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Abstract It is still unclear whether emissions reductions from electric vehicles can be achieved across different regions from a lifecycle perspective. Here we use the life cycle assessment model and Quasi Input-Output model to evaluate the carbon dioxide emissions and air pollutants of internal combustion engine vehicles, plug-in hybrid electric vehicles, and battery electric vehicles in different provinces of China, with the provincial electricity consumption data and the sales data of electric vehicles. We find that battery electric vehicles have achieved 11.8% and 1.1% reduction in carbon dioxide and nitrogen oxide emissions, respectively, compared to internal combustion engine vehicles. In contrast, the emissions of sulfur dioxide and particulate matter 2.5 increased by 10% and 20%, respectively. Due to the coal-based power generation structure and the cold weather, the emission intensity of battery electric vehicles in most northern provinces is higher than that in southern provinces. From 2020 to 2030, improving technological progress and optimizing electricity mix will greatly assist in achieving emissions reduction. The results can help policy-makers better understand the emission characteristics and reasonably plan future emission reduction strategies in transportation.

Objective The transverse tibial transfer technique is employed primarily to treat diabetic foot ulcers (DFUs), aiming to enhance leg circulation and promote new blood vessel growth. This technique is also beneficial for various conditions associated with poor blood flow in the lower extremities. However, there is no clear molecular mechanism to explain the relationship between the transverse tibial transfer technique and angiogenesis in patients with diabetic foot. This study aims to preliminarily explore the change of IL‐6 and related cytokines in promoting angiogenesis during transverse tibial transplantation, providing a direction for future research. Methods We retrospectively assessed a study from April 2022 to November 2023 on 76 patients with severe DFUs at Wagner stages 3–4. Flow cytometry was used to detect the levels of 12 cytokines in serum before the operation and 3, 7, 14, 21, and 35 days after the operation. Ankle‐brachial index (ABI), transcutaneous oxygen tension (TcPO2), and glycosylated hemoglobin (Hba1c) were recorded at admission and discharge. We examined the variations in cytokine levels, wound healing duration, amputation rates, infection incidence, and other key outcomes. Results In our investigation, a total of 76 individuals participated, comprising 49 males and 27 females. These subjects had an average age of 64.7 years, with a standard deviation of 13 years. The mean ulcer healing time was 74 ± 31 days, amputation occurred in 3 patients, pin tract infection occurred in one patient (1.3%), and incision infection occurred in one patient (1.3%). By day 35 following the surgery, both the ABI and TcPO2 values showed a significant increase from their preoperative levels. HbA1c significantly improved compared with presurgery (p

A heterozygous microdeletion of chromosome 7q11.23 causes the rare neuropsychiatric developmental disorder Williams-Beuren Syndrome. The syndrome is more difficult to diagnose before birth than after, even though the syndrome often manifests prenatally as intrauterine growth restriction and cardiovascular defects on prenatal ultrasonography. The potentially poor prognosis of affected individuals highlights the need to improve prenatal diagnosis of the syndrome. This review summarizes recent advances in our understanding of the genetics of Williams-Beuren Syndrome and its manifestations on prenatal ultrasonography, which may facilitate its early detection and inform prenatal genetic counseling.

Abstract Objective To explore the distribution of thrombin–antithrombin complex (TAT), plasmin-α2-antiplasmin inhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) in healthy older Chinese adults, and establish the reference intervals (RIs). Methods The Biotech Shine i2900 chemiluminescence immune assay was used to measure the plasma concentrations of TAT, PIC, TM, and t-PAIC in 1628 adults ≥ 60 years. The RIs were established using the 2.5th and 97.5th percentiles of the distribution. Results TAT levels were lower in males than females across all ages. Differences between the ages of 60–79 and ≥ 80 in both sex groups were statistically significant, with an upward trend with age. PIC levels showed no difference between the sexes but increased with age in both groups. TM levels did not differ between the sex groups, with slight fluctuation with age. The level in females aged 60–69 was slightly higher than that in the other groups; the difference was statistically significant. T-PAIC levels were not significantly different between the sex groups, with less fluctuation with sex and age. The level in males ≥ 80 years old was slightly lower than that in the other groups; the difference was statistically significant. The RIs for all markers in healthy older Chinese adults were determined and statistically reported by age and sex. For TAT, the RIs for males aged 60–79 and ≥ 80 are 0.51–2.30 ng/mL and 0.88–3.72 ng/mL, respectively, whereas for females aged 60–79 and ≥ 80, the RIs are 0.68–2.82 ng/mL and 1.02–3.67 ng/mL, respectively. For PIC, the RIs for the age groups 60–69, 70–79, and ≥ 80 are 0.10–0.89 µg/mL, 0.12–1.00 µg/mL, and 0.21–1.04 µg/mL, respectively. The RI of TM for females aged 60–69 is 3.32–13.22 TU/mL, whereas it is 2.96–13.26 TU/mL for the other groups. The RI of t-PAIC for males aged ≥ 80 is 1.63–10.68 ng/mL, whereas it is 2.33–11.34 ng/mL for the other groups. Conclusions Discrepancies exist in thrombus markers among different sex and age groups. The RIs of TAT, PIC, TM and t-PAIC for healthy older Chinese adults were successfully established.

Titanium hydride (TiH2), a promising high-energy additive, is doped into PTFE/Al to optimize the energy output structure of the reactive jet and strive for better aftereffect damage ability to the target. Six types of PTFE/Al/TiH2 reactive liners with different TiH2 content are prepared by the molding and sintering method. The energy release characteristics of PTFE/Al/TiH2 reactive jet are tested by the transient explosion energy test, and are characterized from pressure and temperature. The reaction delay time, pressure history, and temperature history of the energy release process are obtained, then the actual value of released energy and reaction efficiency of the reactive jet are calculated. The results show that the peak pressure and temperature of the PTFE/Al/TiH2 jet initially increase and then decrease with increasing TiH2 content. When the TiH2 content is 10%, the actual value of released energy and reaction efficiency increased by 24% and 6.4%, respectively, compared to the PTFE/Al jet. The reaction duration of the reactive material is significantly prolonged as the TiH2 content increased from 0% to 30%. Finally, combined with the energy release behaviors of PAT material and the dynamic deformation process of liner, the enhancement mechanism of TiH2 on energy release of the reactive jet is expounded.

Introduction: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive. Objectives: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach. Methods: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro. Results: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro. Conclusion: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.

Abstract The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates β-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-β signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.

Abstract Despite extensive research on the relationship between choline and cardiovascular disease (CVD), conflicting findings have been reported. We aim to investigate the relationship between choline and CVD. Our analysis screened a retrospective cohort study of 14,663 participants from the National Health and Nutrition Examination Survey conducted between 2013 and 2018. Propensity score matching and restricted cubic splines was used to access the association between choline intake and the risk of CVD. A two-sample Mendelian randomization (MR) analysis was conducted to examine the potential causality. Additionally, sets of single cell RNA-sequencing data were extracted and analyzed, in order to explore the role of choline metabolism pathway in the progression and severity of the CVD and the underlying potential mechanisms involved. The adjusted odds ratios and 95% confidence intervals for stroke were 0.72 (0.53–0.98; p = 0.035) for quartile 3 and 0.54 (0.39–0.75; p

Abstract Background Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis. Methods We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. Results Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. Conclusion CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

ObjectiveCognitive impairment is notably prevalent among schizophrenic individuals and is acknowledged as one of the core features of the disorder. Despite the proliferation of literature on cognitive rehabilitation treatments for schizophrenia in recent years, there remains a dearth of systematic reviews and selections of research in this area. From a bibliometric perspective, this study aims to analyze and discuss the current state, developmental trends, and potential research hotspots of cognitive rehabilitation in schizophrenia over the past two decades.MethodsThe Core database of Web of Science was utilized to retrieve articles on cognitive rehabilitation in Schizophrenia that were published from 2004 to 2024. Bibliometrics was applied to perform both quantitative and qualitative analyses of authors, institutions, countries, journals, references, and keywords, leveraging tools such as CiteSpace, VOSviewer, and the R software package Bibliometrix.ResultsA total of 2,413 articles were encompassed in this study, comprising 1,774 regular articles and 373 review articles. The United States emerged as the country with the highest productivity and citation counts, engaging in academic collaborations with over 40 nations. This was followed by the United Kingdom and Spain. King’s College London stood out as the leading institution in the field. However, the article with the highest average citation rate was authored by Susan R. McGurk from the Dartmouth Centre for Psychiatric Research in the United States. Schizophrenia Research proved to be the most influential journal in this domain, with its articles being cited over 10,000 times.ConclusionThis study provides a comprehensive review of research achievements in cognitive rehabilitation for schizophrenia spanning from 2004 to 2024, and outlines global research hotspots and trends with future projections. Currently, methods for cognitive rehabilitation in schizophrenia and neural plasticity in the brain represent the cutting-edge of research. The safety, efficacy, and standardization of virtual reality are poised to emerge as potential future hotspots and trends in research. Additionally, the neurobiological foundations of cognitive remediation therapy constitute an unexplored territory ripe for further investigation.

BackgroundOver the past decade, the proportion of hepatitis C virus (HCV) genotypes (GT) 1 and 2 has decreased in almost all regions of China, while GT 3 and 6 have emerged as new challenges. GT 6 is unique in many respects, like high genetic variability and emerging resistant variants. This study aims to assess the efficacy of sofosbuvir (SOF)-based treatments in patients with GT 6 chronic hepatitis C (CHC).MethodsA retrospective analysis was conducted on patients with GT 6 HCV infection, who were diagnosed between July 2018 and May 2023. All patients received a 12-week course of SOF-based treatments. The primary efficacy endpoint was sustained virologic response (SVR), which is defined as having undetectable HCV RNA at 12 weeks after treatment completion (SVR12). The efficacy data for SVR12 were analyzed using both the evaluated population (EP) and per-protocol population (PP). For the PP populations, efficacy data were stratified using Forrester plots.ResultsA total of 201 patients were included in the study. In PP population, the end of treatment virological response rate was 99.48% (190/191), the SVR12 rate was 99.31% (143/144), and the SVR24 rate was 100.00% (75/75). Only one patient with genotype 6a experienced a relapse 12 weeks after the completion of treatment, but her HCV RNA was undetectable both at the end of treatment and 24 weeks after the end of treatment. Additionally, the normalization rates of alanine transaminase (ALT) and aspartate aminotransferase (AST) were significantly higher at the end of treatment (EOT) compared to baseline (27.36% vs. 93.03%, 36.32% vs. 95.02%, p

Summary: In patients with polycystic ovary syndrome (PCOS), the concentration of homocysteine (Hcy) in follicular fluid is inversely correlated with oocyte and embryo quality. Nevertheless, other metabolic abnormalities associated with PCOS may also impact oocyte and early embryo quality. Therefore, it remains uncertain whether reproductive function is affected in patients without PCOS with hyperhomocysteinemia (HHcy). Here, we observed reduced fertility, increased ovarian atretic follicles, and reduced oocyte maturation rates in HHcy mice. Proteomic analyses revealed that HHcy causes mitochondrial dysfunction and reduced expression of zona pellucida proteins (ZP1, ZP2, and ZP3) in oocytes. Transmission electron microscopy confirmed abnormal formation of the zona pellucida and microvilli in oocytes from HHcy mice. Additionally, in vitro fertilization (IVF) demonstrated a reduction in the rate of 2-cell embryo formation in HHcy mice. These findings reveal that HHcy reduces female reproductive longevity by affecting follicular development and oocyte quality.

Background Intracerebral hemorrhage (ICH) in young adults demands greater attention, given its poor prognosis; however, there has been a paucity of epidemiological data. The objective of this study is to estimate the temporal trends and distribution characteristics of the disease burden in 204 countries or territories between 1990 and 2021. Methods and Results The data, including incidence, mortality, prevalence, and disability‐adjusted life year (DALY) rates were sourced from the Global Burden of Diseases Study 2021. From 1990 to 2021, there was a significant decline in the global incidence (estimated annual percentage change=−1.05), mortality (estimated annual percentage change=−0.92), and DALY (estimated annual percentage change=−1.00) rates of ICH in young adults. In 2021, the highest incidence, mortality, and DALY rates were observed in Southeast Asia, East Asia, and Oceania. Globally, high systolic blood pressure, smoking, and ambient particulate matter pollution were identified as the primary contributors to the largest proportion of DALYs associated with ICH in young adults. The health inequality of ICH in young adults has been reduced over the past 3 decades. Conclusions There is a considerable degree of heterogeneity in the global burden of ICH in young adults. A decline in the incidence, mortality, prevalence, and DALY rates has been observed from 1990 to 2021, however, the number of absolute cases has increased. These results will enable health care professionals, policymakers, and researchers to refine the implementation of cost‐effective policies, the allocation of health care resources, and the management of patients to further mitigate the burden of ICH in young adults.

BackgroundDiabetic foot ulcers (DFUs) are severe complications of diabetes, involving multiple etiological factors including neuropathy, vascular insufficiency, and impaired wound healing. The global burden of DFUs is substantial, with significant morbidity and high management costs. Recent advancements have introduced the tibial cortex transverse transport (TTT) technique, which has shown promising results in the management of severe DFUs by promoting angiogenesis and immunomodulation.MethodsThis prospective cohort study enrolled patients with Wagner grade 3 and 4 DFUs, treated using the TTT technique from May 2022 to September 2023 at MianYang Central Hospital. The study assessed the influence of TTT on the perioperative neutrophil-to-lymphocyte ratio (NLR), an established biomarker of systemic inflammation, and its correlation with wound healing outcomes.ResultsA total of 82 patients were enrolled, with 66 completing the study. The survival analysis revealed that patients with a lower preoperative NLR experienced significantly faster wound healing compared with a high NLR (log rank test P< 0.05; hazard ratio (HR) = 0.46; 95% CI: 0.26–0.83). The optimal NLR cutoff values (4.25) were established to predict wound healing times for DFUs. The median NLR was significantly different before TTT surgery, 3 days after TTT surgery, and 1 month after TTT surgery (P

BackgroundLimitations of conventional treatment methods for sleep disorders have driven the use and development of complementary and alternative therapies such as acupuncture. However, despite the surge in related studies, there is still a lack of visual analysis and detailed elaboration regarding the current status, international collaborations, and research hotspots of acupuncture for sleep disorders.MethodsWe conducted a bibliometric analysis of publications on acupuncture for sleep disorders using the Web of Science Core Collection database from 2004 to 2023. We utilized the R package “bibliometrix” to count publications and citations, VOSviewer to create an inter-institutional referencing network, and CiteSpace to identify references and keywords with the highest citation bursts. Additionally, we employed a bibliometric online analysis platform designed for analyzing national partnerships.ResultsA total of 432 pertinent papers were retrieved, with China being the most prolific contributor, accounting for 61.6% of the publications, followed by the United States and South Korea. Despite China’s high output, its average article citation rate and proportion of international collaborations were notably lower than those of the United States. Key research institutions such as the University of Hong Kong, Shanghai University of Traditional Chinese Medicine, Memorial Sloan Kettering Cancer Center, and Guangzhou University of Chinese Medicine have played significant roles in this field. Among authors, Ka-Fai Chung from the University of Hong Kong stood out as the most productive. In terms of journals, MEDICINE was the most active, while SLEEP was considered the most authoritative. The clinical effects of acupuncture for insomnia have garnered significant attention in recent years, with electroacupuncture emerging as the prevailing technique for addressing sleep disorders.ConclusionThis bibliometric study effectively outlines the basic framework of knowledge surrounding acupuncture for sleep disorders over the past two decades, covering publications, countries, institutions, authors, and sources. It highlights promising clinical effects and underlying mechanisms of acupuncture, particularly for secondary insomnia and specific sleep disorders like restless legs syndrome. Moving forward, the focus and challenge for future research lie in the development of standardized study protocols and harmonization of efficacy assessment metrics.

Abstract Introduction Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. Methods We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. Results One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0–3 was 58.4%. Conclusion Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study.

Abstract Introduction Although antifungal supplementation reduces the fungal load in the corneal storage medium, consensus is lacking on the influence of dosing and temperature. The study aims to evaluate the impact of eye bank warming protocol and timing of antifungal supplements on efficacy in Optisol-GS and tissue. Methods Corneoscleral rims contaminated with Candida albicans (C. albicans) were incubated in Optisol-GS, either without antifungal agents or with the addition of amphotericin B or voriconazole at various concentrations (2 ×, 5 ×, 10 ×, and 20 × MIC), at different time points, and under various preservation temperatures (2–8 °C versus 2 h-room temperature exposure). Antifungal efficacy was evaluated by counting viable yeast colonies cultured from Optisol-GS samples. Tissue sterility was determined through direct tissue culture and histological examination of the contaminated rims after a 14-day incubation period. Results Room temperature exposure did not increase colony growth at the same multiple MIC of antifungal agents. Although antifungal addition reduced C. albicans growth in a concentration-dependent manner, yeast growth was still observed in all Optisol-GS samples with a single supplementation after a 14-day incubation. Only groups with additional antifungal supplementation on either day 2 or day 6 showed a 99% or greater reduction of C. albicans growth in Optisol-GS samples and yielded negative results in direct tissue culture. Conclusions The eye bank warming protocol did not compromise antifungal efficacy. To sustain the required concentration and effectively reduce C. albicans growth in Optisol-GS and contaminated tissue, additional antifungal supplementation on either day 2 or day 6 was necessary during a 2-week preservation period.

A ternary system of PTFE/Al/Bi2O3 is constructed by incorporating PTFE-based reactive material and thermite for enhancing the energy release of the PTFE-based reactive material. The effects of Bi2O3 in the PTFE/Al/Bi2O3 on both mechanical properties and the energy release were investigated through various tests such as thermogravimetry-differential scanning calorimetry, adiabatic oxygen bomb test and split Hopkinson pressure bar test. The microstructure observed through scanning electron microscope and X-ray diffraction results are used to analyze the ignition and reaction mechanism of PTFE/Al/Bi2O3. The results indicate that the PTFE/Al/Bi2O3 are capable of triggering the exothermic reaction of molten PTFE/Bi2O3 and Al/Bi2O3 over the PTFE/Al reactive materials, thereby promoting reactions. The excessive aluminum in the ternary system is beneficial for increasing energy release. The ignition of shock-induced chemical reactions in PTFE/Al/Bi2O3 is closely related to the material fracture. The dominant mechanism for hot-spot generation under Split Hopkinson Pressure Bar test is the frictional temperature rise at the microcrack after failure.

Objective The aim of this study was to evaluate the use of after‐visit instructions (AVIs) in an academic rheumatology clinic and assess the impact of standardized AVIs (sAVIs) and teach‐back (TB) on comprehension of health information. Methods A retrospective review of adult patients seen between October 1 and 8, 2021, at the rheumatology clinic collected data on patient demographics, clinical features, and the presence, content, and readability of AVIs. During a subsequent prospective proof‐of‐concept study, routinely scheduled patients seen at the rheumatology clinic were randomized into three groups: control (received standard of care), received sAVIs only, and received sAVIs plus TB. Patients completed a health literacy questionnaire, satisfaction survey, and a one‐ to two‐week postvisit telephone survey to assess AVI comprehension. Results Out of 316 retrospective patient visits, 82 (25.9%) received AVIs. Among 210 of 316 patients (66.5%) with management changes, 76 (36.1%) received AVI, with 74.2% of the instructions considered concordant with the provider's note. Use of AVIs was higher with management changes, new patient visits, and medical trainee/teaching clinics. AVIs were written at a median 6.8 grade level. A total of 75 patients completed the prospective study: 31 (41.3%) were in the control group, 19 (25.3%) were in the group that received sAVIs only, and 25 (33.3%) were in the group that received AVIs with TB. There were no differences in overall postvisit survey comprehension/retention scores among the three patient groups evaluated. Conclusion Although a lack of AVI use was identified, implementation of sAVIs did not appear to impact patient retention or comprehension of discharge health information.

Abstract The diagnosis of inherited retinal degeneration (IRD) is challenging owing to its phenotypic and genotypic complexity. Clinical information is important before a genetic diagnosis is made. Metabolomics studies the entire picture of bioproducts, which are determined using genetic codes and biological reactions. We demonstrated that the common diagnoses of IRD, including retinitis pigmentosa (RP), cone-rod dystrophy (CRD), Stargardt disease (STGD), and Bietti’s crystalline dystrophy (BCD), could be differentiated based on their metabolite heatmaps. Hundreds of metabolites were identified in the volcano plot compared with that of the control group in every IRD except BCD, considered as potential diagnosing markers. The phenotypes of CRD and STGD overlapped but could be differentiated by their metabolomic features with the assistance of a machine learning model with 100% accuracy. Moreover, EYS-, USH2A-associated, and other RP, sharing considerable similar characteristics in clinical findings, could also be diagnosed using the machine learning model with 85.7% accuracy. Further study would be needed to validate the results in an external dataset. By incorporating mass spectrometry and machine learning, a metabolomics-based diagnostic workflow for the clinical and molecular diagnoses of IRD was proposed in our study.

Abstract Background Multisystem childhood Langerhans cell histiocytosis (LCH) patients, especially those with risk organ (RO) involved, had not been satisfactorily treated under the international traditional schemes as high incidences of reactivation with late sequelae were largely reported. Over years, we have observed that LCH patients with varied clinical symptoms responded differently to different drugs, suggesting the current grouping strategies based only on the number of organs involved might be inadequate. LCH has been defined as an inflammatory myeloid tumor, thus this study has innovatively divided LCH pediatric patients into inflammatory or malignant symptoms group, and given different intensity treatment regimens to different groups. Aim This clinical study aimed to explore a more appropriate patient grouping system according to the LCH symptom presentations and examine the clinical outcomes of treatment strategies in different groups. Methods According to the clinical manifestations, 37 cases of children were divided into Group A (only inflammatory symptoms) and Group B (malignant symptoms with or without inflammatory symptoms). Patients in Group A and B were initially treated with vindesine (VDS) and methylprednisolone (PSL), and VDS, PSL, pirarubicin (THP) and cyclophosphamide (CTX), respectively. Treatment responses were evaluated six weeks after the induction therapy in all patients, and the criteria were disease status and clinical scores of symptoms. Results Pre- and post-treatment scores were 1.22 ± 0.547 and 0.00 ± 0.00 in Group A, and 14.79 ± 1.686 and 1.00 ± 1.563 in Group B, respectively. All patients had subsequentlly received maintenance therapy without progressive disease. The 4-year overall survival (OS) rate was 100% in both groups and the 4-year event-free survival (EFS) was 94.4% in Group A and 89.5% in Group B, respectively. There were no obvious adverse events (AE) in Group A, whereas the main AE in Group B were alopecia and non-lethal hematological toxicity. Conclusion Stratification according to patients’ clinical symptoms, with low-intensity treatment for inflammatory symptoms (mild manifestations) and intensive treatment with multiple drugs for malignant symptoms (severe manifestations), is a positive exploration that simplifies stratification method, achieves good long-term remission of the disease, and obtains a higher survival rate and quality of life, which seemed to be more appropriate for LCH patients.

Abstract Endometrial fibrosis is the histologic appearance of intrauterine adhesion (IUA). Emerging evidences demonstrated umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exo) could alleviate endometrial fibrosis. But the specific mechanism is not clear. In this study, we explored the effect of UCMSC-exo on endometrial fibrosis, and investigated the possible role of miR-140-3p/FOXP1/Smad axis in anti-fibrotic properties of UCMSC-exo. UCMSC-exo were isolated and identified. Transforming growth factor-β (TGF-β) was used to induce human endometrial stromal cell (HESC) fibrosis. Dual luciferase assay was performed to verify the relationship between miR-140-3p and FOXP1. The expressions of fibrotic markers, SIP1, and p-Smad2/p-Smad3 in HESCs stimulated with UCMSC-exo were detected by western blot. In addition, the effects of miR-140-3p mimic, miR-140-3p inhibitor and FOXP1 over-expression on endometrial fibrosis were assessed. The isolated UCMSC-exo had a typical cup-shaped morphology and could be internalized into HESCs. The expressions of fibrotic markers were significantly increased by TGF-β, which was reversed by UCMSC-exo. MiR-140-3p in UCMSC-exo ameliorated TGf-β-induced HESCs fibrosis. FOXP1 was identified as the direct target of miR-140-3p, which could inversely regulate miR-140-3p’s function on HESCs fibrosis. Furthermore, we demonstrated that miR-140-3p in UCMSC-exo regulated Smad signal pathway to exert the anti-fibrotic effect in HESCs. The anti-fibrotic effect of UCMSC-derived exosomes against HESC fibrosis was at least partially achieved by miR-140-3p/FOXP1/Smad axis.

BackgroundExposure to occupational metallic mixtures has a potential impact on olfactory function. However, research evidence is limited on the potential impact of exposure to metallic mixtures and olfactory dysfunction. Furthermore, the coal dust generated contains multiple various metals during coal mining, and no study yet has focus on the olfactory dysfunction of coal miners.ObjectivesIn this study, we evaluate the association between urinary metallic mixtures and olfactory function in coal miners, while also exploring the potential applicability of plasma olfactory marker protein (OMP) as a biomarker for assessing olfaction.MethodsFrom July to October 2023, coal workers from seven different coal mining enterprises were recruited for the survey when they come for the employee health checkup. Ultimately, 376 participants were met the inclusion criteria and, respectively, determined with the concentrations of urine (16 metals) and plasma (OMP). Meanwhile, applying UPSIT to access their olfactory function. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with olfactory function. Bayesian kernel machine regression (BKMR) and Quantile g-computation (QG-C) regression were employed to assess the overall association between metal mixtures and olfactory function and identify the major contributing elements.ResultsIn a single-metal model, two metals in urine were found to be significantly associated with olfactory function. RCS analysis further revealed that the association between Iron (Fe) and olfactory function was linear, while Lead (Pb) exhibited a non-linear. The BKMR model demonstrated a significant positive association between metal mixture concentration and olfactory function. Combined QG-C regression analysis suggested that metals Cr, Fe, Se, Sb, and Pb could impact the performance of the olfactory test (UPSIT), with Pb being identified as the most influential contributor. The correlation between plasma OMP protein levels and urinary metal concentrations was weak.ConclusionMultiple metals are associated with olfactory function in the coal miners. A significant positive association was observed between metal mixture concentrations and olfactory function, with Pb being the most important contributor. In this study, plasma OMP has not been demonstrated to serve as a biomarker for olfactory function.

Lewy body disease (LBD), one of the most common neurodegenerative diseases (NDDs), is characterized by excessive accumulation of α-synuclein (α-syn) in neurons. In recent years, environmental factors such as exposure to herbicides and pesticides have been attributed to the development of this condition. While majority of the studies on neurotoxic effects of paraquat (PQ) have focused on α-syn-mediated neuronal damage in the early stages of α-syn accumulation in neurons, efforts to explore the key target for α-syn degradation are limited. Recent research has suggested that histone deacetylase 6 (HDAC6) might possibly regulate amyloid clearance, and that the metabolism of compounds in neurons is also directly affected by axonal transport in neurons. Dynein predominantly mediates reverse transportation of metabolites and uptake of signal molecules and other compounds at the end of axons, which is conducive to the reuse of cell components. However, the role of interaction of dynein with HDAC6 in metabolites transport is still unclear. Therefore, this study aimed to investigate the role of HDAC6 in α-syn accumulation/clearance in neurons and the associated possible influencing factors. The results revealed that HDAC6 could transport ubiquitinated α-syn, bind to dynein, form an aggresome, and relocate to the center of the microtubule tissue, ultimately reducing abnormal accumulation of α-syn. However, PQ treatment resulted in HDAC6 upregulation, causing abnormal aggregation of α-syn. Taken together, these findings indicated that PQ exposure caused abnormal accumulation of α-syn and decreased effective degradation of α-syn by HDAC6-mediated aggresome-autophagy-lysosome pathway.

Chemotherapy has been the standard treatment for liver cancer. However, intrinsic or acquired drug resistance remains a major barrier to successful treatment. At present, the underlying molecular mechanisms of chemoresistance in liver cancer have not been elucidated. Dipeptidyl peptidase 9 (DPP9) is a member of the dipeptidyl peptidase IV family that has been found to be highly expressed in a variety of tumors, including liver cancer. It is unclear whether DPP9 affects chemoresistance in liver cancer. In this study, we find that DPP9 weakens the responses of liver cancer cells to chemotherapy drugs by up-regulating NQO1 and inhibiting intracellular ROS levels. In terms of mechanism, DPP9 inhibits ubiquitin-mediated degradation of NRF2 protein by binding to KEAP1, up-regulates NRF2 protein levels, promotes mRNA transcription of NQO1, and inhibits intracellular ROS levels. In addition, the NQO1 inhibitor dicoumarol can enhance the efficacy of chemotherapy drugs in liver cancer cells. Collectively, our findings suggest that inhibiting DPP9/NQO1 signaling can serve as a potential therapeutic strategy for liver cancer.

BackgroundScholars have been committed to investigating stroke rehabilitation strategies over many years. Since its invention, transcranial magnetic stimulation (TMS) has been increasingly employed in contemporary stroke rehabilitation research. Evidence has shown the significant potential of TMS in stroke research and treatment.ObjectiveThis article reviews the research conducted on the use of TMS in stroke from 1994 to 2023. This study applied bibliometric analysis to delineate the current research landscape and to anticipate future research hotspots.MethodThe study utilized the Web of Science Core Collection to retrieve and acquire literature data. Various software tools, including VOSviewer (version 1.6.19), CiteSpace (version 6.3.R1), Scimago Graphica (version 1.0.36), and WPS (version 11572), were used for data analysis and visualization. The review included analyses of countries, institutions, authors, journals, articles, and keywords.ResultsA total of 3,425 articles were collected. The top three countries in terms of publication output were the United States (953 articles), China (546 articles), and Germany (424 articles). The United States also had the highest citation counts (56,764 citations), followed by Germany (35,211 citations) and the United Kingdom (32,383 citations). The top three institutions based on the number of publications were Harvard University with 138 articles, the University of Auckland with 81 articles, and University College London with 80 articles. The most prolific authors were Abo, Masahiro with 54 articles, Fregni, Felipe with 53 articles, and Pascual-Leone, Alvaro with 50 articles. The top three journals in terms of article count were Neurorehabilitation and Neural Repair with 139 articles, Clinical Neurophysiology with 128 articles, and Frontiers in Neurology with 110 articles. The most frequently occurring keywords were stroke (1,275 occurrences), transcranial magnetic stimulation (1,119 occurrences), and rehabilitation (420 occurrences).ConclusionThe application of TMS in stroke research is rapidly gaining momentum, with the USA leading in publications. Prominent institutions, such as Harvard University and University College London, show potential for collaborative research. The key areas of focus include post-stroke cognitive impairment, aphasia, and dysphagia, which are expected to remain significant hotspots in future research. Future research should involve large-scale, randomized, and controlled trials in these fields. Additionally, identifying more effective combined therapies with rTMS should be a priority.

In response to the current energy and environmental challenges, reducing or replacing reliance on fossil fuels and striving for carbon neutrality seems to be the only viable choice. Recently, a cutting-edge, eco-friendly method of chemical synthesis via transient Joule heating (JH) demonstrated significant promise across various domains, including methane reforming, ammonia synthesis, volatile organic compounds removal, plastic recycling, the synthesis of functional carbon materials from repurposed solid waste, etc. In this review, the advantages, and latest developments in thermochemical synthesis by flash and transient JH are comprehensively outlined. Unlike the ongoing heating process of conventional furnaces that consume fossil fuels, dynamic and transient JH can get significantly higher reaction rates, energy efficiency, flexibility, and versatility. Subsequently, the transient reaction mechanism, data science optimization, and scale-up production models are discussed, and prospects for the integration of the electrified chemical industry with renewable energy for carbon neutrality and long-term energy storage are also envisioned.

ObjectiveThis study aims to investigate the Knowledge, Attitude, and Practice (KAP) pertaining to constipation during pregnancy among pregnant women in Shanghai.MethodsDemographic data and KAP scores were collected using a questionnaire. Differences across groups were analyzed using either Wilcoxon-Mann–Whitney tests or Kruskal-Wallis analysis of variance. Spearman’s correlation analysis was utilized to evaluate the relationships between KAP scores. Multivariable logistic regression analyses were conducted to identify factors that influence KAP scores.ResultsEncompassing 241 individuals (46.6%) aged between 30 and 34 years, with 349 participants (67.5%) being nulliparous. The median scores for knowledge (possible range: 0–26), attitude (possible range: 7–35), and practice (possible range: 14–70) were 22 (18, 24), 26 (23, 29), and 51 (46, 56), respectively. Multivariate analysis indicated that being a medical professional (OR = 2.222, p = 0.043) and receiving education on constipation during pregnancy (OR = 0.432, p

T cell development in the thymus is dependent on the thymic microenvironment, in which thymic epithelial cells (TECs) are the major component. However, TECs undergo both a qualitative and quantitative loss during aging, which is believed to be the major factor responsible for age-dependent thymic atrophy. FOXN1 plays a critical role in TEC development and adult TECs maintenance. We have previously reported that intrathymic injection of a recombinant (r) protein containing murine FOXN1 and a protein transduction domain increases the number of TECs in mice, leading to enhanced thymopoiesis. However, intrathymic injection may not be an ideal choice for clinical applications. In this study, we produced a rFOXN1 fusion protein containing the N-terminal of CCR9, human FOXN1 and a protein transduction domain. When injected intravenously into 14-month-old mice, the rFOXN1 fusion protein enters the thymus and TECs, and enhances thymopoiesis, resulting in increased T cell generation in the thymus and increased number of T cells in peripheral lymphoid organ. Our results suggest that the rFOXN1 fusion protein has the potential to be used in preventing and treating T cell immunodeficiency in older adults.

Summary: Background: The FDA's alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following CAR-T treatment is lacking. Methods: We extracted adverse event reports of hematological malignancies (HMs) patients with clearly definable SPMs from the FAERS and VigiBase databases (2017–2023). Disproportionality analysis using reporting odds ratio (ROR) and adjusted ROR was performed to assess associations between SPMs and CAR-T therapy. Time-to-onset analysis explored factors affecting SPM manifestation. Findings: SPMs post CAR T-cell therapy include HMs and solid tumors. T-cell lymphoma and myelodysplastic syndromes were consistently identified as positive signals across the overall and subgroup analyses. Hematological SPMs showed earlier onset with increasing annual incidence post CAR-T therapy, whereas solid tumors exhibit delayed manifestation. SPMs in CAR-T recipients had significantly earlier onset than non-recipients. Furthermore, age-specific characteristics reveal earlier SPM manifestations in pediatric, adolescent, and young adult populations compared to older populations post CAR-T therapy. Interpretation: The current SPM profile highlights the necessity of long-term safety monitoring for all CAR-T recipients given the observed yearly increase of SPMs. Customizing long-term SPM screening across different age groups may enhance early detection and intervention strategies, ultimately improving patient outcomes in the follow-up of CAR-T recipients. Funding: This work was supported by grants from the Natural Science Foundation of Guangdong Province (2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (2019A030317020), the National Natural Science Foundation of China (81802257, 81871859, 81772457, 82172750, 82172811, and 82260546), the Guangdong Basic and Applied Basic Research Foundation (Guangdong–Guangzhou Joint Funds) (2022A1515111212), and the Science and Technology Program of Guangzhou (2023A04J1257).

Objective To investigate the effect of high keratin 23 （KRT23） expression promoting cell proliferation on liver cancer. Methods The expression of KRT23 in liver cancer was analyzed by bioinformatics. After overexpression and inhibition of KRT23， the effect of KRT23 on the proliferation of liver cancer cells was analyzed by MTT and clone formation assay. The regulatory relationship between KRT23 and AKT signaling pathway was analyzed by software prediction， qPCRand Western blot. Results The expression level of KRT23 in liver cancer was significantly higher than that in normal control tissues. MTT and clone formation assay showed that overexpression of KRT23 promoted cell proliferation， while downregulation of KRT23 inhibited cell proliferation. GSEA analysis， qPCR and Western blot showed that KRT23 could activate the AKT signaling pathway and promote cell proliferation. Meanwhile， inhibition of AKT signaling pathway in overexpressing KRT23 cells significantly reduced cell proliferation. Conclusions KRT23 affects the proliferation of liver cancer cells by regulating the AKT signaling pathway. These results suggest that KRT23 exerts significant effects upon the malignant procession of liver cancer and may play an important role in the occurrence and development of liver cancer.

Abstract To monitor in situ the temperature, pH, and micro-strain change information of sandstone artifacts in the process of oxalic acid corrosion, the temperature, pH, and micro-strain fiber Bragg grating (FBG) sensors are developed. A theoretical model of the sensors is established. The surface morphology, material composition, pore structure, temperature, pH, and micro-strain of sandstone corroded by oxalic acid solutions of different concentrations are investigated. The experimental results show that the higher the concentration of oxalic acid, the stronger the corrosiveness of the sandstone. Ferrous oxalate and calcium oxalate produced by corrosion continuously precipitate from the inside of the rock, and the dual reaction of crystallization and dissolution occurs, reducing the proportion of fine pores in the rock pore suction and gravity. The oxalic acid solution is transported to the middle of the sandstone (3 cm) and undergoes the strongest chemical reaction with ore particles and debris, resulting in the maximum wavelength drift of the temperature, pH, and micro-strain sensors. The results of this study provide important support for analyzing the acid dissolution mechanism of stone cultural relics and the preventive protection of cultural relics.

Abstract The sialic acid binding Ig like lectin 15 (Siglec-15) was previously identified as tumor immune suppressor gene in some human cancers with elusive molecular mechanism to be elucidated. The continuous focus on both clinical and basic biology of bladder cancer leads us to characterize aberrant abundance of BACH1-IT2 associating with stabilization of Siglec-15, which eventually contributes to local immune suppressive microenvironment and therefore tumor advance. This effect was evidently mediated by miR-4786-5p. BACH1-IT2 functions in this scenario as microRNA sponge, and competitively conceals miR-4786 and up-regulates cancer cell surface Siglec-15. The BACH1-IT2-miR-4786-Siglec-15 axis significantly influences activation of immune cell co-culture. In summary, our data highlights the critical involvements of BACH1-IT2 and miR-4786 in immune evasion in bladder cancer, which hints the potential for both therapeutic and prognostic exploitation.

Purpose: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). Methods: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1–28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks. Results: In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P

In order to uncover the role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) (PI3K/AKT) signaling pathway in metabolic regulation in Tan sheep meat during chilled storage, the transcriptome changes of lamb meat injected with the PI3K inhibitor LY294002 after 0, 4 and 8 days of chilled storage were studied by high-throughput sequencing. Altogether, 474, 96, and 13 differentially expressed genes (DEGs) between the control and LY294002 treatment groups were identified on days 0, 4, and 8, respectively. Functional enrichment analysis showed that the DEGs were mainly related to metabolic homeostasis, such as amino acid biosynthesis, glycolysis/gluconeogenesis, and glyceride metabolism. In addition, tissue section analysis showed that the gap between muscle fibers in the LY294002 group increased and the diameter of muscle fibers decreased significantly relative to the control group, indicating muscle atrophy. These results indicated that the PI3K/AKT signaling pathway played a crucial role in maintaining metabolic balance during the storage of Tan mutton, which in turn ensured the normal growth of muscle. This study provides a new direction for further elucidating the molecular mechanism by which the PI3K/AKT signaling regulates metabolic homeostasis in Tan mutton during chilled storage.