The dose response of erythemal area and intensity on the unprotected skin fits well to a logistic 3P model in SPF tests of a Chinese population, which has the potential to improve the precision and consistency of minimal erythema dose determination.

BACKGROUND: The current ISO guidelines for minimal erythema dose (MED) determination require assessment of erythema area of UV-irradiated skin sites. However, this parameter has not been adequately quantified in daily practice. The aims of this study were to investigate the dose response on the unprotected skin sites by quantifying the erythema area and intensity and to show the potential for improving the precision and consistency of MEDu determination by developing predictive models. METHODS: Standard radiation tests were conducted on the back of 31 healthy Chinese volunteers and the MEDu site of each subject was clinically determined by dermatologists. Images of test sites were captured 24 h after radiation, and the erythema area (%EA) and intensity (∆a*) were measured by image analysis. The data were fitted to a logistic 3P function to obtain dose-response curves, and a set of logit (inverse-logistic) models were then derived. An erythema area threshold of %EA = 52% was established to predict MEDu based on the clinical endpoints defined by ISO 24444:2019. RESULTS: Analysis of the clinically determined MEDu sites revealed wide ranges of %EA (62.3 ± 15% SD) and ∆a* (2.96 ± 0.92 SD). The dose response fitted well to a logistic 3P model (mean R2 = 0.965 and 0.975 for %EA and ∆a*, respectively). Applying the area threshold, values of MEDu were determined by the logit model for the test population, which significantly improved the consistency of MEDu determination (52 ± 0% SD and 2.73 ± 0.61 SD for %EA and ∆a*, respectively). CONCLUSION: This study demonstrated that the dose response of UV-induced erythema can be quantified and modeled once the erythema area and intensity are measured. The results of this study show the potential to improve the precision and consistency of MEDu determination in an SPF test. The similar potential in photodermatological, therapeutic, and diagnostic applications was also implied.

Evaluation the benefits of additional radiotherapy for gastric cancer patients after D2 resection using CT based radiomics.

OBJECTIVES: The value of adding radiotherapy (RT) is still unclear for patients with gastric cancer (GC) after D2 lymphadenectomy. The purpose of this study is to predict and compare the overall survival (OS) and disease-free survival (DFS) of GC patients treated by chemotherapy and chemoradiation based on contrast-enhanced CT (CECT) radiomics. METHODS: A total of 154 patients treated by chemotherapy and chemoradiation in authors' hospital were retrospectively reviewed and randomly divided into the training and testing cohorts (7:3). Radiomics features were extracted from contoured tumor volumes in CECT using the pyradiomics software. Radiomics score and nomogram with integrated clinical factors were developed to predict the OS and DFS and evaluated with Harrell's Consistency Index (C-index). RESULTS: Radiomics score achieved a C index of 0.721(95%CI: 0.681-0.761) and 0.774 (95%CI: 0.738-0.810) in the prediction of DFS and OS for GC patients treated by chemotherapy and chemoradiation, respectively. The benefits of additional RT only demonstrated in subgroup of GC patients with Lauren intestinal type and perineural invasion (PNI). Integrating clinical factors further improved the prediction ability of radiomics models with a C-index of 0.773 (95%CI: 0.736-0.810) and 0.802 (95%CI: 0.765-0.839) for DFS and OS, respectively. CONCLUSIONS: CECT based radiomics is feasible to predict the OS and DFS for GC patients underwent chemotherapy and chemoradiation after D2 resection. The benefits of additional RT only observed in GC patients with intestinal cancer and PNI.

Endometrial microstimulation effects on endometrial receptivity assessed by transvaginal color Doppler sonography.

OBJECTIVE: This study investigated the effect of endometrial microstimulation (EM) on endometrial receptivity using transvaginal color Doppler sonography (TVCDS). METHOD: Women of childbearing age who were preparing to conceive (n = 90) were randomly divided into the EM group (n = 30), who were examined by EM on days 3-5 of the menstrual cycle, and the control group (n = 60). TVCDS was conducted during the implantation window phase, and endometrial thickness, endometrial pattern, endometrial movement, blood flow type, and uterine and spiral arterial hemodynamic parameter measurements were made. The groups were compared to identify differences. RESULTS: Endometrial thickness (0.97 ± 0.18 cm and 0.95 ± 0.17 cm), endometrial movement (type 1: 46.7% and 51.7%; type 2: 30.0% and 28.3%; type 3: 6.7% and 5.0%; type 5: 16.7% and 15.0%), and hemodynamic parameters of the uterine (pulsatility index [PI]: 2.46 ± 0.50 and 2.41 ± 0.48; resistance index [RI]: 0.85 ± 0.05 and 0.84 ± 0.05) and spiral (PI: 1.11 ± 0.32 and 1.19 ± 0.33; RI: 0.48 ± 0.11 and 0.51 ± 0.08) arteries did not differ significantly between groups (P > 0.05). However, the endometrial pattern (a trilaminar pattern: 80.0% and 58.3%; P = 0.041) and blood flow type (type I: 16.7% and 43.3%; type II: 63.3% and 40.0%; type III 20.0% and 16.7%; P = 0.038) differed significantly between groups. CONCLUSION: Endometrial microstimulation did not alter endometrial pathological staging, endometrial thickness, or movement, nor did it affect uterine and spiral arterial blood flow parameters. However, it may be able to abrade abnormal endometrial tissue, optimizing the endometrial pattern. Endometrial microstimulation may support local spiral artery regeneration and increase endometrial blood supply in new cycles.

RefineNet-based 2D and 3D automatic segmentations for clinical target volume and organs at risks for patients with cervical cancer in postoperative radiotherapy.

PURPOSE: An accurate and reliable target volume delineation is critical for the safe and successful radiotherapy. The purpose of this study is to develop new 2D and 3D automatic segmentation models based on RefineNet for clinical target volume (CTV) and organs at risk (OARs) for postoperative cervical cancer based on computed tomography (CT) images. METHODS: A 2D RefineNet and 3D RefineNetPlus3D were adapted and built to automatically segment CTVs and OARs on a total of 44 222 CT slices of 313 patients with stage I-III cervical cancer. Fully convolutional networks (FCNs), U-Net, context encoder network (CE-Net), UNet3D, and ResUNet3D were also trained and tested with randomly divided training and validation sets, respectively. The performances of these automatic segmentation models were evaluated by Dice similarity coefficient (DSC), Jaccard similarity coefficient, and average symmetric surface distance when comparing them with manual segmentations with the test data. RESULTS: The DSC for RefineNet, FCN, U-Net, CE-Net, UNet3D, ResUNet3D, and RefineNet3D were 0.82, 0.80, 0.82, 0.81, 0.80, 0.81, and 0.82 with a mean contouring time of 3.2, 3.4, 8.2, 3.9, 9.8, 11.4, and 6.4 s, respectively. The generated RefineNetPlus3D demonstrated a good performance in the automatic segmentation of bladder, small intestine, rectum, right and left femoral heads with a DSC of 0.97, 0.95, 091, 0.98, and 0.98, respectively, with a mean computation time of 6.6 s. CONCLUSIONS: The newly adapted RefineNet and developed RefineNetPlus3D were promising automatic segmentation models with accurate and clinically acceptable CTV and OARs for cervical cancer patients in postoperative radiotherapy.

Simultaneous determination and determination of sildenafil and its active metabolite in human plasma using LC-MS/MS method.

A sensitive and selective high-performance liquid chromatography-tandam mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of sildenafil and its metabolite N-desmethyl sildenafil in human plasma. Sildenafil-d8 was used as an internal standard. The analytes were extracted by precipitation extraction and chromatographed on a C18 column using mobile phase A of water (containing 0.1% formic acid) and mobile phase B of acetonitrile (containing 0.1% formic acid) with gradient elution. Quantification was done using multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 475.4 → m/z 283.3 for sildenafil, m/z 461.4 → m/z 283.2 for N-desmethyl sildenafil and m/z 483.3 → m/z 108.1 for IS in positive ionization mode. The calibration curve was established over the range of 2.00-1,000 ng/ml and the correlation coefficient was >0.99. The intra-day and inter-day relative standard deviations were <6.5% for sildenafil and 6.3% for N-desmethyl sildenafil respectively. Accuracy determinaed at four concentrations was 86.50-105.67% for sildenafil and 96.83-114.40% for N-desmethyl sildenafil. This method was successfully applied to a pharmacokinetic description of sildenafil and the effect of food intake on the pharmacokinetics of sildenafil was also demonstrated in healthy Chinese volunteers.

Impact of setup errors on multi-isocenter volumetric modulated arc therapy for craniospinal irradiation.

Multi-isocenter volumetric modulated arc therapy (VMAT) is recommended for craniospinal irradiation (CSI) to smooth the dose distribution in the junction regions relying solely on inverse optimization. However, few studies have measured the dosimetric impact of setup errors on this multi-isocenter VMAT in the junction areas. The purpose of this study is to evaluate the impact of positional errors during VMAT CSI with two-dimension (2D) and three-dimension (3D) dosimetric measurements. A total of 20 patients treated by three-isocenter VMAT CSI were retrospectively reviewed and analyzed. A 3D diode array ArcCHECK and radiochromic film EBT3 were applied to measure the percentage gamma passing rates (%GPs) and dose distributions in the junction areas between the cranial/upper-spinal and the upper/lower-spinal fields with intentionally introduced setup errors of ± 1 mm, ±2 mm, ±3 mm, ±5 mm, and ± 8 mm, respectively. The length and volume of planning target volume (PTV) for these CSI patients ranged from 50.14 to 80.8 cm, and 1572.3 to 2114.5 cm3 , respectively. The %GPs for ±3 mm, ±5 mm, and ±8 mm positional errors were around 95%, 90%, and 85%, respectively, in the junction areas. The dosimetric verification results with EBT3 films indicated that cold and hot areas were observed with the increase of introduced setup errors. In conclusion, the dosimetric verification with intentionally introduced setup errors demonstrated that positional errors within 3 mm have a little impact for VMAT CSI, although setup errors should be minimized. Relying on the inverse optimization of VMAT to smooth the dose distribution in the junction areas is feasible for CSI.

Cross verification of independent dose recalculation, log files based, and phantom measurement-based pretreatment quality assurance for volumetric modulated arc therapy.

Independent treatment planning system (TPS) check with Mobius3D software, log files based quality assurance (QA) with MobiusFX, and phantom measurement-based QA with ArcCHECK were performed and cross verified for head-and-neck (17 patients), chest (16 patients), and abdominal (19 patients) cancer patients who underwent volumetric modulated arc therapy (VMAT). Dosimetric differences and percentage gamma passing rates (%GPs) were evaluated and compared for this cross verification. For the dosimetric differences in planning target volume (PTV) coverage, there was no significant difference among TPS vs. Mobius3D, TPS vs. MobiusFX, and TPS vs. ArcCHECK. For the dosimetric differences in organs at risks (OARs), the number of metrics with an average dosimetric differences higher than ±3% for TPS vs Mobius3D, TPS vs MobiusFX, and TPS vs ArcCHECK were 1, 1, 7; 2, 1, 4; 1, 1, 5 for the patients with head-and-neck, abdomen, and chest cancer, respectively. The %GPs of global gamma indices for Mobius3D and MobiousFX were above 97%, while it ranged from 92% to 96% for ArcCHECK. The %GPs of individual volume-based gamma indices were around 98% for Mobius3D and MobiousFX, except for γPTV for chest and abdominal cancer (88.9% to 92%); while it ranged from 86% to 99% for ArcCHECK. In conclusion, some differences in dosimetric metrics and gamma passing rates were observed with ArcCHECK measurement-based QA in comparison with independent dosecheck and log files based QA. Care must be taken when considering replacing phantom measurement-based IMRT/VMAT QA.

An improved LC-MS/MS method for determination of cinacalcet in human plasma and its application to the evaluation of food intake effect on the pharmacokinetics of cinacalcet in healthy volunteers.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of cinacalcet in human plasma was developed and validated. This assay was based on liquid-liquid extraction and cinacalcet-d4 was used as an internal standard (IS). Separation was achieved on a C18 column by the mobile phase A of water (containing 0.1% formic acid) and the mobile phase B of acetonitrile-water (95:5, v/v) (containing 0.2% formic acid) with gradient elution. Quantification was done using multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 358.2 → m/z 155.2 for cinacalcet and m/z 362.3 → m/z 155.0 for IS at positive ionization mode. The calibration curve was established over the range 0.05-20.0 ng/mL and the correlation coefficient was >0.99. The intra- and inter-day relative standard deviations were <5.8%. Accuracy determined at four concentrations ranged between 96.0 and 106.0%. This method was successfully applied to a pharmacokinetic description of oral dose of cinacalcet and the significant effect of food intake on the pharmacokinetics of cinacalcet was first demonstrated in Chinese healthy volunteers.

Differential analysis of quantitative proteome and acetyl-proteome profiling between premenopausal and postmenopausal ovarian tissues.

BACKGROUND: Natural menopause is always accompanied by specific signs and symptoms, suggesting physiological changes in this peoriod. However, no systematic study has assessed the changes at molecular level in the ovaries during the menopausal transition so far. This study integrated quantitative proteome and acetyl-proteome to comprehensively uncover the changes of ovarian protein and protein-acetylation profiles in this transitional period. The findings would provide novel insights into the biology of menopause and help relieve and treat the associated signs and symptoms, further improving the women's health care. METHODS: Freshly thawed ovarian tissue samples obtained from premenopausal and postmenopausal women were assessed with Tandem Mass Tags for the quantitative analysis of the global profile and acetyl-proteomes by 2-dimensional separation and LC-MS/MS. RESULTS: Comprehensively, 4210 types of protein, with 3551 types quantifiable were detected. 3047 acetylated sites in 1583 types of protein with 2256 quantifiable in 1248 proteins were detected. By comparing the global and acetylated proteome profiles for postmenopausal women and premenopausal women, 151 types of proteins were found upregulated and 65 were downregulated, along with 23 acetylated sites upregulated and 220 sites downregulated. For Immune response, the complement and coagulation cascades plus the citrate cycle and cellular detoxification were found to be significantly enhanced, while the extracellular structure and matrix organization, ECM-receptor interactions plus the infections were markedly suppressed. In addition, the amino acids around the acetylated sites were enriched by motif analysis, which can help us uncover amino acid sequence and search for the specific target in the subsequent study. CONCLUSION: Global and acetylated proteome Profiles in ovary differ between the premenopausal and postmenopausal groups. These proteomic-level changes may offer some potential biological markers to identify the pathological changes in ovary and help relieve and treat the associated signs and symptoms, and ultimately improve women's health care.

Individual volume-based 3D gamma indices for pretreatment VMAT QA.

Although gamma analysis is still a widely accepted quantitative tool to analyze and report patient-specific QA for intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), the correlation between the 2D percentage gamma passing rate (%GP), and the clinical dosimetric difference for IMRT and VMAT has been questioned. The purpose of this study was to investigate the feasibility of individual volume-based 3D gamma indices for pretreatment VMAT QA. Percentage dosimetric errors (%DE) of dose-volume histogram metrics (includes target volumes and organ at risks) between the treatment planning system and QA-reconstructed dose distribution, %GPs for individual volume and global gamma indices, as well their correlations and sensitivities were investigated for one- and two-arc VMAT plans. The %GPs of individual volumes had a higher percent of correlation with individual 15 %DE metrics compared with global %GPs. For two-arc VMAT at 2%/2 mm, 3%/3 mm, and 4%/4 mm criteria, individual volume %GPs were correlated with 9, 12, and 9 out of 15 %DE metrics, while global %GPs were correlated with only 2 out of 15 %DE metrics, respectively. For one-arc VMAT at 2%/2 mm, 3%/3 mm, and 4%/4 mm criteria, individual volume %GPs were correlated with 18, 16, and 13 out of 23 %DE metrics, and global %GPs were correlated with 19, 12, and 1 out 23 %DE metrics, respectively. The area under curves (AUC) of individual volume %GPs were higher than those of global %GPs for two-arc VMAT plans, but with mixed results for one-arc VMAT plans. In a conclusion, the idea of individual volume %GP was created and investigated to better serve for VMAT QA and individual volume-based %GP had a higher percent of correlation with DVH 15 %DE metrics compared with global %GP for both one- and two-arc VMAT plans.

Dosimetric benefits of intensity-modulated radiotherapy and volumetric-modulated arc therapy in the treatment of postoperative cervical cancer patients.

As the advantage of using complex volumetric-modulated arc therapy (VMAT) in the treatment of gynecologic cancer has not yet been fully determined, the purpose of this study was to investigate the dosimetric advantages of VMAT by comparing directly with whole pelvic conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT) in the treatment of 15 postoperative cervical cancer patients. Four-field CRT, seven-field IMRT, and two-arc VMAT plans were generated for each patient with identical objective functions to achieve clinically acceptable dose distribution. Target coverage and OAR sparing differences were investigated through dose-volume histogram (DVH) analysis. Nondosimtric differences between IMRT and VMAT were also compared. Target coverage presented by V95% were 88.9% ± 3.8%, 99.9% ± 0.07%, and 99.9% ± 0.1% for CRT, IMRT, and VMAT, respectively. Significant differences on conformal index (CI) and conformal number (CN) were observed with CIs of 0.37 ± 0.07, 0.55 ± 0.04, 0.61 ± 0.04, and CNs of 0.33 ± 0.06, 0.55 ± 0.04, 0.60 ± 0.04 for CRT, IMRT, and VMAT, respectively. IMRT and VMAT decreased the dose to bladder and rectum significantly compared with CRT. No significant differences on the Dmean, V45, and V30 of small bowel were observed among CRT, IMRT, and VMAT. However, VMAT (10.4 ± 4.8 vs. 19.8 ± 11.0, P = 0.004) and IMRT (12.3 ± 5.0 vs. 19.8 ± 11.0, P = 0.02) decreased V40, increased the Dmax of small bowel and the irradiation dose to femoral heads compared with CRT. VMAT irradiated less dose to bladder, rectum, small bowel and larger volume of health tissue with a lower dose (V5 and V10) compared with IMRT, although the differences were not statistical significant. In conclusion, VMAT and IMRT showed significant dosimetric advantages both on target coverage and OAR sparing compared with CRT in the treatment of postoperative cervical cancer. However, no significant difference between IMRT and VMAT was observed except for slightly better dose conformity, slightly less MU, and significant shorter delivery time achieved for VMAT.

Trichophyton rubrum conidia modulate the expression and transport of Toll-like receptor 2 in HaCaT cell.

Trichophyton rubrum (T. rubrum) represents the most important agent of dermatophytosis in humans. T. rubrum infection causes slight inflammation, and tends to be chronic and recurrent. It is suggested that T. rubrum can modulate the innate immune responses of host cells, which result in the failure of host cells to recognize T. rubrum and initiate effective immune responses. In this study we show how T. rubrum conidia modulate the expression and transport of Toll-like receptor 2 in HaCaT cell. Flow cytometric analysis showed that the surface and total expression of Toll-like receptor 2 were upregulated at the very early stage when keratinocytes were exposed to T. rubrum conidia regardless of the dose, and the upregulation of surface TLR2 was much more significant than that of total TLR2. Moreover, TLR2 expression was suppressed after upregulation in the initial stage of T. rubrum exposure, and the decrease of total TLR2 was earlier than that of surface TLR2. Our results suggest that in the early stage, TLR2 of keratinocytes were upregulated and transported to the cell surface. After then, the expression of TLR2 was suppressed by T. rubrum conidia.

Dosimetric benefits of IMRT and VMAT in the treatment of middle thoracic esophageal cancer: is the conformal radiotherapy still an alternative option?

The purpose of this study is to investigate the dosimetric differences among conformal radiotherapy (CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated radiotherapy (VMAT) in the treatment of middle thoracic esophageal cancer, and determine the most appropriate treatment modality. IMRT and one-arc VMAT plans were generated for eight middle thoracic esophageal cancer patients treated previous with CRT. The planning target volume (PTV) coverage and protections on organs at risk of three planning schemes were compared. All plans have sufficient PTV coverage and no significant differences were observed, except for the conformity and homogeneity. The lung V5, V10, and V13 in CRT were 47.9% ± 6.1%, 36.5% ± 4.6%, and 33.2% ± 4.2%, respectively, which were greatly increased to 78.2% ± 13.7% (p < 0.01), 80.8% ± 14.9% (p < 0.01), 48.4% ± 8.2% (p = 0.05) in IMRT and 58.6% ± 10.5% (p = 0.03), 67.7% ± 14.0% (p < 0.01), and 53.0% ± 10.1% (p < 0.01) in VMAT, respectively. The lung V20 (p = 0.03) in VMAT and the V30 (p = 0.04) in IMRT were lower than those in CRT. Both IMRT and VMAT achieved a better protection on heart. However, the volumes of the healthy tissue outside of PTV irradiated by a low dose were higher for IMRT and VMAT. IMRT and VMAT also had a higher MU, optimization time, and delivery time compared to CRT. In conclusion, all CRT, IMRT, and VMAT plans are able to meet the prescription and there is no clear distinction on PTV coverage. IMRT and VMAT can only decrease the volume of lung and heart receiving a high dose, but at a cost of delivering low dose to more volume of lung and normal tissues. CRT is still a feasible option for middle thoracic esophageal cancer radiotherapy, especially for the cost-effective consideration.

2% supramolecular salicylic acid hydrogel vs. adapaline gel in mild to moderate acne vulgaris treatment: A multicenter, randomized, evaluator-blind, parallel-controlled trial.

OBJECTIVE: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. METHODS: A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. RESULTS: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. CONCLUSION: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris.

FOXK2 amplification promotes breast cancer development and chemoresistance.

Oncogene activation through DNA amplification or overexpression is a crucial driver of cancer initiation and progression. The FOXK2 gene, located on chromosome 17q25, encodes a transcription factor with a forkhead DNA-binding domain. Analysis of genomic datasets reveals that FOXK2 is frequently amplified and overexpressed in breast cancer, correlating with poor patient survival. Knockdown of FOXK2 significantly inhibited breast cancer cell proliferation, migration, anchorage-independent growth, and delayed tumor growth in a xenograft mouse model. Additionally, inhibiting FOXK2 sensitized breast cancer cells to chemotherapy. Co-overexpression of FOXK2 and mutant PI3KCA transformed non-tumorigenic MCF-10A cells, suggesting a role for FOXK2 in PI3KCA-driven tumorigenesis. CCNE2, PDK1, and ESR1 were identified as transcriptional targets of FOXK2 in MCF-7 cells. Small-molecule inhibitors of CCNE2/CDK2 (dinaciclib) and PDK1 (dichloroacetate) exhibited synergistic anti-tumor effects with PI3KCA inhibitor (alpelisib) in vitro. Inhibition of FOXK2 by dinaciclib synergistically enhanced the anti-tumor effects of alpelisib in a xenograft mouse model. Collectively, these findings highlight the oncogenic function of FOXK2 and suggest that FOXK2 and its downstream genes represent potential therapeutic targets in breast cancer.

Clinical evidence on the efficacy and safety of an antioxidant optimized 1.5% salicylic acid (SA) cream in the treatment of facial acne: an open, baseline-controlled clinical study.

BACKGROUND/PURPOSE: Acne pathogenesis is multifactorial and includes inflammation. Combining active ingredients targeting multiple components of acne pathogenesis may yield optimal outcomes. This study investigates the safety and efficacy of an antioxidant optimized topical salicylic acid (SA) 1.5% cream containing natural skin penetration enhancers in combination with antioxidant activity for treatment of facial acne. METHODS: A total of 20 patients with facial acne, aged 19-32 years (2 males, 18 females; mean age 26.1 ± 3.2), were enrolled. Patients were treated with topical 1.5% SA cream and instructed to apply the cream as a thin film over the affected area twice daily (in the morning and evening) for 4 weeks. Inflammatory severity, numbers of papules and pustules were evaluated by investigators at day 0 and weekly, and patients ranked their improvement. RESULTS: In all, 95% of patients improved: 20% had complete clearing, 30% had significantly improved, 15% had moderate improvement, 30% had mild improved, and there was no response in 5% of the patients by 4 weeks of treatment. No side effects were observed. CONCLUSION: This study demonstrates the efficacy and safety of this optimized topical 1.5% SA cream containing natural skin penetration enhancers in combination with antioxidant activity when applied twice daily for the reduction of facial acne; in particular, it is most effective for mild-to-moderate acne.

CRT combined with a sequential VMAT boost in the treatment of upper thoracic esophageal cancer.

The purpose of this study is to investigate the potential benefits of conformal radiotherapy (CRT) combined with a sequential volumetric-modulated arc therapy (VMAT) boost in the treatment of upper thoracic esophageal cancer. Ten patients with upper thoracic esophageal cancer previously treated with CRT plus a sequential VMAT boost plan were replanned with CRT plus an off-cord CRT boost plan and a full course of VMAT plan. Dosimetric parameters were compared. Results indicated that CRT plus off-cord CRT boost was inferior in planning target volume (PTV) coverage, as indicated by the volume covered by 93% (p = 0.05) and 95% (p = 0.02) of the prescription dose. The full course VMAT plan was superior in conformal index (CI) and conformation number (CN), and produced the highest protection for the spinal cord. CRT plus a VMAT boost demonstrated significant advantages in decreasing the volume of the lung irradiated by a dose of 10 Gy (V10, p = 0.007), 13 Gy (V13, p = 0.003), and 20 Gy (V20, p = 0.001). The full course VMAT plan demonstrated the lowest volume of lung receiving a dose of 30 Gy. CRT plus a VMAT boost for upper thoracic esophageal cancer can improve the target coverage and reduce the volume of lung irradiated by an intermediate dose. This combination may be a promising treatment technique for patients with upper thoracic esophageal cancer.

[Comparison of ArcCheck and film verification for VMAT in the treatment of nasopharyngeal carcinoma].

To compare the performance of ArcCheck and film verification for volumetric intensity modulated arc therapy (VMAT) in the treatment of nasopharyngeal carcinoma, and to study the feasibility of ArcCheck in VMAT dosimetric verification. Five patients of nasopharyngeal carcinoma treated with VMAT were enrolled in this study. Dose verification was carried out by ArcCheck and film respectively. The result showed that there were no significant differences between ArcCheck and film verification. ArcCheck software can obtain three dimensional dose distribution directly with simple operation. It is convenient for ArcCheck to be used for VMAT dosimetric verification.

Integrating plan complexity and dosiomics features with deep learning in patient-specific quality assurance for volumetric modulated arc therapy.

PURPOSE: To investigate the feasibility and performance of deep learning (DL) models combined with plan complexity (PC) and dosiomics features in the patient-specific quality assurance (PSQA) for patients underwent volumetric modulated arc therapy (VMAT). METHODS: Total of 201 VMAT plans with measured PSQA results were retrospectively enrolled and divided into training and testing sets randomly at 7:3. PC metrics were calculated using house-built algorithm based on Matlab. Dosiomics features were extracted and selected using Random Forest (RF) from planning target volume (PTV) and overlap regions with 3D dose distributions. The top 50 dosiomics and 5 PC features were selected based on feature importance screening. A DL DenseNet was adapted and trained for the PSQA prediction. RESULTS: The measured average gamma passing rate (GPR) of these VMAT plans was 97.94% ± 1.87%, 94.33% ± 3.22%, and 87.27% ± 4.81% at the criteria of 3%/3 mm, 3%/2 mm, and 2%/2 mm, respectively. Models with PC features alone demonstrated the lowest area under curve (AUC). The AUC and sensitivity of PC and dosiomics (D) combined model at 2%/2 mm were 0.915 and 0.833, respectively. The AUCs of DL models were improved from 0.943, 0.849, 0.841 to 0.948, 0.890, 0.942 in the combined models (PC + D + DL) at 3%/3 mm, 3%/2 mm and 2%/2 mm, respectively. A best AUC of 0.942 with a sensitivity, specificity and accuracy of 100%, 81.8%, and 83.6% was achieved with combined model (PC + D + DL) at 2%/2 mm. CONCLUSIONS: Integrating DL with dosiomics and PC metrics is promising in the prediction of GPRs in PSQA for patients underwent VMAT.

FOXK2 amplification and overexpression promotes breast cancer development and chemoresistance.

Activation of oncogenes through DNA amplification/overexpression plays an important role in cancer initiation and progression. Chromosome 17 has many cancer-associated genetic anomalies. This cytogenetic anomaly is strongly associated with poor prognosis of breast cancer. FOXK2 gene is located on 17q25 and encodes a transcriptional factor with a forkhead DNA binding domain. By integrative analysis of public genomic datasets of breast cancers, we found that FOXK2 is frequently amplified and overexpressed in breast cancers. FOXK2 overexpression in breast cancer patients is associated with poor overall survival. FOXK2 knockdown significantly inhibits cell proliferation, invasion and metastasis, and anchorage-independent growth, as well as causes G0/G1 cell cycle arrest in breast cancer cells. Moreover, inhibition of FOXK2 expression sensitizes breast cancer cells to frontline anti-tumor chemotherapies. More importantly, co-overexpression of FOXK2 and PI3KCA with oncogenic mutations (E545K or H1047R) induces cellular transformation in non-tumorigenic MCF10A cells, suggesting that FOXK2 is an oncogene in breast cancer and is involved in PI3KCA-driven tumorigenesis. Our study identified CCNE2, PDK1, and Estrogen receptor alpha (ESR1) as direct transcriptional targets of FOXK2 in MCF-7 cells. Blocking CCNE2- and PDK1-mediated signaling by using small molecule inhibitors has synergistic anti-tumor effects in breast cancer cells. Furthermore, FOXK2 inhibition by gene knockdown or inhibitors for its transcriptional targets (CCNE2 and PDK1) in combination with PI3KCA inhibitor, Alpelisib, showed synergistic anti-tumor effects on breast cancer cells with PI3KCA oncogenic mutations. In summary, we provide compelling evidence that FOXK2 plays an oncogenic role in breast tumorigenesis and targeting FOXK2-mediated pathways may be a potential therapeutic strategy in breast cancer.