Analysis of cartilage loading and injury correlation in knee varus deformity.

Knee varus (KV) deformity leads to abnormal forces in the different compartments of the joint cavity and abnormal mechanical loading thus leading to knee osteoarthritis (KOA). This study used computer-aided design to create 3-dimensional simulation models of KOA with varying varus angles to analyze stress distribution within the knee joint cavity using finite element analysis for different varus KOA models and to compare intra-articular loads among these models. Additionally, we developed a cartilage loading model of static KV deformity to correlate with dynamic clinical cases of cartilage injury. Different KV angle models were accurately simulated with computer-aided design, and the KV angles were divided into (0°, 3°, 6°, 9°, 12°, 15°, and 18°) 7 knee models, and then processed with finite element software, and the Von-Mises stress distribution and peak values of the cartilage of the femoral condyles, medial tibial plateau, and lateral plateau were obtained by simulating the human body weight in axial loading while performing the static extension position. Finally, intraoperative endoscopy visualization of cartilage injuries in clinical cases corresponding to KV deformity subgroups was combined to find cartilage loading and injury correlations. With increasing varus angle, there was a significant increase in lower limb mechanical axial inward excursion and peak Von-Mises stress in the medial interstitial compartment. Analysis of patients' clinical data demonstrated a significant correlation between varus deformity angle and cartilage damage in the knee, medial plateau, and patellofemoral intercompartment. Larger varus deformity angles could be associated with higher medial cartilage stress loads and increased cartilage damage in the corresponding peak stress area. When the varus angle exceeds 6°, there is an increased risk of cartilage damage, emphasizing the importance of early surgical correction to prevent further deformity and restore knee function.

Antimicrobial resistance and population genomics of emerging multidrug-resistant Salmonella 4,[5],12:i:- in Guangdong, China.

Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.

Biochar alters the selectivity of MnFe2O4-activated periodate process through serving as the electron-transfer mediator.

Constructing green and sustainable advanced oxidation processes (AOPs) for the degradation of organic contaminants is of great importance but still remains big challenge. In this work, an effective AOP (MnFe2O4-activated periodate, MnFe2O4/PI) was established and investigated for the oxidation of organic contaminants. To avoid the severe aggregation of MnFe2O4 nanoparticles, a hybrid MnFe2O4-biochar catalyst (MnFe2O4-BC) was further synthesized by anchoring MnFe2O4 nanoparticles on chemically inert biochar substrate. Intriguingly, MnFe2O4-BC/PI exhibited different selectivity towards organic contaminants compared with MnFe2O4/PI, revealing that biochar not only served as the substrate, but also directly participated into the oxidation process. Electron-transfer mechanism was comprehensively elucidated to be responsible for the abatement of pollutants in both MnFe2O4/PI and MnFe2O4-BC/PI. The surface oxygen vacancies (OVs) of MnFe2O4 were identified as the active sites for the formation of high potential complexes MnFe2O4-PI*, which could directly and indirectly degrade the organic pollutants. For the hybrid MnFe2O4-BC catalyst, biochar played multiple roles: (i) substrate, (ii) provided massive adsorption sites, (iii) electron-transfer mediator. The differences in selectivity of MnFe2O4/PI and MnFe2O4-BC/PI were determined by the adsorption affinity between biochar substrate and organics. Overall, the findings of this study expand the knowledge on the selectivity of PI-triggered AOPs.

Physiochemical characterization and ameliorative effect of rice resistant starch modified by heat-stable α-amylase and glucoamylase on the gut microbial community in T2DM mice.

In the presented study, natural rice containing high resistant starch content was used as a raw material to produce rice resistant starch (RRS) through enzymatic hydrolysis with heat-stable α-amylase and glucoamylase. The chemical composition, structural characteristics and in vitro glycemic index (GI) of RRS were evaluated. The effects of RRS at different doses on the body weight, serum biochemical levels, pathological indexes, production of short-chain fatty acids (SCFAs) in the gut and the intestinal microbial composition in T2DM mice were investigated. The results of physiochemical characterization indicated that, relative to rice flour, RRS mainly comprising resistant starch had higher crystallinity (25.85%) and a more stable structure, which contributed to its lower digestibility and decreased GI in vitro. Compared with the model control group, 1 g per kg BW and 2 g per kg BW oral gavage dosages of RRS effectively enhanced the SCFA productivity in the T2DM mouse gut, as well as alleviating T2DM symptoms, involving an increase in body weight, reduction in fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine transaminase and aspartate aminotransferase, and an increase in serum insulin and high-density lipoprotein cholesterol. Besides, 1 g per kg BW and 2 g per kg BW dosages of RRS mitigated T2DM-induced pancreas damage. Furthermore, up-regulation in the abundance of probiotics (Lactobacillus, Ruminococcus, etc.) and down-regulation in the number of harmful bacteria (Desulfovibrio, Prevotella, etc.) were observed in all RRS-treated groups. In summary, this work suggested that RRS prepared using heat-stable α-amylase and glucoamylase could be a potential functional component for amelioration of T2DM applied in the fields of food and pharmaceutics.

A plant NLR receptor employs ABA central regulator PP2C-SnRK2 to activate antiviral immunity.

Defence against pathogens relies on intracellular nucleotide-binding, leucine-rich repeat immune receptors (NLRs) in plants. Hormone signaling including abscisic acid (ABA) pathways are activated by NLRs and play pivotal roles in defence against different pathogens. However, little is known about how hormone signaling pathways are activated by plant immune receptors. Here, we report that a plant NLR Sw-5b mimics the behavior of the ABA receptor and directly employs the ABA central regulator PP2C-SnRK2 complex to activate an ABA-dependent defence against viral pathogens. PP2C4 interacts with and constitutively inhibits SnRK2.3/2.4. Behaving in a similar manner as the ABA receptor, pathogen effector ligand recognition triggers the conformational change of Sw-5b NLR that enables binding to PP2C4 via the NB domain. This receptor-PP2C4 binding interferes with the interaction between PP2C4 and SnRK2.3/2.4, thereby releasing SnRK2.3/2.4 from PP2C4 inhibition to activate an ABA-specific antiviral immunity. These findings provide important insights into the activation of hormone signaling pathways by plant immune receptors.

Garlic Origin Traceability and Identification Based on Fusion of Multi-Source Heterogeneous Spectral Information.

The chemical composition and nutritional content of garlic are greatly impacted by its production location, leading to distinct flavor profiles and functional properties among garlic varieties from diverse origins. Consequently, these variations determine the preference and acceptance among diverse consumer groups. In this study, purple-skinned garlic samples were collected from five regions in China: Yunnan, Shandong, Henan, Anhui, and Jiangsu Provinces. Mid-infrared spectroscopy and ultraviolet spectroscopy were utilized to analyze the components of garlic cells. Three preprocessing methods, including Multiple Scattering Correction (MSC), Savitzky-Golay Smoothing (SG Smoothing), and Standard Normalized Variate (SNV), were applied to reduce the background noise of spectroscopy data. Following variable feature extraction by Genetic Algorithm (GA), a variety of machine learning algorithms, including XGboost, Support Vector Classification (SVC), Random Forest (RF), and Artificial Neural Network (ANN), were used according to the fusion of spectral data to obtain the best processing results. The results showed that the best-performing model for ultraviolet spectroscopy data was SNV-GA-ANN, with an accuracy of 99.73%. The best-performing model for mid-infrared spectroscopy data was SNV-GA-RF, with an accuracy of 97.34%. After the fusion of ultraviolet and mid-infrared spectroscopy data, the SNV-GA-SVC, SNV-GA-RF, SNV-GA-ANN, and SNV-GA-XGboost models achieved 100% accuracy in both training and test sets. Although there were some differences in the accuracy of the four models under different preprocessing methods, the fusion of ultraviolet and mid-infrared spectroscopy data yielded the best outcomes, with an accuracy of 100%. Overall, the combination of ultraviolet and mid-infrared spectroscopy data fusion and chemometrics established in this study provides a theoretical foundation for identifying the origin of garlic, as well as that of other agricultural products.

Hypoglycemic Activity of Rice Resistant-Starch Metabolites: A Mechanistic Network Pharmacology and In Vitro Approach.

Rice (Oryza sativa L.) is one of the primary sources of energy and nutrients needed by the body, and rice resistant starch (RRS) has been found to have hypoglycemic effects. However, its biological activity and specific mechanisms still need to be further elucidated. In the present study, 52 RRS differential metabolites were obtained from mouse liver, rat serum, canine feces, and human urine, and 246 potential targets were identified through a literature review and database analysis. A total of 151 common targets were identified by intersecting them with the targets of type 2 diabetes mellitus (T2DM). After network pharmacology analysis, 11 core metabolites were identified, including linolenic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, lithocholic acid, lithocholylglycine, glycoursodeoxycholic acid, phenylalanine, norepinephrine, cholic acid, and L-glutamic acid, and 16 core targets were identified, including MAPK3, MAPK1, EGFR, ESR1, PRKCA, FYN, LCK, DLG4, ITGB1, IL6, PTPN11, RARA, NR3C1, PTPN6, PPARA, and ITGAV. The core pathways included the neuroactive ligand-receptor interaction, cancer, and arachidonic acid metabolism pathways. The molecular docking results showed that bile acids such as glycoursodeoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, lithocholic acid, deoxycholic acid, and cholic acid exhibited strong docking effects with EGFR, ITGAV, ITGB1, MAPK3, NR3C1, α-glucosidase, and α-amylase. In vitro hypoglycemic experiments further suggested that bile acids showed significant inhibitory effects on α-glucosidase and α-amylase, with CDCA and UDCA having the most prominent inhibitory effect. In summary, this study reveals a possible hypoglycemic pathway of RRS metabolites and provides new research perspectives to further explore the therapeutic mechanism of bile acids in T2DM.

Identifying the Spatial Architecture That Restricts the Proximity of CD8+ T Cells to Tumor Cells in Pancreatic Ductal Adenocarcinoma.

The anti-tumor function of CD8+ T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8+ T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8+ T cells in human pancreatic ductal adenocarcinoma (PDAC). The cellular neighborhood algorithm was used to identify a total of six conserved and distinct cellular neighborhoods. Among these, one unique spatial architecture of CD8+ T and CD4+ T cell-enriched neighborhoods enriched the majority of CD8+ T cells, but heralded a poor prognosis. The proximity analysis revealed that the CD8+ T cells in this spatial architecture were significantly closer to themselves and the CD4+ T cells than to the tumor cells. Collectively, we identified a unique spatial architecture that restricted the proximity of CD8+ T cells to tumor cells in the tumor microenvironment, indicating a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner and providing new insights into the biology of PDAC.

Electrical impedance tomography as a bedside assessment tool for COPD treatment during hospitalization.

For patients with chronic obstructive pulmonary disease (COPD), the assessment of the treatment efficacy during hospitalization is of importance to the optimization of clinical treatments. Conventional spirometry might not be sensitive enough to capture the regional lung function development. The study aimed to evaluate the feasibility of using electrical impedance tomography (EIT) as an objective bedside evaluation tool for the treatment of acute exacerbation of COPD (AECOPD). Consecutive patients who required hospitalization due to AECOPD were included prospectively. EIT measurements were conducted at the time of admission and before the discharge simultaneously when a forced vital capacity maneuver was conducted. EIT-based heterogeneity measures of regional lung function were calculated based on the impedance changes over time. Surveys for attending doctors and patients were designed to evaluate the ease of use, feasibility, and overall satisfaction level to understand the acceptability of EIT measurements. Patient-reported outcome assessments were conducted. User's acceptance of EIT technology was investigated with a five-dimension survey. A total of 32 patients were included, and 8 patients were excluded due to the FVC maneuver not meeting the ATS criteria. Spirometry-based lung function was improved during hospitalization but not significantly different (FEV1 %pred.: 35.8% ± 6.7% vs. 45.3% ± 8.8% at admission vs. discharge; p = 0.11. FVC %pred.: 67.8% ± 0.4% vs. 82.6% ± 5.0%; p = 0.15. FEV1/FVC: 0.41 ± 0.09 vs. 0.42 ± 0.07, p = 0.71). The symptoms of COPD were significantly improved, but the correlations between the improvement of symptoms and spirometry FEV1 and FEV1/FVC were low (R = 0.1 and -0.01, respectively). The differences in blood gasses and blood tests were insignificant. All but one EIT-based regional lung function parameter were significantly improved after hospitalization. The results highly correlated with the patient-reported outcome assessment (R > 0.6, p < 0.001). The overall acceptability score of EIT measurement for both attending physicians and patients was high (4.1 ± 0.8 for physicians, 4.5 ± 0.5 for patients out of 5). These results demonstrated that it was feasible and acceptable to use EIT as an objective bedside evaluation tool for COPD treatment efficacy.

Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. METHODS: We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. RESULTS: Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. CONCLUSIONS: We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.

Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB.

In brief: The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. Abstract: Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF-κB activity compared with wild-type controls. Finally, we applied a selective NF-κB inhibitor named PDTC to validate the role of NF-κB in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.

Effect of Reduced INR in Early Pregnancy on the Occurrence of Preeclampsia: A Retrospective Cohort Study.

To investigate the effect of reduced early-pregnancy activated partial thrombin time (APTT), prothrombin time (PT), and international standardized ratio (INR) on the risk of preeclampsia. A total of 8549 pregnant women with singleton births were included. Early pregnancy APTT, PT, and INR levels, with age, birth, prepregnancy body mass index, fibrinogen (FBG), thrombin time (TT), D-dimer (DD2), antithrombin III (ATIII), fibrin degradation products (FDP) as confounders, generalized linear model of APTT, the relative risk of PT and INR when INR reduction. After adequate adjustment for confounders, the relative risk of preeclampsia was 0.703 for every 1 s increase in plasma PT results in early pregnancy, and for every 0.1 increase in plasma INR results, the relative risk of preeclampsia was 0.767. With a PT less than the P25 quantile (<11 s), the relative risk of preeclampsia was 1.328. The relative risk of preeclampsia at an INR less than the P25 quantile (<0.92) was 1.24. There was no statistical association between APTT on the risk of preeclampsia. The relative risk of preeclampsia is strongly associated with a decrease in PT and INR in early pregnancy. PT and INR in early pregnancy were a potential marker in the risk stratification of preeclampsia. Focusing on reduced PT and INR levels in early pregnancy can help to identify early pregnancies at risk for preeclampsia.

Abnormal phosphorylation / dephosphorylation and Ca2+ dysfunction in heart failure.

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.

Automated and ultrasensitive point-of-care glycoprotein detection using boronate-affinity enhanced organic electrochemical transistor patch.

Quantifying trace glycoproteins in biofluids requires ultrasensitive components, but feedback is not available in the current portable platforms of point-of-care (POC) diagnosis technologies. A compact and ultrasensitive bioelectrochemical patch was based on boronate-affinity amplified organic electrochemical transistors (BAAOECTs) for POC use was developed to overcome this dilemma. Benefit from the cascading signal enhancement deriving from boronate-affinity targeting multiple regions of glycoprotein and OECTs' inherent signal amplification capability, the BAAOECTs achieved a detection limit of 300 aM within 25 min, displaying about 3 orders of magnitude improvement in sensitivity compared with the commercial electrochemical luminescence (ECL) kit. By using a microfluidic chip, a microcontroller module, and a wireless sensing system, the testing workflows of the above patch was automated, allowing for running the sample-to-answer pipeline even in a resource-limited environment. The reliability of such portable biosensing platform is well recognized in clinical diagnostic applications of heart failure. Overall, the remarkable enhanced sensitivity and automated workflow of BAAOECTs biosensing platform provide a prospective and generalized design policy for expanding the POC diagnosis capabilities of glycoproteins.

Visualizing pursed lips breathing of patients with chronic obstructive pulmonary disease through evaluation of global and regional ventilation using electrical impedance tomography.

Objective. This study aims to explore the possibility of using electrical impedance tomography (EIT) to assess pursed lips breathing (PLB) performance of patients with chronic obstructive pulmonary disease (COPD).Methods. 32 patients with COPD were assigned equally to either the conventional group or the EIT guided group. All patients were taught to perform PLB by a physiotherapist without EIT in the conventional group or with EIT in the EIT guided group for 10 min. The ventilation of all patients in the final test were continuously monitored using EIT and the PLB performances were rated by another physiotherapist before and after reviewing EIT. The global and regional ventilation between two groups as well as between quite breathing (QB) and PLB were compared and rating scores with and without EIT were also compared.Results.For global ventilation, the inspiratory depth and the ratio of expiratory-to-inspiratory time during PLB was significantly larger than those during QB for both group (P< 0.001). The inspiratory depth and the ratio of expiratory-to-inspiratory time during PLB in the EIT guided group were higher compared to those in the conventional group (P< 0.001), as well as expiratory flow expiratory uniformity and respiratory stability were better (P< 0.001). For regional ventilation, center of ventilation significantly decreased during PLB (P< 0.05). The expiratory time constant during PLB in the EIT guided group was greater than that in the conventional group (P< 0.001). Additionally, Bland-Altman plots analysis suggested a high concordance between subjective rating and rating with the help of EIT, but the score rated after EIT observation significantly lower than that rated subjectively in both groups (score drop of -2.68 ± 1.1 in the conventional group and -1.19 ± 0.72 in the EIT guided group,P< 0.01).Conclusion.EIT could capture the details of PLB maneuver, which might be a potential tool to quantitatively evaluate PLB performance and thus assist physiotherapists to teach PLB maneuver to patients.

Pyruvate is modified by tea/coffee metabolites and reversely correlated with multiple system atrophy and Parkinson's disease.

Introduction: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods: To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results: We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions: This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.

Medical service quality evaluation based on LDA and sentiment analysis: Examples of seven chronic diseases.

Objective: In this article, we investigate how chronic noncommunicable disease (CND) patients evaluate the medical service, and what obstacles exist in this process, which is useful for hospitals to improve efficiency and enhance patient satisfaction. Methods: Based on the total number of CND patients in China, 7 CNDs were selected as the evaluation objects, and then selected the Haodaifu website as the data source, crawled 15,682 medical service reviews, then the 9 themes were analyzed by the LDA theme model. The evaluation index system of six indicators was constructed based on quality management theory. The binary long short-term memory model was used to analyze the sentiment, and the entropy-valued, TOPSIS and gray correlation model was implemented for medical service quality evaluation; the barrier model was used to find out the key factors limiting medical services. Results: (a) Hypertension was rated at a good level in the degree of gray correlation closeness, bronchitis was rated at a low level and the rest were at an intermediate level. (b) The first two overall barriers were the hospitalization process and registration services which occupy about 30%, respectively. This implies that hospitals should focus on providing registration services and inpatient settings in the future. Conclusion: To promote hospitals to provide better services for patients with CNDs and improve patient satisfaction with medical care. And it is necessary to optimize medical services fundamentally by optimizing the inpatient process and improving the registration process to improve efficiency.

8-shogaol derived from dietary ginger alleviated acute and inflammatory pain by targeting TRPV1.

Ginger, a well-known spice plant, has been used widely in medicinal preparations for pain relief. However, little is known about its analgesic components and the underlying mechanism. Here, we ascertained, the efficacy of ginger ingredient 8-Shogaol (8S), on inflammatory pain and tolerance induced by morphine, and probed the role of TRPV1 in its analgesic action using genetic and electrophysiology approaches. Results showed that 8S effectively reduced nociceptive behaviors of mice elicited by chemical stimuli, noxious heat as well as inflammation, and antagonized morphine analgesic tolerance independent on opioid receptor function. Genetic deletion of TRPV1 significantly abolished 8S' analgesia action. Further calcium imaging and patch-clamp recording showed that 8S could specifically activate TRPV1 in TRPV1-expressing HEK293T cells and dorsal root ganglion (DRG) neurons. The increase of [Ca2+]i in DRG was primarily mediated through TRPV1. Mutational and computation studies revealed the key binding sites for the interactions between 8S and TRPV1 included Leu515, Leu670, Ile573, Phe587, Tyr511, and Phe591. Further studies showed that TRPV1 activation evoked by 8S resulted in channel desensitization both in vitro and in vivo, as may be attributed to TRPV1 degradation or TRPV1 withdrawal from the cell surface. Collectively, this work provides the first evidence for the attractive analgesia of 8S in inflammatory pain and morphine analgesic tolerance mediated by targeting pain-sensing TRPV1 channel. 8S from dietary ginger has potential as a candidate drug for the treatment of inflammatory pain.

Features of thromboelastogram in populations exposed to or transferring from high altitude.

Background: Thromboelastogram (TEG) is an effective indicator that monitors the dynamic changes of blood coagulation in real-time. It still remains controversial about the performance and influence of coagulation at high altitude. The present study intends to describe comprehensively the clinical features of TEG in populations exposed to or transferring from high altitude. Methods: Two groups were recruited in the present study. Group A included young males who worked at high-altitude (4888 m or 5418 m) areas for some time, while Group B included young males who had recently returned from high-altitude (4888 m or 5418 m) areas. Medical examinations were performed using portable devices. Spearman's test was used to evaluate the correlations between thromboelastogram (TEG) variables and other variables. Logistic regression analysis was used to analyze the factors affecting various abnormal TEG variables. Results: A total of 51 adult males were included in the two groups. Significantly increased reaction time (R) and decreased maximum amplitude (MA) were found in group B (P < 0.05). No significant differences were observed in the comparisons of K and angle between the two groups. Various TEG variables were identified to be correlated with different coagulation and biochemical variables. Logistic regression analysis demonstrated that abnormal R was independently associated with direct bilirubin, and abnormal K was independently associated with the platelet count in Group A (P < 0.05). However, none of the factors were independently associated with abnormal TEG variables in Group B. Conclusion: Populations exposed to or transferring from high altitudes are characterized by different TEG characteristics. Our findings give a comprehensive description of the complex interaction between TEG indexes, coagulation dynamics, and hematological parameters, which can help guide the development of appropriate medical approaches tailored to the unique needs of these populations.

Lysimachiadanxiashanensis, a new species of Primulaceae from Guangdong, China.

Lysimachiadanxiashanensis, a new Primulaceae species, endemic to the Danxia landscape in Guangdong Province, China, is described and illustrated. This new species is morphologically similar to L.pseudohenryi, L.phyllocephala, L.congestiflora and L.kwangtungensis, but it differs from the similar species by its purplish-red plants, petiole without wings, calyx with orange glandular and the corolla margin serrated on upper half with orange-red glandular punctates. This new species belongs to Lysimachiasubgen.Lysimachiasect.Nummularia. Phylogenetic analysis confirmed that L.danxiashanensis is a distinct clade, based on the combined data of ITS and rbcL sequences. The conservation status of the new species was evaluated as Endangered (EN) according to IUCN Red List Categories and Criteria.