Causal role of circulating inflammatory cytokines in cardiac diseases, structure and function.

BACKGROUND: Inflammation is implicated in cardiovascular disease (CVD) pathogenesis, but causal roles of specific circulating inflammatory cytokines remain unclear. Mendelian randomization (MR) studies are well-poised to provide etiological insights beyond constraints of conventional research. METHODS: We conducted a large-scale MR study to investigate potential causal relationships of 91 inflammatory proteins with CVD outcomes and cardiac remodeling using summary-level genetic data. Outcomes included coronary artery disease, myocardial infarction, stroke, atrial fibrillation, heart failure, abdominal aortic aneurysm, deep vein thrombosis of lower extremities, pulmonary embolism, cardiac structure and functional parameters. Inverse-variance weighted analysis was undertaken as the primary analysis, with several sensitivity analyses applied. RESULTS: Hepatocyte growth factor (HGF) demonstrated a causal relationship with increased susceptibility to both any stroke (OR 1.111; 95 % CI 1.044 - 1.183; P = 9.50e-04) and ischemic stroke (OR 1.121; 95 % CI 1.047 - 1.200; P = 1.04e-03). Programmed cell death 1 ligand 1 (PD-L1) was negatively associated with atrial fibrillation risk (OR 0.936, 95 % CI 0.901 - 0.973; P = 7.69e-04). CCL20, CDCP1, Flt3L and IL-10RA were identified as causal coronary artery disease risk factors, while LIF and ST1A1 had protective effects. IL-4 and LIF-R demonstrated causal links with right heart functional changes. CONCLUSIONS: Our MR study nominates specific circulating inflammatory cytokines as potential targets for CVD treatment and prevention. Further research into mechanisms and clinical translation are warranted.

Thyroid Function Impact on Cardiac Structure, Function and Disease Risk: Evidence of Causal Associations in European Ancestry.

BACKGROUND: Thyroid hormones play a crucial role in cardiovascular physiology. Subclinical thyroid dysfunction has been associated with adverse cardiovascular outcomes, but evidence is mixed regarding causality. OBJECTIVE: To investigate the potential causal relationships of thyroid-stimulating hormone (TSH), free thyroxine, hypothyroidism, and hyperthyroidism with cardiovascular outcomes, including atrial fibrillation (AF), coronary artery disease, myocardial infarction, heart failure, and ischemic stroke, as well as their impact on cardiac structure and function assessed by cardiac magnetic resonance imaging. METHODS: A comprehensive two-sample Mendelian randomization (MR) analysis was conducted, utilizing summary data from large-scale meta-analyses of European ancestry individuals. RESULTS: Genetically determined lower TSH levels (OR 0.928, 95% CI: 0.884 to 0.974, P = 0.003) and genetic risk of hyperthyroidism (OR 1.049, 95% CI: 1.016 to 1.083, P = 0.003) were associated with increased AF risk. These associations remained significant even after adjusting for cardiovascular risk factors. Colocalization and multivariable MR revealed height as a key mediator between TSH/hyperthyroidism and AF. These findings were further corroborated in the independent FinnGen cohort. However, no clear evidence was found for relationships between thyroid function and other cardiovascular outcomes and cardiac structure and function. CONCLUSIONS: Our study shows that reduced TSH levels and hyperthyroidism heighten AF risk, with height serving as an important mediator in these associations. The primary focus of thyroid management in cardiovascular health should be on preventing and treating arrhythmias, particularly AF. Our research highlights the importance of routine screening and timely treatment of thyroid dysfunction to optimize the prevention and management of arrhythmias.

Surface engineering of biochar toward simultaneously generating superamphiphilicity and catalytic activity for strengthening Pickering interfacial catalysis.

Multifunctional carbon materials have revealed distinctive features and excellent performance in the field of catalysis. However, the facile fabrication of bifunctional carbon materials with special wettability and catalytic activity remains a grand challenge in Pickering emulsion catalysis. Herein, we reported one-step construction of bifunctional biochar with superamphiphilicity and catalytic activity directly from the thermolysis of sawdust and 1-butyl-3-methylimidazolium tetrafluoroborate for enhancing the oxidation of benzyl alcohol in Pickering emulsion. Co-doping of B and F enhanced the hydrophilicity of biochar, and the oleophilicity of biochar was kept simultaneously. Conversion became 4 times using bifunctional biochar compared with blank results during the oxidation of benzyl alcohol. More interestingly, the turnover frequency (TOF) value using bifunctional biochar enhanced 61% than that employing N-doped superamphiphilic carbon without catalytic activity. Catalytic activities of bifunctional biochar could be ascribed to the existence of different chemical bonds containing the element B. This work paves a path toward rational design of bifunctional biochar materials with special wettability and catalytic activity for greatly enhancing the liquid-liquid biphasic reaction efficiencies.

The effect of retirement on physical and mental health in China: a nonparametric fuzzy regression discontinuity study.

BACKGROUND: With the rapid aging of the domestic population, China has a strong incentive to increase the statutory retirement age. How retirement affects the health of the elderly is crucial to this policymaking. The health consequences of retirement have been debated greatly. This study aims to investigate the effects of retirement on physical and mental health among Chinese elderly people. METHODS: The data we use in this study comes from four waves (2011, 2013, 2015, and 2018) of the Harmonized China Health and Retirement Longitudinal Study (Harmonized CHARLS), a prospective cohort. We use the nonparametric fuzzy regression discontinuity design to estimate the effects of retirement on physical and mental health. We test the robustness of our results with respect to different bandwidths, kernel functions, and polynomial orders. We also explore the heterogeneity across gender and education. RESULTS: Results show that retirement has an insignificant effect on a series of physical and mental health outcomes, with and without adjusting several sociodemographic variables. Heterogeneity exists regarding gender and education. Although stratified analyses indicate that the transition from working to retirement leaves minimal effects on males and females, the effects go in the opposite direction. This finding holds for low-educated and high-educated groups for health outcomes including depression and cognitive function. Most of the results are stable with respect to different bandwidths, kernel functions, and polynomial orders. CONCLUSIONS: Our results suggest that it is possible to delay the statutory retirement age in China as retirement has insignificant effects on physical and mental health. However, further research is needed to assess the long-term effect of retirement on health.

The superiority of Pd2+ in CO2 hydrogenation to formic acid.

The hydrogenation of CO2 to formic acid is an essential subject since formic acid is a promising hydrogen storage material and a valuable commodity chemical. In this study, we report for the first time the hydrogenation of CO2 to formic acid catalyzed by a Pd2+ catalyst, Pd-V/AC-air. The catalyst exhibited extraordinary catalytic activity toward the hydrogenation of CO2 to formic acid. The TON and TOF are up to 4790 and 2825 h-1, respectively, representing the top level among reported heterogeneous Pd catalysts. By combining a study of first-principles density functional theory with experimental results, the superiority of Pd2+ over Pd0 was confirmed. Furthermore, the presence of V modified the electronic state of Pd2+, thus promoting the reaction. This study reports the effect of metal valence and electronic state on the catalytic performance for the first time and provides a new prospect for the design of an efficient heterogeneous catalyst for the hydrogenation of CO2 to formic acid.

Selective hydrodeoxygenation of α, ß-unsaturated carbonyl compounds to alkenes.

Achieving selective hydrodeoxygenation of α, ß-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, ß-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry.

Highly Efficient Electrosynthesis of Glycine over an Atomically Dispersed Iron Catalyst.

Glycine is a nonessential amino acid that plays a vital role in various biological activities. However, the conventional synthesis of glycine requires sophisticated procedures or toxic feedstocks. Herein, we report an electrochemical pathway for glycine synthesis via the reductive coupling of oxalic acid and nitrate or nitrogen oxides over atomically dispersed Fe-N-C catalysts. A glycine selectivity of 70.7% is achieved over Fe-N-C-700 at -1.0 V versus RHE. Synergy between the FeN3C structure and pyrrolic nitrogen in Fe-N-C-700 facilitates the reduction of oxalic acid to glyoxylic acid, which is crucial for producing glyoxylic acid oxime and glycine, and the FeN3C structure could reduce the energy barrier of *HOOCCH2NH2 intermediate formation thus accelerating the glyoxylic acid oxime conversion to glycine. This new synthesis approach for value-added chemicals using simple carbon and nitrogen sources could provide sustainable routes for organonitrogen compound production.

Persistent high sepsis-induced coagulopathy and sequential organ failure assessment scores can predict the 28-day mortality of patients with sepsis: A prospective study.

BACKGROUND: The performance of the sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores in predicting the prognoses of patients with sepsis has been validated. This study aimed to investigate the time course of SIC and SOFA scores and their association with outcomes in patients with sepsis. METHODS: This prospective study enrolled 209 patients with sepsis admitted to the emergency department. The SIC and SOFA scores of the patients were assessed on days 1, 2, and 4. Patients were categorized into survivor or non-survivor groups based on their 28-day survival. We conducted a generalized estimating equation analysis to evaluate the time course of SIC and SOFA scores and the corresponding differences between the two groups. The predictive value of SIC and SOFA scores at different time points for sepsis prognosis was evaluated. RESULTS: In the non-survivor group, SIC and SOFA scores gradually increased during the first 4 days (P < 0.05). In the survivor group, the SIC and SOFA scores on day 2 were significantly higher than those on day 1 (P < 0.05); however, they decreased on day 4, dropping below the levels observed on day 1 (P < 0.05). The non-survivors showed higher SIC scores on days 2 (P < 0.05) and 4 (P < 0.001) than the survivors, whereas no significant differences were found between the two groups on day 1 (P > 0.05). The performance of SIC scores on day 4 for predicting mortality was more accurate than that on day 2, with areas under the curve of 0.749 (95% confidence interval [CI]: 0.674-0.823), and 0.601 (95% CI: 0.524-0.679), respectively. The SIC scores demonstrated comparable predictive accuracy for 28-day mortality to the SOFA scores on days 2 and 4. Cox proportional hazards models indicated that SIC on day 4 (hazard ratio [HR] = 3.736; 95% CI: 2.025-6.891) was an independent risk factor for 28-day mortality. CONCLUSIONS: The time course of SIC and SOFA scores differed between surviving and non-surviving patients with sepsis, and persistent high SIC and SOFA scores can predict 28-day mortality.

Acute muscle wasting is associated with poor prognosis in older adults with severe community-acquired pneumonia.

PURPOSE: To investigate the impact of acute muscle wasting on 90-day mortality in older patients with severe pneumonia using ultrasound and chest computed tomography (CT). METHODS: Quadriceps muscle layer thickness was measured via ultrasound on days 1, 7, and 14, and cross-sectional area of the erector spinae muscle was assessed using chest CT on days 1 and 14 in patients aged ≥ 65 years old. The primary outcome was all-cause 90-day mortality. Receiver operating characteristic curves were conducted for muscle loss to predict 90-day mortality. Cox proportional hazard models and Kaplan-Meier survival curves were employed to evaluate the association between muscle loss and 90-day mortality. RESULTS: Sixty-two patients were enrolled with median age of 80.2 years, 29 (46.8%) were men and 28 (45.2%) patients died. Muscle mass measured using ultrasound and CT decreased significantly from baseline to day 14 in the non-survivor group. Muscle loss assessed by ultrasound (with minimum and maximum pressure) and CT independently predicted all-cause 90-day mortality (adjusted hazard ratios = 1.497, 1.400 and 1.082; P < 0.001, P = 0.002, and P = 0.004; respectively), and cutoff values of muscle loss were 0.34 cm, 0.11 cm and 4.92 cm2, correspondingly. A higher muscle loss had an increased risk of 90-day mortality. CONCLUSIONS: Acute muscle wasting assessed by ultrasound and chest CT persisted for 14 days and was an independent predictor of adverse outcomes in older patients with severe pneumonia. A greater decline in muscle mass was associated with a higher 90-day mortality risk.

Exploring the impact of gut microbiota on abdominal aortic aneurysm risk through a bidirectional Mendelian randomization analysis.

OBJECTIVE: The abdominal aortic aneurysm (AAA) is associated with alterations in the composition of the gut microbiota; however, the precise causal relationship remains unclear. Elucidating this complex interplay could provide new insights into the pathogenesis of AAA. METHODS: A bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide association study summary data on the gut microbiota (n = 18,340) and AAA (n = 353,087). A total of 196 gut microbial taxa across taxonomic levels were examined for their potential causal effects on AAA risk. Conversely, the effect of AAA on these microbial taxa was also analyzed. RESULTS: Nine microbial taxa were identified as having a causal influence on AAA risk. Specifically, increased risk were associated with genus Bilophila (odds ratio [OR], 1.359; P = .0119), genus Catenibacterium (OR, 1.348; P = .0058), genus family XIII AD3011 group (OR, 1.507; P = .004), genus Oxalobacter (OR, 1.157; P = .0449), and genus Prevotella 7 (OR, 1.194; P = .0306), whereas decreased risks were linked to class Lentisphaeria (OR, 0.829; P = .0361), order Victivallales (OR, 0.829; P = .0361), family Victivallaceae (OR, 0.814; P = .0057), and genus Anaerotruncus (OR, 0.773; P = .0497). Furthermore, AAA was found to influence the abundance of 14 microbial taxa across various taxonomic levels. Notably, bidirectional associations were observed with the class Lentisphaeria and the order Victivallales. CONCLUSIONS: This study provides novel evidence for a reciprocal causal relationship between gut microbiota and AAA risk, thereby offering new insights into the pathogenesis of AAA. These findings also suggest promising avenues for microbiome-based therapeutic interventions.

Catalytic Conversion of Lignin into Valuable Chemicals: Full Utilization of Aromatic Nuclei and Side Chains.

ConspectusIn recent years, significant efforts have been directed toward achieving efficient and mild lignocellulosic biomass conversion into valuable chemicals and fuels, aiming to address energy and environmental concerns and realize the goal of carbon neutrality. Lignin is one of the three primary building blocks of lignocellulose and the only aromatic renewable feedstock. However, the complex and diverse nature of lignin feedstocks, characterized by their three-dimensional, highly branched polymeric structure and intricate C-O/C-C chemical bonds, results in substantial challenges. To tackle these challenges, we carried out extensive research on selectively activating and transforming chemical bonds in lignin for chemical synthesis. In this Account, we discuss our recent progress in catalytic lignin conversion.Our work is focused on two main objectives: (i) achieving precise and selective transformation of C-O/C-C bonds in lignin (and its model compounds) and (ii) fully utilizing the aromatic nuclei and side chains present in lignin to produce valuable chemicals. Lignin consists of interconnected phenylpropanoid subunits linked by interlaced C-C/C-O bonds. To unlock the full potential of lignin, we propose the concept of "the full utilization of lignin", which encompasses both the aromatic nuclei and the side chains (e.g., methoxyl and polyhydroxypropyl groups).For the conversion of aromatic nuclei, selective activation of C-O and/or C-C bonds is crucial in synthesizing targeted aromatic products. We begin with model compounds (such as anisole, phenol, guaiacol, etc.) and then transition to protolignin feedstocks. Various reaction routes are developed, including self-supported hydrogenolysis, direct Caryl-Csp3 cleavage, coupled Caryl-Csp3 cleavage and Caryl-O hydrogenolysis, and tandem selective hydrogenation and hydrolysis processes. These tailored pathways enable high-yield and sustainable production of a wide range of aromatic (and derived) products, including arenes (benzene, toluene, alkylbenzenes), phenols, ketones, and acids.In terms of side chain utilization, we have developed innovative strategies such as selective methyl transfer, coupling depolymerization-methyl shift, selective acetyl utilization, and new activation methods such as amine-assisted prefunctionalization. These strategies enable the direct synthesis of methyl-/alkyl-derived products, such as acetic acid, 4-ethyltoluene, dimethylethylamine, and amides. Additionally, aromatic residues can be transformed into chemicals or functionalized ingredients that can serve as catalysts or functional biopolymer materials. These findings highlight promising opportunities for harnessing both the aromatic nuclei and side chains of lignin in a creative manner, thereby improving the overall atom economy of lignin upgrading.Through innovative catalyst engineering and reaction route strategies, our work achieves the sustainable and efficient production of various valuable chemicals from lignin. By integrating side chains and aromatic rings, we have successfully synthesized methyl-/alkyl-derived and aromatic-derived products with high yields. The full utilization of lignin not only minimizes waste but also opens up new possibilities for generating chemical products from lignin. These novel approaches unlock the untapped potential of lignin, expand the boundaries of lignin upgrading, and enhance the efficiency and economic viability of lignin biorefining.

Effect of the telemedicine-supported multicomponent exercise therapy in patients with knee osteoarthritis: study protocol for a randomized controlled trial.

INTRODUCTION: The rising prevalence of knee osteoarthritis is placing a considerable strain on the global healthcare system. To address this issue, telemedicine-supported multicomponent exercise therapy has emerged as a promising approach. This therapy combines exercise, patient education, and health coaching to empower knee osteoarthritis patients to manage their condition from the comfort of their homes. Nevertheless, there are some existing limitations in the current research on this approach, including challenges related to patient compliance and the absence of objective evaluation methods. METHODS AND ANALYSIS: Patients diagnosed with knee osteoarthritis, who have not undergone knee surgery in the past year, will be recruited for a randomized controlled trial. The trial will include an intervention group and a control group. The intervention group will receive an mHealth app-based multicomponent exercise therapy, consisting of exercise therapy, patient education, and health coaching. Meanwhile, the control group will receive usual care, involving drug therapy and patient education. The primary outcome of the trial will be the measurement of pain intensity, assessed using a visual analog scale at baseline and at 4, 8, and 12 weeks of the post-intervention. To analyze the data, a two-factor, four-level repeated measures ANOVA will be used if the assumptions of homogeneity of variance and sphericity are met. If not, a mixed effects model will be employed. DISCUSSION: The aim of the study is to evaluate the effectiveness of multicomponent exercise therapy aimed at enhancing pain self-management for knee osteoarthritis patients in the comfort of their own homes. The intervention incorporate wearable devices equipped with advanced deep learning systems to monitor patients' adherence to the prescribed at-home exercise regimen, as well as to track changes in outcomes before and after the exercise sessions. The findings from this trial have the potential to enhance both the accessibility and quality of care provided to knee osteoarthritis patients, offering valuable insights for future improvements in their treatment and management. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR2300073688. Registered on 19 July 2023, https://www.chictr.org.cn/bin/project/edit?pid=199707 . World Health Organization International Clinical Trials Registry Platform, https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300073688 .

Erector spinae muscle-based nomogram for predicting in-hospital mortality among older patients with severe community-acquired pneumonia.

BACKGROUND: No multivariable model incorporating erector spinae muscle (ESM) has been developed to predict clinical outcomes in older patients with severe community-acquired pneumonia (SCAP). This study aimed to construct a nomogram based on ESM to predict in-hospital mortality in patients with SCAP. METHODS: Patients aged ≥ 65 years with SCAP were enrolled in this prospective observational study. Least absolute selection and shrinkage operator and multivariable logistic regression analyses were used to identify risk factors for in-hospital mortality. A nomogram prediction model was constructed. The predictive performance was evaluated using the concordance index (C-index), calibration curve, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis. RESULTS: A total of 490 patients were included, and the in-hospital mortality rate was 36.1%. The nomogram included the following independent risk factors: mean arterial pressure, peripheral capillary oxygen saturation, Glasgow Coma Scale score (GCS), lactate, lactate dehydrogenase, blood urea nitrogen levels, and ESM cross-sectional area. Incorporating ESM into the base model with other risk factors significantly improved the C-index from 0.803 (95% confidence interval [CI], 0.761-0.845) to 0.836 (95% CI, 0.798-0.873), and these improvements were confirmed by category-free NRI and IDI. The ESM-based nomogram demonstrated a high level of discrimination, good calibration, and overall net benefits for predicting in-hospital mortality compared with the combination of confusion, urea, respiratory rate, blood pressure, and age ≥ 65 years (CURB-65), Pneumonia Severity Index (PSI), Acute Physiology and Chronic Health Evaluation II (APACHEII), and Sequential Organ Failure Assessment (SOFA). CONCLUSIONS: The proposed ESM-based nomogram for predicting in-hospital mortality among older patients with SCAP may help physicians to promptly identify patients prone to adverse outcomes. TRIAL REGISTRATION: This study was registered at www.chictr.org.cn (registration number Chi CTR-2300070377).

Infection status and clinical characteristics of COVID-19 in maintenance hemodialysis patients in Wuhan during the omicron pandemic.

Maintenance hemodialysis (MHD) patients are the high-risk population of infection and death of novel coronavirus disease 2019 (COVID-19), our study aimed to investigate the infection status and clinical characteristics of COVID-19 in MHD patients at a single-center in Wuhan during the Omicron pandemic. In this retrospective, single-center study, we analyzed the clinical data of all MHD patients in Hemodialysis Center of Wuhan No. 1 Hospital from December 2, 2022 to January 6, 2023 during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron pandemic outbreak. We analyzed the epidemiological and clinical characteristics of deaths and survivors of MHD patients. The infection rate of SARS-CoV-2 in MHD patients was 93.32% (573/614), mortality rate was 8.14% (50/614), hospitalization rate was 23.29% (143/614), and the vaccination rate of COVID-19 was 4.89% (30/614). The median survival time of dead patients was 11 days, the mortality rate of male MHD patients was significantly higher than female. Elderly MHD patients had a higher mortality rate, with a average age of death higher than 70 years old. Additionally, the mortality rate of MHD patients infected with SARS-CoV-2 was higher if the primary disease was hypertensive renal damage or diabetic nephropathy. Laboratory results showed that the lower the albumin level and the higher the C-reactive protein level of MHD patients who died of SARS-CoV-2 infection and severe and critical survival patients. In surviving MHD patients infected with SARS-CoV-2, the most common symptoms were hypodynamia (84.70%), decreased appetite (81.26%) and cough (80.69%). The symptoms of fever, chest tightness and panting, cough, pharyngalgia, hypodynamia, decreased appetite in surviving MHD patients with severe and critical type were significantly higher than those in patients with mild and moderate type. MHD patients are a highly vulnerable population at increased risk of mortality during the Omicron pandemic. Elderly, male, primary disease was hypertensive renal damage or diabetic nephropathy, hypoproteinemia and high C-reactive protein level, all of which will lead to increased mortality in MHD patients.

Rapid Identification of Alkaloids and Flavonoids in Fissistigma oldhamii var. longistipitatum by Ultra High-Performance Liquid Chromatography and Quadrupole Time-of-Flight Tandem Mass Spectrometry.

The herb Fissistigma oldhamii var. longistipitatum has been used for a long time in Asian folk medicine in the treatment of several diseases, including rheumatoid arthritis and other inflammatory conditions. Researchers in China and elsewhere have analyzed and characterized its chemical content. In this study, a UHPLC-Q-TOF-MS/MS method, run in both positive and negative modes, was used to identify the main chemical compounds in dichloromethane extracts of this F. oldhamii variant. A total of 64 compounds, including 44 alkaloids and 20 flavonoids, were rapidly identified or tentatively characterized by comparing the molecular ion peaks and MS2 mass spectrometry fragment ions, combined with the mass spectrometry information of reference substances, appropriate fragmentation ions and related literatures. For the first time, the developed UHPLC-Q-TOF-MS/MS analysis method allows for the determination of 64 compounds from extracts of the F. oldhamii variant. The method presented here produced results that will be useful in further studies of this herb.

Nonpharmacological Interventions for Management of the Pain-Fatigue-Sleep Disturbance Symptom Cluster in Breast Cancer Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: The pain-fatigue-sleep disturbance symptom cluster is commonly experienced by breast cancer patients, and a variety of nonpharmacological interventions are used to treat this symptom cluster. Objective: To compare the efficacy of nonpharmacological interventions in improving the symptoms of the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Methods: A comprehensive literature search was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL, CNKI, and Wanfang databases to identify randomized controlled studies from database inception to May 2022. Two reviewers independently performed data retrieval and risk of bias assessments. The consistency model was used to conduct network meta-analyses (NMA) based on the frequentist framework to assess the interventions, which were ranked by the surface under the cumulative ranking curve (SUCRA). Finally, the CINeMA application was used to evaluate the results of the NMA and the evidence of quality. The results Twenty-three eligible studies assessing 14 interventions were included. According to SUCRA values, among the management effects of the three symptoms, the effect of progressive muscle relaxation (PMR) ranked first, followed by mindfulness-based stress reduction (MBSR). The overall evidence quality of our study ranges from very low to moderate. Conclusion: PMR and MBSR were effective interventions for the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Clinical recommendations prioritize PMR for symptom management, followed by MBSR. However, this should be interpreted cautiously, as the confidence in the evidence was not high.

Comparison of PD-L1 expression and MMR status between primary and matched metastatic lesions in patients with cervical cancer.

PURPOSE: Programmed death-ligand 1 (PD-L1) and DNA mismatch repair (MMR) are considered predictive biomarkers for immunotherapy in cervical cancer. However, their expression in primary tumors and metastases does not always match affecting the course of treatment. We investigated the consistency of their expression in primary and matched recurrent/metastatic lesions from patients with cervical cancer. METHODS: Primary and matched recurrent/metastatic specimens from patients with recurrent cervical cancer (n = 194) were stained for PD-L1 and MMR (MLHI, MSH6, MSH2, and PMS2) using immunohistochemistry. The degree of consistency of PD-L1 and MMR expression in these lesions was analyzed. RESULTS: The inconsistency rate of PD-L1 expression in primary and recurrent/metastatic lesions was 33.0%, and it varied between the recurrence sites. Positive PD-L1 rate in primary lesions was lower (15.4%) than that in recurrent/metastatic lesions (30.4%). The discordance rate of MMR expression between primary and recurrent/metastatic lesions was 4.1%. CONCLUSION: We conclude that to use PD-L1 as a predictive biomarker for immunotherapy, analysis of both metastatic and primary lesions may be required. High consistency rate of MMR expression between primary and metastatic lesions suggests that testing primary lesions alone can be sufficient for guiding the course of therapy, thereby solving the difficulty of obtaining recurrent/metastatic specimens in clinic.

Aerobic Oxidative Cleavage of C(OH)-C Bonds to Produce Aromatic Aldehydes Catalyzed by CuI -1,10-phenanthroline Complex.

Effective cleavage and functionalization of C(OH)-C bonds is of great importance for the production of value-added chemicals from renewable biomass resources such as carbohydrates, lignin and their derivatives. The efficiency and selectivity of oxidative cleavage of C(OH)-C bonds are hindered by their inert nature and various side reactions associated with the hydroxyl group. The oxidative conversion of secondary alcohols to produce aldehydes is particularly challenging because the generated aldehydes tend to be over-oxidized to acids or the other side products. Noble-metal based catalysts are necessary to get satisfactory aldehyde yields. Herein, for the first time, the efficient aerobic oxidative conversion of secondary aromatic alcohols into aromatic aldehydes is reported using non-noble metal catalysts and environmentally benign oxygen, without any additional base. It was found that CuI -1,10-phenanthroline (Cu-phen) complex showed outstanding performance for the reactions. The C(OH)-C bonds of a diverse array of aromatic secondary alcohols were effectively cleaved and functionalized, selectively affording aldehydes with excellent yields. Detailed mechanism study revealed a radical mediated pathway for the oxidative reaction. We believe that the findings in this work will lead to many explorations in non-noble metal catalyzed oxidative reactions.

Recent progress in patent foramen ovale and related neurological diseases: A narrative review.

Patent foramen ovale (PFO) is a common congenital cardiac abnormality when the opening of the interatrial septum is not closed in adulthood. This abnormality affects 25% of the general population. With the development of precision medicine, an increasing number of clinical studies have reported that PFO is closely related to various neurological diseases such as stroke, migraine, obstructive sleep apnea, and decompression syndrome. It has also been suggested that PFO closure could be effective for preventing and treating these neurological diseases. Therefore, increasing attention has been given to the prevention, diagnosis, and treatment of PFO-related neurological diseases. By reviewing existing literature, this article focuses on the pathogenesis, epidemiology, and clinical characteristics of PFO-related neurological diseases, as well as the prevention and treatment of different neurological diseases to discuss, and aims to provide current progress for this field and decision-making evidence for clinical practice.

Identification of the MALAT1/miR-106a-5p/ZNF148 feedback loop in regulating HaCaT cell proliferation, migration and apoptosis.

Aims: This study aims to investigate the function of positive feedback loops involving noncoding RNA in diabetic wound healing. Methods: We developed a mouse diabetic wound model to confirm that hyperglycemia can impair wound healing. We also used an in vitro keratinocyte model in high-glucose conditions to investigate the mechanism of delayed wound healing. Results: MALAT1 was decreased in diabetic mouse wound tissue and can promote keratinocyte biological functions. MALAT1 could bind to miR-106a-5p to modulate the expression of ZNF148, a target gene of miR-106a-5p. Surprisingly, ZNF148 bound to a region in the MALAT1 promoter to stimulate gene expression. Conclusion: ZNF148-activated MALAT1 increases ZNF148 expression by competitively binding miR-106a-3p, generating a positive feedback loop that enhances keratinocyte function.

Delayed wound repair is a leading cause of diabetic foot ulcers. However, the molecular mechanism underlying impaired wound healing in diabetes is unclear. In our study we found that a positive feedback loop consisting of MALAT1, miR-106a-5p and ZNF148 could promote chronic wound repair. In diabetic skin tissues, MALAT1 levels were lower, causing impairments in skin cell function. On a molecular level, MALAT1 can bind miR-106a-5p to increase ZNF148 levels. Surprisingly, ZNF148 can bind the promoter of MALAT1 to reverse the decline of MALAT1 levels in diabetic wounds. Our findings advance our understanding of chronic diabetic wounds and, more crucially, open new therapeutic possibilities for this disease.