Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

Identification of KU-55933 as an anti-atherosclerosis compound by using a hemodynamic-based high-throughput drug screening platform.

Several compounds have been used for atherosclerosis treatment, including clinical trials; however, no anti-atherosclerotic drugs based on hemodynamic force-mediated atherogenesis have been discovered. Our previous studies demonstrated that "small mothers against decapentaplegic homolog 1/5" (Smad1/5) is a convergent signaling molecule for chemical [e.g., bone morphogenetic proteins (BMPs)] and mechanical (e.g., disturbed flow) stimulations and hence may serve as a promising hemodynamic-based target for anti-atherosclerosis drug development. The goal of this study was to develop a high-throughput screening (HTS) platform to identify potential compounds that can inhibit disturbed flow- and BMP-induced Smad1/5 activation and atherosclerosis. Through HTS using a Smad1/5 downstream target inhibitor of DNA binding 1 (Id-1) as a luciferase reporter, we demonstrated that KU-55933 and Apicidin suppressed Id-1 expression in AD-293 cells. KU-55933 (10 µM), Apicidin (10 µM), and the combination of half doses of each [1/2(K + A)] inhibited disturbed flow- and BMP4-induced Smad1/5 activation in human vascular endothelial cells (ECs). KU-55933, Apicidin, and 1/2(K + A) treatments caused 50.6%, 47.4%, and 73.3% inhibitions of EC proliferation induced by disturbed flow, respectively, whereas EC inflammation was only suppressed by KU-55933 and 1/2(K + A), but not Apicidin alone. Administrations of KU-55933 and 1/2(K + A) to apolipoprotein E-deficient mice inhibited Smad1/5 activation in ECs in athero-susceptible regions, thereby suppressing endothelial proliferation and inflammation, with the attenuation of atherosclerotic lesions in these mice. A unique drug screening platform has been developed to demonstrate that KU-55933 and its combination with Apicidin are promising therapeutic compounds for atherosclerosis based on hemodynamic considerations.

Perillaldehyde: A promising antibacterial agent for the treatment of pneumonia caused by Acinetobacter baumannii infection.

Perillaldehyde is a monoterpene compound mainly from the medicinal plant Perilla frutescens (L.) Britt., which has hypolipidemic, antioxidant, antibacterial and anti-inflammatory functions. In this investigation, we discovered that Perillaldehyde had powerful antimicrobial activity against Acinetobacter baumannii 5F1, and its minimum inhibitory concentration was 287.08 µg/mL. A. baumannii is a conditionally pathogenic bacterium with a high clinical resistance rate and is a major source of hospital infections, especially in intensive care units, which is one of the main causes of pneumonia. Inflammatory immune response is characteristic of pneumonia caused by A. baumannii infection. The results of our in vitro experiments indicate that Perillaldehyde disrupts the cell membrane of A. baumannii 5F1 and inhibits its quorum sensing to inhibit biofilm formation, among other effects. With an experimental model of murine pneumonia, we investigated that Perillaldehyde decreased NLRP3 inflammasome activation and TNF-α expression in lung tissues by inhibiting the NF-κB pathway, and also impacted MAPKs protein signaling pathway through the activation of TLR4. Notably, the use of high doses of Perillaldehyde for the treatment of pneumonia caused by A. baumannii 5F1 infection resulted in a survival rate of up to 80 % in mice. In summary, we demonstrated that Perillaldehyde is promising as a new drug for the treatment of pneumonia caused by A. baumannii 5F1 infection.

Effect of Vitamin D Supplementation on Bone Mass in Infants With 25-Hydroxyvitamin D Concentrations Less Than 50 nmol/L: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: The dose of supplemental vitamin D needed in infants born with serum 25-hydroxyvitamin D (25[OH]D) concentrations less than 50 nmol/L (ie, 20 ng/mL) is unclear. Objective: To determine whether a higher dose (1000 IU vs 400 IU per day) is required in infants born with 25(OH)D concentrations less than 50 nmol/L for bone mineral accretion across infancy. Design, Setting, and Participants: In this prespecified secondary analysis of a double-blinded randomized clinical trial, conducted from March 2016 to March 2019 in a single center in Greater Montreal, Quebec, Canada, a consecutive sample of 139 healthy term singletons were recruited from 866 infants screened for vitamin D status at birth. Data were analyzed from June 2021 to November 2022. Interventions: Capillary blood was collected 24 to 36 hours after birth to measure serum total 25(OH)D concentrations. Infants with 25(OH)D concentrations less than 50 nmol/L were randomized to receive either 1000 IU or 400 IU per day of oral vitamin D3 supplementation from age 1 to 12 months. Infants with 25(OH)D concentrations of 50 nmol/L or greater formed a reference group. Main Outcomes and Measures: Measures at age 1, 3, 6, and 12 months were preplanned and included whole-body bone mineral content, lumbar spine bone mineral content, and bone mineral density using dual-energy x-ray absorptiometry, and serum 25(OH)D3 using liquid chromatography tandem mass spectrometry. Results: Of 139 included infants, 81 (58.3%) were male, and the median (IQR) gestational age at birth was 39.6 (38.9-40.6) weeks. A total of 49 infants were included in the 1000 IU per day group, 49 infants in the 400 IU per day group, and 41 in the reference group. Mean (SD) whole-body bone mineral content was not different between trial groups over time (1000 IU per day, 173.09 [2.36] g; 400 IU per day, 165.94 [66.08] g). Similarly, no differences were observed in lumbar spine bone mineral content or density. Mean (SD) serum 25(OH)D3 concentrations were significantly higher in the 1000 IU per day group from age 3 to 12 months (3 months, 115.2 [35.3] nmol/L; 6 months, 121.6 [34.4] nmol/L; 12 months, 99.6 [28.8] nmol/L) compared with the 400 IU per day trial group (3 months, 77.4 [23.3] nmol/L; 6 months, 85.1 [18.6] nmol/L; 12 months, 82.3 [14.3] nmol/L). Conclusions and Relevance: In this study, a higher dose of vitamin D supplementation in infants born with 25(OH)D concentrations less than 50 nmol/L did not present advantages to bone mass in infancy. This study supports a standard dose of 400 IU per day of vitamin D supplementation for breastfed infants in Montreal. Trial Registration: ClinicalTrials.gov Identifier: NCT02563015.

[Intrinsic "self-consistent" phenomenon based on holistic view of traditional Chinese medicine].

The fundamental principle of traditional Chinese medicine(TCM) is holism, and it is crucial for TCM to address the key issue of the "holistic view" of Chinese herbal medicine. While the overall regulatory effects of Chinese herbal medicine have been widely recognized, the holistic internal logic of individual ingredients of Chinese herbal medicines require further clarification. In order to comprehensively understand the mechanism of action of Chinese herbal medicine, this paper combined the holistic view of Chinese herbal medicine with differentiation thinking to explore the intrinsic logical relationships within Chinese herbal medicine. Starting from the perspective of the coexistence of multiple components in Chinese herbal medicine, this paper systematically examined the "self-consistent" phenomenon within single Chinese herbal medicine. This phenomenon refers to the consistent or opposing actions of various components in terms of their physical and chemical properties, pharmacokinetic effects, biological effects, flavors and properties, and TCM efficacy. The paper summarized various logical relationships of syndrome differentiation exhibited by the same Chinese herbal medicine, analyzed the underlying reasons, and focused on analyzing external factors affecting the "self-consistent" phenomenon in the efficacy of Chinese herbal medicine, aiming to better elucidate the theoretical basis of the pharmacological effects of Chinese herbal medicine, further enrich the scientific connotation of the holistic view of Chinese herbal medicine, and provide theoretical guidance for the preparation process, compatibility patterns, and formulation design of Chinese herbal medicine.

[Natural regeneration of Larix principis-rupprechtii plantations with different densities and its influencing factors]. / ä¸åŒå¯†åº¦åŽåŒ—è½å¶æ¾æž—å¤©ç„¶æ›´æ–°åŠå ¶å½±å“å› å­.

In this study, we analyzed the natural regeneration of Larix principis-rupprechtii pure plantations with stand densities of 128, 240, 320, 400, 480, 560, 640 and 720 trees·hm-2 in the Guandi Mountains and its influencing factors. The results showed that the regeneration index first increased and then decreased with the increases of stand density, and that the regeneration performance of stand with medium density (400-560 trees·hm-2) was significantly better than other stands. Light conditions, herbaceous plants and litter of the understory had a dual effect on the regeneration of L. principis-rupprechtii. Excessive light, herbaceous plant cover or over-thick litter was not instrumental to the regeneration. Soil organic matter promoted stand regeneration by providing soft soil texture, adequate water content, low phosphorus but high nitrogen. The effects of the examined factors on the regeneration index were as follows: soil water content (0.798) > total nitrogen (0.621) > litter thickness (-0.597) > soil porosity (0.504) > soil organic matter (0.493) > total phosphorus (-0.404) > transmitted total light (-0.274) > herbaceous plants cover (-0.021). In the plantation management, stand density could be controlled at about 480 trees·hm-2 by thinning or replanting, while litter could be cleared properly to improve soil condition and to promote natural regeneration of L. principis-rupprechtii.

Polygenic adaptation contributes to the invasive success of the Colorado potato beetle.

How invasive species cope with novel selective pressures with limited genetic variation is a fundamental question in molecular ecology. Several mechanisms have been proposed, but they can lack generality. Here, we addressed an alternative solution, polygenic adaptation, wherein traits that arise from multiple combinations of loci may be less sensitive to loss of variation during invasion. We tested the polygenic signal of environmental adaptation of Colorado potato beetle (CPB) introduced in Eurasia. Population genomic analyses showed declining genetic diversity in the eastward expansion of Eurasian populations, and weak population genetic structure (except for the invasion fronts in Asia). Demographic history showed that all populations shared a strong bottleneck about 100 years ago when CPB was introduced to Europe. Genome scans revealed a suite of genes involved in activity regulation functions that are plausibly related to cold stress, including some well-founded functions (e.g., the activity of phosphodiesterase, the G-protein regulator) and discrete functions. Such polygenic architecture supports the hypothesis that polygenic adaptation and potentially genetic redundancy can fuel the adaptation of CPB despite strong genetic depletion, thus representing a promising general mechanism for resolving the genetic paradox of invasion. More broadly, most complex traits based on polygenes may be less sensitive to invasive bottlenecks, thus ensuring the evolutionary success of invasive species in novel environments.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees.

BACKGROUND: Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PURPOSE: The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. STUDY DESIGN: The CERTAIN is a prospective, multicenter, observational disease registry. METHODS: Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. RESULTS: In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. CONCLUSIONS: The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05219214).

Efficacy and safety of Tibetan medicine Qingpeng ointment for acute gouty arthritis: protocol for a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory arthritis clinically characterized by severe pain, swelling, and restricted movement of joints, which may cause physical disability and decrease quality of life. The use of recommended first-line treatment agents for AGA may be limited by adverse events. There has been a traditional use of alternative therapies for AGA. Tibetan medicine Qingpeng ointment is one of the on-market herbal products used for symptom relief of AGA. Previous clinical studies indicated that Qingpeng ointment can relieve pain, swelling, redness, and dysfunction of joints in patients with AGA. However, there is no rigorous randomized trial to demonstrate its benefit for AGA. In order to evaluate the efficacy and safety of Qingpeng ointment for AGA, we designed a randomized controlled trial. METHODS: This study is designed as a multi-center, randomized, double-blind, placebo-controlled trial. Two hundred and six adults with acute flare of gout, and visual analogue scale (VAS) score of joint pain ≥ 3 points will be recruited. Participants will be randomly assigned to herbal treatment or placebo group at a ratio of 1:1. Qingpeng ointment, or equal placebo ointment, will be applied topically at involved joints twice a day for consecutive 7 days. Patients in both groups would be allowed giving diclofenac sodium sustained-release tablets as rescue therapy when VAS score of joint pain ≥ 7 points during the treatment. The primary outcomes will be joint pain measured by VAS score, and joint swelling measured using width and thickness of affected joints and VAS score. Other outcome measures will be joint mobility, joint redness, C-reactive protein, serum uric acid, and the use of rescue medicine as well as adverse effect. DISCUSSION: To the best of our knowledge, this study is the first multi-center, randomized, double-blind, and placebo-controlled clinical trial to assess the efficacy of Tibetan medicine Qingpeng ointment for AGA. The findings of this study would provide evidence for its use to relieve symptoms of AGA. TRIAL REGISTRATION: ISRCTN ISRCTN34355813 . Registered on 25 January 2021.

The stress-induced metabolites changes in the flavor formation of oolong tea during enzymatic-catalyzed process: A case study of Zhangping Shuixian tea.

To interpret the environmental stresses induced dynamic changes of volatile and non-volatile constitutes in oolong tea leaves during enzymatic-catalyzed processes (ECP), metabolomic and proteomic studies were carried out using the processed leaf samples collected at the different stages of ECP for Zhangping Shuixian tea manufacture. Non-processed leaves were applied as control. Out of identified 980 non-volatiles and 157 volatiles, 40 non-volatiles and 8 volatiles were screened out as biomarkers, respectively. The integrated analysis on metabolites-proteins showed that phenylpropanoid biosynthesis, flavonoid biosynthesis, and phenylalanine metabolism were significantly enriched and highly correlated to the dynamic changes of key metabolites during ECP stage. A biological pathway network was constructed to illuminate the enzymatic-catalyzed production of critical flavoring compounds, including carbohydrates, amino acids, flavonoids, and volatile phenylpropanoids/benzenoids. The electronic-sensory analyses indicated leaf dehydration and mechanical wounding occurred over the sun-withering and turning-over steps are indispensable to form characteristic flavor of Shuixian tea.

Correction of neonatal vitamin D status using 1000 IU vitamin D/d increased lean body mass by 12 months of age compared with 400 IU/d: a randomized controlled trial.

BACKGROUND: Intrauterine exposure to maternal vitamin D status <50 nmol/L of serum 25-hydroxyvitamin D [25(OH)D] may adversely affect infant body composition. Whether postnatal interventions can reprogram for a leaner body phenotype is unknown. OBJECTIVES: The primary objective was to test whether 1000 IU/d of supplemental vitamin D (compared with 400 IU/d) improves lean mass in infants born with serum 25(OH)D <50 nmol/L. METHODS: Healthy, term, breastfed infants (Montréal, Canada, March 2016-2019) were assessed for serum 25(OH)D (immunoassay) 24-36 h postpartum. Infants with serum 25(OH)D <50nmol/L at 24-36 h were eligible for the trial and randomly assigned at baseline (1 mo postpartum) to 400 (29 males, 20 females) or 1000 IU/d (29 males, 20 females) of vitamin D until 12 mo. Infants (23 males, 18 females) with 25(OH)D ≥50 nmol/L (sufficient) formed a nonrandomized reference group provided 400 IU/d. Anthropometry, body composition (DXA), and serum 25(OH)D concentrations were measured at 1, 3, 6, and 12 mo. RESULTS: At baseline, mean ± SD serum 25(OH)D concentrations in infants allocated to the 400 and 1000 IU/d vitamin D groups were 45.8 ± 14.1 and 47.6 ± 13.4, respectively; for the reference group it was 69.2 ± 16.4 nmol/L. Serum 25(OH)D concentration increased on average to ≥50 nmol/L in the trial groups at 3-12 mo. Lean mass varied differently between groups over time; at 12 mo it was higher in the 1000 IU/d vitamin D group than in the 400 IU/d group (mean ± SD: 7013 ± 904.6 compared with 6690.4 ± 1121.7 g, P = 0.0428), but not the reference group (mean ± SD: 6715.1 ± 784.6 g, P = 0.19). Whole-body fat mass was not different between the groups over time. CONCLUSIONS: Vitamin D supplementation (400 or 1000 IU/d) during infancy readily corrects vitamin D status, whereas 1000 IU/d modestly increases lean mass by 12 mo. The long-term implications require further research. This trial was registered at clinicaltrials.gov as NCT02563015.

DNA damage and NF-κB inactivation implicate glycyrrhizic acid-induced G1 phase arrest in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most frequently occurring liver malignancy in Asia. Glycyrrhizic acid is known to reduce the risk of HCC formation in patients with chronic hepatitis C. To identify whether glycyrrhizic acid may play a role in anti-HCC therapy as an adjuvant is important. However, the inhibitory effect of glycyrrhizic acid on cell cycle progression in HCC cells and the mechanism of such have not been fully elucidated. This study used the comet assay, cell cycle analysis, immunofluorescence staining, the TUNEL assay, and Western blotting to identify the anti-HCC role of glycyrrhizic acid. Glycyrrhizic acid may induce DNA damage, apoptosis, activation of ATM, and expression of p21, and p27 in HCC cells. In addition, glycyrrhizic acid may also induce G1 phase arrest and suppress NF-κB-mediated Cyclin D1 expression. DNA damage and NF-κB inactivation may be associated with glycyrrhizic acid-induced G1 phase arrest in HCC cells.

Maternal excess adiposity and serum 25-hydroxyvitamin D < 50 nmol/L are associated with elevated whole body fat mass in healthy breastfed neonates.

BACKGROUND: Vitamin D status of pregnant women is associated with body composition of the offspring. The objective of this study was to assess whether the association between maternal vitamin D status and neonatal adiposity is modified by maternal adiposity preconception. METHODS: Healthy mothers and their term appropriate weight for gestational age (AGA) infants (n = 142; 59% male, Greater Montreal, March 2016-2019) were studied at birth and 1 month postpartum (2-6 weeks). Newborn (24-36 h) serum was collected to measure total 25-hydroxyvitamin D [25(OH)D] (immunoassay); maternal pre-pregnancy BMI was obtained from the medical record. Anthropometry, body composition (dual-energy X-ray absorptiometry) and serum 25(OH)D were measured at 2-6 weeks postpartum in mothers and infants. Mothers were grouped into 4 categories based on their vitamin D status (sufficient 25(OH)D ≥ 50 nmol/L vs. at risk of being insufficient < 50 nmol/L) and pre-pregnancy BMI (< 25 vs. ≥25 kg/m2): insufficient-recommended weight (I-RW, n = 24); insufficient-overweight/obese (I-OW/O, n = 21); sufficient-recommended weight (S-RW, n = 69); and sufficient-overweight/obese (S-OW/O, n = 28). Partial correlation and linear fixed effects model were used while adjusting for covariates. RESULTS: At birth, infant serum 25(OH)D mean concentrations were below 50 nmol/L, the cut-point for sufficiency, for both maternal pre-pregnancy BMI categories; 47.8 [95%CI: 43.8, 51.9] nmol/L if BMI < 25 kg/m2 and 38.1 [95%CI: 33.5, 42.7] nmol/L if BMI ≥25 kg/m2. Infant serum 25(OH)D concentrations at birth (r = 0.77; P < 0.0001) and 1 month (r = 0.59, P < 0.0001) were positively correlated with maternal postpartum serum 25(OH)D concentrations. Maternal serum 25(OH)D concentration was weakly correlated with maternal percent whole body fat mass (r = - 0.26, P = 0.002). Infants of mothers in I-OW/O had higher fat mass versus those of mothers in S-OW/O (914.0 [95%CI: 766.4, 1061.6] vs. 780.7 [95%CI: 659.3, 902.0] g; effect size [Hedges' g: 0.42]; P = 0.04 adjusting for covariates) with magnitude of difference of 220.4 g or ~ 28% difference. CONCLUSIONS: Maternal and neonatal vitamin D status are positively correlated. In this study, maternal adiposity and serum 25(OH)D < 50 nmol/L are dual exposures for neonatal adiposity. These findings reinforce the importance of vitamin D supplementation early in infancy irrespective of vitamin D stores acquired in utero and maternal weight status.

Disparities in Vitamin D Status of Newborn Infants from a Diverse Sociodemographic Population in Montreal, Canada.

BACKGROUND: Vitamin D status at birth is reliant on maternal-fetal transfer of vitamin D during gestation. OBJECTIVES: We aimed to examine the vitamin D status of newborn infants in a diverse population and to subsequently identify the modifiable correlates of vitamin D status. METHODS: In this cross-sectional study, healthy mother-infant dyads (n = 1035) were recruited within 36 h after term delivery (March 2016-March 2019). Demographic and lifestyle factors were surveyed. Newborn serum 25-hydroxyvitamin D [25(OH)D] was measured (standardized chemiluminescence immunoassay) and categorized as deficient [serum 25(OH)D <30 nmol/L] or adequate (≥40 nmol/L). Serum 25(OH)D was compared among categories of maternal characteristics using ANOVA; each characteristic was tested in a separate model. Subgroups (use of multivitamins preconception and continued in pregnancy compared with during pregnancy only) were matched (n = 352/group) for maternal factors (ancestry, age, income, education, parity, and prepregnancy BMI) using propensity scores; logistic regression models were generated for odds of deficiency or adequacy. RESULTS: Infants' mean serum 25(OH)D was 45.9 nmol/L (95% CI: 44.7, 47.0 nmol/L) (n = 1035), with 20.8% (95% CI: 18.3%, 23.2%) deficient and 60.7% (95% CI: 55.2%, 66.2%) adequate. Deficiency prevalence ranged from 14.6% of white infants to 41.7% of black infants. Serum 25(OH)D was higher (P < 0.0001) in infants of mothers with higher income, BMI < 25 kg/m2, exercise and sun exposure in pregnancy, and use of multivitamins preconception. In the matched-subgroup analysis, multivitamin supplementation preconception plus during pregnancy relative to only during pregnancy was associated with lower odds for vitamin D deficiency (ORadj: 0.55; 95% CI: 0.36, 0.86) and higher odds for adequate vitamin D status (ORadj: 1.47; 95% CI: 1.04, 2.07). CONCLUSIONS: In this study most newborn infants had adequate vitamin D status, yet one-fifth were vitamin D deficient with disparities between population groups. Guidelines for a healthy pregnancy recommend maternal use of multivitamins preconception and continuing in pregnancy. An emphasis on preconception use may help to achieve adequate neonatal vitamin D status.This trial was registered at clinicaltrials.gov as NCT02563015.

Endothelial Yin Yang 1 Phosphorylation at S118 Induces Atherosclerosis Under Flow.

RATIONALE: Disturbed flow occurring in arterial branches and curvatures induces vascular endothelial cell (EC) dysfunction and atherosclerosis. We postulated that disturbed flow plays important role in modulating phosphoprotein expression profiles to regulate endothelial functions and atherogenesis. OBJECTIVE: The goal of this study is to discover novel site-specific phosphorylation alterations induced by disturbed flow in ECs to contribute to atherosclerosis. METHODS AND RESULTS: Quantitative phosphoproteomics analysis of ECs exposed to disturbed flow with low and oscillatory shear stress (0.5±4 dynes/cm2) versus pulsatile shear stress (12±4 dynes/cm2) revealed that oscillatory shear stress induces phospho-YY1S118 (serine [S]118 phosphorylation of Yin Yang 1) in ECs. Elevated phospho-YY1S118 level in ECs was further confirmed to be present in the disturbed flow regions in experimental animals and human atherosclerotic arteries. This disturbed flow-induced EC phospho-YY1S118 is mediated by CK2α (casein kinase 2α) through its direct interaction with YY1. Yeast 2-hybrid library screening and in situ proximity ligation assays demonstrate that phospho-YY1S118 directly binds ZKSCAN4 (zinc finger with KRAB [krüppel-associated box] and SCAN [SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA] domains 4) to induce promoter activity and gene expression of HDM2 (human double minute 2), which consequently induces EC proliferation through downregulation of p53 and p21CIP1. Administration of apoE-deficient (ApoE-/-) mice with CK2-specific inhibitor tetrabromocinnamic acid or atorvastatin inhibits atherosclerosis formation through downregulations of EC phospho-YY1S118 and HDM2. Generation of novel transgenic mice bearing EC-specific overexpression of S118-nonphosphorylatable mutant of YY1 in ApoE-/- mice confirms the critical role of phospho-YY1S118 in promoting atherosclerosis through EC HDM2. CONCLUSIONS: Our findings provide new insights into the mechanisms by which disturbed flow induces endothelial phospho-YY1S118 to promote atherosclerosis, thus indicating phospho-YY1S118 as a potential molecular target for atherosclerosis treatment.

Study on the mechanism of active components of Liupao tea on 3CLpro based on HPLC-DAD fingerprint and molecular docking technique.

Liupao tea, a drink homologous to medicine and food. It can treat dysentery, relieve heat, remove dampness, and regulate the intestines and stomach. The objective of this study is to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. We used high performance liquid chromatography to analyze the extract of Liupao tea and establish its fingerprint. The main index components of the fingerprint were determined using SARS-COV-2 3-chymotrypsin-like protease (3CLpro ), and an in vitro drug screening model based on fluorescence resonance energy transfer was used to evaluate its inhibitory activity in vitro. The fingerprint results showed that the alcohol extract of Liupao tea contained gallic acid, epigallocatechin gallate (EGCG), caffeine, epicatechin gallate, rutin, and ellagic acid. The molecular docking binding energies of the six index components of SARS-CoV-2 3Clpro were all less than -5.0 kJ/mol and showed strong binding affinity. The results of in vitro activity showed that the IC50 of EGCG was 8.84 µmol/L, which could inhibit SARS-CoV-2 3Clpro to a certain extent. This study unleashed that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , and Liupao tea has a certain significance as a tea drink for the prevention of COVID-19. PRACTICAL APPLICATIONS: The objective of this study was to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. The molecular docking binding energies of the six index components of Liupao tea with SARS-CoV-2 3CLpro were all less than -5.0 kJ/mol, among them, the enzyme activity experiment shows that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , it can be used as a potential SARS-CoV-2 3CLpro inhibitor. We predicted that the understandings gained in the current research may evidence that Liupao tea has a certain significance as a tea drink for the prevention of COVID-19.

Guizhi-Shaoyao-Zhimu decoction attenuates bone erosion in rats that have collagen-induced arthritis via modulating NF-κB signalling to suppress osteoclastogenesis.

CONTEXT: Guizhi-Shaoyao-Zhimu decoction (GSZD) is commonly used to treat rheumatoid arthritis (RA), but its mechanism is unclear. OBJECTIVE: To investigate the effect of GSZD on bone erosion in type II collagen (CII)-induced arthritis (CIA) in rats and to identify the underlying mechanism. MATERIALS AND METHODS: The CIA model was prepared in male Wistar rats by two subcutaneous injections of CII, 1 mg/mL. Fifty CIA rats were randomized equally into the control group given saline daily, the positive group given saline daily and methotrexate 0.75 mg/kg once a week, and three GSZD-treated groups gavaged daily with 800, 1600 and 3200 mg/kg of GSZD for 21 days. GSZD effects were assessed by paw volume, arthritic severity index and histopathology. Cytokine levels were determined by ELISA. The effects of GSZD on RAW264.7 cells were evaluated by receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption assay. Expression of IκB-α and p65 was measured by Western blotting. Major components of GSZD were identified by HPLC. RESULTS: Arthritis index score, paw volume and bone destruction score showed that GSZD improved inflammatory symptoms and reduced joint tissue erosion (p < 0.01). GSZD decreased RANKL, and the number of osteoclasts (OCs) in joint tissues (p < 0.01) and increased osteoprotegerin levels (p < 0.01). GSZD inhibited RANKL-induced RAW264.7 differentiation and reduced bone resorption by OCs. GSZD upregulated IκB (p < 0.01) and p65 (p < 0.01) in the cytoplasm and downregulated p65 (p < 0.01) in the cell nucleus. CONCLUSIONS: Guizhi-Shaoyao-Zhimu decoction has an anti-RA effect, suggesting its possible use as a supplement and alternative drug therapy for RA.

Effect of Vitamin D Supplementation in Early Life on Children's Growth and Body Composition: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Vitamin D deficiency during pregnancy or infancy is associated with adverse growth in children. No systematic review has been conducted to summarize available evidence on the effect of vitamin D supplementation in pregnancy and infancy on growth and body composition in children. OBJECTIVE: We aim to summarize the available evidence on the effect of vitamin D supplementation in pregnancy and infancy on child growth and body composition. METHOD: A systematic review and meta-analysis were performed on the effects of vitamin D supplementation during early life on children's growth and body composition (bone, lean and fat). A literature search of randomized controlled trials (RCTs) was conducted to identify relevant studies on the effects of vitamin D supplementation during pregnancy and infancy on children's body composition (bone, lean and fat) in PubMed, EMBASE and Cochrane Library from inception to 31 December 2020. A Cochrane Risk Assessment Tool was used for quality assessment. The comparison was vitamin D supplementation vs. placebo or standard care. Random-effects and fixed-effect meta-analyses were conducted. The effects are presented as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 3960 participants from eleven randomized controlled trials were eligible for inclusion. Vitamin D supplementation during pregnancy was associated with higher triceps skinfold thickness (mm) (MD 0.33, 95% CI, 0.12, 0.54; I2 = 34%) in neonates. Vitamin D supplementation during pregnancy or infancy was associated with significantly increased length for age z-score in infants at 1 year of age (MD 0.29, 95% CI, 0.03, 0.54; I2 = 0%), and was associated with lower body mass index (BMI) (kg/m2) (MD -0.19, 95% CI -0.34, -0.04; I2 = 0%) and body mass index z-score (BMIZ) (MD -0.12, 95% CI -0.21, -0.04; I2 = 0%) in offspring at 3-6 years of age. Vitamin D supplementation during early life was not observed to be associated with children's bone, lean or fat mass. CONCLUSION: Vitamin D supplementation during pregnancy or infancy may be associated with reduced adiposity in childhood. Further large clinical trials of the effects of vitamin D supplementation on childhood body composition are warranted.

Traditional Chinese medicine is a useful and promising alternative strategy for treatment of Sjogren's syndrome: A review.

Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease involving exocrine glands. Current studies have found that the occurrence of the disease is closely related to genetic, environmental and neuroendocrine factors, as well as abnormal activation of T and B lymphocytes. The etiology and pathogenesis of pSS is complex, and there is a lack of specific targeted drugs. Traditional Chinese medicines (TCMs) have been comprehensively investigated for their treatment effects on pSS. Through a systematic review of the literature, we summarized the TCMs used to treat pSS, and find that there are four major ways that TCMs are used, including upregulation of aquaporin proteins, suppression of cell apoptosis, suppression of the abnormal activation of B lymphocytes and suppression of the abnormal activation of T lymphocytes (balancing T helper type [Th]1/Th2 & Th17/Treg and suppressing follicular helper T [Tfh] cells). However, there are not enough data about the active constituents, quality control, pharmacokinetics, toxicity and modern preparations of these TCMs; therefore, more investigations are needed. This paper highlights the importance of TCMs for treating pSS and provides guidance for future investigations.

HPLC-DAD fingerprints combined with chemometric techniques for the authentication of plucking seasons of Laoshan green tea.

Laoshan green teas plucked in summer and autumn were measured by high performance liquid chromatography-diode array detector (HPLC-DAD). After baseline correction, the fingerprints data were resolved by multivariate curve resolution-alternating least squares (MCR-ALS) and a total of 57 components were acquired. Relative concentrations of these components were afterwards applied to distinguish plucking seasons using principal component analysis (PCA), support vector machines (SVM) and partial least squares-discriminant analysis (PLS-DA). For both SVM and PLS-DA models, the total recognition rates of training set, cross-validation and testing set were 100%, 91.3% and 100%, respectively. Besides, three variable selection methods were employed to determine characteristic components for the authentication of summer and autumn teas. Results showed that PLS-DA model based on three characteristic components selected by VIP possesses identical predictive ability as the original model. This study demonstrated that our proposed strategy is competent for the authentication of plucking seasons of Laoshan green tea.