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.

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

Objective To evaluate the efficacy and safety of Mirabegron combined with transcutaneous tibial nerve stimulation (TTNS) in the treatment of drug-refractory overactive bladder (OAB), so as to alleviate patients'symptoms, improve their quality of life with optimized treatment plan, and provide reference for clinical practice. Methods A retrospective analysis was conducted on 56 patients with drug-refractory OAB treated at the Department of Urology of Gansu Provincial Hospital during Jan.2023 and Dec.2024. Based on the treatment methods, the patients were divided into two groups:the TTNS group and the combined treatment group, with 28 patients in either group. The daytime urination frequency, nocturia frequency, urgency episodes, urinary incontinence, functional bladder capacity (FBC), OAB symptom scores (OABSS), and incontinence quality of life questionnaire (I-QoL) scores were collected before and after treatment. The therapeutic efficacy was evaluated using the Nimodipine method. Results After 12 weeks of treatment, the 24-hour urination indicators in both groups including daytime urination frequency, nocturia frequency, urgency episodes and FBC, as well as OABSS and I-QoL scores, showed a significant improvement compared to baseline (P<0.001). The combined treatment group exhibited fewer urgency episodes than the TTNS group [ (1.07±0.66) times/24 h vs. (1.64±0.62) times/24 h, P<0.05]. However, no statistically significant differences were observed between the two groups in other urinary parameters (P>0.05). The total effective rate in the combined treatment group was 96.43%, which was significantly higher than that in the TTNS group (82.14%, P<0.05). During treatment, one patient (3.57%) in the TTNS group experienced mild skin allergy, which recovered following symptomatic management. Conclusion The combination of TTNS and Mirabegron in drug-refractory OAB not only alleviates clinical symptoms and improves quality of life, but also shows superior efficacy in reducing urgency episodes. This approach is a safe and effective treatment option.

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 investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Objective To observe the changes in myocardial energy metabolism in elderly patients with chronic heart failure(CHF),and analyze its influence on major adverse cardiovascular events(MACE).Methods A retrospective study was conducted on 90 elderly CHF patients(observation group)admitted to our department from January 2021 to January 2024.They were assigned into Class Ⅱ(23 cases),Ⅲ(37 cases)and Ⅳ subgroups(30 cases)according to NYHA functional classification.And another 30 healthy individuals who taking physical examination in our hospital during same period served as control group.Their myocardial energy metabolism indicators,inclu-ding free fatty acids(FFA),circumferential end-systolic wall stress(cESS)and myocardial energy expenditure(MEE)were compared between the two groups.The patients in the observation group were followed up for 6 months after discharge,and then divided into MACE subgroup(40 cases)and non-MACE subgroup(50 cases)according to whether MACE occurred.The differences of FFA,cESS and MEE were compared between the two subgroups,and Spearman correlation analy-sis was used to analyze the correlation of the indicators,multivariate logistic regression analysis was employed to identify the influencing factors,and ROC curve was plotted to analyze the pre-dictive values of the indicators.Results The values of FFA,cESS and MEE were significantly in-creased in the NYHA Class Ⅱ,Ⅲ and Ⅳ subgroups in turn(P＜0.01),and these values were ob-viously higher in the observation group than the control group(P＜0.05).The MACE group had advanced age,larger proportion of NYHA ClassⅣ,and higher NT-proBNP and FFA levels,cESS and MEE values,but lower LVEF than the non-MACE group(P＜0.01).FFA,cESS and MEE were positively correlated with MACE in elderly CHF patients(r=0.512,0.495,0.503,P＜0.05,P＜0.01).Age(OR=2.344,95％CI:1.255-3.464),NYHA cardiac function grade(OR=2.079,95％CI:1.354-2.804),LVEF(OR=2.173,95％CI:1.179-3.167),NT-proBNP(OR=2.257,95％CI:1.149-3.365),FFA(OR=2.713,95％CI:1.103-4.323),cESS(OR=1.868,95％CI:1.111-2.625)and MEE(OR=3.010,95％CI:1.064-4.956)were risk factors for MACE in eld-erly CHF patients with.The AUC value of FFA,cESS and MEE in predicting the occurrence of MACE in elderly CHF patients was 0.732,0.707 and 0.768,respectively,and the AUC value of their combination was 0.893,which was greater than that of the single indicator(Z=6.325,6.581,6.247;P=0.022,0.015,0.026).Conclusion FFA,cESS and MEE are positively correlated with the occurrence of MACE in elderly CHF patients,and are risk factors for MACE occurrence in them.The three indicators have certain predictive performance for MACE,and their combina-tion can further improve the predictive value.