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 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.

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.

Objective:To analyze the clinical characteristics of long-term survival patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with primary tumor radiotherapy, and to establish a Nomogram prognostic model, aiming to provide a certain reference for making a decision about the treatment of advanced NSCLC.Methods:A retrospective analysis was made on the data of 260 NSCLC patients who participated in two prospective clinical studies from January 2003 to May 2012 and the data of 138 NSCLC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from January 2014 to August 2020. The former 260 cases were used as a training set and the latter 138 cases were used as the validation set. The overall survival (OS) of ≥ 18 months was defined as long-term survival (LTS). The clinical characteristics of LTS patients were compared with those with OS less than 18 months. The clinical characteristics and treatment-related parameters between the two types of patients were compared using the χ2 test. A multivariate analysis was made using logistic regression, and a nomogram model was built using RStudio. Results:The median OS of the training set was 13.4 months (95% CI: 11.9-14.9), with 1-, 2-, and 3-year OS rates of 55.4%, 19.1%, and 11.9%, respectively. In the training set, 87 cases had LTS and were classified as the LTS group, while 173 cases had OS less than 18 months and were classified as the non-LTS group. The univariate analysis showed that the prognostic factors affecting LST included the KPS score, T status, the number of metastatic organs, the number of metastatic lesions, brain metastasis, bone metastasis, the number of chemotherapy cycles, the biologically effective dose (BED) to the primary tumor, hemoglobin level, platelet count, plasma D-dimer, fibrinogen level, lactate dehydrogenase, and lung immune prognostic index (LIPI; χ2=4.72-12.63, P < 0.05). The multivariable analysis showed that the independent prognostic factors of LTS included a number of chemotherapy cycles ≥ 4, BED ≥ 70 Gy, platelets ≤ 220×10 9/L, D-dimer ≤ 0.5 mg/L, and a good LIPI score ( P= 0.002, 0.036, 0.005, 0.008, and 0.002). A nomogram model was established using the meaningful parameters obtained in the multivariable analysis, determining that the training and validation sets had a consistency index (C-index) of 0.750 and 0.727, respectively. As shown by the analytical result of the corrected curves, for the advanced NSCLC patients treated with thoracic radiotherapy, their LTS probability predicted using the nomogram prognostic model was highly consistent with their actual LTS probability. Both the analytical result of the receiver operating characteristic (ROC) curves and the decision curve analysis (DCA) result showed that the composite prediction model was more beneficial than a single prediction model. Conclusions:For patients with advanced NSCLC treated with thoracic radiotherapy, the independent prognostic factors of LTS included the number of chemotherapy cycles, BED, platelet count, pre-chemotherapy D-dimer, and LIPI score. The Nomogram prognostic model built based on these prognostic factors is a convenient, intuitive, and personalized prediction model used to screen patients who can benefit from thoracic radiotherapy.

Objective:To investigate the efficacy and safety of semisupine-lithotomy position placement of Allium ureteral stent to treat ureteral stricture caused by pelvic tumours.Methods:The clinical data of 29 patients who received Allium ureteral stent(URS) placement for ureteral stricture in Sun Yat-sen Memorial Hospital, Sun Yat-sen University between April 2020 and March 2022 were retrospectively analyzed. There were 3 males and 26 females, with the median age of 56(54, 61) years old. All patients had a pathology confirmation of carcinoma before the treatment, including 26 patients with gynaecological tumours, two with urinary system tumours, and one with rectal carcinoma. A preoperative imaging examination confirmed the diagnosis of ureteral stricture. There were 15 patients with unilateral and 14 with bilateral stenosis, median stenosis length was 3.6(2.0, 4.9)cm. Preoperative median urine white blood cell count was 62(21, 354) U/L, median serum creatinine (SCR) was 170.0(85.5, 273.5) μmol/L, and renal pelvis separation was (32.98±6.64) mm. The median time of long-term indwelling double J (D-J)ureteral stent before surgery was 12.0 (6.5, 35.5) months. Seven patients had mild hydronephrosis, 18 had moderate hydronephrosis, and four had severe hydronephrosis. In all patients, Allium URS were placed in the way of the semisupine-lithotomy position (Galdakao-modified supine Valdivia position). Anterograde flexible ureteroscope was inserted into the percutaneous nephrostomy channel, and the retrogradel rigid ureteroscope were advanced simultaneously, looking for location of strictures. Allium URS were inserted retrogradely with transureteroscope when the two ureteroscope were connected. Perioperative conditions and postoperative follow-up for the last examination of SCR, renal pelvis width under ultrasound, and plain abdominal film (KUB). Allium URS patency and complications, hydronephrosis and renal function were evaluated.Results:A total of 61 Allium URS were successfully placed. Seven patients were placed in stages, and 18 patients were placed in series with multiple stents. The mean follow-up period was (12.1±5.8) months. At last follow-up, median SCR was 124.0(81.5, 193.0)μmol/L and renal pelvis separation was(14.96±5.18)mm, which were significantly decreased compared with preoperative(all P<0.01). There were 24 cases of hydronephrosis disappeared and 5 cases of mild hydronephrosis in the last follow-up. Postoperative follow-up, urinary tract infection occurred in 3 patients after operation, such as hematuria and fever within one week, and the symptoms were relieved after anti-infective and symptomatic treatment. One case had mild urine leakage, and 4 patients had occasional low back pain, which may be related to the activity. One case occurred stent displacement due to stent migration to the bladder after eight months, the URS was replaced and a D-J stent was inserted .The patency rate was 96.6%(28/29). Conclusions:Allium URS was placed in the semisupine-lithotomy position for treating pelvic tumour-induced ureteral stricture, with low incidence of complications, high patency and good curative effect.

Objective:To investigate the mechanism by which chronic psychological stress aggravates intestinal barrier damage and promotes the development of enteritis through inhibiting Wnt/β-catenin pathway, so as to provide a new therapeutic strategy for the clinical diagnosis and treatment of inflammatory bowel disease (IBD).Methods:A comorbidity model of chronic psychological stress and enteritis was established using C57BL/6J mice. HE staining was used to analyze the effects of chronic psychological stress on the intestinal pathological damage in mice with enteritis. ELISA was used to detect the expression of proinflammatory cytokines. The ultrastructural changes of colonic cells and the state of intestinal mucus layer were observed under transmission electron microscope and scanning electron microscope. The secretion of mucoprotein 2 (MUC2) and the expression of cell proliferation marker Ki67 were detected by immunofluo rescence staining. The numbers of goblet cells were detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Western blot was performed to analyze the expression of tight junction protein between intestinal epithelial cells, β-catenin which was a key protein of Wnt/β-catenin pathway maintaining crypt proliferation, and downstream protein c-myc.Results:The sugar water consumption ratio decreased, but tail suspension immobility time, the swimming immobility time and the expression of corticotropin releasing hormone (CRH) in hypothalamus increased (all P<0.05) in the stress group as compared with those in the control group. Chronic psychological stress promoted weight loss and colonic shortening in mice with enteritis, exacerbated pathological damage and enhanced the release of pro-inflammatory factors. Moreover, increased disappearance of intestinal epithelial microvilli and severe cellular ultrastructural damage were also observed in the stress+ dextran sulfate sodium salt (DSS) group. There was no pathological damage in the control and stress groups. Chronic psychological stress aggravated intestinal barrier injury and inhibited intestinal barrier repair by inhibiting Wnt/β-catenin pathway. Conclusions:In the mouse model of DSS-induced enteritis, chronic psychological stress preconditioning inhibited the Wnt/β-catenin pathway, weakened the repair ability of intestinal epithelium, aggravated the loss of mucus layer of intestinal barrier and the damage of tight junction structure, and promoted the development of enteritis. In the absence of enteritis, chronic psychological stress had no significant effects on the Wnt/β-catenin pathway and the intestinal barrier.

Objective:To study the relationship between endoplasmic reticulum stress (ERS) and apoptotic protein and myocardial pathological changes in rats after endostar combined with low-dose X-ray irradiation.Methods:Forty SD rats were evenly divided into four groups: control group (intraperitoneal injection of equal volume physiological saline, once per day, 14 d), endostar group (intraperitoneal injection of endostar 6 mg/kg, once per day, 14 d), irradiation group (15 Gy divided into 3 times X-ray irradiation) and combination group (intraperitoneal injection of endostar after irradiation at the same dose and time as the endostar group). At 1 and 6 months after treatment, myocardial tissues of rats were prepared for HE staining and Masson staining to observe the myocardial histological changes. TUNEL assay was used to detect myocardial cell apoptosis, and ImageJ software was utilized to calculate myocardial collagen volume fraction (CVF). The expression levels of ERS and apoptotic protein glucose-regulated protein 78 (GRP78), protein kinase-like endoplasmic reticulum kinases (PERK), CCAAT/enhancer binding protein homologous protein (CHOP) and cysteine-containing aspartate-specific protease-12 (Caspase-12) were detected by Western blot. One-way ANOVA was conducted using GraphPad Prism 8.0.1 software, and comparison between two groups was conducted using t-test. Results:At 6 months after treatment, the myocardial interstitium in the irradiation and combination groups was widened, showing strip-like or reticular fibrosis changes, and the myocardial interstitium had diffuse collagen fiber deposition. Compared with the control group, CVF was increased significantly (both P<0.01). At 1 and 6 months after treatment, the apoptotic index of myocardial cells in the combination group was significantly higher than that in the control group ( P<0.05, <0.001). At 1 and 6 months after treatment, the expression levels of GRP78 protein in the irradiation and combination groups were increased (all P<0.01), and the expression levels of PERK and CHOP proteins in the combination group were increased compared to those in the control group (both P<0.05). At 6 months after treatment, the expression levels of PERK and CHOP proteins in the irradiation group were increased compared to those in the control group (both P<0.05). Compared with the control group, Caspase-12 expression levels at 1 and 6 months after treatment were increased in the endostar, irradiation and combination groups (all P<0.05). Conclusions:The expression levels of ERS and apoptotic proteins are related to cardiac injury caused by irradiation in rats. After low-dose X-ray combined with endostar treatment, ERS is aggravated and myocardial apoptosis is increased.

Objective:To investigate the optimal monoenergetic level of virtual monoenergetic images (VMI) in transplanted renal artery on a dual-layer spectral detector CT.Methods:A retrospective study was performed on 16 renal transplant patients who underwent transplanted renal angiography on a dual-layer spectral detector CT in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to April 2021. Conventional 120 kVp polyenergetic images (PI) were reconstructed, and virtual monoenergetic images (VMIs) in range of 40-200 keV with interval of 10 keV were reconstructed, too. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of 120 kVp PI and VMIs were measured. Meanwhile, the subjective scores of the display of transplanted renal artery were performed on volume rendering images of 120 kVp PI and VMIs. Spearman correlation analysis was used to explore the correlation between energy levels and SNR or CNR. Rank sum tests were performed to compare the parameters of image quality between the VMI which had the highest SNR and CNR, and the other VMIs, or 120 kVp PI.Results:Among the VMIs, SNR or CNR was negatively correlated with energy levels ( r =-0.86 and -0.88, all P<0.001). The SNR [22.80(18.57, 34.16)] and CNR [35.38(25.97, 39.01)] of 40 keV VMI were the highest, and significantly higher than that of 120 kVp PI and 50-200 keV VMIs, all the differences were statistically significant (all P<0.05). The subjective scores of 40 keV VMI and 120 kVp PI were 5 (5, 5) and 4 (3, 5), respectively. The score of 40 keV VMI was significantly higher than that of 120 kVp PI ( Z=-2.60, P=0.009). There were no significant differences in subjective scores between 40 keV VMI and 50-70 keV VMIs ( Z=-1.00, -1.41, -1.73, P=0.317, 0.157, 0.083), but the subjective score of 40 keV VMI was higher than that of 80-200 keV VMIs and the differences were statistically significant (all P<0.05). Conclusions:As for the images of transplanted renal angiography on a dual-layer spectral detector CT, the image quality of 40 keV VMI was best, thus 40 keV was the optimal monoenergetic level.

Objective:To analyze the mediastinal displacement of target volume in the postoperative radiotherapy (PORT) process for non-small cell lung cancer (NSCLC) and the value of mid-term evaluation.Methods:For 100 patients with postoperativeN 2 stage NSCLC, R 1-2 and any N staging, bone anatomy was utilized to measure the change of the first and second CT localization on the same level. Statistical analysis were performed using the WilCoxon, Kruskal-Wallis and χ2 tests. The cut-off values were calculated with the receiver operating characteristic (ROC) curve. Results:Among the included patients, in the PORT process, the mediastinal displacement in the x (front and rear), Y (left and right) and Z (upper and lower) directions were 0.04-0.53 cm, 0.00-0.84 cm and 0.00-1.27 cm, respectively, and the order of mediastinal displacement distance wasz > Y> X,respectively. According to the ROC curve calculation, the cut-off values were 0.263, 0.352 and 0.405, respectively, which were greater than the cut-off values in 25 cases (25%), 30 cases (30%) and 30 cases (30%), respectively. There was significant difference in the three-dimensionalmediastinal displacement ( P=0.007, <0.001 and<0.001). The mediastinal displacement in thex, Y and Z directions had no statistical significance regarding resection site ( P=0.355, 0.239 and 0.256) and operation mode ( P=0.241, 0.110 and 0.064). Comparative analysis of modified whole group mediastinal shift> and cut-off values, medium-simulation (m-S) and the originally planned radiotherapy shown that there was no significant difference in the incidence of radiation esophagitis (RE) and radiation pneumonitis in PORT patients (all P>0.05); however, the incidence of ≥grade 3 RE in the modified plan after m-S was significantly lower than that in the originally planned PORT patients, which were 0 and 7%, respectively ( P<0.001). Conclusions:Mediastinal displacement exists in the PORT process of N 2 or/and R 1-2 cases after radical operation of NSCLC, and obvious movement occurs in 20%-30% of patients. Relocating and modifying the target volume and radiotherapy plan in the middle of the PORT process is beneficial to quality assurance and quality control.

Objective:To investigate the implication of micro RNA-21(miR-21) in Endostar combined with X-ray irradiation of cardiac fibroblasts (CF).Methods:Rat CFs were used in this experiment and been divided into the blank control group, 10 Gy X-ray irradiation group, Endostar group, 10 Gy X-ray+ Endostar group, 10 Gy X-ray+ Endostar+ NC mimic group (negative control 1), 10 Gy X-ray+ Endostar+ miR-21 mimic group, 10 Gy X-ray+ Endostar+ NC inhibitor group (negative control 2) and 10 Gy X-ray+ Endostar+ miR-21 inhibitor group. The proliferation of CF was determined by Methyl thiazolyl tetrazolium (MTT) assay. The expression level of Collagen Ⅰ protein was analyzed by Western blot. The expression levels of Collagen Ⅰ and miR-21 mRNA were assayed by real-time quantitative polymerase chain reaction (q-PCR).Results:In the 10 Gy X-ray+ Endostar+ miR-21 mimic group, the CF proliferation, Collagen Ⅰ and miR-21 mRNA were increased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group, and negative control group 1 (all P<0.05). In the 10 Gy X-ray+ Endostar+ miR-21 inhibitor group, the CF proliferation and expression levels of Collagen Ⅰ mRNA were decreased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group and negative control group 2(all P<0.05). Conclusions:The CF proliferation and Collagen Ⅰ expression are increased when the expression level of miR-21 gene is simulated. When inhibiting the expression of miR-21 gene, the CF proliferation and Collagen Ⅰ expression are reduced.