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 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.

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.
Female ; Humans ; Cervix Uteri/surgery* ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms/surgery* ; Carcinoma, Neuroendocrine/surgery* ; Recurrence