CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Preoperative diagnostic value of coronary CT angiography in acute Stanford type A aortic dissection involving the coronary arteries.

AIM: To assess the diagnostic value of coronary computed tomography angiography (CCTA) in acute type A aortic dissection (ATAAD) with coronary artery involvement and to evaluate whether CCTA could provide potentially useful information for selecting the surgical method. MATERIALS AND METHODS: Patients with ATAAD treated from January 2019 to December 2020 were reviewed retrospectively. Involvement of the coronary arteries based on CCTA findings were grouped into three major types and five subtypes. Interobserver and intraobserver diagnostic agreement for five subtypes were determined. The patients were divided into the coronary artery bypass grafting (CABG) and non-CABG groups, and the proportions of the five subtypes between the two groups were compared. RESULTS: A total of 95 patients were enrolled in this study. Interobserver and intraobserver diagnostic agreement were both substantial in the left and right coronary arteries. Overall, the proportions of the five subtypes of coronary artery involvement were significantly different between the two groups (p<0.001). The proportion of Type A was elevated in the non-CABG group compared with the CABG group (22.6% versus 71.9%); by contrast, the proportions of Type B1 (35.5% versus 14.1%), Type B2 (19.4% versus 10.9%), Type C1 (6.5% versus 0%), and Type C2 (16.1% versus 3.1%) were elevated in the CABG group. CONCLUSION: CCTA is reliable in evaluating coronary artery involvement by ATAAD. The present retrospective study indicated that CABG may be considered if the intimal flap disrupts the coronary orifice and causes luminal stenosis >50%, particularly Type B, or if an intimal tear occurs in the coronary orifice (Type C), which deserve further validation through prospective studies.

Paradoxical androgen receptor regulation by small molecule enantiomers.

Small molecules that target the androgen receptor (AR) are the mainstay of therapy for lethal castration-resistant prostate cancer (CRPC), yet existing drugs lose their efficacy during continued treatment. This evolution of resistance is due to heterogenous mechanisms which include AR mutations causing the identical drug to activate instead of inhibit the receptor. Understanding in molecular detail the paradoxical phenomenon wherein an AR antagonist is transformed into an agonist by structural mutations in the target receptor is thus of paramount importance. Herein, we describe a reciprocal paradox: opposing antagonist and agonist AR regulation determined uniquely by enantiomeric forms of the same drug structure. The antiandrogen BMS-641988, which has (R)-chirality at C-5 encompasses a previously uncharacterized (S)-stereoisomer that is, surprisingly, a potent agonist of AR, as demonstrated by transcriptional assays supported by cell imaging studies. This duality was reproduced in a series of novel compounds derived from the BMS-641988 scaffold. Coupled with in silico modeling studies, the results inform an AR model that explains the switch from potent antagonist to high-affinity agonist in terms of C-5 substituent steric interactions with helix 12 of the ligand binding site. They imply strategies to overcome AR drug resistance and demonstrate that insufficient enantiopurity in this class of AR antagonist can confound efforts to correlate structure with function.

Standardization method, testing scenario, and accuracy of the infrared prediction model affect the standardization accuracy of milk mid-infrared spectra.

The widespread use of milk mid-infrared (MIR) spectroscopy for phenotype prediction has urged the application of prediction models across regions and countries. Spectra standardization is the most effective way to reduce the variability in the spectral signal provided by different instruments and labs. This study aimed to develop different standardization models for MIR spectra collected by multiple instruments, across 2 provinces of China, and investigate whether the standardization method (piecewise direct standardization, PDS, and direct standardization, DS), testing scenario (standardization of spectra collected on the same day or after 7 mo), infrared prediction model accuracy (high or low), and instrument (6 instruments from 2 brands) affect the performance of the standardization model. The results showed that the determination coefficient (R2) between absorbance values at each wavenumber provided by the primary and the secondary instruments increased from less than 0.90 to nearly 1.00 after standardization. Both PDS and DS successfully reduced spectra variation among instruments, and performed significantly better than non-standardization (P < 0.05). However, DS was more prone to overfitting than PDS. Standardization accuracy was higher when tested using spectra collected on the same time compared with those collected 7 mo after (P < 0.05), but great improvement in model transferability was obtained for both scenarios compared with the non-standardized spectra. The less accurate infrared prediction model (for C8:0 and C10:0 content) benefited the most (P < 0.05) from spectra standardization compared with the more accurate model (for total fat and protein content). For spectra collected after 7 mo from standardization, after PDS the RMSE between predictions obtained by different machines decreased on average by 86 and 94% compared with the values before standardization, for C8:0 and C10:0 respectively. The secondary instrument had no significant effect on the R2 between predictions (P > 0.05). The variation in the spectral signal provided by different instruments was successfully reduced by standardization across 2 provinces in China. This study lays the foundations for developing a national MIR spectra database to provide consistent predictions across provinces to be used in dairy farm management and breeding programs in China. Besides, this provides opportunities for data exchange and cooperation at international levels.

Prenatal exposure to PM2.5 components and the risk of different types of preterm birth and the mediating effect of pregnancy complications: a cohort study.

OBJECTIVES: This study aims to reveal the single and mixed associations of PM2.5 and its components with very, moderately, and late preterm births and to explore the potential mediating role of pregnancy complications in PM2.5-induced preterm birth. STUDY DESIGN: This was a retrospective cohort study. METHODS: We enrolled 168,852 mothers and matched the concentrations of PM2.5 and its five components (OM, SO42-, BC, NO3-, and NH4+) based on their geographical location. Next, we used generalized linear models, quantile g-computation, and mediation analysis to evaluate the associations of PM2.5 and its components with very, moderately, and late preterm births and the mediating role of pregnancy complications. RESULTS: Prenatal exposure to PM2.5 and its components was associated with preterm birth, and the association was strongest in the third trimester. Preterm birth was associated with co-exposure to a mixture of PM2.5 components in the third trimester, and the contributions of NO3-, NH4+, and BC to the risk of preterm birth were positive. Meanwhile, pregnancy complications mediated PM2.5-induced preterm birth. Moreover, very and moderately preterm births were associated with PM2.5 and its components in the second and third trimesters, and very and late preterm births were associated with co-exposure to a mixture of PM2.5 components in the third trimester. CONCLUSIONS: Later exposure to PM2.5 during pregnancy will cause earlier preterm birth. Targeted and positive interventions for anthropogenic sources of specific PM2.5 components and pregnancy complications are helpful for preterm birth prevention.

[Retrospective analysis of perioperative anaphylactic shock induced by cefuroxime].

This study investigated the characteristics and frequency of perioperative anaphylactic shock induced by cefuroxime, so as to provide a reference for the safe and rational use of cefuroxime in the perioperative period. Cases of perioperative anaphylactic shock caused by cefuroxime in our hospital from 2011 to 2021 were extracted from the Adverse Drug Reaction Monitoring System. Literature reporting adverse drug reactions (ADR) including cefuroxime-induced anaphylactic shock in perioperative settings was collected from the CNKI, VIP, Wanfang, PubMed, and Web of Science databases from their respective inception to May 2022. Statistical analysis was performed for all cases of cefuroxime-induced perioperative anaphylactic shock. A total of 31 patients were included [13 men (48.1%) and 14 women (51.9%)], most of whom were over 60 years old (n=16, 59.3%); 9 (29.0%) patients had a history of drug allergy; 5 (16.1%) patients had received skin tests, but with negative results; 28 (90.3%) patients received treatment intravenously; 22 (71.0%) patients were treated after anesthesia. For 20 (64.5%) patients the ADR occurred within 10 minutes after anesthesia. The main manifestations were hypotension, dyspnea, rash, and tachycardia. For all patients, symptoms resolved after withdrawal of the drug and active rescue, and there were no deaths. A history of allergy and skin test findings may have limitations in predicting perioperative anaphylactic shock caused by cefuroxime; greater vigilance should be exercised when using cefuroxime in the perioperative period. Close monitoring is recommended for patients undergoing treatment with cefuroxime. Rescue therapy should be administered for allergic shock, and suitable response measures must be taken in a timely manner to ensure the safety of patients.

[Clinicopathological features and prognosis of sporadic mismatch repair deficient colorectal cancer].

Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side (P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Genomic hallmarks of localized, non-indolent prostate cancer.

Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.

The safety of human embryos following long-term cryopreservation ( >6 years) on vitrification.

BACKGROUND: Vitrification of embryos has become the basic means of assisted reproductive technology (ART) therapy in recent years. Concerns have also been raised about the safety of vitrification and the effect of cryopreservation time. Most of the previous studies were on the data within 6 years of cryopreservation. OBJECTIVE: In this study, we aimed to evaluate the impact of long-term cryopreservation (>6 years) on pregnancy and neonatal outcomes. MATERIALS AND METHODS: This research was a single-center, retrospective analysis, including 426 frozen-thawed embryo transfer (FET) cycles. Patients who participated in IVF-FET cycles between January 2013 to December 2020 were analyzed. Preferentially matched participants were divided into three groups according to storage time: group A (>72 months), group B (0-3 months, propensity score matching [PSM] according to the age of oocyte retrieval), and group C (0-3 months, PSM according to the age of embryo transfer). RESULTS: Our results revealed that there were no significant differences in human chorionic gonadotropin [HCG] positive rate, clinical pregnancy rate, miscarriage rate, live birth rate, and neonatal outcomes when the embryo storage duration >72 months. But the proportion of high birth weight was higher in group A (>72 months) when matched according to age at embryo transfer. CONCLUSION: The results of our study showed that long-term cryopreservation had no effect on the pregnancy and neonatal outcomes of vitrification. The results offer evidence for the safety of using long-term cryopreservation embryos after vitrification. DOI: 10.54680/fr23310110612.

[Analysis of the difference in MGMT promoter status in gliomas and its significance in prognosis assessment].

The data of 1 268 newly diagnosed gliomas from the Fourth Ward of Neurosurgery Department of Beijing Tiantan Hospital between April 2013 and March 2022 were retrospectively analyzed. Based on postoperative pathology, the gliomas were divided into groups: oligodendrogliomas (n=308), astrocytomas (n=337) and glioblastomas (n=623). According to the O6-methylguanine-DNA methyl transferase (MGMT) promoter status defined by the 12% of best cut-off value in previous research results, patients were divided into methylation group (n=763) and non-methylation group (n=505). Methylation level [M (Q1, Q3)] in patients with glioblastoma, astrocytoma and oligodendroglioma was 6% (2%, 24%), 17% (10%, 28%) and 29% (19%, 40%), respectively (P<0.001). Compared with non-methylation patients, the progression-free survival (PFS) and overall survival (OS) of glioblastomas patients with methylation of MGMT promoter demonstrated more favorable prognosis [M (Q1, Q3)]) of PFS: 14.0 (6.0, 36.0) months vs 8.0 (4.0, 15.0) months, P<0.001; M (Q1, Q3) of OS: 29.0 (17.0, 60.5) months vs 16.0 (11.0, 26.5) months, P<0.001]. In astrocytomas patients, the PFS was much longer for those with methylation [the median PFS of patients with methylation was not observed at the end of follow-up, but those without methylation showed a median PFS of 46.0 (29.0, 52.0) months] (P=0.001). However, no statistically significant difference was observed in OS [the median OS of patients with methylation was not observed at the end of follow-up, but those without methylation had a median OS of 62.0 (46.0, 98.0) months] (P=0.085). In oligodendrogliomas patients, no statistically significant differences of PFS and OS were observed between patients with methylation and those without methylation. MGMT promoter status was a related factor affecting PFS and OS in glioblastomas (PFS: HR=0.534,95%CI: 0.426-0.668, P<0.001; OS: HR=0.451, 95%CI: 0.353-0.576, P<0.001). Moreover, MGMT promoter status was also a related factor affecting PFS in astrocytomas (HR=0.462, 95%CI: 0.221-0.966, P=0.040), but not for OS (HR=0.664, 95%CI: 0.259-1.690, P=0.389). The methylation level of MGMT promoter differed substantially in different types of gliomas, and the status of MGMT promoter profoundly affected the prognosis of glioblastomas.

[Clinical characteristics of 13 cases with entrapped temporal horn syndrome and efficacy of refined temporal-to-frontal horn shunt].

Thirteen consecutive patients with entrapped temporal horn syndrome in the Department of Neurosurgery of Beijing Tiantan Hospital from February 2018 to September 2022 were retrospectively analyzed, and there were 5 males and 8 females, with a mean age of (43±21) years. Increased intracranial pressure caused by hydrocephalus was the main clinical symptom. All the patients underwent refined temporal-to-frontal horn shunt, and all the symptoms were improved after surgery. Postoperative Karnofsky performance score (KPS) [90 (90, 100)] was higher than preoperative KPS [57 (40, 70)] (P=0.001). However, postoperative entrapped temporal horn volume [13.85 (8.90, 15.25) cm3] decreased, compared with preoperative volume [66.52 (38.65, 88.65) cm3] (P=0.001). Likewise, postoperative midline shift [0.77 (0, 1.50) mm] was longer than preoperative midline shift [6.69 (2.50, 10.00) mm] (P=0.002). No surgery-related complications were observed after the operation. Therefore, the refined temporal-to-frontal horn shunt is safe and effective treatment for entrapped temporal horn syndrome, with favorable outcomes.

[Research progress of transcriptomics and proteomics in schizophrenia].

Schizophrenia is a severe psychiatric disorder with an unclear etiology and various clinical manifestations. The diagnosis and consequent treatment of schizophrenia mainly rely on clinical symptoms. Multiple risk sites associated with schizophrenia have been identified, yet objective indicators have not been found to facilitate clinical diagnosis and treatment of schizophrenia. The development of omics technology provides different perspectives on the etiology of schizophrenia and make the early identification, diagnosis and treatment of the disorder possible. This article summarizes the prevalence of schizophrenia, reviews the research results and shortcomings of transcriptomics and proteomics, as well as the latest achievements and prospects of multi-omics, aiming to reveal the use of omics in SZ, provide more comprehensive biological evidence to reveal the complex pathogenesis of schizophrenia and provide a theoretical basis for the early identification, accurate diagnosis, disease progression control, and prognosis improvement of schizophrenia.

Antimicrobial and anti-dust mite efficacy of Cinnamomum camphora chvar. Borneol essential oil using pilot-plant neutral cellulase-assisted steam distillation.

Cinnamomum camphora chvar. Borneol essential oil (BEO) was efficiently extracted by using pilot-plant neutral cellulase-assisted steam distillation (NCSD). Borneol, ß-cadinene and α-caryophyllene were identified as major components. Bacillus subtilis was the most sensitive bacteria to BEO with the lowest minimal inhibition concentration (MIC) and minimal bactericial concentration (MBC) at 1·75 and 3·50 mg ml-1 , respectively. Antimicrobial activity of the BEO was also reasonably high against Salmonella typhimurium, Escherichia coli and Staphylococcus aureus, but not sensitive against two fungi, i.e. Aspergillus niger and Penicillium aurantiogriseum. Changes in permeability and integrity of cell membrane, damage of cell wall and further leakage out of metabolites and ions were determined as bactericidal mechanisms of BEO against the two gram-positive bacteria. The BEO showed a reasonably high repelling activity of dust mite, which achieved higher than 95% repelling dust mite activity after the treatment of BEO solution at 0·50 mg ml-1 . When the concentration of BEO was higher than 0·50 mg ml-1 , it was B-grade miticide with miticidal activity higher than 95%. Miticidal procedures were characterized as excitation, contraction, relaxation and lastly leading to the death of dust mite. It is speculated that the BEO would cause dehydration and death of dust mite as neuromuscular toxicity.

[The characteristics and risk factors of cardiovascular diseases and psychological status in science and technologyists].

Objectives: To investigate the prevalence and related factors of cardiovascular diseases (CVD) and psychological problems in Chinese science and technology workers. Methods: The investigation was organized and conducted by the Innovative and Development Institute of China Association of Senior Scientists and Technologists and Capital Medical University Affiliated Beijing Anzhen Hospital, and included science and technology workers from research institutions and medical institutions in China by random sampling methods through face-to-face and online questionnaire investigation from July 1, 2019 to March 31, 2021. Information including age, sex, work stress status, CVD history, sleep, depression, and anxiety were included in the questionnaire. Results: This survey included 14 552 subjects. Among them, 25.5% were suffered from CVD, 48.6% were with insomnia, 28.8% experienced depression/anxiety (including only depression, only anxiety, depression combined with anxiety), and 15.6% had CVD in combined with depression/anxiety. Taking those without CVD and depression/anxiety as reference group, multiple logistic regression analyses showed that work stress increased the risk of depression/anxiety in subjects without CVD (manageable work stress, OR=2.253, 95%CI 1.583-3.206, overwhelming work stress OR=7.899, 95%CI 5.094-12.250), and drinking increased the risk of CVD (OR=1.978, 95%CI 1.382-2.833). Moreover, overwhelming work stress (OR=4.012, 95%CI 2.515-6.399) and smoking (OR=2.342, 95%CI 1.603-3.421) increased the risk of depression/anxiety in subjects with CVD (all P<0.001). Conclusion: The high morbidities of depression/anxiety, CVD, and CVD in combination with depression/anxiety urge us to take actions to protect the heart and mental health of scientific and technological workers.

[Analysis of clinical and endoscopic characteristics of colorectal polyps in children].

To analyze the clinical and endoscopic characteristics of colorectal polyps in children, and to explore the detection rate, age and gender distribution characteristics, endoscopic treatment effect and follow-up monitoring of colorectal polyps in children, so as to provide reference for disease management of colorectal polyps in children. The clinical and endoscopic characteristics of children with colorectal polyps in Xi 'an Children's Hospital from January 2019 to December 2019 were retrospectively analyzed. The patients were divided into 5 groups according to age (y): 0

[The outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma].

Objective: To examine the outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma (PCNSL). Methods: The clinical data of 18 patients with PCNSL who were treated according to Tiantan first-aid protocol at Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University from November 2019 to December 2021 were retrospectively analyzed. There were 9 males and 9 females, aged (56.9±11.1)years (range: 29 to 77 years). The median Karnofsky performance status(KPS) score at admission was 40 (range: 20 to 60). Three patients were mild coma, 3 were lethargy and 12 were conscious. The mean midline shift was 0.7 cm (range: 0 to 1.8 cm). After admission, all patients were treated according to the plan of rapid biopsy, rapid routine pathology and rapid salvage chemotherapy. The treatment procedures, clinical and radiographic outcomes, KPS score and adverse reactions of patients after chemotherapy were collected. Results: All of the 18 patients completed the first-aid treatment. The median duration from admission to the biopsy was 1 day (range: 0 to 5 days), from biopsy to routine pathological diagnosis was 1 day (range: 1 to 4 days) and from routine pathology to salvage chemotherapy was 1 day (range: 0 to 4 days). All the patients were pathologically confirmed with diffuse large B cell lymphoma, 1 patient was double-hit lymphoma. Seventeen patients underwent clinical remission and 1 died of cardiac dysfunction. The successful salvage rate was 17/18. Radiologically, complete remission was observed in 1 case, partial remission in 16 cases, and stable disease in 1 case. The median KPS score at discharge was 60 (range: 30 to 80). The mild gastrointestinal, hematological and hepatic adverse effects were observed after chemotherapy. Conclusion: Tiantan first-aid protocol is effective for critically ill patients with PCNSL, which has the merit to be popularly used and improved.

[Vogt-Koyanagi-Harada syndrome in the setting of vemurafenib therapy for metastatic melanoma: a case report].

A 53-year-old female patient complained of 1 week of bilateral visual blurring. She was previously diagnosed with metastatic melanoma of the inguinal lymph nodes and treated with the oral targeted drug vemurafenib. She exhibited aqueous flare in the left eye, and her fundus examination revealed optic disc swelling in the left eye and bilateral serious detachment of the retinal neuroepithelial layer. Fluorescein angiography showed multiple pinpoint hyperfluorescence leakage spots in the prometaphase and appeared as multilobular dye pooling in the late phase. We diagnosed her as Vogt-Koyanagi-Harada syndrome and gave glucocorticoid treatment for eyes. Oral vemurafenib was also taken intermittently under the guidance of an oncologist. After treatment, her bilateral vision improved, the anterior segment inflammation disappeared, and the retinal neuroepithelial layer reattached, with presence of the "sunset glow" fundus.

The true incidence of chromosomal mosaicism after preimplantation genetic testing is much lower than that indicated by trophectoderm biopsy.

STUDY QUESTION: What is the true incidence of chromosomal mosaicism in embryos analyzed by preimplantation genetic testing (PGT). SUMMARY ANSWER: The true incidence of chromosomal mosaicism is much lower than we usually surmise. WHAT IS KNOWN ALREADY: In recent years, contemporary methods for chromosome analysis, along with the biopsy of more than one cell, have given rise to an increased rate of chromosomal mosaicism detection after preimplantation genetic testing for aneuploidy. However, the exorbitant incidence of mosaicism represents a dilemma and imposes restrictions on the application of PGT treatment. Concern has been raised about the possibility that the incidence of chromosomal mosaicism is overestimated and quite a few of the results are false-positive errors. However, studies verifying the diagnosis of chromosomal mosaicism and assessing the true incidence of chromosomal mosaicism are limited. STUDY DESIGN, SIZE, DURATION: A total of 1719 blastocysts from 380 patients who underwent PGT treatment were retrospectively analyzed to evaluate the typical incidence of mosaicism. Then 101 embryos donated by 70 couples were re-biopsied and dissected into three portions if available: trophectoderm (TE), inner cell mass (ICM), and the remaining portions. All the portions were tested using next-generation sequencing (NGS), and the results were compared to the original diagnosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The setting for this study was a university-affiliated center with an in-house PGT laboratory. All samples were amplified with multiple annealing and looping-based amplification cycles (MALBACs) and the NGS was carried out on a Life Technologies Ion Proton platform. MAIN RESULTS AND THE ROLE OF CHANCE: A clinical TE biopsy revealed an incidence of 11.9% for diploid-aneuploid mosaicism (DAM), 17.3% for aneuploid mosaicism (AM) and 29.1% in total. After rebiopsy, 94.1% whole-chromosome aneuploidies and 82.8% segmental-chromosome aneuploidies were confirmed in the embryos. As for the mosaic errors, only 32 (31.7%) out of 101 embryos presented with uniform chromosomal aberrations in agreement with the original biopsy results, 15 (14.8%) embryos presented with de novo chromosomal aberrations, and 54 (53.5%) embryos showed a euploid profile in all portions. Among the 32 uniform embryos, the true mosaicism was confirmed in only 4 cases, where a reciprocal chromosomal aberration was identified; 14 embryos presented with identical mosaicism, providing the moderate evidence for true mosaicism; and 14 embryos displayed uniform full aneuploidies in all portions of embryo, revealing a high-grade mosaicism or a false-negative diagnosis. Logistical regression analysis revealed that the concordance rate with ICM was associated with the type and level of mosaicism. The concordance rate of segmental-chromosome mosaicism was significantly lower than whole-chromosome mosaicism (adjusted Odds Ratio (aOR): 5.137 (1.061, 24.876), P = 0.042) and compared to DAM, the concordance rate of AM was significantly higher (aOR: 6.546 (1.354, 31.655), P = 0.019). The concordance rate also increased with increasing levels of mosaicism (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: This study was limited by a small sample size and the use of a single whole-genome amplification (WGA) method and NGS platform. These findings are only applicable to samples subjected to MALBAC amplification and Ion Proton platform, and studies involving larger sample sizes and multiple WGA methods and NGS platforms are required to prove our findings. WIDER IMPLICATIONS OF THE FINDINGS: TE biopsy is reliable to detect whole-chromosome aneuploidies, but the ability to diagnose mosaicism is doubtful. More attention should be paid to false-positive and false-negative errors in NGS-based PGT, especially for laboratories using less stringent criteria for mosaicism classification (i.e. 20-80%), which might be subject to a much higher false-positive mosaicism rate in the practice. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key R&D Program of China (No. 2016YFC1000206-5) and the National Natural Science Foundation of China (No. 81701509). TRIAL REGISTRATION NUMBER: N/A.

Hydrogen solution in high-entropy alloys.

High-entropy alloys (HEAs) have been reported to have superior ability in hydrogen (H) storage and strong resistance to H embrittlement. These exceptional properties are directly related to the H solution in the HEAs. However, the diversity of atomic environments in the HEAs complicate the calculation of the H solution energy. With regard to this, we clarified an origin causing the variety of solution energy from the viewpoint of chemical and elastic interactions of H with the host atoms. Combining the semi-empirical atom potential and first-principles calculations regarding H in FeCrCoNi, NbMoTaW, and FeCuCrMnMo, we found that the elastic interaction presents a visibly linear relationship with the volume expansion caused by H insertion. By contrast, the chemical interaction shows a non-linear relationship with the volume of the interstitial polyhedron. A universal model was then established to generalize the solution energy of H. This model can expeditiously assess the H distribution and provide insight into evolution of the microstructure in HEAs.