Objective: To investigate the therapeutic benefits and possible mechanism of total flavonoids of Litchi chinensis Sonn. seed (TFLS) on hepatic fibrosis (HF) in vivo and in vitro.
Methods: A carbon tetrachloride (CCl4)-induced rat HF model and transforming growth factor β1 (TGF-β1)-stimulated hepatic stellate cell (HSC)-T6 cells were employed. For in vivo study, rats were randomly divided into 6 groups using a random number table method, including vehicle, CCl4, silybin (50 mg/kg), and low-, medium-, high-dose (25, 50, and 100 mg/kg) TFLS treatment groups. TFLS or silybin was administered daily by gavage for 8 weeks during CCl4 induction period. For in vitro study, HSC-T6 cells were divided into 4 groups, including control, TGF-β1 (20 ng/mL), TGF-β1 + Z-DNA binding protein 1 (ZBP1) siRNA (si-ZBP1), TGF-β1 + low-dose (80 µg/mL) TFLS, and TGF-β1 + high-dose (160 µg/mL) TFLS groups. Serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), total bile acid (TBA), interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay. Hematoxylin-eosin and Masson's trichrome staining were employed to conduct a histological examination of the liver tissue. Apoptosis was assessed by TUNEL. Cysteine-aspartic acid protease (CASP)-8, NLR family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), and receptor-interacting protein kinase (RIPK) 3 were immunohistochemically detected. CASP-8, NLRP3, GSDMD, CASP-3, BCL-2, BCL-2-associated X (BAX), ZBP1, RIPK1, and RIPK3 mRNA levels were measured by quantitative real-time polymerase chain reaction. PANoptosis-related proteins were detected by Western blot.
Results: In CCl4-induced HF rats, TFLS improved liver function, inflammatory response, and liver tissue fibrosis (P<0.05 or P<0.01). TFLs inhibited the activation of PANoptosis initiator ZBP1, which subsequently regulated PANoptosis by increasing BAX, CASP-3, CASP-8 and decreasing BCL-2, NLRP3, GSDMD, CASP-1, RIPK1, RIPK3, and mixed lineage kinase domain-like expressions (P<0.05 or P<0.01). In vitro, TFLS inhibited TGF-β1-induced HSC-T6 cells activation and PANoptosis (P<0.05 or P<0.01).
Conclusion: TFLS might ameliorate HF by targeting ZBP1 to suppress PANoptosis, highlighting its multi-modal regulation of apoptosis, pyroptosis, and necroptosis.
Objective: To explore the effects of electroacupuncture (EA) on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells (GCs) in patients with polycystic ovary syndrome (PCOS) and phlegm-dampness syndrome.
Methods: In this randomized controlled trial, 90 infertile women with PCOS and phlegm-dampness syndrome were recruited between August 2022 and December 2022. Patients were randomly assigned to the EA and control groups using a random sequence of codes in the order of enrolment, with 45 in in each group. Both groups underwent the ovarian stimulation protocol. The patients in the EA group received EA therapy including Zhongwan (CV 12), Qihai (CV 6), bilateral Xuehai (SP 10), Sanyinjiao (SP 6), Yinlingquan (SP 9), Tianshu (ST 25), Zusanli (ST 36), and Fenglong (ST 40), and the patients in the control group was treated with pseudo-acupuncture. The intervention was 25 min twice a week for a total of 6 times until the trigger day after menstruation had ended in the cycle before oocyte retrieval. The primary outcomes were clinical pregnancy rate (CPR) and the number of high-quality embryos. The secondary outcomes were (1) pregnancy-related indicators, including fresh embryo transfer rate (ETR), ovarian hyperstimulation syndrome (OHSS) rate, early pregnancy loss rate (ePLR), ectopic pregnancy rate, live birth rate (LBR), and cumulative CPR; (2) mitochondrial autophagy and mitochondrial membrane potential (MMP) in GCs; and (3) scoring for Chinese medicine syndrome. Adverse events to assess clinical safety were also monitored.
Results: The cumulative CPR was significantly higher in the EA group (42/45, 93.3%) than in the control group (38/45, 84.4%, P=0.036). The number of high-quality embryos and fresh ETR in the EA group were higher than those in the control group (3.80±1.65 vs. 2.44±1.34, P<0.001; 46.7% vs 24.4%, P=0.028). Ectopic pregnancies were not observed in either group. There were no significant differences in the fresh CPR, OHSS rate, ePLR or LBR between the two groups (P>0.05). Compared with the control group, the EA group showed lower expression levels of miR-146a-5p mRNA and P62 protein in GCs and higher levels of MMP and the LC3-II/LC3-I protein ratio (all P<0.01). The phlegm-dampness syndrome scores of the EA group were significantly lower than those of the control group (P<0.01).
Conclusions: EA significantly improved pregnancy outcomes in patients with PCOS and phlegm dampness syndrome. Mechanistically, this effect may be related to EA in decreasing miR-146a-5p mRNA expression, promoting mitochondrial autophagy in GCs, and improving mitochondrial function, which may contribute to improved oocyte quality. (Trial registration No. ChiCTR2200062915).
Objective: To study the clinical efficacy of Wenyang Lishui Formula (WYLSF) in preventing ovarian hyperstimulation syndrome (OHSS) and explore the suitable range of estradiol (E2) on the human chorionic gonadotropin (HCG) day in patients with OHSS using WYLSF.
Methods: Part I: eligible patients at high risk for OHSS undergoing ovulation induction between January and December, 2023 were randomized into 2 groups based on the actual treatment. The treatment group received 200 mL WYLSF formula twice daily for 5 days after oocyte retrieval in a combination of lifestyle coaching (LC) intervention including regular diet and exercise, whereas the LC group received LC intervention alone. The incidence of OHSS, OHSS self-assessment scales, changes in E2 levels on HCG day and 5 days after oocyte retrieval, ovarian morphology changes, and menstrual recovery were compared between the two groups. Part II: patients at high risk for OHSS treated with WYLSF were studied. The optimal E2 threshold on the HCG day was determined using the maximum selection test, and a multivariate analysis was adopted to compare the relationship between different E2 levels on HCG day and hospitalization rate, incidence of moderate to severe OHSS, and self-assessment scales, to explore the preventive effect of WYLSF on OHSS in patients with varying E2 levels.
Results: A total of 120 patients were included in the Part I analysis. The treatment group (60 cases) showed a significant reduction in the incidence, duration, and severity of abdominal distension, as well as the incidence of vomiting compared with the LC group (P<0.05). The post-retrieval E2 levels in the treatment group decreased significantly more (P=0.032). Among 1,652 patients treated with WYLSF in the Part II, 90 patients with ⩽ 10092 pmol/L, 159 with >31074 pmol/L, and 1,403 in the middle range group were formed based on E2 levels on HCG day in Part two analysis. Univariate and regression analyses showed that patients with E2 levels >31073 pmol/L had a significantly higher incidence of moderate to severe OHSS compared to those with E2 levels ⩽ 10092 pmol/L (P<0.05).
Conclusions: WYLSF can effectively reduce specific symptoms in high-risk OHSS patients after ovulation induction and significantly lower E2 levels. It may be more suitable for high-risk OHSS patients with E2 levels <31073 pmol/L on HCG day. (Registration No. MR-11-23-032493, https://www.medicalresearch.org.cn/login ).
Objective: To investigate the antidepressant effects of Xiaoyao Pill (XYP) by exploring its interactions with gut microbiota and tryptophan metabolism.
Methods: Utilizing network pharmacology, the functional substance groups, key targets, and pathways of XYP in the treatment of depression were identified. The chronic unpredictable mild stress (CUMS) protocol was implemented in male Sprague-Dawley rats to establish depression model. Thirty rats were randomly divided into 3 groups according to their body weight (10 for each): control, CUMS and XYP groups (1.8 g/kg). After 28-day interventions, behavioral phenotyping including sucrose preference test (SPT) and open field test (OFT) were performed. Biochemical validation encompassed enzyme-linked immunosorbent assay for serum cortisol, hematoxylin-eosin histopathology, and immunohistochemistry. Liquid chromatography-mass spectrometry was utilized to profile serum metabolites, while fecal samples underwent metagenomic sequencing for gut microbiota characterization.
Results: Network pharmacology studies predicted that key components can protect the nervous system by regulating inflammatory pathways through the blood-brain barrier. SPT and OFT showed that XYP treatment significantly ameliorated depressive-like behaviors (all P<0.05). XYP treatment also restored hippocampal neuronal density, increased serum neurotransmitter levels of neurotransmitters such as 5-hydroxytryptamine and vasoactive intestinal peptide, and while suppressing inflammatory markers such as tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β), and IL-6 (all P<0.05). Metagenomics revealed significant restructuring of gut microbiota, notably the regulation of Parabacteroides distasonis (P<0.05). Non-targeted metabolomics analysis showed that the level of metabolites in the tryptophan and kynurenine pathway significantly changed (variable importance in the projection >1, P<0.05), and the change of metabolic flux was significantly correlated with behavioral improvement (P<0.05).
Conclusions: XYP exerts antidepressant effects by increasing neurotransmitter levels, reducing inflammatory makers and modulating Parabacteroides distasonis. Through further exploration of metabolomics, we found that XYP may play a protective role in depression by regulating tryptophan metabolism.
Objective: To investigate the effect of traditional Chinese Five-body balance exercise on patients with preserved ratio impaired spirometry (PRISm).
Methods: Fifteen patients with PRISm and 15 patients diagnosed with chronic obstructive pulmonary disease (COPD) were recruited from the Outpatient Department of Guang'anmen Hospital and Beijing Niujie Health Service Center from April to December, 2023. Participants in both groups attended supervised Five-body balance exercise training twice a week for 12 weeks. Patients with COPD continued their regular medication regimen during the intervention period. The endpoints were mean changes in the 6-min walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ) score, cardiopulmonary exercise testing (CPET), pulmonary function, and scores of COPD assessment test (CAT), modified British Medical Research Council, Self-Rating Anxiety Scale, and Self-Rating Depression Scale from baseline to 12 weeks. Adverse events were monitored throughout the study.
Results: The PRISm group showed a significant improvement from baseline to week 12 in 6MWT, SGRQ symptom score, and forced vital capacity (FVC) compared to the COPD group (P<0.05). No significant between-group changes were observed in other outcome measurements (P>0.05). In addition, compared with baseline, both groups exhibited improvements in 6MWT, SGRQ score, and CPET at week 12 (P<0.05). The PRISm group also showed a significant increase in forced expiratory volume in 1 s and FVC, as well as a significant decrease in CAT score at week 12 (P<0.05). No adverse events were reported.
Conclusion: Patients with PRISm may benefit from Five-body balance exercise training, which can improve the exercise capacity, health-related quality of life, and lung function. (Registration No. ChiCTR2200059290).
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