The equity road ahead for financing non-national immunization program vaccines in China: challenges and opportunities from a qualitative study.

BACKGROUND: In China, national immunization program (NIP) vaccines benefit from robust financial support and have achieved high coverage. Non-NIP vaccines rely on fragmented funding sources, mostly out-of-pocket payment, and face sub-optimal and inequitable coverage. Sustainable financing needs to be secured for addressing equity in non-NIP vaccine delivery. However, discussion and understanding of this issue remain limited. This study aims to analyze the current situation, comprehensively identify challenges and opportunities in non-NIP vaccine financing, and offer suggestions to enhance vaccine uptake and improve public health. METHODS: Between July and December 2023, we conducted a series of semi-structured, in-person interviews with 55 stakeholders from the Health Bureau, Centers for Disease Control and Prevention, Medical Insurance Bureau, and Finance Bureau across five provinces in China. Participants were selected through stratified sampling, and the interviews mainly included their involvement in non-NIP vaccine financing, challenges faced, and strategies for improvement to enhance financing performance. Informed consent was obtained, and thematic analysis was used to analyze the data. RESULTS: Non-NIP vaccine financing sources include out-of-pocket payments, government fiscal, health insurance and other external funds. These four channels differ in vaccine types covered, costs, and target populations, each with unique challenges and opportunities. High out-of-pocket costs remain a significant barrier to equitable vaccine uptake, while market competition has lowered the vaccine price and improved accessibility. Local fiscal support for free vaccination programs faces challenges related to sustainability and regional disparity, though governmental commitment to vaccination is growing. Nevertheless, centralized procurement organized by the government has lowered the price and reduced the financial burden. Despite legal restrictions on using basic health insurance for vaccinations and limited commercial insurance options, private medical savings accounts and mutual-aid mechanisms present new opportunities. Although the scope and impact of external support are limited, it has successfully increased awareness and social attention to vaccination. CONCLUSION: Relying on individual payments as the main financing channel for non-NIP vaccines is unsustainable and inadequate for ensuring universal vaccine access. A concerted and synergistic approach is essential to ensure sufficient, sustainable resources and enhance public financial management to improve equity in the non-NIP vaccines.

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.

The significance of ferroptosis in renal diseases and its therapeutic potential.

Kidney diseases are significant global public health concern, with increasing prevalence and substantial economic impact. Developing novel therapeutic approaches are essential for delaying disease progression and improving patient quality of life. Cell death signifying the termination of cellular life, could facilitate appropriate bodily development and internal homeostasis. Recently, regulated cell death (RCD) forms such as ferroptosis, characterized by iron-dependent lipid peroxidation, has garnered attention in diverse renal diseases and other pathological conditions. This review offers a comprehensive examination of ferroptosis, encompassing an analysis of the involvement of iron and lipid metabolism, the System Xc - /glutathione/glutathione peroxidase 4 signaling, and additional associated pathways. Meanwhile, the review delves into the potential of targeting ferroptosis as a therapeutic approach in the management of acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy, and renal tumors. Furthermore, it emphasizes the significance of ferroptosis in the transition from AKI to CKD and further accentuates the potential for repurposing drug and utilizing traditional medicine in targeting ferroptosis-related pathways for clinical applications. The integrated review provides valuable insights into the role of ferroptosis in kidney diseases and highlights the potential for targeting ferroptosis as a therapeutic strategy.

From both sides of the needle: Understanding effective interventions for facilitating non-national immunization program vaccine decision making in China.

Vaccination decisions are influenced by various psychological and practical factors. In China, non-National Immunization Program (non-NIP) vaccines, which are voluntary and self-paid, add uncertainty and autonomy to the decision-making process. Effective communication between providers and recipients is crucial but understudied. This study aims to integrate their perspectives, identify strategies for facilitating vaccination decisions, and analyze their mechanisms. From July to December 2023, semi-structured interviews were conducted with 17 caregivers and 12 vaccination providers across five Chinese provinces. Participants shared their experiences and decision-making processes regarding non-NIP vaccines. The Behaviour Change Wheel framework guided the analysis, utilizing iterative coding and directed content analysis. Thirteen Behavior Change Techniques were identified, with feedback, monitoring, and environmental restructuring being the most common. Key intervention functions included Persuasion, Education, and Training. We further mapped how these interventions influence non-NIP vaccine decisions. Capability was enhanced through education and effective communication, providing necessary knowledge and skills. Opportunity was increased via infrastructural improvements and societal support, making vaccines more accessible and endorsed by the community. Motivation was driven by clear communication of vaccination benefits and risks, reinforced by societal norms through public health messaging. By understanding the mechanisms influencing vaccination behaviors and interacting with stakeholders, tailored strategies can be developed. Healthcare providers can enhance service accessibility and offer evidence-based guidance with reminders, monitoring, and incentives to ensure compliance. For recipients, reliable information, sustained engagement, timely communication, and motivational opportunities are essential. A multi-dimensional approach involving multiple stakeholders is crucial for promoting non-NIP vaccine uptake.

Flexible Terahertz Broadband Absorber Based on a Copper Composite Film.

Terahertz absorbers play a crucial role in terahertz detectors, radar stealth, electromagnetic shielding, and other fields. However, the design and fabrication of flexible terahertz broadband absorbers remain a challenge at present. Here, we demonstrated a terahertz broadband absorber based on a copper composite film (CCF) consisting of a copper foam and an organic silica gel doped with Fe3O4 powder. The CCF can be fabricated by the infiltration method. The influence of the thickness and the pore size of the copper foam and the mass fraction of doped Fe3O4 powder on the absorption bandwidth were investigated. When the thickness of the CCF is 1.5 mm, the pore size of the copper foam is 95 pores per inch (ppi), and the mass fraction of Fe3O4 is 1%; a broadband absorption is achieved in the range of 0.11-3.5 THz. It is noted that the mass fraction of Fe3O4 has a significant impact on the absorption bandwidth. In addition, the thickness of the CCF and the pore size of the copper foam also have an impact on the absorption. The impedance matching theory is introduced to understand the mechanism of broadband absorption. This flexible broadband absorber has potential application in terahertz stealth, shielding, and the sixth-generation (6G) broadband wireless communication in the future.

Relationship between right-to-left shunt and white matter lesions in patients with migraine: a single-center study.

Background: Migraine patients have an increased long-term risk of cardio and cerebrovascular events. However, whether these patients are more susceptible to white matter lesions (WMLs) remains debated. To explore this question, our study assessed the proportion of RLS in migraine patients and explored the association between right-to-left shunt (RLS) and WMLs. Methods: In this study, we included 998 migraine patients. Contrast transcranial doppler (c-TCD) was used to diagnose RLS and assess the extent of the shunt in RLS patients. Of the 998 patients, 505 underwent cranial magnetic resonance imaging (MRI) assessments. WMLs were classified into periventricular white matter lesions (pvWMLs) and deep white matter lesions (dWMLs). Results: Among the 998 migraine patients, 946 had migraine without aura (MO; mean age 36.68 ± 10.46 years; 80.5% female), and 52 had migraine with aura (MA; mean age 29.85 ± 8.59 years; 71.2% female). Compared with MO patients, MA patients had an earlier onset age (23.1 ± 7.97 vs. 28.44 ± 10.38 years, p < 0. 001) and a shorter disease duration (6.76 vs. 8.34 years, p = 0.024). The overall proportion of RLS patients was 41.9%, with a greater proportion of RLS patients in the MA group than in the MO group (55.8% vs. 41. 1%, p = 0.037). The percentage of RLS-positive patients with no/small shunt was greater in the MO group than in the MA group (81.5% vs. 65.4%, p = 0.004), whereas the percentage of RLS-positive patients with moderate/large shunt was greater in the MA group (34.6% vs. 18.5%, p = 0.024). The proportion of RLS patients was lower in the WML-positive group (n = 173) than in the WML-negative group (n = 332), but the difference was not significant (40.5% vs. 45.8%, p = 0.253). Conclusion: This study revealed that 41.9% of migraine patients had RLS, and the proportion of RLS patients was 41. 1% in the MO group and 55.8% in the MA group. The rate of RLS positivity in migraine patients may not be related to the incidence of WMLs.

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.

Meis1 Targets Protein Tyrosine Phosphatase Receptor J in Fibroblast to Retard Chronic Kidney Disease Progression.

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with the proliferation and activation of myofibroblasts being definite effectors and drivers. Here, increased expression of Meis1 (myeloid ecotropic viral integration site 1) is observed, predominantly in the nucleus of the kidney of CKD patients and mice, and negatively correlates with serum creatinine. Fibroblast-specific knock-in of Meis1 inhibits myofibroblast activation and attenuates renal fibrosis and kidney dysfunction in CKD models. Overexpression of Meis1 in NRK-49F cells suppresses the pro-fibrotic response induced by transforming growth factor-ß1 but accelerates by its knockdown. Mechanistically, Meis1 targets protein tyrosine phosphatase receptor J (Ptprj) to block renal fibrosis by inhibiting the proliferation and activation of fibroblasts. Finally, a new activator of Ptprj is identified through computer-aided virtual screening, which has the effect of alleviating renal fibrosis. Collectively, these results illustrate that the Meis1/Ptprj axis has therapeutic potential for clinically treating CKD.