Effectiveness of adjuvant traditional Chinese medicine on macrovascular invasion in patients with hepatocellular carcinoma: a real-world propensity score-matched study.

The study aimed to investigate the potential of traditional Chinese medicine (TCM) in reducing the risk of macrovascular invasion (MVI) in Chinese patients with hepatocellular carcinoma (HCC). This retrospective analysis involved 2,267 HCC patients treated at our hospital. Propensity score (PS) matching was used to compare TCM users (n = 485) with non-users (n = 485) in terms of age, Barcelona Clinic Liver Cancer (BCLC) staging, type of treatment, and AFP. The impact of TCM on the hazard ratio (HR) of MVI was evaluated using a Cox multivariate regression model. The efficacy of TCM therapy on MVI was further examined using the log-rank test. The analysis revealed that TCM medication was a significant protective factor for MVI in HCC patients, as evidenced by the Cox analysis (adjusted HR = 0.496, 95% CI: 0.387-0.635, p < 0.001). After PS matching, the Kaplan-Meier curve demonstrated a lower occurrence rate of MVI in TCM users compared to non-users. The study findings suggest that TCM treatment has the potential to decrease the incidence of MVI in HCC patients, irrespective of etiology, BCLC staging, liver function, or treatment type. Notably, as the use of TCM increased, the percentage of MVI in patients showed a gradual decrease, indicating the potential of TCM therapy as a successful strategy for preventing MVI.

Efficacy and safety of acupressure in nausea and vomiting during pregnancy: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of acupressure on nausea and vomiting during pregnancy. METHODS: PubMed, Embase, Springer, Web of Science, and the Cochrane Library were searched for all randomized controlled trials (RCT) of treating nausea and vomiting during pregnancy by acupressure from the inception date of database to July 31st, 2023. Study selection, data extraction, and risk of bias assessment were conducted independently by researchers. The methodological quality of included studies was evaluated by the Cochrane Collaboration's bias risk assessment tool, meta-analysis by Stata 17.0 software, and publication bias by Begg's test. RESULTS: A total of 11 RCTs involving 1378 pregnant women were included in this review, which was assessed to be moderate quality. 10 RCTs involving 1298 pregnant women were assessed for the meta-analysis. The results revealed that acupressure showed significant difference on improvement in symptom score compared with sham acupressure (pooled MD, - 1.33; 95%CI [- 2.06, - 0.61]; P < 0.001) or control group (pooled MD, - 0.73; 95%CI [- 1.08, - 0.39]; P < 0.001), and incidence of effective rate compared with sham acupressure group (pooled RR, 1.78; 95%CI [1.03, 3.07]; P = 0.039). However, no statistical significance was found between acupressure and control group (pooled RR, 4.53; 95%CI [0.67, 30.48]; P = 0.120) on effective rate. On comparing acupressure with sham acupressure, there was no beneficial effect on preventing nausea and vomiting during pregnancy (pooled RR, 0.83; 95%CI [0.50, 1.38]; P = 0.476), shortening the duration of hospital stay (pooled MD, - 0.78; 95%CI [- 1.98, 0.41]; P = 0.199) and improving patient satisfaction (pooled RR, 1.36; 95%CI [0.47, 3.91]; P = 0.570). Begg's test did not reveal any publication bias. Only one RCT reported minimal acupressure-related adverse events. CONCLUSION: Acupressure may have potential favorable or encouraging effect on treating nausea and vomiting during pregnancy, but strong supportive data are not yet available. Well-designed and large-scale RCTs should be conducted for assessing and confirming the efficacy and safety of acupressure in nausea and vomiting during pregnancy.

Quality variation and biosynthesis of anti-inflammatory compounds for Capparis spinosa based on the metabolome and transcriptome analysis.

Introduction: Capparis spinosa L. fruits as edible and medicinal plant, has anti-inflammatory activities. The different morphological characteristics of C. spinosa fruits from Ili, Turpan, and Karamay may affect their anti-inflammatory components and functions. Methods: The anti-inflammatory activity of C. spinosa fruit was assessed using an LPS-induced inflammatory cell model. Furthermore, the differences in anti-inflammatory compounds were analyzed by metabolome and RNA-seq. Additionally, the anti-inflammatory mechanism was elucidated using network pharmacology. Results: In the study, we found that the 95% ethanol extracts (CSE) obtained from the three kinds of fruits showed remarkable anti-inflammatory effects both in vivo and in vitro. However, the CSE derived from Ili fruits significantly reduced CD86 levels on DCs. As a result of metabolomic analysis, the metabolic profiles of Ili fruits differed significantly from those of the other two habitats, which were consistent with transcriptome analysis. A total of 15 compounds exhibiting anti-inflammatory activity were subjected to screening, revealing a greater accumulation of flavonoids in the Turpan and Karamay districts. Notably, phenolic compounds were identified as the principal anti-inflammatory components in C. spinosa. Conclusion: There were significant differences in the morphology, metabolites, transcriptional levels, and anti-inflammatory activity of C. spinosa from the three districts.

The effects of reflexology on symptoms in pregnancy: A systematic review of randomized controlled trials.

Objective: This review assessed the effects of reflexology on symptoms in pregnancy. Methods and analysis: PubMed, Embase, Springer, Web of Science, the Cochrane Library, and reference lists of previous systematic reviews were searched for the eligible randomized controlled trials (RCT) from the inception date of each predefined database up to May 31st, 2023. Data were extracted, and methodological quality was evaluated by the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The efficacy of treatment was assessed using pooled effect sizes (Hedges' g) and 95% confidence intervals (CI). Meta-analysis was performed using the RevMan 5.4 manager, and publication bias was evaluated by Begg's test. Results: The included a total of 13 RCTs in this review, of eleven was high risk of bias and two were low, reported the effects of reflexology on low back and/or pelvic pain (LBPP), labor pain, duration of labor, anxiety, fatigue, sleep quality, constipation symptoms, and ankle and foot edema in pregnancy. The effect sizes (Hedges' g) for reflexology in labor pain, duration of labor, anxiety, fatigue, and sleep quality showed statistical significance, which the meta-analysis also confirmed except for fatigue and sleep quality due to insufficient studies. Conclusion: Reflexology is probably effective and safe for labor pain, duration of labor, and anxiety in pregnancy, while the evidences for reflexology in LBPP, fatigue, sleep quality, constipation symptoms, and ankle and foot edema during pregnancy were insufficient. Based on the low to high quality of included studies, strong supportive evidence is not yet available. Rigorous-design and large-scale clinical trials should be conducted to provide higher-quality, reliable evidence.

Preparation of quinoa bran dietary fiber-based zinc complex and investigation of its antioxidant capacity in vitro.

In order to improve the economic utilization of quinoa bran and develop a safe and highly available zinc ion biological supplement. In this study, a four-factor, three-level response surface optimization of quinoa bran soluble dietary fiber (SDF) complexation of zinc was studied. The effect used four factors on the chelation rate was investigated: (A) mass ratio of SDF to ZnSO4.7H2O, (B) chelation temperature, (C) chelation time, and (D) pH. Based on the results of the single-factor test, the four-factor three-level response surface method was used to optimize the reaction conditions. The optimal reaction conditions were observed as mentioned here: the mass ratio of quinoa bran SDF to ZnSO4.7H2O was 1, the reaction temperature was 65°C, the reaction time was 120 min, and the pH of the reaction system was 8.0. The average chelation rate was 25.18%, and zinc content is 465.2 µg/g under optimal conditions. The hydration method rendered a fluffy quinoa bran SDF structure. The intramolecular functional groups were less stable which made the formation of the lone pairs of electrons feasible to complex with the added divalent zinc ions to form a quinoa bran soluble dietary fiber-zinc complex [SDF-Zn(II)]. The SDF-Zn(II) chelate had higher 2,2-diphenylpicrylhydrazyl (DPPH), ABTS+, hydroxyl radical scavenging ability, and total antioxidant capacity. Therefore, metal ion chelation in dietary fiber is of biological importance.

Supplementary Feeding of Grazing Inner Mongolian Cashmere Goats during Pregnancy-Based on "Nutrient Requirements of Cashmere Goats".

This study aimed to conduct precise supplementation for pregnant cashmere goats under grazing based on the feeding standard. Eight Inner Mongolian pregnant cashmere goats of near-average body weight were selected at early gestation (44.41 ± 4.03 kg) and late gestation (46.54 ± 4.02 kg) to measure their nutrient intake. Then, two pregnant cashmere goat flocks, No. 10 (control group, on-farm supplement) and No. 11 (supplemented group, supplement based on standard), with the same goat herd structure and grassland type, were chosen to conduct the supplemental feeding experiment. The results showed that pregnant cashmere goats lacked daily the intake of dry matter, digestive energy, crude protein and most essential mineral elements under grazing. After supplemental feeding, the supplementation based on the feeding standard increased the cashmere length and cashmere length growth volume and decreased the cashmere fineness, with no statistical significance. The goat cashmere yield, goat weight after shearing, single and twin-birth kid weight and kids' mature secondary hair follicle density were significantly higher in the supplemented group (p < 0.05). In conclusion, supplementation in accordance with "Nutrient Requirements of Cashmere Goats" can enhance pregnant cashmere goats' fiber production, growth performance, fertility and kids' secondary hair follicles development, which is of great importance for the healthy and precise nutrition and management of cashmere goats.

Exploration of the mechanism by which Huangqi Guizhi Wuwu decoction inhibits Lps-induced inflammation by regulating macrophage polarization based on network pharmacology.

BACKGROUND: Huangqi Guizhi Wuwu decoction (HQGZWWD) is a traditional Chinese herbal medicine formulation with significant anti-inflammatory activity. However, its underlying mechanism remains unknown. Through network pharmacology and experimental validation, this study aimed to examine the potential mechanism of HQGZWWD in regulating macrophage polarization and inflammation. METHODS: The active components were obtained from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP), whereas the corresponding targets were obtained from the TCMSP and Swiss Target Prediction database. The GeneCards database identified targets associated with macrophage polarization and inflammation. Multiple networks were developed to identify the key compounds, principal biological processes, and pathways of HQGZWWD that regulate macrophage polarization and inflammation. Autodock Vina is utilized to assess the binding ability between targets and active compounds. Finally, confirm the experiment's central hypothesis. Human histiocytic lymphoma (U-937) cells were transformed into M1 macrophages following stimulation with Lipopolysaccharide (LPS) to evaluate the effect of HQGZWWD drug-containing mouse serum (HQGZWWD serum) on regulating macrophage polarization and inflammation. RESULTS: A total of 54 active components and 859 HQGZWWD targets were obtained. There were 9972 targets associated with macrophage polarization and 11,109 targets associated with inflammation. After screening, 34 overlapping targets were identified, of which 5 were identified as central targets confirmed by experiments, including the α7 nicotinic acetylcholine receptor (α7 nAchR), interleukin 6 (IL-6), Interleukin-1 beta (IL-1ß), interleukin 10 (IL-10) and growth factor beta (TGF-ß1). Pathway enrichment analysis revealed that 34 overlapping targets were enriched in multiple pathways associated with macrophage polarization and inflammation, including the TGF beta signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway, and TNF signaling pathway. Molecular docking confirmed that the majority of HQGZWWD's compounds can bind to the target. In vitro experiments, HQGZWWD serum was shown to up-regulate the expression of α7 nAchR, reduce the number of M1 macrophages, stimulate the production of M2 macrophages, inhibit the expression of pro-inflammatory cytokines IL-6 and IL1-ß, and increase the expression of anti-inflammatory cytokines IL-10 and TGF-ß1. CONCLUSION: HQGZWWD can regulate the number of M1/M2 macrophages and the level of inflammatory cytokines, and the underlying mechanism may be related to the up-regulation of α7 nAchR expression.

Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer.

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation-enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin-4, indicates the opening of tight junction. Moreover, MSN-SH(E)-associated reprogramming of M2 macrophages to M1-like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)-loaded nanovector (MMC@MSN-SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN-γ, TGF-ß1, and TNF-α. These observations substantiated the significance of MMC@MSN-SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non-muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure.

Mechanism of Yiqi Yangying Heluo Formula in the Treatment of IgA Nephropathy by Affecting Gd-IgA1 Based on BAFF Molecular Level and T Lymphocyte Immunity.

Background: Galactose-deficient IgA1 (Gd-IgA1) is a critical initiating factor in the pathogenesis of IgA nephropathy (IgAN), which plays an important role in the diagnosis and evaluation of this disease. Moreover, the whole pathogenesis process has an intimate association with the immune response of T and B lymphocytes and their inflammatory factors. There is no specific therapy for IgAN at present. Yiqi Yangyin Formula can significantly reduce urinary protein and hematuria in patients with IgAN. Yiqi Yangying Heluo Formula (YYHF) is optimized on the basis of the above prescription, but its specific mechanism remains to be further studied. Methods: The effect of YYHF on urinary protein and urinary red blood cell count in patients with IgAN was observed by a self-controlled clinical study before and after treatment. On this basis, flow cytometry was used to detect the proportion of T lymphocyte subsets in peripheral blood of patients with IgAN before and after treatment and healthy controls. Meanwhile, the levels of Gd-IgA1, B cell activation factor (BAFF), and their cytokines (IL-4, IL-6, and IL-17) in peripheral blood were detected by enzyme-linked immunosorbent assay. The changes in mechanism-related indicators of the two groups were observed and subject to correlation analysis. Results: (1) Compared with the levels before treatment, 24-hour urinary protein content decreased by 47.7% and urinary red blood cell number decreased by 67% in patients with IgAN intervened by YYHF after 48 weeks of follow-up. (2) Compared with the healthy control group, patients with IgAN showed a significantly increased proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg, obviously reduced proportion of Th2 cells and Treg cells, and evidently elevated levels of Gd-IgA1, BAFF, and their cytokines (IL-4, IL-6, and IL-17) in the peripheral blood. (3) Following 48 weeks of follow-up after intervention treatment with YYHF, the levels of Gd-IgA1, BAFF, IL-6, and IL-17 were significantly lower, but the level of IL-4 was higher in peripheral blood of patients with IgAN than those before treatment and after 24 weeks of treatment; simultaneously, the proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg decreased while that of Th2 cells and Treg cells increased after 48 weeks of follow-up compared with that before treatment in peripheral blood of patients with IgAN. (4) The results of correlation analysis revealed that the level of Gd-IgA1 in peripheral blood of patients with IgAN was positively correlated with the level of BAFF, as well as the proportion of Th1 cells, Th17 cells, Th1/Th2, IL-6, and IL-17 levels, and negatively correlated with the proportion of Treg cells. In addition, the level of Gd-IgA1 in peripheral blood was positively correlated with proteinuria, yet without correlation with hematuria. Conclusion: YYHF can reduce the quantitative level of 24 h urinary protein and urinary red blood cell count in patients with IgAN. Patients with IgAN have obvious T cell immune imbalance. YYHF can significantly reduce the level of Gd-IgA1 in patients with IgAN, and its mechanism may be explained by the reduced level of BAFF in peripheral blood and improved immune balance of T cells.

How to Evaluate the Effectiveness of Health Promotion Actions Developed Through Youth-Centered Participatory Action Research.

Most actions targeting children's health behaviors have limited involvement of children in the development, potentially contributing to disappointing effectiveness. Therefore, in the 3-year "Kids in Action" study, 9- to 12-year-old children from a lower-socioeconomic neighborhood were involved as coresearchers in the development, implementation, and evaluation of actions targeting health behaviors. The current study describes the controlled trial that evaluated the effects on children's energy balance-related behaviors, physical fitness, and self-rated health, as well as experienced challenges and recommendations for future evaluations. Primary school children from the three highest grades of four intervention and four control schools were eligible for participation. Outcome measures assessed at baseline, and at 1- and 2-year follow-up were as follows: motor fitness by the MOPER test (N = 656, N = 485, N = 608, respectively), physical activity and sedentary behavior by accelerometry (N = 223, N = 149, N = 164, respectively), and consumption of sugar sweetened beverages and snacks and self-rated health by a questionnaire (N = 322, N = 281, N = 275, respectively). Mixed-model analyses were performed adjusted for clustering within schools and relevant confounders. Significant beneficial intervention effects were found on self-reported consumption of energy/sports drinks at T2 versus T0, and on total time and ≥5-minute bouts of moderate-to-vigorous physical activity at T1 versus T0. Significant adverse effects were found on "speed and agility" and "coordination and upper-limb speed." No other significant effects were found. The inconsistent intervention effects may be explained by the dynamic cohort and suboptimal outcome measures. We advise future studies with a similar approach to apply alternative evaluation designs, such as the delayed baseline design.

Mechanisms and network pharmacological analysis of Yangyin Fuzheng Jiedu prescription in the treatment of hepatocellular carcinoma.

OBJECTIVE: To identify the key drugs of Yangyin Fuzheng Jiedu prescription (YFJP) and investigate their therapeutic effects against hepatocellular carcinoma (HCC) and the potential mechanism using network pharmacology. METHODS: The H22 tumor-bearing mouse model was established. Thirty male BALB/c mice were divided randomly into five groups. The mice were orally treated with either disassembled prescriptions of YFJP or saline solution continuously for 14 days. The mice were weighed every 2 days during treatment and the appearance of tumors was observed by photographing. The tumor inhibition rate and the spleen and thymus indexes were calculated. Hematoxylin and eosin and immunohistochemical staining were performed to observe the histological changes and tumor-infiltrating lymphocytes. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. The proportion of CD8+ T cells and the expression of programmed cell death protein 1 (PD-1), T cell immunoglobulin domain and mucin domain-3 (Tim-3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were analyzed using flow cytometry. The production of serum cytokines was detected using the Milliplex® MAP mouse high sensitivity T cell panel kit. The active components of the key drugs and HCC-related target proteins were obtained from the corresponding databases. The putative targets for HCC treatment were screened by target mapping, and potential active components were screened by constructing a component-target network. The interactive targets of putative targets were obtained from the STRING database to construct the protein-protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed based on potential targets. The gene-gene inner and component-target-pathway networks were constructed and analyzed to screen the key targets. Western blotting was used to evaluate the protein expression of the key targets in the tumor-bearing mouse model. The binding activity of the key targets and compounds was verified by molecular docking. RESULTS: Among the three disassembled prescriptions of YFJP, the Fuzheng prescription (FZP) showed significant antitumor effects and inhibited weight loss during the treatment of H22 tumor-bearing mice. FZP increased the immune organ index and the levels of CD8+ and CD3+ T cells in the spleen and peripheral blood of H22 tumor-bearing mice. FZP also reduced the expression of PD-1, TIGIT, and TIM3 in CD8+ T cells and the production of IL-10, IL-4, IL-6, and IL-1ß. Network pharmacology and experimental validation showed that the key targets of FZP in the treatment of HCC were PIK3CA, TP53, MAPK1, MAPK3, and EGFR. The therapeutic effect on HCC was evaluated based on HCC-related signaling pathways, including the PIK3-Akt signaling pathway, PD-L1 expression, and PD-1 checkpoint pathway in cancer. GO enrichment analysis indicated that FZP positively regulated the molecular functions of transferases and kinases on the cell surface through membrane raft, membrane microarea, and other cell components to inhibit cell death and programmed cell death. CONCLUSION: FZP was found to be the key disassembled prescription of YFJP that exerted antitumor and immunoregulatory effects against HCC. FZP alleviated T cell exhaustion and improved the immunosuppressive microenvironment via HCC-related targets, pathways, and biological processes.

Immunomodulatory Effect of Traditional Chinese Medicine Combined with Systemic Therapy on Patients with Liver Cancer: A Systemic Review and Network Meta-analysis.

Objective: As immune combination therapy in the treatment of liver cancer made significant achievements, and the modulating effect of traditional Chinese medicine (TCM) on immunity gradually appeared. The main purpose of this study was to study the effect of different TCM combined with systemic therapy (ST) on immune regulation in patients with liver cancer, as well as the efficacy and safety of combined therapy, and to find the best combined application scheme by ranking. Methods: Nine electronic databases were searched from January 1, 2010, to November 12, 2021, to search for RCTs of TCM combined ST in the field of liver cancer for literature screening, quality evaluation and data extraction. STATA 15.0 and RevMan 5.3 software were used to conduct network meta-analysis to analyze and explore the significance of TCM combined ST in immune regulation, efficacy and safety in clinical application. The probability value of the surface under the cumulative ranking curve was used to rank the processing studied. Results: A total of 25 studies involving 2,152 participants were included in the network meta-analysis, including six traditional Chinese medicine injections and seven proprietary Chinese medicines. The results showed that Dahuang Zhechong Wan and Kangai injection combined with ST were the best choices for immune regulation. Moreover, the Huaier granule was the best choice to reduce vascular endothelial growth factors. Conclusion: For patients with liver cancer, TCM combined with ST was better than that of ST alone and can significantly improve the immune function of patients as well as the efficacy and safety of treatment. However, given the limited sample size and methodological quality of the trials that we included in our study, more centralized and randomized controlled trials with a large sample size are required to verify our findings.

l-arginine supplementation improved neonatal outcomes in pregnancies with hypertensive disorder or intrauterine growth restriction: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Previous research established that the availability of l-arginine affects placental vascular development and fetal growth. However, practical details associated with the effects of l-arginine supplementation on the neonatal outcomes of hypertensive disorder (HD) and intrauterine growth restriction (IUGR) pregnancies are limited. METHODS: The PubMed, ScienceDirect, and Web of Science databases were searched for peer-reviewed literature published by September 30, 2021 to investigate the operational details of l-arginine supplementation in improving neonatal outcomes in complicated pregnancies. Standardized mean difference (SMD) and weighted mean difference (WMD) of continuous variables, as well as the risk ratio (RR) for categorical variables were pooled by random-effects models. RESULTS: The results indicated that l-arginine supplementation increased the plasma nitric oxide (NO) concentrations in IUGR pregnancies (SMD: 0.71; 95% CI: 0.45, 0.97; I2 = 0%), but decreased the risk of preeclampsia in HD mothers (RR: 0.49; 95% CI: 0.31, 0.76; I2 = 0%). Administration with l-arginine elevated birth weights both in hypertensive and IUGR pregnant women, with WMDs of 194.70 g (95% CI: 58.21, 331.20; I2 = 44.2%) and 134.00 g (95% CI: 43.53, 224.46; I2 = 42.4%), respectively. However, the intervention had no effect on gestational age except in HD pregnancies (WMD: 7.05 d; 95% CI: 3.16, 10.95; I2 = 36.5%). l-arginine administration during pregnancy significantly reduced the small for gestational age (SGA) risk of fetus both in HD (RR: 0.51; 95% CI: 0.31, 0.83; I2 = 0.0%) and IUGR mothers (RR: 0.46; 95% CI: 0.25, 0.88; I2 = 0.0%). Subgroup analyses revealed that l-arginine supplementation at <4 g/d dosage or for ≥1-month duration or in the third trimester had a greater effect on birth weights in HD women without proteinuria, but a higher l-arginine dosage was more beneficial for extending gestational age and reducing the risk of SGA in older pregnancies. Additionally, intravenous infusion of l-arginine, but not oral administration, significantly increased birth weight in IUGR pregnancies with elevated NO concentrations, although the recommended amount should be confined to <4 g/d. CONCLUSIONS: These findings provide practical guidelines for l-arginine supplementation to improve the birth outcomes of complicated pregnancies. REGISTRY NUMBER: CRD42021246290 (https://www.crd.york.ac.uk/PROSPERO).

B vitamin intakes modify the association between particulate air pollutants and incidence of all-cause dementia: Findings from the Women's Health Initiative Memory Study.

INTRODUCTION: Particulate air pollutants may induce neurotoxicity by increasing homocysteine levels, which can be lowered by high B vitamin intakes. Therefore, we examined whether intakes of three B vitamins (folate, B12 , and B6 ) modified the association between PM2.5 exposure and incidence of all-cause dementia. METHODS: This study included 7183 women aged 65 to 80 years at baseline. B vitamin intakes from diet and supplements were estimated by food frequency questionnaires at baseline. The 3-year average PM2.5 exposure was estimated using a spatiotemporal model. RESULTS: During a mean follow-up of 9 years, 342 participants developed all-cause dementia. We found that residing in locations with PM2.5 exposure above the regulatory standard (12 µg/m3 ) was associated with a higher risk of dementia only among participants with lower intakes of these B vitamins. DISCUSSION: This is the first study suggesting that the putative neurotoxicity of PM2.5 exposure may be attenuated by high B vitamin intakes.

Effects of magnesium supplementation on improving hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes: A pooled analysis of 24 randomized controlled trials.

Background: Previous studies have demonstrated that diabetes is often accompanied with lower magnesium status. However, practical details regarding the influences of magnesium intervention on hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes (T2D) need to be further investigated. Methods: Web of Science, ScienceDirect, and PubMed were searched for relevant literatures published through April 30, 2022, and high-quality data were pooled to evaluate the effects of magnesium supplementation on glycemic, circulating lipids, and blood pressure control in T2D, and to explore the associated practical details. Results: Pooled analyses of 24 randomized controlled trials with 1,325 T2D individuals revealed that subjects who received magnesium supplementation had statistically significant reductions in fasting plasma glucose, glycated hemoglobin, systolic blood pressure and diastolic blood pressure, with WMD values of -0.20 mM (95% CI: -0.30, -0.09), -0.22% (95% CI: -0.41, -0.03), -7.69 mmHg (95% CI: -11.71, -3.66) and -2.71 mmHg (95% CI: -4.02, -1.40), respectively. Detailed subgroup analyses demonstrated that health status of participants including age, body mass index, country, duration of disease, baseline magnesium level and baseline glycemic control condition as well as magnesium formulation, dosage and duration of intervention influenced the effects of magnesium addition. Dose-effect analysis showed that 279 mg/d for 116 d, 429 mg/d for 88 d and 300 mg/d for 120 d are the average optimal dosages and durations for improving glycemic, circulating lipids, and blood pressure controls, respectively. Conclusion: Our findings provide clinically relevant information on the adjuvant therapy of magnesium for improving hyperglycemia, hypercholesterolemia, and hypertension in T2D.

Structural modulation of gut microbiota during alleviation of experimental passive Heymann nephritis in rats by a traditional Chinese herbal formula.

BACKGROUND: Jianpi-Qushi-Heluo formula (JQHF) has been used to treat idiopathic membranous nephropathy (IMN) in hospitals for many years. PURPOSE: Elucidating the protective effect and exploring the potential mechanism of JQHF against IMN. METHODS: Passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Then, the animals were treated with JQHF at 16.2 g/kg or 32.4 g/kg, with benzepril (10 mg/kg) as a positive control. Renal function was evaluated by biochemical measurements and pathological testing. Fecal samples were collected before and after treatment to analyze the gut microbiota composition by shotgun whole metagenome sequencing. RESULTS: JQHF exhibited potent efficacy in ameliorating PHN at both doses, as revealed by decreasing the deposition of IgG and C5b-9, relieving podocyte injury, and reducing glomerular and tubular cell apoptosis. The lower dose was corresponding to the clinical dosage and showed better therapeutic effects than the higher dose. Metagenomic analysis showed that gavage with 16.2 g/kg of JQHF shifted the structure of the gut microbiota in PHN rats and significantly increased the relative abundances of Prevotella copri, Lactobacillus vaginalis and Subdoligranulum variabile. Particularly, S. variabile was strongly negatively correlated with serum levels of TC and TG, the deposition of IgG and C5b-9, and apoptosis of glomerular cells. CONCLUSIONS: The JQHF is an effective agent for the treatment of experimental PHN. The PHN-allevating effect of JQHF is associated with specific alternation of gut microbiota.

Traditional Chinese Medicine in Treating IgA Nephropathy: From Basic Science to Clinical Research.

IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and end-stage renal disease worldwide. Currently, clinical interventions for IgAN are limited, and many patients seek out alternative therapies such as traditional Chinese medicine (TCM). In the last several years, TCM has accumulated ample application experiences and achieved favorable clinical effects. This article summarizes high-quality research from basic science to clinical applications aimed to provide more evidence-based medicine proof for the clinical treatment of IgAN. In summary, qi and yin deficiency accounted for the largest proportion in IgAN patients, and the treatment of IgAN should be based on supplementing qi and nourishing yin. Further, for patients with severe IgAN, the treatment combination of Chinese and Western medicines is better than pure Chinese medicine or hormone therapy. In addition, the pharmacological mechanism of Chinese herbal medicines is mostly based on restoring the immune function, relieving the inflammation damage, and inhibiting proliferation of the glomerular mesangial cells.

Integrated Network Pharmacology Analysis and Experimental Validation to Investigate the Mechanism of Zhi-Zi-Hou-Po Decoction in Depression.

Zhi-Zi-Hou-Po Decoction (ZZHPD) is a well-known traditional Chinese medicine (TCM) that has been widely used in depression. However, the antidepressant mechanism of ZZHPD has not yet been fully elucidated. The purpose of this study was to explore the pharmacological mechanisms of ZZHPD acting on depression by combining ultra flow liquid chromatography with quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF/MS) and network pharmacology strategy. The chemical components of ZZHPD were identified using UFLC-Q-TOF/MS, while the potential drug targets and depression-related targets were collected from databases on the basis of the identified compounds of ZZHPD. Protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were used to unravel potential antidepressant mechanisms. The predicted antidepressant targets from the pharmacology-based analysis were further verified in vivo. As a result, a total of 31 chemical compounds were identified by UFLC-Q-TOF/MS; 514 promising drug targets were mined by using the Swiss Target Prediction; and 527 depression-related target genes were pinpointed by the GeneCards and OMIM databases. STRING database and Cytoscape's topological analysis revealed 80 potential targets related to the antidepressant mechanism of ZZHPD. The KEGG pathway analysis revealed that the antidepressant targets of ZZHPD were mainly involved in dopaminergic synapse, serotonin synapse, cAMP, and mTOR signaling pathways. Furthermore, based on the animal model of depression induced by chronic corticosterone, the regulatory effects of ZZHPD on the expression of MAOA, MAOB, DRD2, CREBBP, AKT1, MAPK1, HTR1A, and GRIN2B mRNA levels as well as the cAMP signaling pathway and monoaminergic metabolism were experimentally verified in rats. Our study revealed that ZZHPD is expounded to target various genes and pathways to perform its antidepressant effect.

Phosphorus equivalency of phytase with various evaluation indicators of meat duck.

The objective of the present experiment was to determine the efficacy and the phosphorus (P) equivalency of phytase in the corn-soybean meal-rapeseed meal diets of Cherry Valley ducks from 1 to 35 d of age. 320 ducks were randomly divided into 8 blocks of 5 cages with 8 ducks per cage. This experiment included eight treatments diets. The available P levels of I to IV treatments were respectively 0.25%, 0.32%, 0.39%, 0.46% (d 1-14) and 0.20%, 0.27%, 0.34%, 0.41% (d 15-35). And 4 levels of phytase added to low-P basal diet (treatment I) with 300, 600, 900, and 1,200 U/kg (treatment V to VIII). Among them, treatment IV was a P-adequate positive control, treatment I was a low-P negative control. The ratio of calcium (Ca) to P was 1.3:1 for all diets. The other nutritional indexes in all diets were basically the same. Ducks were provided ad libitum access to water and experimental diets. The negative control diet reduced (P < 0.05) body weight, carcase weight, eviscerated weigh, breast muscle weight, leg muscle weight, bone ash, tibia Ca and tibia P, and increasing levels of available P and supplementary phytase significantly (P < 0.05) improved the growth performance and slaughtering performance of meat ducks. Phytase supplementation at a dose of 900 U/kg in the low-P basal diet increased the growth performance of ducks to a level comparable to that of a P-adequate diet. The available P level of 0.39% (1-14 d) and 0.34% (15-35 d) could meet the nutritional needs of meat ducks for P, and the apparent P utilization rate was high, and the effective utilization effect of P was the best. In addition, with the evaluation indexes of feed intake, body weight gain, tibia ash, tibia Ca, tibia P, content of blood Ca and P, the addition of 500 U/kg phytase could release available P of 0.02%, 0.02%, 0.02%, 0.02%, 0.01%, 0.04%, and 0.03%, respectively. In the same way, the addition of 1,000 U/kg phytase could release available phosphorus of 0.14%, 0.04%, 0.04%, 0.05%, 0.02%, 0.12%, and 0.01%, respectively.

Jianpi Qushi Heluo Formula alleviates renal damages in Passive Hemann nephritis in rats by upregulating Parkin-mediated mitochondrial autophagy.

Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.