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Summary: Heart failure (HF) is a global concern, particularly HF with preserved ejection fraction (HFpEF), lacking effective treatments. Understanding the differences of metabolic profiles between HFpEF and HFrEF (heart failure with reduced ejection fraction) patients is crucial for therapeutic advancements. In this study, pseudotargeted metabolomics was employed to analyze for disparities of plasma metabolic profiles between HFpEF and HFrEF in two cohorts: discovery (n = 514) and validation (n = 3368). Plasma-free carnitine levels were significant changed in HF patients. A non-linear and U-shaped (for HFpEF) or J-shaped (for HFrEF) association between circulating free carnitine levels and the composite risk of cardiac events were observed. Interestingly, HFpEF patients with low free carnitine (≤40.18 μmol/L) displayed a poorer survival, contrasting with HFrEF where higher levels (≥35.67 μmol/L) were linked to poorer outcomes, indicating distinct metabolism pathways. In conclusion, these findings offer insights into HFpEF metabolic profiles, suggesting potential therapeutic targets.

BackgroundDementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. Although DLB is characterized by fluctuating cognitive impairment, some symptoms may appear before cognitive impairment, including rapid eye movement, sleep behavior disorder (RBD), psychiatric symptoms, autonomic symptoms, Parkinson's symptoms, etc. Therefore, DLB may be misdiagnosed as other diseases in its early stage.ObjectiveThis study aimed to investigate the characteristics of initial symptoms of DLB, which could potentially offer essential clues for the earliest diagnosis of this disorder.MethodsA total of 239 patients with probable DLB who visited the cognitive impairment outpatient department of Tianjin Huanhu Hospital from September 2015 to March 2021 were consecutively enrolled. We retrospectively evaluated the initial symptoms of all included participants. The time of onset of initial symptoms was also assessed.ResultsThe most frequent initial symptom was memory loss (53.9%), followed by psychiatric symptoms (34.7%), RBD (20.9%), parkinsonism (15.1%), and autonomic symptoms (10.1%). Significant gender and age differences existed in the initial symptoms of patients with DLB.ConclusionsOur study elucidated the initial symptoms in patients with probable DLB. RBD was significantly more reported by men than by women, whereas women showed a higher incidence of visual and auditory hallucinations. A better understanding of the initial symptoms of DLB could lead to a more accurate diagnosis.

Abstract Background Myocardial ischemia–reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. Methods We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. Results CD25+Foxp3+ regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p

Abstract Background Metabolic syndrome (MetS) has been related to the pathogenesis of variety categories of cancers. This meta-analysis aimed to determine the association between MetS and the incidence of lung cancer. Methods Relevant cohort studies were identified by search of PubMed, Embase, and Cochrane’s Library databases. Cochrane’s Q test and I2 statistic were used to analyze the heterogeneity. Random-effect model which incorporates the potential heterogeneity was used for the meta-analysis. Results Five cohort studies with 188,970 participants were included. A total of 1,295 lung cancer cases occurred during follow-up. Meta-analyses showed that neither MetS defined by the revised NCEP-ATP III criteria (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.84 to 1.05, p = 0.25; I2 = 0) nor the IDF criteria (HR: 0.82, 95% CI: 0.61 to 1.11, p = 0.20; I2 = 0) was associated with an affected risk of lung cancer. Subgroup analyses showed consistent results in women and in men, in studies performed in Asian and non-Asian countries, and in prospective and retrospective cohorts (p all > 0.05). Meta-analysis limited to studies with the adjustment of smoking status also showed similar results (HR: 0.91, 95% CI: 0.80 to 1.05, p = 0.21; I2 = 0). No publication bias was detected based on the Egger regression test (p = 0.32). Conclusions Current evidence from cohort studies does not support that MetS is an independent risk factor for the incidence of lung cancer.

BackgroundConstipation and dementia have similar epidemiological characteristics. Changes in intestinal flora and characteristics of the brain-gut axis play roles in the pathogeneses of the two diseases, suggesting that there may be a close connection between the two. Most of the studies on constipation in dementia patients have focused on the population with α-synucleinopathies [Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB)]. Few studies have reported the prevalence of constipation in all-cause dementia and mild cognitive impairment (MCI) populations.ObjectiveTo assess the prevalence of constipation in patients with all-cause dementia and MCI subtypes and to explore the association between constipation with dementia and MCI subtypes.MethodsFrom May 2019 to December 2019, we conducted a population-based cross-sectional survey. A total of 11,743 participants aged 65 or older from nine cities in China were surveyed. Participants underwent a series of clinical examinations and neuropsychological measurements. Constipation, dementia, MCI and MCI subtype were diagnosed according to established criteria through standard diagnostic procedures.ResultsThe overall age- and sex-adjusted prevalence of constipation in individuals aged 65 years and older was 14.8% (95% CI, 14.6–15.0). The prevalence rates of constipation were19.2% (95% CI, 17.3–21.0), 19.1% (95% CI, 16.8–21.5), 14.4% (95% CI, 12.8–15.9), and 13.8% (95% CI, 13.0–14.6) in the dementia, non-amnestic (na)-MCI, amnestic (a)-MCI and normal cognition populations, respectively. Multivariate logistic regression analysis showed that higher prevalence of constipation was associated with dementia (p = 0.0.032, OR = 1.18, 95% CI: 1.02–1.38) and na-MCI (p = 0.003, OR = 1.30, 95% CI: 1.09–1.54).ConclusionThe present study found a high prevalence of constipation in elderly individuals in China, and higher in patients with dementia and na-MCI.

Introduction: Numerous countries went into lockdown to contain the COVID-19 outbreak, which has impeded follow-up of chronic diseases, such as cognitive impairment (CI). Cognitive and neuropsychiatric changes during the COVID-19 pandemic are neglected in China, which is the world's whistleblower. To investigate the cognitive and neuropsychologic changes in CI, as well as the proportions of rapid cognitive decline (RCD) before and during the COVID-19 pandemic to provide clinical evidence for CI intervention during a public health emergency.Methods: We performed a descriptive and retrospective study based on medical records from the memory clinic of Tianjin Dementia Institute collected through face-to-face evaluations. Information of 205 patients with CI, including patients with mild cognitive impairment and dementia, of whom 131 with Alzheimer's disease (AD) were analyzed and compared to a control group before the COVID-19 pandemic.Results: Among the 205 CI patients, the scores on the Chinese Mini Mental State Examination (C-MMSE), the Montreal Cognitive Assessment (MoCA), activities of daily living (ADLs), and the global Neuropsychiatric Inventory (NPI) were significantly different at the baseline and follow-up evaluations (p < 0.05) after 14.07 (±2.87) months. The same findings were recorded among AD patients, and they exhibited more sleep disturbances at the follow-up than at baseline (32.8 vs. 20.6%, p = 0.035). When compared to the control group, slightly worse performance of cognitive, −1.00 (−4.00, 1.00) from the C-MMSE, −1.00 (−2.00, 0.00) on the MoCA, 1.00 (0.00, 9.00) on ADLs and neuropsychological 0.00 (−1.00, 3.50) on the global NPI profile, at the follow-up were presented, particularly for delusion, agitation, irritability, and appetite disturbances (p < 0.05). Twenty-five (19.1%) AD patients and 48 (36.6%) controls suffered RCD during the COVID-19 pandemic. Moreover, AD patients during the COVID-19 pandemic were 0.408 times (95% confidence interval: 0.232–0.716) less likely to suffer RCD than the control.Conclusion: Confinement might ease the cognitive and neuropsychiatric deterioration of AD patients compared to those not in crisis and help prevent RCD in AD patients.

Background: While the lockdown strategies taken by many countries effectively limited the spread of COVID-19, those were thought to have a negative impact on older people. This study aimed to investigate the impact of lockdown on cognitive function and neuropsychiatric symptoms over a 1-year follow-up period in patients with mild cognitive impairment (MCI), Alzheimer's disease (AD) and dementia with Lewy bodies (DLB).Methods: We enrolled consecutive patients with MCI, probable AD or DLB who were receiving outpatient memory care before the COVID-19 pandemic and followed-up with them after 1 year by face-to-face during the COVID-19 pandemic to assess changes in physical activity, social contact, cognitive function and neuropsychiatric symptoms (NPS).Results: Total 105 probable AD, 50 MCI and 22 probable DLB patients were included and completed the 1-year follow-up between October 31 and November 30, 2020. Among the respondents, 42% of MCI, 54.3% of AD and 72.7% of DLB patients had a decline in MMSE scores and 54.4% of DLB patients had worsening Neuropsychiatric inventory (NPI) scores. Patients with DLB showed a more rapid decline of MMSE than those with AD. Diminished physical activity and social contact might have hastened the deterioration of cognition and the worsening of NPS.Conclusion: Social isolation and physical inactivity even after strict lockdown for at least 6 months were correlated with accelerated decline of cognitive function and NPS in patients with AD and DLB.

Abstract Sepsis is a serious clinical condition resulting from severe infection. High rates of mortality and tissue damage have been reported in intensive care unit (ICU) patients with sepsis. Bovine lactoferrin (BLF) is a well-known 80-kDa glycoprotein in the transferrin family that inhibits sepsis in low-birth-weight neonates. The present study investigated the protective effects of BLF in a rat model of sepsis-induced acute lung injury (ALI). The wet/dry ratio, lipid peroxidation, antioxidant markers, total protein, total cell count, inflammatory markers and myeloperoxidase (MPO) levels were assessed. Histopathological analysis was also carried out. BLF treatment reduced the wet/dry ratio of lung tissue by 30.7% and 61.3%, and lipid peroxidation by 22.3% and 67%, at concentrations of 100 and 200 mg/kg, respectively. Superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (Gpx) and catalase were increased by more than 50% under treatment with 200 mg/kg BLF. Inflammatory markers, neutrophils, lymphocytes and total cell count were reduced by more than 50% under treatment with 200 mg/kg BLF. BLF treatment significantly reduced MPO activity, by 28.2% and 74.3%, at concentrations of 100 and 200 mg/kg, respectively. Neutrophilic infiltration and edema were observed in control rats. However, BLF treatment restored intestinal microvilli to the normal range and reduced inflammatory cell invasion. Collectively, these results suggest that BLF is an effective therapeutic agent against sepsis-induced ALI.

Background: Statin, a lipid-lowering drug, has been suggested to confer anticancer efficacy. However, previous studies evaluating the association between statin use and prognosis in breast cancer showed inconsistent results. A meta-analysis was performed to evaluate the association between statin use and clinical outcome in women with breast cancer.Methods: Cohort studies comparing recurrence or disease-specific mortality in women with breast cancer with and without using of statins were identified by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model, incorporating the inter-study heterogeneity, was used to combine the results. Subgroup analyses were performed to evaluate the influences of study characteristics on the outcomesResults: Seventeen cohort studies with 168,700 women with breast cancer were included. Pooled results showed that statin use was significantly associated with a lower risk of breast cancer recurrence (adjusted hazard ratio [HR] = 0.72, p < 0.001) and breast cancer mortality (HR = 0.80, p < 0.001). Subgroup analysis showed that timing of statin use, statin type, study design, sample size, or quality score did not significantly affect the outcomes. However, statin use was associated with more remarkably reduced breast cancer recurrence in studies with mean follow-up duration ≤ 5 years (HR = 0.55, p < 0.001) than that in studies of >5 years (HR = 0.83, p = 0.01).Conclusions: Statin use is associated with reduced recurrence and disease-specific mortality in women with breast cancer. These results should be validated in randomized controlled trials.

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability. However, some excipients are prone to degradation during repeated use and/or improper storage, and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored, affecting the stability of biopharmaceuticals. In this study, we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry (GC-MS). The other polyol excipient, mannitol, was much more stable than glycerol. The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide, thymopentin, were also evaluated. The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol, compared to 95.8% in other formulations after the stress test. Most glycerol impurities (i.e., aldehydes and ketones) reacted with thymopentin, affecting the stability of thymopentin formulations. In conclusion, this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage. Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

In the realm of financial transactions, the allocation of household assets often lacks proper guidance, resulting in suboptimal utilization and limited income for residents. This study aims to address this issue by introducing rational asset allocation strategies, improving efficiency, and increasing household income. Specifically, the study focuses on enhancing Deep Reinforcement Learning (DRIO algorithms, particularly the Deep Q-Network algorithm. The current network is optimized by employing a dual network structure, leading to improved performance. Moreover, the proposed model incorporates Grubbs' improved algorithm to effectively denoise stock data samples, enabling iterative training of diverse stock agents. the results demonstrate the following findings: (1) The application of the Grubbs' improved algorithm to the cumulative returns of different stocks significantly surpasses the results without noise reduction, (2) The Sharpe ratio of the stock agents using the Grubbs improvement algorithm is noticeably higher than that of the unimproved DRL algorithm. The Sharpe ratio of stock agents under the unimproved algorithm consistently remains below 1.0; (3) The maximum drawdown of the stock agents using the Grubbs' improved algorithm is significantly lower than that of the unimproved DRL algorithm. The unimproved algorithm exhibits relatively higher maximum drawdown rates. These findings indicate that Grubbs' improved algorithm possesses notable advantages in noise reduction and enhancing the cumulative returns of assets. [ABSTRACT FROM AUTHOR]

Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantation via the tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These findings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury.