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.

ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.

ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

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 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.

AIM: To investigate the distribution characteristics of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and its correlation with blood Hcy in hypertensive patients and to provide reference for the prevention and treatment of H-type hypertension in southern Anhui Province. METHODS: A total of 657 hypertensive patients were treated in our hospital from October 2019 to August 2020 were selected as the research objects. The MTHFR C677T and A1298C loci were genotyped by fluorescence staining in situ hybridization, and the blood Hcy concentration was determined by the enzyme cycle method. The distribution characteristics of MTHFR gene in the Han nationality hypertensive population in southern Anhui Province were analyzed, and compared with the reported MTHFR gene distribution data of hypertensive populations in other regions and ethnic groups. RESULTS: Among the 657 patients, the distributions of CC, CT and TT types at the C677T site of MTHFR gene were 212(32.27%), 321 (48.86%), 124(18.87%), and the distribution of AA, AC, and TT types at the A1298C site were 467 (71.08%), 171(26.03%), 19(2.89%). There was no gender difference in the distribution of the two loci of this gene in the hypertensive population in southern Anhui Province (P > 0.05). The distribution frequency of CC genotype at C677T locus is lower than that in Foshan and Guangxi, but higher than that in Henan, Xinjiang and Inner Mongolia; the frequency of CT genotype is higher than that in Foshan and Guangxi; the frequency of TT genotype is higher than that in Foshan and Guangxi. Guangxi region was lower than Henan region, Xinjiang region and Inner Mongolia region, and the difference was statistically significant (P < 0.05). The mean blood Hcy of 657 patients was (15.8 ± 7.80) μmol/L, of which 510(77.62%) were in line with the diagnosis of H-type hypertension. The level of Hcy in males was significantly higher than that in females, and the difference was statistically significant (P < 0.000 1). Compared with the different genotypes of the C677T locus, the TT type was higher than the CT type and CC type, and the difference was statistically significant (P < 0.05). There was no significant difference in Hcy levels between different genotypes at the A1298C locus (P > 0.05). CONCLUSION: The distribution of MTHFR gene polymorphism in the Han nationality hypertensive population in southern Anhui is significantly different from other regions, and it is also significantly related to the level of Hcy, which has obvious regional characteristics. The genetic detection technology combined with the determination of Hcy concentration can provide a scientific basis for the prevention and treatment of H-type hypertension in southern Anhui Province.

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.

Objective:To explore the characteristics of failure patterns of three-dimensional radiotherapy combined with first-line drug therapy for primary tumors of stage Ⅳ non-small cell lung cancer(NSCLC)and investigate the influence of radiotherapy-related factors.Methods:708 patients newly-diagnosed with stage Ⅳ NSCLC from March 2003 to July 2020 were selected. Chi-square test was used for univariate analysis of failure patterns. Kaplan-Meier method, Log-rank test and Cox regression model were employed for multivariate analysis. Results:The incidence of first-line treatment failure in 708 cases was 71.2%, and the incidence of treatment failure was 22.7%, 28.8%, 13.3%, and 6.4% for ≤6 months, >6-12 months, >12-24 months, and>24 months, respectively, and the median survival time was 7.2, 13.4, 22.2, and 37.6 months, which was significantly different( χ2=226.013, P<0.001). The incidence of recurrence failure(RF)was 21.3%.There was no significant difference in the incidence of RF between oligometastasis(OM)and non-oligometastasis(NOM). The incidence of DF was 66.3% and the order of incidence was brain>bone>lung>pleural cavity>liver>distant lymph nodes>adrenal gland>other sites, occurring in approximately 1/2 of AM and 1/3 of PSM cases. Metastatic status, time to treatment failure, pathological type, gender, combined treatment intensity were the independent influencing factors for predicting prognosis. Conclusions:The failure pattern of radiotherapy for primary tumors of stage Ⅳ NSCLC is different from that of first-line drug therapy, with significantly lower local failure and predominantly metastatic failure. The incidence of brain metastasis is the highest. The later time to treatment failure, the longer the overall survival(OS). OM, female, non-squamous cell carcinoma, late treatment failure, 4-6 cycles of chemotherapy over the same period ≥63 Gy are the independent prognostic factors for prolonging survival.