Neoadjuvant SBRT combined with immunotherapy in NSCLC: from mechanisms to therapy

The utilisation of neoadjuvant immunotherapy has demonstrated promising preliminary clinical outcomes for early-stage resectable non-small-cell lung cancer (NSCLC). Nevertheless, it is imperative to develop novel neoadjuvant combination therapy regimens incorporating immunotherapy to further enhance the proportion of patients who derive benefit. Recent studies have revealed that stereotactic body radiotherapy (SBRT) not only induces direct tumour cell death but also stimulates local and systemic antitumour immune responses. Numerous clinical trials have incorporated SBRT into immunotherapy for advanced NSCLC, revealing that this combination therapy effectively inhibits local tumour growth while simultaneously activating systemic antitumour immune responses. Consequently, the integration of SBRT with neoadjuvant immunotherapy has emerged as a promising strategy for treating resectable NSCLC, as it can enhance the systemic immune response to eradicate micrometastases and recurrent foci post-resection. This review aims to elucidate the potential mechanism of combination of SBRT and immunotherapy followed by surgery and identify optimal clinical treatment strategies. Initially, we delineate the interplay between SBRT and the local tumour immune microenvironment, as well as the systemic antitumour immune response. We subsequently introduce the preclinical foundation and preliminary clinical trials of neoadjuvant SBRT combined with immunotherapy for treating resectable NSCLC. Finally, we discussed the optimal dosage, schedule, and biomarkers for neoadjuvant combination therapy in its clinical application. In conclusion, the elucidation of potential mechanism of neoadjuvant SBRT combined immunotherapy not only offers a theoretical basis for ongoing clinical trials but also contributes to determining the most efficacious therapy scheme for future clinical application

Pediatric myelin oligodendrocyte glycoprotein antibody-associated disease in southern China: analysis of 93 cases

ObjectiveTo study the clinical features of children diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in southern China.MethodsClinical data of children diagnosed with MOGAD from April 2014 to September 2021 were analyzed.ResultsA total of 93 children (M/F=45/48; median onset age=6.0 y) with MOGAD were involved. Seizures or limb paralysis was the most common onset or course symptom, respectively. The most common lesion locations in brain MRI, orbital MRI, and spinal cord MRI were basal ganglia and subcortical white matter, the orbital segment of the optic nerve, and the cervical segment, respectively. ADEM (58.10%) was the most common clinical phenotype. The relapse rate was 24.7%. Compared with the patients without relapse, relapsed patients had a longer interval from onset to diagnosis (median: 19 days VS 20 days) and higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer positively persistent (median: 3 months VS 24 months). All patients received IVMP plus IVIG at the acute phase, and 96.8% of patients achieved remission after one to three courses of treatment. MMF, monthly IVIG, and maintaining a low dose of oral prednisone were used alone or in combination as maintenance immunotherapy for relapsed patients and effectively reduced relapse. It transpired 41.9% of patients had neurological sequelae, with movement disorder being the most common. Compared with patients without sequelae, patients with sequelae had higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer persistence (median: 3 months VS 6 months) and higher disease relapse rate (14.8% VS 38.5%).ConclusionsResults showed the following about pediatric MOGAD in southern China: the median onset age was 6.0 years, with no obvious sex distribution difference; seizure or limb paralysis, respectively, are the most common onset or course symptom; the lesions of basal ganglia, subcortical white matter, the orbital segment of the optic nerve, and cervical segment were commonly involved in the CNS MRI; ADEM was the most common clinical phenotype; most had a good response to immunotherapy; although the relapse rate was relatively high, MMF, monthly IVIG and a low dose of oral prednisone might effectively reduce relapse; neurological sequelae were common, and possibly associated with MOG antibody status and disease relapse

Power Based Phase-Locked Loop Under Adverse Conditions with Moving Average Filter for Single-Phase System

High performance synchronization methord is citical for grid connected power converter. For single-phase system, power based phase-locked loop(pPLL) uses a multiplier as phase detector(PD). As single-phase grid voltage is distorted, the phase error information contains ac disturbances oscillating at integer multiples of fundamental frequency which lead to detection error. This paper presents a new scheme based on moving average filter(MAF) applied in-loop of pPLL. The signal characteristic of phase error is dissussed in detail. A predictive rule is adopted to compensate the delay induced by MAF, thus achieving fast dynamic response. In the case of frequency deviate from nomimal, estimated frequency is fed back to adjust the filter window length of MAF and buffer size of predictive rule. Simulation and experimental results show that proposed PLL achieves good performance under adverse grid conditions

Development and validation of a nomogram to predict the prognosis of patients with gastric cardia cancer

Abstract Our goal was to develop a prognostic nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric cardia cancer (GCC). Patients diagnosed with GCC from 2004 to 2015 were screened from the surveillance, epidemiology, and end results (SEER) database. A nomogram was developed based on the variables associated with OS and CSS using multivariate Cox analysis regression models, which predicted 3- and 5-year OS and CSS. The predictive performance of the nomogram was evaluated using the consistency index (C-index), calibration curve and decision curve analysis (DCA), and the nomogram was calibrated for 3- and 5-year OS and CSS. A total of 7,332 GCC patients were identified and randomized into a training cohort (5,231, 70%) and a validation cohort (2,200, 30%). Multivariate Cox regression analysis showed that marital status, race, SEER stage, grade, T stage, N stage, M stage, tumor size, and surgery were independent risk factors for OS and CSS in GCC patients. Based on the multivariate Cox regression results, we constructed prognostic nomograms of OS and CSS. In the training cohort, the C-index for the OS nomogram was 0.714 (95% CI = 0.705–0.723), and the C-index for the CSS nomogram was 0.759 (95% CI = 0.746–0.772). In the validation cohort, the C-index for the OS nomogram was 0.734 (95% CI = 0.721–0.747), while the C-index for the CSS nomogram was 0.780 (95% CI = 0.759–0.801). Our nomogram has better prediction than the nomogram based on TNM stage. In addition, in the training and external validation cohorts, the calibration curves of the nomogram showed good consistency between the predicted and actual 3- and 5-year OS and CSS rates. The nomogram can effectively predict OS and CSS in GCC patients, which may help clinicians personalize prognostic assessments and clinical decisions

Preconditioning of Carbon Monoxide Releasing Molecule-derived CO Attenuates LPS-induced Activation of HUVEC

<p>Objective: To investigate the effects and potential mechanisms of preconditioning of tricarbonyldichlororuthenium (III) dimer (CORM-2)-liberated CO on LPS-induced activation of endothelial cells (HUVEC).</p> <p>Methods: HUVEC were pretreated with CORM-2 at the concentration of 50 or 100&#956;M for 2 hrs, washed and stimulated with LPS (10&#956;g/ml) for additional 4 hrs. Activation (oxidative stress) of HUVEC was assessed by measuring intracellular oxidation of DHR 123 or nitration of DAF-FM, specific H₂O₂ and NO fluorochromes, respectively. The expression of HO-1, iNOS (Western blot) and ICAM-1 (cell ELISA) proteins and activation of inflammation-relevant transcription factor, NF-&#954;B (EMSA) were assessed. In addition, PMN adhesion to HUVEC was also assessed.</p> <p>Results: The obtained data indicate that pretreatment of HUVEC with CORM-2 results in: 1) decrease of LPS-induced production of ROS and NO; 2) up-regulation of HO-1 but decrease in iNOS at the protein levels; 3) inhibition of LPS-induced activation of NF-&#954;B; and 4) downregulation of expression of ICAM-1, and this was accompanied by a decrease of PMN adhesion to LPS-stimulated HUVEC.</p> <p>Conclusions: Preconditioning of CO liberated by CORM-2 elicited its anti-inflammatory effects by interfering with the induction of intracellular oxidative stress. In addition, it also supports the notion that CO is a potent inhibitor of iNOS and NF-&#954;B.</p

Clinical Characteristics and Traditional Chinese Medicine of Hyperlipidemia in Estrogen Receptor Positive Breast Cancer Patients during Endocrine Therapy: a Real World Study

Background Breast cancer is the most prevalent malignancy in the world. Endocrine therapy reduces the level of estrogen in vivo, thus affecting the blood lipid level, which reduces the quality of life and the treatment compliance of patients. Objective To analyze the clinical characteristics and traditional Chinese medicine (TCM) prescription of hyperlipidemia in estrogen receptor (ER) positive breast cancer patients during endocrine therapy in real world. Methods Based on method of retrospective study, a total of 238 patients with ER positive breast cancer who received endocrine therapy in Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2012 to March 2022 were selected as the study subjects. The data including age, triglyceride, total cholesterol, low density lipoprotein, endocrine therapy drugs, TCM prescriptions of the patients were exported through the search platform of scientific research big data to establish a clinical data table of the patients. ER positive breast cancer patients with normal baseline blood lipid levels were divided into the normal group and dyslipidemia group according to the blood lipid levels during endocrine therapy, and hyperlipidemia was classified into hypercholesterolemia, hypertriglyceridemia and mixed hyperlipidemia. The exported prescriptions were analyzed for frequency, four properties, five flavors, channel tropism and medication regularity by using the &quot;prescription analysis&quot;, an auxiliary platform for TCM inheritance, to obtain new prescriptions. Results Among 238 ER positive breast cancer patients, 97 patients (40.8%) had normal baseline blood lipid levels, of whom 42 patients (205 person-time return visit) developed dyslipidemia during standardized endocrine therapy. Among the patients with dyslipidemia, 37.6% (77/205) occurred in the age group of 51 to 60 years as the highest number; 86 person-time with dyslipidemia received exemestane treatment, accounting for the highest proportion of 42.0%. Among the 42 patients with dyslipidemia (205 person-time return visit) , hyperlipidemia occurred in 99 person-time, and hypercholesterolemia occurred in 49.5% (49/99) . There was no statistically significance difference in the age of patients with three types of hyperlipidemia (P&gt;0.05) . There were statistically significance differences in the proportion of endocrine therapy types among patients with three types of hyperlipidemia (P&lt;0.05) . There were 189 kinds of TCM prescriptions for hyperlipidemia in ER positive breast cancer patients during endocrine treatment, licorice was the most frequently used medicine (408 times) , the highest frequency of use was tonifying qi drug (22.6%) . The channels of TCM collected by the big data platform were mainly distributed in the spleen, lung and liver channels. The properties of TCM were mainly cold, flat and warm, and the flavors were mainly sweet, bitter and pungent. The combination of &quot;Astragalus and Licorice&quot; had the highest frequency. Six core drug combinations and three new prescriptions were obtained through complex system entropy clustering analysis. Conclusion The highest incidence of hyperlipidemia in ER positive breast cancer patients during endocrine therapy is 51-60 years old, and hypercholesterolemia is the most common. The position of hyperlipidemia in ER positive breast cancer patients during endocrine therapy is in the spleen. The medication are maily used for invigorating spleen to remove dampness, tonifying qi and regulating stomach

Collapsed Deposition of Accelerated C(60) Beam on Solid Surface(II) STM Studies

Mass-selected C(60) beam produced by laser ablation was accelerated and bombarded the (0001) surface of highly oriented pyrolitic graphite and (111) surface of gold single crystal. The samples were characterized by STM. The STM images showed that, the deposited species collapsed and formed planer structure on the solid surface, but the collapsed species were not dissociated and well oriented on the surface. Both positive and negative C(60) ions were observed in the desorption mass spectra, confirming that the species collapsed on the solid surface are still the C(60) clusters

Multiple infections containing the top five prevalent HPV genotypes and their impact on cervical lesions in Changzhou, China

Human papillomavirus (HPV) infection is the primary cause of cervical cancer and its precursor lesions. The overall prevalence of HPV genotypes in Changzhou has previously been reported. However, the distribution of multiple HPV infections and their roles in cervical injury have less been investigated. We aimed to assess the prevalence of multiple HPV infections among the people in Changzhou. Furthermore, we analyzed whether multiple HPV infections comprising the top five prevalent HPVs were more associated with abnormalities in E6 and E7 (E6/E7) mRNA, liquid-based cytology, and cervical histopathology than a single infection. In the current study, HPV 16, 52, 58, 53, and 81 were the top five prevalent HPV types, both in single and multiple infections. Compared to a single infection, multiple infections containing HPV 16/52/58 were closely linked to positivity for E6/E7 mRNA. In addition to HPV 16, multiple infections containing the remaining top four HPVs conferred a significant advantage on atypical squamous cells of undermined significance or worse in comparison to a single infection. Furthermore, women with multiple infections containing the top five prevalent HPV types were more likely to develop cervical intraepithelial neoplasia grade II or worse than those with a single HPV infection. Our results demonstrate the superiority of multiple HPV infections containing the top five prevalent HPV types in cervical disease progression, which should be closely monitored. These findings are conducive for formulating regional preventive strategies for cervical cancer screening and vaccination in Changzhou