Treatment plan complexity quantification for predicting gamma passing rates in patient-specific quality assurance for stereotactic volumetric modulated arc therapy.

PURPOSE: To investigate the beam complexity of stereotactic Volumetric Modulated Arc Therapy (VMAT) plans quantitively and predict gamma passing rates (GPRs) using machine learning. METHODS: The entire dataset is exclusively made of stereotactic VMAT plans (301 plans with 594 beams) from Varian Edge LINAC. The GPRs were analyzed using Varian's portal dosimetry with 2%/2 mm criteria. A total of 27 metrics were calculated to investigate the correlation between metrics and GPRs. Random forest and gradient boosting models were developed and trained to predict the GPRs based on the extracted complexity features. The threshold values of complexity metric were obtained to predict a given beam to pass or fail from ROC curve analysis. RESULTS: The three moderately significant values of Spearman's rank correlation to GPRs were 0.508 (p < 0.001), 0.445 (p < 0.001), and -0.416 (p < 0.001) for proposed metric LAAM, the ratio of the average aperture area over jaw area (AAJA) and index of modulation, respectively. The random forest method achieved 98.74% prediction accuracy with mean absolute error of 1.23% using five-fold cross-validation, and 98.71% with 1.25% for gradient boosting regressor method, respectively. LAAM, leaf travelling distance (LT), AAJA, LT modulation complexity score (LTMCS) and index of modulation, were the top five most important complexity features. The LAAM metric showed the best performance with AUC value of 0.801, and threshold value of 0.365. CONCLUSIONS: The calculated metrics were effective in quantifying the complexity of stereotactic VMAT plans. We have demonstrated that the GPRs could be accurately predicted using machine learning methods based on extracted complexity metrics. The quantification of complexity and machine learning methods have the potential to improve stereotactic treatment planning and identify the failure of QA results promptly.

Association between platelet counts and clinical outcomes in acute fatty liver of pregnancy: A retrospective cohort study.

OBJECTIVES: To investigate whether platelet counts are associated with clinical outcomes in patients with acute fatty liver of pregnancy (AFLP). METHODS: We retrospectively analyzed 140 patients with AFLP admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2010 and August 2022. In this cohort study, we used smooth curve fitting, Kaplan-Meier analysis, and multivariable logistic regression analysis to examine the independent relationship between platelet counts and 42-day postpartum mortality in AFLP. RESULTS: There were 140 patients with AFLP, of which 15 died and 53 (37.86%) had thrombocytopenia. The overall 42-day postpartum maternal mortality was 10.7%. We observed a U-shaped relationship between the platelet counts and 42-day postpartum mortality. Two different slopes were observed below and above the inflection point at approximately 220 × 109 /L. After adjusting for some confounders, patients with thrombocytopenia (<100 × 109 /L) were found to have increased 42-day postpartum mortality compared with middle-tertile and highest-tertile patients. Patients with thrombocytopenia had a higher 42-day postpartum mortality, and higher proportions of intensive care unit admissions, postpartum hemorrhage, and multiple organ failure (P < 0.05). CONCLUSIONS: A U-shaped association between platelet counts and 42-day postpartum mortality was observed in patients with AFLP. Thrombocytopenia is associated with poorer adverse clinical outcomes in women with AFLP.

Assessment of Blood Volume in Liposuction Fluids Using Colorimetry.

OBJECTIVE: The possibility of using a color contrast method to evaluate blood loss during liposuction was assessed. A color chart of blood-lipid content associated with different blood volumes was developed. METHODS: Three color cards with different concentrations of blood were developed based on clinical parameters. The color cards were used to evaluate the volume of blood present in liposuction solutions obtained from 60 clinical liposuction patients. The red blood cell count also was evaluated for each patient. The data obtained using each evaluation method were compared and statistically analyzed to determine the most accurate calculation formula. RESULTS: The red blood cell counts were compared to the color card results. The paired t test results for the calculated values for the 3:1, 2:1, and 1:1 color cards and the red blood cell count values were comparable (44.3 ± 22.1 ml vs. 53.6 ± 25.0 ml, t = 10.5; 45.4 ± 19.0 ml vs. 55.2 ± 20.7 ml, t = 18.1; 41.9 ± 25.6 ml vs. 52.8 ± 28.3 ml, t = 14.0). The P values were < 0.05, and the difference between the two groups was statistically significant. The average standard error of the mean was 0.90, 0.54, and 0.77, respectively. Sixty samples were evaluated in a scatter diagram using the two detection methods. Trend analysis revealed that the two results demonstrated a linear increase (y = 5.6 + 1.1x), R2 = 0.989, indicating that the two inspection methods were highly correlated with only small errors. CONCLUSION: The colorimetric card protocol developed in this study could quickly, accurately, and conveniently calculate blood volumes in liposuction fluids, which has considerable clinical significance. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Et4NCl-Promoted Electrochemical Atherton-Todd Type Reaction to Construct P(O)-F Bonds.

An electrochemical synthetic strategy to construct P(O)-F bonds was developed via the Atherton-Todd reaction. Promoted by Et4NCl, a series of biologically active phosphoric fluorides were synthesized by use of commercially available P(O)-H feedstocks and Et3N·3HF as the F-source. With this protocol, some potentially functional P(O)-OR and P(O)-SR motifs could also be smoothly forged. This sustainable fluorination approach features step-economy, is chemical-oxidant- and metal-catalyst-free, and offers low cost and mild conditions. Additionally, cyclic voltammetry and control experiments were conducted to propose a reasonable mechanism.

Network Pharmacology and Experimental Verification Strategies to Illustrate the Mechanism of Jian-Pi-Yi-Shen Formula in Suppressing Epithelial-Mesenchymal Transition.

Jian-Pi-Yi-Shen formula (JPYSF), a traditional Chinese medicine, has been recommended to treat renal fibrosis for decades. Previous studies had shown that JPYSF could inhibit epithelial-mesenchymal transition (EMT), an important regulatory role in renal fibrosis. However, the mechanism of JPYSF action is largely unknown. In this study, network pharmacology and experimental verification were combined to elucidate and identify the potential mechanism of JPYSF against renal fibrosis by suppressing EMT at molecular and pathway levels. Network pharmacology was first performed to explore the mechanism of JPYSF against renal fibrosis targeting EMT, and then a 5/6 nephrectomy (5/6 Nx)-induced rat model of renal fibrosis was selected to verify the predictive results by Masson's trichrome stains and western blot analysis. Two hundred and thirty-two compounds in JPYSF were selected for the network approach analysis, which identified 137 candidate targets of JPYSF and 4,796 known therapeutic targets of EMT. The results of the Gene Ontology (GO) function enrichment analysis included 2098, 88, and 133 GO terms for biological processes (BPs), molecular functions (MFs), and cell component entries, respectively. The top 10 enrichment items of BP annotations included a response to a steroid hormone, a metal ion, oxygen levels, and so on. Cellular composition (CC) is mainly enriched in membrane raft, membrane microdomain, membrane region, etc. The MF of JPYSF analysis on EMT was predominately involved in proximal promoter sequence-specific DNA binding, protein heterodimerization activity, RNA polymerase II proximal promoter sequence-specific DNA binding, and so on. The involvement signaling pathway of JPYSF in the treatment of renal fibrosis targeting EMT was associated with anti-fibrosis, anti-inflammation, podocyte protection, and metabolism regulation. Furthermore, the in vivo experiments confirmed that JPYSF effectively ameliorated interstitial fibrosis and inhibited the overexpression of α-SMA, Wnt3a, and ß-catenin, and increased the expression of E-cadherin by wnt3a/ß-catenin signaling pathway in 5/6 Nx-induced renal fibrosis rats. Using an integrative network pharmacology-based approach and experimental verification, the study showed that JPYSF had therapeutic effects on EMT by regulating multi-pathway, among which one proven pathway was the Wnt3a/ß-catenin signaling pathway. These findings provide insights into the renoprotective effects of JPYSF against EMT, which could suggest directions for further research of JPYSF in attenuating renal fibrosis by suppressing EMT.

Three-dimensional deep neural network for automatic delineation of cervical cancer in planning computed tomography images.

PURPOSE: Radiation therapy is an essential treatment modality for cervical cancer, while accurate and efficient segmentation methods are needed to improve the workflow. In this study, a three-dimensional V-net model is proposed to automatically segment clinical target volume (CTV) and organs at risk (OARs), and to provide prospective guidance for low lose area. MATERIAL AND METHODS: A total of 130 CT datasets were included. Ninety cases were randomly selected as the training data, with 10 cases used as the validation data, and the remaining 30 cases as testing data. The V-net model was implemented with Tensorflow package to segment the CTV and OARs, as well as regions of 5 Gy, 10 Gy, 15 Gy, and 20 Gy isodose lines covered. The auto-segmentation by V-net was compared to auto-segmentation by U-net. Four representative parameters were calculated to evaluate the accuracy of the delineation, including Dice similarity coefficients (DSC), Jaccard index (JI), average surface distance (ASD), and Hausdorff distance (HD). RESULTS: The V-net and U-net achieved the average DSC value for CTV of 0.85 and 0.83, average JI values of 0.77 and 0.75, average ASD values of 2.58 and 2.26, average HD of 11.2 and 10.08, respectively. As for the OARs, the performance of the V-net model in the colon was significantly better than the U-net model (p = 0.046), and the performance in the kidney, bladder, femoral head, and pelvic bones were comparable to the U-net model. For prediction of low-dose areas, the average DSC of the patients' 5 Gy dose area in the test set were 0.88 and 0.83, for V-net and U-net, respectively. CONCLUSIONS: It is feasible to use the V-Net model to automatically segment cervical cancer CTV and OARs to achieve a more efficient radiotherapy workflow. In the delineation of most target areas and OARs, the performance of V-net is better than U-net. It also offers advantages with its feature of predicting the low-dose area prospectively before radiation therapy (RT).

Cone Beam CT (CBCT) Based Synthetic CT Generation Using Deep Learning Methods for Dose Calculation of Nasopharyngeal Carcinoma Radiotherapy.

Objective: To generate synthetic CT (sCT) images with high quality from CBCT and planning CT (pCT) for dose calculation by using deep learning methods. Methods: 169 NPC patients with a total of 20926 slices of CBCT and pCT images were included. In this study the CycleGAN, Pix2pix and U-Net models were used to generate the sCT images. The Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), Peak Signal to Noise Ratio (PSNR), and Structural Similarity Index (SSIM) were used to quantify the accuracy of the proposed models in a testing cohort of 34 patients. Radiation dose were calculated on pCT and sCT following the same protocol. Dose distributions were evaluated for 4 patients by comparing the dose-volume-histogram (DVH) and 2D gamma index analysis. Results: The average MAE and RMSE values between sCT by three models and pCT reduced by 15.4 HU and 26.8 HU at least, while the mean PSNR and SSIM metrics between sCT by different models and pCT added by 10.6 and 0.05 at most, respectively. There were only slight differences for DVH of selected contours between different plans. The passing rates of 2D gamma index analysis under 3 mm/3% 3 mm/2%, 2 mm/3%and 2 mm/2% criteria were all higher than 95%. Conclusions: All the sCT had achieved better evaluation metrics than those of original CBCT, while the performance of CycleGAN model was proved to be best among three methods. The dosimetric agreement confirmed the HU accuracy and consistent anatomical structures of sCT by deep learning methods.

AIScaffold: A Web-Based Tool for Scaffold Diversification Using Deep Learning.

Molecular scaffolds are widely used in drug design. Many methods and tools have been developed to utilize the information in scaffolds. Scaffold diversification is frequently used by medicinal chemists in tasks such as lead compound optimization, but tools for scaffold diversification are still lacking. Here, we propose AIScaffold (https://iaidrug.stonewise.cn), a web-based tool for scaffold diversification using the deep generative model. This tool can perform large-scale (up to 500,000 molecules) diversification in several minutes and recommend the top 500 (top 0.1%) molecules. Features such as site-specific diversification are also supported. This tool can facilitate the scaffold diversification process for medicinal chemists, thereby accelerating drug design.

[Erectile dysfunction and psychological status in infertile males].

OBJECTIVE: To investigate the relationship of erectile dysfunction (ED) with psychological factors in male patients with infertility. METHODS: We conducted a questionnaire investigation among 252 male patients with infertility, which involved the general condition, results of semen routine examination, sexual life, and scores in IIEF-5, self-reported 9-item patient health questionnaire (PHQ-9) and 7-item generalized anxiety disorder scale (GAD-7). We analyzed the prevalence of ED, depression, and anxiety and their correlations among the patients in comparison with 100 fertile male controls. RESULTS: In 245 of the infertility patients, the most common symptoms of depression and anxiety were "feeling tired or no vitality" and "easily getting worried or impatient", 20.4% of them with depression disorder and 42.9% with anxiety disorder. The PHQ-9 and GAD-7 scores were significantly higher in the infertile males than in the normal fertile controls (P <0.05), and so was the incidence of ED (28.6% vs 12.4%, P <0.05), while the IIEF-5 scores were markedly lower in the former than in the latter group (P <0.01), and so were sex frequency and sexual satisfaction (P <0.05). The PHQ-9 and GAD-7 scores were remarkably higher in the infertility patients with ED than in those without (P <0.01). Logistic regression analysis showed that the level of libido and results of semen routine examination were the risk factors for depression disorder, while age, education level, disease course and experience of assisted reproduction were those for anxiety disorder. CONCLUSIONS: Male infertility patients have a poorer mental health and a higher incidence of ED than normal fertile men, and there is some interaction between psychological status and ED prevalence.

Anti-angiogenic effect of triptolide in rheumatoid arthritis by targeting angiogenic cascade.

Rheumatoid arthritis (RA) is characterized by a pre-vascular seriously inflammatory phase, followed by a vascular phase with high increase in vessel growth. Since angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses, as well as supporting pannus growth and development of RA, inhibition of angiogenesis has been proposed as a novel therapeutic strategy for RA. Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, has been extensively used in treatment of RA patients. It also acts as a small molecule inhibitor of tumor angiogenesis in several cancer types. However, it is unclear whether triptolide possesses an anti-angiogenic effect in RA. To address this problem, we constructed collagen-induced arthritis (CIA) model using DA rats by the injection of bovine type II collagen. Then, CIA rats were treated with triptolide (11-45 µg/kg/day) starting on the day 1 after first immunization. The arthritis scores (P<0.05) and the arthritis incidence (P<0.05) of inflamed joints were both significantly decreased in triptolide-treated CIA rats compared to vehicle CIA rats. More interestingly, doses of 11~45 µg/kg triptolide could markedly reduce the capillaries, small, medium and large vessel density in synovial membrane tissues of inflamed joints (all P<0.05). Moreover, triptolide inhibited matrigel-induced cell adhesion of HFLS-RA and HUVEC. It also disrupted tube formation of HUVEC on matrigel and suppressed the VEGF-induced chemotactic migration of HFLS-RA and HUVEC, respectively. Furthermore, triptolide significantly reduced the expression of angiogenic activators including TNF-α, IL-17, VEGF, VEGFR, Ang-1, Ang-2 and Tie2, as well as suppressed the IL1-ß-induced phosphorylated of ERK, p38 and JNK at protein levels. In conclusion, our data suggest for the first time that triptolide may possess anti-angiogenic effect in RA both in vivo and in vitro assay systems by downregulating the angiogenic activators and inhibiting the activation of mitogen-activated protein kinase downstream signal pathway.

Wen Luo Yin inhibits angiogenesis in collagen-induced arthritis rat model and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Wen Luo Yin (WLY) is a traditional Chinese formula, which has the traditional use of scattering cold pathogen, draining dampness, freeing the flow of network vessels and relieving pains. It is extensively used in the treatment of rheumatoid arthritis (RA) patients for more than 2000 years, but its actions on angiogenesis of RA have not been clarified. The present study aims to determine the anti-angiogenic activity of WLY on collagen-induced arthritis (CIA) rat model and in human fibroblast-like synoviocytes of RA (HFLS-RA) and human umbilical vein endothelial cells (HUVEC). MATERIALS AND METHODS: For in vivo experiment, arthritis was induced by immunization with bovine II collagen in DA rats. Treatment with WLY (3.45, 6.9, 13.8 g/kg, p.o., daily), or vehicle began from day 1 to day 28 of first immunization. The arthritis score, arthritis incidence, microfocal computed tomography analysis and histopathology evaluation of inflamed joints were assessed. Angiogenesis was measured by synovial vessel density with immunohistochemistry and histomorphometric analysis in synovial membrane tissues of joints. For in vitro experiments, HFLS-RA and HUVEC were used. Assays to determine HFLS-RA migration and adhesion were performed in the presence of vascular endothelial growth factor (VEGF)165 or interleukin (IL)-1ß and/or the WLY (8, 16, 32 mg/ml). Angiogenesis was assessed by measuring the migration, adhesion, and tube formation of HUVEC. Further the effect of treatment with WLY on expression levels of angiogenic activators in sera of CIA rats and in IL-1ß-induced HFLS-RA were evaluated by enzyme linked immunosorbent assay. RESULTS: WLY significantly decreased the arthritis score and arthritis incidence, and inhibited inflammation, pannus formation, cartilage and bone destruction of inflamed joints in CIA rats. More interestingly, doses of 3.45-13.8 g/kg WLY could markedly reduce the capillaries, small, medium and large vessel density in synovial membrane tissues of inflamed joints. Moreover, WLY suppressed the VEGF-induced chemotactic migration of HFLS-RA and HUVEC, and inhibited matrigel-induced cell adhesion of them. It also disrupted tube formation of HUVEC on matrigel. Furthermore, WLY significantly reduced the expression of angiogenic activators including tumor necrosis factor-α, IL-1ß, IL-17, VEGF, VEGFR, angiopoietin (Ang)-1, Ang-2 and Ang-2 receptor in sera of CIA rats and/or in IL-1ß-induced HFLS-RA/HUVEC. CONCLUSIONS: Our data suggest for the first time that WLY posses the anti-angiogenic effect in RA both in vivo and in vitro by downregulating angiogenic activators.

[Comparative study of effect of Atractylodes lancea between geo-authentic and non-authentic producing areas on collagen-induced arthritis in rats].

OBJECTIVE: To compare the effects of Atractylodes lancea from different producing area on collagen-induced arthritis (CIA) in rats. METHOD: Wistar rats were induced by type II bovine collagen. CIA rats were treated daily with oral administration of A. lancea from the geo-authentic and non-authentic producing area of Maoshan, Jiangsu province, and non-geo-authentic and non-authentic producing areas of Yingshan, Hubei province and Huayin, Shanxi province from day 7 after the day of the first immunization to day 35. Clinical symptoms as well as clinical scores and incidence were observed. All rats were sacrificed on day 35 after immunization to observe histopathologic and radiologic changes. Antibody to type II collagen in sera was measured by enzyme-linked immunosorbent assay (ELISA), the levels of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in sera and article-homogenated supernants by radiommunoassay, and inflammatory mediator of PGE2 in sera using ELISA. RESULT: A. lancea from Jiangsu province can ameliorate clinical symptom, reduce arthritis index and arthropathy of inflammatory joints, inhibit the production of IgG and IgM in sera, directly suppress the production of exogenous and endogenous cytokines of IL-1beta, TNFalpha and IL-6 and PGE2. A. lances from Hubei and Shanxi provinces can inhibit the production of IgM in sera, and A. lanceas from Hubei province also depress the production of IL-1beta in sera and IL-6 in supernants. CONCLUSION: A. lancea from Jiangsu province is effective in CIA rats through inhibiting the production of pro-inflammatory cytokines and the inflammatory mediators.

[Effect of tadalafil therapy upon penile cavernous tissues in spontaneously hypertensive rats].

UNLABELLED: OBJECTIVE; To observe the plasma concentration change of endothelin-1 (ET-1) and the histomorphological changes in penile cavernous body after administrating a continuous low dose of tadalafil into spontaneously hypertensive rats (SHR). METHODS: Forty SHR rats were randomly divided into four groups of blank group, placebo group, continuous low-dose group and intermittent dose group with 10 rats in each. The animals were administrated with different doses of tadalafil via an intragastric route. To observe the plasma concentration change of ET-1 and cellular morphological changes of penile cavernous tissue in SHR after four weeks, the immunohistochemical method of SABC was employed to detect the expression of alpha-smooth muscle actin (alpha-SMA) in penile corpora cavernous of different groups. RESULTS: The plasma levels of ET-1 were lower in continuous low dose group (12.0 +/- 1.6) and intermittent dose group (14.3 +/- 1.7) as compared with the blank (18.0 +/- 1.9) and placebo groups (17.6 +/- 2.2) (all P < 0.01). And there was significant difference between the continuous low dose and intermittent dose groups (P < 0.05). The A-value level of absorbance in alpha-SMA were significantly different with the blank (0.53 +/- 0.03) and placebo groups (0.52 +/- 0.05) (P > 0.05) and it was lower in the continuous low dose group (0.29 +/- 0.03) than the intermittent dose group (0.38 +/- 0.03) (P < 0.05). It can be observed microscopically that in blank group and placebo group: endothelial cell and vascular smooth muscle cells of penile cavernous tissue in SHR had a disorderly distribution. The disrupted continuity and integrity of endothelial cell were also found. And they improved in continuous low dose group and intermittent dose group, especially the former; it can be viewed under TEM that the endothelial cells of penile cavernous tissue in SHR had mostly reverted to normal condition in the continuous low dose group and its ultra-structure indicated that the tissue morphology improved. CONCLUSION: A continuous low dose of tadalafil can improve the function and structure of vascular endothelium in penile cavernous body. Thus it provides rationales for a continuous low dose of PDE5 inhibitor in the treatment of erectile dysfunction.

[Etiology, diagnosis and management of spontaneous per renal hemorrhage].

OBJECTIVE: To investigate the etiology, diagnosis, and management of spontaneous perirenal hemorrhage (SPH). METHODS: The clinical data of 35 patients, 10 males and 12 females, aged 35.9 (12-77), with the diagnosis of SPH, without history of trauma, anticoagulant use, dialysis, and renal transplantation, were analyzed. RESULTS: The underlying disease of SPH included angiomyolipoma (18 cases), renal cell carcinoma (7 cases), kidney cyst (2 cases), renal artery aneurysm (3 cases), rupture of renal artery aneurysm accompanied with pregnancy (2 cases), renal pheochromocytoma (3 cases 2 of which accompanied with pregnancy), congenital stricture of pelvic ureter junction (1 case), and liver cancer (1 case). The most common underlying diseases were nephrogenic (96%) with angiomyolipoma ranking first (54%) followed by renal cell carcinoma (21%). The underlying diseases were diagnosed correctly in 23 cases (69%). CT helped in diagnosis of 34 cases. Surgery was performed on most of the cases. CONCLUSION: The most common causes of SPH is renal neoplasms more than 50% of which are benign. Renal artery aneurysm and pheochromocytoma tend to rupture during pregnancy. CT is the first method of choice in diagnosis.

Effect of ultrasound on desorption kinetics of phenol from polymeric resin.

This work mainly involves the study of desorption kinetics of phenol from polymeric resins under the influence of an ultrasound field. A new phase equilibrium-kinetics model (PEKM), for estimation of diffusion coefficient was proposed, kinetic experiments of phenol desorption on NKA-II resin in the presence and the absence of ultrasound were separately conducted, and diffusion coefficients of phenol within an adsorbent particle were estimated by means of proposed PEKM. Results showed that the use of ultrasound could enhance the diffusion of phenol within the resin. The diffusion coefficient of phenol in the resin in an ultrasonic field increased by an order of magnitude in comparison with the diffusion coefficient in the absence of ultrasound. The more intense the ultrasonic field the larger was the diffusion coefficient.