The correlation of two bone turnover markers with bone mineral density: a population-based cross-sectional study.

OBJECTIVE: Exploring the correlation between bone turnover marks (BTMs) with lumbar BMD in middle-aged populations. METHODS: The cross-sectional analysis fetched data came from NHANES. The level of serum bone alkaline phosphatase (sBAP) and urinary N-telopeptide (uNTx) were regarded as representative of bone turnover. Lumbar BMD was the outcome of the study. Multivariable linear regression models were utilized to detect the correlation of sBAP and uNTx with Lumbar BMD. RESULTS: The level of sBAP and uNTx was negatively correlated with lumbar BMD in every multivariable linear regression. For sBAP, this inverse correlation was stable in both men and women (P < 0.01). uNTx indicated a negative association after all relevant covariables were adjusted (P < 0.01). The men group remained the negative correlation in gender subgroup analysis (P < 0.01). CONCLUSION: This study indicated that the increased level of sBAP and uNTx associated with lumbar BMD decreased among middle-aged adults. This correlation could prompt researchers to explore further the relationship between bone turnover rate and BMD, which may provide information for the early detection of BMD loss and provide a new strategy for clinical practice.

Vagus nerve stimulated by microbiota-derived hydrogen sulfide mediates the regulation of berberine on microglia in transient middle cerebral artery occlusion rats.

Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.

Catalytic Asymmetric Decarboxylative Mannich Reaction of Malonic Acid Half Esters with Cyclic Aldimines: Access to Chiral ß-Amino Esters and Chroman-4-amines.

An enantioselective decarboxylative Mannich reaction of malonic acid half esters (MAHEs) with cyclic aldimines has been accomplished by employing the copper(I)/(R,R)-Ph-Box complex as chiral catalyst. The desired ß-amino esters were obtained in good to high yields with excellent enantioselectivities. Furthermore, one of the corresponding Mannich products could be readily transformed into chiral chroman-4-amines without loss of enantioselectivity, which is a key intermediate of the human Bradykinin B1 receptor antagonist.

The correlation between high-density lipoprotein cholesterol and bone mineral density in adolescents: a cross-sectional study.

Recent studies have shown a correlation between high-density lipoprotein cholesterol (HDL-C) and bone mineral density (BMD) in adults, but their relationship is unclear in adolescents. This study aimed to explore whether a correlation existed between them among adolescents aged 12-19. Data analyzed in our study was fetched from the National Health and Nutrition Examination Survey (NHANES) database 2011-2018. The relationship between HDL-C level and total BMD value was analyzed by multivariate logistic regression models, fitted smoothing curves, and generalized additive models. 3770 participants participated in this analysis. After adjusting for all relevant covariates involved in this study, we found a negative correlation between HDL-C levels and total bone density in male adolescents.Furthermore, the stratified analysis showed that all covariables-adjusted models retained the negative correlation excepting female, black, or Mexican American subgroups. An inverted U-shaped curve represented the correlation of HDL-C and total BMD among adolescents aged 16 to 19, and the turning point was 1.06 mmol/L. After adjusting for all relevant covariates involved in this study, the study found a negative correlation between HDL-C levels and total BMD in male adolescents aged 12 to 19, particularly among those of races other than Black and Mexican. There was a saturation effect between HDL-C level and total BMD in 16-19-year-old adolescents. The turning point was 1.06 mmol/L. Therefore, HDL-C might be a biomarker to detect bone health and further perform a more detailed examination.

Development and validation of a diabetic retinopathy risk prediction model for middle-aged patients with type 2 diabetes mellitus.

Objectives: The study aims to establish a predictive nomogram of diabetic retinopathy(DR) for the middle-aged population with type 2 diabetes mellitus (T2DM). Methods: This retrospective study screened 931 patients with T2DM between 30 and 59 years of age from the 2011-2018 National Health and Nutrition Examination Survey database. The development group comprised 704 participants from the 2011-2016 survey, and the validation group included 227 participants from the 2017-2018 survey. The least absolute shrinkage and selection operator regression model was used to determine the best predictive variables. The logistic regression analysis built three models: the full model, the multiple fractional polynomial (MFP) model, and the stepwise (stepAIC) selected model. Then we decided optimal model based on the receiver operating characteristic curve (ROC). ROC, calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were used to validate and assess the model. An online dynamic nomogram prediction tool was also constructed. Results: The MFP model was selected to be the final model, including gender, the use of insulin, duration of diabetes, urinary albumin-to-creatinine ratio, and serum phosphorus. The AUC was 0.709 in the development set and 0.704 in the validation set. According to the ROC, calibration curves, and Hosmer-Lemeshow test, the nomogram demonstrated good coherence. The nomogram was clinically helpful, according to DCA. Conclusion: This study established and validated a predictive model for DR in the mid-life T2DM population, which can assist clinicians quickly determining who is prone to develop DR.

Association between urinary nickel with obesity status in adults: A cross-sectional study.

Objectives: The prevalence of obesity is on the rise and is connected to numerous factors. However, the relationship between obesity and nickel has never been investigated. Our study aimed to explore the association between urinary nickel and obesity Status in adults. Methods: From the 2017-2018 National Health and Nutrition Examination Surveys (NHANES), 1,705 participants ≥18 years of age were enrolled. To explore further the relationship among urinary nickel, body mass index (BMI), and waist circumference(WC), Weighted multivariate linear regression analyses and further subgroup analyzes were conducted. Results: Urinary nickel does not correlate with BMI level but positively correlates with WC. In the subgroup analyzed according to sex, Urinary nickel has a positive correlation with BMI and WC in males but has a negative correlation in females. Secondary stratification analysis according to sex and race, Urinary nickel positively correlates with BMI in White males. It also positively correlates with WC in both White and Black males. Conclusions: A correlation was found between urinary nickel levels and BMI and WC in adult males. Adult men, especially those already obese, may need to reduce nickel exposure.

Uncovering the Potential Mechanisms of Coptis chinensis Franch. for Serious Mental Illness by Network Pharmacology and Pharmacology-Based Analysis.

BACKGROUND: Serious mental illness is a disease with complex etiological factors that requires multiple interventions within a holistic disease system. With heat-clearing and detoxifying effects, Coptis chinensis Franch. is mainly used to treat serious mental illness. AIM OF THE STUDY: To explore the underlying mechanisms and therapeutic effect by which Coptis chinensis Franch. treats serious mental illnesses at a holistic level. METHODS: A viable network pharmacology approach was adopted to obtain the potential active ingredients of Coptis chinensis Franch., and serious mental illnesses-related targets and signaling pathways. The interactions between crucial target HTR2A and constituents were verified by molecular docking, and the dynamic behaviors of binding were studied by molecular dynamics simulation. In addition, the anti-anxiety effect of Rhizoma Coptidis (the roots of Coptis chinensis Franch.) extract on lipopolysaccharide-stimulated mice was verified. The anxiety-like behavior was measured through the elevated plus-maze test, light-dark box test, and open field test. Radioimmunoassays detected the levels of interleukin-1ß, tumor necrosis factor-α, interleukin-10, interleukin-4, 5-hydroxytryptamine, and dopamine in the serum, hippocampus, medial prefrontal cortex, and amygdala. Meanwhile, immunohistochemistry protocols for the assessment of neuronal loss (neuron-specific nuclear protein) and synaptic alterations (Synapsin I) were performed in the hippocampus. RESULTS: Based on scientific analysis of the established networks, serious mental illnesses-related targets mostly participated in the calcium signaling pathway, cyclic adenosine monophosphate signaling pathway, mitogen-activated protein kinase signaling pathway, serotonergic and dopaminergic synapse. Molecular docking and molecular dynamics simulation studies illustrated that berberine, epiberberine, palmatine, and coptisine presented favorable binding patterns with HTR2A. The in vivo experiments confirmed that Rhizoma Coptidis extract ameliorated anxiety-like behaviors by improving the survival of neurons, regulating synaptic plasticity, and inhibiting neuroinflammation. CONCLUSION: These findings in the present study led to potential preventative and therapeutic strategies for serious mental illnesses with traditional Chinese medicine.

Observation on clinical effect of Huoxue-Jiangtang decoction formula granules in treating prediabetes: a randomized prospective placebo-controlled double-blind trial protocol.

BACKGROUND: Prediabetes is a hypermetabolic syndrome with blood sugar levels falling between the normal and diabetes. People with prediabetes have a significantly increased chances of developing diabetes, cardiovascular and cerebrovascular diseases, tumors, dementia, and other diseases in the future when compared to the healthy population. However, prediabetes is mainly treated based on lifestyle intervention, currently without targeted drug treatment plan. Traditional Chinese medicine (TCM), which has a longstanding experience, has been shown in clinical studies to be effective for the treatment of diabetes and its related complications. Furthermore, different dosage forms such as decoction and granule have developed gradually in clinical application. Preliminary studies have found that Huoxue-Jangtang Decoction (HJD), with good hypoglycemic and lipid-regulating effects, is potentially one of the complementary and alternative treatments for prediabetes. Therefore, this project intends to perform a prospective clinical study to observe the clinical effectiveness of HJD on prediabetes and the consistency of the efficacy of formula granules and the elixation. METHODS: This is a prospective, randomized, double-blind, and placebo-controlled clinical trial. A total of 183 participants are randomly assigned to HJD Formula Granules plus lifestyle intervention, HJD Elixation plus lifestyle intervention, and placebo plus lifestyle intervention. All subjects undergo 1 day of screening before participating in the study, followed by 84 days of drug intervention and observation. During and after treatment, the main outcome measures include fasting blood glucose and 2-hour postprandial blood glucose. DISCUSSION: This research attempts to verify the clinical efficacy and possible mechanism of HJD in the treatment of prediabetes, and prove the consistency of HJD Formula Granules with HJD Elixation. This study also aims to provide a treatment that is both effective and safe for prediabetic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR2200060813, Registered 12 June 2022.

Involvement of Huanglian Jiedu Decoction on Microglia with Abnormal Sphingolipid Metabolism in Alzheimer's Disease.

Background: Abnormal sphingolipid metabolism is closely related to the occurrence and development of Alzheimer's disease (AD). With heat-clearing and detoxifying effects, Huanglian Jiedu decoction (HLJDD) has been used to treat dementia and improve learning and memory impairments. Purpose: To study the therapeutic effect of HLJDD on AD as it relates to sphingolipid metabolism. Methods: The level of sphingolipids in the brains of APP/PS1 mice and in the supernatant of ß-amyloid (Aß)25-35-induced BV2 microglia was detected by HPLC-QTOF-MS and HPLC-QTRAP-MS techniques, respectively. The co-expression of ionized calcium-binding adapter molecule 1 (Iba1) and Aß as well as four enzymes related to sphingolipid metabolism, including serine palmitoyltransferase 2 (SPTLC2), cer synthase 2 (CERS2), sphingomyelin phosphodiesterase 1 (SMPD1), and sphingomyelin synthase 1 (SGMS1), in the brains of APP/PS1 mice were evaluated by immunofluorescence double labelling. In addition, real-time quantitative reverse transcription-polymerase chain reaction was conducted to determine the mRNA expression of SPTLC2, CERS2, SMPD1, SGMS1, galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2) in Aß25-35-stimulated BV2 microglia. Results: Abnormal sphingolipid metabolism was observed both in APP/PS1 mouse brain tissues and Aß25-35-stimulated BV2 cells. The levels of sphingosine, sphinganine, sphingosine-1-phosphate, sphinganine-1-phosphate and sphingomyelin were significantly reduced, while the levels of ceramide-1-phosphate, ceramide, lactosylceramide and hexosylceramide significantly increased in Aß25-35-stimulated BV2 cells. In AD mice, more microglia were clustered in the Aß-positive region. The decreased level of SGMS1 and increased levels of CERS2, SPTLC and SMPD1 were also found. In addition, the expressions of SPTLC2, CERS2, and SMPD1 in Aß25-35-stimulated BV2 cells were increased significantly, while the expressions of GALC, SPHK2, and SGMS1 were decreased. These changes all showed a significant correction after HLJDD treatment. Conclusion: HLJDD is a good candidate for treating AD. This study provides a novel perspective on the potential roles of the sphingolipid metabolism in AD.

Association between caffeine intake and lumbar spine bone mineral density in adults aged 20-49: A cross-sectional study.

Background: Many epidemiological studies have investigated the connection between coffee intake and bone mineral density (BMD), but the results are controversial. This study aimed to assess the association between caffeine consumption and lumbar BMD in adults aged 20-49. Methods: From a cross-sectional study based on a large sample of the National Health and Nutrition Examination Survey 2011-2018. After controlling for confounders, the weighted multivariate linear regression model was created and stratified by age, gender, and race for subgroup analysis. In addition, we simultaneously stratified analysis by age and sex and divided caffeine intake into quartiles to assess the association between coffee intake and BMD. Results: Caffeine intake was not significantly linked with lumbar BMD in this study of 7041 adults. In subgroup studies stratified by age, there was a significant correlation between lumbar BMD and caffeine consumption in participants aged 30-39 and 40-49. In females, there was a positive correlation between lumbar BMD and coffee consumption stratified by gender. When evaluated by race, the association between lumbar BMD and caffeine intake was independent of race. Consequently, when stratifying for age, sex, and coffee intake quartiles, a significant positive correlation was discovered between the fourth coffee intake quartile and lumbar BMD in females aged 30-39. In addition, a negative correlation was discovered between coffee consumption and lumbar BMD in males aged 40-49. Conclusions: Our research indicates that drinking coffee may benefit 30-39 women's lumbar BMD, but it may adversely affect men aged 40-49.

Identification and validation of immune and prognosis-related genes in hepatocellular carcinoma: A review.

PURPOSE: Bioinformatics methods were used to identify the key genes associated with the immune microenvironment of hepatocellular carcinoma (HCC) to construct an immune risk prognostic model (IRPM) and to study the correlation between IRPM's risk groups and immune characteristics of patients with HCC. METHODS: HCC transcriptome sequencing information was searched for immune-related genes (IRGs) that were regularly expressed in cancer tissues. The IRGs, which were strongly linked to overall survival were screened; the prognostic characteristics model was constructed using Cox regression analysis. IRPM's independent prognostic value was explored; Kaplan-Meier survival and receiver-operating characteristic curves were used to determine the model prediction ability in the led-to queue. RESULTS: Patients in the high-risk group (HRG) showed significantly poor outcomes. Gene Set Enrichment Analysis revealed factors involved in both the HRG and low risk group. Immune-related hub genes (IRHGs) and drug sensitivity expression levels revealed that all IRHGs were correlated with drug sensitivity for certain chemotherapy drugs. CONCLUSION: The study results may serve as a reference for improving prognosis, early screening, and immunotherapy in patients with HCC.

Effect of obesity status on adolescent bone mineral density and saturation effect: A cross-sectional study.

Background: The effect of obesity status on bone mineral density (BMD) in adolescents and whether there is a saturation effect is still insufficient. A cross-sectional study of adolescents aged 12-19 was conducted to investigate them. Methods: Weighted multivariate linear regression models were used to assess the relationship between obesity status and BMD via datasets from the National Health and Nutrition Examination Survey 2011-2018. The nonlinear relationships and saturation values were ascertained by fitting smooth curves and analyzing saturation effects. At the same time, the subgroup stratified analysis was also performed. Results: 4056 adolescents were included in this study. We found that body mass index (BMI) and waist circumference (WC) were significantly associated with total BMD, which remained significant in subgroups stratified by age, gender, standing height, and ethnicity. We also noticed an inverse correlation between left leg fat/lean mass and left leg BMD, which was only significant in males and other races. Fitting smooth curve and saturation effect analysis showed that BMI, WC, left leg fat/lean mass, and BMD had a specific saturation effect. There was a saturation effect on bone mineral density in adolescents with a BMI of 22 kg/m2, a WC of 70.5 cm, or a left leg fat/lean mass of 0.2994. Conclusions: We found a positive saturation effect of BMI and WC with BMD and a negative saturation effect of left leg fat/lean mass with BMD. Appropriate obesity status allows adolescents to have better bone mass development but not excessive obesity.

Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics.

Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.

Organocatalytic Asymmetric Decarboxylative Amination of ß-Keto Acids: Access to Optically Active α-Amino Ketones and 1,2-Amino Alcohols.

An organocatalytic asymmetric decarboxylative amination reaction of ß-keto acids is described. Under mild reaction conditions, a series of chiral α-amino ketones were obtained in good to high yields (up to 99%) and enantioselectivities (up to 95% ee). A chiral 1,2-amino alcohol was synthesized from the corresponding decarboxylative amination product in several steps without loss of enantioselectivity.

Stereoselective Synthesis of Fused Aziridines via One-Pot Sequential Decarboxylative Mannich Reaction and Oxidative C-H Amination of Cyclic Imines with ß-Ketoacids.

A novel one-pot sequential transformation via decarboxylative Mannich reaction (DMR) and oxidative C-H amination of cyclic imines with ß-ketoacids is described. This methodology has been utilized to provide access to fused aziridines with excellent diastereoselectivity. Several examples of catalytic enantioselective sequential transformation are presented.

Cyclic aldimines as superior electrophiles for Cu-catalyzed decarboxylative Mannich reaction of ß-ketoacids with a broad scope and high enantioselectivity.

A novel Cu-catalyzed enantioselective decarboxylative Mannich reaction of cyclic aldimines with ß-ketoacids is described. The cyclic structure of these aldimines, in which the C═N bond is constrained in the Z geometry, appears to be important, allowing Mannich condensation to proceed in high yields with excellent enantioselectivities. A chiral chroman-4-amine was synthesized from the decarboxylative Mannich product in several steps without loss of enantioselectivity.

Catalytic enantioselective addition of terminal 1,3-diynes to N-sulfonyl aldimines: access to chiral diynylated carbinamines.

An efficient method for the asymmetric synthesis of chiral diynylated carbinamines is described. The direct catalytic enantioselective addition of terminal 1,3-diynes to N-sulfonyl aldimines proceeded smoothly under mild reaction conditions to produce diynylated carbinamines in up to 98% yield and 99% ee.