Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To analyze the differences of brain activity between first-episode untreated depressive patients with and without suicidal ideation(SI),and its correlations with clinical characteristics.Methods A total of 40 major depressive disorder(MDD)patients with SI(MDD+SI group),40 patients without SI MDD(MDD+NSI group),and 40 healthy controls(HC)(HC group)were enrolled.The 17-item Hamilton depression scale(HAMD-17)and Beck scale for suicide ideation(BSI)were used to assess the severity of depression and SI,respectively.MRI data were collected.The values of fractional amplitude of low-frequency fluctuation(fALFF)were calculated.Results(1)Compared with the HC group,the MDD+NSI group showed decreases in the fALFF val-ues of the default network and attention network.The fALFF values of the attention network in the MDD+SI group showed decreases.Compared with the MDD+NSI group,the MDD+SI group showed decreases in the fALFF values of the attention network.(2)The fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.55;P<0.001)in the MDD+NSI group,while the fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.53;P<0.001)and the total score of BSI(r=-0.51;P<0.001)in the MDD+SI group.(3)The optimal critical value of fALFF value in left middle frontal gyrus for predicting SI occurrence in MDD patients was-0.039,area under the curve(AUC)was 0.76,sensitivity was 0.63,and specificity was 0.80.Conclusion The decreased local activity intensity in the left middle frontal gyrus of the brain might be the central mechanism for the occurrence of SI in MDD patients.In addition,the left middle frontal gyrus might have certain value in identifying SI and predicting the severity of SI.

Objective To investigate the clinical characteristics of preoperative intestinal symptoms in patients with bowel endometriosis and to compare the effects of shaving versus segmental bowel resection on postoperative intestinal function.Methods A total of 105 patients diagnosed with bowel endometriosis and treated by the same surgical team at the Obstetrics and Gynecology Hospital,Fudan University between Aug 1,2013 and Dec 30,2017 were prospectively enrolled in this study.Clinical data were collected via outpatient visits and telephone follow-ups at four time points:preoperative(T0)and postoperative(T1:Nov 2018;T2:Nov 2020;T3:Apr 2024).The primary outcome was bowel symptoms and gastrointestinal function scores;secondary outcome was pain scores.A generalized estimating equation(GEE)model was used to analyze the interaction effect of surgical approach and follow-up time on outcomes.Results Ultimately,a total of 89 patients were included(15.24%loss to follow-up),among whom 79 patients(88.76%)underwent shaving excision.Preoperatively,46 patients(51.68%)presented with bowel symptoms,primarily anus bulge(21 cases,46.65%)and diarrhea(15 cases,32.61%)during menstruation.Postoperatively,there was a significant increase in constipation rates(T1:71.43%;T2:50.00%;T3:72.00%).Both surgical groups exhibited significant improvements in dysmenorrhea,gastrointestinal discomfort scores as well as gastrointestinal quality of life index(P<0.000 5).However,the segmental resection group had significantly higher scores for low anterior resection syndrome,constipation compared with the shaving excision group(P=0.02 and P=0.05).Conclusion Approximately half of the patients with bowel endometriosis exhibit typical bowel symptoms preoperatively,such as anus bulge and diarrhea.Both shaving excision and segmental resection effectively alleviate pain;however,shaving excision demonstrates an advantage regarding preservation of bowel function,whereas segmental resection may elevate risks associated with postoperative constipation or altered defecation patterns due to structural changes.The selection of surgical approach should carefully balance lesion removal and functional preservation,moreover,be sure that potential risks are thoroughly informed to patients prior to surgery.

Objective To explore the similarities and differences in clinical efficacy and mRNA transcriptomics characteristics between acupuncture and shallow needling at non-acupoints and to provide a basis for determining whether shallow needling at non-acupoints is suitable as a sham acupuncture control in acupuncture clinical trials.Methods Eighty patients with chronic spontaneous urticaria(CSU)who visited the Dermatology Department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between July 8,2018 and to July 29,2019,were included.The patients were randomly divided into the acupuncture group(n=41)and the sham acupuncture group(n=39)using a computerized complete random design.Additionally,12 healthy individuals were included as the healthy control group.For patients in the acupuncture group,"Baihui(GV20),""Shenting(GV24),""Zhongwan(CV12),"and bilateral"Quchi(LI11),""Tianshu(ST25),""Xuehai(SP10),""Zusanli(ST36),"and"Sanyinjiao(SP6)"were selected for regular acupuncture.The sham acupuncture group received non-acupoint shallow needling at eight non-acupoints on the head,upper limbs,lower limbs,and abdomen.Both groups underwent daily treatment,with five consecutive days constituting one treatment course followed by a two-day interval.A total of two courses were administered.The urticaria activity score(UAS)was used to evaluate wheals and pruritus,whereas the visual analog scale(VAS)score was used to evaluate the degree of pruritus.Blinding effectiveness was also evaluated.Based on clinical evaluation and sample quality,serum samples from six patients in each treatment group before and after the intervention,along with those from six healthy individuals,were selected for RNA sequencing using the BGISEQ-500 sequencer.Differentially expressed mRNAs were identified using the"DEGseq"software package,and the similarities and differences in mRNA expression between the two groups were analyzed.Results UAS and VAS scores decreased in both groups at 1,2,3,and 4 weeks of treatment compared with before treatment(P＜0.01).The decrease in UAS and VAS scores in both groups was time-dependent(P＜0.01)but not related to the grouping or the interaction between grouping and time(P＞0.05).By the end of the second week of treatment,the number of patients in both groups who believed they had received true acupuncture was similar between the two groups,with no significant difference.mRNA transcriptomic sequencing revealed that,before and after treatment,the enrichment types and degrees of differentially expressed mRNA were similar between the acupuncture and sham acupuncture groups at the biological process,cellular component,and molecular function levels.In terms of biological processes,both groups were commonly enriched in coagulation,hematoma,oxygen transport,and gas transport.In terms of cellular components,both groups exhibited enrichment in hemoglobin complexes,platelet alpha granules,extracellular exosomes,extracellular organelles,and extracellular vesicles.At the molecular function level,both groups were commonly enriched in actin filament-binding substances,haptoglobin,peroxidase activity,and oxygen blood binding.In the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,both groups showed common enrichment in multiple entries such as cytokine-cytokine receptor interaction,ECM-receptor interaction,microRNAs in cancer,proteoglycans in cancer,bladder cancer,and malaria.Conclusion Acupuncture and sham acupuncture exhibited similar clinical treatment effects and mRNA transcriptomics profiles.In the design of acupuncture clinical trials,disease specificity should be carefully considered.Sham acupuncture control using non-acupoint shallow needling may not be suitable for skin diseases such as urticaria.

Background and purpose:In the quality control of mammography,the signal-to-noise ratio(SNR)refers to the ratio of the useful signal intensity to the background noise in the image,which is one of the important indicators for measuring the quality of the image.The coefficient of variation(CoV)is a commonly used indicator to describe the consistency and repeatability of SNR.This study aimed to assess the stability and repeatability of mammographic device performance by analyzing the changes in SNR CoV in two-dimensional(2D)images and tomosynthesis images(referred to as Tomo images)under different exposure modes using three mammographic devices from different manufacturers.Methods:A polymethylmethacrylate(PMMA)phantom designed for mammography quality control was used to perform automatic exposure detection at PMMA thicknesses ranging from 20-80 mm,with actual compression thickness equivalent to the average density of the breast compressed to 21-103 mm under full-field digital mammography(FFDM),low-dose mammography and digital breast tomosynthesis(DBT)exposure modes.The CoV of SNR in 2D images and tomosynthesis images was calculated for different mammographic devices under different exposure modes and compression thicknesses.Results:Between the compression thicknesses equivalent to the average density of the breast from 21 mm to 103 mm under FFDM,low-dose mammography,and DBT exposure modes,the differences in SNR CoV of 2D images under different exposure modes among mammographic devices 1,2,and 3 were statistically significant only in the DBT exposure mode(P=0.003),with SNR CoV ranging from 0.188%to 0.720%,0.368%to 1.073%and 0.402%to 1.662%,respectively.There were no statistically significant differences in SNR CoV of 2D images among devices 1,2,and 3 under FFDM and low-dose exposure modes(P=0.060).Under the DBT exposure mode,there were no statistically significant differences in the SNR CoV of the first projection image and the 0° projection image of tomosynthesis among devices 1(2 angles),2,and 3(P=0.373,P=0.742,P=0.225,P=0.693,respectively).Conclusion:The SNR CoV in 2D images and tomosynthesis images varies under different mammographic devices and exposure modes,with no fixed or standard values,but all within the required range for mammographic device quality control.The stability and repeatability of 2D images of mammographic devices are better under FFDM and low-dose exposure modes;the SNR CoV values of the first projection image and the 0° projection image of tomosynthesis under the DBT exposure mode show no statistical differences,indicating good stability of the devices.

Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.

Objective:To investigate the application value of exercise rehabilitation mode based on cardiopulmonary exercise testing(CPET)in the treatment and rehabilitation of coronary heart disease(CHD).Methods:This ran-domized controlled study enrolled 260 CHD patients admitted in Hai'an People's Hospital between January 2021 and June 2022.They were divided into control group(n=130,routine nursing)and intervention group(n=130,addi-tional exercise rehabilitation training nursing).After 6-month intervention,scores of Heart Health-Self-Effica-cy and Self-Management(HH-SESM)scale,Chinese Quality of Life Questionnaire for Cardiovascular Patients(CQQC),peak oxygen uptake(VO2peak),percentage of peak oxygen uptake in predicted maximum(VO2peak％Pred),peak metabolic equivalent(peak Mets),cardiac function indexes,and incidence of adverse events were com-pared between two groups.Results:After intervention,compared with patients in control group,those in interven-tion group had significant higher scores of HH-SESM[(76.57±5.88)points vs.(64.51±5.16)points]and CQQC[(111.66±7.93)points vs.(84.16±6.96)points],VO2peak[(1.41±0.11)L/min vs.(1.19±0.26)L/min],VO2peak％Pred[(59.32±3.51)％vs.(51.27±3.11)％],peak Mets[(7.89±1.86)vs.(5.22±1.16)],6MWD[(473.53±18.12)m vs.(354.27±23.11)m],and significant lower serum N-terminal pro brain natri-uretic peptide(NT-proBNP)[(5.13±2.17)pg/ml vs.(13.81±2.22)pg/ml],cardiac troponin Ⅰ(cTnⅠ)[(2.90±0.51)ng/ml vs.(4.76±1.32)ng/ml](P＜0.001 all).Intervention group had significant lower incidence of adverse events comparing to control group(3.85％vs.13.85％,P=0.005).Conclusion:Exercise rehabilitation treatment based on cardiopulmonary exercise test could effectively improve self-efficacy and self-management,quality of life,cardiopulmonary function and reduce risk of adverse events in patients with coronary heart disease.

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*