature resistance characteristics. Therefore, it has potential applications in THz wave stealth and electromagnetic shielding.

Terahertz phase modulator based on a metal-VO2 reconfigurable metasurface.

Actively controlling the phase of a terahertz (THz) wave is of great significance for beaming, tunable focusing, and holography. We present a THz phase modulator based on an electrically triggered vanadium dioxide (V O 2) reconfigurable metasurface. The unit cell of the device consists of two split-ring resonators embedded with a V O 2 ribbon. By electrically triggering the insulator-to-metal transition of V O 2, the resonance mode and resonance intensity of the unit cell can be dynamically controlled. The simulation results show that the structure can achieve a phase shift of about 360° in the range of 1.03-1.13 THz, and the reflection amplitude can reach 80%. The device has potential applications in THz imaging, radar, broadband wireless communications, and array phase control.

Surface-Functionalized Terahertz Metamaterial Biosensor Used for the Detection of Exosomes in Patients.

Owing to their stability in bodily fluids, exosomes have attracted increased attention as colorectal cancer (CRC) biomarkers for early diagnosis. To validate the potential of the plasma exosomes as a novel biomarker for the monitoring of CRC, we demonstrated a terahertz (THz) metamaterials (MMs) biosensor for the detection of exosomes in this work. The biosensor with two resonant frequencies is designed using full wave electromagnetic simulation software based on the finite integration time domain (FITD) method and fabricated by a surface micromachining process. The biosensor surface is first modified using Au nanoparticles (AuNPs), and then, anti-KRAS and anti-CD147, which are specific to the exosomes, are modified on the AuNPs assembled with HS-poly(ethylene glycol)-COOH (HS-PEG-COOH). Exosomes used in the experiment are extracted via the instructions in the exosomes isolation and purification kit and identified by using transmission electron microscopy (TEM), Western blot (WB), and nanoparticle tracking analysis (NTA). The biosensor covered with plasma-derived exosomes of CRC patients has a different resonance frequency shift compared to that with healthy-control-derived exosomes. This study proposes an emerging and quick method for diagnosing the CRC.

The emerging role of MEIS1 in cell proliferation and differentiation.

Cell proliferation and differentiation are the foundation of reproduction and growth. Mistakes in these processes may affect cell survival, or cause cell cycle dysregulation, such as tumorigenesis, birth defects and degenerative diseases, or cell death. Myeloid ecotropic viral integration site 1 (MEIS1) was initially discovered in leukemic mice. Recent research identified MEIS1 as an important transcription factor that regulates cell proliferation and differentiation during cell fate commitment. MEIS1 has a pro-proliferative effect in leukemia cells; however, its overexpression in cardiomyocytes restrains neonatal and adult cardiomyocyte proliferation. In addition, MEIS1 has carcinogenic or tumor suppressive effects in different neoplasms. Thus, this uncertainty suggests that MEIS1 has a unique function in cell proliferation and differentiation. In this review, we summarize the primary findings of MEIS1 in regulating cell proliferation and differentiation. Correlations between MEIS1 and cell fate specification might suggest MEIS1 as a therapeutic target for diseases.

Using the Interaction between Copper and Manganese to Stabilize Copper Single-atom for CO Oxidation.

The interaction between Cu and Mn has been used to immobilize the Cu single-atom on MnO2 surface by redox-driven hydrolysis. Comprehensive structure and property characterizations demonstrate that the existence of an Cu-Mn interaction on the catalyst surface can effectively restrain the aggregation of Cu single atoms and improve carbon monoxide (CO) oxidation activity. The interaction of forming the Cu-O-Mn entity is beneficial for CO catalytic activity as the migration of reactive oxygen species and the coordination effect of active centers accelerate the reaction. In particular, 3%-Cu1 /MnO2 shows an oxygen storage capacity (OSC) value (342.75 µmol/g) more than ten times that of pure MnO2 (27.79 µmol/g) and has high CO catalytic activity (T90% =80 °C), it can maintain CO conversion of 95 % after 15 cycles. This work offers a reliable method for synthesizing Cu single-atom catalysts and deepens understanding of the interaction effect between single transition metal atoms and supports that can improve the catalytic activity of CO oxidation.

Mitochondrial dysfunction and the AKI-to-CKD transition.

Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has adverse consequences and could progress to renal fibrosis, which is the ultimate common pathway for various terminal kidney diseases. Thus, it is urgent to develop a strategy to hinder the transition from AKI to CKD. Some mechanisms of the AKI-to-CKD transition have been revealed, such as nephron loss, cell cycle arrest, persistent inflammation, endothelial injury with vascular rarefaction, and epigenetic changes. Previous studies have elucidated the pivotal role of mitochondria in acute injuries and demonstrated that the fitness of this organelle is a major determinant in both the pathogenesis and recovery of organ function. Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency. Dysregulation of mitochondrial homeostasis, alterations in bioenergetics, and organelle stress cross talk contribute to the AKI-to-CKD transition. In this review, we focus on the pathophysiology of mitochondria in renal recovery after AKI and progression to CKD, confirming that targeting mitochondria represents a potentially effective therapeutic strategy for the progression of AKI to CKD.

Chloroquine attenuates lithium-induced NDI and proliferation of renal collecting duct cells.

Lithium is widely used in psychiatry as the golden standard for more than 60 yr due to its effectiveness. However, its adverse effect has been limiting its long-term use in clinic. About 40% of patients taking lithium develop nephrogenic diabetes insipidus (NDI). Lithium can also induce proliferation of collecting duct cells, leading to microcyst formation in the kidney. Lithium was considered an autophagy inducer that might contribute to the therapeutic benefit of neuropsychiatric disorders. Thus, we hypothesized that autophagy may play a role in lithium-induced kidney nephrotoxicity. To address our hypothesis, we fed mice with a lithium-containing diet with chloroquine (CQ), an autophagy inhibitor, concurrently. Lithium-treated mice presented enhanced autophagy activity in the kidney cortex and medulla. CQ treatment significantly ameliorated lithium-induced polyuria, polydipsia, natriuresis, and kaliuresis accompanied with attenuated downregulation of aquaporin-2 and Na+-K+-2Cl- cotransporter protein. The protective effect of CQ on aquaporin-2 protein abundance was confirmed in cultured cortical collecting duct cells. In addition, we found that lithium-induced proliferation of collecting duct cells was also suppressed by CQ as detected by proliferating cell nuclear antigen staining. Moreover, both phosphorylated mammalian target of rapamycin and ß-catenin expression, which have been reported to be increased by lithium and associated with cell proliferation, were reduced by CQ. Taken together, our study demonstrated that CQ protected against lithium-induced NDI and collecting duct cell proliferation possibly through inhibiting autophagy.

Preferences heterogeneity of health care utilization of community residents in China: a stated preference discrete choice experiment.

BACKGROUND: To tackle the issue with the low usage of primary healthcare service in China, it is essential to align resource distribution with the preferences of the community residents. There are few academic researches for describing residents' perceived characteristics of healthcare services in China. This study aims to investigate the preferences of healthcare services utilization in community residents and explore the heterogeneity. The findings will be useful for the policy makers to take targeted measures to tailor the provision of healthcare services. METHODS: The face-to-face interviews and surveys were conducted to elicit four key attributes (care provider; mode of services; cost; travel time) of the preference from community residents for healthcare utilization. A rational test was presented first to confirm the consistency, and then 16 pairs of choice tasks with 12 sociodemographic items were given to the respondents. Two hypothetical options for each set, without an opt-out option, were presented in each choice task. The latent class analysis (LCA) was used to analyse the data. RESULTS: Two thousand one hundred sixty respondents from 36 communities in 6 cities were recruited for our study. 2019 (93.47%) respondents completed valid discrete choice experiment (DCE) questionnaires. The LCA results suggested that four groups of similar preferences were identified. The first group (27.29%) labelled as "Comprehensive consideration" had an even preference of all four attributes. The second group (37.79%) labelled as "Price-driven" preferred low-price healthcare services. The third group labelled as "Near distance" showed a clear preference for seeking healthcare services nearby. The fourth group (34.18%) labelled as "Quality seeker" preferred the healthcare service provided by experts. Willingness to pay (WTP) results showed that people were willing to accept CNY202.12($29.37) for Traditional Chinese Medicine (TCM) services and willing to pay CNY604.31($87.81) for the service provided by experts. CONCLUSIONS: Our study qualitatively measures the distinct preferences for healthcare utilization in community residents in China. The results suggest that the care provider, mode of services, travel time and cost should be considered in priority setting decisions. The study, however, reveals substantial disagreement in opinion of TCM between different population subgroups.

miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression.

MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR-495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR-495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol-doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre-treatment with miR-495 before chemotherapy could improve the curative effect on MDR1-based MDR cancer.

Provincial inequality of China's progress towards universal health coverage: An empirical analysis in 2016-21.

Background: Achieving universal health coverage (UHC) is a crucial target shared by the Sustainable Development Goals (SDGs). As UHC levels are influenced by factors such as the regional economy and resource allocation, subnational evidence in China is urgently needed. This study aimed to monitor provincial progress from 2016 to 2021, thereby informing the development of region-specific strategies. Methods: Based on the UHC monitoring framework proposed by the World Health Organization, a UHC index was constructed comprising the service coverage dimension (16 indicators) and financial protection dimension (four indicators). In this observational study, routinely collected health data from 25 provinces (autonomous regions and municipalities) in mainland China were obtained from statistical yearbooks, relevant literature, and nationally representative surveys. The indices were calculated using geometric means. Socioeconomic inequalities among provinces were quantified using the slope index of inequality (SII) and relative index of inequality (RII). Results: From 2016 to 2021, China made laudable progress towards achieving UHC, with the index rising from 56.94 in 2016 to 63.03 in 2021. Most provinces demonstrated better performance in service coverage. Western provinces generally presented faster rates of progress, which were attributed to more substantial increases in financial protection. Despite significant disparities, with the UHC index ranging from 77.94 in Shanghai to 54.61 in Fujian in 2021, the overall equity of UHC has improved across the 25 provinces. SII decreased from 17.78 (95% confidence interval (CI) = 11.64, 23.93) to 12.25 (95% CI = 5.86, 18.63) and RII from 1.38 (95% CI = 1.29, 1.46) to 1.22 (95% CI = 1.16, 1.29). However, the non-communicable disease (NCD) domain experienced a drop in both index score and equity, underscoring the need for prioritised attention. Conclusions: In the context of SDGs and the 'Healthy China 2030' initiative, China has made commendable progress towards UHC, and inter-provincial equity has improved. However, substantial differences persisted. The equitable realisation of UHC necessitates prioritising the enhancement of service capacity and financial protection in less developed regions, particularly by addressing shortages in the general practitioner workforce and mitigating catastrophic payments. Developed regions should focus on preventing NCDs through effective interventions targeting key risk factors. This study provides insights for other countries to adopt comprehensive monitoring frameworks, identify subnational disparities, and introduce targeted policy initiatives.

The effect of using mobile phone applications for intelligent pelvic floor rehabilitation on elderly female patients with stress urinary incontinence.

BACKGROUND: Stress urinary incontinence is prevalent among women and the incidence increases with age. OBJECTIVE: To explore the effect of intelligent pelvic floor muscle rehabilitation on elderly female patients with incontinence. METHODS: A total of 209 patients with urinary incontinence who were treated with pelvic floor muscle rehabilitation at Peking University International Hospital from September 2020 to January 2022 were selected by convenient sampling. All subjects were divided into the 50-60 year old patient group (n= 51) and over 60 years old patient group according to age (n= 158). The subjects of different age group were divided into an experimental group and a control group. The patients in the control group received routine nursing and health education, and the patients in the observation group received a combination of mobile application use and smart dumbbells. Based on this, we constructed an intervention model for intelligent, continuous pelvic floor rehabilitation. After 7 and 12 weeks, pelvic floor muscle function knowledge and exercise compliance in the two groups were evaluated. The improvement of urinary incontinence symptoms, pelvic floor muscle strength grades and quality-of-life scales were evaluated. RESULTS: The results showed that pelvic floor knowledge and exercise compliance in the experimental group were better than in the control group at 7 and 12 weeks after intervention (P< 0.05). There was no significant difference in pelvic floor muscle strength and quality of life between the two groups at 7 weeks after intervention (P> 0.05). However, there was a significant difference in pelvic floor muscle strength and quality of life between the two groups at 12 weeks after intervention (P< 0.05). There was no significant difference between different age groups. CONCLUSION: The intelligent pelvic floor rehabilitation model that combines a mobile application with smart dumbbells can maintain and strengthen the clinical treatment effect for elderly patients with urinary incontinence.

Gait Parameters can Reflect Cognitive Performance in Older Adults with Cerebral Small Vessel Disease: A Cross-sectional Research.

BACKGROUND: Cerebral small vessel disease (CSVD) is a common chronic progressive disease. It remains unclear whether high gait variability is a marker of cognitive cortical dysfunction. METHODS: This study included 285 subjects (aged from 60 to 85 years, 60.3% female) including 37 controls, 179 presented as Fazekas II, and 69 presented as Fazekas III. The severity of white matter hyperintensities was assessed by the Fazekas Rating Scale. Gait parameters were assessed using a vision-based artificial intelligent gait analyzer. Cognitive function was tested by MMSE, MoCA, DST, and VFT. RESULTS: Three gait parameters including gait speed, gait length, and swing time were associated with cognitive performance in patients with CSVD. Gait speed was associated with cognitive performance, including MMSE (ß 0.200; 95%CI 1.706-6.018; p <.001), MoCA (ß 0.183; 95%CI 2.047-7.046; p <.001), DST (order) (ß 0.204; 95%CI 0.563-2.093; p =.001) and VFT (ß 0.162; 95%CI 0.753-4.865; p =.008). Gait length was associated with cognitive performance, including MMSE (ß 0.193; 95%CI 3.475-12.845; p =.001), MoCA (ß 0.213; 95%CI 6.098-16.942; p <.001), DST (order) (ß 0.224; 95%CI 1.056-4.839; P <.001) and VFT (ß 0.149; 95%CI 1.088- 10.114; p =.015). Swing time was associated with cognitive performance, including MMSE (ß - 0.242; 95%CI -2.639 to -0.974; p<.001), MoCA (ß -0.211; 95%CI -2.989 to -1.034; p <.001) and DST (reverse order) (ß -0.140; 95%CI -0.568 to -0.049; p =.020). CONCLUSION: This study revealed that the relationship between gait parameters and cognitive performance in patients with CSVD and the deteriorated gait parameters can reflect cognitive impairment and even dementia in older people with CSVD.

The coverage and challenges of increasing uptake of non-National Immunization Program vaccines in China: a scoping review.

BACKGROUND: Non-National Immunization Program (NIP) vaccines have played an important role in controlling vaccine-preventable diseases (VPDs) in China. However, these vaccines are paid out of pocket and there is room to increase their coverage. We focused on four selected non-NIP vaccines in this study, namely Haemophilus influenzae type b (Hib) vaccine, human papillomavirus (HPV) vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine. We aimed to conduct a scoping review of their vaccination rates and the major barriers faced by health systems, providers, and caregivers to increase coverage. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). We searched five English databases (PubMed, Web of Science, EMBASE, Scopus, and WHO IRIS) and four Chinese databases using the search strategy developed by the study team. Two independent reviewers screened, selected studies, and examined their quality. We summarized the non-NIP vaccine coverage data by vaccine and applied the 5A framework (Access, Affordability, Acceptance, Awareness, Activation) to chart and analyze barriers to increasing coverage. RESULTS: A total of 28 articles were included in the analysis (nine pertaining to vaccine coverage, and another 19 reporting challenges of increasing uptake). Among the four selected vaccines, coverage for the Hib vaccine was the highest (54.9-55.9% for 1 dose or more from two meta-analyses) in 2016, while the coverage of the other three vaccines was lower than 30%. Eight of the nine included articles mentioned the regional disparity of coverage, which was lower in under-developing regions. For example, the three-dose Hib vaccination rate in eastern provinces was 38.1%, whereas the rate in central and western provinces was 34.3% and 26.2%, respectively in 2017. Within the 5A framework, acceptance, awareness, and affordability stood out as the most prominent themes. Among the 12 identified sub-themes, high prices, low vaccine awareness, concerns about vaccine safety and efficacy were the most cited barriers to increasing the uptake. CONCLUSIONS: There is an urgent need to increase coverage of non-NIP vaccines and reduce disparities in access to these vaccines across regions. Concerted efforts from the government, the public, and society are required to tackle the barriers and challenges identified in this study, both on the demand and supply side, to ensure everybody has equal access to life-saving vaccines in China. Particularly, the government should take a prudent approach to gradually incorporate non-NIP vaccines into the NIP step by step, and make a prioritizing strategy based on key factors such as disease burden, financial resources, and market readiness, with special attention to high-risk populations and underdeveloped regions.

CDC20 inhibition alleviates fibrotic response of renal tubular epithelial cells and fibroblasts by regulating nuclear translocation of ß-catenin.

Fibrosis is a common pathological phenomenon in progressive kidney disease leading to eventual loss of kidney function. Previous studies demonstrated that CDC20 plays a role in cancers by regulating epithelial-mesenchymal transition (EMT) and the infiltration of fibroblasts, suggesting the potential of CDC20 in regulating fibrotic response. However, the role of CDC20 in renal fibrosis is yet unclear. Herein, we reported that renal CDC20 was remarkably upregulated in renal tubular epithelial cells and fibroblasts in chronic kidney disease (CKD) patients, which was in line with a positive correlation with the severity of kidney fibrosis. In mice with unilateral urinary obstruction, CDC20 was also strikingly enhanced, and treatment with Apcin, an inhibitor of CDC20, ameliorated kidney fibrosis. Consistently, the pharmacological inhibition of CDC20 in mouse proximal tubular epithelial cells and rat fibroblasts attenuated TGF-ß1-induced fibrotic responses, while overexpression of CDC20 aggravated such responses. Additional studies revealed that CDC20 induces nuclear translocation of ß-catenin, which in turn initiates and promotes the pathological process of fibrosis in CKD. Thus, enhanced CDC20 in renal tubular cells and fibroblasts promotes renal fibrosis by activating ß-catenin, and CDC20 inhibition may serve as a promising strategy for the prevention and treatment of renal fibrosis.

Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Impact of White Matter Hyperintensity and Age on Gait Parameters in Patients With Cerebral Small Vessel Disease.

OBJECTIVES: This study aimed to investigate the effect of white matter hyperintensity (WMH), a common cerebral small vessel disease (CSVD) imaging marker, and age on gait parameters in middle-aged and geriatric populations. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 1076 participants (62.9% female; age 61.0 ± 9.3 years), who visited the neurology clinic or obtained a physical check-up from the Affiliated Hospital of Guizhou Medical University. In total, 883 patients with WMH and 193 healthy controls were included in this study. METHODS: The Fazekas scores of patients with CSVD were used to assess the burden of WMH. Based on the Fazekas scores, all participants were divided into 4 groups: 553 patients with Fazekas I, 257 patients with Fazekas II, 73 patients with Fazekas III, and 193 controls. Gait parameters, including step speed, frequency, length, width, stance time, and swing time, were quantitatively assessed using a vision-based artificial intelligence gait analyzer (SAIL system). The relationships among the Fazekas scores, age, and gait parameters were analyzed. RESULTS: Step speed, step length, step width, stance time, and swing time were significantly different among the 4 groups. Furthermore, Fazekas scores and age were both associated with gait parameters, including step speed, step length, stance time, and swing time. The Fazekas scores were associated with step width, whereas age was not. Age was associated with step frequency, whereas Fazekas scores were not. CONCLUSIONS AND IMPLICATIONS: Fazekas score and age are useful for evaluating gait parameters in patients with CSVD. Emerging WMH (such as Fazekas Ⅰ) could be a clinical warning sign of gait disturbance in a geriatric population.

LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease.

Mitochondria comprise the central metabolic hub of cells and their imbalance plays a pathogenic role in chronic kidney disease (CKD). Here, we studied Lon protease 1 (LONP1), a major mitochondrial protease, as its role in CKD pathogenesis is unclear. LONP1 expression was decreased in human patients and mice with CKD, and tubular-specific Lonp1 overexpression mitigated renal injury and mitochondrial dysfunction in two different models of CKD, but these outcomes were aggravated by Lonp1 deletion. These results were confirmed in renal tubular epithelial cells in vitro. Mechanistically, LONP1 downregulation caused mitochondrial accumulation of the LONP1 substrate, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), which disrupted mitochondrial function and further accelerated CKD progression. Finally, computer-aided virtual screening was performed, which identified a novel LONP1 activator. Pharmacologically, the LONP1 activator attenuated renal fibrosis and mitochondrial dysfunction. Collectively, these results imply that LONP1 is a promising therapeutic target for treating CKD.

Community residents' preferences for chronic disease management in Primary Care Facilities in China: a stated preference survey.

BACKGROUND: Although Chinese government has dedicated the past decades to treating chronic diseases by primary healthcare system, many more residents are apt to choose higher-tier facilities to treat minor chronic diseases. Understanding residents' preferences for chronic disease management in primary care facilities can bridge the gap between residents' choices and policy implementation. This study aims to elicit residents' preferences for chronic disease management in primary care facilities in the hypothetical minor chronic disease scenario. METHODS: Six hundred eighty residents were administered a discrete choice experiment that elicited preferences for chronic disease management in primary care facilities. Services attributes were service mode, treatment measure, out-of-pocket expenditure (OOP), traveling time to healthcare facility and title of physician. Mixed logit models were used to estimate stated preferences and willingness to pay for attributes. WTP confidence intervals were estimated by the delta method. RESULTS: A total of 94.44% of the completed questionnaires were valid (680 of 720 respondents). The participants preferred chronic disease management service with modern medicine, traveling time ≤ 30mins, and less OOP expenditure. Compared with Traditional Chinese Medicine (TCM), residents prefer modern medicine, willing to pay 155.53 CNY ($21.97) to change from TCM to modern medicine. Compensation about 86.02 CNY ($12.15) was needed to enable residents to change the choice of the nearer primary care facility to a further one. Integrated medicine in community clinics by experts was residents' most preferred scenario while TCM in the tertiary hospital was their least preferred one. CONCLUSION: In order to increase the utilization of primary healthcare services in chronic diseases management, policy makers need to concern more about the services of medical treatment type, price and convenience. Therefore, we advise policy makers to provide nearer primary healthcare services for residents especially for residents in surrounding areas. Furthermore, balancing the resource allocation between Traditional Chinese Medicine and modern medicine is worthy of consideration.