Effects of ginseng berry saponins from panax ginseng on glucose metabolism of patients with prediabetes: A randomized, double-blinded, placebo-controlled, crossover trial.

BACKGROUND: Prediabetes strongly increases the risk of type 2 diabetes and cardiovascular events. However, lifestyle intervention, the first-line treatment for prediabetes currently, was inconsistently beneficial for glucose metabolism, and the conventional medicines, such as metformin, is controversial for prediabetes due to the possible side effects. PURPOSE: This study was designed to evaluate the effects of Zhenyuan Capsule, a Chinese patented medicine consisting of ginseng berry saponins extracted from the mature berry of Panax Ginseng, on the glucose metabolism of prediabetic patients as a complementary therapy. STUDY DESIGN AND METHODS: In this randomized, double-Blinded, placebo-controlled, crossover trial, 195 participants with prediabetes were randomized 1:1 to receive either placebo followed by Zhenyuan Capsule, or vice versa, alongside lifestyle interventions. Each treatment period lasted 4 weeks with a 4-week washout period in between. The primary outcomes were the changes in fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (2-h PG) from baseline. Secondary outcomes includes the changes in fasting and 2-h postprandial insulin and C-peptide, the homeostatic model assessment-insulin resistance (HOMA-IR) index and quantitative insulin sensitivity check index (QUICKI) from baseline. Blood lipids and adverse events were also assessed. RESULTS: Compared with placebo, Zhenyuan Capsule caused remarkable reduction in 2-h PG (-0.98 mmol/l) after adjusting treatment order. Zhenyuan Capsule also reduced the fasting and 2-h postprandial levels of insulin and C-peptide, lowered HOMA-IR index (-1.26), and raised QUICKI index (+0.012) when compared to placebo. Additionally, a significant increase in high density lipoprotein cholesterol (HDL-C; +0.25 mmol/l) was found in patients with Zhenyuan Capsule. No serious adverse event occurred during the study. CONCLUSIONS: Among prediabetic patients, Zhenyuan Capsule further reduced 2-h PG level, alleviated insulin resistance and raised HDL-C level on the background of lifestyle interventions. The study protocol is registered with the Chinese Clinical Trial Registry (ChiCTR2000034000).

No genetic link between Parkinson's disease and SARS-CoV-2 infection: a two-sample Mendelian randomization study.

Objective: Existing literature has not clearly elucidated whether SARS-CoV-2 infection increases the incidence of Parkinson's disease or if Parkinson's disease patients are more susceptible to the effects of SARS-CoV-2 infection. To clarify the issue, this study employs a genetic epidemiological approach to investigate the association. Methods: This study utilizes a two-sample Mendelian randomization analysis. The primary analysis employs the inverse variance-weighted (IVW) method, supplemented by secondary analyses including MR-Egger regression, weighted median, IVW radial method, and weighted mode, to evaluate the bidirectional causal relationship between Parkinson's disease and SARS-CoV-2 infection. Results: IVW results showed no genetic causality between SARS-CoV-2 susceptibility, hospitalization rate and severity and Parkinson's disease. (IVW method: p = 0.408 OR = 1.10 95% CI: 0.87 ~ 1.39; p = 0.744 OR = 1.11 95% CI: 0.94 ~ 1.09; p = 0.436 OR = 1.05 95% CI: 0.93 ~ 1.17). Parkinson's disease was not genetically associated with susceptibility to new crown infections, hospitalization rates, and severity (IVW method: p = 0.173 OR = 1.01 95% CI: 0.99 ~ 1.03; p = 0.109 OR = 1.05 95% CI: 0.99 ~ 1.12; p = 0.209 OR = 1.03 95% CI: 0.99 ~ 1.07). MR-Egger regression, weighted median, IVW radial method, and weighted mode results are consistent with the results of the IVW method. Conclusion: This study does not support a genetic link between Parkinson's disease and SARS-CoV-2 infection, and the association observed in previous cohort studies and observational studies may be due to other confounding factors.

CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects.

Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet-induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination-proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis.

Mitochondrial glycerol 3-phosphate dehydrogenase deficiency exacerbates lipotoxic cardiomyopathy.

Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocyte-specific deletion of mGPDH promotes high-fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet-induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes.

Plasma Asprosin Concentrations are Associated with Progression of Diabetic Kidney Disease.

Purpose: To explore the expression of asprosin in subjects with pre-DKD and DKD and to analyze its relationship with kidney injury, inflammation, and glucose and lipid metabolism. Methods: Based on urine albumin:creatinine ratio (UACr), participants were divided into DM, pre-DKD, and DKD groups. Relevant human physiological and biochemical parameters were detected in the three groups. Results: We found relatively higher levels of asprosin in both pre-DKD and DKD groups than the DM group. Moreover, data from the Nephroseq database support increased gene expression of asprosin in kidney tissue from DKD patients. Further correlation analysis revealed that the plasma asprosin level was positively correlated with age, waist circumference, waist:hip ratio, systolic blood pressure, creatinine, UACr, triglycerides, HDL-c, fasting insulin, HOMA-IR, and the inflammatory marker G3P and negatively associated with eGFR. Multiple logistical regression analysis showed that asprosin concentration was significantly associated with pre-DKD and DKD after adjusting for sex, age, BMI, WHR, and HOMA-IR, while this correlation was lost after controlling for G3P. Conclusion: Plasma asprosin is associated with kidney injury in diabetic conditions, and this association might be connected through inflammatory response. Further studies are needed to assess the role and mechanism of asprosin in DKD.

Association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event.

BACKGROUND: To test whether dietary magnesium is associated with 10-year risk of a first hard atherosclerotic cardiovascular disease event. METHODS: In this cross-sectional study, a total of 2980 participants, aged 40 to 79 years, from the National Health and Nutrition Examination Survey 1999-2018 were analyzed. The association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease (ASCVD) event was assessed following adjustment for clinical risk factors, including sex, age, race, educational level, body mass index (BMI), alcohol drinking, smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension treated or not, diabetes and low density lipoprotein cholesterol (LDL-C), total energy and dietary fiber. We performed multivariate linear regression models and smooth curve fittings to evaluate the associations between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event. RESULTS: We observed a significant inverse association between dietary magnesium and predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event (ß=-0.01, [95% CI: -0.01, -0.00], P = 0.0256). We divided the 10-year risk into two categories, with a statistically significant reduction of ASCVD risk when the 10-year risk ≥7.5% (ß=-0.01, [95% CI: -0.01, -0.00], P = 0.0440). CONCLUSIONS: Dietary magnesium intake was inversely associated with the predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event.

Enhanced TfR1 Recognition of Myocardial Injury after Acute Myocardial Infarction with Cardiac Fibrosis via Pre-Degrading Excess Fibrotic Collagen.

The fibrosis process after myocardial infarction (MI) results in a decline in cardiac function due to fibrotic collagen deposition and contrast agents' metabolic disorders, posing a significant challenge to conventional imaging strategies in making heart damage clear in the fibrosis microenvironment. To address this issue, we developed an imaging strategy. Specifically, we pretreated myocardial fibrotic collagen with collagenase I combined with human serum albumin (HSA-C) and subsequently visualized the site of cardiac injury by near-infrared (NIR) fluorescence imaging using an optical contrast agent (CI, CRT-indocyanine green) targeting transferrin receptor 1 peptides (CRT). The key point of this strategy is that pretreatment with HSA-C can reduce background signal interference in the fibrotic tissue while enhancing CI uptake at the heart lesion site, making the boundary between the injured heart tissue and the normal myocardium clearer. Our results showed that compared to that in the untargeted group, the normalized fluorescence intensity of cardiac damage detected by NIR in the targeted group increased 1.28-fold. The normalized fluorescence intensity increased 1.21-fold in the pretreatment group of the targeted groups. These data demonstrate the feasibility of applying pretreated fibrotic collagen and NIR contrast agents targeting TfR1 to identify ferroptosis at sites of cardiac injury, and its clinical value in the management of patients with MI needs further study.

Elucidating Iron Metabolism through Molecular Imaging.

Iron is essential for many physiological processes, and the dysregulation of its metabolism is implicated in the pathogenesis of various diseases. Recent advances in iron metabolism research have revealed multiple complex pathways critical for maintaining iron homeostasis. Molecular imaging, an interdisciplinary imaging technique, has shown considerable promise in advancing research on iron metabolism. Here, we comprehensively review the multifaceted roles of iron at the cellular and systemic levels (along with the complex regulatory mechanisms of iron metabolism), elucidate appropriate imaging methods, and summarize their utility and fundamental principles in diagnosing and treating diseases related to iron metabolism. Utilizing molecular imaging technology to deeply understand the complexities of iron metabolism and its critical role in physiological and pathological processes offers new possibilities for early disease diagnosis, treatment monitoring, and the development of novel therapies. Despite technological limitations and the need to ensure the biological relevance and clinical applicability of imaging results, molecular imaging technology's potential to reveal the iron metabolic process is unparalleled, providing new insights into the link between iron metabolism abnormalities and various diseases.

Intelligent chemical profiling of 73 edible flowers by liquid chromatography-high resolution mass spectrometry combined with HRMS database and their authentication based on large-scale fingerprints.

A commercial high-resolution MS database "TCM-PCDL" was innovatively introduced to automatically identify multi-components in 73 edible flowers rapidly and accurately by liquid chromatography-high resolution mass spectrometry, which can be time-consuming and labor-intensive in traditional manual method. The database encompasses over 2565 natural products with various energy levels. Unknown compounds can be identified through direct matching and scoring MS2 spectra with database. A total of 870 compounds were identified from 73 flowers, with polyphenols constituting up to 75%. Focusing on polyphenols, a high performance liquid chromatography (HPLC) method was developed to generate fingerprints from 510 batches, establishing an "HPLC database" that enabled accurate authentication using similarity scores and rankings. This method demonstrated an accuracy rate of 100% when applied to 30 unknown samples. For flowers prone to confusion, additional statistical analysis methods could be employed as aids in authentication. This study provides valuable insights for large-scale sample chemical profiling and authentication.

Comprehensive HRMS Screening and Risk Assessments of Aristolochic Acid Analogues in Asari Radix et Rhizoma and Related Commercial Health Products.

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.

Trends in gut-heart axis and heart failure research (1993-2023): A bibliometric and visual analysis.

Background: The incidence of heart failure, the terminal stage of several cardiovascular diseases, is increasing owing to population growth and aging. Bidirectional crosstalk between the gut and heart plays a significant role in heart failure. This study aimed to analyze the gut-heart axis and heart failure from a bibliometric perspective. Methods: We extracted literature regarding the gut-heart axis and heart failure from the Web of Science Core Collection database (January 1, 1993, to June 30, 2023) and conducted bibliometric and visualization analyses using Microsoft Excel, CiteSpace, VOSviewer, and the R package "bibliometrix." Results: The final analysis included 1646 articles with an average of 35.38 citations per article. Despite some fluctuations, the number of articles published per year has steadily increased over the past 31 years, particularly since 2018. A total of 9412 authors from 2287 institutions in 86 countries have contributed to this field. The USA and China have been the most productive countries, with the Cleveland Clinic in the USA and Charité-Universitätsmedizin Berlin in Germany being the most active institutions. The cooperation between countries/regions and institutions was relatively close. Professor Tang WHW was the most productive author in the field and the journal Shocks published the highest number of articles. "Heart failure," "gut microbiota," "trimethylamine N-oxide," and "inflammation" were the most common keywords, representing the current research hotspots. The keyword burst analysis indicated that "gut microbiota" and "short-chain fatty acids" are the current frontier research topics in this field. Conclusion: Research on the gut-heart axis and heart failure is increasing. This bibliometric analysis indicated that the mechanisms associated with the gut-heart axis and heart failure, particularly the gut microbiota, trimethylamine N-oxide, inflammation, and short-chain fatty acids, will become hotspots and emerging trends in research in this field. These findings provide valuable insights into current research and future directions.

Efficacy and safety of Qingda granule versus valsartan capsule in Chinese grade 1 hypertensive patients with low-moderate risk: A randomized, double-blind, double dummy, non-inferiority, multi-center trial.

BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.

Hypertension in non-obese children and BMI in adulthood: the Bogalusa heart study.

OBJECTIVE: This study explored the association between hypertension(HTN) in non-obese children body mass index (BMI) in adulthood. METHODS: A retrospective analysis of 1111 participants from the Bogalusa Heart Study was conducted, in which data on hypertension history during childhood in non-obese children, anthropometric and cardiovascular risk factors and other indicators from cross-sectional examinations in adulthood were collected. BMI was used as both a continuous and a categorical variable, and multivariate linear regression modelling and logistic regression modelling were used. RESULTS: Of the 1111 participants finally enrolled, 40 (3.60%) had HTN during childhood. After adjusting for demographic characteristics, lipid, glucose and insulin levels in childhood, and smoking status, alcohol intake, and disease history as adults, HTN among non-obese children was positively associated with BMI in adulthood (ß = 2.64 kg/m2, 95% CI: 0.88-4.40, P = 0.0033), and the odds of being overweight or obese was 3.71 times higher in the group with a history of hypertension in childhood than those without a history of HTN(95% CI: 1.11-12.46, P = 0.0337). CONCLUSION: Among non-obese children, hypertension is at risk for higher levels of BMI in adulthood. Identifying and controlling blood pressure and childhood may aid in the prevention of adult obesity.

Quantitative visualization of myocardial ischemia-reperfusion-induced cardiac lesions via ferroptosis magnetic particle imaging.

Myocardial ischemia-reperfusion (MI/R) injury is a complication in vascular reperfusion therapy for MI, occurring in approximately 60% of patients. Ferroptosis is an important process in the development of MI/R cardiac lesions. Transferrin receptor 1 (TfR1), a marker of ferroptosis, corresponds to the changes in MI/R cardiac lesions and is expected to be a biomarker for detecting MI/R-induced ferroptosis. However, the noninvasive in vivo visualization of ferroptosis in MI/R is a big challenge. Thus, this study aimed to develop a novel multimodal imaging platform to identify markers of MI/R cardiac lesions in vivo through targeting TfR1. Methods: Magnetic particle imaging (MPI) modality for ferroptosis based on superparamagnetic cubic-iron oxide nanoparticles (SCIO NPs), named feMPI, has been developed. FeMPI used TfR1 as a typical biomarker. The feMPI probe (SCIO-ICG-CRT-CPPs NPs, CCI NPs) consists of SCIO NPs, TfR1-targeting peptides (CRT), cell-penetrating peptides (CPPs), and indocyanine green (ICG). The specificity and sensitivity of CCI NPs in the MI/R mouse model were evaluated by MPI, magnetic resonance imaging (MRI), and near-infrared (NIR) fluorescent imaging. Results: The intensity of the MPI signal correlates linearly with the percentage of infarct area in MI/R stained by TTC, enabling a quantitative assessment of the extent of cardiac lesions. Notably, these findings are consistent with the standard clinical biochemical indicators in MI/R within the first 24 h. FeMPI detects cardiac injury approximately 48 h prior to the current clinical imaging detection methods of MI/R. Conclusion: The feMPI strategy can be a powerful tool for studying the process of MI/R-induced ferroptosis in vivo, providing clues for molecular imaging and drug development of ferroptosis-related treatments.

Based on functional and histopathological correlations: is diffusion kurtosis imaging valuable for noninvasive assessment of renal damage in early-stage of chronic kidney disease?

PURPOSE: To evaluate the potential of 3 T magnetic resonance diffusion kurtosis imaging (DKI) in assessing the renal damage in early-stage of chronic kidney disease (CKD) patients with normal or slightly changed functional index, using histopathology as reference standard. METHODS: 49 CKD patients and 18 healthy volunteers were recruited in this study. CKD patients were divided into two groups based on estimated glomerular filtration rate (eGFR): Study group I (eGFR ≥ 90 ml/min/1.73 m2 [n = 20]) and Study group II (eGFR < 90 ml/min/1.73 m2 [n = 29]). DKI was performed in all participants. The DKI parameters (mean kurtosis [MK], mean diffusivity [MD], fractional anisotropy [FA]) of renal cortex and medulla were measured. The differences of parenchymal MD, MK and FA values among the different groups were compared. The correlations between DKI parameters and clinicopathological characteristics were assessed. Diagnostic performance of DKI to assess renal damage in early-stage of CKD was analyzed. RESULTS: The cortex MD and MK showed significant difference among three groups (P < 0.05): trend of cortex MD: Study group II < Study group I < control group; trend of cortex MK: control group < Study group I < Study group II. The cortex MD and MK and medulla FA were correlated with eGFR and Interstitial fibrosis/Tubular atrophy score (0.3 < r < 0.5). Cortex MD and MK yielded an AUC of 0.752 for differentiating healthy volunteers from CKD patients with eGFR ≥ 90 ml/min/1.73 m2. CONCLUSION: DKI shows potential in non-invasive and multi-parameter quantitative assessment of renal damage in early-stage of CKD patients and provide additional information for changes in renal function and histopathology.

Species discrimination of multiple botanical origins of Fritillaria species based on infrared spectroscopy, thin layer chromatography-image analysis and untargeted metabolomics.

BACKGROUND: Fritillaria Bulbus (FB), a precious medicinal herb renowned for its heat-clearing, lung-moistening, cough-relieving and phlegm-eliminating effects. In pursuit of profits, unscrupulous merchants have engaged in the substitution or adulteration of valuable varieties with cheaper alternatives. It is, therefore, urgent to develop effective technical approaches to identify FBs from adulterants. METHODS: This paper employed infrared spectroscopy (IR), thin layer chromatography-image analysis (TLC-IA), and untargeted metabolomics techniques to discriminate ten species of FBs. RESULTS: Five species of FBs were successfully differentiated using mid-infrared spectroscopy. Furthermore, the power of TLC-IA technology allowed the differentiation of five species of FBs and two origins of FCBs (Fritillariae Cirrhosae Bulbus). Remarkably, through the application of untargeted metabolomics technique, the precise discrimination of five species of FBs, as well as three origins of FCBs were accomplished. Moreover, a comprehensive identification of 101 markers that reliably distinguished diverse FBs was achieved through the employment of untargeted metabolomics technique. CONCLUSION: The investigation presented powerful means of detection for assuring the quality control of Fritillaria herbs.

Dock5 Deficiency Promotes Proteinuric Kidney Diseases via Modulating Podocyte Lipid Metabolism.

Podocytes are particularly sensitive to lipid accumulation, which has recently emerged as a crucial pathological process in the progression of proteinuric kidney diseases like diabetic kidney disease and focal segmental glomerulosclerosis. However, the underlying mechanism remains unclear. Here, podocytes predominantly expressed protein dedicator of cytokinesis 5 (Dock5) is screened to be critically related to podocyte lipid lipotoxicity. Its expression is reduced in both proteinuric kidney disease patients and mouse models. Podocyte-specific deficiency of Dock5 exacerbated podocyte injury and glomeruli pathology in proteinuric kidney disease, which is mainly through modulating fatty acid uptake by the liver X receptor α  (LXRα)/scavenger receptor class B (CD36) signaling pathway. Specifically, Dock5 deficiency enhanced CD36-mediated fatty acid uptake of podocytes via upregulating LXRα in an m6 A-dependent way. Moreover, the rescue of Dock5 expression ameliorated podocyte injury and proteinuric kidney disease. Thus, the findings suggest that Dock5 deficiency is a critical contributor to podocyte lipotoxicity and may serve as a promising therapeutic target in proteinuric kidney diseases.

MATLAB language assisted data acquisition and processing in liquid chromatography Orbitrap mass spectrometry: Application to the identification and differentiation of Radix Bupleuri from its adulterants.

Comprehensive and rapid analysis of secondary metabolites like saponins remains challenging. This study aimed to establish a semi-automated workflow for filtration, identification, and characterization of saikosaponins in six Bupleurum species. Radix Bupleuri, a high-sales herbal medicine, is often adulterated, restricting its quality control and applications. Two authentic Radix Bupleuri species and four major adulterants were analyzed through UHPLC-LTQ-Orbitrap-MS for targeted saikosaponin analysis. To reveal trace saikosaponins and obtain quality fragment data, a MATLAB-based process automatically enumerating "sugar chain + aglycone + side chain" combinations and deduplicating generated a predicted saikosaponin database covering all possible saikosaponins as a precursor ion list for comprehensive targeted acquisition. To focus on informative ions and reduce MS analysis workload, we utilized MATLAB to automatically filtrate the false positive ions by MS1 and MS2 spectrometry. The newly established MATLAB-assisted data acquisition approach exhibited 50 % improvement in characterization of targeted saikosaponins. Furthermore, positive and negative ionization workflows were designed for accurate saikosaponins characterization based on fragmentation rules. In total, 707 saikosaponins were characterized, including over 500 potential new compounds and previously unreported C29 aglycones. We identified 25 saikosaponins present in both authentic species but absent in adulterants as potential markers. This unprecedented comprehensive multi-origin species differentiation demonstrates the promise of MATLAB-assisted acquisition and processing to advance saponin identification and standardize the Radix Bupleuri market.

Association between weight change and the predicted 10-year risk for atherosclerosis cardiovascular disease among U.S. older adults: data from National Health and Nutrition Examination Survey 1999-2018.

Background: It remains controversial regarding the association between weight change and cardiovascular disease risk in older adults (aged ≥60 years). This study aimed to evaluate the association between weight change and the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risks in older adults. Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES). Older adults aged 60-79 years who were free of self-reported ASCVD at the time of the NHANES interview were included. Data were collected from January 1999 to December 2018 and analyzed in March 2022. We focused on the associations between weight change and the 10-year ASCVD risks with the percentage change in weight during short-term (1 year) and long-term (10 years), which categorized as moderate to high weight loss (≥10%), small weight loss (5.1-9.9%), stable weight (±5%), small weight gain (5.1-9.9%), and moderate to high weight gain (≥10%). Results: The number of participants was 1,867 (mean age 67.49 years; 42.10% female) for the long-term interval (10 years) in our analysis, and 1894 for the short-term interval (1 years). We only observed an inverse association between long-term weight loss and the 10-year ASCVD risk in fully adjusted model (loss ≥ 10%: ß = 2.52, 95%CI = 0.98, 4.05; loss 5.1% ~ 9.9%: ß = 2.99, 95% CI = 1.30, 4.68), but all intervals of weight gain ≥5% were not significant associated with higher risk than stable weight. However, in the subgroup analyses, the association between long-term weight loss and the 10-year ASCVD risk was not significant in old-old (aged 75-79), obesity (BMI ≥ 35 kg/m2), intentional weight loss, moderate physical activity and diabetics. Conclusion: Older adults (aged 60-79 years) with weight loss >5% over the past 10 years have excess predicted 10-year ASCVD risk. Our study supports the benefits of stable weight in promoting cardiovascular health in older adults.

Optimal concentration of ropivacaine for brachial plexus blocks in adult patients undergoing upper limb surgeries: a systematic review and meta-analysis.

Aim of the Study: Brachial plexus block (BPB) is widely used for patients undergoing upper limb surgeries. Ropivacaine is the most commonly used local anesthetic for BPB. This study aimed to identify the optimal ropivacaine concentration for BPB in adult patients undergoing upper limb surgeries. Materials and Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify randomized controlled trials (RCTs) that compared the effects of different concentrations of ropivacaine for BPB in adult patients undergoing upper limb surgeries. The primary outcomes were the onset time of sensory and motor block. RevMan 5.4 software was used for analysis. The GRADE approach was used to assess evidence quality. Results: Nine studies involving 504 patients were included. Compared to 0.5% ropivacaine, 0.75% ropivacaine shortened the onset time of sensory (WMD, -2.54; 95% CI; -4.84 to -0.24; <0.0001, moderate quality of evidence) and motor blockade (WMD, -2.46; 95% CI, -4.26 to -0.66; p = 0.01; moderate quality of evidence). However, 0.5% and 0.75% ropivacaine provided similar duration time of sensory (WMD, -0.07; 95% CI, -0.88 to 0.74; p = 0.81; high quality of evidence) and motor blockade (WMD, -0.24; 95% CI, -1.12 to 0.65; p = 0.55; high quality of evidence), as well as time to first request for oral analgesia (WMD, -1.57; 95% CI, -3.14 to 0.01; p = 0.5; moderate quality of evidence). Conclusion: Moderate-quality evidence suggested that, in terms of the onset time of sensory and motor blockade, 0.75% ropivacaine is a preferred concentration for BPB in upper limb surgeries. Systematic Review Registration: identifier CRD42023392145.