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 explore the association between nocturnal blood pressure decline rate and chronic heart failure(CHF).Methods In this study,a total of 711 individuals who underwent 24-h ambulatory blood pressure monitoring were divided into control group(n=433)and CHF group(n=278).The characteristics of the study population and nocturnal blood pressure decline rate were compared between CHF group and control group.Restricted spline analysis was utilized to examine the linear or non-linear association between nocturnal blood pressure decline rate and the prevalence of CHF.The relationship between nocturnal blood pressure decline rate and CHF was further investigated based on multivariable Logistic regression model.Results Nocturnal systolic blood pressure decline rate was significantly different in CHF group and control group[(3.3±7.1)mmHg vs.(5.0+6.7)mmHg,P=0.001].No significant difference in nocturnal diastolic blood pressure was found between the two groups[(5.7±7.6)mmHg vs.(6.8±7.2)mmHg,P=0.061].Restricted spline analysis showed a significant linear association between nocturnal systolic blood pressure decline rate and CHF risk.After adjusting for age,sex,smoking,body mass index,24-hour systolic blood pressure,24-hour diastolic blood pressure,type 2 diabetes mellitus and hyperlipidemia,multivariate Logistic regression analysis revealed that nocturnal systolic blood pressure decline rate was negatively associated with the prevalence of CHF(OR=0.97,95％CI:0.95-0.99;P=0.010).However,no significant association was found between nocturnal diastolic blood pressure decline rate and CHF risk.Conclusion Nocturnal systolic blood pressure decline rate is associated with the prevalence of CHF.Individuals with decreased nocturnal systolic blood pressure decline have a significantly increased risk of CHF.

Objective:To explore the clinical application value of convolutional neural network（CNN）based on deep learning in the automatic measurement of dynamic pelvic floor ultrasound video parameters and the diagnosis and classification of cystocele.Methods:A retrospective analysis was conducted on dynamic pelvic floor ultrasound videos from 398 postpartum women who underwent examinations at the First People's Hospital of Foshan between June 2020 and June 2022. The lowest point of the posterior bladder wall（PWB），urethral rotation angle（URA），and retrovesical angle（RVA）were manually measured by a senior radiologist（R1）and a junior radiologist（R2），and cystocele was classified according to the Green standard. The CNN model was employed to automatically extract the above parameters and to diagnose and classify cystocele. Using R1 measurements as a reference，intraclass correlation coefficient（ICC）was used to evaluate the consistency between the CNN model and R1，as well as between R2 and R1. The Kappa value was used to assess the agreement between the CNN model，R2，and R1 in the diagnosis and classification of cystocele. Additionally，the time consumption of the three measurement methods was compared.Results:The CNN model showed good consistency with R1 in measuring PWB and URA（ICC = 0.983，0.894），while its consistency in measuring RVA was moderate（ICC = 0.614）. The ICC between R2 and R1 in measuring PWB，URA，and RVA was 0.979，0.815，and 0.627，respectively. In the measurement of PWB and URA，the consistency between the CNN model and R1 was superior to that between R2 and R1. For cystocele diagnosis，the Kappa value between the CNN model and R1 was 0.924，which was higher than that between R2 and R1（0.904）. In cystocele classification，the Kappa value between the CNN model and R1 was 0.503，also higher than that between R2 and R1（0.426）. The CNN model processed a single video in 2.5（0.6）s，significantly faster than R1［59.9（16.9）s］and R2［56.8（11.2）s］（all P < 0.001）. Conclusions:The CNN model demonstrates high accuracy and efficiency in the measurement，diagnosis，and classification of cystocele，outperforming a junior radiologist and showing potential for clinical application.

AIM To improve the quality of Compound Yuxingcao Tablets.METHODS The HPLC fingerprints were established,after which the contents of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,forsythoside I,forsythoside A,quercitrin,3,5-O-dicaffeoylquinic acid,4,5-O-dicaffeoylquinic acid,baicalin,oroxyloside,wogonin and baicalein were determined.The analysis was performed on a 30 ℃ thermostatic Waters XBridge C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 327 nm.Subsequently,principal component analysis and orthogonal partial least squares discriminant analysis were adopted.RESULTS There were 21 common peaks in the fingerprints for 22 batches of samples with the similarities of more than 0.85.Twelve constituents showed good linear relationships within their own ranges(R20.999 8),whose average recoveries were 93.68％-101.16％with the RSDs of 0.95％-2.35％.Baicalin,wogonin and forsythoside A were taken as quality differential components.CONCLUSION This simple and accurate method can be used for the quality control of Compound Yuxingcao Tablets.

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 down-regulated metabolites in sera of RIPS 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[13Cs]-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 infiltration of immune cells in different molecular subtypes of endometrial cancer(EC)at the protein level and explore the correlation between immune infiltration and clinicopathological features.Methods:Clinical data from 75 mismatch repair-deficient(MMR-D)EC cases and 74 mismatch re-pair-proficient(MMR-P)EC cases with comparable differentiation levels,diagnosed at Sichuan Provincial People's Hospital between January 2013 and January 2021,were selected.Molecular classification of EC was con-ducted according to the ProMisE standard.Immunohistochemistry(IHC)staining and fluorescent multiplexed im-munohistochemistry(F-mIHC)techniques were used to quantify the distribution of CD8+T cells,regulatory T cells(Tregs),and macrophages.The clinicopathological features and immune infiltration characteristics of different subtypes were investigated.Results:Among 149 samples,75 were MMR-D,8 were POLE-mutated(POLEmut),13 were p53-mutated(p53abn),and 53 were p53 wild-type(p53wt).The infiltration characteristics of CD8+T cells,Tregs,and macrophages were no statistically significant differences correlated with age and pathological stage(P>0.05).Among the molecular subtypes of EC,MMR-D tumors demonstrated a significantly higher densi-ty of CD8+T cells and Tregs compared to MMR-P tumors(P<0.05).Further comparison across the four EC mo-lecular subtypes revealed that the MMR-D subtype,which had a favorable prognosis,displayed a significantly high density of CD8+T cells compared to the p53abn subtype and the p53wt subtype(P<0.05).Additionally,the Tregs density of the MMR-D tumors was significantly higher than that of the p53wt tumors,in both the tumor area(P<0.05)and the stroma area(P<0.05).The POLEmut type tumors,which had the best prognosis,showed a high infiltration of CD8+T cells and Tregs cells compared to the p53abn and p53wt types,although there was no signifi-cant statistical difference(P>0.05).The p53wt subtype,which had a moderate prognosis,exhibited low density of CD8+T cells(P<0.05)and Tregs(tumor area,P<0.01,stroma area,P<0.05)compared to MMR-D tumors.The p53abn subtype,which was associated with the worst prognosis,exhibited higher infiltration of M2-like macro-phages than the MMR-D subtype(P<0.05)and the p53wt subtype(P<0.05)in tumor region,and lower CD8+T cell density than the MMR-D subtype(P<0.05).No significant statistical difference was observed in the density of M1-like macrophages across the four molecular subtypes in either the tumor or stroma areae(P>0.05).Conclu-sions:There was no statistically significant relation found between infiltration characteristics of immune cells and clinicopathological features.The types and distribution of infiltrated immune cells were different across these EC molecular subtypes.This indicated that ECs with different molecular subtype exhibited different features of immune infiltration which is closely associated with patient prognosis.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for simultaneous determination of seven characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rat plasma, including galangin, kaempferol, kaempferide, pinocembrin, 1,7-diphenyl-4-en-3-heptanone, 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA), and 7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-4-en-3-heptanone(DPHB). The new developed HPLC-MS/MS method was applied to study the pharmacokinetics of the 7 characteristic components in rats with Helicobacter pylori gastritis. A Waters Sunfire C_(18) column(2.1 mm×150 mm, 3.5 μm) was used. The acetonitrile-aqueous solution(containing 0.1% formic acid) was adopted as the mobile phase for gradient elution. Seven components and internal standard(chlorogenic acid) were separated within 12 min. Mass spectrometric detection was performed in multiple reaction monitoring(MRM) mode using electrospray ionization(ESI) source with fast switching between positive and negative ions. The method was verified by specificity, linearity, precision, accuracy, recovery, matrix effect, and stability and met the requirements of pharmacokinetic study on the 7 components in rat plasma. Pharmacokinetic results showed that the average peak time(T_(max)) of the 7 components was 0.31-2.19 h, their elimination half-life(t_(1/2)) was 5.26-16.65 h, and the average residence time(MRT) was 6.29-31.03 h after the oral administration of the active fraction of Alpiniae Officinarum Rhizoma to rats with H. pylori gastritis. The plasma exposure levels of galangin and DHPA were higher than those of the other components. The concentration-time curves of four detected flavonoids showed obvious double peaks. This study elucidated the pharmacokinetic characteristics of 7 characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rats with H. pylori gastritis, providing a scientific basis for the identification of the pharmacodynamic substances of Alpiniae Officinarum Rhizoma for treatment of H. pylori gastritis and the clinical application of Alpiniae Officinarum Rhizoma in the prevention and treatment of H. pylori gastritis.
Animals ; Rats ; Chromatography, High Pressure Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Helicobacter pylori/drug effects* ; Alpinia/chemistry* ; Rats, Sprague-Dawley ; Gastritis/metabolism* ; Helicobacter Infections/metabolism* ; Flavonoids/blood* ; Rhizome/chemistry* ; Liquid Chromatography-Mass Spectrometry

Objective To study the economic burden caused by healthcare-associated infection(HAI)in patients with severe acute pancreatitis(SAP),and provide theoretical basis for formulating HAI prevention and control measures.Methods Patients with SAP discharged from a tertiary first-class hospital in Jiangxi Province from July 1,2023 to June 30,2024 were selected as the study subjects.Information including demographic characteristics,clinical data,and hospitalization expense were collected.Patients were divided into a HAI group and a non-HAI group according to HAI occurrence.A propensity score matching(PSM)method was used to conduct a 1∶2 ma-tching,and differences in the length of hospital stay and hospitalization expense between the two groups of patients after PSM were compared.Results A total of 709 patients were included in the analysis,out of which 65 cases ex-perienced HAI,with a HAI incidence of 9.17％.After PSM,all 65 patients in the HAI group were successfully matched.The length of hospital stay,total hospitalization expense,expenses of medication and hygiene product of patients in the HAI group were all higher than those in the non-HAI group,and differences were all statistically sig-nificant(all P＜0.001).Patients who experienced≥2 episodes of HAI had a higher economic burden than those who experienced only once(P＜0.05).HAI of bloodstream,abdomen,digestive system,and respiratory system significantly increased the economic burden of patients(all P＜0.05).Conclusion HAI in SAP patients can extend the length of hospital stay and increase economic burden of patients.Targeted infection prevention and control mea-sures should be formulated to reduce the incidence of HAI and save medical resources.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.