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The pharmaceuticals industry in China has boomed because of the outbreak of COVID-19, but investors’ overreaction brings it to a sharp volatility. With the time going on, the pandemic has been well controlled recently, and investors have developed a deeper perception of it, thus the situation becomes different. However, few researchers move their attention to problems in the post-pandemic world: how the pharmaceuticals industry perform now and whether investors learn something from the history. These problems do make sense as they are more related to what people face of the moment. By building VAR and ARMA-GARCH-X model, this research conducts a time series analysis on these topics in the post-pandemic background. Since the series are stationary after some processing and the models pass strict test, some reliable conclusions are reached. It is found that the pharmaceuticals industry is less affected by COVID-19 nowadays as the pandemic has been normalized. What’s more, although investors repeat history, the degree of their irrationality is mitigated, indicating that history lessons at least leave some positive impacts on investors’ behaviors. Such conclusions suggest that policy makers should carry out hedging measures to reduce possible overreactions, and that investors should not follow the trend blindly, or the bubble will burst at any time.

To examine the prevalence of different levels of aerobic activity and strength training in older cancer survivors and their associations with psychological distress and sleep difficulties.We used cross-sectional data from the 2016-2018 National Health Interview Survey on 3,425 survivors aged ≥ 65 years. Individuals were classified into active, insufficiently active, and inactive categories, and by whether they reported strength training at least twice per week. The outcome variables were self-reported psychological distress, trouble falling asleep, trouble staying asleep, and trouble waking up feeling rested. Multivariate logistic models were used to calculate the odds ratios (ORs) and the 95% confidence intervals (CIs).Only 35.2% of older survivors reached the recommended aerobic activity guidelines, and 12% had strength training at least twice per week. A total of 626 (18.3%) reported at least moderate psychological distress, and 1,137 (33.2%) had trouble staying asleep. For survivors who reported strength training less than two times per week, being insufficiently active or inactive was associated with worse psychological distress (OR 1.52, 95% CI 1.17-1.97; OR 1.30, 95% CI 1.02-1.64) and more sleep difficulties (OR ranging from 1.33 to 2.07). Among active survivors, strength training two or more times per week was associated with more trouble staying asleep (OR 1.67, 95% CI 1.06-2.58).Most older cancer survivors did not meet the recommended physical activity guidelines and suffered from psychological distress and sleep difficulties. Additional research may be needed to examine the effects of frequent muscle strength training on sleep quality.

Purpose This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88L265P and MYD88other. Methods DLBCL patients with MYD88 variations were collected from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS), and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. Clinicopathological parameters and treatment outcomes between MYD88L265P and MYD88other were investigated. Results A total of 132 patients with MYD88 variations from a cohort of 475 DLBCL patients were included, among which, 78 were MYD88L265P, while 54 were MYD88other. MYD88L265P was more common in non-GCB subtype than MYD88other (83% vs. 60%, P = 0.004). Besides, MYD88L265P was significantly related to higher proportion of testicle/ central nervous system involvement (31% vs. 6%, P P P = 0.018), compared with MYD88other. Compared with MYD88L265P, MYD88other were more likely to have higher percentage of advanced stage (60% vs. 42%, P = 0.044), extranodal site ≥ 2 (45% vs. 28%, P = 0.044), elevated LDH (55% vs. 35%, P = 0.033), positive CD10 expression (36% vs. 16%, P = 0.009), BCL-6 translocation (20% vs. 8%, P = 0.033), and NOTCH pathway gene alteration (24% vs. 13%, P = 0.040). In non-GCB DLBCL subtype, patients with MYD88other were significantly associated with worse progression free survival (PFS) than those with MYD88L265P when treated initially with R-CHOP/R-CHOP-like regimen (P = 0.010). Conclusion The findings of this study indicate that DLBCL patients with MYD88L265P and MYD88other are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88other is not superior than those with MYD88L265P, even poorer when focusing on the non-GCB subtype.

High-voltage cathodes paired with lithium metal anode have aroused extensive interests owing to their application potentials for high-density energy storage. Nevertheless, conventional electrolytes fail to maintain the stability of high-voltage cathodes and Li anode, due to their rigid interfacial chemistry with low adsorption of transition metal and strong bonding with Li+ ions. These inadequate interactions exacerbate issues such as transition metal dissolution and non-uniform Li+ transference, ultimately resulting in low cyclability of high-voltage lithium metal batteries (HVLMBs). By incorporating fluoroethylene carbonate (FEC) into lithium bis(trifluoromethane sulfonyl) imide (LiTFSI)/tetramethylene sulfone (TMS) solution, we design a sulfone-based electrolyte to improve the cyclability of HVLMBs with bi-electrode affinity characteristic—the TMS solvent with outstanding anti-oxidation stability preferentially tends to the aggressive cathodes while the FEC solvent with excellent film-forming ability approaches to the Li anode, attributed to the different adsorption energy between various solvents and electrodes. In addition, the sulfone electrolyte forms ultra-thin fluorine and sulfur-rich interphases, containing LiSO2F with S=O bonds of low electron density, associated with Li+ and e− species attacking the S-C and S-N bonds of LiTFSI and the S-C bonds of TMS. As confirmed by in-situ Raman, Ab initio molecular dynamics, and phase field simulations, the LiSO2F uniformizes in-plane Li+ transfer and mitigates transition metal dissolution, owing to the smallest Li+-LiSO2F bonding value (-1.95 eV) and the largest transition metal absorption value with LiSO2F (-3.86 eV) ever reported in the interfacial components. With Coulombic efficiency of 99.3%, the electrolyte enables an 86.1% retention after 500 cycles for Li/NMC811 (4.40 V) batteries.

This paper discusses the optimization of emergency resource scheduling for major railway emergencies under multiple uncertainties while considering the uncertainties in demand, reserve, and transportation costs of resources. We introduce a novel approach that integrates stochastic mathematical programming, interval parameter programming, and fuzzy mathematical programming to study uncertain parameter interactions and coupling. A two-stage interval fuzzy credibility-constrained model is established and solved using an interval interactive algorithm. Finally, through a case study on China Railway Nanchang Group Co., Ltd., the novelty and effectiveness of the proposed method for optimizing emergency resource scheduling strategies under multiple uncertainties are demonstrated.

Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

Objective: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP. Methods: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry. Results: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes. Conclusions: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.

45.7% of Chinese patients with advanced lung adenocarcinoma were reported to harbour sensitizing epidermal growth factor receptor (EGFR) mutations. Limited therapeutic options are left for non-small cell lung cancer (NSCLC) harbouring sensitizing EGFR mutations after failure of EGFR-tyrosine kinase inhibitor (TKI) therapy and chemotherapy, finding effective options for them is an unmet clinic need. Herein we reported a case that till January 12, 2021, an 82-year-old female with sensitizing EGFR-mutant advanced lung adenocarcinoma received a surprising progression-free survival (PFS) benefit of over 21 months from the combination therapy of pembrolizumab and anlotinib after her failure of treatments of osimertinib, chemotherapy and anlotinib-monotherapy.

Helpful for human health, omega-3 (n-3)-enriched eggs are preferred by consumers. However, antioxidants should be added to the hen’s diet to prevent n-3 fatty acid oxidation due to their unsaturated bonds. A study was designed to investigate the effects of different antioxidants on performance, egg quality, fatty acid profile, oxidation parameters, gene expression, and magnum morphology. A total of 450 hens were divided into five dietary groups. Wheat–flaxseed was used for the basic diet (control) and supplemented with vitamin E (VE), chlorogenic acid (CA), polyphenol (PF), and lutein (L). The experiment lasted for 10 weeks. The eggs were collected on the 5th week and were analyzed for quality, oxidative stability, and fatty acid (FA) content, being stored for 0 d, 7 d, 14 d, 21 d, 28 d, 35 d, and 42 d. The results showed that supplemental VE, PF, CA, and L improved the egg weight and hen day egg production compared to the control group (p < 0.05). The VE, PF, and L groups significantly (p < 0.05) reduced the malondialdehyde (MDA) and maintained the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in the egg yolk. The albumen height and Haugh unit were maintained in the egg yolk till 35 days of storage by the VE, PF, and L groups, while the CA group reduced the albumen quality after 21 d storage. The VE, PF, CA, and lutein maintained the content of alpha-linolenic acid (ALA), during the whole storage period. The total n-3 FA and docosahexaenoic acid (DHA) were retained in the egg yolk till 35 and 28 days of storage, respectively, and slightly decreased after 35 and 28 days in the L groups. The total n-6 (Tn-6) FA was maintained in the yolk till 28 days of storage in the CA and PF groups, respectively. The VE, PF, and L groups upregulated the expression of Nrf-2, P38MAPK, HO-1, SOD-1, and GSH-Px as compared to the CA and control groups. The VE, PF, and L groups significantly increased the magnum primary folds and epithelium height as compared to CA and the control. Thus, it was concluded that the use of PF and L is better at preventing egg quality deterioration and lipid oxidation, maintaining more than 300 mg/egg n-3 FA during storage, by activating the Nrf-2 pathway through the phosphorylation of P38MAPK, and enhancing the phase-2 antioxidant defense enzymes, namely, SOD, GSH-Px, and HO-1.

Data are limited regarding the genetic profiling of diffuse large B-cell lymphoma (DLBCL) with double expression of MYC and BCL2 proteins without underlying rearrangements (double-expressor lymphoma [DEL]). This study aimed to describe the genetic profiling and determine the prognostic significance in patients with DEL and in those with non-DEL.Capture-based targeted sequencing was performed on 244 patients with de novo DLBCL, not otherwise specified. Immunohistochemistry staining was performed for evaluating the MYC and BCL2 expression.Among 244 patients, 46 patients had DEL, and 198 had non-DEL. KMT2D, CD58, EP300, PRDM1, TNFAIP3 and BCL2 gain or amplification (BCL2There was difference in profiling of altered genes and signaling pathways between the DEL group and the non-DEL group. The presence of DEL alone should not be considered as an adverse prognostic indicator, and BCL2 alteration could define a subset of patients with poor prognosis within DEL.

Background: Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma. Methods: In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored. Results: Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 109/L (range 18–219) among patients who received rhTPO and 73 × 109/L (range 42–197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count

Background This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. Method RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.

This study aimed to analyze the clinical features, treatment, survival, and prognostic factors of Chinese patients with peripheral T-cell lymphoma (PTCL) excluding natural killer/T-cell lymphoma (NKTCL).Data on patients with newly diagnosed PTCLs between January 1, 2006 and December 31, 2017 at our hospital were retrospectively reviewed. Patients with NKTCL were excluded.A total of 240 patients were included. PTCL, not otherwise specified (PTCL-NOS), was the most frequent subtype (42.5%), followed by angioimmunoblastic T-cell lymphoma (AITL) (21.3%), anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK-ALCL) (16.7%), ALK-positive ALCL (ALK+ALCL) (10.8%) and others (8.8%). With a median follow-up of 81.1 months, the 5-year progression-free survival (PFS) and overall survival (OS) rates for all patients were 30.4% (95% CI 25.0%-37.0%) and 48.8% (95% CI 42.6%-55.7%), respectively. On multivariate analysis, no consolidative autologous stem cell transplantation (ASCT) and not achieving complete response after first-line chemotherapy retained independently prognostic value for inferior PFS and OS. Besides, bone marrow involvement and serum albumin level were independent factors for PFS, and Eastern Cooperative Oncology Group performance status ≥2 was significantly predictive of inferior OS. Compared with PTCL-NOS, significantly superior PFS and OS were observed for ALK+ALCL and ALK-ALCL.The survival outcomes with current treatment for most PTCL subtypes are still unsatisfactory. Prospective randomized studies are needed to establish the value of consolidative ASCT in PTCL, and novel therapeutic approaches should be explored.

Highlights • Juvenile COVID-19 patients have faster time to RP result than any other aged groups. • Sampling from digestive tract may be better in identifying RP. • No marked difference on imaging change between RP and NRP patients was observed. • Nearly three-quarters of patients had protective antibodies 6 months post-discharge. • The disappearance rate of antibody is more rapid in juveniles than adults., Background Almost a year after the outbreak of coronavirus disease 2019 (COVID-19), numerous hospitalized COVID-19 patients have recovered. However, little is known about the long-term follow-up (>2 months) of discharged patients. Methods We enrolled 527 discharged COVID-19 patients in a study from February 5 to March 11, 2020. These patients’ basic characteristics, imaging features, nucleic acid detection results, and antibody levels were retrospectively reviewed. Results of the 527 discharged patients, 32 (6.1%) had re-detectable positive (RP) nucleic acid results for SARS-CoV-2 during follow-up examinations with 11 and four detections entailing stool samples and anal swabs, respectively, rather than respiratory samples. Juveniles were more accessible to “infection recurrence” than other age groups, with shorter time spans for RP RNA tests (an average of 8.8 days [6.0–9.0 days]), while the reverse was true for the middle-aged group (17.5 days on average [14.0-17.5 days]). Similar improvements in the imaging features of both RP and none RP (NRP) groups were observed. Negative antibody detections in patients 3 and 6 months after discharge were 14.2% and 25.0%, respectively. Cases evidencing negative antibodies were more common among juvenile patients (40% vs. 15.6%, p = 0.03) 6 months post-discharge. Conclusions 6.1% of 527 discharged patients showed RP status, which may be easier to be identified from stool samples than from other samples. Given the dropping rate of SARS-CoV-2 antibody, reinfection may happen especially in juvenile patients (age less than 18 years). Our findings have implications for the long-term management of recovered COVID-19 patients.

Background Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. Results Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. Conclusions In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. Trial registration: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

Rock spectral analysis is an important research field in hyperspectral remote sensing information processing. Compared with the spectra in the short-wave infrared and visible–near-infrared regions, the emittance spectrum of rocks in the thermal infrared (TIR) region is highly significant for identifying some major rock-forming minerals, including feldspar, biotite, pyroxene and hornblende. Even for the same rock type, slight differences in mineral composition generally result in varying spectral signatures, undoubtedly increasing the difficulty in discriminating rock types on the Earth’s surface via TIR spectroscopy. In this study, amounts of monzonite samples from different regions were collected in the central part of Hunan Province, China, and emission spectra at 8–14 μm were measured using a portable thermal infrared spectrometer. The experimental result illustrates 13 remarkable feature positions for all the monzonite samples from different geological environments. Furthermore, by combining the extracted features with the principal component analysis (PCA) method, feature-oriented PCA was applied to establish a model for identifying monzonite accurately and quickly without performing spectral library matching and spectral deconvolution. This study provides an important method for rock type identification in the TIR region that is helpful for the rock spectral analysis, geological mapping and pixel unmixing of remote sensing images.

The force exerted on particles is of great significance to the flow and reaction characteristics of particles in gasifier. In this study, the unbalanced thrust, especially its magnitude, of a single char particle induced by chemical reactions during combustion process is investigated numerically, based on the random distribution of active sites. It is revealed that the nonuniform distribution of active sites directly leads to the nonuniform release of gaseous products, which accounts for the net induced thrust of particles. The effects of active site ratio, ambient gas temperature and particle diameter on the induced thrust of reaction particle were investigated. The results show that the induced thrust on particles could be equal to the magnitude of particle gravity. The induced thrust decreases with the increase of active area and particle diameter. And it is enhanced with the increase of ambient temperature.

Renal cell carcinoma (RCC) with anaplastic lymphoma kinase (ALK) rearrangement is rare, and the genetic profiles of the tumor have not been elucidated. Here, we report a case with recurrent papillary RCC and lung metastasis after nephrectomy for nearly 7 years. The patient first received sunitinib, whereas the drug toxicity was intolerable. Combined Immunohistology (IHC) and fluorescence in situ hybridization (FISH) revealed the patient has an ALK rearrangement, and the patient then was treated with crizotinib. The patient had good tolerance, and a partial response in the target lesions was achieved. In order to further understand the benefit of crizotinib in ALK-rearranged RCC, the patient was detected with whole exome sequencing (WES) to study her genetic profiles. Compared those of RCC cases without ALK rearrangement (nALK-RCC), the patient and nine RCC cases with ALK rearrangement (ALK-RCC) revealed unique genetic characteristics: 1) The common mutations that occurred in RCC were not found in ALK-RCC.; 2) A total of 11 co-existing mutations in ALK-RCC were found, and they occurred in nALK-RCC at a relatively low frequency. DNMT3A mutations were concurrent with ALK fusions in our case. These findings indicated a different genetic alteration pattern of ALK-RCC from nALK-RCC. Our case demonstrated the efficacy of crizotinib in an RCC patient with ALK rearrangement.

Background/aim TP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53 mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53 mut DLBCL patients. Methods A total of 44 DLBCL patients with TP53 mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease. Results Among 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP-like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS (p=0.008) and overall survival (p=0.017) in limited-stage TP53 mut DLBCL patients compared to R-CHOP-only treatment. Conclusion This study presents the characteristics of TP53-mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.

Highlights • Middle-aged adults with no underlying diseases could be a severe COVID-19 patient. • Lung biopsies were rarely reported in patients with serious COVID-19. • Pathological and inflammatory features are investigated in a severe COVID-19 patient., We reported a patient diagnosed with severe pneumonia from coronavirus disease 2019(COVID-19), and did the percutaneous lung biopsy with the guidance of ultrasound. Then we presented the patient's lung morphological, ultrastructure, and some important inflammatory biological markers changes, to help better understand the disease and make a clue for all the multidisciplinary team to save more people.

AIM The prognosis and treatment options for follicular lymphoma (FL) remain heterogenous. This study aimed to analyze the prognostic impact of rituximab maintenance and evaluate the prognostic models in Chinese FL patients. METHODS We retrospectively evaluated patients with treatment-naive advanced stage FL who were treated in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between January 2008 and December 2018. We compared the baseline characteristics, long-term survival outcomes, prognostic factors and the performance of four common prognostic models (i.e., FLIPI, FLIPI2, PRIMA-PI and LDH+β2M) between them. RESULTS A total of 158 patients were included (rituximab maintenance group, 77 patients; observation group, 81 patients). The median follow-up time was 61.0 months. The rituximab maintenance group showed significantly higher 5-year progression-free survival (PFS; 83.3% vs 52.7%, P

Aim The aim of the study was to compare the therapeutic strategies and prognostic factors of patients with primary intestinal diffuse large B-cell lymphoma (PI-DLBCL). Methods A total of 50 PI-DLBCL patients who accepted standard first-line treatment at National Cancer Center in China were included in this retrospective study. Survival analysis was performed to evaluate the prognostic risk factors. Results The 3-year overall survival (OS) and 3-year progression-free survival (PFS) for the entire group were 76.0% and 65.9%, respectively. Univariate analysis showed that B symptom, advanced Lugano stage, elevated LDH status, poor ECOG PS and immunochemotherapy alone were significantly correlated with a poor PFS. Elevated LDH status, poor ECOG PS, advanced Lugano stage, high IPI score and immunochemotherapy alone were significantly correlated with a poor OS. Multivariate analysis revealed that ECOG PS (P= 0.035; HR = 0.233; 95% CI, 0.060-0.905), LDH level (P = 0.010; HR = 0.223; 95% CI, 0.072-0.693) and surgery (P = 0.002; HR = 5.584; 95% CI, 1.883-16.563) were independent prognostic factors for OS. LDH level (P = 0.035; HR = 0.210; 95% CI, 0.049-0.894) and surgery (P = 0.003; HR = 6.410; 95% CI, 1.903-21.593) were independent risk factors for PFS in PI-DLBCL. R-CHOP immunochemotherapy combined surgery treatment was also associated with a lower rate of refractory/relapsed (R/R) disease (P = 0.004). Furthermore, stratified analysis revealed that partial resection or radical resection combined with immunochemotherapy had no significantly difference which affect OS (P = 0.338) and PFS (P = 0.207). Conclusion R-CHOP immunochemotherapy plus surgery was associated with a superior prognosis compared with R-CHOP alone in Chinese PI-DLBCL population.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy. Following front-line immunochemotherapy, 30–40% of DLBCL patients develop relapsed or refractory (r/r) disease, which can be treated with ibrutinib. It has been previously reported that MYD88MUT affects the response to ibrutinib in patients with r/r DLBCL. Here, we aimed to gather understanding of MYD88MUT in r/r DLBCL patients and to evaluate its influence on response to ibrutinib. In this study, tissue samples from DLBCL patients (n = 212) were retrospectively collected and sequenced by target-capturing panels of either 413 or 112 genes that are frequently mutated in non-Hodgkin’s lymphoma. Sixty patients with MYD88 mutations and available clinical information were included for further analysis. Seven MYD88MUT variants were identified, L265P (65.0%, n = 39), S219C (13.3%, n = 8), S243N (8.3%, n = 5), P258L (6.7%, n = 4), F283V (1.7%, n = 1), P141R (1.7%, n = 1), and V217F (1.7%, n = 1). One patient had MYD88 amplification. In addition, mutations in PIM1 (67%, n = 40), IGH fusion (48%, n = 29), CD79B (43%, n = 26), KMT2D (30%, n = 18), and TP53 (27%, n = 17) were identified. For patients with L265P, IRF4 (p = 0.011) was frequently mutated. Otherwise, TET2 (p = 0.016), NOTCH2 (p = 0.044), MET (p = 0.037), SOCS1 (p = 0.011), TNFRSF14 (p = 0.011), EZH2 (p = 0.037), and BCL6 (p

Background: The clinical course of relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) is variable, with limited efficacy data of second-line treatment in a post-rituximab real-world context. Hence, we explored the predictors and constructed a nomogram for risk stratification in this population. Patients and methods: Among 296 r/r DLBCL patients pretreated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) at the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between 2006 and 2017, 231 were included for nomogram construction. After randomization, we constructed the prognostic nomogram in the primary cohort (n=161) based on a multivariate analysis and confirmed it in the validation cohort (n=70). Additionally, we explored predictive factors for second-line therapy using a ordinal regression analysis. Results: Four independent prognostic factors including rituximab in the second-line setting, initial Eastern Cooperative Oncology Group (ECOG) performance status (PS), response to front-line treatment, and invasion on progression/recurrence were used to construct the nomogram. The nomogram had a C index of 0.70 with AUC values of 0.73 and 0.71 for the primary and validation cohorts, respectively. Subsequently, three risk groups (low, intermediate, and high) were determined with median overall survival (OS) of 38.0, 25.0, and 7.0 months, respectively. Additionally, we conducted a multivariate ordinal regression analysis and identified prior response to front-line treatment (odds ratio=4.50, 95% CI: 1.84-11.27, p=0.001) and bulky disease at diagnosis (odds ratio=0.36, 95% CI: 0.182-0.702, p=0.003) were two independent factors for second-line treatment efficacy. Conclusions: The established predictors for treatment efficacy and the novel nomogram for survival in r/r DLBCL patients could potentially be applied for risk stratification and treatment guidance in the post-rituximab era.

In this paper, we report a simple two-step hydrothermal method to improve the cyclic stability and transmittance of Prussian blue (PB) with TiO2 nanorod arrays (TNRAs). TNRAs were used as a nanostructured substrate to investigate the electrochromic properties of the PB/TNRA hybrid film. The PB/TNRA film shows excellent cyclic stability (83.8% after 1000 cycles) compared with the pure PB film (83.8% after 400 cycles). The improved cyclic stability was attributed to the increased adhesion between the PB film and the substrate and the alleviated volume expansion during the ion intercalation/deintercalation process. Moreover, the TNRA can reduce the reflectivity of the PB/TNRA film and increase the loading of PB. Therefore, the PB/TNRA film also shows a larger optical modulation (85.8% at 700 nm).

We aimed to develop a new risk stratification tool to predict freedom from progression (FFP) for newly diagnosed advanced classical Hodgkin lymphoma (cHL).We collected data from 386 patients with advanced cHL diagnosed between December 8, 2000 and October 29, 2018, and treated with curative intent with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or an ABVD-equivalent regimen. Cases were randomly divided into training and validation cohorts at a ratio of 7:3. The new model was constructed based on the results of Cox proportional hazards model in the training cohort. Comparisons of discrimination between the new model and other models in the training and validation cohorts for FFP prediction were measured by time-dependent area under curve (tAUC) and Harrell's C-index. Calibration plots were constructed to compare the consistency between the predicted and observed estimates of survival probability for the new model in the training and validation cohorts.The new model (IPSPLR) composed of International Prognostic Score (IPS)-3 and platelet/lymphocyte ratio (PLR) provided four distinct risk groups. The IPSPLR showed better discriminative ability when compared with IPS-3 and IPS-7. The AUC of IPSPLR was consistently higher than that of IPS-3 and IPS-7 between 12 and 120 months. The C-index of the IPSPLR was higher than that of IPS-7 and IPS-3. The calibration plots showed an excellent agreement between the IPSPLR-predicted and observed estimates of 5-year FFP.The IPSPLR is an easily used tool for FFP prediction for newly diagnosed advanced cHL. Validation of this tool in other large datasets is needed.

Background: To investigate the prognostic role of red blood cell distribution width (RDW) and platelet/lymphocyte ratio (PLR) in early-stage classical Hodgkin lymphoma (cHL). Materials & methods: Data from 402 patients with newly diagnosed early-stage cHL were retrospectively collected. The impact of factors on complete response (CR) rate and freedom from progression (FFP) was analyzed. Results: High PLR was associated with lower CR, but high RDW was not. The univariate analysis showed that RDW and PLR were predictive of FFP. On multivariate analysis, high PLR was an independent risk factor for inferior FFP. Subgroup analysis and a prognostic model for FFP based on PLR validated the prognostic role of PLR. Conclusion: PLR was a robust prognostic factor for newly diagnosed early-stage cHL.

Minerals and rocks are important natural resources that are formed over a long period of geological history. Spectroscopy is the basis of the identification and characterisation of rocks and minerals via proximal sensing in the field or remote sensing systems with multi- and hyper-spectral capabilities. However, spectral data is scattered around different institutions worldwide and stored in various formats, resulting in poor data usability and an unnecessary waste of time and information. To improve the usability and performance of mineral spectral data, we developed an integrated open mineral spectral library (Rock Spectral Library, RockSL). Shared spectral data and related information were collected worldwide, and data cleaning measures were performed to retain the qualified spectra and merge all qualified data (raster, vector, and text formats) in a common framework to establish a reliable and comprehensive digital data set for an easy sharing and matching service. A software system was developed for the RockSL to manage, analyse, and apply the spectral data of minerals and rocks. We demonstrate how the information encoded in RockSL can determine the species of unknown rocks and describe specific mineral compositions. We also provide a reference scheme of the work chain and present key technologies for building different spectral libraries in diverse fields using RockSL. New contributions to RockSL are encouraged for this work to be improved to provide a better service and extend the applications of geo-sciences. This article introduces the characteristics of RockSL and demonstrates an experimental application.

Advances in spatial transcriptomics enlarge the use of single cell technologies to unveil the expression landscape of the tissues with valuable spatial context. However, computational tools developed for single-cell transcriptomics have great limits in dealing with spatial transcriptomic data with high noise on detected transcript signals. Here we propose an unsupervised and manifold learning-based algorithm, STEEL, which identifies different cell types from spatial transcriptome by clustering cells/beads exhibiting both highly similar gene expression profiles and close spatial distance in the manner of graphs. Comprehensive evaluation of STEEL on various spatial transcriptomic datasets from 10X Visium platform demonstrates that it not only achieves a high resolution to characterize fine structures of mouse brain, but also enables the integration of multiple tissue slides individually analyzed into a larger one. STEEL outperforms previous methods to effectively distinguish different cell types of various tissues on Slide-seq datasets, featuring in higher bead density but lower transcript detection efficiency. Application of STEEL on spatial transcriptomes of early-stage mouse embryos (E9.5 to E12.5) successfully delineates a progressive development landscape of tissues from ectoderm, mesoderm and endoderm layers, and futher profiles dynamic changes on cell differentiation in heart and other organs. With the advancement of spatial transcriptome technologies, our method will have great applicability in high-resolution cell type identification and unbiased spatiotemporal data integration.

Background This study aimed to propose a new user-friendly, cost effective and robust risk model to facilitate risk stratification for diffuse large B-cell lymphoma (DLBCL) treated with frontline R-CHOP regimens. Methods Data on 998 patients with de novo DLBCL diagnosed between Jan 1st, 2005 and Dec 31st, 2018 at our center, who received frontline R-CHOP or R-CHOP-like regimens, were retrospectively collected. Patients were randomly divided into the training cohort (n = 701) and the validation cohort (n = 297). A new prognostic model for overall survival (OS) was built based on the training cohort. The performance of the new model was compared with International prognostic index (IPI), revised IPI (R-IPI) and National Comprehensive Cancer Network (NCCN)-IPI (NCCN-IPI). The new model was validated in the validation cohort. Results The multivariate analysis of the training cohort showed that the IPI, β2-microglobulin, platelet count and red blood cell distribution width were independent factors for OS, which were incorporated into the new prognostic model. Patients were stratified into low risk, low-intermediate risk, high-intermediate risk, high risk and very high risk groups, with distinct survival outcomes. The new model achieved good C-indexes for 5-year OS prediction of 0.750 (95%CI 0.719–0.781) and 0.733 (95%CI 0.682–0.784) in the training and validation cohorts, respectively, and displayed well-fitted calibration curves. The C-index and the time-dependent ROC analysis demonstrated better performance of the new model than the IPI, R-IPI and NCCN-IPI in both training and validation cohorts. The integrated Brier score for predicting 5-year OS of the new model was lower than that of the IPI, R-IPI and NCCN-IPI in both cohorts, and decision curve analysis also showed a higher net benefit, indicating the superiority of the new model over the conventional models. Conclusion The new prognostic model might be a useful predictive tool for DLBCL treated with R-CHOP regimens. Further external validation is warranted.

Aim. To explore the potential relationship between NLR and micronutrient deficiency in patients with severe COVID-19 infection. Methods. Sixteen patients were categorized into the mild group (mild COVID-19) and severe group (severe COVID-19) based on the guideline of the management of COVID-19. The lactate dehydrogenase (LDH); superoxide dismutase (SOD), the inflammatory markers (neutrophil lymphocyte ratio (NLR)), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), selenium (Se), iron (Fe), zinc (Zn), nickel (Ni), copper (Cu), chromium (Cr), cadmium (Cd), arsenic (As), and manganese (Mn) were measured in the blood. Results. Compared to the mild group, the NLR ( P < 0.05 ) and the level of Se ( P < 0.01 ), Fe ( P < 0.05 ), and Zn ( P < 0.05 ) were significantly decreased in the severe group. The level of Se, Fe, and Zn was significantly correlated to NLR levels. Furthermore, close positive correlation was found between NLR and severity of COVID-19. Conclusion. The micronutrient deficiency in the blood is associated with NLR in the severity of COVID-19 patients.

Limited data about the prognostic significance ofProbe capture-based high-resolution sequencing was performed on 191 patients diagnosed withThe presence ofThis study showed that DLBCL patients treated with R-CHOP