Safety and efficacy of minimally invasive gastrectomy for older patients with gastric cancer after neoadjuvant chemotherapy and immunotherapy: a propensity score-matched analysis.

BACKGROUND: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) in older patients with gastric cancer remains controversial. This study aimed to evaluate the safety, and efficacy of MIG for older patients who underwent neoadjuvant chemotherapy and immunotherapy (NICT). METHODS: The clinical data of 726 older patients aged over 65 years who underwent upfront MIG or MIG after NICT in the Department of General Surgery, Chinese PLA General Hospital First Medical Center between Jan 2020 and Nov 2023 were retrospectively analyzed. Propensity score-matched (PSM) analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables, short- and long-term outcomes were compared between the two groups. RESULTS: The baseline characteristics were comparable between 61 patients in the NICT-MIG group and 114 patients in the MIG group after PSM (P > 0.05). The major pathological response (MPR) rate and pathological complete response (pCR) rate were 44.2% and 21.3%, respectively, in the NICT-MIG group. Patients in the NICT-MIG group had longer operation times (P = 0.005) and postoperative days (P = 0.030) than those in the MIG group. No significant differences were found in intraoperative bleeding, number of retrieved lymph nodes, first flatus day, R0 resection rate, overall postoperative complication (POC) morbidity, severe POC morbidity, 2-year overall, and recurrence-free survival between the MIG and NICT-MIG groups (P > 0.05). Multivariate logistic analysis revealed that an estimated blood loss > 200 mL (P = 0.010) and a lymphocyte-to-monocyte ratio (LMR) ≤ 3.25 (P = 0.006) were independent risk factors for POCs after MIG in older patients. CONCLUSION: The safety, and efficacy of NICT-MIG were comparable to those of upfront MIG in older patients with GC. Patients with an estimated blood loss > 200 mL or an LMR ≤ 3.25 should be carefully evaluated for an increased risk of POCs in older patients who undergo MIG. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2400086827).

A high reticulocyte count is a risk factor for the onset of metabolic dysfunction-associated steatotic liver disease: Cross-sectional and prospective studies of data of 310,091 individuals from the UK Biobank.

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

Polygenic risk score of metabolic dysfunction-associated steatotic liver disease amplifies the health impact on severe liver disease and metabolism-related outcomes.

BACKGROUND: Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes. METHODS: Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes. RESULTS: Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes. CONCLUSIONS: High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.

Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Multimodal Machine Learning-Based Marker Enables Early Detection and Prognosis Prediction for Hyperuricemia.

Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism-related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre-emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in-silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism-related outcomes, effectively classifying individuals into low- and high-risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high-risk group shows increased susceptibility to metabolism-related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism-related outcomes. The multimodal machine learning-based ISHUA marker enables personalized risk stratification for gout and metabolism-related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high-risk group, providing guidance for preventive interventions.

Genetic and recombination heterogeneity of Canine Bufaviruses detected in diarrheal dogs in China.

Bufavirus (BuV) was first identified in feces from children with acute diarrhea, and a genetically related Canine bufavirus (CBuV) was first reported in Italy in 2018. In this study, through the investigation of CBuV in 622 anal swabs from dogs with diarrhea symptoms collected from various provinces in northern, central and eastern China during 2018-2022, 14 samples were detected to be positive. And 5 samples were from dogs co-infected with other canine diarrhea related viruses, which consist of CPV-2, CDV and CCoV. The complete genome sequences (4219 nt) of the fourteen strains were amplified and sequenced. Through comparative analysis with 51 reference BuV strains, six strains might recombinate from the CBuV strains (HUN/2012/22, CaBuV/9AS/2005/ITA and CaBuV/35/2016/ITA) in Hungary and Italy as the parents, and two genetic recombination events from various parents were predicted to occur on the BUV-422 strain. Combined analyzing the phylogenetic tree and sequence alignment, it was found that these CBuVs are highly conserved in the nonstructural protein NS1, but indeed various amino acid mutation sites in the capsid protein VP2, and even some amino acid sites coincide with putative protein plastic regions and potential epitopes. The BUV-422 and BUV-512 strains show sequential mutation sites identical to the divergent strains of CaBuV/9AS/2005/ITA and CaBuV/35/2016/ITA. This study would enrich the molecular data of CBuV in China and provide essential reference for the epidemiological research and vaccine development of CBuV in the future.

Regulation of the PD-1/PD-L1 Axis and NK Cell Dysfunction by Exosomal miR-552-5p in Gastric Cancer.

OBJECTIVE: NK cells play a vital role in tumor immune resistance. Various factors affect NK cell activity. While NK cell dysfunction has been observed in numerous malignancies, the underlying mechanisms in gastric cancer remain unclear. METHOD: Flow cytometry was used to identify the phenotypic distribution and expression of activated receptors on NK cells. ELISA was used to determine the expression of cytokines. We examined the expression of NK cell-related genes and explored their association with survival and prognosis. Additionally, we conducted PCR detection of miR-552-5p expression levels in plasma exosomes of patients and investigated its correlation with phenotypic distribution and activated receptors. We used flow cytometry and ELISA to verify the role of miR-552-5p in NK cell dysfunction. Furthermore, we investigated the potential role of PD-1/PD-L1 in regulating NK cell dysfunction in patients' cells. RESULTS: We observed a significant decrease in the percentage of NKG2D and NKp30 and IFN-γ and TNF-α in patients than in healthy volunteers. Patients with low levels of CD56, CD16, NKG2D, and NKP46 exhibited poorer survival prognoses. Moreover, increased expression levels of plasma exosomal miR-552-5p in patients were negatively associated with NK cell phenotypic distribution and activated receptor expression. MiR-552-5p downregulated the secretion of perforin, granzyme, and IFN-γ as well as the expression of NKp30, NKp46, and NKG2D. Additionally, it suppressed the cytotoxicity of NK cells. The inhibitory effect of miR-552-5p, on NK cell function was reversed when anti-PD-L1 antibodies were used. CONCLUSION: Exosomal miR-552-5p targets the PD-1/PD-L1 axis, leading to impaired NK cell function.

The abnormalities of free fatty acid metabolism in patients with hypertrophic cardiomyopathy, a single-center retrospective observational study.

BACKGROUND: Previous studies have shown the importance of energy deficiency and malfunctioning mitochondria in the pathophysiology of hypertrophic cardiomyopathy (HCM). There has been a little research into the relationship between plasma free fatty acids (FFA), one of the heart's main energy sources, and HCM. We evaluated its clinical importance in HCM to see if there was a link between plasma FFA metabolism and HCM. METHODS: In a single-center retrospective observational study, we investigated 420 HCM patients diagnosed at Beijing Anzhen Hospital between January 1, 2018, and December 31, 2022. Meanwhile, 1372 individuals without HCM (non-HCM) were recruited. 391 non-HCM patients were chosen as controls via a propensity score matching (PSM) study with a 1:1 ratio. RESULTS: FFA in HCM patients showed statistically significant correlations with creatinine (r = 0.115, p = 0.023), estimated GFR (r=-0.130, p = 0.010), BNP (r = 0.152, p = 0.007), LVEF (r=-0.227, p < 0.001), LVFS (r=-0.160, p = 0.002), and LAD (r = 0.112, p = 0.028). Higher FFA levels were found in HCM patients who had atrial fibrillation and NYHY functional classes III or IV (p = 0.015 and p = 0.022, respectively). In HCM patients, multiple linear regression analysis revealed that BNP and LVEF had independent relationships with increasing FFA (Standardized = 0.139, p = 0.013 and =-0.196, p < 0.001, respectively). CONCLUSIONS: Among HCM patients, the plasma FFA concentration was lower, and those with AF and NYHY functional class III or IV had higher FFA levels, and LVEF and BNP were independently associated with increasing FFA. The findings of the study should help inspire future efforts to better understand how energy deficiency contributes to hypertrophic cardiomyopathy (HCM) development.

Exploring Spatiotemporal Patterns of Algal Cell Density in Lake Dianchi with Explainable Machine Learning.

The escalating global occurrence of algal blooms poses a growing threat to ecosystem services. In this study, the spatiotemporal heterogeneity of water quality parameters was leveraged to partition Lake Dianchi into three clusters. Considering water quality parameters and both the delayed and instantaneous effects of meteorological factors, ensemble learning, and quasi-Monte Carlo methods were employed to predict daily algal cell density (AD) between January 2021 and January 2024. Consistently, superior predictive accuracy across all three clusters was exhibited by the Stacking-Elastic-Net regularization model. Furthermore, the minimum combination of drivers that achieved near-optimal accuracy for each cluster was identified, striking a balance between accuracy and cost. The ranking of the effect of drivers on AD varied by cluster, while the delayed effect of meteorological factors on AD generally outweighed their instantaneous effect for all clusters. Additionally, the heterogeneous or homogeneous thresholds and responses between drivers and AD were explored. These findings could serve as a scientific and cost-effective basis for government agencies to develop regional sustainable strategies for managing water quality.

Akkermansia muciniphila-derived pentadecanoic acid enhances oxaliplatin sensitivity in gastric cancer by modulating glycolysis.

Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy. Further, metagenomics data showed that Akkermansia muciniphila (A. muciniphila) ranked first among the bacterial species with decreased relative abundances after antibiotic treatment. Metabolically active A. muciniphila promotes oxaliplatin efficacy. As shown by metabolomics analysis, the metabolic pattern of gut microbiota was disrupted with significantly downregulated levels of pentadecanoic acid (PEA), and the use of PEA significantly promoted oxaliplatin efficacy. Mechanistically, FUBP1 positively regulated aerobic glycolysis of GC cells to hinder the therapeutic efficacy of oxaliplatin. A. muciniphila-derived PEA functioned as an inhibitory factor of glycolysis by directly antagonizing the activity of FUBP1, which potentiated GC responses to oxaliplatin. Our research suggested a key role for intestinal A. muciniphila and its metabolite PEA in promoting oxaliplatin efficacy, thus providing a new perspective for probiotic and prebiotic intervention in GC patients during chemotherapy.

Trends in the burden and determinants of HIV in the Asia-Pacific region (1990-2019): An age-period-cohort analysis of the 2019 Global Burden of Disease Study.

Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.

Diallyl disulfide, the bioactive component of Allium species, ameliorates pulmonary fibrosis by mediating the crosstalk of farnesoid X receptor and yes-associated protein 1 signaling pathway.

Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species. The present study aims to explore the preventive effect and potential mechanism of DADS on pulmonary fibrosis. C57BL/6J mice were intratracheally injected with bleomycin (BLM) to establish pulmonary fibrosis and then administrated with DADS. Primary lung fibroblasts or A549 were stimulated with BLM, followed by DADS, farnesoid X receptor (FXR) agonist (GW4064), yes-associated protein 1 (YAP1) inhibitor (verteporfin), or silencing of FXR and YAP1. In BLM-stimulated mice, DADS significantly ameliorated histopathological changes and interleukin-1ß levels in bronchoalveolar lavage fluid. DADS decreased fibrosis markers, HIF-1α, inflammatory cytokines, and epithelial-mesenchymal transition in pulmonary mice and activated fibroblasts. DADS significantly enhanced FXR expression and inhibited YAP1 activation, which functions as GW4064 and verteporfin. A deficiency of FXR or YAP1 could result in the increase of these two protein expressions, respectively. DADS ameliorated extracellular matrix deposition, hypoxia, epithelial-mesenchymal transition, and inflammation in FXR or YAP1 knockdown A549. Taken together, targeting the crosstalk of FXR and YAP1 might be the potential mechanism for DADS against pulmonary fibrosis. DADS can serve as a potential candidate or dietary nutraceutical supplement for the treatment of pulmonary fibrosis.

Tetrahydroberberrubine exhibits preventive effect on obesity by activating PGC1α-mediated thermogenesis in white and brown adipose tissue.

The escalating prevalence of obesity presents formidable challenges, necessitating the development of effective therapeutic strategies. In this study, we aimed to elucidate the preventive effects on obesity of tetrahydroberberrubine (THBru), a derivative of berberine (BBR) and to unravel its underlying mechanism. Using an obese mouse model induced by a high-fat diet (HFD), THBru was found to markedly ameliorate obesity, as evidenced by reduced body weight, decreased Lee's index, diminished fat mass in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT), alongside improved dyslipidemia. Notably, at the same dose, THBru exhibited superior efficacy compared to BBR. RNA-sequencing and gene set enrichment analysis indicated THBru activated thermogenesis, which was further confirmed in WAT, BAT, and 3T3-L1 cells. Bioinformatics analysis of RNA-sequencing data revealed the candidate gene Pgc1α, a key regulator involved in thermogenesis. Moreover, THBru was demonstrated to elevate the expression of PGC1α by stabilizing its mRNA in WAT, BAT and 3T3-L1 cells. Furthermore, PGC1α knockdown blocked the pro-thermogenic and anti-obesity action of THBru both in vivo and in vitro. This study unravels the preventive effects of THBru on obesity through the activation of PGC1α-mediated thermogenesis, thereby delineating its potential therapeutic implications for obesity and associated disorders.

Characteristics of methane and carbon dioxide in ice caves at a high-mountain glacier of China.

The exploration of the spatiotemporal distribution of greenhouse gas (GHG) exchange in the cryosphere (including ice sheet, glaciers, and permafrost) is important for understanding its future feedback to the atmosphere. Mountain glaciers and ice sheets may be potential sources of GHG emissions, but the magnitude and distribution of GHG emissions from glaciers and ice sheets remain unclear because observation data are lacking. In this study, in situ CH4 and CO2 and the mixing ratios of their carbon isotope signatures in the air inside an ice cave were measured, and CH4 and CO2 exchange in the meltwater of Laohugou glacier No. 12, a high-mountain glacier in an arid region of western China, was also analyzed and compared with the exchange in downstream rivers and a reservoir. The results indicated elevated CH4 mixing ratios (up to 5.7 ppm) and depleted CO2 (down to 168 ppm) in the ice cave, compared to ambient levels during field observations. The CH4 and CO2 fluxes in surface meltwater of the glacier were extremely low compared with their fluxes in rivers from the Tibetan Plateau (TP). CH4 and CO2 mixing ratios in the air inside the ice cave were mainly controlled by local meteorological conditions (air temperature, wind speed and direction) and meltwater runoff. The carbon isotopic compositions of CH4 and CO2 in the ice cave and terminus meltwater indicated δ13C-CH4 depletion compared to ambient air, suggesting an acetate fermentation pathway. The abundances of key genes for methanogenic archaea/genes encoding methyl coenzyme M reductase further indicated the production of CH4 by methanogenic archaea from the subglacial meltwater of high-mountain glaciers. The discovery of CH4 emissions from even small high-mountain glaciers indicates a more prevalent characteristic of glaciers to produce and release CH4 from the subglacial environment than previously believed. Nevertheless, further research is required to understand the relationship between this phenomenon and glacial dynamics in the third pole.

Limited Revision with a Newly Designed Hinge Device for the Treatment of Mega-Prosthesis Hinge Failure: Two Case Reports.

BACKGROUND: Surgical treatment for hinge failure in mega-prosthesis continues to be a challenge. This study introduces a new method for treating hinge failure by using a unilateral prosthesis and hinge revision. CASE PRESENTATION: We here present two patients who underwent mega-prosthesis reconstruction after resection of osteosarcoma in the distal femur. To address the issue of knee hyperextension after mega-prosthesis reconstruction, one patient underwent three revision surgeries, two surgeries were performed using the original hinge, and one surgery involved a newly designed hinge. To resolve the problem of dislocation, one patient underwent three revisions, with the first two revisions not involving hinge replacement and the third revision involving a newly designed hinge. Two replacements of unilateral prosthesis and hinge renovations were successful. CONCLUSIONS: Unilateral prosthesis and newly designed hinge device revision are effective in treating the failure of old-fashioned mega-prosthesis hinges.

A Novel Continuous Sleep State Artificial Neural Network Model Based on Multi-Feature Fusion of Polysomnographic Data.

Purpose: Sleep structure is crucial in sleep research, characterized by its dynamic nature and temporal progression. Traditional 30-second epochs falter in capturing the intricate subtleties of various micro-sleep states. This paper introduces an innovative artificial neural network model to generate continuous sleep depth value (SDV), utilizing a novel multi-feature fusion approach with EEG data, seamlessly integrating temporal consistency. Methods: The study involved 50 normal and 100 obstructive sleep apnea-hypopnea syndrome (OSAHS) participants. After segmenting the sleep data into 3-second intervals, a diverse array of 38 feature values were meticulously extracted, including power, spectrum entropy, frequency band duration and so on. The ensemble random forest model calculated the timing fitness value for all the features, from which the top 7 time-correlated features were selected to create detailed sleep sample values ranging from 0 to 1. Subsequently, an artificial neural network (ANN) model was trained to delineate sleep continuity details, unravel concealed patterns, and far surpassed the traditional 5-stage categorization (W, N1, N2, N3, and REM). Results: The SDV changes from wakeful stage (mean 0.7021, standard deviation 0.2702) to stage N3 (mean 0.0396, standard deviation 0.0969). During the arousal epochs, the SDV increases from the range (0.1 to 0.3) to the range around 0.7, and decreases below 0.3. When in the deep sleep (≤0.1), the probability of arousal of normal individuals is less than 10%, while the average arousal probability of OSA patients is close to 30%. Conclusion: A sleep continuity model is proposed based on multi-feature fusion, which generates SDV ranging from 0 to 1 (representing deep sleep to wakefulness). It can capture the nuances of the traditional five stages and subtle differences in microstates of sleep, considered as a complement or even an alternative to traditional sleep analysis.

Strained Au skin on Mesoporous Intermetallic AuCu3 Nanocoral for Electrocatalytic Conversion of Nitrate to Ammonia across a Wide Concentration Range.

Electrochemical nitrate reduction reaction (NitRR) uses nitrate from wastewater, offering a hopeful solution for environmental issues and ammonia production. Yet, varying nitrate levels in real wastewater greatly affect NitRR, slowing down its multi-step process. Herein, a multi-strategy approach was explored through the design of ordered mesoporous intermetallic AuCu3 nanocorals with ultrathin Au skin (meso-i-AuCu3@ultra-Au) as an efficient and concentration-versatile catalyst for NitRR. The highly penetrated structure, coupled with the compressive stress exerted on the skin layer, not only facilitates rapid electron/mass transfer, but also effectively modulates the surface electronic structure, addressing the concentration-dependent challenges encountered in practical NitRR process. As expected, the novel catalyst demonstrates outstanding NitRR activities and Faradaic efficiencies exceeding 95% across a real and widespread concentration range (10-2000 mM). Notably, its performance at each concentration matched or exceeded that of the best-known catalyst designed for that concentration. Multiple operando spectroscopies unveiled the catalyst concurrently optimized the adsorption behavior of different intermediates (adsorbed *NOx and *H) while expediting the hydrogenation steps, leading to an efficient overall reduction process. Moreover, the catalyst also displays promising potential for use in ammonia production at industrial-relevant current densities and in conceptual zinc-nitrate batteries, serving trifunctional nitrate conversion, ammonia synthesis and power supply.

Outcomes of surgical septal myectomy for obstructive hypertrophic cardiomyopathy after previous septal reduction therapy.

OBJECTIVE: To compare early and late outcomes of septal myectomy in patients with obstructive hypertrophic cardiomyopathy who presented with residual or recurrent left ventricular outflow tract (LVOT) obstruction after previous septal-reduction therapy (SRT). METHODS: From January 1989 to March 2022, 145 patients underwent reintervention by septal myectomy for residual LVOT obstruction after previous SRT; 72 patients had previous alcohol septal ablation (ASA) and 73 had previous surgical septal myectomy. Baseline patient characteristics, echocardiographic parameters, and surgical outcomes were compared between these 2 groups. RESULTS: Patients who had previous ASA were more likely to be male (50.0% vs 30.1%; P = .015), be older (median age 57.5 years vs 48.3 years; P < .001), and have a greater body mass index (32.7 kg/m2 vs 30.0 kg/m2; P = .011). After repeat SRT by septal myectomy, there was no significant difference in the incidence of postoperative complete heart block, necessitating permanent pacemaker, between the 2 groups (8.3% vs 2.7%; P = .151). One (0.7%) patient died within 30 days of surgery. Over a median follow-up of 7.5 years (interquartile range, 3.0-13.8), there were 20 deaths. Kaplan-Meier 5-, 10-, and 15-year survival rates were 100%, 91%, and 76% for the previous septal myectomy group, and 93%, 81%, and 64% for the previous ASA group (P = .207). CONCLUSIONS: Septal myectomy for residual or recurrent LVOT obstruction in patients who had previous ASA is safe, with an acceptably low rate of postoperative complete heart block. Surgical outcomes and late survival rates in patients with complete heart block ASA were satisfactory and comparable with patients who underwent repeat myectomy.

Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy.

Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.