Successful guselkumab treatment of a refractory psoriasis patient with Graves' disease: a case report.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn's disease and thyroid diseases. Graves' disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

Excessive dietary iron exposure increases the susceptibility of largemouth bass (Micropterus salmoides) to Aeromonas hydrophila by interfering with immune response, oxidative stress, and intestinal homeostasis.

Iron is an essential cofactor in the fundamental metabolic pathways of organisms. Moderate iron intake can enhance animal growth performance, while iron overload increases the risk of pathogen infection. Although the impact of iron on the pathogen-host relationship has been confirmed in higher vertebrates, research in fish is extremely limited. The effects and mechanisms of different levels of iron exposure on the infection of Aeromonas hydrophila in largemouth bass (Micropterus salmoides) remain unclear. In this study, experimental diets were prepared by adding 0, 800, 1600, and 3200 mg/kg of FeSO4∙7H2O to the basal feed, and the impact of a 56-day feeding period on the mortality rate of largemouth bass infected with A. hydrophila was analyzed. Additionally, the relationships between mortality rate and tissue iron content, immune regulation, oxidative stress, iron homeostasis, gut microbiota, and tissue morphology were investigated. The results showed that the survival rate of largemouth bass infected with A. hydrophila decreased with increasing iron exposure levels. Excessive dietary iron intake significantly increased iron deposition in the tissues of largemouth bass, reduced the expression and activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, increased the content of lipid peroxidation product malondialdehyde, and thereby induced oxidative stress. Excessive iron supplementation could influence the immune response of largemouth bass by upregulating the expression of pro-inflammatory cytokines in the intestine and liver, while downregulating the expression of anti-inflammatory cytokines. Additionally, excessive iron intake could also affect iron metabolism by inducing the expression of hepcidin, disrupt intestinal homeostasis by interfering with the composition and function of the gut microbiota, and induce damage in the intestinal and hepatic tissues. These research findings provide a partial theoretical basis for deciphering the molecular mechanisms underlying the influence of excessive iron exposure on the susceptibility of largemouth bass to pathogenic bacteria.

Effects of mindfulness-based interventions on cardiovascular risk factors: An umbrella review of systematic reviews and meta-analyses.

OBJECTIVE: Reviews have shown that mindfulness-based interventions (MBIs) were effective in improving cardiovascular risk factors (CVRFs), but the results were contradictory. This umbrella review aimed to summarize and grade the existing reviews on CVRFs associated with MBIs. METHODS: The protocol of this umbrella review had been registered in PROSPERO (CRD42022356812). PubMed, Web of science, Embase, The Cochrane Library, Scopus, Medline, PsycINFO and CINAHL were searched from database inception to 20 July 2022. The quality of evidence was assessed through GRADE. RESULTS: Twenty-seven reviews with 14,923 participants were included. Overall, 45% of reviews had low heterogeneity (I2 < 25%). For the quality of evidence, 31% were rated very low, 42% were rated low, 17% were rated moderate and 10% were rated high. MBIs significantly improved systolic blood pressure [SMD -5.53 mmHg (95% CI -7.81, -3.25)], diastolic blood pressure [SMD -2.13 mmHg (95% CI -2.97, -1.30)], smoking [Cohen's d 0.42 (95% CI 0.20, 0.64)], glycosylated hemoglobin [MD 0.01 (95% CI -0.43, -0.07)], binge eating behavior [SMD -6.49 (95% CI -10.80, -2.18)], depression [SMD -0.72 (95% CI -1.23, -0.21)] and stress [SMD -0.67 (95% CI -1.00, -0.34)]. CONCLUSIONS: In conclusion, this umbrella review provided evidence for the role of MBIs in the improvement of CVRFs.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Regulatory effects of Zishen Yutai Pill on endometrial epithelial response in vitro in immunology microenvironment.

Objective: Zishen Yutai Pill (ZYP) is a frequently used traditional Chinese medicine (TCM) preparation in women's health. However, the effects of ZYP on endometrial epithelial response have not been fully explored. Herein, uterine natural killer cell (uNK) secretion medium was used to mimic the uterine microenvironment. Thereafter, an endometrial epithelial cell line (Ishikawa cells) was treated with ZYP-containing serum to elucidate the effects of ZYP on endometrial receptivity.Methods: uNK cells were isolated from decidual tissues of pregnant women undergoing pregnancy termination surgery, and thereafter, uNK secretion medium was collected. ZYP-containing serum was collected from rats after intragastrical administration of ZYP. Ishikawa cells were divided into three groups, one treated with blank control (control group), one treated with uNK secretion medium (uNK group), and one treated with both uNK secretion medium and ZYP-containing serum (ZYP + uNK group). Total RNAs were extracted. Gene expression profiles of Ishikawa in different groups were determined through microarray analysis. mRNA expressions of selected genes were determined through quantitative real-time polymerase chain reaction (qRT-PCR). Expression of intercellular cell adhesion molecule-1 (ICAM-1) was determined using Western blotting (WB). Results: Compared with the uNK group, the gene expressions of ZYP group with a total of 1117 genes were significantly altered, among which 510 genes were upregulated and 607 genes were downregulated. Compared with uNK group, expressions of CSF1, CSF2, SPP1, and ICAM1 were upregulated (P < 0.05). Up-regulation of ICAM-1 expression after treatment of ZYP was further confirmed by WB analysis. Conclusion: In brief, in the presence of uNK cell medium, ZYP could improve the expressions of ICAM1, CSF1, CSF2, TNF, SPP1, etc. However, further exploration should be carried out in in vivo experiments for the validation of the mechanisms of ZYP on endometrial epithelial response.

[Resource components and utilization values of different parts of Panax quinquefolium in Shandong province].

To explore the resource components and availability of different parts of Panax quinquefolium in Shandong province, the paper employed the non-targeted metabolomics technology based on ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) to analyze the metabolites and their metabolic pathways in the root, fibril, stem, and leaf of P. quinquefolium. The content of seven ginsenosides and polysaccharides in different parts was determined by high performance liquid chromatography(HPLC) and ultraviolet-visible spectrophotometry(UV-Vis). The results showed that the metabolites were mainly sugars, glycosides, organic acids, amino acids and their derivatives, terpenoids, etc. The total abundance of metabolites followed the trend of leaf > root > fibril > stem. Most of the differential metabolites were concentrated in phenylpropane biosynthesis, flavonoid biosynthesis, citric acid cycle, and amino acid biosynthesis. The leaf contained high levels of sugars, glycosides, amino acids and their derivatives, and flavonoids; the root was rich in terpenoids, volatile oils, vitamins, and lignin; the fibril contained rich organic acids; and the stem had high content of nucleotides and their derivatives. The content of ginsenosides Re and Rb_1 was significantly higher in the root; the content of ginsenosides Rg_1, Rg_2, Rd, F_(11), and polysaccharide was significantly higher in the leaf; and the content of ginsenoside Rb_2 was significantly higher in the stem. We analyzed the resource components and availability of different parts of P. quinquefolium, aiming to provide basic information for the comprehensive development and utilization of P. quinquefolium resources in Shandong province.

Methionine Supplementation Affects Fecal Bacterial Community and Production Performance in Sika Deer (Cervus nippon).

Amino acid balance is central to improving the efficiency of feed protein utilization and for reducing environmental pollution caused by intensive farming. In previous studies, supplementation with limiting amino acids has been shown to be an effective means of improving animal nutrient utilization and performance. In this experiment, the effects of methionine on the apparent digestibility of nutrients, antler nutrient composition, rumen fluid amino acid composition, fecal volatile fatty acids and intestinal bacteria in antler-growing sika deer were investigated by randomly adding different levels of methionine to the diets of three groups of four deer at 0 g/day (CON), 4 g/day (LMet) and 6 g/day (HMet). Methionine supplementation significantly increased the apparent digestibility of organic matter, neutral detergent fiber (NDF) and acid detergent fiber (ADF) in the LMet group (p < 0.05). The crude protein and collagen protein of antlers were significantly higher in the LMet and HMet groups compared to the CON group and also significantly higher in the HMet group compared to the LMet group, while the calcium content of antlers was significantly lower in the HMet group (p < 0.05). Ruminal fluid free amino acid composition was altered in the three groups of sika deer, with significant changes in aspartic acid, citrulline, valine, cysteine, methionine, histidine and proline. At the phylum level, Firmicutes and Bacteroidetes were highest in the rectal microflora. Unidentified bacterial abundance was significantly decreased in the HMet group compared to the CON group. Based on the results of principal coordinate analysis (PCoA) and Adonis analysis, there was a significant difference in the composition of the intestinal flora between the CON and HMet groups (p < 0.05). At the genus level, compared with the CON group, the abundance of Rikenellaceae_RC9_gut_group and Lachnospiraceae_UCG-010 in the LMet group increased significantly (p < 0.05), the abundance of dgA-11_gut_group in the HMet group decreased significantly (p < 0.05) and the abundance of Lachnospiraceae_UCG-010, Saccharofermentans and Lachnospiraceae_NK3A20_group increased significantly. Taken together, the results showed that methionine supplementation was beneficial in increasing the feed utilization efficiency and improving antler quality in sika deer, while affecting the composition of fecal bacteria.

Transcriptomics and metabolomics reveal the changes induced by arbuscular mycorrhizal fungi in Panax quinquefolius L.

BACKGROUND: Panax quinquefolius L. is one of the most important foods and herbs because of its high nutritional value and medicinal potential. In our previous study we found that the ginsenoside content in P. quinquefolius was improved by arbuscular mycorrhizal fungi (AMFs). However, little research has been conducted on the molecular mechanisms in P. quinquefolius roots induced by AMFs colonization. To identify the metabolomic and transcriptomic mechanisms of P. quinquefolius induced by AMFs, non-mycorrhized (control) and mycorrhized (AMF) P. quinquefolius were used as experimental materials for comparative analysis of the transcriptome and metabolome. RESULTS: Compared with the control, 182 metabolites and 545 genes were significantly changed at the metabolic and transcriptional levels in AMFs treatment. The metabolic pattern of AMFs was changed, and the contents of ginsenosides (Rb1, Rg2), threonine, and glutaric acid were significantly increased. There were significant differences in the expression of genes involved in plant hormone signal transduction, glutathione metabolism, and the plant-pathogen interaction pathway. In addition, several transcription factors from the NAC, WRKY, and basic helix-loop-helix families were identified in AMFs versus the control. Furthermore, the combined analysis of 'transcriptomics-metabolomics' analysis showed that 'Plant hormone signal transduction', 'Amino sugar and nucleotide sugar metabolism' and 'Glutathione metabolism' pathways were the important enriched pathways in response to AMFs colonization. CONCLUSION: Overall, these results provide new insights into P. quinquefolius response to AMFs, which improve our understanding of the molecular mechanisms of P. quinquefolius induced by AMFs. © 2023 Society of Chemical Industry.

The effect of tomato and lycopene on clinical characteristics and molecular markers of UV-induced skin deterioration: A systematic review and meta-analysis of intervention trials.

Lycopene as a natural antioxidant that have been studied for ultraviolet radiation (UVR) photo protection and is one of the most effective carotenoids to scavenge reactive oxygen species (ROS). This review aims to summarize the protective effect of tomato and lycopene on skin photo damage and skin photoaging in healthy subjects by reviewing the existing population intervention experiments. A total of five electronic databases including PubMed, Scopus, EBSCO, Web of Science and Cochrane Library were searched from inceptions to January 2021 without any restriction. Out of 19336 publications identified, 21 fulfilled the inclusion criteria and were meta-analysis. Overall, interventions supplementing tomato and lycopene were associated with significant reductions in Δa*, MMP-1, ICAM-1 and skin pigmentation; while tomato and lycopene supplementation were associated with significant increase in MED, skin thickness and skin density. Based on the results of this systematic review and meta-analysis, supplementation with tomato and lycopene could reduce skin erythema formation and improve the appearance and pigmentation of the skin, thereby preventing light-induced skin photodamage and skin photoaging. Lycopene-rich products could be used as endogenous sun protection and may be a potential nutraceutical for sun protection.

Effects of fermented dairy products on inflammatory biomarkers: A meta-analysis.

AIM: Fermented dairy products (FDPs) are made from raw milk under the action of specific microorganisms by lactic acid bacteria fermentation or co-fermentation of lactic acid bacteria, bifidobacteria, and yeast. The aim of this study was to explore the effects of FDPs on inflammatory biomarkers. DATA SYNTHESIS: A comprehensive search was conducted on four electronic databases, including PubMed, Web of Science, Embase, and the Cochrane Library. Finally, fourteen trials (15 arms) were included in this meta-analysis: yogurt (n = 9), fermented milk (n = 4), and kefir (n = 2). Additionally, the random effects model or fixed-effects model was used to pool the study results. Firstly, the analysis indicated that FDPs' supplementation decreased the levels of C-reactive protein (CRP) (SMD = -0.21; 95% CI: -0.40, -0.02; P = 0.033) and increased interferon-gamma (IFN-γ) levels (SMD = 0.12; 95% CI: 0.01, 0.23; P = 0.033). Furthermore, we obtained some statistically significant results in the following subgroups: CRP decreased in participants with metabolic diseases. IFN-γ increased in the intervention that lasted ≥12 weeks, Asian, yogurt, and healthy population. Finally, there was no significant effect on tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and IL-2. CONCLUSIONS: FDPs reduced CRP and increased IFN-γ, but they had no effect on other inflammatory markers. The results showed that the consumption of FDPs was slightly associated with reduced inflammation, but because of the limited literature, these results should be interpreted with caution.

Glutamine alleviates intestinal injury in a murine burn sepsis model by maintaining intestinal intraepithelial lymphocyte homeostasis.

Intestinal intraepithelial lymphocytes (IELs) play a sentinel role in the mucosal immune system because of their unique anatomical location in the epithelial layer. The disruption of IEL homeostasis is implicated in driving the intestinal injury of many typical inflammatory disorders, such as inflammatory bowel disease (IBD) and sepsis. Therefore, it is meaningful to alleviate intestinal injury by restoring IEL homeostasis in disease conditions. This study explores the effects of glutamine on intestinal IEL homeostasis in a murine model of burn sepsis. We report that glutamine inhibits inflammatory response and reduces injury in the small intestine of burn septic mice. This effect is attributed to the maintaining of IEL homeostasis by suppressing apoptosis and restoring the disrupted subpopulation balance induced by burn sepsis. Mechanistically, we show that glutamine does not affect the IL-15 dependent mechanisms that drive the maintenance and differentiation of IELs. Instead, glutamine sustains IEL homeostasis by upregulate aryl hydrocarbon receptor (AHR) and interleukin (IL)-22 transcription and expression. Consistently, the protective roles of glutamine in burn septic mice were repressed by further supplement with an AHR antagonist CH-223191. Collectively, our study reveals a new role of glutamine to maintain IEL homeostasis by activating the AHR signaling pathway, which in turn ameliorates intestinal injury in burn sepsis.

Electroacupuncture Enhances Gastric Accommodation via the Autonomic and Cytokine Mechanisms in Functional Dyspepsia.

BACKGROUND: Due to complex pathophysiology of functional dyspepsia, medications to treat functional dyspepsia are not effective for all patients. Transcutaneous electrical acustimulation (TEA) is an potentially effective therapy for functional dyspepsia without proofs of definite mechanisms. AIMS: We aimed to investigate the therapeutic impacts of TEA on postprandial distress syndrome (PDS) and explore potential neuroimmune mechanisms. METHODS: We conducted a double-blinded, randomized, controlled trial in 30 PDS patients randomized for 4-week TEA or sham-TEA. Dyspeptic symptoms, gastric accommodation, gastric emptying and heart rate variability (HRV) were assessed. Duodenal mucosal inflammation was also evaluated. RESULTS: The dyspeptic symptoms were improved with TEA compared with sham-TEA (P = 0.03). The initial satiety volume and the maximum tolerable volume (MTV) were both improved after the TEA treatment, compared with the sham-TEA group (P all < 0.05). The gastric emptying time (T1/2) was not altered with TEA or sham-TEA. The TEA treatment increased vagal activity and decreased sympathovagal ratio assessed by HRV (P all < 0.01). The IL-6 expression in bulb mucosa was downregulated by the TEA treatment compared to the baseline (P < 0.05). CONCLUSIONS: Noninvasive TEA improves gastric accommodation and dyspeptic symptoms, possibly by downregulating the IL-6 expression in duodenal bulb mucosa via the vagal efferent pathway.

Effects of telemedicine interventions on essential hypertension: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Essential hypertension is a major preventable risk factor for early cardiovascular disease, premature death and disability. It has been reported that telemedicine interventions can provide an innovative solution to essential hypertension to overcome the barriers that exist in traditional treatment or control. Nevertheless, this subject has not been thoroughly investigated. The goal of this study is to systematically evaluate and describe the impact of telemedicine interventions on essential hypertension. METHODS AND ANALYSIS: To find relevant research, we will conduct a systematic literature search of three databases (PubMed, Embase and Cochrane Library), with no language limitations, in addition to researching grey literature. Two reviewers will extract the data individually, and any disagreements will be resolved by discussion or by a third reviewer. The randomised controlled trials will be chosen based on predetermined inclusion criteria. Primary outcomes will include systolic blood pressure and diastolic blood pressure after the telemedicine intervention. Secondary outcomes will include medication adherence (eg, the Morisky Medication Adherence Questionnaire), quality of life (eg, the MOS item scale of the Health Survey Short Form 36 questionnaire), blood pressure control rate and adverse events (eg, stroke, chronic renal failure, aortic dissection, myocardial infarction and heart failure). The quality of the included studies will be assessed using the Cochrane risk-of-bias method. The data will be analysed using RevMan V.5.3.5 software and STATA V.16.0 software. If heterogeneity testing reveals little or no statistical heterogeneity, a fixed effect model will be used for data synthesis; otherwise, a random effect model would be employed. We will synthesise the available evidence to perform a high-quality meta-analysis. ETHICS AND DISSEMINATION: This project does not require ethical approval because it will be conducted using publicly available documents. The review's findings will be published in peer-reviewed journals and publications. PROSPERO REGISTRATION NUMBER: CRD42021293539.

Zingiberaceae plants/curcumin consumption and multiple health outcomes: An umbrella review of systematic reviews and meta-analyses of randomized controlled trials in humans.

This umbrella review is to recapitulate and grade the available evidence of associations between consumption of Zingiberaceae plants/curcumin (Cur) and multiple health-related outcomes. This study included 161 meta-analyses of randomized controlled trials in 76 articles with 67 unique health outcomes. Data on heterogeneity and publication bias are considered to assess the quality of evidence. Based on the different impact of Zingiberaceae plants/Cur on human health, the advantages outweigh the disadvantages. Zingiberaceae plants/Cur can mainly improve metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and some chronic inflammatory diseases, likewise, obviously relief the pain of osteoarthritis and related diseases. Ginger supplements have been shown to improve vomiting during pregnancy and to relieve nausea and vomiting caused by chemotherapy and surgery. The surgery is any type of surgery, including laparoscopic surgery, gynecological surgery and mixed surgery. Beneficial associations were found with Cur intervention in gastrointestinal, neurological and oral diseases. Zingiberaceae plants/Cur are generally safe and favorable for multiple health outcomes in humans. High-quality research is further needed to prove the observed associations.

Effects of medical plants from Zingiberaceae family on cardiovascular risk factors of type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

We performed a meta-analysis on randomized controlled trials (RCTs) to evaluate the efficacy of Zingiberaceae on cardiovascular risk factors in type 2 diabetes mellitus (T2DM). PubMed, Web of Science, Embase, The Cochrane Library, and Scopus were searched systematically until October 18, 2021. Thirty-four RCTs with 2154 patients met our inclusion. Pooled analysis indicated that Zingiberaceae can significantly improve body weight (BW) (WMD = -1.012, 95% CI: -1.673, -0.351, p = .003), fasting blood glucose (FBG) (WMD = -14.292, 95% CI: -18.588, -9.995, p < .001), glycosylated hemoglobin 1c (HbA1c) (WMD = -0.432, 95% CI: -0.607, -0.257, p < .001), serum insulin (WMD = -2.036, 95% CI: -2.857, -1.216, p < .001), homeostasis model assessment insulin resistance (HOMA-IR) (WMD = -0.886, 95% CI: -1.375, -0.398, p < .001), high density lipoprotein-cholesterol (HDL-C) (WMD = 0.850, 95% CI: 0.018, 1.682, p = .045), triglyceride (TG) (WMD = -17.636, 95% CI: -27.121, -8.151, p < .001), diastolic blood pressure (DBP) (WMD = -0.642, 95% CI: -1.148, -0.137, p = .013), C-reactive protein (CRP) (WMD = -0.623, 95% CI: -1.061, -0.186, p = .005), tumor necrosis factor-α (TNF-α) (WMD = -3.020, 95% CI: -4.327, -1.712, p < .001), and interleukin 6 (IL-6) (WMD = -1.147, 95% CI: -1.887, -0.406, p = .002). The supplementation of Zingiberaceae may be an effective adjunctive therapy in management of T2DM and prevention cardiovascular complications by decreasing BW, improving blood glucose control, insulin resistance, lipid profiles (HDL-C and TG), blood pressure (DBP), and reducing inflammation (CRP, TNF-α, and IL-6). PRACTICAL APPLICATIONS: Approximately half of the deaths of individuals with diabetes mellitus (DM) are attributable to cardiovascular disease (CVD), and individuals with T2DM have a two-fold increased risk of cardiovascular mortality than healthy individuals. Currently, T2DM is mainly treated with hypoglycemic medication such as sulfonylureas, thiazolidinediones, meglitinides, and biguanides. Nevertheless, most of them with long-term usage could cause side effects, including hypoglycemia and gastrointestinal troubles. Several species of the Zingiberaceae family are used in traditional herbal medicines, which have been widely used in traditional and complementary medicine. Proving the potential benefits of Zingiberaceae on T2DM and its cardiovascular complications has positive clinical implications for the use of this practical herb.

Effects of the Zishen Yutai Pill Compared With Placebo on Live Births Among Women in a Fresh Embryo Transfer Cycle: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles. METHODS: We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, and maternal, fetal, and neonatal complications. A total sample size of 2,265 women (1:1 in two groups) was used to detect a live birth rate difference between the Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of the Zishen Yutai Pill or placebo orally, three times per day during the study. RESULTS: Recruitment was completed between April 2014 and June 2017, with 2,580 patients screened. Two thousand two hundred sixty-five patients were randomized: 1,131 to the Zishen Yutai Pill and 1,134 to placebo. Characteristics were similar between groups. In intention-to-treat analysis, the rates of live birth in the Zishen Yutai Pill (ZYP) group and placebo group were 26.8% and 23.0% (rate ratio [RR], 1.16; 95% CI 1.01-1.34; P=.038), respectively. The implantation rates were 36.8% and 32.6% in the ZYP and placebo groups, respectively (RR 1.13; 95% CI 1.01-1.25; P=.027). The biochemical pregnancy rate for the ZYP group was 35.5% compared with 31.1% in the placebo group (RR 1.14; 95% CI 1.02-1.28; P=.026). The rates of clinical pregnancy in the ZYP and placebo groups were 31.2% compared with 27.3%, respectively (RR 1.14; 95% CI 1.00-1.30; P=.043). There were no significant between-group differences in the rates of pregnancy loss, maternal, or neonatal complications (all P>.05). CONCLUSION: The Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, Chictr-TRC-14004494.

Flavonoid constituents of Amomum tsao-ko Crevost et Lemarie and their antioxidant and antidiabetic effects in diabetic rats - in vitro and in vivo studies.

Amomum tsao-ko Crevost et Lemarie (A. tsao-ko) is a well-known dietary spice and traditional Chinese medicine. This study aimed to identify the flavonoids in A. tsao-ko and evaluate their antioxidant and antidiabetic activities in in vitro and in vivo studies. A. tsao-ko methanol extracts possessed a high flavonoid content (1.21 mg QE per g DW) and a total of 29 flavonoids were identified by employing UPLC-MS/MS. In vitro, A. tsao-ko demonstrated antioxidant activity (ORAC value of 34276.57 µM TE/100 g DW, IC50 of ABTS of 3.49 mg mL-1 and FRAP value of 207.42 µM Fe2+ per g DW) and α-amylase and α-glucosidase inhibitory ability with IC50 values of 14.23 and 1.76 mg mL-1, respectively. In vivo, type 2 diabetes mellitus (T2DM) models were induced by a combined high-fat diet (HFD) and streptozotocin (STZ) injection in rats. Treatment with the A. tsao-ko extract (100 mg freeze-dried powder per kg bw) for 6 weeks could significantly improve impaired glucose tolerance, decrease the levels of fasting blood glucose (FBG), insulin, and malondialdehyde (MDA), and increase the superoxide dismutase (SOD) level. Histopathology revealed that the A. tsao-ko extract preserved the architecture and function of the pancreas. In conclusion, the flavonoid composition of A. tsao-ko exhibits excellent antioxidant and antidiabetic activity in vitro and in vivo. A. tsao-ko could be a novel natural material and developed as a related functional food and medicine in T2DM management.

Effect of cold and heat therapies on pain relief in patients with delayed onset muscle soreness: A network meta-analysis.

OBJECTIVE: To comprehensively compare the effectiveness of cold and heat therapies for delayed onset muscle soreness using network meta-analysis. METHODS: Eight Chinese and English databases were searched from date of establishment of the database to 31 May 2021. Cochrane risk-of-bias tool was used to analyse the included randomized controlled trials. Potential papers were screened for eligibility, and data were extracted by 2 independent researchers. RESULTS: A total of 59 studies involving 1,367 patients were eligible for this study. Ten interventions were examined: contrast water therapy, phase change material, the novel modality of cryotherapy, cold-water immersion, hot/warm-water immersion, cold pack, hot pack, ice massage, ultrasound, and passive recovery. Network meta-analysis results showed that: (i) within 24 h after exercise, hot pack was the most effective for pain relief, followed by contrast water therapy; (ii) within 48 h, the ranking was hot pack, followed by the novel modality of cryotherapy; and (iii) over 48 h post-exercise, the effect of the novel modality of cryotherapy ranked first. CONCLUSION: Due to the limited quality of the included studies, further well-designed research is needed to draw firm conclusions about the effectiveness of cold and heat therapies for delayed onset muscle soreness.

Mechanism of Fei-Xian Formula in the Treatment of Pulmonary Fibrosis on the Basis of Network Pharmacology Analysis Combined with Molecular Docking Validation.

OBJECTIVE: This study aimed to clarify the mechanism of Fei-Xian formula (FXF) in the treatment of pulmonary fibrosis based on network pharmacology analysis combined with molecular docking validation. METHODS: Firstly, ingredients in FXF with pharmacological activities, together with specific targets, were identified based on the BATMA-TCM and TCMSP databases. Then, targets associated with pulmonary fibrosis, which included pathogenic targets as well as those known therapeutic targets, were screened against the CTD, TTD, GeneCards, and DisGeNet databases. Later, Cytoscape was employed to construct a candidate component-target network of FXF for treating pulmonary fibrosis. In addition, for nodes within the as-constructed network, topological parameters were calculated using CytoHubba plug-in, and the degree value (twice as high as the median degree value for all the nodes) was adopted to select core components as well as core targets of FXF for treating pulmonary fibrosis, which were subsequently utilized for constructing the core network. Furthermore, molecular docking study was carried out on those core active ingredients together with the core targets using AutoDock Vina for verifying results of network pharmacology analysis. At last, OmicShare was employed for enrichment analysis of the core targets. RESULTS: Altogether 12 active ingredients along with 13 core targets were identified from our constructed core component-target network of FXF for the treatment of pulmonary fibrosis. As revealed by enrichment analysis, the 13 core targets mostly concentrated in regulating biological functions, like response to external stimulus (from oxidative stress, radiation, UV, chemical substances, and virus infection), apoptosis, cell cycle, aging, immune process, and protein metabolism. In addition, several pathways, like IL-17, AGE-RAGE, TNF, HIF-1, PI3K-AKT, NOD-like receptor, T/B cell receptor, and virus infection-related pathways, exerted vital parts in FXF in the treatment of pulmonary fibrosis. CONCLUSIONS: FXF can treat pulmonary fibrosis through a "multicomponent, multitarget, and multipathway" mean. Findings in this work lay foundation for further exploration of the FXF mechanism in the treatment of pulmonary fibrosis.

Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells.

With age, hematopoietic stem cells (HSC) undergo changes in function, including reduced regenerative potential and loss of quiescence, which is accompanied by a significant expansion of the stem cell pool that can lead to haematological disorders. Elevated metabolic activity has been implicated in driving the HSC ageing phenotype. Here we show that nicotinamide riboside (NR), a form of vitamin B3, restores youthful metabolic capacity by modifying mitochondrial function in multiple ways including reduced expression of nuclear encoded metabolic pathway genes, damping of mitochondrial stress and a decrease in mitochondrial mass and network-size. Metabolic restoration is dependent on continuous NR supplementation and accompanied by a shift of the aged transcriptome towards the young HSC state, more youthful bone marrow cellular composition and an improved regenerative capacity in a transplant setting. Consequently, NR administration could support healthy ageing by re-establishing a more youthful hematopoietic system.