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

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

OBJECTIVES: To study the clinical characteristics, efficacy, and prognosis of pediatric Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis was conducted on 72 children with newly diagnosed LCH. RESULTS: The median age of the 72 children was 5 years (range: 0-14 years), with skull involvement being the most common (56 cases, 77.8%). The BRAF-V600E mutation was not associated with clinical characteristics, efficacy, or prognosis (P>0.05). The 5-year overall survival rate was 91.6%±4.2%, and the 5-year event-free survival (EFS) rate was 67.5%±5.8%. The 6-week chemotherapy response rate and 5-year EFS rate were lower in the risk organ involvement group compared to the no risk organ involvement group (P<0.05). The five-year overall survival rates for the group with multi-system involvement and the group with platelet count ≥450×10⁹/L were respectively lower than those for the single-system involvement group and the group with platelet count <450×10⁹/L (P<0.05). Risk organ involvement is an independent risk factor for 5-year EFS (P<0.05). CONCLUSIONS Skull is the most commonly affected site in pediatric LCH. The BRAF-V600E mutation is not related to clinical characteristics, efficacy, or prognosis. Elevated platelet count, risk organ involvement, and multisystem involvement are associated with poor prognosis, with risk organ involvement being an independent risk factor for 5-year EFS.
Humans ; Histiocytosis, Langerhans-Cell/therapy* ; Child, Preschool ; Child ; Male ; Infant ; Female ; Adolescent ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/genetics* ; Prognosis ; Infant, Newborn ; Mutation

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

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.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Objective To investigate the effect and safety of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy.Methods The subjects of this study,112 female patients who underwent axillary endoscopic thyroidectomy in our hospital from January 2022 to October 2024,were randomly divided into an observation group and a control group,each with 56 cases.All patients were administered with ultrasound-guided cervical plexus block followed by general anesthesia.The observation group was injected with 0.1 mg/kg of esketamine prior to anesthesia induction and continuously pumped with esketamine at a rate of 0.1 mg/(kg·h)during the operation until sutures were completed,while the control group was administered with an equal volume of normal saline following the same procedure.The vital sign indicators[mean arterial pressure(MAP),heart rate(HR)and percutaneous arterial oxygen saturation(SpO2)]immediately after establishing electrocardiogram monitoring(T0),immediately before tracheal intubation(T1),immediately after tracheal intubation(T2),immediately after skin incision(T3)and immediately after the operation(T4)were compared between the two groups.Surgical related indicators such as propofol dosage,remifentanil dosage,and extubation time were also compared between them.Pain visual analogue scale(VAS)scores were performed on patients from the two groups at 1,6,12,and 24 h postoperatively.The 40-item quality of recovery score(QoR-40)was used before the surgeries and 1 d after surgeries to assess the patients.Adverse reactions were also compared.Results The difference was significant in terms of MAP,HR time effect in the two groups(F=24.63,F=20.11,P<0.05)and inter-group MAP,HR values(F=13.54,F=11.49,P<0.05).There were statistically significant differences in the interaction effects of MAP and HR between the two groups(F=4.10,F=3.46,P<0.05).The difference was not statistically significant in time,inter group,and interaction effects of SpO2(P>0.05).The dosage of propofol,remifentanil,and postoperative 1 d drainage in the observation group were less than those in the control group,the differences were statistically significant(P<0.05).The differences were not statistically signiciant in extubation time and awakening time between the two groups(P>0.05).The VAS scores at 1,6,12,and 24 h after operation in the observation groups were lower than those in the control group,the differences were statistically significant(P<0.05).Physical comfort,pain dimension ratings,and total score of the QoR-40 scale:1)those 1 d after operation were lower than those before operation in both groups(P<0.05);2)1 d after operation:those in the control group were lower than those in the observation group(P<0.05).The control group witnessed a remarkable decrease in QoR-40 emotional state rating 1 d after operation than it did before operation(P<0.05),while no significant change was seen by the observation group in this regard(P>0.05).The incidence of coughing after extubation in the observation group was lower than that in the control group(14.29%and 37.50%),the difference was statistically significant(P<0.05).The differences were not statistically signiciant in the incidence of other adverse reactions such as nausea,vomiting,dizziness,headache,respiratory depression,awakening restlessness and awakening delirium between the two groups(P>0.05).The total incidence of adverse reactions in the observation group was significantly lower than that in the control group(25.00%and 66.07%,P<0.05).Conclusion The application of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy can significantly stabilize hemodynamics in patients,reduce postoperative pain,and promote postoperative recovery.It is worthy clinical application.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective To investigate the effect and safety of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy.Methods The subjects of this study,112 female patients who underwent axillary endoscopic thyroidectomy in our hospital from January 2022 to October 2024,were randomly divided into an observation group and a control group,each with 56 cases.All patients were administered with ultrasound-guided cervical plexus block followed by general anesthesia.The observation group was injected with 0.1 mg/kg of esketamine prior to anesthesia induction and continuously pumped with esketamine at a rate of 0.1 mg/(kg·h)during the operation until sutures were completed,while the control group was administered with an equal volume of normal saline following the same procedure.The vital sign indicators[mean arterial pressure(MAP),heart rate(HR)and percutaneous arterial oxygen saturation(SpO2)]immediately after establishing electrocardiogram monitoring(T0),immediately before tracheal intubation(T1),immediately after tracheal intubation(T2),immediately after skin incision(T3)and immediately after the operation(T4)were compared between the two groups.Surgical related indicators such as propofol dosage,remifentanil dosage,and extubation time were also compared between them.Pain visual analogue scale(VAS)scores were performed on patients from the two groups at 1,6,12,and 24 h postoperatively.The 40-item quality of recovery score(QoR-40)was used before the surgeries and 1 d after surgeries to assess the patients.Adverse reactions were also compared.Results The difference was significant in terms of MAP,HR time effect in the two groups(F=24.63,F=20.11,P<0.05)and inter-group MAP,HR values(F=13.54,F=11.49,P<0.05).There were statistically significant differences in the interaction effects of MAP and HR between the two groups(F=4.10,F=3.46,P<0.05).The difference was not statistically significant in time,inter group,and interaction effects of SpO2(P>0.05).The dosage of propofol,remifentanil,and postoperative 1 d drainage in the observation group were less than those in the control group,the differences were statistically significant(P<0.05).The differences were not statistically signiciant in extubation time and awakening time between the two groups(P>0.05).The VAS scores at 1,6,12,and 24 h after operation in the observation groups were lower than those in the control group,the differences were statistically significant(P<0.05).Physical comfort,pain dimension ratings,and total score of the QoR-40 scale:1)those 1 d after operation were lower than those before operation in both groups(P<0.05);2)1 d after operation:those in the control group were lower than those in the observation group(P<0.05).The control group witnessed a remarkable decrease in QoR-40 emotional state rating 1 d after operation than it did before operation(P<0.05),while no significant change was seen by the observation group in this regard(P>0.05).The incidence of coughing after extubation in the observation group was lower than that in the control group(14.29%and 37.50%),the difference was statistically significant(P<0.05).The differences were not statistically signiciant in the incidence of other adverse reactions such as nausea,vomiting,dizziness,headache,respiratory depression,awakening restlessness and awakening delirium between the two groups(P>0.05).The total incidence of adverse reactions in the observation group was significantly lower than that in the control group(25.00%and 66.07%,P<0.05).Conclusion The application of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy can significantly stabilize hemodynamics in patients,reduce postoperative pain,and promote postoperative recovery.It is worthy clinical application.

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.