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The main aim of this study was to evaluate the incidence rate of radiation pneumonitis (RP) in advanced lung adenocarcinoma treated with first-generation, second-generation, or third-generation EGFR-TKIs combined with thoracic radiotherapy. We retrospectively evaluated advanced lung adenocarcinoma patients simultaneously treated with first-generation EGFR-TKIs, second-generation, or third-generation EGFR-TKIs and thoracic radiotherapy between January 2015 to December 2021 at Shandong Cancer Hospital and Institute. The clinical grades of RP were evaluated according to the pneumonitis of Common Toxicity Criteria (CTC) 5.0 Grading System, and the imaging grading of RP was evaluated using the pulmonary fibrosis of CTC 5.0 Grading System. Consecutive 100 patients who were treated with first-generation EGFR-TKIs were enrolled, 20 patients were treated with second-generation EGFR-TKIs and 50 patients who received third-generation EGFR-TKIs (10:2:5 matched with patients and tumor characteristics), and all three groups were concurrent with thoracic radiotherapy. In terms of overall incidence of RP, first-generation group versus second-generation group versus third-generation group of clinical grades were 2.083 vs 2.389 vs 1.935, and their imaging grades were 1.753 vs 1.895 vs 1.524. The incidence of the imaging grading of grade greater than or equal to 3 RP in three groups were 22% vs 15% vs 4%, and the clinical grades of grade greater than or equal to 3 RP in three groups were 28% vs 55% vs 20%. Other details can be referred to in the Table. Patients treated with third-generation EGFR-TKIs combined with thoracic radiotherapy achieved minimum probability of RP. In contrast, the second-generation EGFR-TKIs concomitant thoracic radiotherapy are the most likely to happen RP. The clinical grades and imaging grades were not completely same in RP. [ABSTRACT FROM AUTHOR]

Since the response to ocean acidification is species specific, differences in responses between predator and prey will alter their interactions, hence affect the population dynamics of both species. Changes in predator prey interactions between a predatory muricid gastropod Reishia clavigera and its prey, the barnacle Amphibalanus amphitrite amphitrite and mussel Brachidontes variabilis under three pCO 2 levels (380, 950, and 1250 μatm) were investigated. The searching time for barnacles increased and the ability to locate them decreased at higher pCO 2 levels. The movement speed and the prey consumption rate, however, were independent of pCO 2. There was no preference towards either B. variabilis or A. amphitrite amphitrite regardless of pCO 2. Exposure experiments involving multiple generations are suggested to assess transgenerational effects of ocean acidification and the potential compensation responses before any realistic predictions on the long term changes of population dynamics of the interacting species can be made. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator of adipogenesis. Our previous study revealed that chicken PPARγ has 3 alternative promoters named as P1, P2, and P3, and the DNA methylation of promoter P3 was negatively associated with PPARγ mRNA expression in abdominal adipose tissue (AAT). However, the methylation status of promoters P1 and P2 is unclear. Here we assessed promoter P1 methylation status in AAT of Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF). The results showed that promoter P1 methylation differed in AAT between the lean and fat lines of NEAUHLF at 7 wk of age (p < 0.05), and AAT expression of PPARγ transcript 1 ( PPARγ1 ), which was derived from the promoter P1, was greatly higher in fat line than in lean line at 2 and 7 wk of age. The results of the correlation analysis showed that P1 methylation was positively correlated with PPARγ1 expression at 7 wk of age (Pearson's r = 0.356, p = 0.0242), suggesting P1 methylation promotes PPARγ1 expression. To explore the underlying molecular mechanism of P1 methylation on PPARγ1 expression, bioinformatics analysis, dual-luciferase reporter assay, pyrosequencing, and electrophoresis mobility shift assay (EMSA) were performed. The results showed that transcription factor NRF1 repressed the promoter activity of the unmethylated P1, but not the methylated P1. Of all the 4 CpGs (CpG48, CpG49, CpG50, and CpG51), which reside within or nearby the NRF1 binding sites of the P1, only CpG49 methylation in AAT was remarkably higher in the fat line than in lean line at 7 wk of age (3.18 to 0.57, p < 0.05), and CpG49 methylation was positively correlated with PPARγ1 expression (Pearson's r = 0.3716, p = 0.0432). Furthermore, EMSA showed that CpG49 methylation reduced the binding of NRF1 to the P1. Taken together, our findings illustrate that P1 methylation promotes PPARγ1 expression at least in part by preventing NRF1 from binding to the promoter P1. [ABSTRACT FROM AUTHOR]

The SLIT/Roundabout (ROBO) pathway is involved in follicle development of mammalian ovary, and 2 secreted hormones activin A and inhibin A have potential roles in modulation of the SLIT/ROBO system, but the related actions remain poorly understood in bird. The aims of the present study were to examine the spatial and temporal expression of the SLIT ligand genes (SLIT1, SLIT2, and SLIT3) and their receptor ROBO1, ROBO2, ROBO3, and ROBO4 genes in various-sized prehierarchical follicles during hen ovary development and the effects of activin A and inhibin A on the expression of these genes in the cultured hen follicles. Our result demonstrated that the transcripts of the 3 SLIT genes were highly expressed in the developing follicles and expression patterns of the SLIT transcripts were different from those of ROBO genes detected by real-time quantitative reverse transcriptase PCR. Both SLIT and ROBO transcripts were predominantly expressed in oocytes and granulosa cells from the prehierarchichal follicles examined by in situ hybridization. The localization for SLIT and ROBO proteins was revealed by immunohistochemistry similar to the spatial distribution of their transcript. In cultured follicles (4 to 8 mm in diameter), the expression levels of SLIT and ROBO members are hormonally regulated by activin A (10 ng/mL) and/or inhibin A (20 ng/mL) after treatment for 24 h. However, the expression of only SLIT2, SLIT3, and ROBO3 mRNA presented a directly opposite response to activin A and inhibin A hormones. These results indicate that SLIT/ROBO pathway is implicated in the prehierarchical follicular development of the hen ovary by an intrafollicular autocrine and/or paracrine action, and is influenced by activin A and inhibin A hormones. [ABSTRACT FROM AUTHOR]

Transcription factor forkhead box L2 (FOXL2) and growth differentiation factor-9 (GDF9) genes have critical roles in the regulation of hen ovarian development. In the present study, these genes were explored as possible molecular markers associated with BW, hen-housed egg production, and egg weight in Chinese Dagu hens. Samples were analyzed using the PCR–single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing analysis, and two novel single nucleotide polymorphisms (SNPs) were identified within these candidate genes. Among them, an A/G transition at base position 238 in the coding region of the FOXL2 gene and a G/T transversion at base position 1609 in exon 2 of the GDF9 gene were found to be polymorphic and named SNPs A238G and G1609T, respectively. The SNP A238G (FOXL2) leads to a nonsynonymous substitution (isoleucine77-to-valine), and when the 360 Dagu hen samples were divided into genotypes AA and AB, allele A was found to be present at a higher frequency. Furthermore, the AA genotype correlated with significantly higher hen-housed egg production at 30, 43, 57, and 66 wk of age and with a higher egg weight at 43 wk (P < 0.05). For the SNP G1609T (GDF9), the hens were typed into TT and TC genotypes, with the T allele shown to be dominant. The TC genotype was also markedly correlated with higher hen-housed egg production and a higher egg weight (P < 0.05). Moreover, four haplotypes were reconstructed based on these two SNPs, with the AATC haplotype found to be correlated with the highest hen-housed egg production at 30 to 66 wk of age and with higher egg weights at 43 wk (P < 0.05). Collectively, the two SNPs identified in this study might be used as possible genetic molecular markers to aid in the improvement of egg production traits in chicken breeding. [ABSTRACT FROM AUTHOR]

Background: We aimed to retrospectively assess the effect of cryotherapy in patients with metastatic breast cancer that had not recurred locally after resection of the primary lesion. Methods: We divided 120 patients with metastatic breast cancer into those who had received cryotherapy (91 patients) and those who had received chemotherapy (29 patients). In the cryotherapy group, 37 patients with tumour recurrence received multiple cryoablations, while 54 patients received only a single cryoablation. 62 of the patients who received cryotherapy underwent cryoablation immediately after the detection of metastases (timely cryotherapy); 35 patients received simultaneous immunotherapy (cryo-immunotherapy), and 29 patients underwent cryoablation in our hospital 3months after receiving chemotherapy in other centres (chemo-cryotherapy and delayed cryotherapy). Overall survival after the diagnosis of metastatic breast was assessed after a 10-year follow-up. Findings: Median overall survival was higher in those who received cryotherapy (55months) than in those who received chemotherapy (27months; p<0.0001). In those who received cryotherapy, longer median overall survival was associated with multiple rather than single cryoablations (76months versus 48months; p=0.0005) and with timely rather than delayed cryoablation (67months versus 48months; p=0.0012). Median overall survival was higher after cryo-immunotherapy than after chemo-cryotherapy or cryotherapy alone (83months versus 48months versus 43months; p<0.0001 for both). Interpretation: Timely and multiple cryoablations, especially when combined with immunotherapy, offer significant advantages over chemotherapy in extending the overall survival of patients with metastatic breast cancer. [ABSTRACT FROM AUTHOR]

This analysis compared the efficacy of the migraine preventive treatments fremanezumab and erenumab in patients with episodic migraine (EM) who had failed 2-4 prior migraine preventive treatments/classes using an indirect treatment comparison approach. Two trials were identified: the FOCUS study of fremanezumab in migraine patients failing 2-4 prior migraine preventive treatment classes and the LIBERTY study of erenumab in migraine patients failing 2-4 prior migraine preventive treatments. [Extracted from the article]

Background: Thymomas are the most common tumours of the mediastinum. These tumours often compress vital mediastinal organs and severely impact the quality of life of patients. To avoid the side effects of chemoradiotherapy, some patients with unresectable malignant thymomas have opted to undergo cryotherapy in our hospital. Methods: We reviewed the cryosurgery, nursing, and follow-up records of our hospital for the past 8years, and evaluated the safety and efficacy of cryotherapy in 19 patients with unresectable malignant thymomas. Findings: No severe complications involving the vital organs surrounding the tumour occurred during or after cryosurgery. The most common side effect was pleural effusion, which occurred in 11 patients and healed after drainage within 1week. Cough, mediastinal and pericardial effusions, pneumothorax, mild fever, and chest tightness also occurred and resolved 1week after symptomatic treatment. Since our patients had high KPS scores and mild myasthenia gravis symptoms before the treatment, myasthenia gravis did not occur after the treatment. The progression-free survival of the patients was 14-29months (median, 18months), and did not differ between patients with large tumours and those with small tumours (p=0.6753). Interpretation: Cryotherapy is a safe and efficient method for the treatment of unresectable malignant thymoma. [ABSTRACT FROM AUTHOR]

Background: Coagulopathy after liver cryoablation was first reported many years ago; the cause is local platelet trapping and destruction within the margin of the cryolesion. However, the prognosis and therapeutic effects of coagulopathy remain unclear. Methods: This study retrospectively reviewed clinical data from 372 patients (525 sessions) who underwent liver cryoablation in our hospital during the past 4.5years. Small tumours (major diameter <6cm) were treated with a single complete ablation; massive tumours (major diameter 6-10cm or >10cm) were divided into two or three parts that were dealt with in turn. Findings: Platelet counts decreased to an average of 46.12 (± 68.13) ×109/L after each session of cryoablation. The decline was most evident in patients with high pretreatment platelet counts, while those with low pretreatment counts had the highest risk of coagulopathy. Change in platelet count was not correlated with the diameter of the tumour. Interpretation: Slight coagulopathy (platelet count 70-100×109/L) can resolve without treatment within 1week and administration of recombinant human interleukin-11 can assist recovery from severe coagulopathy (platelet count <70×109/L). [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the therapeutic effect of cryoablation treatment and palliative treatment in stage IV lung cancer. Methods: Fifty-four patients with intrapulmonary and extrapulmonary tumours were enrolled into the study. 31 patients received cryoablation treatment and 23 patients had palliative treatment (no cryoablation). Both the safety of the procedure and overall survival (OS) for stage IV lung cancer were assessed during a 6.5-year follow-up period. The OS of patients in both groups and the effects of treatment timing and frequency were compared. Findings: The OS in the cryoablation group was significantly longer than in the palliative group (median OS: 14months versus 7months, p=0.0009). The OS of those who received delayed cryoablation treatment was longer than that observed for those who received timely treatment (median OS: 18.5months versus 10months, p=0.0485), but this was not observed in those who received palliative treatment (median OS: 7months versus 7.5months, p=0.9814). Multiple treatments compared with single treatments played an important part in improving the OS of patients who received cryoablation treatment (median OS: 18months versus 14months, p=0.0376). Interpretation: There was a significant difference between cryoablation and palliative treatment in terms of OS. In addition, multiple cryoablation treatments may have an advantage over single treatments. [ABSTRACT FROM AUTHOR]

Background: We sought to investigate the analgesic effect of cryosurgery on bone-tumour-induced pain. Methods: Thirty-four patients with bone malignancy were given percutaneous cryosurgery 43 times. Bone biopsies and PET-CT were performed to observe metabolic activity after cryosurgery. NRS scores were recorded and analysed to evaluate the pain-killing effect of cryosurgery. Findings: After cryosurgery most of the metastatic foci (10 of 13) showed necrosis. Seven of nine showed significant inhibition of metabolism and two showed partial inhibition. 3days after cryosurgery, NRS scores indicated a complete response of pain in 18 patients (53%), partial response in 10 patients (29%), stable disease in four patients (12%), and progressive disease in two patients (6%). At 10days after cryosurgery, complete response of pain was seen in 25 patients (74%), partial response in six patients (18%), stable disease in two patients (6%), and progressive disease in one patient (3%). Twenty (59%) major complications were observed, including 12 cases of local subcutaneous dropsy, one case of skin necrosis over a local small area, and seven cases of fever; no fracture occurred during the hospitalisations. Six patients died at 34, 58, 69, 88, 105days, and 16months, respectively, after cryosurgery. Among them, two patients died of dyscrasia failure, one died of airway obstruction and lung infection, one died of encephalic metastasis, and two died of liver and renal failure. No cause of death was directly related to cryosurgery. The remission time of pain of other patients was 46-232days, median time was 128days. Nine patients' tumours (27%) were recurrent or had a progressive destruction of bone. Interpretation: Cryosurgery can be accepted as a relatively safe and effective procedure for the palliative treatment of bone tumours, especially for stopping pain. [ABSTRACT FROM AUTHOR]

Background: We aimed to retrospectively assess the effect of comprehensive cryosurgery (ablation of intrahepatic and extrahepatic tumours) plus dendritic cell-cytokine-induced killer cell immunotherapy in metastatic hepatocellular cancer. Methods: We divided 45 patients into cryoimmunotherapy (n= 21), cryotherapy (n=12), immunotherapy (n=5) and untreated (n=7) groups. Overall survival (OS) after diagnosis of metastatic hepatocellular cancer was assessed after an 8-year follow-up. Findings: Median OS was higher following cryoimmunotherapy (32months) or cryotherapy (17.5months; p<0.05) than in the untreated group (3months) and was higher in the cryoimmunotherapy group than in the cryotherapy group (p<0.05). In the cryoimmunotherapy group, median OS was higher after multiple treatments (36.5months) than after a single treatment (21months; p<0.05). Interpretation: Cryotherapy and, especially, cryoimmunotherapy significantly increased OS in metastatic hepatocellular cancer patients. Multiple cryoimmunotherapy treatments was associated with a better prognosis than single cryoimmunotherapy. [ABSTRACT FROM AUTHOR]