MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach. METHODS: This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1-3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/ß = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated. DISCUSSION: MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs. TRIAL REGISTRATION: The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, "Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)", NCT05027711.

[Occurrence of radiation-induced injury in vagina after radical radiotherapy of cervical cancer and its affecting factors].

Objective: To investigate the occurrence and degree of radiation-induced injury in vagina after radical radiotherapy of cervical cancer. Methods: A total of 282 cases of patients with cervical cancer were collected from November 2016 to September 2017. All of the above patients underwent radical radiotherapy from 2008 to 2017 in the First Affiliated Hospital of Xi'an Jiaotong University. The patients' International Federation of Gynecology and Obstetrics (FIGO) staging (2009) , brachytherapy dose, whether receive synchronous chemotherapy or not, age and body mass index (BMI) for the occurrence and severity of vaginal radiation injury at different time periods were analyzed by cross-sectional survey method. The single factor would be analyzed by the method of Chi-square test and the multiple factors would be analyzed by logistic regression method to checkout. Results: Of the 282 patients, the incidence of radiation-injury in vaginal was 84.4% (238/282) , with the incidence rate of degree Ⅰ,Ⅱ and Ⅲ radiation injury were respectively 50.7% (143/282), 29.8% (84/282) and 3.9% (11/282; χ(2)=153.375, P<0.05) , and there was no degree Ⅳ. Until the end of the follow-up time, the incidence of radiation-induced injury in vaginal after completing the treatment within 1 year, 1-2 years,>2-<5 years and ≥5 years were respectively 80.0% (24/30) , 87.2% (102/117) , 88.2% (60/68) and 77.6% (52/67; χ(2)=4.231, P=0.238) . There were 30 cases be followed within 1 year after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ of radiation injury in vagina was 60.0% (18/30) , 20.0% (6/30) and 0, respectively (χ(2)=28.636, P<0.05). There were 117 cases be followed between 1-2 years after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ vaginal radiation-induced injury were 54.7% (64/117) , 29.9% (35/117) and 2.6% (3/117) , respectively (χ(2)=77.198, P<0.05) . There were 68 cases be followed between >2-<5 years after treatment, the incidence rate of degree Ⅰ,Ⅱ and Ⅲ vaginal radiation-induced injury were 51.5% (35/68) ,33.8% (23/68) and 2.9% (2/68) , respectively (χ(2)=39.525, P<0.05) . There were 67 cases be followed ≥5 years after treatment, the incidence rate of degree Ⅰ,Ⅱ and Ⅲ vaginal radiation injury were 38.8% (26/67) , 29.9% (20/67) and 9.0% (6/67) , respectively (χ(2)=16.395, P<0.05) . The single-factor analysis result indicated that the brachytherapy dose had an obvious effect on vaginal radiation-induced injury (χ(2)=5.344, P=0.021) ; however, other factors, such as age, BMI, FIGO stages and synchronous chemotherapy, had no obvious effect on vaginal radiation-induced injury (all P>0.05) . The multifactor analysis indicated that the brachytherapy dose was an independent factor affecting the occurrence of vaginal radiation-induced injury (P=0.043) . Conclusion: After the radical radiotherapy of cervical cancer, the vaginal radiation-induced injury is associated with the dose of brachytherapy.

Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2DM: a meta-analysis of randomized controlled trials.

Testosterone supplementation may be effective for the treatment of hypogonadism in men with type 2 diabetes mellitus (T2DM), but the evidence from randomized controlled trials (RCTs) is inconclusive. We aimed to systematically summarize results from intervention studies and assess the effects of testosterone supplementation therapy (TST) on lipid metabolism in RCTs of hypogonadal men with T2DM by meta-analysis. PubMed, Embase, and Cochrane Library databases were searched for studies reporting the effect of TST on lipid metabolism in hypogonadal men with T2DM until December 31, 2016. Seven RCTs from 252 trials, enrolling a total of 612 patients in the experimental and control groups with a mean age of 58.5 years, were included in this study. The pooled results of the meta-analysis demonstrated that TST significantly decreased TC and TG levels in hypogonadal men with T2DM compared with the control group, with mean differences (MDs) of -6.44 (95% CI: -11.82 to -1.06; I2  = 28%; p = 0.02) and -27.94 (95% CI: -52.33 to -3.54; I2  = 76%; p = 0.02). Subgroup analyses revealed that the heterogeneity (I2  = 76%) of TG originated from different economic regions, in which economic development, genetic and environmental factors, and dietary habits affect lipid metabolism of human, with a decrease (I2  = 45%) in developed countries. Additionally, subgroup analyses showed that TST increased HDL-C level in developing countries compared with the control group (MD = 2.79; 95% CI: 0.73 to 4.86; I2  = 0%; p = 0.008), but there was no improvement in developed countries (MD = 1.02; 95% CI: -4.55 to 6.60; I2  = 91%; p = 0.72). However, LDL-C levels were not improved consistently. Because the relationship between lipid metabolism and atherosclerosis is unequivocal, TST, which ameliorates lipid metabolism, may decrease the morbidity and mortality of cardiovascular disease in hypogonadal men with T2DM by preventing atherogenesis.

[Unilateral patellar resurfacing in bilateral total knee arthroplasty: a randomized controlled study].

OBJECTIVE: To perform unilateral patellar resurfacing and contralateral patellar retention in bilateral total knee arthroplasty (TKA) randomly, and to compare the clinical effects of patellar retention with patellar resurfacing in TKA. METHODS: In the study, 14 bilateral knee osteoarthritis (OA) patients were randomized in the bilateral TKA to receive unilateral patellar resurfacing and contralateral patellar retention, including 28 knees, all were females, 53 to 78 years old, with average (66.9±7.8) years, and the BMI was (26.3±1.8) kg/m2. All subjects were followed up from 3 to 12 months. The clinical effects were evaluated based on measurements of American Knee Society score (KSS), range of motion (ROM), anterior knee pain, patellar clunk, and patellar tilt angle (PTA). RESULTS: All the wounds healed primarily without significant complications, such as infection, aseptic loosening, patellar fracture and so on. The preoperative KSS scores of patellar resurfacing group were 38.9±22.2, and the scores changed to be 92.4±6.7 after operation, which were added by 53.5±20.3. While in the patellar retention group, the KSS scores were 38.4 ± 20.5 preoperatively, and after operation, which were added to be 92.1±4.2, and improved by 53.7±21.4. The differences in the changed KSS scores between TKA with and without patellar resurfacing were not statistically significant (Independent t-test, P=0.98). The ROM was changed from 95.4°±13.5° preoperatively to 120.4°±8.9° postoperatively in the patellar resurfacing group and from 92.9°±19.1° preoperatively to 120.4±8.4° postoperatively in the patellar retention group. The ROM of the two group were increased by 25.0°±14.5° and 27.5°±19.4° respectively. However, no remarkable differences were observed between the 2 groups in the knee ROM (Independent t-test, P=0.70). At the end of the latest follow-up, 3 knees in the patellar resurfacing group and 2 knees in the patellar retention group had knee anterior pain, the incidences of anterior knee pain were 21.4% and 14.3% respectively. There was no obvious difference for the incidence of post-operative anterior knee pain (Chi-square test, P=0.62). The incidences of post-operative patellar clunk in the 2 groups were all with 3 knees (21.4%), which had no significant difference in the 2 groups (Chi-square test, P=1.00). The post-operative PTA were 2.6°±2.6° in the patellar resurfacing group and 3.6°±2.9° in the patellar retention group, respectively. There was also no statistical difference between the 2 groups (Chi-square test, P=0.36). CONCLUSION: For knee OA patients with mild or moderate patellar cartilage damage, performing patellar resurfacing or not didn't significantly affect anterior knee pain, patellar clunk, functional outcomes or patellar tracking after TKA. So we suggest retain patella in TKA for OA patients with mild or moderate patellar cartilage damage.

Effect of photoperiod on serum hormone concentrations during the annual reproductive cycle in geese.

The poor egg-laying rate of geese hinders the development of the goose industry; therefore, the reproductive performance of geese is an important area of investigation. To evaluate the relationship between photoperiod, reproductive hormones, and reproductive activity during the egg-laying cycle in geese under natural conditions, we collected blood samples from Sichuan white geese and Xupu geese to quantify changes in prolactin (PRL), estradiol (E2), vasoactive intestinal polypeptide (VIP), follicle stimulating hormone (FSH), gonadotropin-inhibitory hormone (GnIH), and luteinizing hormone (LH). We also calculated the rate of egg laying for the two populations during the egg-laying cycle. We show that the egg-laying rate and the serum concentration of some hormones (PRL, E2, VIP, FSH, GnIH, and LH) differed significantly between the two populations during the pre-laying, laying, and ceased-laying periods. Serum LH concentrations may be associated with maturation of the ovary and oviducts, whereas FSH, PRL, and GnIH play important roles in egg laying. These results provide a useful resource for future studies examining the laying rate in geese.

Effects of feeding conditions on gene expression in chicken breast muscle.

Chicken meat quality is becoming increasingly important among breeders and consumers. To understand the effect of feeding conditions on chicken meat quality, we investigated the profiles of genes expressed in chicken breast muscle. Using RNA sequencing, we identified 336, 321, and 387 differentially expressed genes among Chengkou, Daninghe, and Qingjiaoma chickens under scatter- and captivity-feeding conditions. Twenty-two genes differentially expressed between different feeding conditions were shown to be common among the three breeds. Seven of these genes were assessed by real-time quantitative PCR, which confirmed the findings of RNA sequencing and suggested that the results were viable. The differentially expressed genes showed enrichment for a series of significant pathways, including energy metabolism, xenobiotics biodegradation and metabolism, and the immune system. These results provide a solid foundation for elucidating the molecular mechanisms underlying chicken meat quality.

The activation of G protein-coupled receptor 30 (GPR30) inhibits proliferation of estrogen receptor-negative breast cancer cells in vitro and in vivo.

There is an urgent clinical need for safe and effective treatment agents and therapy targets for estrogen receptor negative (ER-) breast cancer. G protein-coupled receptor 30 (GPR30), which mediates non-genomic signaling of estrogen to regulate cell growth, is highly expressed in ER--breast cancer cells. We here showed that activation of GPR30 by the receptor-specific agonist G-1 inhibited the growth of ER--breast cancer cells in vitro. Treatment of ER--breast cancer cells with G-1 resulted in G2/M-phase arrest, downregulation of G2-checkpoint regulator cyclin B, and induction of mitochondrial-related apoptosis. The G-1 treatment increased expression of p53 and its phosphorylation levels at Serine 15, promoted its nuclear translocation, and inhibited its ubiquitylation, which mediated the growth arrest effects on cell proliferation. Further, the G-1 induced sustained activation and nuclear translocation of ERK1/2, which was mediated by GPR30/epidermal growth factor receptor (EGFR) signals, also mediated its inhibition effects of G-1. With extensive use of siRNA-knockdown experiments and inhibitors, we found that upregulation of p21 by the cross-talk of GPR30/EGFR and p53 was also involved in G-1-induced cell growth arrest. In vivo experiments showed that G-1 treatment significantly suppressed the growth of SkBr3 xenograft tumors and increased the survival rate, associated with proliferation suppression and upregulation of p53, p21 while downregulation of cyclin B. The discovery of multiple signal pathways mediated the suppression effects of G-1 makes it a promising candidate drug and lays the foundation for future development of GPR30-based therapies for ER- breast cancer treatment.

Enantiomeric recognition of chiral 3,3-bridged-1,1'-binaphthol dimer toward alpha-phenylethylamine and alpha-amino acid ester.

The 1,1'-binaphthol-based dimers with p-phenylenebis(2-ethynyl) spacer, (+)-6 and (+)-2, were synthesized as chiral host compounds. (1)H NMR, UV-vis, and fluorescent titration were used to evaluate the enantiomeric recognition abilities of the chiral host dimers toward the guest amine 7 and alpha-amino acid ester 8. The chiral BINOL-based dimers were found to have good enantiomeric recognition ability. The computer simulation of the host-guest complex molecules was carried out to describe the conformational changes of both naphthyl ring in the molecule of chiral host dimer after complexation with the guest molecule.