Superoxide dismutase 1-modified dental pulp stem cells alleviate high-altitude pulmonary edema by inhibiting oxidative stress through the Nrf2/HO-1 pathway.

High-altitude pulmonary edema (HAPE) is a deadly form of altitude sickness, and there is no effective treatment for HAPE. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell isolated from dental pulp tissues and possess various functions, such as anti-inflammatory and anti-oxidative stress. DPSCs have been used to treat a variety of diseases, but there are no studies on treating HAPE. In this study, Sprague-Dawley rats were exposed to acute low-pressure hypoxia to establish the HAPE model, and SOD1-modified DPSCs (DPSCsHiSOD1) were administered through the tail vein. Pulmonary arterial pressure, lung water content (LWC), total lung protein content of bronchoalveolar lavage fluid (BALF) and lung homogenates, oxidative stress, and inflammatory indicators were detected to evaluate the effects of DPSCsHiSOD1 on HAPE. Rat type II alveolar epithelial cells (RLE-6TN) were used to investigate the effects and mechanism of DPSCsHiSOD1 on hypoxia injury. We found that DPSCs could treat HAPE, and the effect was better than that of dexamethasone treatment. SOD1 modification could enhance the function of DPSCs in improving the structure of lung tissue, decreasing pulmonary arterial pressure and LWC, and reducing the total lung protein content of BALF and lung homogenates, through anti-oxidative stress and anti-inflammatory effects. Furthermore, we found that DPSCsHiSOD1 could protect RLE-6TN from hypoxic injury by reducing the accumulation of reactive oxygen species (ROS) and activating the Nrf2/HO-1 pathway. Our findings confirm that SOD1 modification could enhance the anti-oxidative stress ability of DPSCs through the Nrf2/HO-1 signalling pathway. DPSCs, especially DPSCsHiSOD1, could be a potential treatment for HAPE. Schematic diagram of the antioxidant stress mechanism of DPSCs in the treatment of high-altitude pulmonary edema. DPSCs can alleviate oxidative stress by releasing superoxide dismutase 1, thereby reducing ROS production and activating the Nrf2/HO-1 signalling pathway to ameliorate lung cell injury in HAPE.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice.

BACKGROUND: Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases. AIM: To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE-/-) mouse model and an in vitro cellular model. METHODS: ApoE-/- mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways. RESULTS: DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway. CONCLUSION: This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/- mice on a HFD, and could be of greater value in stem cell-based treatments for AS.

The MRI-guided two adaptive brachytherapy fractions versus one adaptive brachytherapy fraction in one application for the cervical cancer: a retrospective study.

PURPOSE: This study retrospectively compared the clinical and toxicity outcomes for the cervical cancer of the MRI-guided two adaptive brachytherapy (IGABT) fractions versus one IGABT fraction in one application. METHODS: One hundred and twenty patients with cervical cancer received external beam radiotherapy combined with or without concurrent chemotherapy, which was followed by the IGABT. The IGABT in 63 patients had one IGABT in each application (Arm 1), while in the other 57 patients, at least one treatment was two continuous IGABT every other day in one application (Arm 2). Clinical outcomes including overall survival (OS), cancer specific survival (CSS), progression free survival (PFS), local control (LC) were analyzed. Brachytherapy-related toxicities were evaluated, which included pain, dizziness, nausea/vomiting, fever/infection, blood loss during the removal of applicator and needles, the deep venous thrombosis, and other acute toxicities. The Common Terminology Criteria for Adverse Events (CTC-AE 5.0) was used to evaluate the incidence and severity of toxicities of the urinary system, lower digestive system, and reproduction system. Kaplan-Meier and the Log-rank test were used to analyze the clinical outcomes. RESULTS: The median follow-up time of the patients in Arm 1 and Arm 2 was 23.5 and 12.0 months, respectively. The overall treatment time was significantly shorter in Arm 2 than Arm 1 (60 vs. 64 d; P = 0.017). The OS, CSS, PFS, and LC in Arm1 and Arm 2 was 77.8% vs. 86.0% (P = 0.632), 77.8% vs. 87.7% (P = 0.821), 68.3% vs. 70.2% (P = 0.207), and 92.1% vs. 94.7% (P = 0.583), respectively. The highest NRS of the pain during brachytherapy waiting period (2.22 ± 1.84 vs. 3.02 ± 1.65; P < 0.001) and at the time of the removal of the applicator (4.69 ± 1.49 vs. 5.30 ± 1.18; P < 0.001) in the patients who received one hybrid intracavitary and interstitial brachytherapy (IC/ISBT) in one application and two continuous IC/ISBT every other day in one application were significantly different. So far four patients with grade 3 late toxicities have been reported. CONCLUSIONS: The findings of this study demonstrated that the two continuous IGABT every other day in one application is a logistically applicable, safe, and effective treatment strategy that could shorten the overall treatment time and reduce the medical cost, comparing with the one IGABT in one application.

Dose-effect relationship between dose-volume parameters of residual gross tumor volume and clinical prognosis in MRI-guided adaptive brachytherapy for locally advanced cervical cancer: a single-center retrospective study.

PURPOSE: To investigate the dose-effect relationship between the dose-volume parameters of residual gross tumor volume (GTVres) and clinical prognosis in MRI image-guided adaptive brachytherapy (IGABT) of patients with locally advanced cervical cancer in our center. MATERIALS AND METHOD: The clinical data of 93 patients with locally advanced cervical squamous cell cancer who received external beam radiotherapy (EBRT) combined with IGABT ± chemotherapy in our center were retrospectively analyzed. The disease stage, overall treatment time (OTT), chemotherapy, and the dose-volume parameters D90, D98, and D100 of GTVres, the intermediate-risk clinical target volume (CTVIR), and the high-risk clinical target volume (CTVHR) of the patients were statistically analyzed. Kaplan-Meier and uni- and multivariable Cox regression analyses were used to analyze 2­year overall survival (OS), progression-free survival (PFS), and local control rate (LC). A probit model was employed to assess the dose-effect relationship between the volume and dose-volume parameters of GTVres and 2­year OS, PFS, and LC. RESULTS: The median follow-up time was 19.6 months and 2­year OS, PFS, and LC were 79.6%, 68.8%, and 94.6%, respectively. CTVHR D90 was an independent influencing factor for 2­year PFS (P = 0.041); GTVresBT1 volume was an independent factor for 2­year OS, PFS, and LC (P < 0.001). The probit model showed that at GTVresBT1 volume < 32.86 cm3, the expected 2­year LC was > 90%; at GTVres D98 > 129.12 GyEQD2, the expected 2­year OS was > 90%. CONCLUSION: Both the volume and dose-volume parameters of GTVres are promising predictors in assessment of IGABT prognosis of cervical cancer.

3D-printed vaginal cylindrical template with curved needle channels in MRI-guided vaginal cuff brachytherapy.

Purpose: To present a new technique for the treatment of vaginal cuff recurrences using 3D-printed vaginal cylindrical template (3D-PVCT) with curved needle channels in brachytherapy. Material and methods: Two patients with vaginal cuff tumor treated with external beam radiotherapy and MRI-guided interstitial brachytherapy were selected for the present study. Prior to treatment, a vaginal cylinder with the same size as 3D-PVCT was inserted into the vagina. Magnetic resonance scan was performed to identify target volumes and organs at risk (OARs). By registration techniques, the implantation angle was determined, appropriate needle channels were selected, and the depth of each needle position was recorded. During the actual treatment, patients were under general anesthesia, and real-time guidance of trans-rectal ultrasound was applied referring to a pre-determined treatment plan. Results: For patient No. 1, 9 needles were inserted into the tumor, with 4 curved needle channels and 5 straight channels. For patient No. 2, 7 needles were inserted into the vaginal cuff tumor, with 6 curved needle channels and 1 straight channel. Doses delivered to volumes of targets and OARs for both patients met the EMBRACE II dose constraints. After follow-up of 15 and 18 months, respectively, both patients showed complete response, with no evidence of tumor recurrence. No significant acute or late toxicities were reported. Conclusions: With careful pre-planning, 3D-PVCT provides good target coverage and sparing of OARs. The results from these two patients indicate that this approach is very promising due to its flexibility and potential widespread application in the future.

A prospective study of radical external beam radiotherapy versus external beam radiotherapy combined with intraluminal brachytherapy for primary esophageal cancer.

PURPOSE: This study compared the efficacy and side effects of external beam radiotherapy (EBRT) + intraluminal brachytherapy (IBT) with EBRT alone in patients with primary thoracic esophageal cancer. MATERIALS AND METHODS: Between 2013 and 2020, 64 patients with primary thoracic esophageal cancer without surgery received radiotherapy. Thirty-two patients received EBRT + IBT. EBRT dose was 50 Gy, 2 Gy/f, 5 times a week, and IBT dose was 10 Gy, 5 Gy/f, once a week. Thirty-two patients received EBRT alone, and the total dose was 60 Gy. The median followup was 19 months. RESULTS: The local control rates (LCR) of EBRT + IBT and EBRT alone group at 1, 2, and 3 years after treatment were 88% and 72%, 53% and 22%, 25%, and 9%, respectively. The overall survival (OS) of the EBRT + IBT and EBRT alone group at 3 years after treatment were 38% and 9%. The 3-year local recurrence-free survival (LRFS) rates of EBRT + IBT and EBRT alone group were 25% and 9%. Univariate analysis showed that EBRT + IBT could be the prognostic factor improving OS (p = 0.04), and tumor located in the mid-thoracic region exhibited a poorer prognosis on LRFS (p = 0.03). Grade 3 or higher acute side effects included two cases of dysphagia and three cases of bone marrow suppression. Severe late side effects included three cases of fistula, three cases of radiation pneumonia, and five cases of stenosis requiring treatment. CONCLUSIONS: Compared with EBRT alone, EBRT + IBT is an effective treatment modality for T1∼3NanyM0 primary thoracic esophageal cancer with good local control. It can prolong the survival time of patients and has acceptable toxicity.

Clinical Outcomes of MRI-Guided Adaptive Brachytherapy for Each Fraction in Locally Advanced Cervical Cancer: A Single Institution Experience.

Purpose: This study aims to evaluate clinical outcomes of MRI-guided adaptive brachytherapy (MR-IGABT) for each brachytherapy fraction in patients with locally advanced cervical cancer (LACC). Methods and Materials: A retrospective analysis was performed on 97 consecutive patients with LACC treated with 44.0-50.4 Gy external beam radiotherapy (EBRT) ± concurrent platinum-containing chemotherapy followed by 4 × 7 Gy MR-IGABT between September 2014 and April 2019. Intracavitary (IC)/interstitial (IS)/hybrid intracavitary and interstitial (IC/IS) brachytherapy was used in MR-IGABT. Brachytherapy planning and dose reporting followed the GEC-ESTRO recommendations. Clinical outcomes including overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), local control (LC), and treatment-related toxicity evaluated by the RTOG criteria were analyzed. Kaplan-Meier and univariable and multivariable Cox regression analyses were used to analyze the prognostic factor. Results: Median follow-up was 21.1 months. Median dose to 90% (D90) of the high-risk clinical target volume (HR-CTV) was 91.7 Gy (range 76.7~107.2 Gy). Two-year OS, CSS, PFS, and LC were 83.5%, 84.1%, 71.1%, and 94.8%, respectively. Four patients (4.1%) suffered from grade 3 late gastrointestinal radiation toxicity, and no other grade 3 or greater radiation toxicity occurred. Initial HR-CTV was an independent factor of OS (p = 0.001, HR = 1.018/cm3), PFS (p = 0.012, HR = 1.012/cm3), and LC (p = 0.011, HR = 1.028/cm3). The HR-CTV D90 (p = 0.044, HR = 0.923/Gy) was an independent factor of PFS. Age was an independent factor of LC (p = 0.010, HR = 1.111/year). Conclusion: For patients with LACC, MR-IGABT was effective and safe. It showed favorable LC, OS, and minimal toxicity. Moreover, initial HR-CTV, HR-CTV D90, and age were significant prognostic factors.

Metabolite features and oxidative response in kidney of red crucian carp (Carassius auratus red var) after Aeromonas hydrophila challenge.

Aeromonas hydrophila can threaten the survival of freshwater fish. In this study, A. hydrophila challenge could induce tissue damage, promote antioxidant imbalance as well as alter the transcript levels of oxidative stress indicators, apoptotic genes and metabolic enzyme genes in kidney of red crucian carp (RCC). Metabolomics analysis revealed that A. hydrophila challenge had a profound effect on amino acid metabolism and lipid metabolism. In addition, we further identified dipeptides, fatty acid derivatives, cortisol, choline and tetrahydrocortisone as crucial biomarkers in kidney of RCC subjected to A. hydrophila infection. These results highlighted the importance of metabolic strategy against bacterial infection.

Blood cell characterization and transcriptome analysis reveal distinct immune response and host resistance of different ploidy cyprinid fish following Aeromonas hydrophila infection.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila infection could decrease blood cell numbers, promote blood cell damage as well as alter the levels of alkaline phosphatase (ALP), lysozyme (LZM), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in immune-related tissues of red crucian carp (RCC, 2 N = 100) and triploid cyprinid fish (3 N fish, 3 N = 150). In addition, the significant alternation of antioxidant status was observed in PBMCs isolated from RCC and 3 N following LPS stimulation. The core differential expression genes (DEGs) involved in apoptosis, immunity, inflammation and cellular signals were co-expressed differentially in RCC and 3 N following A. hydrophila challenge. NOD-like receptor (NLR) signals appeared to play a critical role in A. hydrophila-infected fish. DEGs of NLR signals in RCCah vs RCCctl were enriched in caspase-1-dependent Interleukin-1ß (IL-1ß) secretion, interferon (IFN) signals as well as cytokine activation, while DEGs of NLR signals in 3Nah vs 3Nctl were enriched in caspase-1-dependent IL-1ß secretion and antibacterial autophagy. These results highlighted the differential signal regulation of different ploidy cyprinid fish to cope with bacterial infection.

Comparative analysis of erythrocyte hemolysis, plasma parameters and metabolic features in red crucian carp (Carassius auratus red var) and triploid hybrid fish following Aeromonas hydrophila challenge.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila challenge could promote the erythrocyte hemolysis, increase free hemoglobin (FHB) level and generate malondialdehyde (MDA) production in plasma but decrease the levels of total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT), alkaline phosphatase (ALP) and lysozyme (LZM) of red crucian carp (RCC, 2 N = 100) and triploid hybrid fish (3 N fish, 3 N = 150) following A. hydrophila challenge. Elevated expression levels of heat shock protein 90 alpha (HSP90α), matrix metalloproteinase 9 (MMP-9), free fatty acid receptor 3 (FFAR3), paraoxonase 2 (PON2) and cytosolic phospholipase A2 (cPLA2) were observed in A. hydrophila-infected fish. In addition, A. hydrophila challenge could significantly increase expressions of cortisol, leucine, isoleucine, glutamate and polyunsaturated fatty acids (PUFAs) in RCC and 3 N, while glycolysis and tricarboxylic acid cycle appeared to be inactive. We identified differential fatty acid derivatives and their metabolic networks as crucial biomarkers from metabolic profiles of different ploidy cyprinid fish subjected to A. hydrophila infection. These results highlighted the comparative metabolic strategy of different ploidy cyprinid fish against bacterial infection.

Clinical values of transrectal ultrasound in judging GTV of cervical cancer.

PURPOSE: To investigate the clinical value of transrectal ultrasound in judging the Gross Target Volume (GTV) of cervical cancer (CC). METHODS: A total of 196 CC patients admitted to the Department of Radiotherapy, China-Japan Union Hospital, Jilin University, from January 2016 to June 2019 were selected as the study subjects. The GTVs before and after applicator insertion were determined by transrectal ultrasound and compared with those judged by MRI. RESULTS: All 196 patients were successfully undergoing applicator insertion according to the pretreatment plan. The GTV doses reached the clinical requirements during treatment. There was no significant difference between the GTVs judged by MRI and ultrasound before insertion in terms of upper/lower diameter (MRI Before 1 vs. Ultrasound Before 1) (MB1 vs. UB1), left/right diameter (MB2 vs. UB2), or ventral/dorsal diameter (MB3 vs. UB3), and the intragroup correlation coefficients (ICC) were 0.59, 0.77, and 0.66, respectively; moreover, there was no significant difference between the GTVs judged by MRI and ultrasound after insertion in terms of MRI After one vs. Ultrasound After one (MA1 vs. UA1), MA2 vs. UA2, and MA3 vs. UA3, and the ICC values were 0.62, 0.79, and 0.76, respectively. CONCLUSIONS: Transrectal ultrasound can satisfactorily determine the GTV of CC and has certain value in brachytherapy for CC.

Ferritin H can counteract inflammatory response in hybrid fish and its parental species after Aeromonas hydrophila infection.

Ferritin H can participate in the regulation of fish immunity. Tissue-specific analysis revealed that the highest expressions of Ferritin H in parental species were observed in spleen, while peaked level of Ferritin H mRNA in hybrid fish was observed in liver. In addition, A. hydrophila challenge could sharply enhance their Ferritin H mRNA expression in liver, kidney and spleen. To further investigate their roles in immune regulation, their Ferritin H fusion proteins were produced in vitro. Ferritin H fusion proteins could exhibit a direct binding activity to A. hydrophila and endotoxin in a dose-dependent manner, restrict dissemination of A. hydrophila to tissues and abrogate inflammatory cascades. Moreover, treatment with Ferritin H fusion proteins could reduce A. hydrophila-induced lipid peroxidation. These results indicated that Ferritin H in hybrid fish elicited a similar immune regulation of A. hydrophila-induced inflammatory signals in comparison with those of its parents.

The Relationship Between Late Morbidity and Dose-Volume Parameter of Rectum in Combined Intracavitary/Interstitial Cervix Cancer Brachytherapy: A Mono-Institutional Experience.

PURPOSE: To establish a dose volume-effect relationship for predicting late rectal complication (LRC) in locally advanced cervical cancer patients treated with external beam radiotherapy (EBRT) followed by combined intracavitary/interstitial brachytherapy (IC/IS-BT). MATERIALS AND METHODS: A retrospective analysis was performed in 110 patients with locally advanced cervical cancer who underwent definitive radiotherapy combined with IC/IS-BT from July 2010 to September 2018. We report the 90% of the target volume receiving the minimum dose for high risk clinical target volume (HR-CTV D90) and intermediate risk clinical target volume (IR-CTV D90), and the minimum doses to the most exposed 0.1, 1, and 2 cm³ D 0.1 c m 3 , D 1 c m 3 , D 2 c m 3 doses at the International Commission on Radiation Units and Measurements (DICRU) for organs at risk (OARs). The total dose of EBRT plus brachytherapy was transformed to the biologically equivalent dose in 2 Gy fractions (EQD2) with α/ß value of 10 Gy for target, 3 Gy for organs at risk using the linear quadratic model. The morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria. The Probit model was used to establish a prediction model on rectum between the organs at risk for dose and LRC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of dose volume parameters for LRC. RESULTS: The median follow-up time was 72.3 months. The mean ( ± standard deviation) D 2 c m 3 , D 1 c m 3 , D 0.1 c m 3 , and DICRU values of rectum were 64.72 ± 7.47 GyEQD2, 70.18 ± 5.92 GyEQD2, 79.32 ± 7.86 GyEQD2, and 67.22 ± 7.87 GyEQD2, respectively. The Probit model showed significant relationships between D 1 c m 3  or  D 0.1 c m 3 , and the probability of grade1-4, grade 2-4 rectal events at 1 year, and between D 1 c m 3 and the probability of grade2-4 rectal events at 3 and 5 years. The dose values for 10% complication rates (ED10) of D 1 c m 3 were 74.18 (70.42-76.71) GyEQD2, 67.80 (59.91, 71.08) GyEQD2, 66.37 (52.00, 70.27) GyEQD2 for grade 2-4 with rectal morbidity at 1, 3, and 5 years, respectively. CONCLUSION: Our study proved that D 1 c m 3  and D 0.1 c m 3 were considered as useful dosimetric parameters for predicting the risk of grade1-4 and grade2-4 LRC at 1-year, and D 1 c m 3 might be an indicator for predicting grade2-4 LRC at 3/5years. The patients with rectal D 1 c m 3 >66.37-74.18 GyEQD2 should be closely observed for grade2-4 LRC.

Analysis of Applicator Insertion Related Acute Side Effects for Cervical Cancer Treated With Brachytherapy.

PURPOSE: To report applicator insertion-related acute side effects during brachytherapy (BT) procedure for cervical cancer patients. MATERIALS AND METHODS: Between November 2017 and December 2019, 407 BT fractions were performed in 125 patients with locally advanced cervical cancer. Acute side effects recorded comprised anesthesia-related side effects, mechanical-related side effects and infection, whose frequency and degree were recorded. Pain was assessed using numeric rating scale; vaginal bleeding volume was counted by weighing gauze pieces used in packing. The BT procedure comprised eight stages: anesthesia, applicator insertion, image acquisition, transport, waiting for treatment, dose delivery, applicator removal, and removed which denoted 0.5-12.0 h period after removal, with time of each stage recorded. Factors influencing acute side effects were assessed by Spearman correlation and Mann-Whitney U test. RESULTS: The most common acute side effect was pain, followed by vaginal bleeding. The mean scores for pain were highest during removal time, 4.9 ± 1.6 points. The mean vaginal bleeding volume was 44.4 ml during removal time. Mean total procedure time was 218.8 (175-336) min, having positive relationship with frequency of acute side effects. The total procedure time with acute side effects was longer than that without acute side effects. The longest procedure time was waiting time, 113.0 (91.0-132.0) min. More needles generated higher pain scores and larger volume of vaginal bleeding. CONCLUSION: Pain and vaginal bleeding were the most common acute side effects, especially during removal time, which physicians should focus on. Shortening patients' waiting time helps to reduce the total procedure time, thus, reduce acute side effects. While meeting dose requirement, less needles are helpful to reduce acute side effects.

A novel NK-lysin in hybrid crucian carp can exhibit cytotoxic activity in fish cells and confer protection against Aeromonas hydrophila infection in comparison with Carassius cuvieri and Carassius auratus red var.

NK-lysin, an effector of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), not only exhibits cytotoxic effect in fish cells, but also participates in the immune defense against pathogenic infection. In this study, ORF sequences of RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin were 369 bp. Tissue-specific analysis revealed that the highest expressions of RCC-NK-lysin and WCC-NK-lysin were observed in gill, while the peaked level of WR-NK-lysin mRNA was observed in spleen. A. hydrophila infection sharply increased RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin mRNA expression in liver, trunk kidney and spleen. In addition, elevated levels of NK-lysin mRNA were observed in cultured fin cell lines of red crucian carp (RCC), white crucian carp (WCC) and their hybrid offspring (WR) after Lipopolysaccharide (LPS) challenge. RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin exerted regulatory roles in inducing ROS generation, modulating mitochondrial membrane potential, decreasing fish cell viability and antagonizing survival signalings, respectively. RCC/WCC/WR-NK-lysin-overexpressing fish could up-regulate expressions of inflammatory cytokines and decrease bacterial loads in spleen. These results indicated that NK-lysin in hybrid fish contained close sequence similarity to those of its parents, possessing the capacities of cytotoxicity and immune defense against bacterial infection.

Chimeric ferritin H in hybrid crucian carp exhibits a similar down-regulation in lipopolysaccharide-induced NF-κB inflammatory signal in comparison with Carassius cuvieri and Carassius auratus red var.

Ferritin H can participate in the regulation of teleostean immunity. ORF sequences of RCC/WCC/WR-ferritin H were 609 bp, while WR-ferritin H gene possessed chimeric fragments or offspring-specific mutations. In order to elucidate regulation of immune-related signal transduction, three fibroblast-like cell lines derived from caudal fin of red crucian carp (RCC), white crucian carp (WCC) and their hybrid offspring (WR) were characterized and designated as RCCFCs, WCCFCs and WRFCs. A sharp increase of ferritin H mRNA was observed in RCCFCs, WCCFCs and WRFCs following lipopolysaccharide (LPS) challenge. Overexpression of RCC/WCC/WR-ferritin H can decrease MyD88-IRAK4 signal and antagonize NF-κB, TNFα promoter activity in RCCFCs, WCCFCs and WRFCs, respectively. These results indicated that ferritin H in hybrid offspring harbors highly-conserved domains with a close sequence similarity to those of its parents, playing a regulatory role in inflammatory signals.

Three-dimensional image-guided combined intracavitary and interstitial high-dose-rate brachytherapy in cervical cancer: A systematic review.

PURPOSE: To evaluate the local control and toxicities of three-dimensional image-guided combined intracavitary and interstitial (IC/IS) high-dose-rate brachytherapy (BT) in cervical cancer through a systematic review. METHODS AND MATERIALS: A systematic review of relevant studies was performed through the PubMed, Web of Science, and Cochrane Library databases through May 10, 2020. Articles reporting on IC/IS technology, volumetric doses to high-risk clinical target volume (HR-CTV) and organs at risk (OARs), tumor control and/or treatment-related side effects were identified. The key information, including the type of applicator, implantation technology, characteristics of implantation, volumetric doses, tumor control, and/or treatment-related side effects, was extracted. A probit model analysis between HR-CTV D90 and tumor local control was performed. RESULTS: Twelve studies encompassing 520 patients were included in the probit model between HR-CTV D90 and the local control rate. The probit model showed a significant relationship between the HR-CTV D90 value and the local control probability, p = 0.003. The prescribed dose of 85 GyEQD2,10 would in theory warrant an 87.4% (95% confidence interval 82.5%-90.5%) local control rate. CONCLUSION: IC/IS BT is an appropriate method to achieve a high therapeutic ratio for tumors with large volumes or poor responses after external irradiation in cervical cancer. The probit model showed that the dose escalation of HR-CTV D90 was helpful to improve the local tumor control rate.

Predictive value of Excel forms based on an automatic calculation of dose equivalent in 2 Gy per fraction in adaptive brachytherapy for cervical cancer.

PURPOSE: External beam radiotherapy (EBRT) combined with brachytherapy (BT) is the standard mode of radical radiotherapy for locally advanced cervical cancer. The cumulative equivalent doses in 2 Gy per fraction (EQD2) is an important basis for estimating the probability of local control of tumors and monitoring the occurrence of side effects in normal tissues. The purpose of this study was to explore the predictive value of Excel forms based on an automatic calculation in radical adaptive BT for cervical cancer. MATERIAL AND METHODS: A retrospective analysis of 119 patients suffering from cervical cancer, treated with radical radiotherapy. All patients were treated with EBRT and adaptive BT. EBRT prescribed dose was 42.0-50.4 Gy in 21-28 fractions. BT nominal prescribed dose was 28 Gy in 4 fractions, separated by one week. Total EQD2 prediction at nth (n = 1-3) BT (TEPBn) or actual cumulative EQD2 (ACEQD2) can be calculated automatically by inputting the physical dose based on an in-house designed application. The relationship between TEPBn and ACEQD2 was evaluated, and the predictive value of Excel forms based on the automatic calculation was analyzed. RESULTS: For the volume of high-risk clinical target, there was a significant decrease between BT1 and BT2. Similarly, for the volume of intermediate-risk clinical target, there was a significant decrease between BT2 and BT3. The sensitivity ranges of TEPB1, TEPB2, and TEPB3 prediction were 74.5-91.3%, 83.7-95.7%, and 92.9-99.1%, respectively, and the specificity ranges were 46.7-80.0%, 53.3-90.5%, and 66.7-90.5%, respectively. CONCLUSIONS: The in-house designed application has the function of quickly reading dose-volume histogram (DVH) parameters from the treatment planning system, which allows for balance between the total dose to target volumes and organs at risk (OARs). Excel forms based on EQD2 automatic calculation presents high predictive accuracy.

Analysis of clinical utilization of ring applicator for combined intracavitary/interstitial image-guided brachytherapy treatment in Chinese patients with locally advanced cervical cancer.

PURPOSE: To analyze the results of clinical utilization of ring applicator for combined intracavitary (IC)/interstitial (IS) image-guided brachytherapy (BT) technique in locally advanced cervical cancer (LACC), and to explore the application conditions of IC/IS BT approach with this applicator for Chinese patients. MATERIAL AND METHODS: IC/IS BT was performed in total of 95 LACC patients, who already received external beam radiotherapy. In forty-three of these patients, utilization of ring applicator in brachytherapy was done, including IC/IS BT approach with ring applicator for 65 fractions. Clinically optimized IC/IS BT plan with ring applicator (IC/IS treatment) and additionally generated optimized plan without needle use (IC research) were designed, respectively. Dosage differences in target regions and organs at risk (OARs) were analyzed between both the plans. Four planes were selected in the longitudinal direction of uterine cervix and divided the 360° area around the tandem into eight equal sectors. Tumor target features and prescription dose distributions on different planes were described. RESULTS: The usage rate of ring applicator with most suitable ring diameter of 26 mm was 45.3% in Chinese cervical cancer patients. The high-risk clinical target volume (HR-CTV) D90/D98 and intermediate-risk CTV (IR-CTV) D90/D98 in IC/IS treatment were significantly higher than IC research. As compared with IC research plan, the D2.0 cm3 of bladder and rectum in IC/IS treatment were significantly lower (p < 0.05). There was no significant difference in D2.0 cm3 of sigmoid and small bowel between two plans. When the target volume was larger than 36 cm3, IC alone had an inadequate coverage of target. CONCLUSIONS: Nearly half of Chinese patients with LACC could be treated with the ring applicator. The application conditions of IC/IS BT approach with ring applicator for Chinese patients were achieved. Combined IC/IS image-guided BT based on magnetic resonance imaging (MRI) planning is clinically feasible in Chinese patients.

The 100 most cited articles in prostate cancer brachytherapy: systematic review and bibliometric analysis.

PURPOSE: The aim of this study was to identify the 100 most cited research articles in prostate cancer brachytherapy (PCB) and to review the characteristics of these citation. MATERIAL AND METHODS: The Web of Science Core Collection was used to identify the 100 most cited articles in PCB as of December 31st, 2019. The following important information was extracted: year and month of publication, title, journal, country of origin, authors, type of article, treatment modality, and topics. RESULTS: The 100 most cited articles in PCB were published between 1999 and 2018, and the number of citations ranged from 455 to 54; these articles had collectively been cited 10,331 times at the time of search. These articles were from 11 countries, with most publications being from the United States (n = 61), followed by Canada (n = 10), the United Kingdom (n = 8), and Germany (n = 5). The "International Journal of Radiation Oncology, Biology, Physics" published the most articles (n = 47), followed by the "Journal of Urology" (n = 11), "Radiotherapy and Oncology" (n = 10), "Cancer" (n = 7), and "Urology" (n = 6). Permanent interstitial brachytherapy (n = 52) was the most widely used treatment modality, followed by temporary brachytherapy (n = 45). Disease control (n = 51) was the most common topic, followed by side effects (n = 44) and quality of life (n = 27). CONCLUSIONS: The bibliometric analysis presents a detailed list of the 100 most cited articles in prostate cancer brachytherapy. There are clear recommendations for treatment with prostate cancer brachytherapy. The goal of prostate cancer brachytherapy is to improve long-term outcomes and quality of life.