Role of the V2R-ßarrestin-Gßγ complex in promoting G protein translocation to endosomes.

Classically, G protein-coupled receptors (GPCRs) promote signaling at the plasma membrane through activation of heterotrimeric Gαßγ proteins, followed by the recruitment of GPCR kinases and ßarrestin (ßarr) to initiate receptor desensitization and internalization. However, studies demonstrated that some GPCRs continue to signal from internalized compartments, with distinct cellular responses. Both ßarr and Gßγ contribute to such non-canonical endosomal G protein signaling, but their specific roles and contributions remain poorly understood. Here, we demonstrate that the vasopressin V2 receptor (V2R)-ßarr complex scaffolds Gßγ at the plasma membrane through a direct interaction with ßarr, enabling its transport to endosomes. Gßγ subsequently potentiates Gαs endosomal translocation, presumably to regenerate an endosomal pool of heterotrimeric Gs. This work shines light on the mechanism underlying G protein subunits translocation from the plasma membrane to the endosomes and provides a basis for understanding the role of ßarr in mediating sustained G protein signaling.

Establishment of diagnostic model and identification of diagnostic markers between liver cancer and cirrhosis based on multi-chip and machine learning.

OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.

Leisure-time physical activity and the incidence of atrial fibrillation in senior adults: a prospective cohort study.

OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.

Development of a diagnostic nomogram for alpha-fetoprotein-negative hepatocellular carcinoma based on serological biomarkers.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Serum biomarkers play an important role in the early diagnosis and prognosis of HCC. Because a certain percentage of HCC patients are negative for alpha-fetoprotein (AFP), the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC. AIM: To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers. METHODS: A total of 180 HCC patients were enrolled in this study. The expression levels of GP73, des-γ-carboxyprothrombin (DCP), CK18-M65, and CK18-M30 were detected by a fully automated chemiluminescence analyser. The variables were selected by logistic regression analysis. Several models were constructed using stepwise backward logistic regression. The performance of the models was compared using the C statistic, integrated discrimination improvement, net reclassification improvement, and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: The results showed that the expression levels of GP73, DCP, CK18-M65, and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls (P < 0.001). Multivariate logistic regression analysis revealed that GP73, DCP, and CK18-M65 were independent factors for diagnosing AFP-negative HCC. By comparing the diagnostic performance of multiple models, we included GP73 and CK18-M65 as the model variables, and the model had good discrimination ability (area under the curve = 0.946) and good goodness of fit. The DCA curves indicated the good clinical utility of the nomogram. CONCLUSION: Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC. The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.

Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute bipyridine herbicide poisoning.

OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning. METHODS: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed. RESULTS: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1ß were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal. CONCLUSION: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.

COVID-19 is associated with changes in brain function and structure: A multimodal meta-analysis of neuroimaging studies.

The actual role of coronavirus disease 2019 (COVID-19) in brain damage has been increasingly reported, necessitating a meta-analysis to collate and summarize the inconsistent findings from functional imaging and voxel-based morphometry (VBM) studies. A comprehensive voxel-wise meta-analysis of the whole brain was conducted to identify alterations in functional activity and gray matter volume (GMV) between COVID-19 patients and healthy controls (HCs) by using Seed-based d Mapping software. We included 15 functional imaging studies (484 patients with COVID-19, 534 HCs) and 9 VBM studies (449 patients with COVID-19, 388 HCs) in the analysis. Overall, patients with COVID-19 exhibited decreased functional activity in the right superior temporal gyrus (STG) (extending to the right middle and inferior temporal gyrus, insula, and temporal pole [TP]), left insula, right orbitofrontal cortex (OFC) (extending to the right olfactory cortex), and left cerebellum compared to HCs. For VBM, patients with COVID-19, relative to HCs, showed decreased GMV in the bilateral anterior cingulate cortex/medial prefrontal cortex (extending to the bilateral OFC), and left cerebellum, and increased GMV in the bilateral amygdala (extending to the bilateral hippocampus, STG, TP, MTG, and right striatum). Moreover, overlapping analysis revealed that patients with COVID-19 exhibited both decreased functional activity and increased GMV in the right TP (extending to the right STG). The multimodal meta-analysis suggests that brain changes of function and structure in the temporal lobe, OFC and cerebellum, and functional or structural alterations in the insula and the limbic system in COVID-19. These findings contribute to a better understanding of the pathophysiology of brain alterations in COVID-19. SIGNIFICANCE STATEMENT: This first large-scale multimodal meta-analysis collates existing neuroimaging studies and provides voxel-wise functional and structural whole-brain abnormalities in COVID-19. Findings of this meta-analysis provide valuable insights into the dynamic brain changes (from infection to recovery) and offer further explanations for the pathophysiological basis of brain alterations in COVID-19.

Humid heat environment causes anxiety-like disorder via impairing gut microbiota and bile acid metabolism in mice.

Climate and environmental changes threaten human mental health, but the impacts of specific environmental conditions on neuropsychiatric disorders remain largely unclear. Here, we show the impact of a humid heat environment on the brain and the gut microbiota using a conditioned housing male mouse model. We demonstrate that a humid heat environment can cause anxiety-like behaviour in male mice. Microbial 16 S rRNA sequencing analysis reveals that a humid heat environment caused gut microbiota dysbiosis (e.g., decreased abundance of Lactobacillus murinus), and metabolomics reveals an increase in serum levels of secondary bile acids (e.g., lithocholic acid). Moreover, increased neuroinflammation is indicated by the elevated expression of proinflammatory cytokines in the serum and cortex, activated PI3K/AKT/NF-κB signalling and a microglial response in the cortex. Strikingly, transplantation of the microbiota from mice reared in a humid heat environment readily recapitulates these abnormalities in germ-free mice, and these abnormalities are markedly reversed by Lactobacillus murinus administration. Human samples collected during the humid heat season also show a decrease in Lactobacillus murinus abundance and an increase in the serum lithocholic acid concentration. In conclusion, gut microbiota dysbiosis induced by a humid heat environment drives the progression of anxiety disorders by impairing bile acid metabolism and enhancing neuroinflammation, and probiotic administration is a potential therapeutic strategy for these disorders.

Association of Perinatal Cardiovascular Features with Angiotensin System Expressions in Maternal Preeclampsia.

We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N (ANPEP) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor (AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.

Effectiveness of exercise training on arterial stiffness and blood pressure among postmenopausal women: a systematic review and meta-analysis.

BACKGROUND: The acute and long-term benefits of exercise training on cardiovascular health have been well established. The systematic review and meta-analysis aimed to systematically assess the effectiveness of exercise training on arterial stiffness and blood pressure among postmenopausal women with elevated blood pressure. METHODS: A comprehensive search was conducted on PubMed, Embase, Web of Science, ProQuest, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov website from inception to September 30, 2023, to identify the randomized controlled trials (RCTs), which evaluated the effectiveness of exercise training on arterial stiffness and blood pressure in postmenopausal women. Standardized mean differences (SMD), weighted mean differences (WMD), and 95% confidence intervals (95% CIs) were calculated using random/fixed effects models. Quality assessment was performed using the modified Jadad scale and the Cochrane Risk of Bias Tool. Sensitivity analysis and subgroup analysis were conducted based on drug dosage, treatment duration, and age of administration to further explore potential heterogeneity. Funnel plots were performed to assess publication bias and Begg's regression test was carried out for funnel plot asymmetry. RESULTS: Twenty-two RCTs involving 1978 participants were included in the quantitative analysis. The mean quality of eligible studies was 4.2 out of 7 based on the modified Jadad scale. The results indicated that exercise training had a significant effect on reducing brachial-ankle pulse wave velocity [MD = - 0.69, 95%CI (- 1.11, - 0.27), P = 0.001], decreasing augmentation index (AIx) [MD = - 6.00, 95%CI (- 6.39, - 5.61), P < 0.00001] and AIx normalized to a heart rate of 75 beats per minute (AIx@75%) [MD = - 7.01, 95%CI - 7.91 to - 6.12, P < 0.00001], lowering systolic blood pressure [MD = - 6.19, 95%CI - 9.24 to - 3.15, P < 0.0001], diastolic blood pressure [MD = - 3.57, 95%CI (- 6.10, - 1.03), P = 0.006) and pulse pressure [MD = - 8.52, 95%CI (- 16.27, - 0.76), P = 0.03]. Subgroup analysis revealed that baseline blood pressure levels had a large impact on the effect of exercise training. CONCLUSIONS: The systematic review and meta-analysis suggested that exercise training may ameliorate arterial stiffness and reduce blood pressure in postmenopausal women with elevated blood pressure. However, the optimal mode of exercise training that improves arterial stiffness and blood pressure in this population requires further investigation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021211268.

COVID-19 vaccination: 2023 Taiwan Association of Gerontology and Geriatrics (TAGG) consensus statements.

The COVID-19 pandemic remains challenging due to the rapid evolution of the severe acute respiratory syndrome coronavirus 2. This article discusses recent findings on high-risk groups for COVID-19 mortality and morbidity, along with consensus statements from the 2023 Taiwan Association of Gerontology and Geriatrics (TAGG) meeting. It examines evidence on viral mutation mechanisms, emerging variants, and their implications for vaccination strategies. The article underscores advanced age, immunocompromised status, chronic medical conditions, occupational exposure, and socioeconomic disparities as significant risk factors for severe COVID-19 outcomes. TAGG's consensus emphasizes robust vaccination promotion, prioritizing elderly, and immunocompromised groups, individualized multi-dose regimens for immunocompromised patients, and simplified clinical guidelines. Discussions on global and regional recommendations for regular, variant-adapted boosters highlight the non-seasonal nature of COVID-19. Key agreements include escalating domestic preparedness, implementing vigorous risk-based vaccination, and adapting global guidelines to local contexts. Given ongoing viral evolution, proactive adjustment of vaccination policies is essential. Scientific consensus, tailored recommendations, and rapid knowledge dissemination are vital for optimizing COVID-19 protection among vulnerable groups in Taiwan. This article seeks to inform clinical practice and public health policy by summarizing expert-driven vaccination perspectives.

Construction of Diverse Fused Chromene Frameworks via Isocyanide-Based Three-Component Reaction.

A convenient synthetic protocol for diverse fused chromenes was successfully developed by a three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates, and various cyclic 1,3-dipolarophiles containing o-hydroxyphenyl group. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates, and 3-(o-hydroxyarylidene)indolin-2-ones in tetrahydrofuran at 60 °C resulted in unique functionalized spiro[cyclobuta[c]chromene-1,3'-indolines] in good yields and with high diastereoselectivity. However, the similar three-component reaction with 2-(5-halo-2-hydroxyarylidene)indolin-2-ones afforded unexpected chain products in satisfactory yields. In addition, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates, and 2-(o-hydroxyarylidene)-1,3-indanediones in tetrahydrofuran at 60 °C resulted in complex indeno[2',1':5,6]pyrano[3,4-c]chromene derivatives in high yields and with high diastereoselectivity.

Liver X receptor inverse agonist SR9243 attenuates rheumatoid arthritis via modulating glycolytic metabolism of macrophages.

Liver X receptors (LXRs) which link lipid metabolism and inflammation, were overexpressed in experimental rheumatoid arthritis (RA) rats as observed in our previous studies, while suppression of LXRα by silybin ameliorates arthritis and abnormal lipid metabolism. However, the role of LXRs in RA remains undefined. In this study, we investigated the inhibition role of LXRs in the polarization and activation of M1 macrophage by using a special LXRs inverse agonist SR9243, which led to ameliorating the progression of adjuvant-induced arthritis (AIA) in rats. Mechanistically, SR9243 disrupted the LPS/IFN-γ-induced Warburg effect in M1 macrophages, while glycolysis inhibitor 2-DG attenuated the inhibition effect of SR9243 on M1 polarization and the cytokines expression of M1 macrophages including iNOS, TNF-α, and IL-6 in vitro. Furthermore, SR9243 downregulated key glycolytic enzymes, including LDH-A, HK2, G6PD, GLUT1, and HIF-1α in M1 macrophages, which is mediated by increased phosphorylation of AMPK (Thr172) and reduced downstream phosphorylation of mTOR (Ser2448). Importantly, gene silencing of LXRs compromises the inhibition effect of SR9243 on M1 macrophage polarization and activation. Collectively, for the first time, our findings suggest that the LXR inverse agonist SR9243 mitigates adjuvant-induced rheumatoid arthritis and protects against bone erosion by inhibiting M1 macrophage polarization and activation through modulation of glycolytic metabolism via the AMPK/mTOR/HIF-1α pathway.

Research on improved gangue target detection algorithm based on Yolov8s.

An improved algorithm based on Yolov8s is proposed to address the slower speed, higher number of parameters, and larger computational cost of deep learning in coal gangue target detection. A lightweight network, Fasternet, is used as the backbone to increase the speed of object detection and reduce the model complexity. By replacing Slimneck with the C2F part in the HEAD module, the aim is to reduce model complexity and improve detection accuracy. The detection accuracy is effectively improved by replacing the Detect layer with Detect-DyHead. The introduction of DIoU loss function instead of CIoU loss function and the combination of BAM block attention mechanism makes the model pay more attention to critical features, which further improves the detection performance. The results show that the improved model compresses the storage size of the model by 28%, reduces the number of parameters by 28.8%, reduces the computational effort by 34.8%, and improves the detection accuracy by 2.5% compared to the original model. The Yolov8s-change model provides a fast, real-time and efficient detection solution for gangue sorting. This provides a strong support for the intelligent sorting of coal gangue.

Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious complication of chronic obstructive pulmonary disease, often characterized by increased morbidity and mortality. In traditional Chinese medicine, AECOPD is linked to phlegm-heat and blood-stasis, presenting symptoms like thick sputum, fever, and chest pain. It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD, suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD. AIM: To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD. METHODS: One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups. The treatment group received acetylcysteine inhalation (10% solution, 5 mL, twice daily) along with conventional therapy, whereas the control group received only conventional therapy. The treatment duration was 14 d. Inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) in the serum and sputum as well as lung function parameters (forced expiratory volume in one second, forced vital capacity, and peak expiratory flow) were assessed pre- and post-treatment. Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group (P < 0.05). This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD. RESULTS: Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group. These differences were statistically significant (P < 0.05). The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD, suggesting its potential as an adjuvant therapy for such cases. CONCLUSION: Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum, as well as enhancing lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD. These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD, offering benefits for managing microinflammation and optimizing lung function.

Natural soil biotin application activates soil beneficial microorganisms to improve the thermotolerance of Chinese cabbage.

Chinese cabbage (Brassica campestris L. syn. B. rapa), a widely cultivated leafy vegetable, faces significant challenges in annual production due to high-temperature stress, which adversely affects plant weight and quality. The need for an effective solution to mitigate these impacts is imperative for sustainable horticulture. This study explored the effects of a novel biofertilizer, natural soil biotin (NSB), on Chinese cabbage under high-temperature conditions. NSB, rich in organic matter-degrading enzymes, was applied to assess its impact on crop yield, growth, nutrient use efficiency, product quality, and safety. The study also examined the soil microbial community response to NSB application, particularly the changes in the rhizosphere soil's fungal population. The application of NSB led to an increase in the abundance of Oleomycetes, which was associated with a decrease in the diversity and abundance of harmful fungi in the rhizosphere soil. This microbial shift promoted the growth of Chinese cabbage, enhancing both plant weight and quality by fostering a more favorable growth environment. Furthermore, NSB was found to reduce lipid peroxidation in Chinese cabbage leaves under high-temperature stress (40°C/30°C, 16 h/8 h, 24 h) by boosting antioxidant enzyme activity and osmoregulatory substance content. The findings suggest that the NSB application offers a promising approach to environmentally friendly cultivation of Chinese cabbage during high-temperature seasons. It contributes to improving the crop's adaptation to climate change and soil degradation, supporting the development of sustainable agricultural practices. The integration of NSB into agricultural practices presents a viable strategy for enhancing the resilience of Chinese cabbage to high-temperature stress, thereby potentially increasing yield and improving the quality of the produce, which is crucial for the advancement of sustainable horticulture.

Cerebral autoregulation-directed optimal blood pressure management reduced the risk of delirium in patients with septic shock.

Background: When resuscitating patients with septic shock, cerebrovascular reactivity parameters are calculated by monitoring regional cerebral oxygen saturation (rSO2) using near-infrared spectroscopy to determine the optimal blood pressure. Here, we aimed to analyze the impact of cerebral autoregulation-directed optimal blood pressure management on the incidence of delirium and the prognosis of patients with septic shock. Methods: This prospective randomized controlled clinical study was conducted in the Xiangya Hospital of Central South University, China. Fifty-one patients with septic shock (December 2020-May 2022) were enrolled and randomly allocated to the experimental (n=26) or control group (n=25). Using the ICM+ software, we monitored the dynamic changes in rSO2 and mean arterial pressure (MAP) and calculated the cerebrovascular reactivity parameter tissue oxygen reactivity index to determine the optimal blood pressure to maintain normal cerebral autoregulation function during resuscitation in the experimental group. The control group was treated according to the Surviving Sepsis Campaign Guidelines. Differences in the incidence of delirium and 28-day mortality between the two groups were compared, and the risk factors were analyzed. Results: The 51 patients, including 39 male and 12 female, had a mean age of (57.0±14.9) years. The incidence of delirium was 40.1% (23/51), and the 28-day mortality rate was 29.4% (15/51). The mean MAP during the first 24 h of intensive care unit (ICU) admission was higher ([84.5±12.2] mmHg vs. [77.4±11.8] mmHg, P=0.040), and the incidence of delirium was lower (30.8% vs. 60.0%, P=0.036) in the experimental group than in the control group. The use of cerebral autoregulation-directed optimal blood pressure (odds ratio [OR]=0.090, 95% confidence interval [CI]: 0.009 to 0.923, P=0.043) and length of ICU stay (OR=1.473, 95% CI: 1.093 to 1.985, P=0.011) were risk factors for delirium during septic shock. Vasoactive drug dose (OR=8.445, 95% CI: 1.26 to 56.576, P=0.028) and partial pressure of oxygen (PaO2) (OR=0.958, 95% CI: 0.921 to 0.996, P=0.032) were the risk factors for 28-day mortality. Conclusions: The use of cerebral autoregulation-directed optimal blood pressure management during shock resuscitation reduces the incidence of delirium in patients with septic shock. Trial Registration: ClinicalTrials.gov ldentifer: NCT03879317.

Optimal image quality and radiation doses with optimal tube voltages/currents for pediatric anthropomorphic phantom brains.

OBJECTIVE: Using pediatric anthropomorphic phantoms (APs), we aimed to determine the scanning tube voltage/current combinations that could achieve optimal image quality and avoid excessive radiation exposure in pediatric patients. MATERIALS AND METHODS: A 64-slice scanner was used to scan a standard test phantom to determine the volume CT dose indices (CTDIvol), and three pediatric anthropomorphic phantoms (APs) with highly accurate anatomy and tissue-equivalent materials were studied. These specialized APs represented the average 1-year-old, 5-year-old, and 10-year-old children, respectively. The physical phantoms were constructed with brain tissue-equivalent materials having a density of ρ = 1.07 g/cm3, comprising 22 numbered 2.54-cm-thick sections for the 1-year-old, 26 sections for the 5-year-old, and 32 sections for the 10-year-old. They were scanned to acquire brain CT images and determine the standard deviations (SDs), effective doses (EDs), and contrast-to noise ratios (CNRs). The APs were scanned by 21 combinations of tube voltages/currents (80, 100, or 120 kVp/10, 40, 80, 120, 150, 200, or 250 mA) and rotation time/pitch settings of 1 s/0.984:1. RESULTS: The optimal tube voltage/current combinations yielding optimal image quality were 80 kVp/80 mA for the 1-year-old AP; 80 kVp/120 mA for the 5-year-old AP; and 80 kVp/150 mA for the 10-year-old AP. Because these scanning tube voltages/currents yielded SDs, respectively, of 12.81, 13.09, and 12.26 HU, along with small EDs of 0.31, 0.34, and 0.31 mSv, these parameters and the induced values were expediently defined as optimal. CONCLUSIONS: The optimal tube voltages/currents that yielded optimal brain image quality, SDs, CNRs, and EDs herein are novel and essentially important. Clinical translation of these optimal values may allow CT diagnosis with low radiation doses to children's heads.