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

The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia(AML)cells.Methods:Juglone and AML targets were collected from public databases,and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML.Then wet experiments were performed to verify.AML cell lines including KG-1a,MV-411,THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h.MTT assay was used to detect cell viability and determine the IC50,and the most sensitive cell line was screened for subsequent experiments.Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone.Western blot was performed to check the expression of relevant proteins.Results:Eleven targets were obtained as potential targets for juglone in the treatment of AML,and the top ten significantly enriched pathways were intrinsic pathway of apoptosis,programmed cell death,cytochrome c-mediated apoptotic response,apoptosis,apoptotic factor-mediated response,regulated necrosis,cytokine signaling in immune system,signaling by interleukins,oncogene induced senescence,and signal transduction.The cell viability of KG-1a,MV-411,THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment(r=-0.992,-0.886,-0.956,-0.910).Among them,MOLM-13 was the most sensitive to juglone.The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone(r=0.99).At the same time point,p-RIPK1/RIPK1,p-RIPK3/RIPK3,and p-MLKL/MLK were decreased in each juglone concentration group compared with control group.Conclusion:Juglone inhibits the viability of KG-1a,MV-411,THP-1 and MOLM-13 cells,and induces apoptosis of MOLM-13 cells,the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.

Objective To investigate the current situation of skin tests for β-lactams in 155 hospitals in Beijing.Methods The questionnaires were sent to medical institutions in Beijing to statistically described the current situation of β-lactams skin test,and the relevant influencing factors were analyzed by Fisher exact test,and Chi-square test.Results A total of 3 097 questionnaires were received from 155 medical institutions,of which 3 057 were valid questionnaires(effective rate is 98.71％).In this study,122 hospitals conducted skin test before using intravenous penicillins,accounting for 99.19％of 123 hospitals with intravenous penicillins.Hospitals with infectious disease pharmacists conducted more skin tests before using intravenous penicillins(98.59％vs 88.46％,P＜0.001),and some hospitals didn't conduct skin tests before using oral penicillins.Seventy hospitals(45.16％)had not yet cancelled skin tests for cephalosporins,more hospitals with infectious disease pharmacists cancelled routine skin test(59.74％vs 50.00％,P＜0.05),and more tertiary hospitals cancelled cephalosporin skin test(80.65％vs 51.40％,29.41％,all P＜0.01).After the promulgation of the"Guiding Principle for Skin Test of β-lactams(2021 edition)",more primary hospitals have developed or updated the rules or regulation for skin test of β-lactams according to the Guiding Principle,compared with secondary hospitals(72.22％vs 41.18％,P＜0.05).Hospitals with infectious disease pharmacists developed or updated the rules or regulation for skin test of β-lactams in their hospitals(78.57％vs 60.00％,P＜0.05).Infectious disease pharmacists had promoting effect on the publicity of the rules or regulation of skin test in the hospital(92.65％vs 80.46％,P＜0.05).Conclusion Many hospitals in Beijing have not cancelled cephalosporins skin test,and the current situation of cancelling cephalosporins skin test in tertiary hospitals is better than that in primary and secondary hospitals.

Aim To investigate the expression level of CBX4 in esophageal squamous cell carcinoma(ESCC)and the effect of CBX4 on ESCC proliferation and un-derlying molecular mechanisms.Methods The ex-pression of CBX4 in different cancers was analyzed in Pan-cancers.The expression level of CBX4 in ESCC was analyzed by t-test based on Gene Expression Omni-bus(GEO)data.The viability of CBX4-overex-pressed/knockdown ESCC cells was detected by MTT assay,colony formation assay and flow cytometry assay.Furthermore,the tumor volumn,tumor weight and Ki67 expression were measured by mouse xenograft assay and immunohistochemistry.The mRNA and protein ex-pression levels of apoptosis-related genes PARP、Bcl-2、Bax were determined by qRT-PCR and Western blot,respectively.In addition,the underlying molecular mechanism of CBX4 in ESCC was revealed by qRT-PCR and Western blot.Results CBX4 was upregulat-ed in various cancers.The expression level of CBX4 in ESCC was higher than that in normal tissues(P＜0.05)based on Gene Expression Omnibus(GEO)da-ta.Compared with the normal group,the proliferation of CBX4 knockdown ESCC cells was significantly in-hibited and the apoptosis was promoted(P＜0.05).Meanwhile,the mRNA and protein expression levels of cleaved PARP and Bax were upregulated while that of Bcl-2 was downregulated.In CBX4 overexpression group,tumor volume in vivo increased(P＜0.05).Immunohistochemical results also showed an increase in Ki67 expression.Furthermore,the results of RNA-seq,bioinformatics analysis and qRT-PCR experiments indicated that CBX4 probably regulated the prolifera-tion and apoptosis of ESCC through p38 MAPK signa-ling pathway.Conclusion CBX4 is highly expressed in ESCC and plays as an oncogene role,which might regulate cell proliferation through the p38 MAPK signa-ling pathway.

Objective The causes of bleeding after endoscopic duodenal papilloma resection were analyzed and discussed,and the prediction model of nomogram was established.Methods A total of 233 patients who underwent endoscopic duodenal papilloma resection in our hospital from January 2018 to December 2023 were retrospectively analyzed,and they were divided into bleeding group(n=31 cases)and non-bleeding group(n=202 cases)according to whether postoperative bleeding occurred.The clinical data of the two groups were compared,the independent risk factors for postoperative bleeding were analyzed by multi-factor logistic regression,the risk nomogram prediction model was constructed,and the Bootstrap method was used for 1000 repeated samples to carry out internal verification.Results Anticoagulant drugs(OR=9.063,95％CI:2.132-38.525),lesion diameter ≥2 cm(OR=2.802,95％CI:1.073-7.321),intraoperative fragment resection(OR=27.653,95％CI:3.055～619.174)and pancreatic complications(OR=6.859,95％CI:1.930～24.377)were independent risk factors for postoperative bleeding after endoscopic duodenal papilloma resection(P＜0.05).A risk prediction nomogram model was constructed according to the Logistic regression analysis results.The samples were repeatedly sampled 1000 times through Bootstrap method for internal verification.The area under the ROC curve was 0.850,and the 95％CI was 0.780-0.913,indicating good differentiation ability of the model.Calibration curve analysis indicated that the prediction probability of postoperative bleeding predicted by the nomogram prediction model was in good agreement with the actual probability of postoperative bleeding,and Hosmer-Lemeshow showed good goodness of fit(x2=3.304 9,P=0.913 8).Conclusion Taking anticoagulant drugs,lesion diameter ≥2 cm,intraoperative segmentary resection,and postoperative combination of pancreas were independent risk factors for bleeding after endoscopic duodenal papilloma resection.A nomogram prediction model was established to help clinical assessment of postoperative bleeding risk in patients and improve decision-making basis for early prevention.