Feasibility and safety of contrast-enhanced magnetic resonance-guided adaptive radiotherapy for upper abdominal tumors: A preliminary exploration.

This study investigates the use of contrast-enhanced magnetic resonance (MR) in MR-guided adaptive radiotherapy (MRgART) for upper abdominal tumors. Contrast-enhanced T1-weighted MR (cT1w MR) using half doses of gadoterate was used to guide daily adaptive radiotherapy for tumors poorly visualized without contrast. The use of gadoterate was found to be feasible and safe in 5-fraction MRgART and could improve the contrast-to-noise ratio of MR images. And the use of cT1w MR could reduce the interobserver variation of adaptive tumor delineation compared to plain T1w MR (4.41 vs. 6.58, p < 0.001) and T2w MR (4.41 vs. 7.42, p < 0.001).

Changes in plasma concentrations of per- and Polyfluoroalkyl substances after bariatric surgery in adolescents from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study.

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate longitudinal changes in plasma-PFAS after the time of bariatric surgery. This study included 214 adolescents with severe obesity who had available longitudinal measures of plasma-PFAS and underwent bariatric surgery between 2007 and 2012. Underlying effects related to undergoing bariatric surgery were found to be associated with an initial increase or plateau in concentrations of circulating PFAS up to 6 months after surgery followed by a persistent decline in concentrations of 36 months (p < 0.001 for all plasma-PFAS). Bariatric surgery in adolescents was associated with a decline in circulating PFAS concentrations. Initially following bariatric surgery (0-6 months) concentrations were static followed by decline from 6 to 36 months following surgery. This may have large public health implications as PFAS are known to be associated with numerous metabolic related diseases and the significant reduction in circulating PFAS in individuals who have undergone bariatric surgery may be related to the improvement of such metabolic related diseases following bariatric surgery.

Establishment of human acute monocytic leukemia model with systemic infiltration in NPG mice.

A model construction of systemic acute leukemia is challenging. Herein, we established a systemic leukemia mouse model using highly immunodeficient NPG mice without any immunosuppressive treatments. NPG mice received tail intravenous injection of SHI-1 cells at the concentration of 1×107 cells (group A) or 5×107 cells (group B) and randomly sacrificed each seven days post-inoculation. Tumor development was monitored using nested-PCR, peripheral blood-smear analysis, flow cytometry, pathological examinations, and immunohistochemistry. The median survival of mice in groups A and B were 33.0 and 30.0 days, respectively. Blast cells in peripheral blood appeared on day 14 in group B, and on day 21 in group A. In addition, SHI-1 cell specific MLL-AF6 mRNA was detected in both spleen and bone marrow on day 14 post-inoculation. 21 days after inoculation, we observed human CD45+CD33+ cells with an SH-1-immunophenotype in the peripheral blood, spleen, and bone marrow, as well as solid neoplasms in multiple organs. Moreover, the histologically infiltrated leukemic cells expressed CD45. In conclusion, the current study demonstrated the normal growth of SHI-1 cells in the NPG mice without immunosuppression, which caused systemic leukemia similar to that observed in acute leukemia patients. We developed an efficient and reproducible model to study leukemia pathogenesis and progression.

In situ anchored ternary hierarchical hybrid nickel@cobaltous sulfide on poly(3,4-ethylenedioxythiophene)-reduced graphene oxide for highly efficient non-enzymatic glucose sensing.

A ternary hierarchical hybrid Ni@CoxSy/poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@CoxSy/PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@CoxSy/PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@CoxSy/PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.2 µM ~ 2.0 mM) with high sensitivity (1546.32 µA cm-2 mM-1), a rapid response time (5 s), an ultralow detection limit (0.094 µM), superior anti-interference performance, excellent reproducibility and considerable stability. Furthermore, the sensor demonstrates an acceptable accuracy and appreciable recoveries ranging from 90.0 to 102.0% with less than 3.98% RSD in human blood serum samples, indicating the prospect of the sensor for the real samples analysis. It will provide a strategy to rationally design and fabricate ternary hierarchical hybrid as nanozyme for glucose assay.

Rapamycin increases leukemia cell sensitivity to chemotherapy by regulating mTORC1 pathway-mediated apoptosis and autophagy.

This study investigated the effect of rapamycin alone and in combination with chemotherapy (doxorubicin and cytarabine) on AML. Human acute monocytic leukemia cell line SHI-1 and NPG AML model mice created by intravenous injection of SHI-1 cell were treated with rapamycin, chemotherapy, or rapamycin plus chemotherapy. Analysis by cell counting kit-8, western blot, flow cytometry, and immunohistochemistry was performed, and results suggested that both rapamycin and chemotherapy inhibited proliferation of SHI-1 cells both in vitro and in vivo, suppressed neoplasm growth in vivo, and promoted survival of NPG AML mice. The antitumor effect of rapamycin plus chemotherapy was better than that of rapamycin alone and chemotherapy alone. In addition, western blot results demonstrated that rapamycin inhibited the phosphorylation of mTOR downstream targets 4EBP1 and S6K1 in SHI-1 cells, and increased the pro-apoptosis-related protein Bax and autophagy-associated proteins Beclin-1, LC3B-II, and ATG5 while reducing the anti-apoptosis-related protein Bcl-2. In conclusion, the results of this study indicate that rapamycin acts synergistically with doxorubicin and cytarabine in AML treatment, and its underlying mechanism might be associated with mTORC1 pathway-mediated apoptosis and autophagy.

Exposure to 4,4'-DDE in visceral adipose tissue and weight loss in adolescents from the Teen-LABS cohort.

OBJECTIVE: Dichlorodiphenyldichloroethylene (DDE), an obesogen accumulating in adipose tissue, is released into circulation with weight loss, although its impact is underexplored among adolescents. We tested the association using an integrative translational approach of epidemiological analysis among adolescents with obesity and in vitro measures exploring the impact of DDE on adipogenesis via preadipocytes. METHODS: We included 63 participants from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. We assessed 4,4'-DDE in visceral adipose tissue at surgery and BMI and waist circumference at surgery and 0.5, 1, 3, and 5 years after. We conducted longitudinal analysis to estimate the interaction on weight loss between DDE and time since surgery. In vitro analysis quantified adipogenic differentiation in commercial human preadipocytes exposed to 4,4'-DDE via fluorescent staining and imaging. RESULTS: A dose-response relationship was observed, with the low-exposure group having a greater reduction in BMI during the first year compared to higher-exposure groups and showing smaller regains compared to higher-exposure groups after the first year. In vitro analysis of preadipocytes treated with 4,4'-DDE during adipogenic differentiation for 12 days showed a concentration-dependent increase in lipid accumulation. CONCLUSIONS: DDE could contribute to weight trajectory among adolescents undergoing bariatric surgery, potentially mediated via promoted adipogenesis in preadipocytes.

A virtual phantom for patient-specific QA On A 1.5T MR-linac.

Create a virtual ArcCHECK-MR phantom, customized for a 1.5T MR-linac, with consideration of the different density regions within the quality assurance (QA) phantom, aiming to streamline the utilization of this specialized QA device. A virtual phantom was constructed in the treatment planning system (TPS) to replicate the ArcCHECK-MR's composition, consisting of five distinct layers: "Outer" (representing the outer PMMA ring), "Complex" (simulating the printed circuit boards), "Detectors" (encompassing the detector area), "Inner" (signifying the inner PMMA ring) and "Insert" (representing the PMMA insert). These layers were defined based on geometric data and represented as contour points on a set of dummy CT images. Additionally, a setup platform was integrated as contoured structures. To determine the relative electron density (RED) values of the external and internal PMMA components, measurements were taken at 25 points in the insert using an ion chamber. A novel method for establishing the exit/entrance dose ratio (EEDR) for ArcCHECK-MR was introduced. The RED of higher density region was derived by evaluating the local gamma index passing rate results with criteria of 2% dose difference and 2 mm distance-to-agreement. The performance of the virtual phantom was assessed for Unity 7 FFF beams with a 1.5T magnetic field. The radii of the five ring structures within the virtual phantom measured 133.0 mm, 110.0 mm, 103.4 mm, 100.0 mm, and 75.0 mm for the "Outer," "Complex," "Detectors," "Inner" and "Insert" regions, respectively. The RED values were as follows: ArcCHECK-MR PMMA had a RED of 1.130, "Detectors" were assumed to have a RED of 1.000, "Complex" had a RED of 1.200, and the setup QA phantom justified a RED of 1.350. Early validation results demonstrate that the 5-layer virtual phantom, when compared to the commonly used bulk overridden phantom, offers improved capability in MR-linac environments. This enhancement led to an increase in passing rates for the local gamma index by approximately 5 ∼ 6%, when applying the criteria of 2%, 2 mm. We have successfully generated a virtual representation of the distinct regions within the ArcCHECK-MR using a TPS, addressing the challenges associated with its use in conjunction with a 1.5T MR-linac. We consistently observed favorable local gamma index passing rates across two 1.5T MR-linac and ArcCHECK-MR unit combinations. This approach has the potential to minimize uncertainties in the creation of the QA phantom for ArcCHECK-MR across various institutions.

Assessing the Impact of a 1.5†T Transverse Magnetic Field in Radiotherapy for Esophageal Cancer Patients.

Purpose: Magnetic resonance (MR)-guided radiotherapy enables visualization of static anatomy, capturing tumor motion, and extracting quantitative image features for treatment verification and outcome monitoring. However, magnetic fields in online MR imaging (MRI) require efforts to ensure accurate dose measurements. This study aimed to assess the dosimetric impact of a 1.5 T magnetic field in esophageal cancer radiotherapy using MR-linac, exploring treatment adaptation potential and personalized medicine benefits. Methods: A prospective cohort study enrolled 100 esophageal squamous cell carcinoma patients undergoing 4DCT and 3DCT scans before radiotherapy. The heart was contoured on 3DCT, 4DCT end expiration (EE), and 4DCT end inhalation (EI) images by the same radiation oncologist. Reference RT plans were designed on 3DCT, with adjustments for different phases generating 5 plan types per patient. Variations in dose-volume parameters for organs at risk and the target area among different plans were compared using Monaco 5.40.04. Results: Slight dose distortions at air-tissue interfaces were observed in the magnetic field's presence. Dose at air-tissue interfaces (chest wall and heart wall) was slightly higher in some patients (3.0% tissue increased by 4.3 Gy on average) compared to nonmagnetic conditions. Average clinical target volume coverage V100 dropped from 99% to 95% compared to reference plans (planEI and planEE). Dose-volume histogram variation between the original plan and reference plans was within 2.3%. Superior-inferior (SI) direction displacement was significantly larger than lateral and anterior-posterior directions (P < .05). Conclusion: Significant SI direction shift in lower esophageal cancerous regions during RT indicates the magnetic field's dosimetric impact, including the electron return effect at tissue-air boundaries. Changes in OAR dose could serve as valuable indicators of organ impairment and target dose alterations, especially for cardiac tissue when using the 1.5 T linac method. Reoptimizing the plan with the magnetic field enhances the feasibility of achieving a clinically acceptable treatment plan for esophageal cancer patients.

CT synthesis from MR images using frequency attention conditional generative adversarial network.

Magnetic resonance (MR) image-guided radiotherapy is widely used in the treatment planning of malignant tumors, and MR-only radiotherapy, a representative of this technique, requires synthetic computed tomography (sCT) images for effective radiotherapy planning. Convolutional neural networks (CNN) have shown remarkable performance in generating sCT images. However, CNN-based models tend to synthesize more low-frequency components and the pixel-wise loss function usually used to optimize the model can result in blurred images. To address these problems, a frequency attention conditional generative adversarial network (FACGAN) is proposed in this paper. Specifically, a frequency cycle generative model (FCGM) is designed to enhance the inter-mapping between MR and CT and extract more rich tissue structure information. Additionally, a residual frequency channel attention (RFCA) module is proposed and incorporated into the generator to enhance its ability in perceiving the high-frequency image features. Finally, high-frequency loss (HFL) and cycle consistency high-frequency loss (CHFL) are added to the objective function to optimize the model training. The effectiveness of the proposed model is validated on pelvic and brain datasets and compared with state-of-the-art deep learning models. The results show that FACGAN produces higher-quality sCT images while retaining clearer and richer high-frequency texture information.

Regeneration of Thyroid Glands in the Spleen Restores Homeostasis in Thyroidectomy Mice.

Surgical removal of the thyroid gland (TG) for treating thyroid disorders leaves the patients on lifelong hormone replacement that partially compensates the physiological needs, but regenerating TG is challenging. Here, an approach is reported to regenerate TG within the spleen for fully restoring the thyroid's functions in mice, by transplanting thyroid tissue blocks to the spleen. Within 48 h, the transplanted tissue efficiently revascularizes, forming thyroid follicles similar to the native gland after 4 weeks. Structurally, the ectopically generated thyroid integrates with the surrounding splenic tissue while maintaining its integrity, separate from the lymphatic tissue. Functionally, it fully restores the native functions of the TG in hormone regulation in response to physiological stimuli, outperforming the established method of oral levothyroxine therapy in maintaining systemic homeostasis. The study demonstrates the full restoration of thyroid functions post-thyroidectomy by intrasplenic TG regeneration, providing fresh insights for designing novel therapies for thyroid-related disorders.

Influence and optimization strategy of the magnetic field in 1.5 T MR-linac liver stereotactic radiotherapy.

OBJECTIVE: To compare intensity reduction plans for liver cancer with or without a magnetic field and optimize field and subfield numbers in the intensity-modulated radiotherapy (IMRT) plans designed for liver masses in different regions. METHODS: This retrospective study included 62 patients who received radiotherapy for liver cancer at Shandong Cancer Hospital. Based on each patient's original individualized intensity-modulated plan (plan1.5 T), a magnetic field-free plan (plan0 T) and static intensity-modulated plan with four different optimization schemes were redesigned for each patient. The differences in dosimetric parameters among plans were compared. RESULTS: In the absence of a magnetic field in the first quadrant, PTV Dmin increased (97.75 ± 17.55 vs. 100.96 ± 22.78)%, Dmax decreased (121.48 ± 29.68 vs. 119.06 ± 28.52)%, D98 increased (101.35 ± 7.42 vs. 109.35 ± 26.52)% and HI decreased (1.14 ± 0.14 vs. 1.05 ± 0.01). In the absence of a magnetic field in the second quadrant, PTV Dmin increased (84.33 ± 19.74 vs. 89.96 ± 21.23)%, Dmax decreased (105 ± 25.08 vs. 104.05 ± 24.86)%, and HI decreased (1.04 ± 0.25 vs. 0.99 ± 0.24). In the absence of a magnetic field in the third quadrant, PTV Dmax decreased (110.21 ± 2.22 vs. 102.31 ± 26)%, L-P V30 decreased (10.66 ± 9.19 vs. 5.81 ± 3.22)%, HI decreased (1.09 ± 0.02 vs. 0.98 ± 0.25), and PTV Dmin decreased (92.12 ± 4.92 vs. 89.1 ± 22.35)%. In the absence of a magnetic field in the fourth quadrant, PTV Dmin increased (89.78 ± 6.72 vs. 93.04 ± 4.86)%, HI decreased (1.09 ± 0.01 vs. 1.05 ± 0.01) and D98 increased (99.82 ± 0.82 vs. 100.54 ± 0.84)%. These were all significant differences. In designing plans for tumors in each liver region, a total number of subfields in the first area of 60, total subfields in the second zone of 80, and total subfields in the third and fourth zones of 60 or 80 can achieve the dose effect without a magnetic field. CONCLUSION: In patients with liver cancer, the effect of a magnetic field on the target dose is more significant than that on doses to organs at risk. By controlling the max total number of subfields in different quadrants, the effect of the magnetic field can be greatly reduced or even eliminated.

Case Report: MR-LINAC-guided adaptive radiotherapy for gastric cancer.

Background: The stomach is one of the most deformable organs. Its shape can be easily affected by breathing movements, and daily diet, and it also varies when the body position is different. The susceptibility of stomach has made it challenging to treat gastric cancer using the conventional image-guided radiotherapy, i.e., the techniques based on kilovoltage X-ray imaging. The magnetic resonance imaging guided radiotherapy (MRgRT) is usually implemented using a hybrid system MR-LINAC. It is feasible to implement adaptive radiotherapy using MR-LINAC for deformable organs such as stomach. In this case report, we present our clinical experience to treat a gastric cancer patient using MR-LINAC. Case description: The patient is a 58-year-old male who started having black stools with no apparent cause a year ago. Gastroscopy result showed pancreatic cancer, pathology: adenocarcinoma on gastric cancer biopsy, adenocarcinoma on gastric body minor curvature biopsy. The patient was diagnosed with gastric cancer (adenocarcinoma, cTxN+M1, stage IV, HER-2 positive). The patient was treated in 25 fractions with radiotherapy using MR-LINAC with online adaptive treatment plans daily. The target area in daily MR images varied considerably when compared with the target area on the CT simulation images. During the course of treatment, there have even been instances where the planned target area where the patient received radiotherapy did not cover the lesion of the day. Conclusion: Online adaptive MRgRT can be a meaningful innovation for treating malignancies in the upper abdomen. The results in the current study are promising and are indicative for further optimizing online adaptive MRgRT in patients with inoperable tumors of the upper abdomen.

Transhepatectomy combined with arterial chemoembolization and transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a clinical prognostic analysis.

BACKGROUND: The prognosis of patients undergoing hepatectomy combined with transarterial chemoembolization (TACE) and TACE alone was examined in order to better understand the role of hepatectomy in the treatment of hepatocellular carcinoma (HCC). In this work, we also created a model and investigated the variables influencing overall survival (OS) in HCC patients. METHODS: Retrospective analysis of 1083 patients who received TACE alone as the control group and 188 patients who received TACE after surgery in a total of 1271 HCC patients treated with LR + TACE or TACE at three third-class hospitals in China. It was done using the Propensity Score Matching (PSM) technique. The differences in OS between the two groups were compared, and OS-influencing factors were looked at. The main endpoint is overall survival. In this study, the COX regression model was used to establish the nomogram. RESULTS: The median OS of the LR + TACE group was not attained after PSM. The median OS for the TACE group was 28.8 months (95% CI: 18.9-38.7). The median OS of the LR + TACE group was higher than that of the TACE group alone, indicating a significant difference between the two groups (χ2 = 16.75, P < 0.001). While it was not achieved in the LR + TACE group, the median OS for patients with lymph node metastases in the TACE group alone was 18.8 months. The two groups differed significantly from one another (χ2 = 4.105, P = 0.043). In patients with distant metastases, the median OS of the LR + TACE treatment group was not achieved, and the median OS of the TACE group alone was 12.0 months. The difference between the two groups was sizable (χ2 = 5.266, P = 0.022). The median OS for patients with PVTT following PSM was 30.1 months in the LR + TACE treatment group and 18.7 months in the TACE alone group, respectively. The two groups differed significantly from one another (χ2 = 5.178, P = 0.023); There was no discernible difference between the two groups in terms of median overall survival (OS), which was 30.1 months for patients with lymph node metastasis and 19.2 months for those without (P > 0.05); Regarding the median OS for patients with distant metastases, which was not achieved and 8.5 months, respectively, there was a significant difference between the two groups (χ2 = 5.759, P = 0.016). We created a new nomogram to predict 1-, 2-, and 3-year survival rates based on multiple independent predictors in COX multivariate analysis. The cohort's C-index is 0.705. The area under the curve (AUC value) for predicting 1-, 2-, and 3-year survival rates were shown by the subject operating characteristic (ROC) curve linked to the nomogram to be 0.730, 0.728, and 0.691, respectively. CONCLUSIONS: LR + TACE can increase OS, delay tumor recurrence, and improve prognosis in HCC patients when compared to TACE alone. Additionally, the nomogram we created does a good job of forecasting the 1-year survival rate of hepatocellular carcinoma.

Using RegGAN to generate synthetic CT images from CBCT images acquired with different linear accelerators.

BACKGROUND: The goal was to investigate the feasibility of the registration generative adversarial network (RegGAN) model in image conversion for performing adaptive radiation therapy on the head and neck and its stability under different cone beam computed tomography (CBCT) models. METHODS: A total of 100 CBCT and CT images of patients diagnosed with head and neck tumors were utilized for the training phase, whereas the testing phase involved 40 distinct patients obtained from four different linear accelerators. The RegGAN model was trained and tested to evaluate its performance. The generated synthetic CT (sCT) image quality was compared to that of planning CT (pCT) images by employing metrics such as the mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM). Moreover, the radiation therapy plan was uniformly applied to both the sCT and pCT images to analyze the planning target volume (PTV) dose statistics and calculate the dose difference rate, reinforcing the model's accuracy. RESULTS: The generated sCT images had good image quality, and no significant differences were observed among the different CBCT modes. The conversion effect achieved for Synergy was the best, and the MAE decreased from 231.3 ± 55.48 to 45.63 ± 10.78; the PSNR increased from 19.40 ± 1.46 to 26.75 ± 1.32; the SSIM increased from 0.82 ± 0.02 to 0.85 ± 0.04. The quality improvement effect achieved for sCT image synthesis based on RegGAN was obvious, and no significant sCT synthesis differences were observed among different accelerators. CONCLUSION: The sCT images generated by the RegGAN model had high image quality, and the RegGAN model exhibited a strong generalization ability across different accelerators, enabling its outputs to be used as reference images for performing adaptive radiation therapy on the head and neck.

Online prediction for respiratory movement compensation: a patient-specific gating control for MRI-guided radiotherapy.

BACKGROUND: This study aims to validate the effectiveness of linear regression for motion prediction of internal organs or tumors on 2D cine-MR and to present an online gating signal prediction scheme that can improve the accuracy of MR-guided radiotherapy for liver and lung cancer. MATERIALS AND METHODS: We collected 2D cine-MR sequences of 21 liver cancer patients and 10 lung cancer patients to develop a binary gating signal prediction algorithm that forecasts the crossing-time of tumor motion traces relative to the target threshold. Both 0.4 s and 0.6 s prediction windows were tested using three linear predictors and three recurrent neural networks (RNNs), given the system delay of 0.5 s. Furthermore, an adaptive linear regression model was evaluated using only the first 30 s as the burn-in period, during which the model parameters were adapted during the online prediction process. The accuracy of the predicted traces was measured using amplitude metrics (MAE, RMSE, and R2), and in addition, we proposed three temporal metrics, namely crossing error, gating error, and gating accuracy, which are more relevant to the nature of the gating signals. RESULTS: In both 0.6 s and 0.4 s prediction cases, linear regression outperformed other methods, demonstrating significantly smaller amplitude errors compared to the RNNs (P < 0.05). The proposed algorithm with adaptive linear regression had the best performance with an average gating accuracy of 98.3% and 98.0%, a gating error of 44 ms and 45 ms, for liver cancer and lung cancer patients, respectively. CONCLUSION: A functional online gating control scheme was developed with an adaptive linear regression that is both more cost-efficient and accurate than sophisticated RNN based methods in all studied metrics.

Alteration of gut microbiome and correlated amino acid metabolism are associated with acute myelocytic leukemia carcinogenesis.

BACKGROUND: The aim of this study is to investigate the profiles of gut microbiota and metabolites in acute myelocytic leukemia (AML) patients treated with/without chemotherapy. METHODS: Herein, high-throughput 16S rRNA gene sequencing was performed to analysis gut microbiota profiles, and liquid chromatography and mass spectrometry were performed to analysis metabolites profiles. The correlation between gut microbiota biomarkers identified by LEfSe and differentially expressed metabolites were determined by spearman association analysis. RESULTS: The results showed the distinguished gut microbiota and metabolites profiles between AML patients and control individuals or AML patients treated with chemotherapy. Compared to normal populations, the ratio of Firmicutes to Bacteroidetes was increased at the phylum level than that in AML patients, and LEfSe analysis identified Collinsella and Coriobacteriaceae as biomarkers of AML patients. Differential metabolite analysis indicated that, compared to AML patients, numerous differential amino acids and analogs could be observed in control individuals and AML patients treated with chemotherapy. Interestingly, spearman association analysis demonstrated that plenty of bacteria biomarkers shows statistical correlations with differentially expressed amino acid metabolites. In addition, we found that both Collinsella and Coriobacteriaceae demonstrate remarkable positive correlation with hydroxyprolyl-hydroxyproline, prolyl-tyrosine, and tyrosyl-proline. CONCLUSION: In conclusion, our present study investigated the role of the gut-microbiome-metabolome axis in AML and revealed the possibility of AML treatment by gut-microbiome-metabolome axis in the further.

A systematic review and meta-analysis of primary bypass surgery compared with bypass surgery after endovascular treatment in peripheral artery disease patients.

OBJECTIVE: Both bypass surgery and endovascular treatment are well-recognized interventions for the treatment of peripheral artery disease; however, the effect of failed endovascular treatment on subsequent surgeries remains controversial. A systematic review was conducted to compare the outcomes of primary bypass and bypass surgery after endovascular treatment. METHODS: Three academic databases (Embase, PubMed, and Scopus) were searched from their inception to August 2022. Two independent investigators searched for studies that reported the outcomes of primary bypass surgery and bypass surgery after endovascular treatment in patients with peripheral artery disease. Abstracts and full-text studies were screened independently using duplicate data abstraction. Dichotomous outcome measures were reported using a random-effects model to generate a summary odds ratio (OR) and 95% confidence interval (CI). The risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Seventeen retrospective observational studies were selected from 3911 articles and included 8064 patients, 6252 of whom underwent primary bypass surgery and 1812 underwent bypass surgery after endovascular treatment. The mean age was 69.0 years and 61.2% (n = 4938) were male. For perioperative outcomes, the 30-day results showed no difference in mortality (OR, 0.76; 95% CI, 0.53-1.10), or amputation (OR, 0.89; 95% CI, 0.67-1.20). For short- to mid-term outcomes, primary patency did not differ at 6 months (OR, 0.98; 95% CI, 0.81-1.19), 1 year (OR, 1.12; 95% CI, 0.97-1.30), or 2 years (OR, 1.17; 95% CI, 0.85-1.61) follow-up. Amputation-free survival did not differ at 6 months (OR, 1.03; 95% CI, 0.82-1.30), 1 year (OR, 1.09; 95% CI, 0.89-1.32), 2 years (OR, 1.18; 95% CI, 0.93-1.50), or 3 years (OR, 1.09; 95% CI, 0.84-1.40) of follow-up. No significant difference was found in overall survival or second patency. CONCLUSIONS: This meta-analysis of retrospective, nonrandomized, observational studies suggests that prior endovascular treatment of lower extremity arterial disease does not result in worse perioperative, short-term, or mid-term clinical outcomes of subsequent infrainguinal bypass surgery compared with patients without prior endovascular treatment.

Study on the mechanism of Shujin Tongluo granules in treating cervical spondylosis based on network pharmacology and molecular docking.

BACKGROUND: To investigate the potential active ingredients and possible mechanisms of Shujin Tongluo granules (SJTLG) in the treatment of cervical spondylosis (CS) by network pharmacology and molecular docking. METHODS: The active ingredients and potential targets of SJTLG were obtained through databases such as traditional Chinese medicine system (TCMSP) and BATMAN-traditional Chinese medicine (TCM), and the relevant human targets of CS were identified through databases such as OMIM, GeneCards, and DisGeNET. The intersection targets were imported into STRING for protein-protein interaction (PPI) analysis. The obtained data were imported into Cytoscape 3.9.0 software for visualization, and module analysis was performed using the MCODE plug-in. The representative targets were screened through the Metascape website for pathway enrichment analysis in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Cytoscape software was used to build networks such as "drug-compound-target" and "drug-compound-target-pathway." Finally, the key targets were selected for molecular docking with the corresponding compounds by Autodock Tools 1.5.7 and visualized by PyMol. RESULTS: A total of 132 active compounds and 996 targets from SJTLG and 678 targets from CS were screened with 116 intersection targets. The key targets were AKT1, GAPDH, ALB, IL-6, TP53, TNF, VEGFA, IL-1ß, EGFR, HSP90AA1, ESR1, and JUN. The results of GO and KEGG enrichment analysis showed that the treatment of CS was mainly related to biological processes such as cellular response to nitrogen compound, cellular response to organonitrogen compound, and positive regulation of locomotion, and the targets were mainly focused on pathways in cancer, Kaposi sarcoma-associated herpesvirus infection, PI3K-Akt signaling pathway, lipid, and atherosclerosis. Molecular docking results showed that the minimum binding energy between the core targets and the corresponding compound was <-5.0 kcal·mol-1. CONCLUSION: This study preliminarily elucidates the potential active ingredients and mechanism of anti-inflammatory, analgesic, microcirculation improvement, vasodilation, osteoporosis inhibition and nerve nutrition effects of SJTLG in the treatment of CS and provides a reference for its clinical application.

Environmental, social and behavioral risk factors in association with spatial clustering of childhood cancer incidence.

Childhood cancer incidence is known to vary by age, sex, and race/ethnicity, but evidence is limited regarding external risk factors. We aim to identify harmful combinations of air pollutants and other environmental and social risk factors in association with the incidence of childhood cancer based on 2003-2017 data from the Georgia Cancer Registry. We calculated the standardized incidence ratios (SIR) of Central Nervous System (CNS) tumors, leukemia and lymphomas based on age, gender and ethnic composition in each of the 159 counties in Georgia, USA. County-level information on air pollution, socioeconomic status (SES), tobacco smoking, alcohol drinking and obesity were derived from US EPA and other public data sources. We applied two unsupervised learning tools (self-organizing map [SOM] and exposure-continuum mapping [ECM]) to identify pertinent types of multi-exposure combinations. Spatial Bayesian Poisson models (Leroux-CAR) were fit with indicators for each multi-exposure category as exposure and SIR of childhood cancers as outcomes. We identified consistent associations of environmental (pesticide exposure) and social/behavioral stressors (low socioeconomic status, alcohol) with spatial clustering of pediatric cancer class II (lymphomas and reticuloendothelial neoplasms), but not for other cancer classes. More research is needed to identify the causal risk factors for these associations.

Feasibility study of adaptive radiotherapy for esophageal cancer using artificial intelligence autosegmentation based on MR-Linac.

Objective: We proposed a scheme for automatic patient-specific segmentation in Magnetic Resonance (MR)-guided online adaptive radiotherapy based on daily updated, small-sample deep learning models to address the time-consuming delineation of the region of interest (ROI) in the adapt-to-shape (ATS) workflow. Additionally, we verified its feasibility in adaptive radiation therapy for esophageal cancer (EC). Methods: Nine patients with EC who were treated with an MR-Linac were prospectively enrolled. The actual adapt-to-position (ATP) workflow and simulated ATS workflow were performed, the latter of which was embedded with a deep learning autosegmentation (AS) model. The first three treatment fractions of the manual delineations were used as input data to predict the next fraction segmentation, which was modified and then used as training data to update the model daily, forming a cyclic training process. Then, the system was validated in terms of delineation accuracy, time, and dosimetric benefit. Additionally, the air cavity in the esophagus and sternum were added to the ATS workflow (producing ATS+), and the dosimetric variations were assessed. Results: The mean AS time was 1.40 [1.10-1.78 min]. The Dice similarity coefficient (DSC) of the AS model gradually approached 1; after four training sessions, the DSCs of all ROIs reached a mean value of 0.9 or more. Furthermore, the planning target volume (PTV) of the ATS plan showed a smaller heterogeneity index than that of the ATP plan. Additionally, V5 and V10 in the lungs and heart were greater in the ATS+ group than in the ATS group. Conclusion: The accuracy and speed of artificial intelligence-based AS in the ATS workflow met the clinical radiation therapy needs of EC. This allowed the ATS workflow to achieve a similar speed to the ATP workflow while maintaining its dosimetric advantage. Fast and precise online ATS treatment ensured an adequate dose to the PTV while reducing the dose to the heart and lungs.