The novel nanomaterials PNA-TN (PN) and PNA-TN-Dox (PND) have been shown to have strong inhibitory effects on breast cancer; however, it is unclear whether PN and PND have anti-head and neck squamous cell carcinoma (HNSCC) activity, and their potential mechanisms of activity are unknown. So, our study aims to explore the therapeutic effects of PN and PND on HNSCC and their possible mechanisms. We used a series of phenotypic research to evaluate the effects of PN + Laser (L) and PND + L on the biological function of HNSCC cells in vitro and in vivo. We subsequently used mechanism research to examine changes in mRNA and protein expression related to apoptosis, epithelial‒mesenchymal transition (EMT), and the JNK signalling pathway. Our study revealed that PN and PND have strong inhibitory effects on HNSCC cells both in vitro and in vivo. In vitro, PN and PND significantly inhibited the proliferation, migration, invasion and EMT ability of HNSCC cells and promoted apoptosis; the inhibitory effect in the PND + L group was significantly greater than that in the PN + L group. In vivo, both treatments led to significant reductions in tumour volume and weight. Notably, the tumour volume and weight in the PND + L group were significantly lower than those in the PN + L group. Mechanism research confirmed that PN + L activated the expression of apoptosis-related proteins and inhibited the expression of EMT-related proteins via the JNK pathway. Furthermore, the anti-HNSCC effect of PN + L was blocked after the use of a JNK pathway inhibitor. Treatment with PN + L or PND + L significantly inhibited the malignant progress of HNSCC cells, and the therapeutic effect of PND + L was significantly stronger than that of PN + L. The JNK signalling pathway is a key mechanism by which PN exerts its anti-HNSCC activity.

Aberrant gene expression is a key mechanism underlying pulmonary hypertension (PH) development. The alterations of genomic chromatin accessibility and their relationship with the aberrant gene expressions in PH are poorly understood. We used bulk Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) in pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxia-exposed rats mimicking group 3 human PH. Adult Sprague Dawley rats were commercially obtained from Hunan SJA (Hunan SJA Laboratory Animal Co., Changsha, China) and randomizedly allocated into four groups exposing to nomobaric hypoxia or normoxia for 1 or 28 days respectively. After the assessment of pulmonary hemodynamics, smooth muscle cells were isolated from intralobular arteries and simultaneously subjected to bulk Assay of ATAC-seq and RNA-seq. Hypoxic exposure for continuous 28-days, but not for 1-day, induced established PH phenotypes in rats. ATAC-seq revealed a major distribution of differential accessibility regions (DARs) annotated to the genome in out-of-promoter regions, following 1-day or 28-days hypoxia. 1188 DAR-associated genes and 378 differentially expressed genes (DEGs) were identified in rats after exposure to 1-day hypoxia, while 238 DAR-associated genes and 452 DEGs for 28-days hypoxia. Most of the DAR-associated genes or DEGs in 1-day did not overlap with that of 28-days hypoxia. A Pearson correlation analysis indicated no significant correlation between ATAC-seq and RNA-seq. The alterations in genomic chromatin accessibility and genes expression of PASMCs in the initial stage of hypoxia are distinct from the established stage of hypoxia-induced PH. The genomic differential accessibility regions may not be the main mechanisms directly underlying the differentially expressed genes observed either in the initial or established stages of PH. Thus the time-course alterations of gene expression and their possible indirect link with genomic chromatin accessibility warrant more attention in mechanistic study of pulmonary hypertension.

It remains unclear whether immune responses following natural infection can be sustained or potentially prove critical for long-term immune protection against SARS-CoV-2 reinfection. Here, we systematically mapped the phenotypic landscape of SARS-CoV-2-specific immune responses in peripheral blood samples of convalescent patients with COVID-19 by single-cell RNA sequencing. The relative percentage of the CD8 + effector memory subset was increased in both convalescent moderate and severe cases, but NKT-CD160 and marginal zone B clusters were decreased. Innate immune responses were attenuated reflected by decreased expression of genes involved in interferon-gamma, leukocyte migration and neutrophil mediated immune response in convalescent COVID-19 patients. Functions of T cell were strengthened in convalescent COVID-19 patients by clear endorsement of increased expression of genes involved in biological processes of regulation of T cell activation, differentiation and cell-cell adhesion. In addition, T cell mediated immune responses were enhanced with remarkable clonal expansions of TCR and increased transition of CD4 + effector memory and CD8 + effector-GNLY in severe subjects. B cell immune responses displayed complicated and dualfunctions during convalescence of COVID-19, providing a novel mechanism that B cell activation was observed especially in moderate while humoral immune response was weakened. Interestingly, HLA class I genes displayed downregulation while HLA class II genes upregulation in both T and B cell subsets in convalescent individuals. Our results showed that innate immunity was declined but SARS-CoV-2-specific T cell responses were retained even strengthened whereas complicated and dualfunctions of B cells, including declined humoral immunity were presented at several months following infections.

The impact of the COVID-19 pandemic on cancer death was reported recently [[1]Maringe C. Spicer J. Morris M. et al.The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study.Lancet Oncol. 2020; 21: 1023-1034Abstract Full Text Full Text PDF PubMed Scopus (1054) Google Scholar]. Wuhan where COVID-19 broke out has been critically hit [2Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (32454) Google Scholar, 3Li Q. Guan X. Wu P. et al.Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia.N Engl J Med. 2020; 382: 1199-1207Crossref PubMed Scopus (10589) Google Scholar]. The emergence has affected every aspect of health care, including the delivery of standard radiotherapy to patients with cancer. Those patients was facing disruption because of concerns about their susceptibility to the serious risks of COVID-19, travel restrictions, and the shortage of personnel, beds and personal protective equipment, and it has been reported that many cancer patients in hospitals of Wuhan got into such difficulties, so the number of patients receiving radiotherapy significantly decreased during the pandemic [4Xie C. Wang X. Liu H. Bao Z. Yu J. Zhong Y. et al.Outcomes in radiotherapy-treated patients with cancer during the COVID-19 outbreak in Wuhan, China.JAMA Oncol. 2020; 6 ([published online ahead of print]): 1457https://doi.org/10.1001/jamaoncol.2020.2783Crossref PubMed Scopus (18) Google Scholar, 5Bi J. Wei W. Hu D. Han G. Response letter: Letter to the editor regarding Wei W et al.: "Experience of the Hubei cancer hospital in Wuhan, China".Radiother Oncol. 2021; 155: e8-e9https://doi.org/10.1016/j.radonc.2020.08.030Abstract Full Text Full Text PDF Scopus (2) Google Scholar]. The radiotherapy center of Renmin Hospital of Wuhan University (RHWU) was shut down on January 24, and reopened until March 9, 2020. Thus, many patients were unplanned interrupted of radiotherapy during this period. Our survey of 140 consecutive patients in RHWU from March 9 to June 30, 2020, summarizes the clinical characteristics and outcome of these patients whose radiotherapy interrupted for 45 days or longer. The median age at diagnosis was 57 (range 27–83) years, 70 patients (50%) were men, and 70 (50%) were women. Including lung (n = 26 [18.6%]), breast (n = 21 [15%]), head and neck cancer (n = 24 [17.1%]), or gastrointestinal (n = 25[17.9%]) or gynecological cancer (n = 17 [12.1%]). During the pandemic, 76 patients stayed at home without any cancer treatments. Twenty-six patients took traditional Chinese medicine, 12 took oral chemotherapy or molecular targeted therapy medications, 10 continued radiotherapy in other hospitals. 87 (62.1%) patients have returned to our center. The result indicated that stage IV was associated with poor prognosis compared with stage I-III. But the delivered radiation dose was not associated with disease prognosis (Table1). After 5 months of follow-up, 16 patients including nine females and seven males were died (11.4%), age from 40 to 77 years old. 11 were diagnosed with stage IV cancer and five with stage III cancer. 14 (10.0%) died of cancer and 2 (1.4%) died of COVID-19.Table 1Characteristics of patients with interrupted radiotherapy.*Only including the 87 patients who came back to our hospital to continue therapy.No.Tumor TNM stagePDSDPRPIV171310.000**Stage I, II, III were compared as a whole group with stage IV.III6144II1203I071Radiation dose delivered/prescribed (radical radiotherapy)>=50%41250.153<50%6102Aim of radiotherapyPalliative940/#P value was not calculated as sample size is too small for statistical analyze.Radical10227Postoperative5281Preoperative001Site of primary cancerIntracranial461/#P value was not calculated as sample size is too small for statistical analyze.Head and neck4114Chest11233Abdomen110Pelvic cavity291Others240List of abbreviations: PD: progressive disease; SD: stable disease; PR: partial response.* Only including the 87 patients who came back to our hospital to continue therapy.** Stage I, II, III were compared as a whole group with stage IV.# P value was not calculated as sample size is too small for statistical analyze. Open table in a new tab List of abbreviations: PD: progressive disease; SD: stable disease; PR: partial response. Suboptimal delivery of radiotherapy (including delays, interruptions or omissions) has been demonstrated to compromise both local control and survival, especially for stage IV cancer patients. Other anti-tumor therapies (oral chemotherapy, endocrinotherapy or molecular targeted therapy) maybe improve the situation. Salvage radiotherapy was practicable, such as weekend treatments or increased number of daily fractions; increased dose per fraction; delivering extra fractions [[6]Bese N.S. Hendry J. Jeremic B. et al.Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation.Int J Radiat Oncol Biol Phys. 2007; 68: 654-661https://doi.org/10.1016/j.ijrobp.2007.03.010Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar]. Balancing the risks of infection and subsequent mortality with the increased risks of cancer mortality derived from delaying treatment is of utmost importance, to date, many cancer centers have shared their strategies and experiences, which were effective in protecting the patient and staff from infection [7Zhang L. Zheng Z. Hu G.Y. Yuan X.L. Prevention control measure to avoid cross infection during radiotherapy in coronavirus disease 2019 (COVID-19) epidemic in Wuhan, China.Radiother Oncol. 2020; 149: 104-106https://doi.org/10.1016/j.radonc.2020.04.011Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 8Wei W. Zheng D.D. Lei Y. Wu S. Verma V. Liu Y.S. et al.Radiotherapy workflow and protection procedures during the Coronavirus Disease 2019 (COVID-19) outbreak: Experience of the Hubei Cancer Hospital in Wuhan, China.Radiother Oncol. 2020; 148: 203-210https://doi.org/10.1016/j.radonc.2020.03.029Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 9Bi N. Yi J.L. Dai J.R. Wang S.L. Zhou Z.M. Men K. et al.Managing a radiotherapy center safely and efficiently using risk-adaptive strategies during coronavirus disease pandemic: Experience from national cancer center of China.Radiother Oncol. 2020; 148: 243-244https://doi.org/10.1016/j.radonc.2020.05.031Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar]. Further follow-up may clearly demonstrate the consequence of treatment interruption on local control and survival of cancer patients. Drs Li and Song had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. They are co-senior authors. Drs Yu and Hu are co-first authors who contributed equally to this work.

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread to many countries around the world. In addition to lung disease, severe cases also displayed varying degrees of liver injury. This article will describe the latest developments regarding coronavirus and the pathogenesis of liver injury, the prone population and clinical characteristics of these patients, as well as providing some suggestions for clinical treatment.

SUMMARY Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTS Large-scale scRNA-seq analysis depicts the immune landscape of COVID-19 Lymphopenia and active T and B cell responses coexist and are shaped by age and sex SARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses Cytokine storms with systemic S100A8/A9 are associated with COVID-19 severity

OBJECTIVE:The skin marking method (SMM) and bow-form-ruler marking method (BFRM) are two commonly used patient marking methods in mainland China. This study aims to evaluate SMM and BFRM by comparing the inter-fraction setup errors from using these two methods together with vacuum cushion immobiliz ation in patients underwent radiotherapy for different treatment sites. MATERIALS AND METHODS:Eighteen patients diagnosed with pelvic, abdominal and thoracic malignant tumors (with 6 patients per treatment site) were enrolled in this prospective study. All patients were immobilized with vacuum cushion. Each patient was marked by both SMM and BFRM before computed tomography (CT) simulation. Target location was verified by cone beam CT images with displacements assessed prior to each sampled treatment session. The localization errors in three translational and three rotational directions were recorded and analyzed. RESULTS:Images from 108 fractions in 18 patients produced 324 translational and 324 rotational comparisons for SMM and BFRM. The setup errors of all treatment sites showed no difference in two marking methods in any directions (p > 0.05). In subgroups of treatment site analysis, SMM significantly lessened the lateral and yaw setup errors compared to BFRM in the pelvic sites (0.39±1.85 mm vs –1.28±1.13 mm, p < 0.01 and –0.19±0.59° vs –0.61±0.59°, p < 0.05). However, in the abdominal subgroup, BFRM was superior to SMM for reduced vertical errors (0.17±2.73 mm vs 2.28±3.16 mm, p < 0.05). For the underweight or obese patients (with Body Mass Index, BMI < 18.5 or BMI≥24), SMM resulted in less yaw errors compared to BFRM (–0.05±0.38° vs –0.43±0.48°, p < 0.05). No significant difference between SMM and BFRM in setup errors of normal weighted patients (18.5≤BMI < 24) was observed for all three studied treatment sites. CONCLUSIONS:This study shows no significant difference in patient setup errors for various treatment sites between SMM and BFRM in general. SMM may be suitable for the pelvic tumor and patients with BMI < 18.5 or BMI≥24, while BFRM is recommended for the abdominal tumor sites.

Adult brainstem gliomas belong to a rare and heterogeneous group of brain tumors. The overall prognosis is poor; therapeutic options are limited, given the resistance to radiotherapy and the unclear role of chemotherapy/antiangiogenic therapy. Apatinib, a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor and mildly inhibits c-Kit, PDGFR-β, RET, and c-SRC, has been reported to show efficacy among some patients with malignant supratentorial gliomas. However, its effect on brainstem glioma has not been reported so far. Herein, a 66-year-old man with brainstem anaplastic astrocytoma isocitrate dehydrogenase (IDH) wild type was treated initially with combined radiotherapy, temozolomide, and apatinib. The patient achieved a complete response by MRI and continues to have an ongoing progression-free survival of over 8 months. To our knowledge, this is the first case report using apatinib to treat brainstem IDH wild-type anaplastic astrocytoma, displaying an excellent outcome. We also summarize cases of adult brainstem glioma treated with antiangiogenic therapy. Experiences using various regimens may improve understanding of this rare disease, and thus help physicians to seek more effective treatments for these patients.

This study aimed to clarify the association between serum total cholesterol (TC) levels and overall cancer risk. Study-specific relative risks (RR) and 95% confidence intervals (CI) were pooled using a random-effects model, and dose-response relation was also evaluated. Twelve prospective studies were identified with a total of 1,926,275 participants and 13,1676 cases. High levels of serum TC showed an inverse association with overall cancer risk (RR for the highest versus the lowest category: 0.87, 95% CI: 0.83 ∼ 0.90; I2 = 52.5%). A linear dose-response relation between serum TC levels and overall cancer risk was found (p = .004 for Wald test; I2 = 49.6%), and the pooled RR was 0.92 (95% CI: 0.89 ∼ 0.94) for 3 mmol/L, 0.86 (95% CI: 0.81 ∼ 0.90) for 5 mmol/L, 0.80 (95% CI: 0.74 ∼ 0.87) for 7 mmol/L. Our dose-response meta-analysis of 12 prospective studies indicated that higher serum TC levels were significantly associated with reduced cancer risk.