Objective: To investigate the therapeutic effects and pharmacological mechanisms of Yishen Xingyang capsule (YXC) in oligoasthenospermia (OA) rats.Methods: Forty-eight male Sprague-Dawley rats were randomly divided into eight groups of six rats each:normal control (NC);model control (MC);three different positive drug (PD);and low-, medium-, and high-dose YXC groups. A rat model of OA was established by administering glucosides of Triptery-gium wilfordii Hook. F (GTW). After YXC administration, penile erectile function was observed. The epididymis, blood, and testes of the rats were harvested for analysis of sperm quality, sex hormone levels, mitochondrial membrane potential, and the transforming growth factor (TGF)-β1/Smad signaling pathway. Results: Compared with that in the MC group, penile erectile function in the YXC groups and three PD groups increased (all P<.01). Moreover, sperm quality in the YXC groups and three PD groups improved (all P < .001). The levels of testosterone, follicle stimulating hormone, and luteinizing hormone in the three PD and YXC groups increased (all P<.05). The mitochondrial membrane potential in the three PD and YXC groups significantly improved (all P<.001). Furthermore, the YXC and three PD groups showed decreased TGF-β1 expression (all P< .05) compared with the MC group. The high-dose YXC group and three PD groups improved Smad2 and Smad4 expression (all P<.05). Conclusion: YXC improved penile erectile function and sperm quality in OA rats, and the underlying mechanism included increase in sex hormones, inhibition of sperm apoptosis, and regulation of the TGF-β1/Smad signaling pathway. Meanwhile, this study provides a new effective drug option for the treat-ment of OA, which is beneficial to male reproductive health and social harmony.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Gancao Fuzitang originates from the Treatise on Febrile Diseases and Miscellaneous Diseases （《伤寒杂病论》） and is mainly used to treat pain in the bones and joints and symptoms such as no flexion or extension. It has the effect of tonifying the spleen and kidney and removing dampness and turbidity， so it is widely used in the clinical treatment of various bone and joint diseases. This article reviewed the clinical research and mechanism of Gancao Fuzitang in the treatment of bone and joint diseases. The research has found that this prescription has good efficacy in treating bone and joint diseases such as rheumatoid arthritis， rheumatoid arthritis， ankylosing spondylitis， gout， and intervertebral disc herniation. Its mechanism of action may be related to regulating the level of inflammatory factors， antioxidation， and the protein expression of inflammatory and apoptotic cell-related pathways， improving bone and joint diseases， and alleviating related symptoms. This study can provide a reference for further deepening the research on the prevention and treatment of bone and joint diseases with Gancao Fuzitang.