Obesity Paradox in Patients with Acute Coronary Syndrome: Is Malnutrition the Answer?

BACKGROUND: Obesity paradox has been reported in patients with cardiovascular disease, showing an inverse association between obesity as defined by BMI (in kg/m2) and prognosis. Nutritional status is associated with systemic inflammatory response and affects cardiovascular disease outcomes. OBJECTIVES: This study sought to examine the influence of obesity and malnutrition on the prognosis of patients with acute coronary syndrome (ACS). METHODS: This study included consecutive patients diagnosed with ACS and underwent coronary angiogram between January 2009 and February 2023. At baseline, patients were categorized according to their BMI as follows: underweight (<18), normal weight (18-24.9), overweight (25.0-29.9), and obese (>30.0). We assessed the nutritional status by Prognostic Nutritional Index (PNI). Malnutrition was defined as a PNI value of <38. RESULTS: Of the 21,651 patients with ACS, 582 (2.7%) deaths from any cause were observed over 28.7 months. Compared with the patient's state of normal weight, overweight, and obesity were associated with decreased risk of all-cause mortality. Malnutrition was independently associated with poor survival (hazards ratio: 2.64; 95% CI: 2.24, 3.12; P < 0.001). In malnourished patients, overweight and obesity showed a 39% and 72% reduction in the incidence of all-cause mortality, respectively. However, in nourished patients, no significant reduction in the incidence of all-cause mortality was observed (all P > 0.05). CONCLUSIONS: Obesity paradox appears to occur in patients with ACS. Malnutrition may be a significant independent risk factor for prognosis in patients with ACS. The obesity paradox is influenced by the status of malnutrition.

Clinical characteristics and prognosis of patients with hypertrophic cardiomyopathy and heart failure with preserved ejection fraction.

BACKGROUND: Whether heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of developing systolic dysfunction and a poor prognosis in hypertrophic cardiomyopathy (HCM) patients is unknown. OBJECTIVE: We aimed to assess risk factors for the development of end-stage (ES) heart failure (HF) (ejection fraction < 50%) and compare the prognosis of different HF phenotypes. METHODS: This retrospective study was conducted on patients with HCM in China between January 2009 and February 2023. Patients were stratified into three different groups: HCM-non-HF, HCM-HFpEF and HCM-heart failure with reduced ejection fraction (HCM-HFrEF). The primary outcome was a composite of major adverse cardiac events (MACEs), including all-cause deaths, HF hospitalization, sudden cardiac death and ventricular tachycardia. RESULTS: Of 3,620 HCM patients enrolled, 1,553 (42.9%) had non-HF, 1,666 (46.0%) had HFpEF, and 579 patients (11.1%) had HFrEF at baseline. During the median follow-up period of 4.0 years (IQR 1.4-9.4 years), patients with HCM-HFpEF exhibited a higher incidence of ES-HF than those with HCM-non-HF (12.4% vs. 2.7%, P < 0.001). HFpEF was an independent risk factor for ES-HF development (HR 3.84, 2.54-5.80, P < 0.001). MACEs occurred in 26.9% with a higher incidence in HCM-HFpEF than HCM-non-HF (36.6% vs 12.2%, P < 0.001). HFpEF was an independent predictor of MACEs (HR 2.13, 1.75-2.59, P < 0.001). CONCLUSIONS: HFpEF is common in HCM. Compared to non-HF, it increases the risk of LVEF decline and poor prognosis. It may aid in risk stratification and need close echocardiography follow-up.

Using Contactless Facial Image Recognition Technology to Detect Blood Oxygen Saturation.

Since the outbreak of COVID-19, as of January 2023, there have been over 670 million cases and more than 6.8 million deaths worldwide. Infections can cause inflammation in the lungs and decrease blood oxygen levels, which can lead to breathing difficulties and endanger life. As the situation continues to escalate, non-contact machines are used to assist patients at home to monitor their blood oxygen levels without encountering others. This paper uses a general network camera to capture the forehead area of a person's face, using the RPPG (remote photoplethysmography) principle. Then, image signal processing of red and blue light waves is carried out. By utilizing the principle of light reflection, the standard deviation and mean are calculated, and the blood oxygen saturation is computed. Finally, the effect of illuminance on the experimental values is discussed. The experimental results of this paper were compared with a blood oxygen meter certified by the Ministry of Health and Welfare in Taiwan, and the experimental results had only a maximum error of 2%, which is better than the 3% to 5% error rates in other studies The measurement time was only 30 s, which is better than the one minute reported using similar equipment in other studies. Therefore, this paper not only saves equipment expenses but also provides convenience and safety for those who need to monitor their blood oxygen levels at home. Future applications can combine the SpO2 detection software with camera-equipped devices such as smartphones and laptops. The public can detect SpO2 on their own mobile devices, providing a convenient and effective tool for personal health management.

Adsorption and desorption characteristics of heavy metals onto conventional and biodegradable plastics.

Biodegradable plastics have been widely used to replace conventional plastics to minimize environmental impacts of plastic packaging. However, before biodegradable plastics decompose in the environment, they could pose a threat to terrestrial and aquatic creatures by acting as vectors of contaminants in the food chain. In this study, conventional plastic bags (CPBs) made of polyethylene and biodegradable plastic bags (BPBs) made of polylactic acid were examined for their heavy metal adsorption. Effects of solution pHs and temperatures on adsorption reactions were investigated. Because of a larger BET surface area, presence of oxygen-containing function groups, and smaller crystallinity, the heavy metal adsorption capacities of BPBs are significantly larger than those of CPBs. Among Cu (up to 791.48 mg⋅kg-1), Ni (up to 60.88 mg⋅kg-1), Pb (up to 1414.58 mg⋅kg-1), and Zn (up to 295.17 mg⋅kg-1), Pb and Ni show the largest and the lowest extents of adsorption onto the plastic bags, respectively. In the different waterbodies in nature, Pb adsorption on the CPBs and the BPBs were 318.09-379.91 and 528.41-764.22 mg⋅kg-1, respectively. Consequently, Pb was selected as the target contaminant in the desorption experiments. After Pb was adsorbed onto the CPBs and the BPBs, Pb could be completely desorbed and released into simulated digestive systems in 10 h. In conclusion, BPBs could be potential vectors of heavy metals, and their suitability as a substitute for CPBs must be thoroughly investigated and confirmed.

Discovery, evaluation and mechanism study of WDR5-targeted small molecular inhibitors for neuroblastoma.

Neuroblastoma is the most common and deadliest tumor in infancy. WDR5 (WD Repeat Domain 5), a critical factor supporting an N-myc transcriptional complex via its WBM site and interacting with chromosome via its WIN site, promotes the progression of neuroblastoma, thus making it a potential anti-neuroblastoma drug target. So far, a few WIN site inhibitors have been reported, and the WBM site disruptors are rare to see. In this study we conducted virtual screening to identify candidate hit compounds targeting the WBM site of WDR5. As a result, 60 compounds were selected as candidate WBM site inhibitors. Cell proliferation assay demonstrated 6 structurally distinct WBM site inhibitors, numbering as compounds 4, 7, 11, 13, 19 and 22, which potently suppressed 3 neuroblastoma cell lines (MYCN-amplified IMR32 and LAN5 cell lines, and MYCN-unamplified SK-N-AS cell line). Among them, compound 19 suppressed the proliferation of IMR32 and LAN5 cells with EC50 values of 12.34 and 14.89 µM, respectively, and exerted a moderate inhibition on SK-N-AS cells, without affecting HEK293T cells at 20 µM. Analysis of high-resolution crystal complex structure of compound 19 against WDR5 revealed that it competitively occupied the hydrophobic pocket where V264 was located, which might disrupt the interaction of MYC with WDR5 and further MYC-medicated gene transcription. By performing RNA-seq analysis we demonstrated the differences in molecular action mechanisms of the compound 19 and a WIN site inhibitor OICR-9429. Most interestingly, we established the particularly high synergy rate by combining WBM site inhibitor 19 and the WIN site inhibitor OICR-9429, providing a novel therapeutic avenue for neuroblastoma.

Effect of light irradiation on heavy metal adsorption onto microplastics.

Microplastics are frequently found in many environmental media. Polypropylene (PP) is one of the plastics commonly used, resulting in more and more PP fragments in natural waters. Contaminants, such as lead (Pb), could get adsorbed onto microplastics after the exposure to sunlight, and pose a larger threat to aquatic species. In this study, the oxidative indices of PP pellets after different exposure times to a Xenon lamp were evaluated by Fourier transform infrared (FTIR) and energy-dispersive X-ray spectrometry. The results show that the percentage of oxygen content increased from 2.80 to 20.95 wt% and changes of characteristic peaks of the FTIR pattern, implying that the exposure to the Xenon lamp could initiate oxidation. Due to the changes of functional groups after the exposure to the Xenon lamp for 28 days, the adsorption capacities of the PP pellets were up to 274.4 mg⋅kg-1, 1.7 to 2.5 times higher than that of the raw PP pellets depending on the solution pHs. The adsorption behavior can be described by a pseudo-second-order model with rate constants of adsorption of 0.00212-0.01404 kg⋅mg-1⋅h-1. The increase of adsorption capacity due to changes of the PP pellets after the Xenon lamp exposure increased the potential risk to the aquatic species.

Design, synthesis and antitumour evaluation of novel anthraquinone derivatives.

We report the design, synthesis, and biological evaluation of 13 new and 1 known anthraquinone derivatives which exerted cytotoxicity against PC3, A549 and NTUB1 cell lines. The results indicate that, among these 14, compounds-1 and 14 showed the highest growth inhibitory effect on NTUB1 and PC3 cells, respectively. Compound-1 at lower doses targets DNA, induces DNA damage and subsequently triggers G2/M arrest and apoptotic cell death at 24 h. Previously we reported that 14 induced PC3 cell autophagy and in treated PC3 cells, cleaved caspase-3 and cleaved PARP, and survivin did not increase and increase, respectively. The autophagic and necrotic cell deaths mediated by 14-triggered ROS generation. Our study is the first to investigate the biological mechanism of 14 action in detail. We find that when 14 was co-administrated with Bafilomycin A1 (BAF) in PC3 cells, rapid necrotic cell death occurred with no cleaved caspase-3 and cleaved PARP activation and increasing the expression of survivin. We further show that necrotic signaling in these cells coincided with production of reactive oxygen species. In the present study, we developed methods to synthesize five new 14 analogues for studing the structure-activity relationships. This study could provide valuable sight to find new antitumor agents for cancer therapy.

Higher Concentration of Plasma Glial Fibrillary Acidic Protein in Wilson Disease Patients with Neurological Manifestations.

BACKGROUND: Wilson disease is a rare, disabling, neurological genetic disease. Biomarkers of brain damage are less well developed. OBJECTIVE: The aim of this study was to evaluate the utility of plasma glial fibrillary acidic protein as a biomarker for neurological involvement in patients with Wilson disease. METHODS: This prospective cross-observational study compared plasma glial fibrillary acidic protein concentration among different subtypes of patients with Wilson disease and healthy control subjects. Plasma glial fibrillary acidic protein levels were measured in 94 patients and 25 healthy control subjects. Patients were divided into two subtypes: patients with neurological manifestations (n = 74) or hepatic manifestations (n = 20). RESULTS: Median levels of plasma glial fibrillary acidic protein were significantly elevated in patients with neurological manifestations (143.87 pg/mL) compared with those with hepatic manifestations (107.50 pg/mL) and healthy control subjects (86.85 pg/mL). Receiver operating characteristic curve revealed that a plasma glial fibrillary acidic protein cutoff value of 128.8 pg/mL provides sufficient sensitivity (80.0%) and specificity (63.5%) to differentiate patients with neurological manifestations from those with hepatic manifestations. CONCLUSIONS: Plasma glial fibrillary acidic protein may serve as a biomarker for distinguishing different subtypes of Wilson disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Difference of musculoskeletal ultrasound imaging of focus of knee joint tendon between patients with knee osteoarthritis and healthy subjects / 中国针灸

OBJECTIVE@#To observe the imaging features of focus of knee joint tendon in patients with knee osteoarthritis (KOA) by musculoskeletal ultrasound (MSUS) technique.@*METHODS@#One hundred KOA patients and 100 healthy subjects were included. All the KOA patients were palpated by the sequence of foot @*RESULTS@#The top-5 focus of knee tendon of KOA patients were located in medial inferior patella, medial tibial condyle, inferior patella, Zusanlici and Hedingci. The thickness of ligaments and tendons in extension and flexion positions in KOA patients were thicker than that in healthy subjects (@*CONCLUSION@#The focus of knee joint tendon in KOA patients shows significantly thickened musculoskeletal imaging features.

Helicobacter pylori infection with atrophic gastritis: An independent risk factor for colorectal adenomas.

BACKGROUND: The significance of Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) in the prevalence of colorectal adenomas has been examined in a limited number of studies. However, these studies reported disputed conclusions. AIM: To investigate whether H. pylori infection, AG, and H. pylori-related AG increase the risk of colorectal adenomas. METHODS: This retrospective cross-sectional study included 6018 health-check individuals. The relevant data for physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy and histopathological examination of gastric and colorectal biopsies were recorded. Univariate and multivariate logistic regression analyses were performed to determine the association between H. pylori-related AG and colorectal adenomas. RESULTS: Overall, 1012 subjects (16.8%) were diagnosed with colorectal adenomas, of whom 143 (2.4%) had advanced adenomas. Among the enrolled patients, the prevalence of H. pylori infection and AG was observed as 49.5% (2981/6018) and 10.0% (602/6018), respectively. Subjects with H. pylori infection had an elevated risk of colorectal adenomas (adjusted odds ratio [OR] of 1.220, 95% confidence interval (CI): 1.053-1.413, P = 0.008) but no increased risk of advance adenomas (adjusted OR = 1.303, 95%CI: 0.922-1.842, P = 0.134). AG was significantly correlated to an increased risk of colorectal adenomas (unadjusted OR = 1.668, 95%CI: 1.352-2.059, P < 0.001; adjusted OR = 1.237, 95%CI: 0.988-1.549, P = 0.064). H. pylori infection accompanied by AG was significantly associated with an increased risk of adenomas (adjusted OR = 1.491, 95%CI: 1.103-2.015, P = 0.009) and advanced adenomas (adjusted OR = 1.910, 95%CI: 1.022-3.572, P = 0.043). CONCLUSION: H. pylori-related AG was associated with a high risk of colorectal adenomas and advanced adenomas in Chinese individuals.

Quantitative assessment of postural instability in spinocerebellar ataxia type 3 patients.

OBJECTIVE: Spinocerebellar ataxia type 3 (SCA3) is one of the most common hereditary neurodegenerative diseases, with balance instability as main symptom. Balance quantification is crucial for evaluating the efficacy of therapeutic interventions. However, balance evaluation in SCA3 is often subject to bias. Here, we aimed to quantitatively evaluate postural instability and investigate the relationship between postural instability and clinical characteristics in SCA3 patients. METHODS: Sixty-two SCA3 patients and 62 normal controls were recruited, and their postural balance was measured using a posturographic platform. Principal component analysis was performed as data reduction to identify postural instability factors. Multivariable linear regression was used to investigate potential risk factors for postural instability and to explore whether postural instability predicts the severity and progression of ataxia in SCA3 patients. RESULTS: We found SCA3 patients experience postural instability characterized by significant impairment in static and dynamic stability. The condition without visual feedback was the most sensitive measure in differentiating SCA3 from controls. Regression analyses revealed that ataxia severity predicted both static (P = 0.014) and dynamic stability (P = 0.001). Likewise, along with expanded CAG repeats (P < 0.001), both static (P < 0.001) and dynamic stability (P < 0.001) predicted ataxia severity, but not ataxia progression. INTERPRETATION: Our findings demonstrate the validity of using the Pro-kin system for assessing postural instability in SCA3 patients. This type of quantitative assessment of balance dysfunction can contribute to clinical trials and balance rehabilitation in SCA3 patients.

Temperature and isotope effects in the reaction of CH3CHOO with methanol.

Carbonyl oxides, also known as Criegee intermediates, are generated from ozonolysis of unsaturated hydrocarbons in the atmosphere. Alcohols are often used as a scavenger of the Criegee intermediates in laboratory studies. In this work, the reaction kinetics of CH3CHOO with methanol vapor was investigated at various temperatures, pressures, and isotopic substitutions using time-resolved UV absorption spectroscopy. The observed rate coefficients of the reaction of anti-CH3CHOO with methanol show a linear dependence on [CH3OH]. The bimolecular rate coefficient was determined to be k1Ha = (4.8 ± 0.5) × 10-12 cm3 s-1 at 298 K and 250 Torr with a negative activation energy Ea = -2.8 ± 0.3 kcal mol-1 for T = 288-315 K [k(T) = A exp(-Ea/RT)]. For the reaction of syn-CH3CHOO with methanol vapor, the observed rate coefficients show a quadratic dependence on [CH3OH], indicating that two methanol molecules participate in the reaction. The termolecular rate coefficient was determined to be k2Hs = (8.0 ± 1.0) × 10-32 cm6 s-1 at 298 K and 250 Torr with a strong negative temperature dependence (Ea = -13.2 ± 0.3 kcal mol-1) at 273-323 K. No significant pressure effect was observed at 250-760 Torr. A kinetic isotope effect, k2Hs/k2Ds = 2.5, was observed by changing CH3OH to CH3OD. Quantum chemistry and transition state theory calculations suggest that the observed isotope effect is mainly attributed to the changes of the vibrational zero-point energies and partition functions while tunneling plays a very minor role. The reaction of syn-CH3CHOO with one CH3OH molecule was not observed in the studied concentration range.

Criegee Intermediate Reaction with Alcohol Is Enhanced by a Single Water Molecule.

The role of water in gas-phase reactions has gained considerable interest. Here we report a direct kinetic measurement of the reaction of syn-CH3CHOO (a Criegee intermediate or carbonyl oxide) with methanol at various relative humidity (RH = 0-80%) under near-ambient conditions (298 K, 250-755 Torr). The data indicate that a single water molecule expedites the reaction by up to a factor of three. The rate coefficient of the corresponding reaction, syn-CH3CHOO + CH3OH + H2O → products, has been determined to be (1.95 ± 0.11) × 10-32 cm6 s-1 at 298 K, with no observable pressure dependence for 250-755 Torr. Quantum chemistry calculation shows that the dominating pathway involves a hydrogen-bonded ring structure, in which methanol is donating a hydrogen atom to water, water is donating a hydrogen atom to the terminal oxygen atom of the Criegee intermediate, and, on the product side, H2O is reformed and acts as a catalyst.

Overexpression of OqxAB and MacAB efflux pumps contributes to eravacycline resistance and heteroresistance in clinical isolates of Klebsiella pneumoniae.

This study investigated the characteristics and mechanisms of eravacycline resistance and heteroresistance in clinical Klebsiella pneumoniae isolates. A total of 393 clinical K. pneumoniae isolates were collected and subjected to eravacycline and tigecycline MIC determinations using the agar dilution method. Eravacycline heteroresistance was assessed by a population analysis profile (PAP). The expression levels of efflux pumps and their regulators were determined by quantitative reverse-transcription PCR (qRT-PCR). This study identified 67 eravacycline-nonsusceptible isolates; among the extended-spectrum ß-lactamase (ESBL)-positive isolates, eravacycline-nonsusceptible isolates were detected more frequently than tigecycline-nonsusceptible isolates (21.7% vs. 9.4%, p = 0.001). The study sample was observed to include 20 K. pneumoniae isolates with eravacycline heteroresistance. Compared to the reference strain, oqxA or oqxB overexpression was observed in nine eravacycline-nonsusceptible isolates (range, 35.64-309.02-fold) and 13 eravacycline-heteroresistant isolates (8.42-296.34-fold). The overexpression of macA or macB was detected in 12 eravacycline-heteroresistant isolates (3.23-28.35-fold). Overexpression of the efflux pump regulator gene ramA was observed in 11 eravacycline-nonsusceptible isolates (3.33-94.05-fold) and 18 eravacycline-heteroresistant isolates (3.89-571.70-fold). The eravacycline MICs were increased by one-fourfold by overexpression of oqxAB or macAB in three eravacycline-sensitive isolates. In conclusion, the overexpression of OqxAB and MacAB efflux pumps and the transcriptional regulator RamA were suggested to be involved in K. pneumoniae eravacycline resistance and heteroresistance.

1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate induced autophagic cell death in human PC3 cells.

The autophagy of human prostate cancer cells (PC3 cells) induced by a new anthraquinone derivative, 1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate (PA) was investigated, and the relationship between autophagy and reactive oxygen species (ROS) generation was studied. The results indicated that PA induced PC3 cell death in a time- and dose-dependent manner, could inhibit PC3 cell growth by G1 phase cell cycle arrest and corresponding decrease in the G2/M cell population and induced S-phase arrest accompanied by a significant decrease G2/M and G1 phase numbers after PC3 cells treated with PA for 48 h, and increased the accumulation of autophagolysosomes and microtubule-associated protein LC3-ll, a marker of autophagy. However, these phenomenon were not observed in the group pretreated with the autophagy inhibitor 3-MA or Bafilomycin A1 (BAF), suggesting that PA induced PC3 cell autophagy. In addition, we found that PA triggered ROS generation in cells, while the levels of ROS decreased in the N-acetylcysteine (NAC) co-treatment, indicating that PA-mediated autophagy was partly blocked by NAC. In summary, the autophagic cell death of human PC3 cells mediated by PA-triggered ROS generation.

Fibroblast growth factors stimulate hair growth through ß-catenin and Shh expression in C57BL/6 mice.

Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of ß-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent.