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.

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.

Objective: To explore the effects of bicycle ergometer rehabilitation training on quadriceps and walking ability of patients with lower limb dysfunction caused by extensive burns. Methods: A prospective randomized controlled study was conducted. A total of 40 patients with extensive burns who met the inclusion criteria and were admitted to Tongren Hospital of Wuhan University＆Wuhan Third Hospital from December 2017 to December 2020 were selected. According to the random number table, the patients were divided into conventional training group (16 males, 4 females, aged (45±10) years) and combined training group (13 males, 7 females, aged (39±8) years). Patients in conventional training group were given conventional rehabilitation therapy such as joint loosening, lower limb strength training, walking training, and pressure therapy, while patients in combined training group were given additional bicycle ergometer rehabilitation training on the basis of conventional rehabilitation. For patients in the 2 groups before and after a 2-month's treatment, the thickness of quadriceps was measured by ultrasonic diagnostic instrument, the muscle strength of quadriceps was measured by portable muscle strength tester, the walking ability was tested with a 6-min and a 10-meter walk tests, and the patients' satisfaction for treatment effects was assessed using the modified Likert scale. Data were statistically analyzed with independent or paired sample t test, Mann-Whitney U test, Wilcoxon signed rank test, or chi-square test. Results: After 2-month's treatment, the quadriceps thickness of patients in combined training group was (3.76±0.39) cm, which was significantly thicker than (3.45±0.35) cm in conventional training group (t=2.67, P<0.05); quadriceps thickness of patients in conventional training group and combined training group after 2-month's treatment was significantly thicker than that before treatment (with t values of 5.99 and 8.62, respectively, P<0.01). After 2-month's treatment, the quadriceps muscle strength of patients in combined training group was significantly greater than that in conventional training group (Z=2.69, P<0.01); quadriceps muscle strength of patients in conventional training group and combined training group after 2-month's treatment was significantly greater than that before treatment (with Z values of 3.92 and 3.92, respectively, P<0.01). After 2-month's treatment, the 6-min walking distance of patients in combined training group was (488±39) m, which was significantly longer than (429±25) m in conventional training group (t=5.66, P<0.01); the 6-min walking distance of patients after 2-month's treatment in conventional training group and combined training group was significantly longer than that before treatment (with t values of 13.16 and 17.92, respectively, P<0.01). After 2-month's treatment, the 10-meter walking time of patients in combined training group was significantly shorter than that in conventional training group (t=3.20, P<0.01); and the 10-meter walking time in conventional training group and combined training group was significantly shorter than that before treatment (with t values of 7.21 and 13.13, respectively, P<0.01). The patients' satisfaction score for treatment effects in combined training group was significantly higher than that in conventional training group (Z=3.14, P<0.01), and the patients' satisfaction scores for treatment effects in conventional training group and combined training group after 2-month's treatment were significantly greater than those before treatment (with Z values of 3.98 and 4.04, respectively, P<0.01). Conclusions: Bicycle ergometer rehabilitation training can be used to improve quadriceps thickness, muscle strength, and walking ability of patients with lower limb dysfunction caused by extensive burns. It can also improve the satisfaction of patients with the treatment outcome, and therefore is worthy of promotion.
Bicycling ; Burns/therapy* ; Female ; Humans ; Lower Extremity ; Male ; Prospective Studies ; Quadriceps Muscle ; Treatment Outcome ; Walking

Objective To explore and analyze the risk factors of severe falciparum malaria cases,and to provide evidence for early clinical prevention and intervention measures. Methods A total of 114 imported cases of falciparum malaria in Wuhan from March 2012 to November 2019 were selected,divided into mild group(n=87)and severe group(n=27),and logistic regression analysis was performed on the risk factors of severe disease. Results There were significant differences in length of stay, erythrocyte, hemoglobin, platelet, urea, creatinine, albumin, creatine kinase isoenzyme, lactate dehydrogenase, urine occulting blood and urine protein between mild group and severe group (P<0.05).Multivariate Logistic regression analysis showed that alanine aminotransferase (OR=0.167, 95%CI: 0.042-0.668), albumin (OR=24.843, 95% CI: 5.170-119.383), urea (OR=0.240,95%CI: 0.074-0.779) and occulted blood in urine (OR=0.204, 95%CI: 0.062-0.672) were independent influencing factors for the occurrence of severe falciparum malaria. Conclusion Patients with liver function damage and alanine aminotransferase increased by more than 2 times(≥80U/L),albumin decreased(<30g/L),renal function damage,increased urea nitrogen,hematuria and other abnormal results, the possibility of severe falsiparum malaria development should be highly suspected.

Objective To establish an artificial intelligence model based on B-mode thyroid ultrasound images to predict central compartment lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC). Methods We retrieved the clinical manifestations and ultrasound images of the tumors in 309 patients with surgical histologically confirmed PTC and treated in the First Medical Center of PLA General Hospital from January to December in 2018.The datasets were split into the training set and the test set.We established a deep learning-based computer-aided model for the diagnosis of CLNM in patients with PTC and then evaluated the diagnosis performance of this model with the test set. Result The accuracy,sensitivity,specificity,and area under receiver operating characteristic curve of our model for predicting CLNM were 80%,76%,83%,and 0.794,respectively. Conclusion Deep learning-based radiomics can be applied in predicting CLNM in patients with PTC and provide a basis for therapeutic regimen selection in clinical practice.
Artificial Intelligence ; Humans ; Lymph Nodes/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Risk Factors ; Thyroid Cancer, Papillary/diagnostic imaging* ; Thyroid Neoplasms/diagnostic imaging*

Objective:To investigate the effects of oxymatrine（OM） on proliferation，migration， and invasion of non-small cell lung cancer（NSCLC） A549 and H1299 cells and to explore the possible mechanism. Method:A549 and H1299 cells were treated by OM of different concentrations（0， 1.0，2.0，4.0，8.0，16.0， 32.0， and 64.0 mmol·L^-1） and the cell viability was detected by cell counting kit-8 （CCK-8） assay. Transwell invasion and wound healing assays were applied to determine the effect of OM of different concentrations （8.0，16.0， and 32.0 mmol·L^-1） on the invasion and migration of A549 and H1299 cells. Western blot was adopted to detect the changes in the expression of proteins related to the Notch signaling pathway after the treatment by OM of different concentrations （8.0，16.0， and 32.0 mmol·L^-1）. Result:Compared with the control，OM could inhibit the proliferation （P<0.05，P<0.01） and hinder the cell invasion and migration of A549 and H1299 cells （P<0.01） in a dose-dependent manner. The results of Western blot showed that OM（32.0 mmol·L^-1） could effectively counteract the expression levels of Notch1 intracellular domain（NICD），transcriptional complex proteins ［TNF-alpha converting enzyme（TACE） and recombining binding protein suppressor of hairless（RBPSUH）］， and Hes family hairy and enhancer of split 1（Hes1） in A549 and H1299 cells. Conclusion:OM was capable of inhibiting the proliferation，migration， and invasion of A549 and H1299 cells and also hindering the expression of proteins related to Notch signaling pathway.

Objective To investigate the short-term outcome of T1bN0M0 papillary thyroid cancer after ultrasonography-guided radiofrequency ablation(RFA). Methods Eighty-nine patients with T1bN0M0 papillary thyroid cancer who were treated with ultrasonography-guided RFA in our center from April 2014 to January 2019 were retrospectively analyzed.Trans-isthmus approach and moving shot technique were used during the RFA procedure.Ultrasonography and contrast-enhanced ultrasonography were performed before ablation,and immediately,1,3,6 and 12 months after ablation and then every 6 months thereafter. Results RFA was performed in 89 cases of papillary thyroid cancer,and no major complications were observed during the RFA.The mean follow-up was(18.8±7.3)months.The ablation zones decreased gradually during follow-up,and 38 ablation zones(42.7%)completely disappeared.The volume reduction rate was(99.2±2.3)% 30 months after ablation.During follow-up,2 patients(2.2%)developed tumor recurrence and 1 patient(1.1%)developed cervical lymph node metastasis. Conclusion Ultrasonography-guided RFA may be a safe and effective method for patients with T1bN0M0 papillary thyroid cancer.
Catheter Ablation ; Humans ; Lymphatic Metastasis ; Neoplasm Recurrence, Local ; Radiofrequency Ablation ; Retrospective Studies ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/surgery* ; Treatment Outcome ; Ultrasonography

To analyze the potential associations of ultrasound-guided fine-needle aspiration(FNA),BRAF gene mutation detection,and the combination of these two techniques with the clinicopathological features of papillary thyroid cancer(PTC). Methods Patients with PTC confirmed by surgery from April 2016 to July 2017 were included in this study.The relationship between clinicopathological features and BRAF mutation,FNA results,and the combination of them were explored. Results The sensitivity of FNA was 86.3%(227/263)and the mutation rate of BRAF was 85.9%(226/263)in 263 patients with PTC.The mutation rate of papillary thyroid microcarcinoma(PTMC)was 91.1%(153/168)and that of non-PTMC was 76.8%(73/95).A total of 225 patients underwent lymph node dissection.The lymph node metastasis rate was 35.6%(80/225),and it was 23.8%(34/143)in PTMC,56.1%(46/82)in non-PTMC;in addition,9.9%(26/263)of PTC patients had extracapsular invasion.BRAF mutation rate was higher in patients with the following features:aged over 45 years(=0.043);the tumor was FNA diagnosed as malignant or suspected malignant(=0.011);the tumor had a maximum diameter of ≤1 cm(=0.001);and the primary tumor was in stage T(=0.039);however,there was no significant difference in BRAF mutation rate among patients with different sex,capsule invasion,or lymph node metastasis.The diagnostic sensitivity of FNA was not statistically different under different clinical and pathological characteristics.The clinicopathologic features of FNA and BRAF double-positive patients were not significantly different from those of other patients. Conclusion FNA-confirmed malignancy,BRAF gene mutation,and their double-positive results are not correlated with the invasive pathological features of PTC,and thus their roles in guiding an extended operation(or not)are limited.
Biopsy, Fine-Needle ; Humans ; Lymphatic Metastasis ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Cancer, Papillary ; diagnosis ; genetics ; Thyroid Neoplasms ; diagnosis ; genetics

Objective To evaluate the effect of dexmedetomidine on cell apoptosis during lung is-chemia-reperfusion(I/R)injury in a rat model of cardiopulmonary bypass(CPB).Methods Ninety-six SPF healthy adult male Sprague-Dawley rats,weighing 350-500 g,were divided into 4 groups(n＝24 each)using a random number table method: sham operation group(group S),CPB group(group C),CPB plus left lung I/R group(group IR),and CPB plus left lung I/R plus dexmedetomidine group(group D).The chest was only opened,and the rats underwent no CPB in group S.Only the CPB model was es-tablished in group C.The model of left lung I/R injury was established based on the CPB model in group IR.In group D,the model of CPB plus left pulmonary I/R injury was established,dexmedetomidine was intrave-nously infused in a dose of 3 μg/kg through the tail vein,followed by a continuous infusion of 1.5 μg?kg-1?h-1 until the end of surgery.Eight rats were selected in each group before operation(T0),at 10 min after opening the left hilum(T1),and at the end of operation(T2),the left lung tissues were taken for examination of pathological changes(with a light microscope)which were scored and for determination of cell apoptosis,and immunohistochemistry score(IHS)was assessed.The apoptosis index was calculated.Results Compared with group S,the pathological changes of lung tissues,IHS and apoptosis index were significantly increased at T1,2 in the other three groups(P＜0.05).Compared with group C,the pathologi-cal changes of lung tissues,IHS and apoptosis index were significantly increased at T1,2 in IR and D groups(P＜0.05).Compared with group IR,the pathological changes of lung tissues,IHS and apoptosis index were significantly decreased at T2 in group D(P＜0.05).Conclusion The mechanism by which dexme-detomidine reduces lung I/R injury during CPB is related to inhibiting cell apoptosis in rats.