Gut microbiome and metabolome alterations in traditional Chinese medicine damp-heat constitution following treatment with a Chinese patent medicine and lifestyle intervention.

BACKGROUND: The gut microbiota is crucial in human health and diseases. Traditional Chinese Medicine Constitution (TCMC) divides people into those with a balanced constitution (Ping-he [PH]) and those with an unbalanced constitution. Dampness-heat constitution (Shi-re [SR]) is a common unbalanced constitution in the Chinese population and is susceptible to diseases. However, unbalanced constitutions can be regulated by Chinese medicine and lifestyle interventions in clinical practice. Ermiao Pill (EMP) is a Chinese medicine known for clearing heat and draining dampness and improving SR. However, the efficacy and mechanism of EMP are unclear. HYPOTHESIS/PURPOSE: To determine alterations in the gut microbiota and metabolome in SR and any changes after EMP treatment combined with lifestyle intervention. STUDY DESIGN: Randomized clinical trial. METHODS: We enrolled 112 healthy SR individuals and evaluated the efficacy of EMP along with lifestyle interventions. We further assessed serum cytokine levels, serum and urinary metabolomes, and the gut microbiota by 16S rRNA gene sequencing analysis before and after the EMP and lifestyle interventions. RESULTS: 107 SR individuals (55 in the intervention group and 52 in the control group) completed the 1-month-intervention and 1-year-follow-up. The intervention group significantly improved their health status within 1 month, with a reduced SR symptom score, and the efficacy lasted to the 1-year follow-up. The control group needed a further 6 months to reduce the SR symptom score. The gut microbiota of PH individuals was more diverse and had significantly higher proportions of many bacterial species than the SR. Microbiota co-occurrence network analysis showed that SR enriches metabolites correlating with microbial community structure, consistent with traits of healthy SR-enriched microbiota. CONCLUSION: EMP combined with lifestyle intervention produced health benefits in SR individuals. Our study indicates a pivotal role of gut microbiota and metabolome alterations in distinguishing between healthy SR and PH. Furthermore, the study reveals structural changes of gut microbiota and metabolites induced by EMP and lifestyle intervention. The treatment enriched the number of beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus in the gut. Our findings provide a strong indication that several metabolite factors are associated with the gut microbiota. Moreover, the gut microbiome and metabolome might be powerful tools for TCMC diagnosis and personalized therapy.

First Report of Fusarium fujikuroi Causing Postharvest Rot of Kiwifruit (Actinidia chinensis) in Jiangxi Province, China.

Kiwifruits (Actinidia chinensis) are among the most widely planted fruit in Jiangxi Province, China. Infected kiwifruits of the cultivars 'Hongyang' and 'Jinyan' were obtained from a commercial orchard in Fengxin county, Jiangxi Province (28°67' N; 115°42' E) from September to November 2022. The 1200 kiwifruits were collected from cold storage (cold stored for 3 months at 2°C), and moved to room temperatures (15 to 20°C), approximately 20% had symptoms of postharvest soft rot 7 days later. The infected fruits had brown or dark gray spots on the peel. Most were round or oval, with a diameter of approximately 1~3 cm. The pulp was milky white, and there was a waterlogged ring at the junction of decay. The pathogen was isolated by removing several small pieces (3×3 mm) of infected tissue from the diseased kiwifruits, which were sterilized with 75% ethanol for 30 s, dipped in 1% NaClO for 1 min, and rinsed three times with sterile distilled water. These pieces were transferred onto potato dextrose agar (PDA) and incubated for 5 days at 28°C, 75% relative humidity (RH), separated, and repurified. Eight unidentified isolates with similar morphology were obtained on PDA (D3-1 to D3-8). These isolates had abundant aerial fluffy mycelia. The colonies were white during the early stage of culture and turned light purple in the later stage. The mycelia grew 5.8 mm day-1 (n=5) on average and produced abundant conidia 10 days later. The microconidia were solitary, transparent, ovoid, with 0 to 1 septa, and 3.6 to 11.2 × 1.6 to 3.5 µm (average 6.5 × 2.9 µm, n = 50). The macroconidia were sickle-shaped, slender and slightly curved, with 3 to 5 septa, and 22.3 to 53.9 × 2.6 to 5.4 µm (average 39.5 × 4.3 µm, n = 50). Chlamydospores were absent. The morphological characteristics enabled the identification of the pathogen as Fusarium spp. (Leslie and Summerell, 2006). Isolate D3-2 was further confirmed, and the primers ITS1/ITS4 (White et al. 1990), 5F2/7CR and EF1/EF2 (O'Donnell et al. 2022) were used to amplify the internal transcribed spacer (ITS) region, RNA polymerase II largest subunit (RPB2) gene and translation elongation factor-1 alpha regions (TEF-1α). The ITS (accession no. PP077075), RPB2 (PP566653) and TEF-1α (PP566654) sequences shared 99.62 to 100% identities with ITS (ON564593.1), RPB2 (ON734380.1) and TEF-1α (ON697186.1) of F. fujikuroi from NCBI, respectively. Thus, the pathogen was identified as F. fujikuroi based on morphological and molecular characteristics. Each of the three isolates was inoculated on surface-disinfected (75% ethanol, 5 min) disease-free kiwifruits of cv. 'Jinyan' and 'Hongyang'. The six kiwifruits were pierced by a sterile inoculation needle and inoculated with 20 µl spore suspension (1×106 spores/ml), and six kiwifruits were treated with spore suspension without any wounds, four control fruits were inoculated with sterile distilled water. All the fruits were sealed in a storage box, kept at an RH of 90%-95%, and incubated at a constant temperature of 28°C for 5 days. After 3 days, the fruit rotted at the inoculation site, and after 5 days, the lesions gradually increased, and the symptoms were the same as those of the original sample. The control fruits remained disease-free. The pathogenicity tests were repeated three times. Koch's postulates were completed by reisolating the fungus from infected kiwifruits, which was identified as F. fujikuroi by sequencing. Although F. solani (Yang et al. 2018) and F. acuminatum (Wang et al. 2015) have been previously reported to rot kiwifruits in China, this is the first report of F. fujikuroi causing postharvest rot on kiwifruits in China. This discovery can alert agronomists to prevent and control this pathogen.

Identification of inhibitors from a functional food-based plant Perillae Folium against hyperuricemia via metabolomics profiling, network pharmacology and all-atom molecular dynamics simulations.

Introduction: Hyperuricemia (HUA) is a metabolic disorder caused by purine metabolism dysfunction in which the increasing purine levels can be partially attributed to seafood consumption. Perillae Folium (PF), a widely used plant in functional food, has been historically used to mitigate seafood-induced diseases. However, its efficacy against HUA and the underlying mechanism remain unclear. Methods: A network pharmacology analysis was performed to identify candidate targets and potential mechanisms involved in PF treating HUA. The candidate targets were determined based on TCMSP, SwissTargetPrediction, Open Targets Platform, GeneCards, Comparative Toxicogenomics Database, and DrugBank. The potential mechanisms were predicted via Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) analyses. Molecular docking in AutoDock Vina and PyRx were performed to predict the binding affinity and pose between herbal compounds and HUA-related targets. A chemical structure analysis of PF compounds was performed using OSIRIS DataWarrior and ClassyFire. We then conducted virtual pharmacokinetic and toxicity screening to filter potential inhibitors. We further performed verifications of these inhibitors' roles in HUA through molecular dynamics (MD) simulations, text-mining, and untargeted metabolomics analysis. Results: We obtained 8200 predicted binding results between 328 herbal compounds and 25 potential targets, and xanthine dehydrogenase (XDH) exhibited the highest average binding affinity. We screened out five promising ligands (scutellarein, benzyl alpha-D-mannopyranoside, elemol, diisobutyl phthalate, and (3R)-hydroxy-beta-ionone) and performed MD simulations up to 50 ns for XDH complexed to them. The scutellarein-XDH complex exhibited the most satisfactory stability. Furthermore, the text-mining study provided laboratory evidence of scutellarein's function. The metabolomics approach identified 543 compounds and confirmed the presence of scutellarein. Extending MD simulations to 200 ns further indicated the sustained impact of scutellarein on XDH structure. Conclusion: Our study provides a computational and biomedical basis for PF treating HUA and fully elucidates scutellarein's great potential as an XDH inhibitor at the molecular level, holding promise for future drug design and development.

Transcriptome and metabolome analyses of anthocyanin biosynthesis in post-harvest fruits of a full red-type kiwifruit (Actinidia arguta) 'Jinhongguan'.

Anthocyanin is the main component of pigment in red-fleshed kiwifruit. 'Jinhongguan' is a new cultivar of Actinidia arguta with red peel and flesh after harvest. However, the specific types of anthocyanin in the 'Jinhongguan' fruit and its biosynthesis pathways remain largely unknown. Here, the total anthocyanin content in the fruit color conversion process was determined. The results showed that total anthocyanin content increased with the deepening color of the peel and flesh. To identify the genes related to anthocyanin biosynthesis and the types of anthocyanins in the 'Jinhongguan' fruit, a combined analysis of transcriptome and anthocyanin-targeted metabolome was carried out. A total of 5751 common differentially expressed genes (DEGs) at different stages of peel and flesh were identified, of which 2767 were common up-DEGs and 2976 were common down-DEGs. KEGG and GO enrichment analyses showed that the common up-DEGs were significantly enriched in anthocyanin synthesis-related pathways, suggesting some up-DEGs are involved in anthocyanin biosynthesis. In total, 29 metabolites were detected in the flesh by anthocyanin-targeted metabolome. Among these, nine were differential accumulation metabolites (DAMs) in comparison to red flesh vs green flesh. Six DAMs were up-regulated, with five of them were cyanidins. The content of cyanidin-3-O-galactoside was much higher than that of other DAMs, making it the main pigment in 'Jinhongguan'. Moreover, a total of 36 anthocyanin synthesis-related structural genes, 27 MYB transcription factors (TFs), 37 bHLH TFs and 9 WDR TFs were screened from the common DEGs. Correlation analysis of transcriptome and metabolome revealed that 9 structural genes, 6 MYB TFs, 6 bHLH TFs and 1 WDR TF were significantly associated with cyanidin-3-O-galactoside. Further, qRT-PCR analysis demonstrated that structural genes (AaPAL3, Aa4CL3, AaCHS2/3/8/9/11, AaDFR1/2, AaANR1, UFGT3a and UFGT6b) and TFs (MYB108, bHLH30, bHLH94-1 and WD43) play important roles in cyanidin biosynthesis. Overall, this study identified cyanidin-3-O-galactoside as the main anthocyanin type and revealed key candidate genes of red coloration of post-harvest fruit in Actinidia arguta. These findings provided new insights into the color formation mechanism of post-harvest fruit and offered a theoretical basis for color regulation in kiwifruit.

Anaesthesia-related mortality within 24 h following 9,391,669 anaesthetics in 10 cities in Hubei Province, China: a serial cross-sectional study.

Background: The mortality risk related to anaesthesia in China remains poorly characterized. The objective of this study was to evaluate the anaesthesia-related mortality in terms of its incidence, changes, causes and preventability in Hubei, China, between 2017 and 2021 using a series of annual surveys. Methods: We prospectively collected information on patient, surgical, anaesthesia, and hospital characteristics for 9,391,669 anaesthesia procedures performed between 2017 and 2021 in 10 cities within Hubei Province, China. Anaesthesia-related death was defined as death that deemed to be entirely or partially attributable to anaesthesia, occurring within 24 h following anaesthesia administration. All fatalities were scrutinized consecutively to determine their root causes and preventability. The incidence and patterns of anaesthesia-related deaths were analysed from 2017 to 2021. A mixed-effects model with a Poisson link function was fitted to evaluate the city-level annual changes in risk-adjusted incidence of anaesthesia-related deaths. Findings: 600 cases of anaesthetic deaths occurred from 2017 to 2021, yielding an incidence of 6.4 per 100,000 anaesthesia procedures [95% confidence interval (95% CI): 5.9, 6.9], and most were preventable (71.3%). There was a significant decrease from 2017 to 2021, in the incidences of anaesthesia-related death across all patients, those with American Society of Anaesthesiologists physical status (ASAPS) ≥III, and those who had general anaesthesia, with a percentage reduction of 57.6%, 59.1%, and 55.9%, respectively. The risk-adjusted annual changes indicated significant downward trends for the incidence of anaesthetic mortality from 2017 to 2018, 2019, 2020, and 2021. For instance, the risk-adjusted annual changes for the anaesthetic mortality incidence from 2017 to 2021 was -2.5 (95% CI: -1.4, -4.7). Interpretation: In this large, comprehensive database study conducted in Central China, the anaesthesia-related death incidence was 6.4 per 100,000. Notably, the incidence of anaesthesia-related deaths decreased between 2017 and 2021. However, further in-depth analysis is needed to understand the extent to which these trends represent a change in patient safety. Funding: Innovation and optimization of perioperative respiratory system management strategy (Hubei Technological Innovation Special Fund, 2019ACA167).

Zhenwu decoction ameliorates cardiac hypertrophy through activating sGC (soluble guanylate cyclase) - cGMP (cyclic guanosine monophosphate) - PKG (protein kinase G) pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhenwu Decoction (ZWD) is a traditional Chinese medicine (TCM) formula which has wide scope of indications related to Yang deficiency and dampness retention in TCM syndrome. Cardiac hypertrophy can induce similar symptoms and signs to the clinical features of Yang deficiency and dampness retention syndrome. ZWD can increase the left ventricular ejection fraction, reduce cardiac hypertrophy of patients with chronic heart failure. However, its underlying pharmacological mechanism remains unclear. AIM OF THE STUDY: The study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms. MATERIALS AND METHODS: The potential targets and pathways of ZWD in cardiac hypertrophy were highlighted by network pharmacology and validated by mechanistic and functional studies. RESULTS: Our network pharmacology analysis suggests that the protective effects of ZWD on cardiac hypertrophy are related to cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. Subsequent animal studies showed that ZWD significantly ameliorated cardiac function decline, cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. To explore the underlying mechanisms of action, we performed Western blotting, immunohistochemical analysis, and detection of inflammatory response and oxidative stress. Our results showed that ZWD activated the soluble guanylate cyclase (sGC) - cGMP - PKG signaling pathway. The sGC inhibitor ODQ that blocks the sGC-cGMP-PKG signaling pathway in zebrafish abolished the protective effects of ZWD, suggesting sGC-cGMP-PKG is the main signaling pathway mediates the protective effect of ZWD in cardiac hypertrophy. In addition, three major ingredients from ZWD, poricoic acid C, hederagenin and dehydrotumulosic acid, showed a high binding energy with prototype sGC. CONCLUSION: ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway.

Genome-wide analysis of MADS-box gene family in kiwifruit (Actinidia chinensis var. chinensis) and their potential role in floral sex differentiation.

Kiwifruit (Actinidia chinensis Planch.) is a functionally dioecious plant, which displays diverse morphology in male and female flowers. MADS-box is an ancient and huge gene family that plays a key role in plant floral organ differentiation. In this study, we have identified 89 MADS-box genes from A. chinensis Red 5 genome. These genes are distributed on 26 chromosomes and are classified into type I (21 genes) and type II (68 genes). Overall, type II AcMADS-box genes have more complex structures than type I with more exons, protein domains, and motifs, indicating that type II genes may have more diverse functions. Gene duplication analysis showed that most collinearity occurred in type II AcMADS-box genes, which was consistent with a large number of type II genes. Analysis of cis-acting elements in promoters showed that AcMADS-box genes are mainly associated with light and phytohormone responsiveness. The expression profile of AcMADS-box genes in different tissues showed that most genes were highly expressed in flowers. Further, the qRT-PCR analysis of the floral organ ABCDE model-related genes in male and female flowers revealed that AcMADS4, AcMADS56, and AcMADS70 were significantly expressed in female flowers. It indicated that those genes may play an important role in the sex differentiation of kiwifruit. This work provided a comprehensive analysis of the AcMADS-box genes and may help facilitate our understanding of the sex differentiation regulatory mechanism in kiwifruit.

Baseline serum uric acid level is associated with progression-free survival, disease control rate, and safety in postoperative patients with colorectal cancer treated by FOLFOX, FOLFIRI, or XELOX.

Background: High serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy. Patients and Methods: We conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center. Results: Data from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety. Conclusions: These findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.

Sleep Quality Improvement Enhances Neuropsychological Recovery and Reduces Blood Aß42/40 Ratio in Patients with Mild-Moderate Cognitive Impairment.

Background and objectives: Alzheimer's disease is a progressive brain degeneration and is associated with a high prevalence of sleep disorders. Amyloid ß peptide-42/40 (Aß42/40) and Tau-pT181 are the core biomarkers in cerebrospinal fluid and blood. Accumulated data from studies in mouse models and humans demonstrated an aberrant elevation of these biomarkers due to sleep disturbance, especially sleep-disordered breathing (SDB). However, it is not clear if sleep quality improvement reduces the blood levels of Ab42/40 ratio and Tau-pT181 in Alzheimer's disease patients. Materials and Methods: In this prospective study, a longitudinal analysis was conducted on 64 patients with mild-moderate cognition impairment (MCI) due to Alzheimer's disease accompanied by SDB. Another 33 MCI cases without sleep-disordered breathing were included as the control group. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) score system. Neuropsychological assessments were conducted using the Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Clinical Dementia Rating (CDR), 24-h Hamilton Rating Scale for Depression (HRSD-24), and Hamilton Anxiety Rating Scale (HAMA) scoring systems. Aß42, Aß40, and Tau-pT181 protein levels in blood specimens were measured using ELISA assays. All patients received donepezil treatment for Alzheimer's disease. SDB was managed with continuous pressure ventilation. Results: A significant correlation was found among PSQI, HRSD-24, HAMA, Aß42/40 ratio, and Tau-pT181 level in all cases. In addition, a very strong and negative correlation was discovered between education level and dementia onset age. Compared to patients without SDB (33 non-SD cases), patients with SDB (64 SD cases) showed a significantly lower HRSD-24 score and a higher Aß42/40 ratio Tau-pT181 level. Sleep treatment for patients with SDB significantly improved all neuropsychological scores, Aß42/40 ratio, and Tau-pT181 levels. However, 11 patients did not completely recover from a sleep disorder (PSQI > 5 post-treatment). In this subgroup of patients, although HAMA score and Tau-pT181 levels were significantly reduced, MoCA and HRSD-24 scores, as well as Aß42/40 ratio, were not significantly improved. ROC analysis found that the blood Aß42/40 ratio held the highest significance in predicting sleep disorder occurrence. Conclusions: This is the first clinical study on sleep quality improvement in Alzheimer's disease patients. Sleep quality score was associated with patient depression and anxiety scores, as well as Aß42/40 ratio and Tau-pT181 levels. A complete recovery is critical for fully improving all neuropsychological assessments, Aß42/40 ratio, and Tau-pT181 levels. Blood Aß42/40 ratio is a feasible prognostic factor for predicting sleep quality.

Exploring transition durations of rear-end collisions based on vehicle trajectory data: A survival modeling approach.

The time-to-collision (TTC) index and its extended variants have been widely utilized to assess rear-end collision risks, but the characteristics of the time-series data have not been fully explored, especially for the transition from safe to risky conditions. This study proposes a novel approach in rear-end collision risk analysis based on the concept of transition durations. The vehicle trajectory data were extracted and the TTC index was used to identify risky and safe conditions. Three important transition durations are defined and their rationalities for evaluating rear-end collision risks are examined by developing random-parameters accelerated failure time (AFT) survival models. Furthermore, a typical case from real trajectory data is taken to discuss the limitations of using TTC and its variants, and the advantage of the proposed transition durations. The results of random-parameters AFT models reveal contributing factors affecting the length of three durations and demonstrate the rationality of transition durations in rear-end collision risks analysis. It is indicated that the proposed method outperforms TTC and its variants in evaluating rear-end collision risks, because it could not only provide the information of time point but also the variation of time-series data.

The dynamic tradeoff between safety and efficiency in discretionary lane-changing behavior: A random parameters logit approach with heterogeneity in means and variances.

The discretionary lane-changing behavior is highly associated with crash occurrence. This paper investigates the dynamic tradeoff between safety and efficiency and influencing factors of the decision-making process for the discretionary lane-change. A random parameters logit approach with heterogeneity in means and variances is employed on a microscopic vehicle trajectory dataset. Four vehicles are analyzed as a discretionary lane-changing group, and both the distance-related and speed-related factors are taken into account to examine their dynamic effects. The modeling results indicate that (1) two distance-related variables produce significant random parameters with heterogeneity in means and variances, while there is only one speed-related variable having significant result for heterogeneity in means and variances; (2) the relationship between the speed of lane-changing vehicle and the heterogeneity in mean of vehicle clearance distance between leading vehicle in current lane and lane-changing vehicle quantitatively demonstrates that when the driver decides whether to change lanes, the driver considers the tradeoff between distance (i.e., safety) and speed (i.e., efficiency) at the same time; and (3) the number of significant variables is gradually decreased during the lane-changing decision-making process. It demonstrates that the lane-changing decision is a dynamic process where drivers gradually select more critical factors and pay more attention to them.

Using vehicular trajectory data to explore risky factors and unobserved heterogeneity during lane-changing.

This study aims to investigate contributing factors to potential collision risks during lane-changing processes from the perspective of vehicle groups and explore the unobserved heterogeneity of individual lane-changing maneuvers. Vehicular trajectory data, extracted from the Federal Highway Administration's Next Generation Simulation dataset, are utilized and 579 lane-changing vehicle groups are examined. Stopping distance indexes are developed to evaluate the potential collision risks of lane-changing vehicle groups. Three mixed binary logit models and three mixed logit models with heterogeneity in means and variances are established based on different perception reaction time. Model estimation results show that several variables significantly affect the risk status of lane-changing vehicle groups, including the mean values of clearance distance and speed differences between the leading vehicle in the current lane and the subject vehicle, standard deviations of clearance distance, and speed differences between these two vehicles, as well as standard deviations of the speed difference between the subject vehicle and the following vehicle in the target lane. Interestingly, the influences of the last three variables differ considerably across the observations and the mean of the random parameter for standard deviations of clearance distance between CLV and SV is associated with the mean speed difference between CLV and SV. Since one of the explanations is individual heterogeneity, personalized designs for advanced driver assistance system would be an effective measure to reduce the risk.

Roles, molecular mechanisms, and signaling pathways of TMEMs in neurological diseases.

Transmembrane protein family members (TMEMs) span the entire lipid bilayer and act as channels that allow the transport of specific substances through biofilms. The functions of most TMEMs are unexplored. Numerous studies have shown that TMEMs are involved in the pathophysiological processes of various nervous system diseases, but the specific mechanisms of TMEMs in the pathogenesis of diseases remain unclear. In this review, we discuss the expression, physiological functions, and molecular mechanisms of TMEMs in brain tumors, psychiatric disorders, abnormal motor activity, cobblestone lissencephaly, neuropathic pain, traumatic brain injury, and other disorders of the nervous system. Additionally, we propose that TMEMs may be used as prognostic markers and potential therapeutic targets in patients with various neurological diseases.

Role of Anesthesia Nurses in the Treatment and Management of Patients With COVID-19.

As the backbone for the treatment of patients with coronavirus disease 2019 (COVID-19), nurses have been playing key roles in cabin hospitals, isolation wards, and intensive care units for critical cases. Anesthesia nurses have their own professional specialties, such as airway management, the use and maintenance of life support equipment, including ventilators, and the use of high-flow oxygen equipment. With rich experience in emergency responses and nursing, anesthesia nurses, along with emergency nurses and critical care nurses, play important roles during the treatment of patients with COVID-19. In our hospital, 27 of 34 anesthesia nurses participated in the front-line fight against COVID-19 and did an excellent job. Anesthesia care by nurses is relatively new in China, and the role of anesthesia nurses during a disaster response has not been fully appreciated. Given their specialty, anesthesia nurses have played important roles in the treatment of patients with COVID-19. We hope that authorities will consider including anesthesia nurses in national disaster response medical rescue teams.

Amelioration of Lipopolysaccharide-Induced Acute Lung Injury in Rats by Na-H Exchanger-1 Inhibitor Amiloride Is Associated with Reversal of ERK Mitogen-Activated Protein Kinase.

BACKGROUND: Na-H exchanger-1 (NHE-1) is expressed in the lung of rats. Accumulating evidence shows that Na-H exchangers are involved in inflammation. Amiloride, an inhibitor of NHE-1, inhibits the activation of macrophages and endothelial cells and reduces their production of cytokines. Since these processes have been implicated in acute lung injury (ALI) induced by lipopolysaccharide (LPS), we examined the protective effect of amiloride on ALI induced by LPS in rats. MATERIAL AND METHODS: ALI in specific pathogen-free male Sprague-Dawley rats was induced by an intravenous injection of 6 mg/kg LPS. Amiloride pretreated rats received an intravenous injection of 10 mg/kg amiloride 30 min before the administration of LPS. Controls received normal saline in a similar manner. All animals were sacrificed 6 h after LPS or normal saline administration. The degree of ALI was assessed by wet-to-dry weight ratio (W/D) and lung histological examination. Neutrophilic infiltration was determined by myeloperoxidase (MPO) activity in lung tissue. Concentrations of total protein (TP), tumor necrosis factor-alpha (TNF-α), and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid (BALF) were also measured. Expression of NHE-1 and mitogen-activated protein kinase (MAPK) p38, p-p38, ERK, and p-ERK was evaluated by western blot analysis. RESULTS: Pretreatment with amiloride significantly reduced the increase in W/D, ALI score, lung tissue MPO activity, concentrations of TP, TNF-α, and MIP-2 in BALF, resulting in attenuation of ALI induced by LPS. Meanwhile, levels of NHE-1 and p-ERK proteins were reversed, whereas that of p-p38 was not. CONCLUSIONS: These findings suggest that NHE-1 inhibitor amiloride could attenuate ALI induced by LPS in rats. This effect is mediated through reversal of ERK.

[Change patterns, influencing factors and predictors of quality of life in patients with Alzheimer's disease].

OBJECTIVE: To explore the change patterns, influencing factors and predictors of quality of life for 4 years in patients with Alzheimer's disease (AD). METHODS: A total of 96 mild-moderate AD patients on combined therapies of medicine and recuperation were enrolled. Their clinical symptoms were graded by mini-mental state examination (MMSE), activity of daily living (ADL), global deterioration scale (GDS), neuropsychiatric inventory (NPI), Hamilton depression scale (HRSD), Hamilton anxiety scale (HAMA) and Pittsburgh sleep quality index (PQSI). And their qualities of life were evaluated by Quality of Life-Alzheimer's Disease (QOL-AD) at baseline and at the end of 1, 2, 3, 4 year. RESULTS: (1) During a 4-year follow-up, the scores of QOL-AD, MMSE, ADL, GDS, NPI, HRSD, HAMA and PQSI decreased markedly compared with baseline [(17.5±1.9), (12±3), (45±9), (5.2±0.8), (31±11), (20±6), (14±6), (14±4) vs (30.5±4.6), (21±4), (34±10), (3.3±0.9), (22±9), (18±6), (11±4), (12±4) respectively, t=25.31, 15.42, -7.16, -14.83, -5.56, -2.94, -4.45, -5.60, all P<0.01]. With the deterioration of AD, their qualities of life decreased significantly. (2) Spearman's correlation analysis showed that the scores of 4-year QOL-AD were correlated with the 4-year score changes of MMSE, ADL, GDS (r=0.344, 0.368, 0.213; P=0.002, 0.001, 0.047). (3) Multiple Logistic regression model showed that the baseline scores of NPI and HRSD were strong predictors of loss of quality of life (OR=1.697, 1.269; P=0.000, 0.006). And the area under the curve of receiver operating characteristic (ROC) of NPI and HRSD were 0.918 (95% CI: 0.844-0.991) and 0.878 (95% CI: 0.804-0.953) respectively. CONCLUSION: With the deterioration of AD, the quality of life decreases significantly and has correlations with the score changes of MMSE, ADL and GDS. High scores of NPI and HRSD are the important predictors for a loss of quality of life in AD patients. Early detection and timely interventions are necessary.