Research on the spatiotemporal evolution and influencing factors of urbanization and carbon emission efficiency coupling coordination: From the perspective of global countries.

Strategic coordination between urbanization and carbon emission efficiency (CEE) is vital for promoting low-carbon urbanization and sustainable urban planning. In order to assess the coupled coordination degree (CCD) of urbanization and CEE and investigate the factors influencing the CCD, this research employs the Super slacks-based measure (SBM) model, the coupled coordination degree model (CCDM), and the Tobit model. Four key findings emerge from the analysis of the temporal and spatial evolution traits of the CCD based on data from 106 nations worldwide between 2005 and 2020. (1) The global CEE shows a significant downward trend, and the spatial disparity is unambiguous. high CEE countries hang in the north and west of Europe, while those in Asia, Africa and the east of Europe have lower CEE. (2) The combined urbanization level and demographic, economic and social urbanization are all on an upward trend. Singapore has the greatest degree of urbanization overall globally. (3) The CCD of urbanization and CEE shows a fluctuating upward trend, with particularly strong changes in 2018-2020. 2017 and 2018 are the years with better global coupling coordination status. During the study period, the CCD results of countries are mostly uncoordinated and low coordination, and the CCD of the United States, China, India and Japan is in the front. (4) The effect of urban electrification rate on the CCD is positive; the effect of foreign trade and net inflow of foreign direct investment is negative; while energy structure and industrial structure have no significant effect. A number of policy proposals are put forth in light of the outcomes of the research to enhance the coordination.

Predicting haemorrhagic transformation through serum biochemical indices for patients after endovascular treatment: a retrospective study.

INTRODUCTION: The aim of this study was to determine the serum biochemical markers that can predict the risk of haemorrhagic transformation (HT) before and after endovascular treatment (EVT). MATERIAL AND METHODS: This study included patients with anterior circulation large vessel occlusion (ACLVO) who underwent EVT within six hours of symptom onset between September 2017 and September 2022. These patients were retrospectively categorised into two groups: an HT group and a No-HT group. RESULTS: A total of 180 patients were included in the study, of whom 55 (30.6%) had HT. The monocyte count before EVT (p = = 0.005, OR = 0.694, 95% CI 0.536-0.898), the activated partial thromboplastin time before EVT (p = 0.009, OR = 0.186, 95% CI 0.699-0.952), and the eosinophil count after EVT (p = 0.038, OR = 0.001, 95% CI 0.000-0.018) were all found to be independent predictors of HT, with warning values of 6.65%, 22.95 seconds, and 0.035*10^9/L, respectively. When compared to prediction using only demographic data [AUC = 0.662,95% CI (0.545, 0.780)], adding biochemical indices before EVT [AUC = 0.719,95% CI (0.617, 0.821)], adding biochemical indices after EVT [AUC = 0.670,95% CI (0.566, 0.773)], and adding both [AUC = 0.778,95% CI (0.686, 0.870)], the prediction efficiency of HT was improved among all three combinations, with no statistical significance. CONCLUSIONS: The levels of serum biochemical markers were found to show significant changes before and after EVT in ACLVO patients. A combination of demographic data and serum biochemical markers proved to be effective in predicting the occurrence of HT in patients with ACLVO who underwent EVT.

SIRT4 promotes neuronal apoptosis in models of Alzheimer's disease via the STAT2-SIRT4-mTOR pathway.

Alzheimer's disease (AD) is the leading cause of dementia and presents a considerable disease burden. Its pathology involves substantial neuronal loss, primarily attributed to neuronal apoptosis. Although sirtuin 4 (SIRT4) has been implicated in regulating apoptosis in various diseases, the role of SIRT4 in AD pathology remains unclear. The study employed APP/PS1 mice as an animal model of AD and amyloid-ß (Aß)1-42-treated HT-22 cells as an AD cell model. SIRT4 expression was determined by quantitative real-time polymerase chain reaction, western blot, and immunofluorescence. A Sirt4 knockdown model was established by intracranial injection of lentivirus-packaged sh-SIRT4 and cellular lentivirus transfection. Immunohistochemistry and flow cytometry were used to examine Aß deposition in mice and apoptosis, respectively. Protein expression was assessed by western blot analysis. The UCSC and JASPAR databases were used to predict upstream transcription factors of SIRT4. Subsequently, the binding of transcription factors to SIRT4 was analyzed using a dual-luciferase assay and chromatin immunoprecipitation. SIRT4 expression was upregulated in both APP/PS1 mice and Aß-treated HT-22 cells in comparison to their respective control groups. Sirt4 knockdown in animal and cellular models of AD resulted in reduced apoptosis, decreased Aß deposition, and amelioration of learning and memory impairments in mice. Mechanistically, SIRT4 modulates apoptosis via the mTOR pathway and is negatively regulated by the transcription factor signal transducer and activator of transcription 2 (STAT2). Our study findings suggest that targeting the STAT2-SIRT4-mTOR axis may offer a new treatment approach for AD.

Effects of alendronate on cartilage lesions and micro-architecture deterioration of subchondral bone in patellofemoral osteoarthritic ovariectomized rats with patella-baja.

BACKGROUND: Patellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks. METHODS: Patella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague-Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 µg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT). RESULTS: Our results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone. CONCLUSION: The early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

How to achieve green development? A study on spatiotemporal differentiation and influence factors of green development efficiency in China.

For a long time, China 's extensive economic development model has produced a large amount of emissions, which has brought indelible damage to the environment. Green development is of vital importance for China to achieve high-quality development, and it is the core of alleviating environmental problems and promoting sustainable development. How to achieve China 's green development requires us to evaluate the level of green development in China 's provinces and analyze the reasons. In this study, an evaluation index system including undesired output of green development efficiency is constructed, and then the Supe-SBM model is used to assess the green development efficiency of 30 Chinese provinces. This paper also discusses the spatial and temporal differences as well as the factors affecting green development efficiency of green development efficiency among provinces. The findings demonstrate: (1) The green development efficiency in the eastern region is the highest, followed by the western region, while the central region has the lowest, but they all show a downward trend. (2) The spatial characteristics of green development efficiency are remarkable, according to the Global Moran's I index. However, the results of local spatial agglomeration demonstrate "small agglomeration and large dispersion," with the majority of provinces exhibiting L-L agglomeration. (3) Technological Progress, Opening Up, Urbanization Level are positively correlated with the green development efficiency. Industrial Structure, Financial Development, Energy Structure and green development efficiency are significantly negatively correlated, while Environmental Regulation shows no significant impact.

Clinical application of instant 3D printed cast versus polymer orthosis in the treatment of colles fracture: a randomized controlled trial.

BACKGROUND: The shortcomings of plaster in water resistance, air permeability, skin comfort, fixed stability and weight of wearing are still to be solved. 3D printed cast can overcome the above shortcomings. At present, there is a relative lack of data on the clinical application of 3D printed cast, probably due to its complexity, relatively long operating time, and high price. We aimed to compare and evaluate the short-term effectiveness, safety and advantages of 3D printed wrist cast versus polymer orthosis in the treatment of Colles fracture. METHODS: Forty patients with Colles fracture in our hospital from June to December 2022 were selected and divided into an observation group (20 patients, treated with instant 3D printed cast) and a control group (20 cases, treated with polymer orthosis). Both groups treated with manual reduction and external fixation. The visual analogue scale (VAS), immobilization effectiveness and satisfaction scores, Disability of the Arm, Shoulder and Hand (DASH) score, complications and imaging data were collected and compared before immobilization and at 2, 6 and 12 weeks after the fracture. RESULTS: VAS at 2 weeks after the fracture was significantly lower in the observation group than in the control group ( P < 0.05). The immobilization effectiveness and satisfaction scores at 6 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). The DASH scores at 2 and 6 weeks after the fracture were significantly lower in the observation group than in the control group (all P < 0.05). There wasn't rupture of the printed cast or orthosis in both groups. There were 2 cases of skin irritation in the control group, and no skin irritation occurred in the observation group. The palmar tilt angle and ulnar inclination angle at 2 weeks and 12 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). CONCLUSIONS: Both instant 3D printed cast and polymer orthosis are effective in the treatment of Colles fracture. But instant 3D printed cast is better than polymer orthosis in areas of good clinical and imaging performance, and high patient satisfaction and comfort.

Prediction of Death in Intracerebral Hemorrhage Patients After Minimally Invasive Surgery by Vital Signs and Blood Glucose.

OBJECTIVE: This study examined the impact of vital signs and blood glucose levels on the long-term prognosis of intracerebral hemorrhage (ICH) patients treated with minimally invasive surgery (MIS). METHODS: The patients diagnosed with ICH and treated with MIS within 24 hours of admission at the ∗∗ Hospital between January 2020 and October 2021 were included. The relationship between a range of indicators, including vital signs, blood glucose levels, and patient mortality at discharge and 3 or 12 months postdischarge were analyzed. RESULTS: A total of 195 consecutive patients were included, of which 16 patients passed away during hospitalization, 29 and 34 within 3 and 12 months postdischarge, respectively. The multivariate analysis revealed that hospital death positively correlated with age ≥66.50 years, fasting blood glucose ≥8.25 mmol/L on the third day after MIS, systolic blood pressure ≥166.00 mmHg on the third day, and heart rate ≥89.50 beats/min at discharge (area under the curve [AUC] = 0.927). Death at 3 months positively correlated with male sex, blood glucose before dinner ≥8.15 mmol/L on the second day after MIS, body temperature ≥36.95°C at discharge, and heart rate ≥89.50 beats/minute at discharge (AUC = 0.810). Death at 12 months positively correlated with age ≥61.50 years, body temperature ≥36.95°C at discharge, and heart rate ≥92.50 beats/min on the third day after MIS (AUC = 0.824). CONCLUSIONS: The prognosis of ICH patients after MIS is closely related to their vital signs and blood glucose levels at various stages of hospitalization.

Predictive factors of poor outcome and mortality among anterior ischaemic stroke patients despite successful recanalisation in China: a secondary analysis of the CAPTURE trial.

OBJECTIVES: This work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation. SETTING AND PARTICIPANTS: This study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18-80 years with LVO in anterior circulation. INTERVENTIONS: Thrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the χ2 test or Fisher's exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach. RESULTS: Among the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass. CONCLUSIONS: Age, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy. TRIAL REGISTRATION NUMBER: NCT04995757.

Spatiotemporal evolution and influencing factors of water resource green efficiency in the cities of the Yangtze River Economic Belt.

Effectively utilizing water resources, which is a fundamental natural resource and a vital economic resource, directly impacts how a country's economy develops. In this study, the Super-SBM model is used to calculate the city water resource green efficiency (CWRGE) of the Yangtze River Economic Belt (YREB), 108 cities that are prefecture level or higher, from 2006 to 2021. And its temporal and spatial evolution as well as its affecting variables are examined. The results indicate that, as a whole, the YREB's CWRGE has not yet achieved an effective level. The CWRGE in the YREB generally exhibits a trend of "first decreasing and then increasing, then decreasing and then increasing" and shows a "W"-shaped evolution law, and the overall trend is upward. There are just seven cities with effective data envelopment analysis (DEA), namely Changzhou, Hangzhou, Shanghai, Xuzhou, Changde, Changsha, and Yuxi. During the reporting period, the CWRGE of cities of various scales showed significant gaps: mega cities > big cities > small and medium-sized cities. From a regional perspective, the highest rate of CWRGE was found downstream of the YREB cities, then upstream, and the middle was the lowest. Spatial correlation findings demonstrated that both the agglomeration range and the outlier range were distributed, and there were mainly two positive aggregations of space forms ("high-high (H-H) type" and "low-low (L-L) type"), and the spatial distribution changed. The results of the spatiotemporal evolution demonstrate that there are more and more cities with high efficiency, as well as cities with low efficiency. From the results of the Tobit regression model, the CWRGE in the YREB are significantly improved by the economical development level, industrial scale, and water usage structure. While foreign direct investment and environmental regulation have considerable detrimental impacts, the impact of scientific and technological investment is not significant.

What were the spatiotemporal evolution characteristics and the influencing factors of urban land green use efficiency? A case study of the Yangtze River Economic Belt.

China's rapid urbanization has had a tremendous impact on the country's limited land resources, and one of the major issues of green development is how to utilize the limited land resources to maximize social, economic, and environmental advantages. From 2005 to 2019, the super epsilon-based measure model (EBM) was employed to assess the green land use efficiency of 108 prefecture-level and above cities in the Yangtze River Economic Belt (YREB), as well as investigate its spatial and temporal evolution and influential factors. The findings demonstrate that overall, urban land green use efficiency (ULGUE) in the YREB has been ineffective; in terms of city scale, megacities have the highest efficiency, followed by large cities and small and medium-sized cities; and at the regional level, downstream efficiency does have the greatest average value, followed by upstream efficiency and middle efficiency. The results of temporal and spatial evolution reveal that the number of cities with a high ULGUE is increasing in general but that their spatial characteristics are relatively dispersed. Population density, environmental regulation, industrial structure, technology input, and the intensity of urban land investment all have major beneficial effects on ULGUE, whereas urban economic development level and urban land use scale clearly have inhibitory effects. In light of the previous conclusions, some recommendations are made to continuously improve ULGUE.

Effect of intravenous thrombolysis on core growth rate in patients with acute cerebral infarction.

Objective: This study aimed to investigate the effects of recombinant tissue plasminogen activator intravenous thrombolysis (IVT) on the core growth rate of acute ischemic stroke. Methods: Stroke patients with large vessel occlusion and non-recanalization from IVT treatment were retrospectively included in this study and divided into two groups: IVT and non-IVT. The core growth rate was estimated by the acute core volume on perfusion CT divided by the last known well time from stroke to CT perfusion. The primary endpoint was the core growth rate, the tissue outcome was 24 h-ASPECTS, and the clinical outcome was a 3-month modified Rankin score. Results: A total of 94 patients were included with 53 in the IVT group and 41 in the non-IVT group. There was no significant difference in age, gender, hypertension, diabetes, atrial fibrillation, acute NIHSS, and last known well time from stroke to CT perfusion acquisition between the two groups. The core growth rate in the IVT group was lower than that in the non-IVT group, which was statistically significant after multivariate adjustment (coefficient: -5.20, 95% CI= [-9.85, -0.56], p = 0.028). There was a significant interaction between the IVT and the collateral index in predicting the core growth rate. The analysis was then stratified according to the collateral index, and the results suggested that IVT reduced the core growth rate more significantly after the worsening of collateral circulation (coefficient: 15.38, 95% CI= [-26.25, -4.40], p = 0.007). The 3-month modified Rankin score and 24 h-ASPECTS were not statistically significant between the two groups. Conclusion: Intravenous thrombolysis reduces the core growth rate in patients with AIS, especially those with poor collateral status.

Spatiotemporal differentiation of carbon emission efficiency and influencing factors: From the perspective of 136 countries.

The severity of the global climate issue is rising, primarily as a result of excessive carbon dioxide emissions. Climate change is a global problem. How to reduce carbon dioxide emissions while promoting social and economic development is a problem that all countries need to face. This study examines global carbon emission efficiency in order to make recommendations for comprehensively improving global low-carbon development level. We extend the research scale of carbon emission efficiency from countries, regions, economic belts and sectors to the world, which can show the differences of countries and has theoretical guiding significance for global low-carbon development. This study calculates the carbon emission efficiency for 136 countries from 2000 to 2019 using the Super-EBM model. The discussion that follows examines the temporal and spatial characteristics of carbon emissions efficiency in 136 countries from the perspective of countries, developed and developing countries, and regions. Finally, the Tobit model is used to comprehensively analyze the factors that affect carbon emission efficiency. The results show that: (1) There are great differences in carbon emission efficiency among countries and regions. Only a few countries reach the production frontier, mainly in Europe, which are Switzerland, Luxembourg, Iraq, Norway, Denmark and the United Kingdom. The carbon emission efficiency of most countries is not ideal, being mainly concentrated in Asia and Africa, and has not achieved significant improvement over time. Asia has the lowest carbon emission efficiency. Mongolia, Ukraine, Iran, Angola, Belarus and Uzbekistan are the key governance areas for global energy conservation and carbon emissions reduction. (2) Developed countries have the much higher average carbon emission efficiency than developing countries. Combined with the industrial development stages of developed and developing countries, this is in line with the environmental Kuznets curve (EKC) hypothesis. The average carbon emission efficiency gap between developing and developed countries shows a trend of "first narrowing and then widening", which demonstrates that developing countries' reliance on energy input to boost their economies will improve carbon emission efficiency, but only temporarily. (3) Urbanization level, foreign trade and proportion of renewable energy effectively improve the carbon emission efficiency, while industrial structure and proportion of electricity users have an inhibitory effect on the carbon emission efficiency. Global low-carbon development should be hastened by strengthening international cooperation, optimizing industrial structure, promoting urbanization and foreign trade, and adjusting the energy structure.

Green Total-Factor Energy Efficiency of Construction Industry and Its Driving Factors: Spatial-Temporal Heterogeneity of Yangtze River Economic Belt in China.

With the proposal of the "carbon peak, carbon neutral" goal, energy efficiency has become one of the key means to achieve energy conservation and emission reduction at this stage. The construction industry, as a cornerstone of China's economy, is characterized by serious overcapacity, energy waste, and pollution. As a result, academic research on its energy efficiency is gaining traction. This paper employed the Super-EBM model considering undesirable output to evaluate the green total-factor energy efficiency of the construction industry (CIGTFEE) in the Yangtze River Economic Belt (YREB) from 2003 to 2018. The spatial-temporal evolution characteristics and spatial heterogeneity of CIGTFEE were analyzed in detail through geospatial analysis. Finally, the driving factors of CIGTFEE were analyzed through a spatial econometric model. The results indicated that, during the sample research period, the CIGTFEE showed a holistic growth trend with volatility. By region, the downstream CIGTFEE grew sharply until 2006 and then remained fairly stable, while the midstream conformed to the "M" trend and the upstream region showed an inverted u-shaped trend; From the perspective of spatial differentiation, the CIGTFEE in YREB shows a significant spatial agglomeration situation, while the spatial agglomeration degree weakened. It existed a ladder-shaped change trend, with the regional average CIGTFEE from high to low levels as follows: Downstream, Midstream, and Upstream, and showed an obvious polarization in the upstream and downstream. From the analysis of the driving factors, CIGTFEE is significantly promoted by economic growth, energy structure, and human capital and suppressed by urbanization level, yet the impact of technological progress and the level of technology and equipment is not significant. In summary, province-specific policies based on spatial and temporal heterogeneity were proposed to improve the CIGTFEE of YREB.

Biocatalytic Depletion of Tumorigenic Energy Sources Driven by Cascade Reactions for Efficient Antitumor Therapy.

Glucose and lactate play important roles for tumor growth. How to simultaneously deprive tumors of glucose and lactate is a big challenge. We have developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx), and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H2 O2 ) generation. Meanwhile, CAT catalyzes H2 O2 into O2 , which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual depletion of glucose and lactate with O2 supply is a promising strategy for efficient antitumor starvation therapy.

The efficacy of dynamic compression locking system vs. dynamic hip screw in the treatment of femoral neck fractures: a comparative study.

BACKGROUND: There is still a lack of consensus on which internal fixation method can better maintain the stability of femoral neck fractures (FNF), promote fracture healing, and reduce postoperative complications such as femoral head necrosis and nonunion. Therefore, the purpose of this study was to evaluate the clinical efficacy of the novel dynamic compression locking system (DCLS) versus dynamic hip screw (DHS) in the treatment of FNF. METHODS: Fifty cases of FNF from July 2018 to February 2020 were retrospectively analyzed. According to different treatment methods, they were divided into DCLS group (26 cases) and DHS group (24 cases). Baseline data, intraoperative and postoperative clinical data, reoperation rate, and Harris score were collected to evaluate the clinical efficacy. RESULTS: All patients were followed up for 24 months. All "fractures" were caused by fall. The baseline data of the two groups were comparable (P > 0.05). There weren't significant differences in the length of hospital stay and mobility after two years postoperatively between the two groups (P > 0.05). The operation time, blood loss, incision length, fluoroscopy times and the degree of femoral neck shortening after two years postoperatively in the DCLS group were significantly less than those in the DHS group (all P < 0.05). Harris score after two years postoperatively in the DCLS group was significantly higher than that in the DHS group (P < 0.05). Although the reoperation rate in the DHS group was slightly higher than that in the DCLS group, it wasn't statistical significance (P > 0.05). CONCLUSIONS: Compared with DHS, DCLS in the treatment of FNF had less surgical trauma, shorter incision length, shorter operation time, lower radiation dose and higher Harris scores. Although the reoperation rate in the DHS group was slightly higher than that in the DCLS group, it wasn't statistical difference. Further research is needed.

Parathyroid Hormone (1-34) Attenuates Cartilage Degradation and Preserves Subchondral Bone Micro-architecture in Rats with Patella Baja-Induced-Patellofemoral Joint Osteoarthritis.

Several studies have revealed that PTH1-34 may possess the potential for treating osteoarthritis (OA) and osteoporosis. However, no study has yet determined whether PTH1-34 can be used for the treatment of patella baja-induced patellofemoral joint OA (PFJOA). Thus, this study sought to assess the efficacy of PTH1-34 for the treatment of PFJOA in a rat model. Patella baja was induced in 3-month-old female Sprague-Dawley (SD) rats by patellar ligament shortening (PLS), after which the rats were randomly divided into three groups (n = 12): Sham, PLS, and PTH group (PTH + PLS, PTH1-34, 30 µg/kg/d, 5 days per week for 10 weeks). Thereafter, radiographic imaging, macroscopic and microscopic analyses, immunohistochemistry, and microcomputed tomography (CT) analysis were performed. The appearance of PLS-induced PFJOA promoted obvious changes in the patellar position and structure in the PLS group, which were characterized by cartilage degeneration, subchondral bone microstructure deterioration, patella baja, and increasing patella length. However, these negative characteristics were markedly ameliorated by PTH1-34, which not only inhibited cartilage catabolism by decreasing MMP-13 and ADAMTS-4 but also enhanced anabolism by increasing Col-II and Aggrecan. Furthermore, the micro-CT results showed a marked improvement in subchondral bone microarchitecture. The findings presented herein demonstrated that early treatment with PTH1-34 could improve cartilage metabolism and subchondral bone health in this PFJOA model.

Endovascular treatment of acute ischemic stroke with a fully radiopaque retriever: A randomized controlled trial.

Objective: The Neurohawk retriever is a new fully radiopaque retriever. A randomized controlled non-inferiority trial was conducted to compare the Neurohawk and the Solitaire FR in terms of safety and efficacy. In order to evaluate the efficacy and safety of endovascular treatment in acute ischemic stroke (AIS) caused by intracranial atherosclerotic disease (ICAD) larger vessel occlusion (LVO), a sub-analysis was performed. Methods: Acute ischemic stroke patients aged 18-80 years with LVO in the anterior circulation were randomly assigned to undergo thrombectomy with either the Neurohawk or the Solitaire FR. The primary efficacy endpoint was successful reperfusion (mTICI 2b-3) rate by the allocated retriever. A relevant non-inferiority margin was 12.5%. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality within 90 days. Secondary endpoints included first-pass effect (FPE), modified FPE, and favorable outcomes at 90 days. In subgroup analysis, the patients were divided into the ICAD group and non-ICAD group according to etiology, and baseline characteristics, angiographic, and clinical outcomes were compared. Results: A total of 232 patients were involved in this analysis (115 patients in the Neurohawk group and 117 in the Solitaire group). The rates of successful reperfusion with the allocated retriever were 88.70% in the Neurohawk group and 90.60% in the Solitaire group (95%CI of the difference, -9.74% to 5.94%; p = 0.867). There were similar results in FPE and mFPE in both groups. The rate of sICH seemed higher in the Solitaire group (13.16% vs. 7.02%, p = 0.124). All-cause mortality and favorable outcome rates were comparable as well. In subgroup analysis, 58 patients were assigned to the ICAD group and the remaining 174 to the non-ICAD group. The final successful reperfusion and favorable outcome rates showed no statistically significant differences in two groups. Mortality within 90 days was relatively lower in the ICAD group (6.90% vs. 17.24%; p = 0.054). Conclusion: The Neurohawk retriever is non-inferior to the Solitaire FR in the mechanical thrombectomy of large vessel occlusion-acute ischemic stroke (LVO-AIS). The sub-analysis suggested that endovascular treatment including thrombectomy with the retriever and essential rescue angioplasty is effective and safe in AIS patients with intracranial atherosclerotic disease-larger vessel occlusion (ICAD-LVO). Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04995757, number: NCT04995757.

Mechanical Thrombectomy for Acute Stroke Due to Large-Vessel Occlusion Presenting With Mild Symptoms.

Purpose: To evaluate the safety and efficacy of mechanical thrombectomy (MT) for acute stroke due to large vessel occlusion (LVO), presenting with mild symptoms. Methods: A prospective cohort study of patients with mild ischemic stroke and LVO was conducted. Patients were divided into two groups: MT group or best medical management (MM) group. Propensity score matching (PSM) was conducted to reduce the confounding bias between the groups. The primary outcome was functional independence at 90 days. The safety outcome was symptomatic intracranial hemorrhage (sICH). Univariate and multivariate logistic regression analyses were used to identify the independent factors associated with outcomes. Results: Among the 105 included patients, 43 were in the MT group and 62 in the MM group. Forty-three pairs of patients were generated after PSM. There were no significant differences in sICH rates between two groups (p = 1.000). The MT group had a higher proportion of independent outcomes (83.7% MT vs. 67.4% MM; OR 2.483; 95% CI 0.886-6.959; p = 0.079) and excellent outcomes (76.7% MT vs. 51.2% MM; OR 3.150; 95% CI 1.247-7.954; p = 0.013) compared to the MM group, especially in patients with stroke of the anterior circulation (p < 0.05). Multivariate logistic regression analysis showed that small infarct core volume (p = 0.015) and MT treatment (p = 0.013) were independently associated with excellent outcomes. Conclusions: Our results suggest that MT in stroke patients, presenting with mild symptoms, due to acute LVO in the anterior circulation may be associated with satisfactory clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04526756.

Reconstituting neurovascular unit with primary neural stem cells and brain microvascular endothelial cells in three-dimensional matrix.

Neurovascular dysfunction is a primary or secondary cause in the pathogenesis of several cerebrovascular and neurodegenerative disorders, including stroke. Therefore, the overall protection of the neurovascular unit (NVU) is a promising therapeutic strategy for various neurovascular diseases. However, the complexity of the NVU limits the study of the pathological mechanisms of neurovascular dysfunction. Reconstituting the in vitro NVU is important for the pathological study and drug screening of neurovascular diseases. In this study, we generated a spontaneously assembled three-dimensional NVU (3D NVU) by employing the primary neural stem cells and brain microvascular endothelial cells in a Matrigel extracellular matrix platform. This novel model exhibits the fundamental structures and features of the NVU, including neurons, astrocytes, oligodendrocytes, vascular-like structures, and blood-brain barrier-like characteristics. Additionally, under oxygen-glucose deprivation, the 3D NVU exhibits the neurovascular- or oxidative stress-related pathological characteristics of cerebral ischemia and the injuries can be mitigated, respectively, by supplementing with the vascular endothelial growth factor or edaravone, which demonstrated that the availability of 3D NVU in ischemic stroke modeling. Finally, the 3D NVU promoted the angiogenesis and neurogenesis in the brain of cerebral ischemia rats. We expect that the proposed in vitro 3D NVU model will be widely used to investigate the relationships between angiogenesis and neurogenesis and to study the pathology and pharmacology of neurovascular diseases.

Epiberberine ameliorated diabetic nephropathy by inactivating the angiotensinogen (Agt) to repress TGFß/Smad2 pathway.

BACKGROUND: Diabetic nephropathy (DN) is a severe microvascular complication of diabetes with prominent morbidity and mortality. At present, there are hardly any effective drugs to treat DN. Epiberberine (EPI), an isoquinoline alkaloid, has attracted considerable attention due to its anti-hyperglycemic, anti-hyperlipidemic, and anti-inflammatory functions. However, whether there is a protective effect of EPI on DN has not been reported. PURPOSE: The research was aimed to investigate the activities of EPI alleviating kidney damage in db/db mice and to explore its possible mechanisms. STUDY DESIGN: The db/db mice and high-glucose (HG) induced glomerular mesangial cells (GMCs) were used to explore the protective effect of EPI on DN in vivo and in vitro. METHODS: The changes in fasting blood glucose, metabolic index, renal function, and histopathological morphology in db/db mice were detected to evaluate the therapeutic effect of EPI. Then, renal transcriptome and molecular docking were used to screen the key targets. Subsequently, HG-induced GMCs through mimicing the pathological changes in DN were utilized to study the renal protective effects of EPI and its potential mechanism. RESULTS: The results in vivo showed that EPI administration for 8 weeks significantly alleviated diabetes-related metabolic disorders, improved renal functions, and relieved the histopathological abnormalities of renal tissue, especially renal fibrosis in db/db mice. The results in vitro showed that EPI inhibited the proliferation and induced the G2/M phase arrest of HG-induced GMCs. Moreover, a key gene Angiotensinogen (Agt) was screen out by the RNA-seq of kidney and molecular docking, and EPI reduced Agt, TGFß1, and Smad2 expression in vitro and in vivo. Noteworthy, Agt knockdown by siRNA significantly attenuated these beneficial efficacies exerted by EPI, indicating that Agt played a crucial role in the process of EPI improving DN. CONCLUSION: These findings suggested that EPI might be a potential drug for the treatment of DN dependent on the Agt-TGFß/Smad2 pathway.