Objective: To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. Methods: A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. Results: A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. Conclusions WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Objective To observe the regulating effect of electroacupuncture on the polarization level of decidual macrophages in rats with thin endometrium and the repairing effect of electroacupuncture on thin endometrium.Methods Thirty SPF female SD rats were randomly divided into control group,model group and electroacupuncture group.The electroacupuncture group was treated with acupuncture of"Guanyuan"(CV4),"Zigong"(EX-CA1)and"Sanyinjiao"(SP6)and intervened continuously for 4 estrous cycles.After the intervention,the estrous cycle of rats in each group was observed,the number of implantation embryos in the uterus was recorded,the uterine morphology and decidualization,the thickness of endometrium,the number of glands and blood vessels were observed by HE staining,the polarization level of macrophages was detected by flow cytometry,and the expression levels of IGFBP-1,CD86 and CD206 genes were detected by qRT-PCR.Results Compared with the control group,the estrous cycle of rats in the model group was disturbed;compared with the model group,the estrous cycle of rats in the electroacupuncture group recovered;compared with the control group,the number of embryos in the model group decreased significantly(P<0.01);compared with the model group,the number of embryos in the electroacupuncture group increased(P<0.05),and the morphology of endometrium in the model group was damaged and the thickness of endometrium decreased compared with the control group(P<0.01).The number of glands and blood vessels decreased(P<0.01).Compared with the model group,the morphology of endometrium in the electroacupuncture group recovered,the thickness of endometrium increased(P<0.01),and the number of glands and blood vessels increased(P<0.01).Compared with the control group,the ratio of M2 to M1 macrophages in the model group decreased significantly(P<0.01).Compared with the model group,the ratio of M2 to M1 macrophages in the endometrium of the electroacupuncture group was significantly increased(P<0.05).Compared with the control group,the expression of IGFBP-1 mRNA in the model group decreased significantly(P<0.01),the expression of CD86 mRNA increased significantly(P<0.01),and the expression of CD206 mRNA decreased significantly(P<0.01).Compared with the model group,the expression of IGFBP-1 mRNA in the endometrium of the electroacupuncture group increased significantly(P<0.01),the expression of CD86 mRNA decreased significantly(P<0.01),and the expression of CD206 mRNA increased significantly(P<0.01).Conclusion Electroacupuncture can effectively regulate the polarization level of decidual macrophages in endometrium,and effectively repair thin endometrium,which is beneficial to embryo implantation.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*