Self-assembling peptide hydrogel scaffold integrating stem cell-derived exosomes for infected bone defects.

Infected bone defect (IBD) is a great challenge in orthopedics, which involves in bone loss and infection. Here, a self-assembling hydrogel scaffold (named AMP-RAD/EXO), integrating antimicrobial peptides(AMPs), RADA16 and BMSCs exosomes with an innovative strategy, is developed and applied in IBD treatment for sustained antimicrobial ability, accelerating osteoblasts proliferation and promoting bone regeneration. AMPs present an excellent ability to inhibit infection, RADA16 is a self-assembling peptide hydrogel for AMPs delivery, and BMSCs exosomes can promote the bone regeneration. The prepared AMP-RAD/EXO exhibited a polyporous 3D structure for imbibition of BMSCs exosomes and migration of osteoblasts. In vitro studies indicate AMP-RAD/EXO can inhibit the growth of Staphylococcus aureus, accelerate the proliferation and migration of BMSCs. More importantly, in vivo results also prove that AMP-RAD/EXO exhibit an excellent effect on IBD treatment. Thus, the prepared AMP-RAD/EXO provides a multifunctional scaffold concept for bone tissue engineering technology.

Parallel CSF and serum temporal profile assessment of axonal injury biomarkers NF-L and pNF-H: Associations with patient outcome in moderate-severe traumatic brain injury.

Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels, 2) to evaluate CSF and serum NF-L and pNF-H associations with each other, and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). In this multi-cohort study, we measured serum and CSF NF-L and pNF-H levels in samples collected from two clinical cohorts (University of Pittsburgh [UPITT] and Baylor College of Medicine [BCM]) of individuals with moderate-to-severe TBI. The UPITT cohort includes 279 subjects from an observational cohort study; we obtained serum (n=277 unique subjects) and CSF (n=95 unique subjects) daily for one week, and serum every two weeks for six months. The BCM cohort included 103 subjects from a previous randomized clinical trial of erythropoietin and blood transfusion threshold after severe TBI, which showed no effect on neurological outcome between treatment arms; serum (n=99 unique subjects) and CSF (n=54 unique subjects) NF-L and pNF-H levels were measured at least daily during days (D) 0-10 post-injury. GOS-E and DRS were assessed at 6 months (both cohorts) and 12 months (UPITT cohort only). Results show serum NF-L and pNF-H gradually rise during the first 10 days and peak at D20-30 post-injury. In the UPITT cohort, acute (D0-6) NF-L and pNF-H levels correlate within CSF and serum (Spearman r=0.44-0.48; p<0.05). In the UPITT cohort, acute NF-L CSF and serum levels, as well as chronic (M2-6) serum NF-L levels, were higher among individuals with unfavorable GOS-E and worse DRS at 12 months (p<0.05, all comparisons). In the BCM cohort, higher acute serum NF-L levels were also associated with unfavorable GOS-E. Higher pNF-H serum concentrations (D0-6 and M2-6), but not CSF pNF-H, were associated with unfavorable GOS-E and worse DRS (p<0.05, all comparisons) in the UPITT cohort. Relationships between biomarker levels and favorable outcome persisted after controlling for age, sex, and GCS. This study shows for the first time that serum levels of NF-L and pNF-H peak at D20-30 post-TBI. Serum NF-L levels, and to a lesser extent pNF-H levels, are robustly associated with global patient outcomes and disability after moderate-to-severe TBI. Further studies on clinical utility as prognosis and treatment-response indicators are needed.

Fire acupuncture for plaque psoriasis case series.

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.

Safety, Tolerability, and Pharmacokinetics of Anaprazole, a Novel Proton Pump Inhibitor, in Healthy Chinese Subjects.

Anaprazole, a newly developed oral proton pump inhibitor, was evaluated for safety, tolerability, and pharmacokinetics in healthy Chinese subjects. This study involved administering either anaprazole sodium enteric-coated tablet or placebo, followed by monitoring the incidence and severity of any adverse events (AEs). The pharmacokinetic parameters of anaprazole, its isomer, and main metabolisms were determined. The results showed that both single-dose (2.5-120 mg) and multiple-dose (20 mg once daily, 40 mg once daily, or 20 mg twice daily) oral administration of anaprazole sodium enteric-coated tablet were safe and well tolerated. Following single-dose administration, the median time to reach maximum plasma concentration of anaprazole was between 3.50 and 5.25 hours, with mean elimination half-life of 1.22-3.79 hours. The absorption and elimination of anaprazole in the human body appeared to basically follow linear kinetics. After repeated dosing, steady-state concentrations of anaprazole, its isomer, and primary metabolites were achieved, with a median time to reach maximum plasma concentration of 3-3.75 hours and a mean elimination half-life of 1.61-2.27 hours for anaprazole. There was no significant drug accumulation after multiple-dose oral administration. In conclusion, anaprazole sodium enteric-coated tablets were found to be safe and well tolerated in healthy Chinese individuals. Anaprazole is absorbed and metabolized consistently in the human body without any accumulation.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment. AIM: To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT). METHODS: This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT. RESULTS: A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR (P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS. CONCLUSION: This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Controllable Blue Shift and Enhancement Emission during the Gradually Increasing Molecular Weight of Polyacrylamide.

Nonconventional luminescent polymers have become research hotspots due to their advantages such as persistent room temperature phosphorescence (p-RTP) emission and strong film-forming properties. It is proven that the molecular weight (MW) of such luminescent polymers has a significant impact on their emission over a large range, generally with a red shift as the MW increases. Herein, four controllable MW polyacrylamides are prepared via reversible addition-fragmentation chain transfer polymerization (RAFT), and their photoluminescence quantum yield and p-RTP lifetimes gradually increase with the increasing MW. The emission of p-RTP gradually shifts blue with increasing MW, which is likely due to the gradually changing interactions between the electron-rich portion in RAFT reagent and the increasing acrylamide (AM) units in the molecular chain. These can be reasonably explained through small angle X-ray scattering, the clustering-triggered emission (CTE) mechanism, and supported by theoretical calculations. Powder with controllable p-RTP capability has the potential for strategic anti-counterfeiting encryption. The above results not only promote the development of the CTE mechanism toward more precise explanations but also provide new ideas for the preparation of nonconventional luminescent polymers with controllable p-RTP emission performance.

Temporal characteristics and associated factors of discontinuation and outcomes after percutaneous coronary intervention.

Background: Medication adherence in patients after percutaneous coronary intervention (PCI) is suboptimal, and discontinuation is common. Information on the temporal characteristics and associated factors of discontinuation and outcomes after PCI is insufficient to improve medication adherence interventions. Methods: We conducted a single-center retrospective study of post-PCI patients by telephone survey and medical record extraction. Temporal characteristics and associated factors of discontinuation and outcomes were examined by survival curve analysis, Cox regression, or time-dependent Cox regression. Results: Discontinuation and major adverse cardiovascular events (MACE) after PCI had similar temporal characteristics, with the highest incidence in the first year, followed by a decline. Temporary discontinuation was associated with pre-PCI medication nonadherence (HR 1.63; 95% CI: 1.09-2.43), lack of medication necessity (HR 2.33; 95% CI: 1.44-3.78), economic difficulties (HR 2.09; 95% CI: 1.26-3.47), routine disruption (HR 2.09; 95% CI: 1.10-3.99), and emotional distress (HR 2.76; 95% CI: 1.50-5.09). Permanent discontinuation was associated with residence in rural areas (HR 4.18; 95% CI: 1.84-9.46) or small to medium-sized cities (HR 4.21; 95% CI: 1.82-9.73), lack of medication necessity (HR 10.60; 95% CI: 6.45-17.41), and side effects (HR 3.30; 95% CI: 1.94-5.62). The MACE after PCI was associated with pre-PCI hypertension (HR 1.42; 95% CI: 1.04-1.96), two coronary stents (HR 1.42; 95% CI: 1.01-1.99) or three coronary stents (HR 1.66; 95% CI: 1.11-2.49) compared to one coronary stent up to this PCI, and temporary discontinuation (≤60 months HR 2.18; 95% CI: 1.47-3.25; >60 months HR 8.82; 95% CI: 3.65-21.28). Conclusion: Discontinuation and MACE after PCI have similar temporal characteristics, temporary discontinuation and permanent discontinuation have different associated factors, and the former is associated with MACE. These findings may provide guidance for medication adherence interventions.

Current status of emergency medical service use in ST-segment elevation myocardial infarction in China: Findings from China Acute Myocardial Infarction (CAMI) Registry.

BACKGROUND: The mortality rate of myocardial infarction in China has increased dramatically in the past three decades. Although emergency medical service (EMS) played a pivotal role for the management of patients with ST-segment elevation myocardial infarction (STEMI), the corresponding data in China are limited. METHODS: An observational analysis was performed in 26,305 STEMI patients, who were documented in China acute myocardial infarction (CAMI) Registry and treated in 162 hospitals from January 1st, 2013 to January 31th, 2016. We compared the differences such as demographic factors, social factors, medical history, risk factors, socioeconomic distribution and treatment strategies between EMS transport group and self-transport group. RESULTS: Only 4336 patients (16.5%) were transported by EMS. Patients with symptom onset outside, out-of-hospital cardiac arrest and presented to province-level hospital were more likely to use EMS. Besides those factors, low systolic blood pressure, severe dyspnea or syncope, and high Killip class were also positively related to EMS activation. Notably, compared to self-transport, use of EMS was associated with a shorter prehospital delay (median, 180 vs. 245 min, P < 0.0001) but similar door-to-needle time (median, 45 min vs. 52 min, P = 0.1400) and door-to-balloon time (median, 105 min vs. 103 min, P = 0.1834). CONCLUSIONS: EMS care for STEMI is greatly underused in China. EMS transport is associated with shorter onset-to-door time and higher rate of reperfusion, but not substantial reduction in treatment delays or mortality rate. Targeted efforts are needed to promote EMS use when chest pain occurs and to set up a unique regionalized STEMI network focusing on integration of prehospital care procedures in China. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01874691), retrospectively registered June 11, 2013.

Effect of Low-Intensity Bloodflow Restriction Training on Nontraumatic Knee Joint Conditions: A Systematic Review and Meta-analysis.

CONTEXT: Nontraumatic knee conditions are common in clinical practice. Existing pharmaceutical and immobilization approaches provide limited pain relief and functional enhancement. Low-intensity bloodflow restriction training (LI-BFRT) is being investigated as a nonpharmacological alternative; however, its efficacy is uncertain. OBJECTIVE: To assess the effectiveness of LI-BFRT for nontraumatic knee conditions and compare it with high-intensity resistance training (HI-RT) and low-intensity resistance training (LI-RT). DATA SOURCES: PubMed, EBSCO, Science Direct, Cochrane Library, China Knowledge Infrastructure, Wanfang Data, and VIP databases were searched until May 30, 2023. STUDY SELECTION: Original randomized controlled trials involving nontraumatic knee joint conditions with interventions consisting mainly of LI-BFRT, HI-RT, or LI-RT. The results assessed mainly pain and muscle performance. STUDY DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: Sample characteristics, study design, country, disease, groups, evaluation time, duration, and outcomes were extracted. RESULTS: A total of 13 randomized controlled trials were included in the systematic review. Compared with pretreatment, LI-BFRT significantly alleviated pain (weighted standardized mean difference [SMD], -1.33; 95% CI, -1.62 to -1.05), with better additional effects on hip muscle training (SMD, -3.14; 95% CI, -4.07 to -2.75). Compared with LI-RT, LI-BFRT significantly relieved pain in male patients (SMD, -1.47; 95% CI, -1.92 to -1.01). LI-BFRT significantly increased quadriceps cross-sectional area (SMD, 0.53; 95% CI, 0.27-0.78), knee extension strength (SMD, 0.84; 95% CI, 0.48-1.2), and leg press strength (SMD, 0.64; 95% CI, 0.34-0.94) compared with pretreatment. Its effects were superior to those of LI-RT and similar to those of HI-RT. However, sex differences in muscle strength improvement were observed. CONCLUSION: In patients with nontraumatic knee joint conditions, LI-BFRT effectively alleviated pain, increased muscle cross-sectional area, and enhanced muscle strength. LI-BFRT showed pain relief comparable with that of LI-RT while surpassing LI-RT in muscle growth and strength improvement.

Contemporary spectrum, characteristics, and outcomes of adult patients with rheumatic valvular disease in China: Insights from the China-VHD study.

Background: Rheumatic valvular disease (RVD) represents a significant health concern in developing countries, yet a scarcity of detailed data exists. This study conducts a comprehensive examination of RVD patients in China, exploring aspects of the disease's spectrum, characteristics, investigation, management, and outcomes. Methods: The China Valvular Heart Disease (China-VHD) study, a nationwide, multicenter, prospective observational study, enrolled 13,917 adults with moderate-to-severe valvular heart disease from April to June 2018. Among these, 2402 patients with native RVD (19.7% of native VHD patients) were analyzed. Results: Among the RVD patients, the median age was 57 years (interquartile range 50-65), with 82.5% falling within the 40-70 age range; females were notably predominant (63.9%). Rheumatic etiology prevailed, particularly in southern regions (48.8%). Multivalvular involvement was observed in 47.4% of RVD cases, and atrial fibrillation emerged as the most common comorbidity (43.2%). Severe RVD affected 64.2% of patients. Valvular interventions were undertaken by 66.9% of RVD patients, predominantly involving surgical valve replacement (90.8%). Adverse events, encompassing all-cause mortality and heart failure hospitalization, occurred in 7.3% of patients during the 2-year follow-up. Multivariable analysis identified factors such as age, geographical region, low body mass index, renal insufficiency, left atrial diameter, and left ventricular ejection fraction <50% (all P < 0.05) associated with adverse events, with valvular intervention emerging as a protective factor (HR: 0.201; 95%CI: 0.139 to 0.291; p < 0.001). Conclusions: This study delivers a comprehensive evaluation of RVD patients in China, shedding light on the spectrum, characteristics, investigation, management, and outcomes of this prevalent condition.

Lysosome-Related Genes and RNF19B as Prognostic Markers for Survival and Immunotherapy Efficacy in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) poses a considerable worldwide health concern due to its associated high risk of death. The heterogeneity of HCC poses challenges in developing practical risk stratification tools and identifying prognostic markers for personalized targeted treatments. Recently, lysosomes were shown to be crucial contributors to numerous cellular activities, including tumor initiation and regulating immune responses. Here, we aimed to construct a reliable prognostic signature based on lysosome-related genes and determine its association with the immune microenvironment. METHODS: We comprehensively analyzed lysosome-related genes in HCC to investigate their influence on patient survival and the tumor immune microenvironment. A prognostic signature comprising 14 genes associated with lysosomes was created to estimate the survival outcomes of individuals with HCC. Additionally, we verified the prognostic importance of Ring Finger Protein 19B (RNF19B) in HCC patients through multiplex immunohistochemistry analysis. RESULTS: Our constructed lysosome-related prediction model could significantly discriminate between HCC patients with good and poor survival outcomes (P < 0.05). We also found that elevated RNF19B expression was linked to unfavorable prognostic outcomes and showed a connection with specific clinicopathological characteristics. Moreover, it was observed that RNF19B could facilitate the transformation of macrophages into M2-polarized macrophages and showed a significant positive correlation with PD-1 and CTLA-4. CONCLUSION: In summary, our study proposes that the expression of lysosome-related genes is associated with the immune microenvironment, serving as a predictor for HCC patients' survival. Meanwhile, RNF19B was identified as a novel prognostic marker for predicting OS and immunotherapy effects in HCC patients.

Identification and bioactivity evaluation of ring-opening and lactone forms of enterolactone from sheep fed flaxseed cake.

The previously undescribed lactone ring-opening enterolactone and its sulphate were purified along with the lactone counterparts from the urine of dairy sheep fed flaxseed cake. The structures were determined by NMR and MS analyses. The ring-opening and lactone forms underwent mutual transformation with changes in pH and milk could protect the lactone form. Enterolactone exhibited more effective anti-proliferation activity on MDA-MB-231 breast cancer cells than its ring-opening counterpart, while the ring-opening enterolactone demonstrated more effective anti-osteoporosis activity than the lactone form. The results indicated the potential for targeting biological functions through pH and medium manipulation.

Activation of the PI3K/AKT signaling pathway by ARNTL2 enhances cellular glycolysis and sensitizes pancreatic adenocarcinoma to erlotinib.

BACKGROUND: Pancreatic adenocarcinoma (PC) is an aggressive malignancy with limited treatment options. The poor prognosis primarily stems from late-stage diagnosis and when the disease has become therapeutically challenging. There is an urgent need to identify specific biomarkers for cancer subtyping and early detection to enhance both morbidity and mortality outcomes. The addition of the EGFR tyrosine kinase inhibitor (TKI), erlotinib, to gemcitabine chemotherapy for the first-line treatment of patients with advanced pancreatic cancer slightly improved outcomes. However, restricted clinical benefits may be linked to the absence of well-characterized criteria for stratification and dependable biomarkers for the prediction of treatment effectiveness. METHODS AND RESULTS: We examined the levels of various cancer hallmarks and identified glycolysis as the primary risk factor for overall survival in PC. Subsequently, we developed a glycolysis-related score (GRS) model to accurately distinguish PC patients with high GRS. Through in silico screening of 4398 compounds, we discovered that erlotinib had the strongest therapeutic benefits for high-GRS PC patients. Furthermore, we identified ARNTL2 as a novel prognostic biomarker and a predictive factor for erlotinib treatment responsiveness in patients with PC. Inhibition of ARNTL2 expression reduced the therapeutic efficacy, whereas increased expression of ARNTL2 improved PC cell sensitivity to erlotinib. Validation in vivo using patient-derived xenografts (PDX-PC) with varying ARNTL2 expression levels demonstrated that erlotinib monotherapy effectively halted tumor progression in PDX-PC models with high ARNTL2 expression. In contrast, PDX-PC models lacking ARNTL2 did not respond favorably to erlotinib treatment. Mechanistically, we demonstrated that the ARNTL2/E2F1 axis-mediated cellular glycolysis sensitizes PC cells to erlotinib treatment by activating the PI3K/AKT signaling pathway. CONCLUSIONS: Our investigations have identified ARNTL2 as a novel prognostic biomarker and predictive indicator of sensitivity. These results will help to identify erlotinib-responsive cases of PC and improve treatment outcomes. These findings contribute to the advancement of precision oncology, enabling more accurate and targeted therapeutic interventions.

Genome-wide identification and expression analysis of the Dof gene family reveals their involvement in hormone response and abiotic stresses in sunflower (Helianthus annuus L.).

DNA binding with one finger (Dof), plant-specific zinc finger transcription factors, can participate in various physiological and biochemical processes during the life of plants. As one of the most important oil crops in the world, sunflower (Helianthus annuus L.) has significant economic and ornamental value. However, a systematic analysis of H. annuus Dof (HaDof) members and their functions has not been extensively conducted. In this study, we identified 50 HaDof genes that are unevenly distributed on 17 chromosomes of sunflower. We present a comprehensive overview of the HaDof genes, including their chromosome locations, phylogenetic analysis, and expression profile characterization. Phylogenetic analysis classified the 366 Dof members identified from 11 species into four groups (further subdivided into nine subfamilies). Segmental duplications are predominantly contributed to the expansion of sunflower Dof genes, and all segmental duplicate gene pairs are under purifying selection due to strong evolutionary constraints. Furthermore, we observed differential expression patterns for HaDof genes in normal tissues as well as under hormone treatment or abiotic stress conditions by analyzing RNA-seq data from previous studies and RT-qPCR data in our current study. The expression of HaDof04 and HaDof43 were not detected in any samples, which implied that they may be gradually undergoing pseudogenization process. Some HaDof genes, such as HaDof25 and HaDof30, showed responsiveness to exogenous plant hormones, such as kinetin, brassinosteroid, auxin or strigolactone, while others like HaDof15 and HaDof35 may participate in abiotic stress resistance of sunflower seedling. Our study represents the initial step towards understanding the phylogeny and expression characterization of sunflower Dof family genes, which may provide valuable reference information for functional studies on hormone response, abiotic stress resistance, and molecular breeding in sunflower and other species.

Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1.

MCL-1 is essential for promoting the survival of many normal cell lineages and confers survival and chemoresistance in cancer. Beyond apoptosis regulation, MCL-1 has been linked to modulating mitochondrial metabolism, but the mechanism(s) by which it does so are unclear. Here, we show in tissues and cells that MCL-1 supports essential steps in long-chain (but not short-chain) fatty acid ß-oxidation (FAO) through its binding to specific long-chain acyl-coenzyme A (CoA) synthetases of the ACSL family. ACSL1 binds to the BH3-binding hydrophobic groove of MCL-1 through a non-conventional BH3-domain. Perturbation of this interaction, via genetic loss of Mcl1, mutagenesis, or use of selective BH3-mimetic MCL-1 inhibitors, represses long-chain FAO in cells and in mouse livers and hearts. Our findings reveal how anti-apoptotic MCL-1 facilitates mitochondrial metabolism and indicate that disruption of this function may be associated with unanticipated cardiac toxicities of MCL-1 inhibitors in clinical trials.

MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study.

Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.

The radiomics nomogram predicts the prognosis of pancreatic cancer patients with hepatic metastasis after chemoimmunotherapy.

OBJECTIVE: To construct a prognostic model based on MR features and clinical data to evaluate the progression free survival (PFS), overall survival (OS) and objective response rate (ORR) of pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy. METHODS: 105 pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy were assigned to the training set (n = 52), validation set (n = 22), and testing set (n = 31). Multi-lesion volume of interest were delineated, multi-sequence radiomics features were extracted, and the radiomics models for predicting PFS, OS and ORR were constructed, respectively. Clinical variables were extracted, and the clinical models for predicting PFS, OS and ORR were constructed, respectively. The nomogram was jointly constructed by radiomics model and clinical model. RESULT: The ORR exhibits no significant correlation with either PFS or OS. The area under the curve (AUC) of nomogram for predicting 6-month PFS reached 0.847 (0.737-0.957), 0.786 (0.566-1.000) and 0.864 (0.735-0.994) in the training set, validation set and testing set, respectively. The AUC of nomogram for predicting 1-year OS reached 0.770 (0.635-0.906), 0.743 (0.479-1.000) and 0.818 (0.630-1.000), respectively. The AUC of nomogram for predicting ORR reached 0.914 (0.828-1.00), 0.938 (0.840-1.00) and 0.846 (0.689-1.00), respectively. CONCLUSION: The prognostic models based on MR imaging features and clinical data are effective in predicting the PFS, OS and ORR of chemoimmunotherapy in pancreatic cancer patients with hepatic metastasis, and can be used to evaluate the prognosis of patients.

Outcomes for patients undergoing transcatheter aortic valve replacement with ascending aorta dilation.

BACKGROUND: We aim to compare the short and long-term outcomes for aortic stenosis (AS) patients undergone TAVR with and without ascending aorta dilation (AAD). METHODS: Consecutive patients diagnosed with native severe AS who underwent TAVR from September 2012 to September 2021 were enrolled. They were stratified into the moderate/severe dilation group (greatest ascending aorta width ≥ 45 mm) and the non/mild dilation group. Survival outcomes were illustrated using Kaplan-Meier curves and evaluated with the log-rank test. Data from patients with CT follow-up of >6 months was used to investigate the progression rate of AAD. RESULTS: The study cohort comprised 556 patients, with a mean age of 75.5 ± 7.3 years. Among them, 107 patients (19.2%) had a moderate/severe AAD (≥45 mm), with an average diameter of 48.6 mm (±2.8). During hospitalization, both groups witnessed two cases of ascending aortic dissection (1.9% vs 0.4%, P = 0.380). The median follow-up duration was 3.9 years (95% CI: 3.8-4.0 years). No deaths were caused by aortic events and no patients experienced a new aortic dissection. The AAD cohort's 4-year all-cause and cardiovascular mortality rates were not significantly different to the non/mild dilation group's (log-rank test, P = 0.109 and P = 0.698, respectively). Follow-up CT data revealed that the rate of aortic dilation progression in the moderate/severe dilation group was not significantly different from that in the non/mild group (0.0 mm/year, 25-75%th: -0.3-0.2 vs 0.1 mm/year, 25-75%th: -0.3-0.4, P = 0.122). CONCLUSION: This study found no significant difference regarding short-term and long-term outcomes in AS patients with/without moderate/severe AAD undergoing TAVR.

Prolonged Dual Antiplatelet Therapy in Acute Myocardial Infarction Patients Without Revascularization: China Acute Myocardial Infarction Registry Study.

At least 12 months of dual antiplatelet therapy (DAPT) is 1 of the standards of care following percutaneous coronary intervention in patients with acute coronary syndrome. However, study on prolonged DAPT for patients with acute myocardial infarction (AMI) without revascularization is limited. We studied 1,744 patients with AMI without revascularization from the China Acute Myocardial Infarction registry between January 2013 and September 2014. These patients were on DAPT and did not experience AMI, stroke, or bleeding events at the 12-month follow-up. We divided them into 2 groups: 12-month DAPT group (DAPT for at least 12 months but <18 months) and 18-month DAPT group (DAPT for at least 18 months). The primary outcome was 24-month all-cause death. Overall, 1,221 patients (70.0%) took DAPT for ≥12 months but <18 months, whereas 523 patients (30.0%) took DAPT for ≥18 months. The proportion of patients at high ischemic risk and the proportion of patients at high bleeding risk were similar in the 2 groups. At 24 months, the all-cause mortality rate of the 18-month DAPT group was significantly lower than that for the 12-month DAPT group (3.7% vs 5.9%, p = 0.0471). The adjusted hazard ratio for all-cause death also showed statistical significance (0.59, 95% confidence interval 0.35 to 0.99, p = 0.0444). In conclusion, DAPT for at least 18 months appears to be associated with lower 24-month mortality for non-revascularization AMI patients without events within 12 months after onset.

Effect of Unfermented Soy Product Consumption on Blood Lipids in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clinical studies have reported the beneficial effects of unfermented soy product consumption on blood lipids in various populations. However, contradictory results have been reported regarding the influence of unfermented soy product consumption on blood lipids in postmenopausal women. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the effects of diets with unfermented soy products compared with diets without unfermented soy products on blood lipids in postmenopausal women. METHODS: The Cochrane Library, PubMed, Scopus, Web of Science, and Embase electronic databases were searched for eligible randomized controlled trials (RCTs) published up to February 21, 2023. RCTs were included if they were published in English and investigated the effect of unfermented soy product consumption on blood lipids in postmenopausal women who had discontinued hormone replacement therapy at least 3 months before randomization. A random-effects model was used to calculate the overall effect size of the mean difference (MD) and 95% CI. Risk of bias was assessed using the Cochrane Risk-of-Bias Tool for Randomized Trials, version 2. RESULTS: Twenty-nine RCTs involving 2,457 participants were included. The results showed that, compared with the control group that did not consume unfermented soy products, consumption of unfermented soy products significantly reduced total cholesterol (TC) (MD, -9.46 mg/dL [to convert mg/dL cholesterol to mmol/L, multiply mg/dL by 0.0259; to convert mmol/L cholesterol to mg/dL, multiply by 38.7]; 95% CI -15.04 to -3.89 mg/dL; P = .001) and triglycerides (TGs) (MD, -10.86 mg/dL [to convert mg/dL TGs to mmol/L, multiply mg/dL by 0.0113; to convert mmol/L TGs to mg/dL, multiply mmol/L by 88.6]; 95% CI -19.70 to -2.02 mg/dL; P = .016), while significantly increasing high-density lipoprotein cholesterol (MD, 2.32 mg/dL; 95% CI 0.87 to 3.76 mg/dL; P = .002) in postmenopausal women, but had no significant effect on low-density lipoprotein cholesterol (MD, -4.55 mg/dL; 95% CI -10.90 to 1.80 mg/dL; P = .160). Results of soy preparation subgroup analysis showed that soy isolate protein significantly reduced TC and soy protein-containing isoflavones significantly reduced TC and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Furthermore, unfermented soy product consumption significantly reduced TC, low-density lipoprotein cholesterol, and TG levels in postmenopausal women with lipid disorders and TGs in healthy postmenopausal women. CONCLUSIONS: The results showed that unfermented soy product consumption reduced TC and TG levels significantly, and increased high-density lipoprotein cholesterol levels in postmenopausal women. The findings of this review contribute to the evidence-base for dietary management of blood lipids in postmenopausal women.