Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Objective To explore the mechanism of electroacupuncture in improving lipid metabolism in polycystic ovary syndrome(PCOS)based on metabolomics combined with transcriptomics.Methods Eight-een SD rats were divided into the control group,the PCOS group and the electroacupuncture group,with 6 rats in each group.The PCOS group and the electroacupuncture group used intragastric letrozole to establish the PCOS model.After the model was established,the electroacupuncture group was intervened with electroacu-puncture,while the control group was only given sodium carboxymethyl cellulose by gavage.Observed the changes in body weight and estrous cycle of the three groups,detected the sex hormones,blood lipids,liver function,ovarian morphology,plasma metabolism and liver function indicators of the three groups.Metabolo-mics was used to analyze the differences in metabolites in plasma,the differences in gene expression in the liv-er were detected by RT-qPCR.Results Weight gain and estrous cycle disorder occurred in the PCOS group,and the ovarian morphology showed a thinning of the granulosa cell layer,with a significant reduction in the number of corpus luteum and mature follicles.Meanwhile,sex hormones were abnormal(total testosterone and androgen levels were increased,estradiol and progesterone levels were decreased),dyslipidemia occurred(TC,TG,LDL-C were increased,HDL-C level was decreased),and liver function was abnormal(AST,total protein,ALB,TBIL were increased).The electroacupuncture group significantly reduced weight.It improved the estrous cycle,and the granulosa cell layer of the ovary thickened,with a significant increasing in the num-ber of corpus luteum and mature follicles.Meanwhile,sex hormone levels were improved(androgen and total testosterone levels were decreased,estradiol level was increased),lipid balance(TC,TG,LDL-C levels were reduced,HDL-C level was increased)and liver function(AST,total protein,ALB,and TBIL levels were de-creased)was restored.Transcriptomics suggested that electroacupuncture down-regulated the expression of cytochrome P450(CYPs)family genes related to steroid hormones and lipid metabolism,and the results were confirmed by RT-qPCR.Combined omics analysis revealed that electroacupuncture might mainly exert its effect on improving lipid metabolism disorders in PCOS rats through the linoleic acid metabolic pathway.Con-clusion Electroacupuncture can regulate lipid metabolism in rats with PCOS.

Objective:To explore the etiological rules of multifactorial refractory infertility patients by association analysis.Methods:A total of 283 patients with refractory infertility met the inclusion criteria from January 2019 to December 2021 in Nanping People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,were analyzed retrospectively.Using the Apriori algorithm,association rule analysis was performed on 7 etiological fac-tors:fallopian tube obstruction(FTO),intrauterine adhesions(IUA),ovarian dysfunction[diminished ovarian re-serve(DOR),premature ovarian insufficiency(POI)],polycystic ovary syndrome(PCOS),endometriosis(EMT),adenomyosis(AM)and thin endometrium(TE).Further stratified analysis was performed to assess the combina-tions of causes based on the severity of 4 major factors(EMT,FTO,IUA and DOR/POI).Results:①Among 283 patients,EMT(59.0%)and FTO(50.5%)were identified as the most frequent etiological factors,significantly more prevalent than the other causes(P=0.0000,P＜α').②The 5 most common etiological combinations were:FTO with EMT,PCOS with EMT,AM with FTO,DOR/POI with EMT,and AM with EMT.③After stratified analysis,it was found that the following combination of causes was ranked in the top three:with EMT stages I-IV being highly associated with FTO;the degree of merger between low stage with PCOS is high,while the degree of merger be-tween high stage with AM and DOR/POI is high.Different degrees of IUA are highly associated with EMT,FTO and DOR/POI,while severe IUA also being highly associated with TE.Both unilateral and bilateral FTO have a high degree of merger with EMT and AM.DOR and POI have a high degree of merger with EMT,FTO and AM.Conclusions:EMT and FTO are the main causes of refractory infertility.There are correlations among the causes combinations.The etiological factors combined with different stages of endometriosis are also different.These findings underscore the importance of a comprehensive diagnostic framework to address multifactorial etiologies and reduce missed diagnoses.

Objective:To explore the etiological rules of multifactorial refractory infertility patients by association analysis.Methods:A total of 283 patients with refractory infertility met the inclusion criteria from January 2019 to December 2021 in Nanping People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,were analyzed retrospectively.Using the Apriori algorithm,association rule analysis was performed on 7 etiological fac-tors:fallopian tube obstruction(FTO),intrauterine adhesions(IUA),ovarian dysfunction[diminished ovarian re-serve(DOR),premature ovarian insufficiency(POI)],polycystic ovary syndrome(PCOS),endometriosis(EMT),adenomyosis(AM)and thin endometrium(TE).Further stratified analysis was performed to assess the combina-tions of causes based on the severity of 4 major factors(EMT,FTO,IUA and DOR/POI).Results:①Among 283 patients,EMT(59.0%)and FTO(50.5%)were identified as the most frequent etiological factors,significantly more prevalent than the other causes(P=0.0000,P＜α').②The 5 most common etiological combinations were:FTO with EMT,PCOS with EMT,AM with FTO,DOR/POI with EMT,and AM with EMT.③After stratified analysis,it was found that the following combination of causes was ranked in the top three:with EMT stages I-IV being highly associated with FTO;the degree of merger between low stage with PCOS is high,while the degree of merger be-tween high stage with AM and DOR/POI is high.Different degrees of IUA are highly associated with EMT,FTO and DOR/POI,while severe IUA also being highly associated with TE.Both unilateral and bilateral FTO have a high degree of merger with EMT and AM.DOR and POI have a high degree of merger with EMT,FTO and AM.Conclusions:EMT and FTO are the main causes of refractory infertility.There are correlations among the causes combinations.The etiological factors combined with different stages of endometriosis are also different.These findings underscore the importance of a comprehensive diagnostic framework to address multifactorial etiologies and reduce missed diagnoses.

Objective:To explore the etiological rules of multifactorial refractory infertility patients by association analysis.Methods:A total of 283 patients with refractory infertility met the inclusion criteria from January 2019 to December 2021 in Nanping People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,were analyzed retrospectively.Using the Apriori algorithm,association rule analysis was performed on 7 etiological fac-tors:fallopian tube obstruction(FTO),intrauterine adhesions(IUA),ovarian dysfunction[diminished ovarian re-serve(DOR),premature ovarian insufficiency(POI)],polycystic ovary syndrome(PCOS),endometriosis(EMT),adenomyosis(AM)and thin endometrium(TE).Further stratified analysis was performed to assess the combina-tions of causes based on the severity of 4 major factors(EMT,FTO,IUA and DOR/POI).Results:①Among 283 patients,EMT(59.0%)and FTO(50.5%)were identified as the most frequent etiological factors,significantly more prevalent than the other causes(P=0.0000,P＜α').②The 5 most common etiological combinations were:FTO with EMT,PCOS with EMT,AM with FTO,DOR/POI with EMT,and AM with EMT.③After stratified analysis,it was found that the following combination of causes was ranked in the top three:with EMT stages I-IV being highly associated with FTO;the degree of merger between low stage with PCOS is high,while the degree of merger be-tween high stage with AM and DOR/POI is high.Different degrees of IUA are highly associated with EMT,FTO and DOR/POI,while severe IUA also being highly associated with TE.Both unilateral and bilateral FTO have a high degree of merger with EMT and AM.DOR and POI have a high degree of merger with EMT,FTO and AM.Conclusions:EMT and FTO are the main causes of refractory infertility.There are correlations among the causes combinations.The etiological factors combined with different stages of endometriosis are also different.These findings underscore the importance of a comprehensive diagnostic framework to address multifactorial etiologies and reduce missed diagnoses.

Objective:To explore the etiological rules of multifactorial refractory infertility patients by association analysis.Methods:A total of 283 patients with refractory infertility met the inclusion criteria from January 2019 to December 2021 in Nanping People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,were analyzed retrospectively.Using the Apriori algorithm,association rule analysis was performed on 7 etiological fac-tors:fallopian tube obstruction(FTO),intrauterine adhesions(IUA),ovarian dysfunction[diminished ovarian re-serve(DOR),premature ovarian insufficiency(POI)],polycystic ovary syndrome(PCOS),endometriosis(EMT),adenomyosis(AM)and thin endometrium(TE).Further stratified analysis was performed to assess the combina-tions of causes based on the severity of 4 major factors(EMT,FTO,IUA and DOR/POI).Results:①Among 283 patients,EMT(59.0%)and FTO(50.5%)were identified as the most frequent etiological factors,significantly more prevalent than the other causes(P=0.0000,P＜α').②The 5 most common etiological combinations were:FTO with EMT,PCOS with EMT,AM with FTO,DOR/POI with EMT,and AM with EMT.③After stratified analysis,it was found that the following combination of causes was ranked in the top three:with EMT stages I-IV being highly associated with FTO;the degree of merger between low stage with PCOS is high,while the degree of merger be-tween high stage with AM and DOR/POI is high.Different degrees of IUA are highly associated with EMT,FTO and DOR/POI,while severe IUA also being highly associated with TE.Both unilateral and bilateral FTO have a high degree of merger with EMT and AM.DOR and POI have a high degree of merger with EMT,FTO and AM.Conclusions:EMT and FTO are the main causes of refractory infertility.There are correlations among the causes combinations.The etiological factors combined with different stages of endometriosis are also different.These findings underscore the importance of a comprehensive diagnostic framework to address multifactorial etiologies and reduce missed diagnoses.

Objective:To explore the etiological rules of multifactorial refractory infertility patients by association analysis.Methods:A total of 283 patients with refractory infertility met the inclusion criteria from January 2019 to December 2021 in Nanping People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,were analyzed retrospectively.Using the Apriori algorithm,association rule analysis was performed on 7 etiological fac-tors:fallopian tube obstruction(FTO),intrauterine adhesions(IUA),ovarian dysfunction[diminished ovarian re-serve(DOR),premature ovarian insufficiency(POI)],polycystic ovary syndrome(PCOS),endometriosis(EMT),adenomyosis(AM)and thin endometrium(TE).Further stratified analysis was performed to assess the combina-tions of causes based on the severity of 4 major factors(EMT,FTO,IUA and DOR/POI).Results:①Among 283 patients,EMT(59.0%)and FTO(50.5%)were identified as the most frequent etiological factors,significantly more prevalent than the other causes(P=0.0000,P＜α').②The 5 most common etiological combinations were:FTO with EMT,PCOS with EMT,AM with FTO,DOR/POI with EMT,and AM with EMT.③After stratified analysis,it was found that the following combination of causes was ranked in the top three:with EMT stages I-IV being highly associated with FTO;the degree of merger between low stage with PCOS is high,while the degree of merger be-tween high stage with AM and DOR/POI is high.Different degrees of IUA are highly associated with EMT,FTO and DOR/POI,while severe IUA also being highly associated with TE.Both unilateral and bilateral FTO have a high degree of merger with EMT and AM.DOR and POI have a high degree of merger with EMT,FTO and AM.Conclusions:EMT and FTO are the main causes of refractory infertility.There are correlations among the causes combinations.The etiological factors combined with different stages of endometriosis are also different.These findings underscore the importance of a comprehensive diagnostic framework to address multifactorial etiologies and reduce missed diagnoses.

Objective:To explore the etiological rules of multifactorial refractory infertility patients by association analysis.Methods:A total of 283 patients with refractory infertility met the inclusion criteria from January 2019 to December 2021 in Nanping People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,were analyzed retrospectively.Using the Apriori algorithm,association rule analysis was performed on 7 etiological fac-tors:fallopian tube obstruction(FTO),intrauterine adhesions(IUA),ovarian dysfunction[diminished ovarian re-serve(DOR),premature ovarian insufficiency(POI)],polycystic ovary syndrome(PCOS),endometriosis(EMT),adenomyosis(AM)and thin endometrium(TE).Further stratified analysis was performed to assess the combina-tions of causes based on the severity of 4 major factors(EMT,FTO,IUA and DOR/POI).Results:①Among 283 patients,EMT(59.0%)and FTO(50.5%)were identified as the most frequent etiological factors,significantly more prevalent than the other causes(P=0.0000,P＜α').②The 5 most common etiological combinations were:FTO with EMT,PCOS with EMT,AM with FTO,DOR/POI with EMT,and AM with EMT.③After stratified analysis,it was found that the following combination of causes was ranked in the top three:with EMT stages I-IV being highly associated with FTO;the degree of merger between low stage with PCOS is high,while the degree of merger be-tween high stage with AM and DOR/POI is high.Different degrees of IUA are highly associated with EMT,FTO and DOR/POI,while severe IUA also being highly associated with TE.Both unilateral and bilateral FTO have a high degree of merger with EMT and AM.DOR and POI have a high degree of merger with EMT,FTO and AM.Conclusions:EMT and FTO are the main causes of refractory infertility.There are correlations among the causes combinations.The etiological factors combined with different stages of endometriosis are also different.These findings underscore the importance of a comprehensive diagnostic framework to address multifactorial etiologies and reduce missed diagnoses.

Objective:To explore the etiological rules of multifactorial refractory infertility patients by association analysis.Methods:A total of 283 patients with refractory infertility met the inclusion criteria from January 2019 to December 2021 in Nanping People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,were analyzed retrospectively.Using the Apriori algorithm,association rule analysis was performed on 7 etiological fac-tors:fallopian tube obstruction(FTO),intrauterine adhesions(IUA),ovarian dysfunction[diminished ovarian re-serve(DOR),premature ovarian insufficiency(POI)],polycystic ovary syndrome(PCOS),endometriosis(EMT),adenomyosis(AM)and thin endometrium(TE).Further stratified analysis was performed to assess the combina-tions of causes based on the severity of 4 major factors(EMT,FTO,IUA and DOR/POI).Results:①Among 283 patients,EMT(59.0%)and FTO(50.5%)were identified as the most frequent etiological factors,significantly more prevalent than the other causes(P=0.0000,P＜α').②The 5 most common etiological combinations were:FTO with EMT,PCOS with EMT,AM with FTO,DOR/POI with EMT,and AM with EMT.③After stratified analysis,it was found that the following combination of causes was ranked in the top three:with EMT stages I-IV being highly associated with FTO;the degree of merger between low stage with PCOS is high,while the degree of merger be-tween high stage with AM and DOR/POI is high.Different degrees of IUA are highly associated with EMT,FTO and DOR/POI,while severe IUA also being highly associated with TE.Both unilateral and bilateral FTO have a high degree of merger with EMT and AM.DOR and POI have a high degree of merger with EMT,FTO and AM.Conclusions:EMT and FTO are the main causes of refractory infertility.There are correlations among the causes combinations.The etiological factors combined with different stages of endometriosis are also different.These findings underscore the importance of a comprehensive diagnostic framework to address multifactorial etiologies and reduce missed diagnoses.

Objective:To explore the etiological rules of multifactorial refractory infertility patients by association analysis.Methods:A total of 283 patients with refractory infertility met the inclusion criteria from January 2019 to December 2021 in Nanping People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,were analyzed retrospectively.Using the Apriori algorithm,association rule analysis was performed on 7 etiological fac-tors:fallopian tube obstruction(FTO),intrauterine adhesions(IUA),ovarian dysfunction[diminished ovarian re-serve(DOR),premature ovarian insufficiency(POI)],polycystic ovary syndrome(PCOS),endometriosis(EMT),adenomyosis(AM)and thin endometrium(TE).Further stratified analysis was performed to assess the combina-tions of causes based on the severity of 4 major factors(EMT,FTO,IUA and DOR/POI).Results:①Among 283 patients,EMT(59.0%)and FTO(50.5%)were identified as the most frequent etiological factors,significantly more prevalent than the other causes(P=0.0000,P＜α').②The 5 most common etiological combinations were:FTO with EMT,PCOS with EMT,AM with FTO,DOR/POI with EMT,and AM with EMT.③After stratified analysis,it was found that the following combination of causes was ranked in the top three:with EMT stages I-IV being highly associated with FTO;the degree of merger between low stage with PCOS is high,while the degree of merger be-tween high stage with AM and DOR/POI is high.Different degrees of IUA are highly associated with EMT,FTO and DOR/POI,while severe IUA also being highly associated with TE.Both unilateral and bilateral FTO have a high degree of merger with EMT and AM.DOR and POI have a high degree of merger with EMT,FTO and AM.Conclusions:EMT and FTO are the main causes of refractory infertility.There are correlations among the causes combinations.The etiological factors combined with different stages of endometriosis are also different.These findings underscore the importance of a comprehensive diagnostic framework to address multifactorial etiologies and reduce missed diagnoses.