Individualized Weight Management and Its Impact on Pregnancy Outcomes in Overweight/Obese Infertile Women: A Retrospective Study.

Background: Previous studies link overweight/obesity to reduced fertility, highlighting weight intervention as vital for better pregnancy outcomes. However, clarity on the role and efficacy of weight loss in enhancing pregnancy is inconsistent. Objective: This study aimed to assess the impact of individualized weight intervention on pregnancy among Chinese overweight/obese infertile women and explore body composition indexes influencing pregnancy outcomes. Methods: This retrospective study involved 363 overweight/obese infertile women admitted to the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from June 2017 to November 2020. Among them, 249 received personalized weight intervention (intervention group), while 114 did not (control group). Pregnancy outcomes were compared between the two groups, and changes in body composition before and after intervention were measured. Multivariate logistic regression was employed to analyze factors influencing pregnancy outcomes. Results: The intervention group exhibited significantly higher clinical pregnancy rates, natural pregnancy rates, assisted reproductive pregnancy rates, and induced ovulation (IO) pregnancy rates compared to the control group (all P < .05). Following weight intervention, there were significant decreases in body weight, body mass index (BMI), visceral fat area, and body fat (all P < .01). Logistic regression analysis identified polycystic ovary syndrome as the reason for infertility (OR=3.446, P = .016), ∆body weight %≥10% (OR=2.931, P = .014), and ∆visceral fat area% (OR=1.025, P = .047) as positive factors for a successful pregnancy. Conversely, age≥35 years old (OR=0.337, P = .001), BMI≥25 kg/m2 after intervention (OR=0.279, P < .001), and visceral fat area≥100 cm2 after intervention (OR=0.287, P = .007) were identified as negative factors. Conclusions: Individualized weight management enhances pregnancy outcomes in overweight/obese infertile women. Achieving a reduction in body weight by 10% or more, combined with effective control of visceral fat, proves important in improving pregnancy outcomes. Excess visceral fat emerges as an adverse factor impacting successful pregnancy.

Abscisic acid inhibited reactive oxygen species-mediated endoplasmic reticulum stress by regulating the PPAR-γ signaling pathway in ARDS mice.

Acute respiratory distress syndrome (ARDS) is a life-threatening form of a respiratory disorder, and there are few effective therapies. Abscisic acid (ABA) has been proven to be effective in influenza and asthma. Herein, we explored the protective effect of ABA on the resolution of ARDS and the underlying mechanism. Mice were challenged with lipopolysaccharide (LPS) to establish an ARDS model. We found that ABA reduced pulmonary injury, with concomitant suppression of endoplasmic reticulum (ER) stress and reduction of reactive oxygen species (ROS) production. Furthermore, after the elimination of ROS by the specific inhibitor N-acetyl-L-cysteine (NAC), ABA did not further inhibit airway inflammation or ER stress in ARDS mice. In addition, ABA inhibited ROS production through nuclear factor erythroid 2-related factor 2 (Nrf2) activation in parallel with elevated levels of peroxisome proliferator activated receptor γ (PPAR-γ). Furthermore, the addition of a PPAR-γ antagonist abrogated the suppressive action of ABA on inflammation as well as on ER stress and oxidative stress, while NAC restored the protective effect of ABA in ARDS mice treated with a PPAR-γ antagonist. Collectively, ABA protects against LPS-induced lung injury through PPAR-γ signaling, and this effect may be associated with its inhibitory effect on ROS-mediated ER stress.

Network Pharmacology and Molecular Docking Suggest the Mechanism for Biological Activity of Rosmarinic Acid.

Rosmarinic acid (RosA) is a natural phenolic acid compound, which is mainly extracted from Labiatae and Arnebia. At present, there is no systematic analysis of its mechanism. Therefore, we used the method of network pharmacology to analyze the mechanism of RosA. In our study, PubChem database was used to search for the chemical formula and the Chemical Abstracts Service (CAS) number of RosA. Then, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to evaluate the pharmacodynamics of RosA, and the Comparative Toxicogenomics Database (CTD) was used to identify the potential target genes of RosA. In addition, the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of target genes were carried out by using the web-based gene set analysis toolkit (WebGestalt). At the same time, we uploaded the targets to the STRING database to obtain the protein interaction network. Then, we carried out a molecular docking about targets and RosA. Finally, we used Cytoscape to establish a visual protein-protein interaction network and drug-target-pathway network and analyze these networks. Our data showed that RosA has good biological activity and drug utilization. There are 55 target genes that have been identified. Then, the bioinformatics analysis and network analysis found that these target genes are closely related to inflammatory response, tumor occurrence and development, and other biological processes. These results demonstrated that RosA can act on a variety of proteins and pathways to form a systematic pharmacological network, which has good value in drug development and utilization.

Abscisic acid suppresses the activation of NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation.

Abscisic acid (ABA), a well-known natural phytohormone reportedly exerts anti-inflammatory and anti-oxidative properties in diabetes and colitis. However, the efficacy of ABA against allergic airway inflammation and the underlying mechanism remain unknown. Herein, an OVA-induced murine allergic airway inflammation model was established and treated with ABA in the presence or absence of PPAR-γ antagonist GW9662. The results showed that ABA effectively stunted the development of airway inflammation, and concordantly downregulated OVA-induced activation of NLRP3 inflammasome, suppressed oxidative stress and decreased the expression of mitochondrial fusion/fission markers including Optic Atrophy 1 (OPA1), Mitofusion 2 (Mfn2), dynamin-related protein 1 (DRP1) and Fission 1 (Fis1). Moreover, ABA treatment further increased OVA-induced expression of PPAR-γ, while GW9662 abrogated the inhibitory effect of ABA on allergic airway inflammation as well as on the activation of NLRP3 inflammasome and oxidative stress. Consistently, ABA inhibited the activation of NLRP3 inflammasome, suppressed oxidative stress and mitochondrial fusion/fission in LPS-stimulated Raw264.7 cells via PPAR-γ. Collectively, ABA ameliorates OVA-induced allergic airway inflammation in a PPAR-γ dependent manner, and such effect of ABA may be associated with its inhibitory effect on NLRP3 inflammasome and oxidative stress. Our results suggest the potential of ABA or ABA-rich food in protecting against asthma.

Comparison of PSORI-CM01 granules and Yinxieling tablets for patients with chronic plaque psoriasis: a pilot study for a randomized, double-blinded, double-dummy, multicentre trial.

BACKGROUND: To compare the efficacy and safety of PSORI-CM01 granules with Yinxieling tablets in patients with chronic plaque psoriasis (CPP), we plan to conduct a multicentre, randomized, double-blinded, double-dummy, controlled trial. This pilot study was conducted to determine the feasibility and the potential of the protocol for the full-scale randomized controlled trial (RCT). METHODS: This pilot study was conducted in three centers, and compared PSORI-CM01 granules with Yinxieling tablets in patients with CPP during a 12-week treatment and 3-month follow-up period. The primary efficacy endpoint was the decrease of the psoriasis area severity index (PASI) at week 12. The secondary outcome measures included reduction rates of PASI, pruritus scores on the Visual Analogue Scale (VAS), body surface area (BSA), and the Dermatology Life Quality Index (DLQI). Safety was assessed via the incidence of adverse events (AEs) in each treatment group. RESULTS: A total of 211 patients were screened, and 63 subjects who met the inclusion criteria were randomised to PSORI-CM01 granule group (N=31) or Yinxieling tablets group (N=32) while 39 subjects finished the study. The primary outcome measure showed a mean decrease of PASI of 2.03 in the PSORICM01 group compared to 0.89 in the Yinxieling group at week 12. Except for the VAS score (t=-2.261, P=0.027), the secondary outcomes showed no significant improvement from baseline in both groups at week 12. No safety or tolerability concerns related to the drugs were observed in either group. CONCLUSIONS: This pilot study showed that the RCT is feasible for randomization, patient recruitment, and assessment. Major strategies are necessary to reduce the patient dropout rate before conducting the full RCT. In this pilot study, the PSORI-CM01 granule exhibited greater potential for development compared to its original formula (Yinxieling tablets) for the treatment of CPP.

Add-on effect of PSORI-CM01 to topical calcipotriol for moderate psoriasis vulgaris: A multi-center, randomized, double-blind pilot study.

BACKGROUND: Mild-moderate psoriasis vulgaris is a common dermatological autoimmune condition with limited conventional therapeutic options. Safe and effective adjunct therapies to topical non-steroidal antipsoriatic therapy are needed. The oral Chinese herbal medicine (CHM) formula PSORI-CM01 has been evidenced potential antipsoriatic pharmacological activity. This article reports a pilot study which was designed as a double-blinded, placebo-controlled randomized controlled trial (RCT) evaluating the effects of PSORI-CM01 when added to topical calcipotriol cream. METHODS: People with moderate psoriasis vulgaris were randomized to receive oral PSORI-CM01 or placebo administered for 12 weeks in combination with calcipotriol. The primary clinical outcome was the change of psoriasis area severity index (PASI) score at week 12 and week 24. Secondary clinical outcomes were PASI75, PASI50, relapse rate, change in body surface area, dermatology life quality index and Skindex29, and adverse events (AEs). Participants' satisfaction and willingness to repeat were also assessed. RESULTS: The pilot study was conducted in Australia and China, 29 participants were randomized with 26 completed the treatment and follow-up. Participants' baseline basic characteristics were comparable. No between-group statistical significance was found on pre-defined clinical outcome measures, although there seemed a trend of treatment effects favoring the combination of PSORI-CM01 with calcipotriol. Frequency and severity of AEs were similar between two groups, with no severe AEs reported. CONCLUSIONS: The design and duration of the study appears feasible. A proper powered RCT with slight adjustments in the methods is needed to reveal the add-on effects of oral CHM PSORI-CM01. The experience and results from this pilot study will contribute to the refine of objectives and design of a future study, and assist the sample size calculation for the full-scale RCT.

Oral Chinese herbal medicine for psoriasis vulgaris: protocol for a randomised, double-blind, double-dummy, multicentre clinical trial.

INTRODUCTION: Psoriasis vulgaris is a common skin disease that is characterised by persistent localised erythematous scaly plaques. Yinxieling is a Chinese herbal formula for psoriasis that has been used for more than 20 years in China. To facilitate application, PSORI-CM01 was developed based on the optimisation and simplification of Yinxieling tablets performed in a previous study and in clinical practice. However, the scientific evidence regarding whether PSORI-CM01 is more effective for psoriasis than the original Yinxieling remains insufficient. Therefore, we designed a randomised clinical trial to investigate the effect, safety and cost-effectiveness of PSORI-CM01 granules compared with those of Yinxieling tablets for the treatment of patients with psoriasis. METHODS AND ANALYSIS: This ongoing study is a two-arm parallel, randomised, double-blind, double-dummy clinical trial. Five hundred and fifty-six participants with psoriasis will be recruited and then randomly allocated into two groups in a 1:1 ratio. Participants in PSORI-CM01 group will receive a 5.5 g granule of PSORI-CM01 two times daily and five placebo tablets three times daily for 12 weeks. The participants in the Yinxieling group will receive five Yinxieling tablets three times daily and a placebo granule two times daily for 12 weeks. The primary outcome is the reduction of the Psoriasis Area and Severity Index. The secondary outcomes include relapse rate, Visual Analogue Scale scores, body surface area and the Dermatology Life Quality Index. Cost-effectiveness analysis will be performed from a health and community care provider perspective. ETHICS AND DISSEMINATION: This research protocol had been reviewed and approved by the institutional review boards of three trial centres (Guangdong Provincial Hospital of Chinese Medicine (B2014-026-01), Affiliated Hospital of Tianjin Chinese Medicine Academy (2014-KY-001) and Third Hospital of Hangzhou (B2014-026-01)). The findings will be disseminated to the public through conference presentations and open-access journals. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-TRC-14005185); Pre-results.

Upregulation of Mineralocorticoid Receptor in the Hypothalamus Associated with a High Anxiety-like Level in Apolipoprotein E4 Transgenic Mice.

Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3 months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice. However, corticotropin releasing factor levels in the hypothalamus and plasma corticosterone secretion were similar in GFAP-ApoE3 and GFAP-ApoE4 transgenic male mice. Additionally, increased expression of the mineralocorticoid receptor (MR) and unchanged expression of the glucocorticoid receptor were observed in the hypothalamus of GFAP-ApoE4 mice. However, no significant differences were found in the expression levels of the MR in GFAP-ApoE3 and GFAP-ApoE4 mice at postnatal day 2. In conclusion, we found that MR upregulation rather than corticosterone level changes in the early stage of adulthood was associated with the higher anxiety-like level measured in GFAP-ApoE4 mice.

A meta-analysis of dehydroepiandrosterone supplementation among women with diminished ovarian reserve undergoing in vitro fertilization or intracytoplasmic sperm injection.

BACKGROUND: Evidence for the efficacy of dehydroepiandrosterone (DHEA) in improving ovarian responsiveness among poor responders, especially women with diminished ovarian reserve (DOR), remains inconsistent. OBJECTIVES: To evaluate the effectiveness of DHEA in women with DOR undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). SEARCH STRATEGY: PubMed and Embase were searched for reports published in any language before October 31, 2014, using keywords such as "DHEA," "poor ovarian response," "diminished ovarian reserve," and "premature ovarian aging." SELECTION CRITERIA: Studies that explored the effects of DHEA in women with DOR undergoing IVF/ICSI were included if they evaluated the number of oocytes retrieved and/or the rates of clinical pregnancy, implantation, and spontaneous abortion. DATA COLLECTION AND ANALYSIS: Risk ratios (RRs) and standardized mean differences with 95% confidence intervals (CIs) were calculated, combined with subgroup and sensitivity analyses. MAIN RESULTS: Eight studies were included. The use of DHEA increased the clinical pregnancy rate (RR 2.13; 95% CI 1.12-4.08). Similar results were obtained in subgroup analyses including randomized controlled trials and case-control studies (RR 2.57; 95% CI 1.43-4.63) and self-controlled studies (RR 3.95; 95% CI 1.28-12.19). However, the effects of DHEA on oocyte retrieval, implantation, and abortion were not significant. CONCLUSIONS: Supplementation with DHEA has a positive effect in women undergoing IVF/ICSI treatment for DOR.