[Chest computed tomography manifestations in neonates with chronic granulomatous disease]. / æ–°ç”Ÿå„¿æ ¢æ€§è‚‰èŠ½è‚¿ç— èƒ¸éƒ¨è®¡ç®—æœºæ–­å±‚æ‰«æçš„ç‰¹å¾åˆ†æž.

OBJECTIVES: To study chest computed tomography (CT) manifestations in neonates with chronic granulomatous disease (CGD) to provide clues for early diagnosis of this disease. METHODS: A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital. RESULTS: Nine neonates with CGD were included, with eight presenting respiratory symptoms as the initial sign. Chest CT findings included: consolidation in all 9 cases; nodules in all 9 cases, characterized by multiple, variably sized scattered nodules in both lungs; masses in 4 cases; cavities in 3 cases; abscesses in 6 cases; bronchial stenosis in 2 cases; pleural effusion, interstitial changes, and mediastinal lymphadenopathy each in 1 case. CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement; no signs of pulmonary emphysema, lung calcification, halo signs, crescent signs, bronchiectasis, or scar lesions were observed. There was no evidence of rib or vertebral bone destruction. Fungal infections were present in 8 of the 9 cases, including 6 with Aspergillus infections; three of these involved mixed infections with Aspergillus, with masses most commonly associated with mixed Aspergillus infections (3/4). CONCLUSIONS: The primary manifestations of neonatal CGD on chest CT are consolidation, nodules, and/or masses, with Aspergillus as a common pathogen. These features can serve as early diagnostic clues for neonatal CGD.

[Clinical phenotypic and genetic analysis of syndrome families with EYA1 gene variants].

Objective:To investigate the clinical phenotype of a family with branchio-oto syndrome （BOS） and to explore the genetic etiology of the syndrome in this family. Methods:Clinical data were collected from a child diagnosed with BOS and his family members. Genomic DNA was extracted from peripheral blood of the proband and his family members. Whole-exome sequencing was performed, and the mutation sites were verified and analyzed by Sanger sequencing. Results:The family consists of two generations with four members, three of whom exhibit the phenotype. Two members have hearing loss and bilateral preauricular fistulas and bilateral branchial cleft fistulas. One member has bilateral preauricular fistulas and bilateral branchial cleft fistulas. All of which were in line with the clinical diagnosis of gill ear syndrome, the inheritance mode of the family was autosomal dominant inheritance, genetic testing showed that all members of the family had c. 1744delC（p. L592Cfs*47） mutation in the EYA1 gene, while unaffected members have the wild-type allele at this locus. This mutation is a frameshift mutation, which results in the early appearance of the stop codon, and has not been reported so far. According to ACMG guidelines, the variant was preliminarily determined to be suspected pathogenic. Conclusion:The newly discovered EYA1c. 1744delC（p. L592Cfs*47） mutation in this family is the pathogenic mutant gene of the patients in this family, which further expands the mutation spectrum of EYA1 gene, gives us a new understanding of the disease, and provides an important reference for clinical diagnosis and genetic counseling.

Tumour vasculature at single-cell resolution.

Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply1. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network2,3. Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN+ tip cells at the SI stage (APLN+ TipSI) advanced to TipSIII cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN+ TipSI cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1+ matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy.

Modern perspectives of heavy metals alleviation from oil contaminated soil: A review.

Heavy metal poisoning of soil from oil spills causes serious environmental problems worldwide. Various causes and effects of heavy metal pollution in the soil environment are discussed in this article. In addition, this study explores new approaches to cleaning up soil that has been contaminated with heavy metals as a result of oil spills. Furthermore, it provides a thorough analysis of recent developments in remediation methods, such as novel nano-based approaches, chemical amendments, bioremediation, and phytoremediation. The objective of this review is to provide a comprehensive overview of the removal of heavy metals from oil-contaminated soils. This review emphasizes on the integration of various approaches and the development of hybrid approaches that combine various remediation techniques in a synergistic way to improve sustainability and efficacy. The study places a strong emphasis on each remediation strategy that can be applied in the real-world circumstances while critically evaluating its effectiveness, drawbacks, and environmental repercussions. Additionally, it discusses the processes that reduce heavy metal toxicity and improve soil health, taking into account elements like interactions between plants and microbes, bioavailability, and pollutant uptake pathways. Furthermore, the current study suggests that more research and development is needed in this area, particularly to overcome current barriers, improve our understanding of underlying mechanisms, and investigate cutting-edge ideas that have the potential to completely transform the heavy metal clean up industry.

Occurrence of Dumping Syndrome After Esophageal Cancer Surgery: Systematic Review and Meta-analysis.

BACKGROUND: Dumping syndrome occurs frequently after esophageal cancer surgery, but the reported prevalence varied across previous studies. This systematic review and meta-analysis aimed to clarify the prevalence of dumping syndrome after esophageal cancer surgery, particularly exploring the sources of heterogeneity in previous studies. METHODS: A comprehensive literature search was conducted in PubMed, MEDLINE, Web of Science, Embase, and the Cochrane Library databases, supplemented by hand-search of reference lists, through March 2023. Random-effects meta-analysis estimated the average prevalence of dumping syndrome after esophageal cancer surgery. Heterogeneity across studies was examined by the I2 statistic and Cochran's Q test. RESULTS: Among the 2949 articles retrieved from the databases, 16 articles (15 cohort studies and 1 randomized controlled trial) met the inclusion criteria. The prevalence of dumping syndrome ranged 0-74% in these studies, showing high heterogeneity (I2 = 99%, P < 0.01), with the pooled prevalence of 27% (95% confidence interval [CI] 14-39%). The pooled prevalence in the three studies using specialized questionnaires was 67% (95% CI 60-73%), with reduced heterogeneity (I2 = 43%, P = 0.17). The prevalence also varied by year of publication, study population, and length and completeness of follow-up. CONCLUSIONS: Our findings revealed that dumping syndrome is common after esophageal cancer surgery. The varying prevalence across previous studies was probably owing to differences in measurement of dumping syndrome. Using specific patient reported outcome questionnaires is recommended for future investigations on dumping syndrome after esophageal cancer surgery.

Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.

BACKGROUNDS & AIMS: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH. METHODS: PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a-knockout (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a-knockout (Htr1aΔVSMC) mice were used to confirm the regulatory role of HTR1A on PP. RESULTS: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3',5'-cyclic monophosphate pathway-mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation-, and partial PV ligation-induced PH. CONCLUSIONS: Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.

[Effects of tramadol hydrochloride preemptive analgesia in kyphoplasty of thoracolumbar osteoporotic fractures under local anesthesia].

OBJECTIVE: To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty (PKP) of vertebrae following local anesthesia. METHODS: From August 2019 to June 2021, 118 patients with thoraco lumbar osteoporotic fractures were treated and divided into observation group and control group, with 59 patients in each gruop. In observation group, there were 26 males and 33 females, aged from 57 to 80 years old with an average of (67.69±4.75)years old;14 patients on T11, 12 patients on T12, 18 patients on L1, 15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group. In control group, there were 24 males and 35 females, aged from 55 to 77 years old with an average of (68.00±4.43) years old;19 patients on T11, 11 patients on T12, 17patients on L1, 12 patients on L2;the same amount of normal saline was injected intramuscularly in control group. Observation indicators included operation time, intraoperative bleeding, visual analogue scale (VAS) evaluation and recording of preoperative (T0), intraoperative puncture(T1), and working cannula placement (T2) between two groups of patients, at the time of balloon dilation (T3), when the bone cement was injected into the vertebral body (T4), 2 hours after the operation (T5), and the pain degree at the time of discharge(T6);adverse reactions such as dizziness, nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery. RESULTS: All patients were successfully completed PKP via bilateral pedicle approach, and no intravenous sedative and analgesic drugs were used during the operation. There was no significant difference in preoperative general data and VAS(T0) between two groups (P>0.05). There was no significant difference in operation time and intraoperative blood loss between the two groups (P>0.05). VAS of T1, T2, T3, T4 and T5 in observation group were all lower than those in control group(P<0.05), and there was no significant difference in T6 VAS (P>0.05). T6 VAS between two groups were significantly lower than those of T0, and the difference was statistically significant (P<0.05). There was no significant difference in incidence of total adverse reactions between two groups (P>0.05). There was a statistically significant difference in the acceptance of repeat PKP surgery (P<0.05). CONCLUSION: Half an hour before operation, intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia, which could increase the comfort of patients during operation and 2 hours after operation, and improve patients satisfaction with surgery.

Prior frequency guided diffusion model for limited angle (LA)-CBCT reconstruction.

Objective.Cone-beam computed tomography (CBCT) is widely used in image-guided radiotherapy. Reconstructing CBCTs from limited-angle acquisitions (LA-CBCT) is highly desired for improved imaging efficiency, dose reduction, and better mechanical clearance. LA-CBCT reconstruction, however, suffers from severe under-sampling artifacts, making it a highly ill-posed inverse problem. Diffusion models can generate data/images by reversing a data-noising process through learned data distributions; and can be incorporated as a denoiser/regularizer in LA-CBCT reconstruction. In this study, we developed a diffusion model-based framework, prior frequency-guided diffusion model (PFGDM), for robust and structure-preserving LA-CBCT reconstruction.Approach.PFGDM uses a conditioned diffusion model as a regularizer for LA-CBCT reconstruction, and the condition is based on high-frequency information extracted from patient-specific prior CT scans which provides a strong anatomical prior for LA-CBCT reconstruction. Specifically, we developed two variants of PFGDM (PFGDM-A and PFGDM-B) with different conditioning schemes. PFGDM-A applies the high-frequency CT information condition until a pre-optimized iteration step, and drops it afterwards to enable both similar and differing CT/CBCT anatomies to be reconstructed. PFGDM-B, on the other hand, continuously applies the prior CT information condition in every reconstruction step, while with a decaying mechanism, to gradually phase out the reconstruction guidance from the prior CT scans. The two variants of PFGDM were tested and compared with current available LA-CBCT reconstruction solutions, via metrics including peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM).Main results.PFGDM outperformed all traditional and diffusion model-based methods. The mean(s.d.) PSNR/SSIM were 27.97(3.10)/0.949(0.027), 26.63(2.79)/0.937(0.029), and 23.81(2.25)/0.896(0.036) for PFGDM-A, and 28.20(1.28)/0.954(0.011), 26.68(1.04)/0.941(0.014), and 23.72(1.19)/0.894(0.034) for PFGDM-B, based on 120°, 90°, and 30° orthogonal-view scan angles respectively. In contrast, the PSNR/SSIM was 19.61(2.47)/0.807(0.048) for 30° for DiffusionMBIR, a diffusion-based method without prior CT conditioning.Significance. PFGDM reconstructs high-quality LA-CBCTs under very-limited gantry angles, allowing faster and more flexible CBCT scans with dose reductions.

Chemical Composition and Phytotoxic Activity of Mentha vagans Boriss. Essential Oil.

This study explored the composition of essential oil (EO) and the first phytotoxic screening of EO obtained from the stems and leaves of Mentha vagans Boriss (MVEO) via hydro-distillation technique. The EO ingredients were detected through Gas Chromatography-Mass Spectrometry (GC-MS). GC-MS analysis revealed that MVEO contained 49 constituents, constituting 93.95 % of the total oil. Among MVEO constituents, dihydrocarvone was observed as the dominant constituent (24.14 %), followed by D-carvone (16.28 %) and piperitone (18.14 %). The phytotoxic effects of MVEO and its dominant compounds were examined against Amaranthus retroflexus, Lolium perenne, and Poa annua. Significant inhibition was observed by MVEO in comparison with the major constituents and their mixture, suppressing the seedling growth of tested species at the lowest dosage (0.01 mg/mL); in general, seedling growth of all tested species was markedly inhibited when applied concentration of the EO and its constituents reached 0.05 mg/mL. Our results also indicated that constituents other than the dominant compounds of MVEO possessed considerable phytotoxic effects because the EO's activity was stronger than its major constituents and their mixture. Thus, additional studies are required to investigate MVEO and its constituents and commercialize them as environment-friendly bio-herbicides.

Incidence of cardiovascular mortality among head and neck cancer patients.

BACKGROUND: While treatment advancements have prolonged the lives of patients with head and neck cancer, the subgroups of these patients at higher risk for cardiovascular disease (CVD) mortality remain unclear. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with head and neck cancer from 2000 to 2019. We compared their CVD mortality against the general US population using standardized mortality ratios (SMRs). RESULTS: Our analysis included 474,366 patients, identifying that 14% of deaths were due to CVD, with an SMR of 1.19. Notably, patients under the age of 39 had a CVD SMR increase of over 100-fold. Those with distant tumor stages showed the highest CVD SMR of 1.52 (95% CI 1.50-1.54). An upward trend in SMR to 2.53 (95% CI 2.51-2.56) was observed from 2011 to 2019. Within the initial 5-year post-diagnosis, the SMR for CVD was 3.17 (95% CI 3.14-3.20), which exceeded the general population's rates but declined in the 5-20-year range after diagnosis. Patients who did not any therapy had the greatest CVD SMR of 2.26 (95% CI 2.24-2.28). Hypopharyngeal cancer patients exhibited the highest CVD SMR of 1.54 (95% CI 1.52-1.56). CONCLUSIONS: The study highlights that head and neck cancer patients, especially younger individuals and those with advanced disease stages, face substantial CVD mortality risks. The CVD SMR peaks within 5 years following diagnosis. Patients abstaining from treatment bear the highest risk of CVD mortality. Cardioprotective measures should be considered critical for this patient population.

Evaluation of the value of combined detection of tumor markers CA724, carcinoembryonic antigen, CA242, and CA19-9 in gastric cancer.

BACKGROUND: Gastric cancer is a global health concern that poses a significant threat to human well-being. AIM: To detecting serum changes in carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 724, CA242, and CA19-9 expression among patients with gastric cancer. METHODS: Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group, while 80 patients with benign gastric diseases were included in the control group. Both groups were tested for tumor markers (CA724, CEA, CA242, and CA19-9]. Tumor marker indicators (CA724, CEA, CA242, and CA19-9) were compared between the two groups, assessing positive rates of tumor markers across various stages in the observation group. Additionally, single and combined detection of various tumor markers were examined. RESULTS: The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value observed for the combined detection of CA724, CEA, CA242, and CA19-9 were higher than those of CA724, CEA, CA242, and CA19-9 individually. Therefore, the combined detection of CA724, CEA, CA242, and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases, facilitating the early diagnosis and treatment of patients. CONCLUSION: CA724, CEA, CA242, and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients (P < 0.05). Their combined detection can improve the diagnostic accuracy for gastric cancer, warranting clinical promotion.

Factors Affecting the Diagnostic Discordance Between Frozen and Permanent Sections in Mucinous Ovarian Tumors.

Purpose: To investigate the accuracy of intraoperative frozen section (FS) diagnosis for predicting the permanent section (PS) diagnosis of mucinous ovarian tumors and evaluate the factors affecting the diagnostic discordance. Patients and Methods: This retrospective cohort study was performed in Tianjin Medical University General Hospital. All women who underwent ovarian surgery with FS between January 2011 and December 2022 were identified, and those with a diagnosis of mucinous ovarian tumor (MOT) by FS or PS were reviewed. Clinical and pathologic data were extracted. Results: A total of 180 women were included, of which 141 (78.33%) had diagnostic concordance between FS and PS, yielding a sensitivity of 83.43% and a positive predictive value (PPV) of 92.76%. Under- and over-diagnosis occurred in 28 cases (15.56%) and 11 cases (6.11%). Tumor size > 13cm (OR 3.79, 95% CI 1.12-12.73) was an independent risk factor for under-diagnosis, and tumor size ≤ 13cm (OR 16.78, 95% CI 0.01-0.49), laparoscopic surgery (OR 0.14, 95% CI 0.02-0.92), the combination of other tumor components (including serous, Brenner tumor, and chocolate cyst; OR 7.00, 95% CI 1.19-41.12) were independently associated with over-diagnosis. The Kaplan-Meier survival curves and the Log rank test showed no significant difference between misdiagnosed and accurately diagnosed patients (all P > 0.05). Conclusion: Intraoperative frozen pathology of MOT is problematic for under- and over-diagnosis. The incorrect diagnosis of FS was related to determining the extent of surgery but had no impact on the patients' long-term recurrence and survival outcomes. In future clinical practice, surgeons need to obtain material accurately and enhance communication with pathologists during the operation to improve the accuracy of FS diagnosis.

TransEBUS: The interpretation of endobronchial ultrasound image using hybrid transformer for differentiating malignant and benign mediastinal lesions.

The purpose of this study is to establish a deep learning automatic assistance diagnosis system for benign and malignant classification of mediastinal lesions in endobronchial ultrasound (EBUS) images. EBUS images are in the form of video and contain multiple imaging modes. Different imaging modes and different frames can reflect the different characteristics of lesions. Compared with previous studies, the proposed model can efficiently extract and integrate the spatiotemporal relationships between different modes and does not require manual selection of representative frames. In recent years, Vision Transformer has received much attention in the field of computer vision. Combined with convolutional neural networks, hybrid transformers can also perform well on small datasets. This study designed a novel deep learning architecture based on hybrid transformer called TransEBUS. By adding learnable parameters in the temporal dimension, TransEBUS was able to extract spatiotemporal features from insufficient data. In addition, we designed a two-stream module to integrate information from three different imaging modes of EBUS. Furthermore, we applied contrastive learning when training TransEBUS, enabling it to learn discriminative representation of benign and malignant mediastinal lesions. The results show that TransEBUS achieved a diagnostic accuracy of 82% and an area under the curve of 0.8812 in the test dataset, outperforming other methods. It also shows that several models can improve performance by incorporating two-stream module. Our proposed system has shown its potential to help physicians distinguishing benign and malignant mediastinal lesions, thereby ensuring the accuracy of EBUS examination.

Dynamic CBCT imaging using prior model-free spatiotemporal implicit neural representation (PMF-STINR).

Objective. Dynamic cone-beam computed tomography (CBCT) can capture high-spatial-resolution, time-varying images for motion monitoring, patient setup, and adaptive planning of radiotherapy. However, dynamic CBCT reconstruction is an extremely ill-posed spatiotemporal inverse problem, as each CBCT volume in the dynamic sequence is only captured by one or a few x-ray projections, due to the slow gantry rotation speed and the fast anatomical motion (e.g. breathing).Approach. We developed a machine learning-based technique, prior-model-free spatiotemporal implicit neural representation (PMF-STINR), to reconstruct dynamic CBCTs from sequentially acquired x-ray projections. PMF-STINR employs a joint image reconstruction and registration approach to address the under-sampling challenge, enabling dynamic CBCT reconstruction from singular x-ray projections. Specifically, PMF-STINR uses spatial implicit neural representations to reconstruct a reference CBCT volume, and it applies temporal INR to represent the intra-scan dynamic motion of the reference CBCT to yield dynamic CBCTs. PMF-STINR couples the temporal INR with a learning-based B-spline motion model to capture time-varying deformable motion during the reconstruction. Compared with the previous methods, the spatial INR, the temporal INR, and the B-spline model of PMF-STINR are all learned on the fly during reconstruction in a one-shot fashion, without using any patient-specific prior knowledge or motion sorting/binning.Main results. PMF-STINR was evaluated via digital phantom simulations, physical phantom measurements, and a multi-institutional patient dataset featuring various imaging protocols (half-fan/full-fan, full sampling/sparse sampling, different energy and mAs settings, etc). The results showed that the one-shot learning-based PMF-STINR can accurately and robustly reconstruct dynamic CBCTs and capture highly irregular motion with high temporal (∼ 0.1 s) resolution and sub-millimeter accuracy.Significance. PMF-STINR can reconstruct dynamic CBCTs and solve the intra-scan motion from conventional 3D CBCT scans without using any prior anatomical/motion model or motion sorting/binning. It can be a promising tool for motion management by offering richer motion information than traditional 4D-CBCTs.

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity.

Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4-dione derivatives (MY1-41) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds (MY1-41) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC50) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 µM, compared with that of the positive control lithocholic acid (IC50 = 9.62 ± 0.14 µM). The most potent compound, MY17 (IC50 = 0.41 ± 0.05 µM), was a reversible, noncompetitive inhibitor of PTP1B. Circular dichroism spectroscopy and molecular docking were employed to analyze the binding interaction between MY17 and PTP1B. In HepG2 cells, MY17 treatment could alleviate palmitic acid (PA)-induced insulin resistance by upregulating the expression of phosphorylated insulin receptor substrate and protein kinase B. In vivo, oral administration of MY17 could reduce the fasting blood glucose level and improve glucose tolerance and dyslipidemia in mice suffering from DM.

piSTING: A Pocket-Independent Agonist Based on Multivalency-Driven STING Oligomerization.

The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket-dependent small-molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical trials owing to the limitations of the STING pocket. In this study, we developed novel pocket-independent STING-activating agonists (piSTINGs), which act through multivalency-driven oligomerization to activate STING. Additionally, a piSTING-adjuvanted vaccine elicited a significant antibody response and inhibited tumour growth in therapeutic models. Moreover, a piSTING-based vaccine combination with aPD-1 showed remarkable potential to enhance the effectiveness of immune checkpoint blockade (ICB) immunotherapy. In particular, piSTING can strengthen the impact of STING pathway in immunotherapy and accelerate the clinical translation of STING agonists.

Cervical Sagittal Alignment and Related Factor Analysis and Prediction Model in Patients Undergoing Revision Surgery After Anterior Cervical Fusion.

INTRODUCTION: Patients with myelopathy or radiculopathy commonly undergo anterior cervical fusion surgery (ACFS), which has a notable failure rate on occasion. The goal of this study was to compare revision and nonrevision surgery patients in cervical sagittal alignment (CSA) subsequent to ACFS; additionally, to identify the best CSA parameters for predicting clinical outcome after ACFS; and furthermore, to create an equation model to assist surgeons in making decisions on patients undergoing ACFS. METHODS: The data of 99 patients with symptomatic cervical myelopathy/radiculopathy who underwent ACFS were analyzed. Patients were divided into group A (underwent revision surgery after the first surgery failed) and group B (underwent only the first surgery). We measured and analyzed both preoperative and postoperative CSA parameters, including C2 slope, T1 slope, cervical lordosis C2-C7 (CL), C2-C7 sagittal vertical axis (C2C7 SVA), occiput-C2 lordosis angle (C0-C2), and chin brow vertical angle, and we further computed the correlation between the CSA parameters and created a prediction model. RESULTS: The (T1S-CL)-C2S mismatch differed significantly between groups A and B ([9.95 ± 9.95] 0 , [3.79 ± 6.58] 0 , P < 0.05, respectively). A significant correlation was observed between C2 slope and T1CL in group B relative to group A postoperatively (R 2 = 0.42 versus R 2 = 0.09, respectively). Compared with group B, patients in group A had significantly higher C2C7SVA values, more levels of fusion, and more smokers. The sensitivity, specificity, accuracy, and discrimination of the model were, respectively, 73.5%, 84%, 78.8%, and 85.65%. CONCLUSION: The causes of revision surgery in cervical myelopathic patients after anterior cervical corpectomy and fusion/anterior cervical diskectomy and fusion are multifactorial. (T1S-CL)-C2S mismatch and high C2C7SVA are the best cervical sagittal parameters that increase the odds of revision surgery, and the effect is more enhanced when comorbidities such as smoking, low bone-mineral density, and increased levels of fusion are taken into account.

Prior Frequency Guided Diffusion Model for Limited Angle (LA)-CBCT Reconstruction.

Cone-beam computed tomography (CBCT) is widely used in image-guided radiotherapy. Reconstructing CBCTs from limited-angle acquisitions (LA-CBCT) is highly desired for improved imaging efficiency, dose reduction, and better mechanical clearance. LA-CBCT reconstruction, however, suffers from severe under-sampling artifacts, making it a highly ill-posed inverse problem. Diffusion models can generate data/images by reversing a data-noising process through learned data distributions; and can be incorporated as a denoiser/regularizer in LA-CBCT reconstruction. In this study, we developed a diffusion model-based framework, prior frequency-guided diffusion model (PFGDM), for robust and structure-preserving LA-CBCT reconstruction. PFGDM uses a conditioned diffusion model as a regularizer for LA-CBCT reconstruction, and the condition is based on high-frequency information extracted from patient-specific prior CT scans which provides a strong anatomical prior for LA-CBCT reconstruction. Specifically, we developed two variants of PFGDM (PFGDM-A and PFGDM-B) with different conditioning schemes. PFGDM-A applies the high-frequency CT information condition until a pre-optimized iteration step, and drops it afterwards to enable both similar and differing CT/CBCT anatomies to be reconstructed. PFGDM-B, on the other hand, continuously applies the prior CT information condition in every reconstruction step, while with a decaying mechanism, to gradually phase out the reconstruction guidance from the prior CT scans. The two variants of PFGDM were tested and compared with current available LA-CBCT reconstruction solutions, via metrics including PSNR and SSIM. PFGDM outperformed all traditional and diffusion model-based methods. PFGDM reconstructs high-quality LA-CBCTs under very-limited gantry angles, allowing faster and more flexible CBCT scans with dose reductions.

Neoadjuvant low-dose radiotherapy plus durvalumab and chemotherapy for potentially resectable stage III NSCLC: A phase Ib dose-escalation study.

BACKGROUND AND PURPOSE: This phase Ib study was designed to assess the safety/tolerability and preliminary antitumor activity of neoadjuvant low-dose radiotherapy (LDRT) plus durvalumab and chemotherapy for potentially resectable stage III non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Eligible patients received dose-escalated radiotherapy (10 Gy in 5 fractions [cohort 1], 20 Gy in 10 fractions [cohort 2], and 30 Gy in 15 fractions [cohort 3]) according to a 3 + 3 design, with concurrent durvalumab plus standard chemotherapy for two cycles. Primary objective was safety/tolerability. Secondary objectives included major pathological response (MPR), pathological complete response (pCR), event-free survival (EFS), and exploratory biomarker analysis. RESULTS: Nine patients were enrolled and completed the planned neoadjuvant therapy. No dose-limiting toxicity was recorded. Grade 3-4 treatment-related adverse events were observed in three (33.3 %) patients. Seven (77.8 %) patients successfully converted to resectable cases with R0 resection. No treatment-related surgical delay or death was reported. The MPR and pCR rates were both 33.3 % % (1/3) for cohort 1, 66.7 % (2/3) and 0.0 % for cohort 2, and 100.0 % (3/3), and 66.7 % (2/3) for cohort 3. At data cutoff, the 12 month-EFS rates were 33.3 %, 66.7 %, and 100 % for three cohorts, respectively. By biomarker analysis, TMB values were higher in either pathologically or radiologically responders than in others (all p > 0.05). CONCLUSION: Neoadjuvant LDRT plus durvalumab and chemotherapy was well-tolerated in potentially resectable stage III NSCLC. The preliminary efficacy supports this combined regimen's potential, the optimal radiotherapy dosage was determined to be 30 Gy in 15 fractions, warranting further clinical investigation.

Buffalo-bur (Solanum rostratum Dunal) invasiveness, bioactivities, and utilization: a review.

Solanum rostratum Dunal, belongs to the Solanaceae family and has drawn attention for its intricate interplay of invasiveness, phytochemical composition, and potential bioactivities. Notably invasive, S. rostratum employs adaptive mechanisms during senescence, featuring thorn formation on leaves, fruits, and stems seed self-propulsion, and resistance to drought. This adaptability has led to its proliferation in countries such as China, Canada, and Australia, extending beyond its Mexican origin. Despite its invasive historical reputation, recent studies unveil a rich array of phytochemicals in S. rostratum, suggesting untapped economic potential due to under-exploration. This review delves into exploring the potential uses of S. rostratum while elucidating the bioactive compounds associated with diverse identified bioactivities. In terms of phytochemistry, S. rostratum reveals an abundance of various bioactive compounds, including alkaloids, flavonoids, phenols, saponins, and glycosides. These compounds confer a range of beneficial bioactivities, encompassing antioxidant, antifungal, anticarcinogenic, anti-inflammatory, phytotoxic, and pesticidal properties. This positions S. rostratum as a reservoir of valuable chemical constituents with potential applications, particularly in medicine and agriculture. The review provides comprehensive insights into the phytochemistry, bioactivities, and bioactivity-guided fractionation of S. rostratum. In this review, we focus on the potential utilization of S. rostratum by emphasizing its phytochemical profile, which holds promise for diverse applications. This review is the first that advocates for further exploration and research to unlock the plant's full potential for both economic and environmental benefit.