Factors influencing the detection rate of fumarate peak in 1H MR spectroscopy of fumarate hydratase-deficient renal cell carcinoma at 3 T MRI.

AIM: To identify factors that may be associated with fumarate detection rate in 1H-magnetic resonance spectroscopy (MRS) in fumarate hydratase-deficient renal cell carcinoma (FH-RCC). MATERIALS AND MEHODS: Between February 2018 and March 2022, 16 FH-RCC patients with 30 lesions underwent 1H-MRS. Detection results were classified as having a detected fumarate peak (n=12), undetected peak (n=10), or technical failure (n=8). Factors including tumour size, tumour location, treatment history, and metastasis status were collected and analysed. A Bayesian logistic regression model was applied to evaluate the association between these factors and the detection result. RESULTS: Bayesian analysis demonstrated significant associations between fumarate detection results and the following factors: long-axis diameter (odds ratio [OR] of 1.64; 95% confidence interval [CI] of 1.07-2.53), short-axis diameter (OR of 1.90; 95% CI of 1.19-3.06), voxel size (OR of 2.85; 95% CI of 1.70-4.75), treatment history (OR of 0.35; 95% CI of 0.21-0.58), non-metastatic state (OR of 2.45; 95% CI of 1.48-4.06), and lymph node metastasis (OR of 0.35; 95% CI of 0.21-0.58). Technical failure results were associated with factors such as treatment history (OR of 2.59; 95% CI of 1.37-4.66), non-metastatic state (OR of 0.36; 95% CI of 0.19-0.66), and lymph node metastasis (OR of 2.61; 95% CI of 1.39-4.74). CONCLUSION: Tumour size, treatment history, and metastasis character were associated with the detection of abnormal fumarate accumulation. This finding will serve as a reference for interpreting 1H-MRS results and for selecting suitable scenarios to evaluate FH-RCC.

Retraction Note: MiR-195-5p inhibits the cell migration and invasion of cervical carcinoma through suppressing ARL2.

The article "MiR-195-5p inhibits the cell migration and invasion of cervical carcinoma through suppressing ARL2", by S.-S. Pan, H.-E. Zhou, H.-Y. Yu, L.-H. Xu, published in Eur Rev Med Pharmacol Sci 2019; 23 (24): 10664-10671-DOI: 10.26355/eurrev_201912_19764-PMID: 31858533 has been retracted by the Authors for the following reasons: The authors found some inaccuracies in the research due to the number of experiments, as well as problems in the editing process of pictures. These errors may mislead readers and affect scientific research in this field. Figures 2D and 5D have also been questioned on PubPeer in April 2023. https://www.europeanreview.org/article/19764 This manuscript has been withdrawn. The Publisher apologizes for any inconvenience this may cause.

Proton Beam Therapy in the Reirradiation Setting of Brain and Base of Skull Tumour Recurrences.

The therapeutic management of local tumour recurrence after a first course of radical radiotherapy is always complex. Surgery and reirradiation carry increased morbidity due to radiation-induced tissue changes. Proton beam therapy (PBT) might be advantageous in the reirradiation setting, thanks to its distinct physical characteristics. Here we systematically reviewed the use of PBT in the management of recurrent central nervous system (CNS) and base of skull (BoS) tumours, as published in the literature. The research question was framed following the Population, Intervention, Comparison and Outcomes (PICO) criteria: the population of the study was cancer patients with local disease recurrence in the CNS or BoS; the intervention was radiation treatment with PBT; the outcomes of the study focused on the clinical outcomes of PBT in the reirradiation setting of local tumour recurrences of the CNS or BoS. The identification stage resulted in 222 records in Embase and 79 in Medline as of March 2023. Sixty-eight duplicates were excluded at this stage and 56 were excluded after screening as not relevant, not in English or not full-text articles. Twelve full-text articles were included in the review and are presented according to the site of disease, namely BoS, brain or both brain and BoS. This review showed that reirradiation of brain/BoS tumour recurrences with PBT can provide good local control with acceptable toxicity rates. However, reirradiation of tumour recurrences in the CNS or BoS setting needs to consider several factors that can increase the risk of toxicities. Therefore, patient selection is crucial. Randomised evidence is needed to select the best radiation modality in this group of patients.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

Assessing Equity of Access to Proton Beam Therapy: A Literature Review.

Proton beam therapy (PBT) is one of the most advanced radiotherapy technologies, with growing evidence to support its use in specific clinical scenarios and exponential growth of demand and capacity worldwide over the past few decades. However, geographical inequalities persist in the distribution of PBT centres, which translate into variations in access and use of this technology. The aim of this work was to look at the factors that contribute to these inequalities, to help raise awareness among stakeholders, governments and policy makers. A literature search was conducted using the Population, Intervention, Comparison, Outcomes (PICO) criteria. The same search strategy was run in Embase and Medline and identified 242 records, which were screened for manual review. Of these, 24 were deemed relevant and were included in this analysis. Most of the 24 publications included in this review originated from the USA (22/24) and involved paediatric patients, teenagers and young adults (61% for children and/or teenagers and young adults versus 39% for adults). The most reported indicator of disparity was socioeconomic status (16/24), followed by geographical location (13/24). All the studies evaluated in this review showed disparities in the access to PBT. As paediatric patients make up a significant proportion of the PBT-eligible patients, equity of access to PBT also raises ethical considerations. Therefore, further research is needed into the equity of access to PBT to reduce the care gap.

[Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis: analysis of a Chinese pedigree].

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.

A Salivary Gland Resident Macrophage Subset Regulating Radiation Responses.

Radiotherapy of head and neck cancers frequently leads to irreversible hypofunction of salivary glands, which severely compromises the quality of life and is extremely difficult to treat. We found recently that salivary gland resident macrophages are sensitive to radiation and interact with epithelial progenitors and endothelial cells through homeostatic paracrine factors. Heterogeneous subpopulations of resident macrophages are present in other organs with distinct functions, whereas subpopulations of salivary gland resident macrophages with distinct functions or transcriptional profiles have not been reported yet. Using single-cell RNA sequencing, we found that mouse submandibular glands (SMGs) contain 2 distinct self-renewing resident macrophage subsets, an MHC-IIhi subset present in many other organs and an uncommon Csf2r+ subset. The main source of Csf2 in SMGs are innate lymphoid cells (ILCs) that rely on IL15 for maintenance, while the main source of IL15 protein is Csf2r+ resident macrophages, indicating a homeostatic paracrine interaction between these cells. Csf2r+ resident macrophages are the major source of hepatocyte growth factor (Hgf) that regulates homeostasis of SMG epithelial progenitors. Meanwhile, Csf2r+ resident macrophages are responsive to Hedgehog signaling that can rescue salivary function impaired by radiation. Consistently, irradiation persistently decreased numbers of ILCs and levels of IL15 and Csf2 in SMGs, which were all recovered by transient activation of Hedgehog signaling after radiation. Csf2r+ resident macrophages and MHC-IIhi resident macrophages share transcriptome profiles of perivascular macrophages and macrophages associated with nerves and/or epithelial cells in other organs, respectively, and such niche preferences were supported by lineage tracing and immunofluorescent staining. These findings reveal an uncommon resident macrophage subset that regulates the homeostasis of the salivary gland and is promising as the target to restore salivary gland function impaired by radiation.

[Adult-onset immunodeficiency induced by anti-interferon-γ autoantibodies: report of 13 cases].

Objective: To investigate the clinical characteristics of a group of patients with adult-onset immunodeficiency (AOID) induced by anti-interferon-γ autoantibodies (AIGA). Methods: Thirteen cases of AOID in a northern China medical center (Peking Union Medical College Hospital) from October 2020 to April 2022 were included. Data comprising clinical manifestations, laboratory results, infection sites and pathogens were collected. Results: Among the 13 patients, 5 were male. The median age of disease onset was 47 (14 to 71) years. The median time from symptom onset to diagnosis was 4 years (1 to 8 years). Four patients were from northern China, and 9 from southern China. Common symptoms included lymphadenopathy (13/13), fever (12/13), respiratory tract symptoms (12/13), and weight loss (11/13). Laboratory tests showed increased levels of white blood cell count (9/13), neutrophil count and proportion (9/13), erythrocyte sedimentation rate (ESR) (12/13), and C reactive protein (CRP) (11/13). The median plasma titers of AIGA upon diagnosis were 5681(3194, 13246). Sites of infection included lungs (12/13), lymph nodes (9/13), bones and joints (9/13), skin and soft tissue (7/13), blood flow and bone marrow (4/13), and glands (3/13). Most patients had nontuberculous mycobacteria (NTM) (12/13) infection. Seven patients had more than one pathogen. Conclusions: AOID also affects patients visiting northern China hospitals. AIGA screening is recommended among patients with disseminated NTM infections or recurrent infections.

[Efficacy of transcatheter pulmonary valve perforation in neonates with pulmonary atresia with intact ventricular septum].

Objective: To explore the efficacy and safety of transcatheter pulmonary valve perforation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The clinical data on surgical treatment and follow-up in 16 patients with PA-IVS who underwent transcatheter pulmonary valve perforation in Women and Children's Hospital, Qingdao University from October 2018 to October 2021 were analyzed retrospectively. The right ventricular systolic pressure and percutaneous oxygen saturation (SpO2) were compared before and after operation. In addition, the SpO2 and echocardiographic data at preoperative and the last follow-up were compared. Comparisons between groups were performed using paired-samples t test. Results: Among the 16 patients (10 males and 6 females) with the age at operation of 19 (14, 26) days, 12 cases underwent transcatheter pulmonary valve perforation successfully, 2 cases were transferred to surgery department for open-heart pulmonary valvulotomy, and the remaining 2 cases were transmitted to surgery department for transthoracic pulmonary valve perforation. The age at operation of the 12 patients who underwent transcatheter pulmonary valve perforation was 18 (14, 27) days, and the weight was (3.6±0.4) kg. The immediate postoperative right ventricular systolic pressure decreased significantly ((57±16) vs. (95±19) mmHg (1 mmHg=0.133 kPa), t=7.49, P<0.001), and the postoperative SpO2 was improved effectively (0.90±0.48 vs.0.75±0.09, t=-5.61, P<0.001). The follow-up time was 22 (7, 33) months for 12 patients who underwent transcatheter pulmonary valve perforation successfully. At the last follow-up, the ratio of right to left ventricular transverse diameter was significantly higher than that before operative (0.55±0.05 vs. 0.45±0.05, t=-3.27,P=0.007). Furthermore, the Z-scores of pulmonary valvular diameter (-0.78±0.23 vs. -1.73±0.56, t=-8.52, P<0.001) and the tricuspid valvular diameter (-0.52±0.12 vs. -1.46±0.38, t=-10.40, P<0.001) were all significantly higher than preoperative data. At last, all the patients achieved biventricular circulation without death or major complications. Conclusion: Transcatheter pulmonary valve perforation is a safe and effective therapy for neonatal PA-IVS, and its curative effect has been confirmed by the medium follow-up data.

[Comparison of three methods for establishing rat peri-implantitis model].

OBJECTIVE: To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods. METHODS: Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1ß (IL-1ß). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death. RESULTS: After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1ß in the test groups were higher than those in the control group (P < 0.05). CONCLUSION: Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

Chimeric Antigen Receptor-Natural Killer Cells: A New Breakthrough in the Treatment of Solid Tumours.

Natural killer (NK) cells can quickly and directly eradicate tumour cells without recognising tumour-specific antigens. NK cells also participate in immune surveillance, which arouses great interest in the development of novel cancer therapies. The chimeric antigen receptor (CAR) family is composed of receptor proteins that give immune cells extra capabilities to target specific antigen proteins or enhance their killing effects. CAR-T cell therapy has achieved initial success in haematological tumours, but is prone to adverse reactions, especially with cytokine release syndrome in clinical applications. Currently, CAR-NK cell therapy has been shown to successfully kill haematological tumour cells with allogeneic NK cells in clinical trials without adverse reactions, proving its potential to become an off-the-shelf product with broad clinical application prospects. Meanwhile, clinical trials of CAR-NK cells for solid tumours are currently underway. Here we will focus on the latest advances in CAR-NK cells, including preclinical and clinical trials in solid tumours, the advantages and challenges of CAR-NK cell therapy and new strategies to improve the safety and efficacy of CAR-NK cell therapy.

Transcriptome analysis of the binucleate ciliate Tetrahymena thermophila with asynchronous nuclear cell cycles.

Tetrahymena thermophila harbors two functionally and physically distinct nuclei within a shared cytoplasm. During vegetative growth, the "cell cycles" of the diploid micronucleus and polyploid macronucleus are offset. Micronuclear S phase initiates just before cytokinesis and is completed in daughter cells before onset of macronuclear DNA replication. Mitotic micronuclear division occurs mid-cell cycle, while macronuclear amitosis is coupled to cell division. Here we report the first RNA-seq cell cycle analysis of a binucleated ciliated protozoan. RNA was isolated across 1.5 vegetative cell cycles, starting with a macronuclear G1 population synchronized by centrifugal elutriation. Using MetaCycle, 3244 of the 26,000+ predicted genes were shown to be cell cycle regulated. Proteins present in both nuclei exhibit a single mRNA peak that always precedes their macronuclear function. Nucleus-limited genes, including nucleoporins and importins, are expressed before their respective nucleus-specific role. Cyclin D and A/B gene family members exhibit different expression patterns that suggest nucleus-restricted roles. Periodically expressed genes cluster into seven cyclic patterns. Four clusters have known PANTHER gene ontology terms associated with G1/S and G2/M phase. We propose that these clusters encode known and novel factors that coordinate micro- and macronuclear-specific events such as mitosis, amitosis, DNA replication, and cell division.

[Differential diagnosis model of benign and malignant breast BI-RADS category 4 nodules based on serum SP70 and conventional laboratory indicators].

Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.

[Analysis and forecast of burden of pancreatic cancer along with attributable risk factors in Asia countries between 1990 and 2019].

Objective: To analyze the disease burden of pancreatic cancer in major Asian countries and forecast the burden of that in China, which helps to provide reference for the prevention and control of pancreatic cancer. Methods: Data on disease burden of pancreatic cancer among global and major Asian countries from on the Global Burden of Disease (GBD) 2019 were collected to describe burden distribution through the absolute numbers or standardized rates of incidence, death and disability adjusted life years (DALY) by year, sex and socio-demographic index. Estimated annual percentage changes (EAPC) was used to assess the trend of standardized rate. The proportion of deaths attributable to risk factors for pancreatic cancer in 2019 was used to compare by age, sex and region. ARIMA model was performed with R language to predict change of age-standardized incidence and death rates of pancreatic cancer from 2020 to 2029. Results: From 1990 to 2019, the standardized incidence rates of pancreatic cancer in China increased from 3.17/100 000 to 5.78/100 000, and the standardized death rate increased from 3.34/100 000 to 5.99/100 000. The increases exceeded other high-income Asia countries. In the past three decades, the standardized incidence, death and DALY rates of pancreatic cancer in global have increased year by year. Among the major countries in Asia, China has the highest growth rate of disease burden (EAPC of standardized incidence rates=2.32%, 95% CI: 2.10%-2.48% and EAPC of standardized death rate=2.25%, 95% CI: 2.03%-2.42%). In addition, incidence and death rates of pancreatic cancer in China are expected to continue on the rise between 2000 and 2029 by ARIMA model. Incidence rate is expected to increase 15.92% and death rate is expected to increase 15.86%. Conclusions: The standardized incidence and death rates of pancreatic cancer in China increase year by year with an increasing trend for the burden of disease. The disease burden of pancreatic cancer is expected to rise due to the increase and aging of the population. Preventive measures should be adopted to decrease the burden of the pancreatic cancer.

Experimental Investigation of Different Fineness and Firing Temperatures on Pellets Properties of Different Iron Ore fines from Indian Mines.

In India, during mining and ore processing, ore fine generation is a common phenomenon, in which more than 60% of process ore becomes discarded material. To explore the alternative of high-grade ores, mutual replacement with the utility of dump ore fines is the best way. With this perspective, Kiruburu iron ore mine (Iron Ore No.1) and Meghataburu iron ore mine (Iron Ore No.2) dumped fines were chosen for a Blaine no. investigation, in the connection of firing temperatures, to get optimum desirable physical properties, Cold Compression Strength (C.C.S.),and Apparent Porosity (A.P.), with physico-chemical properties, Reducibility Degradation Index (R.D.I.), and Reducibility Index (R.I.). To characterize pellet properties with input variables, a microstructure phase study has been conducted using a scanning electron microscope (S.E.M.), energy dispersive spectroscopy (EDS), and X-ray diffraction analysis (XRD). The Iron Ore No.1 and 2 fine pellets survey showed good, desirable properties, at the Blaine no., of 1678 cm2/g and 2311 cm2/g (corresponding to 200 mesh size), and the best results are attained at a firing temperature of 1300 °C. Thermal kinetic analysis of the heating of pellets has been done to knowthe activation energy of different ore characteristics. The results showed that Iron Ore No.2 pellets have high activation energy.

Neoadjuvant chemoradiation alters the immune microenvironment in pancreatic ductal adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) have a grim prognosis despite complete surgical resection and intense systemic therapies. While immunotherapies have been beneficial with many different types of solid tumors, they have almost uniformly failed in the treatment of PDAC. Understanding how therapies affect the tumor immune microenvironment (TIME) can provide insights for the development of strategies to treat PDAC. We used quantitative multiplexed immunofluorescence (qmIF) quantitative spatial analysis (qSA), and immunogenomic (IG) analysis to analyze formalin-fixed paraffin embedded (FFPE) primary tumor specimens from 44 patients with PDAC including 18 treated with neoadjuvant chemoradiation (CRT) and 26 patients receiving no treatment (NT) and compared them with tissues from 40 treatment-naïve melanoma patients. We find that relative to NT tumors, CD3+ T cell infiltration was increased in CRT treated tumors (p = .0006), including increases in CD3+CD8+ cytotoxic T cells (CTLs, p = .0079), CD3+CD4+FOXP3- T helper cells (Th, p = .0010), and CD3+CD4+FOXP3+ regulatory T cells (Tregs, p = .0089) with no difference in CD68+ macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p < .001). These findings demonstrate that, while CRT can achieve high T cell densities in PDAC compared to melanoma, phenotype and spatial organization of T cells may limit benefit of T cell infiltration in this immunotherapy-resistant tumor.

[Early histological changes detected by confocal microscopy in patients with advanced keratoconus receiving collagen cross-linking therapy].

Objective: To investigate the early histological changes by confocal microscopy of patients with advanced keratoconus receiving collagen cross-linking therapy. Methods: In this prospective case series study, confocal microscopy was used to observe 23 patients (32 eyes) who were diagnosed with advanced keratoconus and treated with collagen cross-linking at the Department of Ophthalmology, Chinese PLA General Hospital from September 2017 to March 2019, aged (26±10) year. All patients were examined before and at 1 week, 1 month and 3 months after the therapy. The tissue structure changes, the density of nerve fibers, stromal cells and endothelial cells, and the depth of the corneal stroma were recorded and compared. The overall differences at different times were compared by repeated measurement analysis of variance or Friedman test, and the pairwise comparison was corrected by LSD-t test or Bonferroni test. Results: One week after collagen cross-linking, the epithelial cells were in the repair stage, showing an increased nucleolar size and an enhanced reflection, and the activated cells could be detected under the epithelium. The superficial corneal stroma was swollen and spongiform, while the deep corneal stroma was patchy or cord-like, scattered and with a strong reflection. One month after the therapy, epithelial cells recovered, subepithelial nerves began to grow, the superficial corneal stroma still showed a spongy structure, and the reflection was further enhanced. The activation of the deep corneal stroma exhibited as thicker plaques or cord-like structure. Three months after the therapy, the continuous elongation of single nerve fibers could be detected occasionally. There was statistically significant difference in the density of nerve fibers before and early after the therapy (F=233.30, P<0.001). Compared with the preoperative value [(14.60±2.57) mm/mm2], the density of subepithelial nerve fibers decreased significantly in the early postoperative period, which was (0.51±0.31), (3.65±2.21) and (8.50± 4.02) mm/mm2, respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). There was also statistically significant differences in the density of anterior stromal cells before and early after the therapy (χ2=92.48, P<0.001). Compared with the preoperative value [347.00(345.00,395.75) cells/mm2] the density of anterior stromal cells decreased significantly in the early postoperative period, which was 2.00(1.00,5.75), 2.50(1.00,5.75) and 79.00(64.25,94.00) cells/mm2, respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). Within 3 months after the therapy, the depth of the corneal stroma observed by confocal microscopy ranged from 245 to 536 µm, with an average of (400.56±86.12) µm. Histologically, the depth of the corneal stroma ranged from 245 to 536 µm [average, (402.13±89.20) µm], from 251 to 527 µm [average, (399.88±85.92) µm] and from 259 to 530 µm [average, (399.69±85.94) µm] at 1 week, 1 month and 3 months, respectively, with no significant difference (F=0.797, P=0.455). There was no significant difference in the density of posterior stromal cells [(260.6±33.2) cells/mm2 preoperatively, (264.4±44.5) cells/mm2 at 1 week, (263.9±37.6) cells/mm2 at 1 month and (266.3±40.2) cells/mm2 at 3 months] and endothelial cells [(2 707±152.6) cells/mm2 preoperatively, (2 704±148.5) cells/mm2 at 1 week, (2 705±152.6) cells/mm2 at 1 month and (2 704±150.1) cells/mm2 at 3 months] between different time points (F=1.380, 1.011; P=0.259, 0.351). Conclusions: Confocal microscopy is able to clearly document the early morphological characteristics after collagen cross-linking in the treatment of keratoconus, including the epithelial and subepithelial nerve injury repair, the spongiform superficial corneal stroma, the patchy or cord-like deep corneal stroma, and the relatively stable stromal depth change.

Normal Tissue Complication Probability Modelling for Toxicity Prediction and Patient Selection in Proton Beam Therapy to the Central Nervous System: A Literature Review.

Normal tissue complication probability (NTCP) models can guide clinical decision making in radiotherapy. In recent years, they have been used for patient selection for proton beam therapy (PBT) for some anatomical tumour sites. This review synthesizes the published evidence regarding the use of NTCP models to predict the toxicity of PBT, for different end points in patients with brain tumours. A search of Medline and Embase using the Patients, Intervention, Comparison, Outcome (PICO) criteria was undertaken. In total, 37 articles were deemed relevant and were reviewed in detail. Nineteen articles on NTCP modelling of toxicity end points were included. Of these, 11 were comparative NTCP studies of PBT versus conventional photon radiotherapy (XRT), which evaluated differences in plan dosimetry and then assumed that XRT-derived literature estimates of NTCP would be applicable to both. Seven papers derived NTCP models based on PBT outcome data, two of which provided model parameters. Among analysed end points, the reduced risk of secondary tumours with PBT as compared with XRT is estimated - through modelling studies - to be considerable and was highlighted by most authors. For other analysed end points, the clinical benefit of PBT mainly depends on tumour location in relation to organs at risk as well as prescription doses. NTCP models can be useful tools for treatment plan comparison. However, most published toxicity data were derived from XRT cohorts; this review has highlighted the need for further studies relating dose-volume parameters to observed toxicity in PBT-treated patients. Specifically, there is a need for PBT-specific NTCP models that can be implemented in the clinical practice. NTCP models built on robust clinical data for the most common radiotherapy toxicities in the brain would potentially redefine the current indications for PBT.

[Clinical value of tumor-associated autoantibodies in diagnosis of early non-small cell lung cancer].

Objective: To investigate the auxiliary diagnostic value of seven tumor-associated autoantibodies (AABs) P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE in early non-small cell lung cancer (NSCLC). Methods: The case-control study enrolled 195 patients with early NSCLC [71 males and 124 females, aged (55.70±11.78) years old], 114 patients with benign lung disease [44 males and 70 females, aged (52.85±12.31) years old] and 100 healthy subjects [39 males and 61 females, aged (53.62±9.97) years old] from the First Affiliate Hospital of Nanjing Medical University from June 2020 to December 2020. AABs were detected by enzyme-linked-immunosorbent serologic assay (ELISA), and carcinoembryonic antigen (CEA),cytokeratin 19-fragments (CYFRA21-1) and neuron specific enolase (NSE) were detected by electrochemiluminescence. The levels of AABs,CEA,CYFRA21-1 and NSE in the 3 groups were compared. Patients with benign lung diseases and healthy subjects were combined into the control group, and the positive rate of each indicator in the NSCLC group and the control group was compared. The diagnostic efficacy of single and combined tests for NSCLC were obtained using receiver operating characteristic (ROC) curves. Besides, the relationship between the levels of AABs, CEA, CYFRA21-1 and NSE and their clinicopathological features and preoperative imaging parameters in NSCLC patients was assessed. Results: The levels of SOX2 [0.70 (0.10, 2.40) U/mL] and GBU4-5 [1.30 (0.30, 8.90) U/mL] in NSCLC group were higher than those in benign disease group [SOX2: 0.50 (0.10, 1.60) U/mL, GBU4-5: 0.80 (0.10, 2.30) U/mL, Z values were 27.258 and 45.797; P values were all<0.05] and health control group [SOX2: 0.45 (0.10, 1.08) U/mL, GBU4-5: 0.75 (0.20, 1.78) U/mL, Z values were 32.551 and 40.456; P values were all<0.05], and there was no significant difference between benign disease group and health control group (Z values were 5.293 and 5.340, P values were all>0.05). The levels of CEA [1.75 (1.08, 2.72) U/mL] and CYFRA21-1 [1.81 (1.41, 2.36) U/mL] in NSCLC group were higher than those in healthy control group [CEA: 1.22 (0.68, 1.81) U/mL, CYFRA21-1: 1.43 (1.14, 1.74) U/mL, Z values were 64.100 and 37.597; P values were all<0.05], but there was no significant difference between NSCLC group and benign group [CEA: 1.74 (1.01, 2.51) U/mL, CYFRA21-1: 1.82 (1.45, 2.46) U/mL, Z values were 7.275 and 10.621; P values were all>0.05]. The positive rates of P53, SOX2, GAGE7, GBU4-5 and CEA in NSCLC group were higher than those in the control group [P53: 10.3% vs 0.9%, SOX2: 11.3% vs 2.3%, GAGE7: 11.3% vs 0.5%, GBU4-5: 30.1% vs 5.6%, CEA: 9.7% vs 0.9%, χ2 values were 17.420, 13.242, 22.485, 43.211, 16.255, respectively; P values were all<0.05]. The diagnostic efficiency of the combined detection of seven AABs was better than that of single detection. Seven AABs combined with CEA [area under curve (AUC): 0.732, sensitivity: 64.10%] and with CYFRA21-1 (AUC: 0.737, sensitivity: 58.97%) greatly improved the diagnostic efficiency and sensitivity of CEA (AUC: 0.583, sensitivity: 50.77%) and CYFRA21-1 (AUC: 0.552, sensitivity: 44.10%). The levels of SOX2 and CEA in NSCLC patients were correlated with the degree of tumor invasion (H values were 6.436 and 14.071; P values were all<0.05); the levels of GAGE7 and CEA were correlated with the nodule density (H values were 7.643 and 12.268; P values were all<0.05); and the levels of SOX2, GAGE7, CEA and CYFRA21-1 were all correlated with the nodule size (H values were 10.837, 11.528, 31.835, 20.338; P values were all<0.05). Conclusion: The detection of AABs combined with CEA and CYFRA21-1 is helpful for the early auxiliary diagnosis of NSCLC, and plays an important role in prevention and screening for early lung cancer.