Development and Application of a Mitochondrial Genetically Encoded Voltage Indicator in Narcosis.

Mitochondrial membrane potential (MMP) plays a crucial role in the function of cells and organelles, involving various cellular physiological processes, including energy production, formation of reactive oxygen species (ROS), unfolded protein stress, and cell survival. Currently, there is a lack of genetically encoded fluorescence indicators (GEVIs) for MMP. In our screening of various GEVIs for their potential monitoring MMP, the Accelerated Sensor of Action Potentials (ASAP) demonstrated optimal performance in targeting mitochondria and sensitivity to depolarization in multiple cell types. However, mitochondrial ASAPs also displayed sensitivity to ROS in cardiomyocytes. Therefore, two ASAP mutants resistant to ROS were generated. A double mutant ASAP3-ST exhibited the highest voltage sensitivity but weaker fluorescence. Overall, four GEVIs capable of targeting mitochondria were obtained and named mitochondrial potential indicators 1-4 (MPI-1-4). In vivo, fiber photometry experiments utilizing MPI-2 revealed a mitochondrial depolarization during isoflurane-induced narcosis in the M2 cortex.

Waiting for self-healing as a primary management strategy for lower lip mucoceles.

OBJECTIVES: Oral mucoceles are most frequently encountered on the lower lip. A variety of treatment options are currently employed, including surgical excision, pharmacological injections, and laser therapy. However, each of these approaches may introduce risks and potential complications. Clinical practice has demonstrated a potential for self-healing in lower lip mucoceles, making a conservative observational approach more appealing. This research is a prospective study aimed at evaluating the self-healing capacity of lower lip mucoceles. METHODS: In this prospective study, patients with mucoceles were encouraged to intentionally delay medical intervention and to wait for self-healing. Disappearance of the mucocele for at least 3 months was defined as self-healing. RESULTS: Thirty patients with lower lip mucoceles were included. With no intervention, 24 patients (80%) reported self-healing of lower lip mucoceles. The mean natural duration of the mucoceles was 3.63 (± 4.7; 1-24) months. After self-healing of the mucocele, the patients were followed up for 17.21 (± 9.45; 2-30) months and there were no reported recurrences. CONCLUSIONS: Lower lip mucoceles have a high potential for self-healing and patients may be routinely encouraged to wait for self-healing. CLINICAL RELEVANCE: The high self-healing rate observed in this study suggests that a conservative, non-interventional approach might be considered as the first-line management for lower lip mucoceles.

Integration of C3H15-mediated transcriptional and post-transcriptional regulation confers plant thermotolerance in Arabidopsis.

Heat stress is an environmental factor that significantly threatens crop production worldwide. Nevertheless, the molecular mechanisms governing plant responses to heat stress are not fully understood. Plant zinc finger CCCH proteins have roles in stress responses as well as growth and development through protein-RNA, protein-DNA, and protein-protein interactions. Here, we reveal an integrated multi-level regulation of plant thermotolerance that is mediated by the CCCH protein C3H15 in Arabidopsis. Heat stress rapidly suppressed C3H15 transcription, which attenuated C3H15-inhibited expression of its target gene HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2), a central regulator of heat stress response (HSR), thereby activating HEAT SHOCK COGNATE 70 (HSC70.3) expression. The RING-type E3 ligase MED25-BINDING RING-H2 PROTEIN 2 (MBR2) was identified as an interacting partner of C3H15. The mbr2 mutant was susceptible to heat stress compared to wild-type plants, whereas plants overexpressing MBR2 showed increased heat tolerance. MBR2-dependent ubiquitination mediated the degradation of phosphorylated C3H15 protein in the cytoplasm, which was enhanced by heat stress. Consistently, heat sensitivities of C3H15 overexpression lines increased in MBR2 loss-of-function and decreased in MBR2 overexpression backgrounds. Heat stress-induced accumulation of HSC70.3 promoted MBR2-mediated degradation of C3H15 protein, implying that an auto-regulatory loop involving C3H15, HSFA2, and HSC70.3 regulates HSR. Heat stress also led to the accumulation of C3H15 in stress granules (SGs), a kind of cytoplasmic RNA granule. This study advances our understanding of the mechanisms plants use to respond to heat stress, which will facilitate technologies to improve thermotolerance in crops.

Enormous myxoid/round cell liposarcoma: A case report.

Myxoid/round cell liposarcomas (MRCLPS) are a rare soft tissue sarcoma. We report the largest sarcoma in our institutional history. We discuss the patient's surgical management and treatment of the tumor and challenges given its dimensions. Several complications arose following primary resection that were managed by a multidisciplinary team. Although MRCLPS can vary in size, large MRCLPS must be treated cautiously given the potential for complications. Additionally, multidisciplinary treatment of MRCLPS is essential in diagnosing and treating these complex cases.

Cognitive shadows in perimenopause: linking subjective cognitive decline (SCD) to menopausal symptom severity.

OBJECTIVE: As women approach perimenopause, the incidence of Subjective Cognitive Decline (SCD) rises. This study aims to investigate the association between SCD and the severity of perimenopausal symptoms. SETTING: Conducted at The Affiliated Hospital of Guizhou Medical University Menopause Clinic from November 2022 to June 2023. Participants, aged 40-55 years, were classified as perimenopausal using the STRAW + 10 criteria. METHODS: SCD was assessed separately using the Chinese version of the SCD-Q9 scale and the SCD International Working Group (SCD-I) conceptual framework, while perimenopausal symptoms were evaluated with the Modified Kupperman Index (MKI). Linear relationships between MKI scores and SCD-Q9 scores were clarified using both univariate and multivariate linear regression analyses. Additionally, a multivariate Logistic regression analysis was conducted to examine the association between MKI scores and SCD classification based on SCD-I criteria. MAIN OUTCOME MEASURES: The primary outcomes were the Modified Kupperman Index scores, SCD-Q9 questionnaire scores, and the diagnosis of SCD based on SCD-I criteria. RESULTS: Among 101 participants, the average MKI score was 18.90 ± 9.74, and the average SCD-Q9 score was 4.57 ± 2.29. Both univariate and multivariate linear regressions demonstrated a positive correlation between these scores. A multivariate Logistic regression analysis, using MKI as the independent variable and SCD-I criteria classification as the dependent variable, revealed a significant positive association. CONCLUSIONS: A notable association exists between SCD and perimenopausal symptoms severity. This underscores the potential clinical importance of addressing perimenopausal symptoms to mitigate SCD risks in women. Further studies should focus on clarifying the causality between these factors.

Neurotransmitter accumulation and Parkinson's disease-like phenotype caused by anion channelrhodopsin opto-controlled astrocytic mitochondrial depolarization in substantia nigra pars compacta.

Parkinson's disease (PD) is a mitochondria-related neurodegenerative disease characterized by locomotor deficits and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Majority of PD research primarily focused on neuronal dysfunction, while the roles of astrocytes and their mitochondria remain largely unexplored. To bridge the gap and investigate the roles of astrocytic mitochondria in PD progression, we constructed a specialized optogenetic tool, mitochondrial-targeted anion channelrhodopsin, to manipulate mitochondrial membrane potential in astrocytes. Utilizing this tool, the depolarization of astrocytic mitochondria within the SNc in vivo led to the accumulation of γ-aminobutyric acid (GABA) and glutamate in SNc, subsequently resulting in excitatory/inhibitory imbalance and locomotor deficits. Consequently, in vivo calcium imaging and interventions of neurotransmitter antagonists demonstrated that GABA accumulation mediated movement deficits of mice. Furthermore, 1 h/day intermittent astrocytic mitochondrial depolarization for 2 weeks triggered spontaneous locomotor dysfunction, α-synuclein aggregation, and the loss of DA neurons, suggesting that astrocytic mitochondrial depolarization was sufficient to induce a PD-like phenotype. In summary, our findings suggest the maintenance of proper astrocytic mitochondrial function and the reinstatement of a balanced neurotransmitter profile may provide a new angle for mitigating neuronal dysfunction during the initial phases of PD.

Optimization of Composite Enzymatic Extraction, Structural Characterization and Biological Activity of Soluble Dietary Fiber from Akebia trifoliata Peel.

In order to reduce the waste of Akebia trifoliata peel and maximize its utilization, in this study, on the basis of a single-factor experiment and the response surface method, the optimum technological conditions for the extraction of soluble dietary fiber from Akebia trifoliata peel with the compound enzyme method were obtained. The chemical composition, physical and chemical properties, structural characterization and biological activity of the purified soluble dietary fiber (AP-SDF) from the Akebia trifoliata peel were analyzed. We discovered that that the optimum yield was 20.87% under the conditions of cellulase addition 600 U/g, enzymolysis time 100 min, solid-liquid ratio 1:24 g/mL and enzymolysis temperature 51 °C. At the same time, AP-SDF was a porous network structure cellulose type I acidic polysaccharose mainly composed of arabinoxylan (36.03%), galacturonic acid (27.40%) and glucose (19.00%), which possessed the structural characteristic peaks of the infrared spectra of polysaccharides and the average molecular weight (Mw) was 95.52 kDa with good uniformity. In addition, the AP-SDF exhibited high oil-holding capacity (15.11 g/g), good water-holding capacity and swelling capacity, a certain antioxidant capacity in vitro, hypoglycemic activity in vitro for α-glucosidase inhibition and hypolipidemic activity in vitro for the binding ability of bile acids and cholesterol. These results will provide a theoretical basis for the development of functional products with antioxidant, hypoglycemic and hypolipidemic effects, which have certain application value in related industries.

Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.

The Effects of Lentinan on the Hematological and Immune Indices of Dairy Cows.

In this study, we investigated the effects of lentinan (LNT) on hematological parameters, immune indices, and metabolite levels in dairy cows. We randomly assigned forty Holstein cows to four treatment groups. The treatments consisted of 0, 5, 10, and 15 g/d of LNT. Compared with the control group, the addition of 10 g/d of LNT decreased the content of ALT and IL-8 but simultaneously increased the content of IL-4 in the cows' serum. Supplementation with 10 g/d of LNT decreased the levels of lymphocyte, RDW, ALT, AST, TC, IL-2, and IL-8, but, concurrently, in-creased the levels of granulocytes and IL-4 in their serum. In addition, supplementation with 15 g/d of LNT decreased the levels of RDW, TC, IL-2, and IL-8, but, at the same time, increased the levels of IL-4 and IgM in their serum. For the metabolomic analysis, cows fed with 0 and 10 g/d of LNT were selected. The results showed that 10 metabolites, including reduced nicotinamide riboside and trehalose, were upregulated in the 10 g/d group. These differential metabolites were enriched in tyrosine metabolism and trehalose degradation and altered two metabolic pathways of ubiquinone and other terpene quinone biosynthesis, as well as starch and sucrose metabolism. These findings provide evidence that LNT could be used to reduce the risk of inflammation in dairy cows.

Oral bacteriome and mycobiome of patients with idiopathic membranous nephropathy with different tongue coatings treated with a Chinese herbal formula.

ETHNOPHARMACOLOGICAL RELEVANCE: Moshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined. AIM OF THE STUDY: In this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome. MATERIALS AND METHODS: We enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing. RESULTS: The therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN. CONCLUSION: The regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.

Construction of AlGaN/GaN high-electron-mobility transistor-based biosensor for ultrasensitive detection of SARS-CoV-2 spike proteins and virions.

The COVID-19 pandemic has highlighted the need for rapid and sensitive detection of SARS-CoV-2. Here, we report an ultrasensitive SARS-CoV-2 immunosensor by integration of an AlGaN/GaN high-electron-mobility transistor (HEMT) and anti-SARS-CoV-2 spike protein antibody. The AlGaN/GaN HEMT immunosensor has demonstrated the capability to detect SARS-CoV-2 spike proteins at an impressively low concentration of 10-22 M. The sensor was also applied to pseudoviruses and SARS-CoV-2 ΔN virions that display the Spike proteins with a single virion particle sensitivity. These features validate the potential of AlGaN/GaN HEMT biosensors for point of care tests targeting SARS-CoV-2. This research not only provides the first HEMT biosensing platform for ultrasensitive and label-free detection of SARS-CoV-2.

Does the opening of producer services promote the wage growth of the downstream manufacturing industry?-Empirical evidence from Chinese manufacturing listed companies.

Based on the vertical connection between upstream and downstream industries, a unique theoretical model is constructed to analyse the impact mechanism of the opening of producer services on downstream manufacturing wage growth. The empirical tests are carried out using the data of China's manufacturing listed companies from 1999 to 2020. Our findings indicate that the opening of producer services has an inverted-U-shaped impact on downstream manufacturing wage growth, and the average level of the opening of producer services in the sample period is lower than the corresponding threshold. Overall, it is in the stage of promoting the wage growth of the downstream manufacturing industry. The opening of producer services mainly affects the wage growth of the downstream manufacturing industry through two channels: labour productivity and labour income share. The results of heterogeneity analysis show that the wages of capital and technology-intensive and low-competitive manufacturing industries are relatively strongly promoted by the opening of producer services. Therefore, promoting the orderly opening of producer services and strengthening the technological links between industries will help promote the wage growth of downstream manufacturing industries.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B: A meta-analysis.

BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Open-Set Recognition of Individual Cows Based on Spatial Feature Transformation and Metric Learning.

The automated recognition of individual cows is foundational for implementing intelligent farming. Traditional methods of individual cow recognition from an overhead perspective primarily rely on singular back features and perform poorly for cows with diverse orientation distributions and partial body visibility in the frame. This study proposes an open-set method for individual cow recognition based on spatial feature transformation and metric learning to address these issues. Initially, a spatial transformation deep feature extraction module, ResSTN, which incorporates preprocessing techniques, was designed to effectively address the low recognition rate caused by the diverse orientation distribution of individual cows. Subsequently, by constructing an open-set recognition framework that integrates three attention mechanisms, four loss functions, and four distance metric methods and exploring the impact of each component on recognition performance, this study achieves refined and optimized model configurations. Lastly, introducing moderate cropping and random occlusion strategies during the data-loading phase enhances the model's ability to recognize partially visible individuals. The method proposed in this study achieves a recognition accuracy of 94.58% in open-set scenarios for individual cows in overhead images, with an average accuracy improvement of 2.98 percentage points for cows with diverse orientation distributions, and also demonstrates an improved recognition performance for partially visible and randomly occluded individual cows. This validates the effectiveness of the proposed method in open-set recognition, showing significant potential for application in precision cattle farming management.

[Progress on treatment of acetabular quadrilateral plate injury].

Acetabular quadrilateral plate injury has become a hot spot and focus in the field of orthopaedic trauma and pelvic floor function in recent years. Although there are five fracture types,they are all based on fracture morphology,without considering the pulling force of ligaments,joint capsular and muscles. A perfect classification needs to describe the displacement of bone mass in three-dimensional space to better guide reduction and fixation. The seven incision and exposure methods are still the traditional open-eye surgery,and how to protect the criss-crossing vascular neural network and pelvic organs is still the focus. Quadrilateral defect causes dislocation of artificial hip joint,and quantitative evaluation of quadrilateral defect volume and revision techniques are still a hot topic. In this paper,the viewpoints of three-dimensional network structure of acetabular pelvic vascular anatomy,anatomical surgical target channel and fixation anchor point of acetabular fracture reduction are proposed to design new techniques for accurate and minimally invasive surgical operations,in order to realize the requirements of rapid orthopedic rehabilitation.

Design of High-Gain Antenna Arrays for Terahertz Applications.

A terahertz band (0.1-10 THz) has the characteristics of rich spectrum resources, high transmission speed, strong penetration, and clear directionality. However, the terahertz signal will suffer serious attenuation and absorption during transmission. Therefore, a terahertz antenna with high gain, high efficiency, and wide bandwidth is an indispensable key component of terahertz wireless systems and has become a research hotspot in the field of antennas. In this paper, a high-gain broadband antenna is presented for terahertz applications. The antenna is a three-layer structure, fed by a grounded coplanar waveguide (GCPW), using polytetrafluoroethylene (PTFE) material as the dielectric substrate, and the metal through-hole of the dielectric substrate forms a substrate-integrated waveguide (SIW) structure. The metal fence structure is introduced to reduce the coupling effect between the radiation patches and increase the radiation bandwidth and gain. The center frequency is 0.6366 THz, the operating bandwidth is 0.61-0.68 THz, the minimum value of the voltage standing wave ratio (VSWR) is 1.00158, and the peak gain is 13.14 dBi. In addition, the performance of the designed antenna with a different isolation structure, the length of the connection line, the height of the substrate, the radius of the through-hole, and the thickness of the patch is also studied.

Polyaspartic acid increases potassium content and reduces the ratio of total sugar to nicotine in tobacco leaves.

Tobacco is an important cash crop in China, but the low potassium (K) content and high ratio of total sugar to nicotine in tobacco leaves have seriously affected the quality of tobacco leaves. As a fertilizer synergist, polyaspartic acid (PASP) can improve the K content in tobacco leaves, but it is unknown how it affects the K content in different parts of tobacco leaves, and how PASP affects the ratio of total sugar to nicotine in tobacco leaves has not been reported. Therefore, "Zhongyan 100" was selected for pot experiments with 5 different PASP addition levels: CK (0.0 %), P1 (0.1 %), P2 (0.2 %), P3 (0.4 %) and P4 (0.6 %), to reveal the effects of PASP on tobacco growth, K content, sugar content, nicotine content and the ratio of total sugar to nicotine in different tobacco parts, and determine the optimal PASP dosage for regulating the K content and the ratio of total sugar to nicotine in tobacco. The results showed that P1 (0.1 %) and P2 (0.2 %) only had slighter effects on tobacco growth and quality, while P3 (0.4 %) and P4 (0.6 %)treatments significantly promoted dry matter accumulation, increased K and nicotine content in leaves, decreased reducing sugar and total soluble sugar content in leaves, thereby reducing the ratio of total sugar to nicotine in tobacco leaves, especially in upper leaves. Considering the economic cost savings, 0.4% PASP was determined as the best application level to improve the growth and quality of tobacco. Thus, proper application of PASP is beneficial to improve tobacco leaf quality and reduce chemical K fertilizer application, thereby decreasing agricultural environmental risks of chemical fertilizer and alleviating the rapid depletion of potash in the world.

Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Long-Term Results From the PKUFH Randomized Phase 3 Trial.

PURPOSE: In the randomized, single-center, PKUFH phase 3 trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the 2 cohorts at 4 years. In the current analysis, we provide 7-year outcomes. METHODS AND MATERIALS: Patients with stage pT3-4, positive surgical margins, or a prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image guided intensity modulated radiation therapy. The primary endpoint was bPFS. Secondary endpoints were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) as estimated using the Kaplan-Meier method. RESULTS: Between September 2011 and November 2016, 144 patients were enrolled with 73 and 71 in the 72- and 66-Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72- and 66-Gy cohorts (70.3% vs 61.2%; hazard ratio [HR], 0.73; 95% CI, 0.41-1.29; P = .274). However, in patients with a higher Gleason score (8-10), the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66-Gy cohort (66.5% vs 30.2%; HR, 0.37; 95% CI, 0.17-0.82; P = .012). In addition, in patients with multiple positive surgical margins, the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR, 0.36; 95% CI, 0.13-0.99; P = .037). The 7-year DMFS (88.4% vs 84.9%; HR, 0.93; 95% CI, 0.39-2.23; P = .867), CSS (94.1% vs 95.5%; HR, 1.19; 95% CI, 0.42-3.39; P = .745), and OS (92.8% vs 94.1%; HR, 1.29; 95% CI, 0.51-3.24; P = .594) had no statistical differences between the 72- and 66-Gy cohorts. CONCLUSIONS: The current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared with the 66-Gy regimen. However, patients with a higher Gleason score (8-10) or multiple positive surgical margins might benefit from the 72-Gy regimen, but this requires further prospective research.

Multiparametric Magnetic Resonance Imaging- Guided Dose-Escalated Radiation Therapy for Localized Prostate Cancer: A Prospective Phase 2 Trial.

PURPOSE: This trial's purpose was to determine the late toxicity associated with dose escalation to Prostate Imaging Reporting and Data System (PI-RADS) III-V lesions on multiparametric magnetic resonance imaging (MRI) with an image guided combined IMRT-stereotactic body radiation therapy (SBRT) approach in men with localized prostate cancer. METHODS AND MATERIALS: In this phase 2 trial patients with localized prostate cancer with clinical tumor stage T1-T3bN0 and at least one PIRADS III-V lesion were recruited to receive 45 Gy in 25 fractions to the prostate and seminal vesicles followed by a boost of 18 Gy in 3 fractions to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions to the PI-RADS lesion(s). The primary endpoint was the cumulative incidence of late grade ≥3 genitourinary and gastrointestinal toxicity by 18 months (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). RESULTS: Overall, 50 patients were enrolled in this study, and 43 patients completed at least 18 months of follow-up. The cumulative incidence of grade 1, 2, and 3 late genitourinary toxicity at 18 months was 18%, 53%, and 2%. One patient was noted to have grade 3 hematuria and needed cystoscopy-guided cauterization. No acute grade 3 gastrointestinal or genitourinary toxicities were observed. The cumulative incidence of grade 1, 2, and 3 late gastrointestinal toxicity at 18 months was 31%, 4%, and 0%, respectively. At a median follow-up of 43.5 months, 3 patients developed biochemical recurrence, each with distant bone metastases without local or nodal recurrence. At 3 years, freedom from biochemical failure rate was 95.3% (95% CI, 89.2%-100%). CONCLUSIONS: Multiparametric MRI-guided dose escalation to PI-RADS III-V lesions using a combined image guided IMRT-SBRT approach is associated with an acceptable risk of late gastrointestinal and genitourinary toxicity. The results should be interpreted with caution considering their single institutional nature, small sample size, and short follow-up and should be validated in a larger study.