ObjectiveTo investigate the mechanisms through which Shugan Bushen Yulin decoction ameliorates spermatogenic dysfunction and sperm quality degradation caused by propylthiouracil （PTU） via the endoplasmic reticulum stress pathway in rats. MethodsSixty male rats were randomly assigned into six groups： a control group， a model group， low- （6.75 g·kg^-1）， medium- （13.5 g·kg^-1）， and high-dose （27 g·kg^-1） Shugan Bushen Yulin decoction groups， and an L-carnitine （0.27 g·kg^-1） group， with ten rats in each group. Other groups except the control group were administrated with PTU （10 mg·kg^-1） by gavage for 12 consecutive days. After the completion of modeling， rats were administrated with corresponding agents or normal saline （control group） via gavage for 28 consecutive days. Twenty-four hours after the last administration， rats were sacrificed， and the body and organ （testis， epididymis， and seminal vesicle） weights were measured to calculate the organ indices. Hematoxylin-eosin staining was employed to observe the pathological changes in the testes and epididymis， and the testicular spermatogenic function of rats was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of thyroid-stimulating hormone （TSH）， triiodothyronine （T3）， thyroxine （T4）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， estradiol （E₂）， and malondialdehyde （MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in the rat serum. Terminal deoxynucleotidyl transferase dUTP nick end labeling was adopted to assess the rate of testicular cell apoptosis. Western blot was conducted to determine the expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， protein kinase RNA-like endoplasmic reticulum kinase （PERK）， phosphorylated eukaryotic translation initiation factor 2α kinase （p-EIF2α）， eukaryotic translation initiation factor 2α kinase （EIF2α）， and activating transcription factor 4 （ATF4） in the testicular tissue of rats. ResultsCompared with the control group， the model group exhibited reductions in volumes and indexes of testes， epididymides， and seminal vesicles （P<0.01）， pathological damage of testes and epididymides， and declines in spermatogenic function and sperm density and motility （P<0.01）. In addition， the model group demonstrated elevated serum levels of TSH and MDA， lowered levels of T3， T4， FSH， LH， T， and E₂， decreased activities of SOD and GSH-Px （P<0.05， P<0.01）， an increased apoptosis rate of testicular cells （P<0.01）， and up-regulated expression of GRP78， CHOP， p-PERK/PERK， p-EIF2α/EIF2α， and ATF4 in the testicular tissue （P<0.01）. Compared with the model group， Shugan Bushen Yulin decoction at different doses improved the morphology and indexes of testes， epididymides， and seminal vesicles （P<0.05）， restored the spermatogenic function （P<0.05， P<0.01）， increased the sperm density and motility （P<0.05， P<0.01）， and decreased the percentage of apoptotic testicular cells （P<0.05）. Furthermore， the decoction lowered the serum level of MDA， elevated the serum levels of FSH， LH， T， and E₂， and increased the activities of SOD and GSH-Px （P<0.05， P<0.01）. Moreover， the expression levels of GRP78， CHOP， p-PERK/PERK， p-EIF2α/EIF2α， and ATF4 in the testicular tissue were down-regulated （P<0.05， P<0.01）. ConclusionShugan Bushen Yulin decoction can ameliorate the spermatogenic dysfunction and sperm quality degradation induced by PTU in a rat model of hypothyroidism by repairing the testicular oxidative damage and regulating the PERK/EIF2α/ATF4 signaling pathway， thereby alleviating spermatogenic cell apoptosis.

ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.

ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.

ObjectiveTo study the effects of Epimedii Folium polysaccharides on mice with exercise-induced fatigue and explore its possible mechanism of action. MethodICR male mice screened by swimming training were randomly divided into a control group， model group， vitamin C group， and low， medium， and high dose groups of Epimedii Folium polysaccharides， with eight mice in each group. The exercise-induced fatigue model was established by weight-bearing swimming training in each group except for the control group. After two weeks of weight-bearing swimming， the Epimedii Folium polysaccharide groups were given 100， 200， 400 mg∙kg^-1 of Epimedii Folium polysaccharides by gavage， and the vitamin C group was given 200 mg∙kg^-1 of vitamin C by gavage. The control group and the model group were given equal amounts of saline for 14 d. At the end of the experimental period， the body mass of the mice in each group and the time of last swimming due to exhaustion were recorded. Serum urea nitrogen （BUN）， lactic acid （LA）， lactate dehydrogenase （LDH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidation （GSH-Px）， myoglycogen （MG） in skeletal muscle， hepatic glycogen （HG） in the liver were detected by kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in muscle tissue. Western blot was used to detect the protein expression of p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylation （p）-p38 MAPK， extracellular signal-regulated kinase1/2 （ERK1/2）， nuclear factor-κB （NF-κB）， p-NF-κB， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in muscle tissue. The immunofluorescence （IF） method was used to detect the expression of tumor necrosis factor-α （TNF-α） in skeletal muscle tissue of mice in each group. ResultCompared with the control group， the body mass of mice in the model group decreased， and the time of last swimming due to exhaustion decreased （P<0.01）. In addition， there were significantly higher serum levels of the fatigue metabolites LA， LDH， BUN， and lipid peroxidation product MDA （P<0.01） and decreased levels of MG， HG， SOD， and GSH-Px （P<0.01）. The protein expressions of p-p38 MAPK， ERK1/2， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue were significantly higher than those of the control group （P<0.01）. Compared with the model group， the body mass and time of last swimming due to exhaustion of the mice in the low， medium， and high dose groups of Epimedii Folium polysaccharides and the vitamin C group were increased （P<0.05， P<0.01）， and the contents of LA， LDH， BUN， and MDA were significantly decreased （P<0.05， P<0.01）. The levels of MG， HG， SOD， and GSH-Px increased （P<0.05， P<0.01）， and the protein expression levels of p-p38 MAPK， ERK， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue decreased （P<0.05， P<0.01）. ConclusionEpimedii Folium polysaccharides can play a role in alleviating exercise-induced fatigue by inhibiting the p38 MARK/NF-κB signaling pathway， thereby reducing the accumulation of metabolites， improving the activity of antioxidant enzymes， increasing the glycogen content of the body， and reducing inflammation in skeletal muscle.

ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress （PS） and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 （TLR4/NF-κB p65） signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups （n=8）： control， model， Zuoguiwan （18.9 mg·kg^-1）， and vitamin E （1.44 mg·kg^-1）. Except the control group， the other three groups were subjected to chronic unpredictable mild stress （CUMS） from day 11 of pregnancy， and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test， open field test， and serum corticosterone （CORT） level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol （E₂）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， and anti-Mullerian hormone （AMH） in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay （ELISA） to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence （IF） assay. The expression of TLR4， NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group， the model group showed reduced primordial follicles in the offspring on the day of birth （P<0.01） as well as disturbed estrous cycle， decreased ovary index and uterus index （P<0.01）， reduced corpus luteum， increased atretic follicles （P<0.01）， lowered serum levels of AMH and E₂ （P<0.01）， elevated serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and up-regulated protein levels of TLR4， NF-κB p65， recombinant myeloid differentiation factor 88 （MyD88）， and phosphorylated NF-κB inhibitor （p-IκBα） （P<0.01） in the 75-day-old offspring rats. Compared with the model group， Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth （P<0.01）. Moreover， they resumed the estrous cycle， increased the ovary and uterine indices （P<0.05， P<0.01） and corpus luteum （P<0.01）， reduced atretic follicles （P<0.01）， elevated the serum levels of AMH and E₂ （P<0.05， P<0.01）， lowered the serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and down-regulated the expression of TLR4， NF-κB p65， MyD88， and p-IκB-α （P<0.05， P<0.01） in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.

ObjectiveTo observe the effect of Youguiwan on the leptin/Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） due to kidney-Yang deficiency. MethodForty rats were modeled for COPD with the syndrome of kidney-Yang deficiency by intratracheal instillation of lipopolysaccharide on day 1 and day 14 and continuous fumigation for 6 weeks， during which hydrocortisone was injected intramuscularly at an interval of 3 days. The modeled rats were randomized into model， high- （11.7 g·kg^-1）， medium- （5.85 g·kg^-1）， and low-dose （2.93 g·kg^-1） Youguiwan， and aminophylline （0.054 g·kg^-1） group. In addition， 8 SD rats were set as the blank group. After the completion of modeling， the rats in each group were administrated with the corresponding drug by gavage for 28 consecutive days. After the last administration， samples were collected. A lung function analyzer was used to evaluate the lung function of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-17A （IL-17A）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF）. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung tissue， and Masson staining was employed to observe the deposition of blue collagen fibers around bronchi in the lung tissue and calculate the inflammation score. The immunofluorescence assay was employed to measure the protein content of collagen type Ⅰ （ColⅠ） and α-smooth muscle actin （α-SMA） in the bronchi. The protein and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed decreased lung function （P<0.01）， elevated levels of IL-6， IL-17A， and TNF-α in the BALF （P<0.01）， and increased lung inflammation score， deposition of subcutaneous collagen fibers in the airway， and ColⅠ and α-SMA proteins （P<0.01）. Furthermore， the modeling up-regulated the proteins and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue （P<0.01） and enhanced the phosphorylation of JAK2 and STAT3 （P<0.01）. Compared with the model group， high- and medium-dose Youguiwan improved the lung function， decreased the inflammation score， reduced collagen fiber deposition and ColⅠ and α-SMA proteins， lowered the levels of IL-6， IL-17A， and TNF-α in the BALF， down-regulated the mRNA and protein levels of leptin， JAK2， STAT3， and IL-17A， and weakened the phosphorylation of JAK2 and STAT3 （P<0.05， P<0.01）. The aminophylline group had higher IL-17A and TNF-α levels than the high-dose Youguiwan group， lower IL-17A level than the medium and low-dose Youguiwan groups， and lower TNF-α level than the low-dose Youguiwan group. Compared with the aminophylline group， the high- and medium-dose Youguiwan groups showed reduced deposition of collagen fibers and protein levels of ColⅠ and α-SMA around the bronchi in the lung tissue （P<0.05， P<0.01）， decreased inflammation score， and down-regulated protein and mRNA levels of leptin， JAK2， STAT3， and IL-17A in the lung tissue. ConclusionYouguiwan can prevent airway remodeling by inhibiting IL-17A to reduce inflammation and collagen deposition in COPD rats， which may be related to the inhibition of the leptin/JAK2/STAT3 signaling pathway.

ObjectiveTo investigate the effect and possible mechanism of Sishenwan in ameliorating visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency. MethodForty male SPF-grade rats were randomly assigned into five groups： blank control， model， low- （3.51 g·kg^-1） and high-dose （7.02 g·kg^-1） Sishenwan， and Peifikang （0.54 g·kg^-1） groups. Except the blank control group， the other groups underwent maternal separation stress and Sennae Folium decoction gavage for the modeling of IBS-D due to spleen-kidney Yang deficiency. After corresponding drug interventions， the general conditions of the rats were observed， and the number of defecation pellets within 6 h and the minimum threshold of abdominal withdrawal reflex （AWR） were measured. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of tumor necrosis factor （TNF）-α， gastrin （GAS）， corticosterone （CORT）， and adrenocorticotropic hormone （ACTH）. Hematoxylin-eosin （HE） staining was employed to observe pathological changes in the colon tissue. Toluidine blue staining was used to assess mast cell degranulation in the colon tissue. Western blot was performed to determine the protein levels of p38 mitogen-activated protein kinase （MAPK）， c-Jun N-terminal kinase （JNK）， transient receptor potential vanilloid 1 （TRPV1）， and protease-activated receptor 2 （PAR2） in the colon tissue. Immunohistochemistry was employed to measure the protein level of TRPV1 in the colon tissue， and immunofluorescence was used to detect the positive expression of substance P （SP） and calcitonin gene-related peptide （CGRP） in the colon tissue. ResultCompared with the blank control group， the model group showed increased number of defecation pellets within 6 h （P<0.01）， decreased minimum threshold of AWR （P<0.01）， elevated serum TNF-α level （P<0.01）， lowered levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， increased mast cell degranulation rate （P<0.01）， increased positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and upregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.01）. Compared with the model group， the high-dose Sishenwan group showed increased minimum threshold of AWR （P<0.01）， reduced defecation frequency in both the high-dose Sishenwan and Peifikang groups （P<0.05， P<0.01）， lowered TNF-α level （P<0.05， P<0.01）， elevated levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， decreased mast cell degranulation rate （P<0.01）， reduced positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and downregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.05， P<0.01）. ConclusionSishenwan can ameliorate visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome due to spleen-kidney Yang deficiency by regulating the p38 MAPK/JNK/TRPV1 signaling pathway.

ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg^-1·d^-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg^-1·d^-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E₂， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.

ObjectiveTo observe the clinical efficacy and safety of Shugan Bushen Yulin Decoction （疏肝补肾毓麟汤， SBYD） in the treatment of asthenospermia and infertility with liver constraint and kidney deficiency. MethodsA multicenter， randomized， controlled clinical study was conducted in three hospitals in central China. Totally 95 patients with asthenospermia and infertility were controlled. According to random number table， the patients were divided into treatment group （47 cases） and control group （48 cases）. The control group was given vitamin E soft capsules （100 mg per time， twice daily） orally， and the treatment group was given SBYD （one dose daily， 30 min after breakfast and dinner， about 200 ml each time） orally. The course of treatment was 12 weeks in both groups. After the treatment， the sperm concentration， percentage of forward motile sperm （PR）， and percentage of total sperm activity， that is PR + percentage of non-progressively motile sperm （NP） were compared between groups， and the clinical efficacy was judged. Traditional Chinese medicine （TCM） syndrome score （inlcuding 6 single symptom scores and total symptoms score） and 21-item depression， anxiety， and stress scale （DASS-21） scores （including depression， anxiety and stress scores） were compared between the two groups before and after treatment. The patients were followed up for 6 months， and the pregnancy status of spouse between groups was compared. The occurrence of adverse events and vital signs during the trial were recorded for safety assessment. ResultsTwo cases in the treatment group and three cases in the control group dropped out. Finally， 45 cases in each group were included in the statistical analysis. The total effective rate was 86.67% （39/45） in the treatment group， significantly higher than 73.74% （33/45） in the control group （P＜0.05）. After treatment， PR and PR + NP significantly increased in both groups， and were much higher in the treatment group than in the control group （P＜0.05）. The scores of lumbar and knee soreness， emotional disturbance， cold sperm， chest and rib-side and lesser abdomen distension and pain， frequent sighing， and the total TCM syndrome score in the treatment group decreased after treatment （P＜0.05）； and except for cold sperm， the scores of other symptoms mentioned above as well as the total TCM syndrome score in the treatment group were lower than those in the control group （P＜0.05）. The scores of depression， anxiety and stress of DASS-21 in the treatment group decreased after treatment， and were lower than those in the control group （P＜0.05）. After 6 months of follow-up， the spouses of 5 patients in the treatment group and 3 patients in the control group got pregnant （P＞0.05）. No adverse events occurred in both groups during the treatment， and their vital signs were stable. ConclusionSBYD can obviously improve sperm vitality and effectively improve the clinical symptoms， anxiety and depression， and is safe in treating asthenospermia and infertility with liver constraint and kidney deficiency.

Objective We aimed to investigate the effect of ferroptosis on Shenling Baizhu Powder,a compound prescription of Chinese herbal medicine,in improving testicular spermatogenic function in hyperuricemic mice with spermatogenic dysfunction. Methods Sixty BALB/c mice were randomly divided into normal group,model group,Shenling Baizhu Powder high-,medium-,and low-dose groups (20.14,10.07,5.04 g/kg,by gavage),and ferrostatin-1(Fer-1) group (0.8 mg/kg,by tail vein injection),with 10 mice each group. Except for the normal group,the other groups were intraperitoneally injected with potassium oxonate suspension[600mg/(kg·d)]for 7 days to establish the hyperuricemic model,and then the corresponding intervention was given for consecutive 14 days. Content of serum uric acid (UA),testicular Fe2+,reduced glutathione (GSH),malondialdehyde (MDA) and superoxide dismutase (SOD) activity were detected by biochemical method. Epididymal and testicular indices were measured. The spermatogenic function of testes was evaluated by eosin-hematoxylin staining. Sperm quality was detected by an automatic animal sperm analyzer. Prussian blue staining was used to detect iron deposition in testicular tissue. Immunohistochemistry was used to detect the related protein expressions of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) in testicular tissue. Western blotting was used to detect the related protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1)/GPX4 signaling pathway in testicular tissue. Results Compared with the normal group,the contents of serum UA,MDA,and Fe2+in the testis tissue of the model group were increased,the GSH content and SOD activity were decreased,the epididymal and testicular index,testicular spermatogenic function,sperm density and activity rate were decreased,and the iron deposition and ACSL4 protein expression in the testis tissue were increased. The expressions of kelch-like ECH-associated protein-1 (Keap1) and Nrf2 were increased. The expressions of nuclear Nrf2,HO-1,GPX4,and recombinant solute carrier family 7 member 11 (SLC7A11) protein were decreased (P<0.01). Compared with the model group,the above indexes in the Shenling Baizhu Powder groups and the Fer-1 group were improved to varying degrees (P<0.05,P<0.01). Conclusion Shenling Baizhu Powder can inhibit the ferroptosis of testicular cells through the Nrf2/HO-1/GPX4 signaling pathway,and improve the testicular spermatogenic function of mice with hyperuricemia spermatogenic dysfunction.