Effectiveness of meaning-centered interventions on existential distress and mental health outcomes in cancer survivors and their family caregivers: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cancer is a global public health concern that causes psychosocial and spiritual challenges in those who suffer from it and their family caregivers. Meaning-centered interventions have a positive impact on improving anxiety and depression in patients with advanced cancer. However, the impact of meaning-centered interventions on existential distress of patients with cancer and family caregivers' mental health is still unclear. AIMS: To examine the efficacy of meaning-centered interventions in alleviating existential distress, enhancing quality of life, and fostering a sense of meaning among cancer survivors and their family caregivers. METHODS: This systematic review and meta-analysis were conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-analysis 2020 statement. A comprehensive search was conducted from inception until September 2023 across nine databases: PubMed, Embase, Web of Science, PsycINFO, The Cochrane Library, CINAHL, Scopus, WANFANG, and CNKI. Heterogeneity testing and meta-analyses were conducted using Review Manger 5.3. We calculated standard mean deviations and 95% confidence intervals and presented forest plots for assessing intervention effects. Two reviewers independently evaluated the risk of bias of all included articles. STATA 17.0 was used for publication bias analysis. RESULTS: The review included 25 studies with 2399 participants, and 22 were included in the meta-analysis. Meaning-centered interventions enhanced quality of life, alleviated existential distress, and reduced depressive symptoms and cancer-related fatigue. They did not affect spiritual well-being. The subgroup analysis showed that the individual form and long-term intervention (≥3 months) enhanced the quality of life in cancer survivors. Meaning-centered interventions reduce depression in advanced cancer survivors more than in mixed-stage cancer survivors. Meaning-centered interventions significantly enhanced benefit finding for family caregivers. LINKING EVIDENCE TO ACTION: Meaning-centered interventions may improve mental health for patients with cancer and their family caregivers. Future research must include diverse cultural perspectives to understand the impact of meaning-centered interventions on various groups.

Exploring the association between magnesium deficiency and chronic obstructive pulmonary diseases in NHANES 2005-2018.

Chronic Obstructive Pulmonary Disease (COPD) significantly impacts patients' quality of life and burdens healthcare systems. Magnesium is crucial for lung function and reducing respiratory disease risk. This study investigates the association between Magnesium Depletion Score (MDS) and COPD and explores whether inflammatory markers mediate this relationship. A cross-sectional analysis was conducted using data from 30,490 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. MDS was calculated based on diuretic use, proton pump inhibitors, renal function, and alcohol consumption. Univariable and multivariable logistic regression analyses were performed to assess the association between MDS and COPD, adjusting for potential confounders. Mediation analysis was used to examine the roles of neutrophils, serum albumin, and the Systemic Immune-Inflammation Index (SII). In the univariable logistic model, higher MDS was significantly associated with increased COPD risk. Specifically, compared to MDS = 0, the odds ratios (OR) for COPD were 2.50, 4.12, 6.13, 8.53, and 7.81 for MDS = 1, 2, 3, 4, and 5, respectively (all P < 0.001). In the multivariable model, the ORs were 1.79, 2.25, 2.71, and 3.44 for MDS = 1, 2, 3, and 4, respectively (all P < 0.001). Higher neutrophil levels and SII were positively associated with increased COPD risk, while higher serum albumin levels were inversely associated. Mediation analysis indicated that neutrophils, serum albumin, and SII significantly mediated the MDS-COPD relationship. Higher MDS is significantly associated with increased COPD risk, mediated by systemic inflammation markers. Improving magnesium levels could potentially reduce COPD risk, warranting further research on magnesium supplementation in COPD prevention and management.

Simvastatin alleviates experimental autoimmune encephalomyelitis through regulating the balance of Th17 and Treg in mice.

The aim of this study was to elucidate the therapeutic effect of simvastatin on experimental autoimmune encephalomyelitis (EAE) by regulating the balance between Th17 and Treg cells in mice. C57BL/6 mice were randomly divided into four groups: normal group, EAE group, simvastatin (2 and 10 mg/kg) group, and AG490 group (with AG490 serving as the positive control). Neurological function scores of mice were assessed daily. The four groups received treatments of normal saline, normal saline, and simvastatin (2 and 10 mg/kg), respectively. In the AG490 group, mice were injected intraperitoneally with AG490 (1 mg) every other day, and treatment was halted after 3 weeks. The spinal cord was stained with hematoxylin and eosin (H&E), and immunohistochemical staining for retinoic acid receptor-related orphan receptor γ(RORγ) and Foxp3 (Foxp3) was performed. Spleen samples were taken for Th17 and Treg analysis using flow cytometry. The levels of interleukin-17 and transforming growth factor-ß (TGF-ß) were detected using enzyme-linked immunosorbent assay (ELISA). In the simvastatin and AG490 groups, recovery from neurological impairment was earlier compared to the EAE group, and the symptoms were notably improved. Both simvastatin and AG490 reduced focal inflammation, decreased RORγ-positive cell infiltration, and significantly increased the number of FOXP3-positive cells. The number of Th17 cells and the level of IL-17 in the spleen were decreased in the simvastatin and AG490 treatment groups, while the number of Treg cells and TGF-ß levels were significantly increased across all treatment groups. Simvastatin exhibits anti-inflammatory and immunomodulatory effects, potentially alleviating symptoms of neurological dysfunction of EAE. Regulating the balance between Th17 and Treg may represent a therapeutic mechanism for simvastatin in treating EAE.

ImmunoPET imaging of EpCAM in solid tumours with nanobody tracers: a preclinical study.

PURPOSE: Epithelial cell adhesion molecule (EpCAM) is a potential therapeutic target and anchoring molecule for circulating and disseminated tumour cells (CTC/DTC) in liquid biopsy. In this study, we aimed to construct EpCAM-specific immuno-positron emission tomography (immunoPET) imaging probes and assess the diagnostic abilities in preclinical cancer models. METHODS: By engineering six single-domain antibodies (e.g., EPCD1 - 6) targeting EpCAM of different binding properties and labelling with 68Ga (T1/2 = 1.1 h) and 18F (T1/2 = 110 min), we developed a series of EpCAM-targeted immunoPET imaging probes. The probes' pharmacokinetics and diagnostic accuracies were investigated in cell-derived human colorectal (LS174T) and esophageal cancer (OE19) tumour models. RESULTS: Based on in vitro binding affinities and in vivo pharmacokinetics of the first three tracers ([68Ga]Ga-NOTA-EPCD1, [68Ga]Ga-NOTA-EPCD2, and [68Ga]Ga-NOTA-EPCD3), we selected [68Ga]Ga-NOTA-EPCD3 for tumour imaging which showed an average tumour uptake of 2.06 ± 0.124%ID/g (n = 3) in LS174T cell-derived tumour model. Development and characterisation of [18F]AIF-RESCA-EPCD3 showed comparable tumour uptake of 1.73 ± 0.0471%ID/g (n = 3) in the same tumour model. Further validation of [68Ga]Ga-NOTA-EPCD3 in OE19 cell-derived tumour model showed an average tumour uptake of 4.27 ± 1.16%ID/g and liver uptake of 13.5 ± 1.30%ID/g (n = 3). Near-infrared fluorescence imaging with Cy7-EPCD3 confirmed the in vivo pharmacokinetics and relatively high liver accumulation. We further synthesized another three 18F-labeled nanobody tracers ([18F]AIF-RESCA-EPCD4, [18F]AIF-RESCA-EPCD5, and [18F]AIF-RESCA-EPCD6) and found that [18F]AIF-RESCA-EPCD6 had the best pharmacokinetics with low background. [18F]AIF-RESCA-EPCD6 showed explicit uptake in the subcutaneously inoculated OE19 tumour model with an average uptake of 4.70 ± 0.26%ID/g (n = 3). In comparison, the corresponding tumour uptake (0.17 ± 0.25%ID/g, n = 3) in the EPCD6 blocking group was substantially lower (P < 0.001), indicating the targeting specificity of the tracer. CONCLUSIONS: We developed a series of 68Ga/18F-labeled nanobody tracers targeting human EpCAM. ImmunoPET imaging with [18F]AIF-RESCA-EPCD6 may facilitate better use of EpCAM-targeted therapeutics by noninvasively displaying the target's expression dynamics.

High-frequency magnetic paired associated stimulation promotes motor function recovery in ischemic stroke patients: a study protocol for single-center, sham stimulation randomized controlled trials (H2MPAS).

BACKGROUND: Numerous studies have validated the clinical effectiveness of electromagnetic pairing-associated stimulation. Building upon this foundation, we have developed a novel approach involving high-frequency magnetic paired-associated stimulation, aiming to enhance clinical applicability and potentially improve efficacy. However, the clinical effectiveness of this approach remains unclear. Our objective is to demonstrate the therapeutic efficacy of this novel approach by employing high-frequency pairing to intervene in patients experiencing motor dysfunction following a stroke. METHODS: This is a single-center, single-blind, sham stimulation controlled clinical trial involving patients with upper limb motor dysfunction post-stroke. The intervention utilizes paired magnetic stimulation, combining peripheral and central magnetic stimulation, in patients with Brunnstrom stage III-V stroke lasting from 3 months to 1 year. Evaluation of patients' upper limb motor function occurred before the intervention and after 3 weeks of intervention. Follow-up visits will be conducted after 5 weeks and 3 months of intervention. The primary outcome measure is the Action Research Arm Test, with secondary measures including the Fugl-Meyer Assessment-upper, Modified Barthel Index, modified Tardieu scale, functional near-infrared spectroscopy, and neuroelectrophysiology. DISCUSSION: The high-frequency magnetic paired associative stimulation used in this study combined high-frequency magnetic stimulation with paired stimulation, potentially facilitating both cortical excitation through high-frequency stimulation and specific circuit enhancement through paired stimulation. As dual-coil magnetic stimulation equipment becomes increasingly popular, magnetic-magnetic paired associated stimulation may offer patients improved clinical outcomes at reduced costs. TRIAL REGISTRATION: Chinese Clinical Trial Registry,ChiCTR2400083363. Registered on 23 April 2024.

Cortical response characteristics of passive, active, and resistance movements: a multi-channel fNRIS study.

Objective: This study aimed to explore the impact of exercise training modes on sensory and motor-related cortex excitability using functional near-infrared spectroscopy technology (fNIRS) and reveal specific cortical effects. Materials and methods: Twenty participants with no known health conditions took part in a study involving passive, active, and resistance tasks facilitated by an upper-limb robot, using a block design. The participants wore functional near-infrared spectroscopy (fNIRS) devices throughout the experiment to monitor changes in cortical blood oxygen levels during the tasks. The fNIRS optode coverage primarily targeted key areas of the brain cortex, including the primary motor cortex (M1), primary somatosensory cortex (S1), supplementary motor area (SMA), and premotor cortex (PMC) on both hemispheres. The study evaluated cortical activation areas, intensity, and lateralization values. Results: Passive movement primarily activates M1 and part of S1, while active movement mainly activates contralateral M1 and S1. Resistance training activates brain regions in both hemispheres, including contralateral M1, S1, SMA, and PMC, as well as ipsilateral M1, S1, SMA, and PMC. Resistance movement also activates the ipsilateral sensorimotor cortex (S1, SMA, PMC) more than active or passive movement. Active movement has higher contralateral activation in M1 compared to passive movement. Resistance and active movements increase brain activity more than passive movement. Different movements activate various cortical areas equally on both sides, but lateralization differs. The correlation between lateralization of brain regions is significant in the right cortex but not in the left cortex during three movement patterns. Conclusion: All types of exercise boost motor cortex excitability, but resistance exercise activates both sides of the motor cortex more extensively. The PMC is crucial for intense workouts. The right cortex shows better coordination during motor tasks than the left. fNIRS findings can help determine the length of treatment sessions.

Effect of anionic groups in zwitterionic hydrophilic stationary phases on their chromatographic characteristics.

The structure of zwitterion has great impact on the separation properties of zwitterionic hydrophilic stationary phases. To better understand the role of anionic groups of zwitterions, a novel carboxybetaine-based zwitterionic monolithic column was first prepared through thermo-initiated copolymerization of functional monomer (3-acrylamidopropyl)-dimethyl-(2-carboxymethyl) ammonium (CBAA) and crosslinker ethylene dimethacrylate (EDMA) within 100 µm ID capillary. The optimal poly(CBAA-co-EDMA) monolithic column exhibited satisfactory mechanical and chemical stability, good repeatability, high column efficiency (96,000 plates/m), and excellent separation performance for different classes of polar compounds (i.e., phenols, monophosphate nucleotides, urea and allantoin). A comparative study was then performed among three zwitterionic hydrophilic stationary phases containing different anionic groups, i.e. poly(CBAA-co-EDMA) (carboxybetaine), poly(2-{2-(methacryloyloxy) ethyldimethylammonium}ethyl n-butyl phosphate-co-EDMA) (phosphocholine), and poly(N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl) ammonium betaine-co-EDMA) (sulfobetaine) using benzoic acid derivatives, amine compounds, nucleobases and nucleosides as model analytes. The carboxybetaine-based monolithic column exhibited much higher positive zeta-potential and hydrophilicity, which endows it with a stronger retention capacity for acidic and neutral compounds, but sulfobetaine-based monolithic column exhibited much higher selectivity and retention capacity for the amines. Moreover, their enrichment efficiencies for N-glycopeptides were also evaluated based on their different hydrophilicity, and it was observed that the poly(CBAA-co-EDMA) monolithic material captured 4-8 times more N-glycopeptides compared to the other two materials.

Factors Contributing to the Recurrence of Urinary Tract Infections and Revisit amongst Children in the Emergency Department: A Single-Centre Retrospective Study.

BACKGROUND: Urinary tract infections (UTIs) are prevalent amongst paediatric patients, and they can lead to emergency department (ED) visits. A subset of patients requires a second ED visit, creating a burden on healthcare resources. This study aimed to shed light on the clinical, laboratory, treatment-related and environmental determinants associated with the recurrence of ED visits in this specific paediatric population. METHODS: This single-centre retrospective study involved paediatric patients diagnosed with UTIs and admitted to the paediatric ED of our hospital from September 2021, to August 2023. In accordance with whether a second visit was required, the ED patients were grouped into non-second-visit group or second-visit group. The demographic, clinical, laboratory, diagnostic, and environmental factors were analysed in detail. Statistical analyses, including chi-square tests, t-tests and correlation analyses, were employed to assess the associations between various factors and subsequent ED visits. RESULTS: A total of 357 patients, including 324 patients without a second visit and 33 patients with a second visit, were included in this study. Factors significantly associated with second ED visits included fever (≥38.5 °C) at initial presentation (p = 0.034), longer symptom duration (p = 0.022), increased C-reactive protein (CRP) levels (p = 0.018), hydronephrosis (p = 0.033) and lack of oral antibiotic use before the first visit (45.45% vs. 67.9%, p = 0.017). More bubble bath exposure (p = 0.037) and lower consultation rates with paediatric urology services (p = 0.020) were associated with repeated visits. Multifactor logistic regression analysis showed that the factors significantly associated with second ED visits were longer symptoms duration, fever (≥38.5 °C) at initial presentation, presence of flank pain, increased CRP levels, hydronephrosis, renal stones, vesicoureteral reflux, underlying anatomical abnormalities, lack of oral antibiotic use before the first visit, bubble bath exposure and lower consultation rates with paediatric urology services. CONCLUSIONS: A series of clinical indicators, laboratory findings, diagnostic measures and environmental factors may be associated with the need for a second ED visit amongst paediatric patients with UTI. Early antibiotic intervention, identification of underlying anatomical anomalies and management of environmental exposures may mitigate recurrent ED visits.

The relationship between rehabilitation motivation and upper limb motor function in stroke patients.

Objective: Insufficient motivation among post-stroke survivors may be an important factor affecting their motor function recovery. This study seeks to investigate the relationship between motivation and functional recovery in stroke patients undergoing rehabilitation training. Materials and methods: 103 stroke patients with upper limb impairments were studied during their hospital stays. Assessments were done before and after rehabilitation training to measure motivation, emotional state, motor function, and independence in daily activities. Data analysis was conducted to examine the distribution of these factors among the participants. Pearson and Spearman correlation analyses were used to study the relationships between motivation, emotional state, and motor function. Patients were divided into high and low motivation groups based on the Rehabilitation Motivation Scale (RMS), and chi-square and rank-sum tests were used to compare functional differences before and after treatment among patients with varying levels of motivation. Results: 66 participants were found to have low motivation in the initial assessment of the RMS (64.08%). Consistency in motivation levels was observed among patients with high motivation (r = 0.648, P<0.001). Apathy was identified as the main factor affecting motivation in patients with low motivation (p = 0.027), while depression and anxiety were not significantly correlated. Motivation was strongly linked to improvements in upper limb motor function, daily living activities, and self-exercise duration (p < 0.001) for stroke patients undergoing rehabilitation. Post-training, there was a notable increase in motivation, motor function, and independence in daily activities (p < 0.001). Increased rehabilitation motivation was linked to better upper limb motor function and daily independence in patients, particularly those with low motivation. This correlation was significant for both the FMA-UE and FIM scores. Discussion: Old patients with poor upper limb motor function often have low motivation, which hinders their recovery. Using strategies to boost motivation in stroke patients with impaired upper limb function could greatly improve their rehabilitation and motor skills. It is crucial to prioritize these intervention strategies. Conclusion: Enhancing rehabilitation motivation in stroke patients with low motivation and upper limb motor impairments can foster the restoration of their functional capabilities.

Improving rehabilitation motivation and motor learning ability of stroke patients using different reward strategies: study protocol for a single-center, randomized controlled trial.

Background: Stroke survivors often face challenges in motor learning and motivation during rehabilitation, which can impede their recovery progress. Traditional rehabilitation methods vary in effectiveness, prompting the exploration of novel approaches such as reward strategies. Previous research indicates that rewards can enhance rehabilitation motivation and facilitate motor learning. However, most reward paradigms have utilized fixed reward amounts, which also have limitations. Exploring alternative, more effective reward strategies, such as probabilistic rewards, is warranted to optimize stroke patient rehabilitation. Methods: A total of 81 stroke patients will be recruited and randomly assigned to control, fixed reward, or probabilistic reward groups at a ratio of 1:1:1 using a randomized number table method. Participants will undergo 10 days of daily hand motor function rehabilitation training, with sessions lasting 20 min each. The training will involve pegboard tests and box and block tests. Control group participants will receive standard training, while fixed reward group members will receive monetary incentives for completing tests, and probabilistic reward group members will have the chance to win monetary rewards through a lottery box. Rehabilitation motivation and motor performance and functional near-infrared spectroscopy brain imaging will be conducted at designated time points. The primary outcome measure is the stroke rehabilitation motivation scale, and the second outcome measures include motor performance, simple test for evaluating hand function, motivation and pleasure scale self-report, and Pittsburgh rehabilitation participation scale. Discussion: Reward-based training enhance rehabilitation participation and adherence, it also improve motor learning speed and memory retention of stroke patients. The fixed reward applied in the past studies could diminish the sensitivity of stroke patients to rewards, while probabilistic reward may provide unpredictable or variable incentives or reinforcements for motor rehabilitation. This study will compare the efficacy of different reward strategies in enhancing motor learning ability and rehabilitation motivation among stroke patients. By conducting a randomized controlled trial, the study seeks to provide valuable insights into optimizing stroke rehabilitation protocols and improving patient outcomes.Clinical Trial Registration:https://www.chictr.org.cn/, ChiCTR2400082419.

Solar Energy-Driven Reverse Water Gas Shift Reaction: Photothermal Effect, Photoelectric Activation and Selectivity Regulation.

Excessive carbon dioxide (CO2) emissions are one of the main causes of the greenhouse effect. Thermal catalytic reverse water gas shift (RWGS) reaction, which is a pre reaction for Fischer-Tropsch synthesis, is considered an effective way to convert CO2 and synthesize high value-added chemicals in industry. However, traditional thermal catalysis requires a large amount of fossil fuels to drive reactions, which cannot achieve the true goal of carbon neutrality. Photothermal catalysis, as a novel conversion pathway, can achieve efficient CO2 conversion while significantly improving solar energy utilization. This review provides a detailed introduction of CO2 and H2 adsorption/activation and reaction pathways in thermal catalysis, as well as the catalytic mechanisms of thermal and chemical effects in photothermal catalytic RWGS to supply readers valuable insights on the mechanism of photothermal catalytic RWGS reaction and provide a reference for better catalyst design.

Anti-ferroptosis exosomes engineered for targeting M2 microglia to improve neurological function in ischemic stroke.

BACKGROUND: Stroke is a devastating disease affecting populations worldwide and is the primary cause of long-term disability. The inflammatory storm plays a crucial role in the progression of stroke. In the acute phase of ischemic stroke, there is a transient increase in anti-inflammatory M2 microglia followed by a rapid decline. Due to the abundant phospholipid in brain tissue, lipid peroxidation is a notable characteristic of ischemia/reperfusion (I/R), constituting a structural foundation for ferroptosis in M2 microglia. Slowing down the decrease in M2 microglia numbers and controlling the inflammatory microenvironment holds significant potential for enhancing stroke recovery. RESULTS: We found that the ferroptosis inhibitor can modulate inflammatory response in MCAO mice, characterizing that the level of M2 microglia-related cytokines was increased. We then confirmed that different subtypes of microglia exhibit distinct sensitivities to I/R-induced ferroptosis. Adipose-derived stem cells derived exosome (ADSC-Exo) effectively decreased the susceptibility of M2 microglia to ferroptosis via Fxr2/Atf3/Slc7a11, suppressing the inflammatory microenvironment and promoting neuronal survival. Furthermore, through plasmid engineering, a more efficient M2 microglia-targeted exosome, termed M2pep-ADSC-Exo, was developed. In vivo and in vitro experiments demonstrated that M2pep-ADSC-Exo exhibits significant targeting specificity for M2 microglia, further inhibiting M2 microglia ferroptosis and improving neurological function in ischemic stroke mice. CONCLUSION: Collectively, we illustrated a novel potential therapeutic mechanism that Fxr2 in ADSC-Exo could alleviate the M2 microglia ferroptosis via regulating Atf3/Slc7all expression, hence inhibiting the inflammatory microenvironment, improving neurofunction recovery in cerebral I/R injury. We obtained a novel exosome, M2pep-ADSC-Exo, through engineered modification, which exhibits improved targeting capabilities toward M2 microglia. This provides a new avenue for the treatment of stroke.

Preparation and evaluation of a piperidinium-sulfonate based zwitterionic monolith for HILIC separation.

In this study, a novel piperidinium-sulfonate based zwitterionic hydrophilic monolith was prepared through thermally initiated co-polymerization of a piperidinium-sulfonate monomer 3-(4-((methacryloyloxy)methyl)-1-methylpiperidin-1-ium-1-yl)propane-1-sulfonate (MAMMPS), and a hydrophilic crosslinker N,N'-methylenebisacrylamide (MBA) using n-propanol and H2O as porogenic system. Satisfactory mechanical and chemical stabilities, good repeatability and high column efficiency (120,000 N/m) were obtained on the optimal monolith. The resulting poly(MAMMPS-co-MBA) monolith showed a typical HILIC retention behavior over an ACN content range between 5 and 95 %. Furthermore, this column exhibited good separation performance for various polar compounds. Compared to quaternary ammonium-sulfonate based zwitterionic hydrophilic monolith, i.e. poly(N,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl)ammonium betaine-co-MBA), the poly(MAMMPS-co-MBA) monolith displayed stronger retention and better selectivity for the tested phenolic and amine compounds at different pH conditions. Finally, this column was applied for the separation of six sulfonamide antibiotics, and the analytical characteristics of the method were evaluated in terms of precision, repeatability, limits of detection (LOD) and quantitation (LOQ). Overall, this study not only developed a novel HILIC monolithic column, but also proved the potential of piperidinium-sulfonate based zwitterionic chemistry as stationary phase, which further increased the structure diversity of zwitterionic HILIC stationary phases.

A systematic review and meta-analysis on sodium tanshinone IIA sulfonate injection for the adjunctive therapy of pulmonary heart disease.

AIMS: Sodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study. METHODS: Randomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed. RESULTS: 19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p < 0.001), partial pressure of oxygen (MD = 10.16; 95% CI, 5.07 to 15.24; p < 0.001), left ventricular ejection fraction (MD = 8.66; 95% CI, 6.14 to 11.18; p < 0.001) and stroke volume (MD = 13.10; 95% CI, 11.83 to 14.38; p < 0.001), meanwhile decreasing the low shear blood viscosity (MD = -1.16; 95% CI, -1.57 to -0.74; p < 0.001), high shear blood viscosity (MD = -0.64; 95% CI, -0.86 to -0.42; p < 0.001), plasma viscosity (MD = -0.23; 95% CI, -0.30 to -0.17; p < 0.001), hematokrit (MD = -8.52; 95% CI, -11.06 to -5.98; p < 0.001), fibrinogen (MD = -0.62; 95% CI, -0.87 to -0.37; p < 0.001) and partial pressure of carbon dioxide (MD = -8.56; 95% CI, -12.09 to -5.02; p < 0.001). CONCLUSION: STS injection as adjunctive therapy seemed to be more effective than Western medicine alone for PHD. However, due to low quality of the included RCTs, more well-designed RCTs were necessary to verify the efficacy of STS injection.

TEAD4 Activates PCSK9 to Promote Stomach Adenocarcinoma Cell Stemness through Fatty Acid Metabolism.

INTRODUCTION: This study attempted to investigate how proprotein convertase subtilisin/kexin type 9 (PCSK9) influences the stemness of stomach adenocarcinoma (STAD) cells. METHODS: CCK-8 and sphere-formation assays were used to detect cell viability and stemness. qRT-PCR and Western blot were used to detect PCSK9 and TEAD4 expression. The binding relationship was verified by dual-luciferase and chromatin immunoprecipitation assays. The effect of TEAD4 activating PCSK9 on the stemness of STAD cells was detected by bioinformatics, BODIPY 493/503, Oil red O, Western blot, and kits. In vivo experiments verified the role of the TEAD4/PCSK9 axis in tumor formation in nude mice. RESULTS: PCSK9 and TEAD4 were highly expressed in STAD. PCSK9 was enriched in the fatty acid metabolism (FAM) pathway. PCSK9 activated the fatty acid metabolism and promoted the proliferation and stemness of STAD cells. TEAD4 as a transcription factor upstream of PCSK9, cell experiments revealed that knockdown of PCSK9 inhibited STAD cell stemness, whereas further addition of fatty acid inhibitors could attenuate the promoting effect on STAD cell stemness brought by STAD overexpression. Rescue experiments showed overexpressed PCSK9 exerted an inhibitory effect on the stemness of STAD cells brought by TEAD4 knockdown. The hypothesis that TEAD4/PCSK9 axis can promote STAD cell growth was confirmed by in vivo experiments. CONCLUSION: Transcription factor TEAD4 could activate PCSK9 to promote the stemness of STAD cells through FAM. These results added weight to the assumption that TEAD4/PCSK9 axis has the potential to be the therapeutic target that inhibits cancer stem cell in STAD.

ImmunoPET imaging of Trop2 in patients with solid tumours.

Accurately predicting and selecting patients who can benefit from targeted or immunotherapy is crucial for precision therapy. Trophoblast cell surface antigen 2 (Trop2) has been extensively investigated as a pan-cancer biomarker expressed in various tumours and plays a crucial role in tumorigenesis through multiple signalling pathways. Our laboratory successfully developed two 68Ga-labelled nanobody tracers that can rapidly and specifically target Trop2. Of the two tracers, [68Ga]Ga-NOTA-T4, demonstrated excellent pharmacokinetics in preclinical mouse models and a beagle dog. Moreover, [68Ga]Ga-NOTA-T4 immuno-positron emission tomography (immunoPET) allowed noninvasive visualisation of Trop2 heterogeneous and differential expression in preclinical solid tumour models and ten patients with solid tumours. [68Ga]Ga-NOTA-T4 immunoPET could facilitate clinical decision-making through patient stratification and response monitoring during Trop2-targeted therapies.

The effect of reward on motor learning: different stage, different effect.

Motor learning is a prominent and extensively studied subject in rehabilitation following various types of neurological disorders. Motor repair and rehabilitation often extend over months and years post-injury with a slow pace of recovery, particularly affecting the fine movements of the distal extremities. This extended period can diminish the motivation and persistence of patients, a facet that has historically been overlooked in motor learning until recent years. Reward, including monetary compensation, social praise, video gaming, music, and virtual reality, is currently garnering heightened attention for its potential to enhance motor motivation and improve function. Numerous studies have examined the effects and attempted to explore potential mechanisms in various motor paradigms, yet they have yielded inconsistent or even contradictory results and conclusions. A comprehensive review is necessary to summarize studies on the effects of rewards on motor learning and to deduce a central pattern from these existing studies. Therefore, in this review, we initially outline a framework of motor learning considering two major types, two major components, and three stages. Subsequently, we summarize the effects of rewards on different stages of motor learning within the mentioned framework and analyze the underlying mechanisms at the level of behavior or neural circuit. Reward accelerates learning speed and enhances the extent of learning during the acquisition and consolidation stages, possibly by regulating the balance between the direct and indirect pathways (activating more D1-MSN than D2-MSN) of the ventral striatum and by increasing motor dynamics and kinematics. However, the effect varies depending on several experimental conditions. During the retention stage, there is a consensus that reward enhances both short-term and long-term memory retention in both types of motor learning, attributed to the LTP learning mechanism mediated by the VTA-M1 dopaminergic projection. Reward is a promising enhancer to bolster waning confidence and motivation, thereby increasing the efficiency of motor learning and rehabilitation. Further exploration of the circuit and functional connections between reward and the motor loop may provide a novel target for neural modulation to promote motor behavior.

Determination of viable myocardium through delayed enhancement cardiac magnetic resonance imaging combined with 18F-FDG PET myocardial perfusion/metabolic imaging before CABG.

PURPOSE: Study aims to investigate the consistency of delayed enhancement cardiac magnetic resonance imaging (DE-CMR) and 18F-FDG PET myocardial imaging in evaluating myocardial viability before CABG. METHODS: The study analyzed data from 100 patients who were examined with DE-CMR, PET imaging, and echocardiography before and after CABG. All subjects were followed up for 6-12 month post- CABG. RESULTS: DE-CMR and PET imaging have high consistency (90.1%; Kappa value = 0.71, p < 0.01) in determining myocardial viability. The degree of delayed enhancement was negatively correlated with the improvement in myocardial contractile function in this segment after revascularization (P < 0.001). The ratio of scarred myocardial segments and total DE score was significantly lower in the improvement group than non-improvement group. Multivariate regression identified that hibernating myocardium (OR = 1.229, 95%CI: 1.053-1.433, p = 0.009) was influencing factor of LVEF improvement after CABG. CONCLUSION: Both imaging techniques are consistent in evaluating myocardial viability. Detecting the number of hibernating myocardium by PET is also important to predict the left heart function improvement after CABG.

A comprehensive evaluation of a polymeric zwitterionic hydrophilic monolith for nucleotide separation.

Rapid and effective separation of nucleotides (NTs) and their derivatives is crucial for studying their physiological functions. In this work, we comprehensively evaluated the separation ability of a zwitterionic hydrophilic monolith, i.e., poly(N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl)ammonium betaine-co-N,N'-methylenebisacrylamide) (poly(SPP-co-MBA)) for NTs analysis, including its selectivity, chemical stability under extremely basic condition and compatibility with hydrophilic interaction liquid chromatography (HILIC) coupled with mass spectrometry (HILIC-MS). The poly(SPP-co-MBA) monolith exhibited excellent chemical stability, as evidenced by the low relative standard deviation of retention time (0.16-1.05%) after 4000 consecutive injections over one month under strong alkaline elution condition (pH 10). After optimizing the separation conditions, including buffer pH and concentration, organic solvent content and column temperature, four nucleoside triphosphates, five nucleoside diphosphates and five nucleoside monophosphates were baseline separated within 7 min. Additionally, the mixtures containing one nucleoside and its corresponding mono-, di-, and triphosphates were baseline separated within only 3 min, respectively. It is good HILIC-MS compatibility was also confirmed by the satisfactory peak shape and high response of nine NTs. Overall, the proposed poly(SPP-co-MBA) monolith exhibited good mechanical stability and compatibility of HILIC-MS, making it a promising technique for NTs analysis.

Cortical activity in patients with high-functioning ischemic stroke during the Purdue Pegboard Test: insights into bimanual coordinated fine motor skills with functional near-infrared spectroscopy.

After stroke, even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity, leading to reduced functional independence. Bilateral arm training has been proposed as a promising intervention to address these deficits. However, the neural basis of the impairment of functional fine motor skills and their relationship to bimanual coordination performance in stroke patients remains unclear, limiting the development of more targeted interventions. To address this gap, our study employed functional near-infrared spectroscopy to investigate cortical responses in patients after stroke as they perform functional tasks that engage fine motor control and coordination. Twenty-four high-functioning patients with ischemic stroke (7 women, 17 men; mean age 64.75 ± 10.84 years) participated in this cross-sectional observational study and completed four subtasks from the Purdue Pegboard Test, which measures unimanual and bimanual finger and hand dexterity. We found significant bilateral activation of the sensorimotor cortices during all Purdue Pegboard Test subtasks, with bimanual tasks inducing higher cortical activation than the assembly subtask. Importantly, patients with better bimanual coordination exhibited lower cortical activation during the other three Purdue Pegboard Test subtasks. Notably, the observed neural response patterns varied depending on the specific subtask. In the unaffected hand task, the differences were primarily observed in the ipsilesional hemisphere. In contrast, the bilateral sensorimotor cortices and the contralesional hemisphere played a more prominent role in the bimanual task and assembly task, respectively. While significant correlations were found between cortical activation and unimanual tasks, no significant correlations were observed with bimanual tasks. This study provides insights into the neural basis of bimanual coordination and fine motor skills in high-functioning patients after stroke, highlighting task-dependent neural responses. The findings also suggest that patients who exhibit better bimanual performance demonstrate more efficient cortical activation. Therefore, incorporating bilateral arm training in post-stroke rehabilitation is important for better outcomes. The combination of functional near-infrared spectroscopy with functional motor paradigms is valuable for assessing skills and developing targeted interventions in stroke rehabilitation.