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 construct a risk prediction model for post-stroke dysphagia(PSD)based on clinical and laboratory indicators of elderly stroke patients with explainable machine learning.Methods A retrospective analysis was conducted on 3994 stroke patients hospitalized in Depart-ment of Neurology of First Medical Center of Chinese PLA General Hospital from October 2010 to December 2021.Among them,the 1390 cases admitted during January 2019 and December 2021 were assigned into an external validation set,and the 2604 cases admitted during October 2010 to January 2019 were into a training group.Those from the training group were further divided into a training set(1823 cases)and an internal validation set(781 cases)in a 7∶3 ratio,and also grouped into a PSD subgroup(773 cases)and a non-PSD group(1831 cases).With occurrence of swallowing difficulties as an endpoint,risk prediction models were constructed using random for-est(RF),eXtreme Gradient Boosting(XGBoost),Support Vector Machine(SVM),and logistic regression.ROC curve analysis was employed to evaluate the performance of our models.After the optimal model was selected,SHAP was employed to interpret feature contributions.Results There were significant differences in muscle strength,right/left-sided stroke,and area of brain in-jury between the PSD and the non-PSD groups(P＜0.01).The PSD group had obviously larger proportions of hypertension,diabetes,and drinking history,increased neutrophil counts,and de-creased levels of potassium and albumin when compared with the non-PSD group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that age,drinking history,diabetes,hyper-tension,muscle strength grade,area of brain injury,hemispheric stroke,neutrophil count,and al-bumin and potassium levels were risk factors for PSD(P＜0.05,P＜0.01).The external validation results showed that the area under curve value of the RF model,XGBoost model,SVM model,and our logistic model was 0.883,0.902,0.877,and 0.868,respectively.The distribution of SHAP value showed that drinking history,hypertension and diabetes were positively correlated with PSD risk;Muscle strength was negatively correlated with the risk;Age growth was positively correlated with the risk;Subtentorial lesions showed stronger predictive efficacy than supratentorial lesions and entire lesions;The bilateral and right-sided stroke had higher risk for PSD than the left-sided stroke.Conclusion The model based on the XGBoost model shows best performance in predicting the risk for swallowing disorders in elderly patients after stroke.

Objective:To investigate the clinical manifestations, pathological features, treatment methods and prognosis of primary renal synovial sarcoma (PRSS) in order to improve the clinical understanding and treatment level of the disease.Methods:The clinical data, pathological features, immunohistochemical indexes, SYT gene detection, treatment and follow-up results of 21 patients with PRSS reported in the First Affiliated Hospital of Soochow University from 2018 to 2023 were retrospectively analyzed. Kaplan-Meier method was used to calculate the relationship between age and cumulative survival rate. Results:The male to female ratio of PRSS patients was 16∶5, the ratio of left and right kidneys was 7∶14, the median age was 50 years old, the mean age was 44.5 years old, the median tumor length diameter was 9.7 cm, and the mean tumor length diameter was 6.7 cm. 57%(12/21) reported low back pain and 48%(10/21) reported gross hematuria. Immunohistochemical examination showed 100% positive for Vimentin(16/16), BCL-2(18/18) and TLE-1(10/10), 69%(9/13) and 85%(6/7) positive for CD99 and CD56, respectively. Genetic testing found SYT translocation signal in 92% of cases (12/13). Next generation sequencing (NGS) detected SS18- SSX1 fusion in 2 cases and SS18- SSX2 fusion in 1 case. SS18- SSX1+ S18- SSX2 fusion was found in 1 case, and one case of SS18- NEDD4 fusion occurred. Preoperative neoadjuvant chemotherapy was performed in 2 cases, postoperative chemotherapy in 11 cases, postoperative chemoradiotherapy in 2 cases, and surgery only in 5 cases. All patients were followed up for 3 to 42 months, and 4 cases were lost to follow-up. Patients with younger onset had a longer cumulative survival time. Patients had a median survival time of 13 months and a mean survival time of 15.4 months. Conclusions:PRSS is more common in middle-aged men, the right kidney is easy to occur, the length of the mass is usually >7 cm, most cases can be initially diagnosed by pathologic morphology, immunophenotype, fluorescence in situ hybridization or NGS STY gene detection can provide accurate diagnosis. The prognosis of PRSS is very poor, and the cumulative survival rate is negatively correlated with the age of onset. Surgical resection combined with chemotherapy is the main treatment for PRSS.

Objective:To investigate the clinical manifestations, pathological features, treatment methods and prognosis of primary renal synovial sarcoma (PRSS) in order to improve the clinical understanding and treatment level of the disease.Methods:The clinical data, pathological features, immunohistochemical indexes, SYT gene detection, treatment and follow-up results of 21 patients with PRSS reported in the First Affiliated Hospital of Soochow University from 2018 to 2023 were retrospectively analyzed. Kaplan-Meier method was used to calculate the relationship between age and cumulative survival rate. Results:The male to female ratio of PRSS patients was 16∶5, the ratio of left and right kidneys was 7∶14, the median age was 50 years old, the mean age was 44.5 years old, the median tumor length diameter was 9.7 cm, and the mean tumor length diameter was 6.7 cm. 57%(12/21) reported low back pain and 48%(10/21) reported gross hematuria. Immunohistochemical examination showed 100% positive for Vimentin(16/16), BCL-2(18/18) and TLE-1(10/10), 69%(9/13) and 85%(6/7) positive for CD99 and CD56, respectively. Genetic testing found SYT translocation signal in 92% of cases (12/13). Next generation sequencing (NGS) detected SS18- SSX1 fusion in 2 cases and SS18- SSX2 fusion in 1 case. SS18- SSX1+ S18- SSX2 fusion was found in 1 case, and one case of SS18- NEDD4 fusion occurred. Preoperative neoadjuvant chemotherapy was performed in 2 cases, postoperative chemotherapy in 11 cases, postoperative chemoradiotherapy in 2 cases, and surgery only in 5 cases. All patients were followed up for 3 to 42 months, and 4 cases were lost to follow-up. Patients with younger onset had a longer cumulative survival time. Patients had a median survival time of 13 months and a mean survival time of 15.4 months. Conclusions:PRSS is more common in middle-aged men, the right kidney is easy to occur, the length of the mass is usually >7 cm, most cases can be initially diagnosed by pathologic morphology, immunophenotype, fluorescence in situ hybridization or NGS STY gene detection can provide accurate diagnosis. The prognosis of PRSS is very poor, and the cumulative survival rate is negatively correlated with the age of onset. Surgical resection combined with chemotherapy is the main treatment for PRSS.

Objective To investigate the occurrence risk for common complications of internal jugular vein(IJV)and subclavian vein(SCV)catheterization,and provide reference for the prevention and treatment of common com-plications during clinical intravenous infusion therapy.Methods Data from China National Knowledge Infrastruc-ture(CNKI),Wanfang Database,VIP Database,Embase(via OVID),PubMed,Cochrane Library,CINAHL,Web of Science,and ScienceDirect were retrieved,with the search period from database establishment to August 3,2023.Prospective cohort and experimental studies on common complications in patients with IJV and SCV cathete-rization were collected.Meta-analysis on the extracted data was performed with RevMan 5.3 software.Results A total of 29 studies involving 14 096 patients were included in the analysis,including 6 355 patients with SCV cathe-terization(SCV group)and 7 741 patients with IJV catheterization(IJV group).Meta-analysis results showed that the occurrence risk for hemopneumothorax(OR=0.23,95％CI[0.14-0.37])and catheter tip ectopic(OR=0.16,95％CI[0.03-0.85])in SCV group was higher than that in IJV group,and the occurrence risk for central venous catheter-related deep venous thrombosis in IJV group was higher than that in SCV group(OR=2.35,95％CI[1.31-4.21]),with statistically significant differences(all P＜0.01).There were no statistical differences in the occurrence risk of vascular catheter-related bloodstream infection(CRBSI),catheter blockage,and catheter local he-matoma between the two groups(all P＞0.05),there was difference in the combined result of subgroup analysis re-garding catheter bacterial colonization.Conclusion Compared with IJV,patients in SCV group have a higher risk of developing hemopneumothorax and catheter tip ectopic,while patients with catheterization in IJV group have a high-er risk of deep veinous thrombosis.There are no significant differences in the occurrence risk for CRBSI,catheter blockage,and catheter local hematoma between two groups of patients.It is suggested that patient's own conditions and the accessibility of deep vein catheterization should be considered more when selecting the site of deep venous catheterization.

Purpose This study aimed to explore the mucinous phenotype characteristics,key points of differenti-al diagnosis and prognosis of invasive non-mucinous adenocarcinoma(INMA)and invasive mucinous adenocarcinoma(IMA)under the WHO(2021)lung adenocarcinoma classification.Methods We retrospectively collected clinico-pathological data from 522 cases of lung adenocarcinoma,including 425 INMA(66 with mucin secretion,259 without mucin secretion)and 97 IMA.Immunohistochemical(IHC)staining using the EnVision method was performed on the mucin-secreting adenocarcinoma to assess expression of TTF-1,HNF4α,MUC1,MUC4,MUC5AC,MUC5B,and MUC6.Unsupervised clustering analysis was conducted to explore phenotypic subgroups.Results 522 patients with lung adenocarcinoma ranged from 32 to 83 years old(median:61).251 cases(48.1％)were male and 271 cases(51.9％)were female.Clustering analysis divided lung adenocarcinomas into two major groups:one characterized by TTF-1-/HNF4α+and gastric-type mucins MUC5AC+/MUC6+,predominantly IMA;the other,TTF-1+/HNF4α-/MUC4+,largely INMA.A three-marker IHC panel(TTF-1,HNF4α,MUC6)distinguished IMA from mucinous IN-MA with an area under the ROC curve(AUC)of 0.957(95％CI:0.928-0.986)and a Youden's index of 0.860.Further cluster analysis of INMA cases identified four phenotypic subgroups.Prognostic analysis demonstrated that pa-tients with advanced-stage mucin-secreting INMA had significantly shorter overall survival(OS)and progression-free survival(PFS)than those without mucin secretion(5-year OS:57.1％ vs 81.8％,P=0.004;3-year PFS:40.9％ vs 62.4％,P=0.004).No significant survival differences were noted among INMA subgroups stratified by varying mucin proportions.Multivariate analysis identified pathological stage,tumor necrosis,KRAS mutation,and TTF-1 negativity as independent adverse prognostic factors for both OS and PFS in mucinous INMA.Conclusion A three-marker im-munohistochemical panel of TTF-1,HNF4α,and MUC6 is recommended to distinguish IMA from mucinous INMA.Mucus component portends a worse prognosis in advanced INMA,with necrosis,KRAS mutations,and TTF-1 negativi-ty serving as independent adverse prognostic factors in mucinous INMA.

Objective: To understand the influence of the concept of movement education on the fundamental motor skills of preschool children aged 3-6, so as to provide a reference for improving the quality of preschool education and promoting the all round development of preschool children. Methods: From August 2022 to June 2023, 592 normally developing preschool children aged 3- 6 in a certain kindergarten in Qingdao were selected as the research objects by convenience sampling. They were randomly divided into the intervention group (physical education activities designed based on the concept of movement education) and the control group (original teaching plan). The intervention lasted for 24 weeks (twice a week, 40 minutes each time). Test of Gross Motor Development-2 (TGMD-2) was used to evaluate the children s gross motor skills, and repeated measures analysis of variance was used to analyze the data of the two groups before and after the intervention. Results: Except for running and kicking, the group main effects ( F group =18.78-104.77), time main effects( F time =243.23-3 003.19), and other interactive effects between group and time ( F group×time =14.01-322.91) were of statistical significances for gross motor, movement motor, manipulative motor and each sub indicator between intervention group and control group. Further simple effect analysis results showed that, before intervention, there were no statistically significant differences in the total scores of gross motor (48.95±10.65,45.87±10.98), movement motor ( 25.93± 7.31,23.46±7.32) and manipulative motor (23.15±4.40,22.40±4.69) between the intervention group and the control group ( F=3.69, 2.94, 1.90, P >0.05); and two goups were also found of no statistical significance in the each sub indicator of movement and manipulative motor ( F=0.01-3.58, P >0.05); after intervention, the total scores of gross motor, movement motor, and manipulative motor in the intervention group (75.92±9.48, 38.12±5.40, 37.80±4.92) were all better than those in the control group ( 59.52± 12.12, 30.71±7.47, 28.81±5.54) ( F =168.15, 97.58, 210.71), and the total indicators of both goups had better scores than those before the intervention ( F intervention = 3 498.90 , 1 438.27, 2 431.24; F control =545.58, 309.18, 283.29)(all P <0.01); after intervention, the intervention group had better scores in all sub indicators (except for running and kicking) than the control group ( F =43.57-297.71), and the each sub indicator of both goups had better scores than those before the intervention ( F intervention = 300.58-858.65; F control =12.28-135.64)(all P <0.01). Conclusion Physical education activities designed based on the concept of movement education could better promote the development of children s fundamental motor skills.

Purpose This study aimed to explore the mucinous phenotype characteristics,key points of differenti-al diagnosis and prognosis of invasive non-mucinous adenocarcinoma(INMA)and invasive mucinous adenocarcinoma(IMA)under the WHO(2021)lung adenocarcinoma classification.Methods We retrospectively collected clinico-pathological data from 522 cases of lung adenocarcinoma,including 425 INMA(66 with mucin secretion,259 without mucin secretion)and 97 IMA.Immunohistochemical(IHC)staining using the EnVision method was performed on the mucin-secreting adenocarcinoma to assess expression of TTF-1,HNF4α,MUC1,MUC4,MUC5AC,MUC5B,and MUC6.Unsupervised clustering analysis was conducted to explore phenotypic subgroups.Results 522 patients with lung adenocarcinoma ranged from 32 to 83 years old(median:61).251 cases(48.1％)were male and 271 cases(51.9％)were female.Clustering analysis divided lung adenocarcinomas into two major groups:one characterized by TTF-1-/HNF4α+and gastric-type mucins MUC5AC+/MUC6+,predominantly IMA;the other,TTF-1+/HNF4α-/MUC4+,largely INMA.A three-marker IHC panel(TTF-1,HNF4α,MUC6)distinguished IMA from mucinous IN-MA with an area under the ROC curve(AUC)of 0.957(95％CI:0.928-0.986)and a Youden's index of 0.860.Further cluster analysis of INMA cases identified four phenotypic subgroups.Prognostic analysis demonstrated that pa-tients with advanced-stage mucin-secreting INMA had significantly shorter overall survival(OS)and progression-free survival(PFS)than those without mucin secretion(5-year OS:57.1％ vs 81.8％,P=0.004;3-year PFS:40.9％ vs 62.4％,P=0.004).No significant survival differences were noted among INMA subgroups stratified by varying mucin proportions.Multivariate analysis identified pathological stage,tumor necrosis,KRAS mutation,and TTF-1 negativity as independent adverse prognostic factors for both OS and PFS in mucinous INMA.Conclusion A three-marker im-munohistochemical panel of TTF-1,HNF4α,and MUC6 is recommended to distinguish IMA from mucinous INMA.Mucus component portends a worse prognosis in advanced INMA,with necrosis,KRAS mutations,and TTF-1 negativi-ty serving as independent adverse prognostic factors in mucinous INMA.

Objective To observe the characteristics of sublingual collaterals of patients with hypertension and the correlation between TCM syndromes and characteristics of sublingual collaterals based on image data.Methods Totally 303 patients with hypertension were selected from three hospitals in Anhui Province from October 2022 to April 2024,and were divided into liver fire hyperactivity syndrome,yin deficiency and yang hyperactivity syndrome,phlegm and blood stasis syndrome,and yin yang deficiency syndrome according to the syndromes.The patients'sublingual collateral images were captured using smartphones,and the AI open platform system for TCM tongue diagnosis was used to obtain the color,length,width,tortuous degree and concurrent manifestations of the sublingual collaterals,as well as the characteristic indexes,such as color HSV,Lab value,etc.of sublingual collaterals,using a combination of computer vision and manual interpretation,so as to analyze the correlation between the TCM syndromes and the characteristics of the sublingual collaterals.Results The color,length,width,tortuous degree and concurrent manifestations of sublingual collaterals in different syndrome types were statistically significant.The values of V,Lab-L,Lab-a and Lab-b in the phlegm and blood stasis syndrome were significantly lower than those in other syndrome types.The S value of yin-yang deficiency syndrome was significantly lower than that of other syndromes(P＜0.05).Correlation analysis showed that the color of sublingual collaterals was negatively correlated with the values of S,V,Lab-L,Lab-a and Lab-b of patients with different syndrome types(P＜0.05).The degree of stasis of sublingual collaterals in the phlegm and blood stasis syndrome was higher than that in other groups.Conclusion There are differences in color,length,width,tortuous degree and concurrent manifestations among the sublingual collaterals of patients with hypertension,and there is close correlation between the color of sublingual collaterals and its parameters.The objective index of sublingual collaterals is sensitive to hypertension,which is basically consistent with the theory and clinical conclusion of TCM,and can be used as the basis for syndrome differentiation and treatment.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.