Efficiency and Toxicity of Imatinib Mesylate combined with Atorvastatin Calcium in the Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease: A Single-center, Prospective, Single-arm, Open-label study.

INTRODUCTION: Steroid-refractory cGVHD (SR-cGVHD) presents new great challenges for treatment. We have reported imatinib monotherapy was effective to SR-cGVHD, but the CR rate was not satisfactory and the benefit was not showed specific to some target organs, previously. Imatinib and statin drugs have been recognized to regulate T-cell function, statins also have been demonstrated endothelia protection, but whether this combination therapy was able to improve the efficacy remains unknown. Therefore, we designed this prospective, single-arm, open-label trial to investigate the efficacy of imatinib-based combination therapy in the treatment of SR-cGVHD for the first time. METHODS: 60 SR-cGVHD patients were entered into this trial to investigated the combination of imatinib mesylate and atorvastatin calcium for the treatment of SR-cGVHD. The primary endpoint included the overall response rate (ORR) after 6 months of combined treatment. The secondary endpoints included an evaluation of survival, changes in T-cell subsets and adverse events. RESULTS: At baseline, 45% (27/60) of patients had moderate cGVHD, and 55.0% (33/60) of patients had severe cGVHD. At the 6-month follow-up, a clinical response was achieved in 70.0% of patients, and a complete response (CR) was achieved in 26.7%. A total of 11.7% (7/60) of patients stopped immunosuppressive therapy at this point. After 6 months of treatment, the ORR rates of the liver, skin, eyes and oral cavity were 80.6%, 78.1%, 61.5%, and 60.9%, respectively, with the liver also having the highest CR of 58.1%. The patients with moderate cGVHD had a better CR rate than those with severe cGVHD (55.6% vs. 3.0%, P<0.0001). The overall survival in patients who with ORR was improved (P = 0.0106). Lung involvement is an independent risk factor to affected ORR achievement (P = 0.021, HR = 0.335, 95%CI 0.133-0.847), and the dosage of steroids was reduced in ORR patients. In clinical response patients, the ratio of CD8+ T cells (P = 0.0117) and Th17 cells (P = 0.0171) decreased, while the number of Treg cells (P = 0.0147) increased after 3 months. The most common adverse events were edema, nausea, and neutropenia which were 13.3%, 11.7%, and 11.7%, respectively. CONCLUSION: Combination treatment with imatinib mesylate and atorvastatin calcium was effective in treating SR-cGVHD and significantly decreased target organ injury, especially liver damage, indicating that T-cell regulatory function may play an important role in this process.

Maternal exposure to E 551 during pregnancy leads to genome-wide DNA methylation changes and metabolic disorders in the livers of pregnant mice and their fetuses.

The widespread use of nanoparticles in the food industry has raised concerns regarding their potential adverse effects on human health, particularly in vulnerable populations, including pregnant mothers and fetuses. However, studies evaluating the reproductive and developmental toxicity of food-grade nanomaterials are limited. This study investigated the potential risks of prenatal dietary exposure to food-grade silica nanoparticles (E 551) on maternal health and fetal growth using conventional toxicological and epigenetic methods. The results showed that prenatal exposure to a high-dose of E 551 induces fetal resorption. Moreover, E 551 significantly accumulates in maternal and fetal livers, triggering a hepatic inflammatory response. At the epigenetic level, global DNA methylation is markedly altered in the maternal and fetal livers. Genome-wide DNA methylation sequencing revealed affected mCG, mCHG, and mCHH methylation landscapes. Subsequent bioinformatic analysis of the differentially methylated genes suggests that E 551 poses a risk of inducing metabolic disorders in maternal and fetal livers. This is further evidenced by impaired glucose tolerance in pregnant mice and altered expression of key metabolism-related genes and proteins in maternal and fetal livers. Collectively, the results of this study highlighted the importance of epigenetics in characterizing the potential toxicity of maternal exposure to food-grade nanomaterials during pregnancy.

Thrombopoietin receptor agonists for refractory thrombocytopenia in patients after autologous hematopoietic stem cell transplantation.

OBJECTIVE: Autologous hematopoietic stem cell (ASC) transplantation (ASCT) is an effective treatment method for patients with hematological disorders and malignant diseases. The patient's ASCs are harvested prior to radiotherapy/chemotherapy, cryopreserved and then transfused back after the high-dose radiotherapy/chemotherapy conditioning treatment. Since some patients develop thrombocytopenia after receiving ASCT, it is difficult for them to bear simultaneously the management of their original disease and thrombocytopenia. The present study aimed to evaluate the efficacy and safety of thrombocytopenia therapy with thrombopoietin receptor agonists (TPORAs) after ASCT. METHODS: We retrospectively analyzed the clinical safety and efficacy of TPORA treatment for the enrolled 20 patients who developed thrombocytopenia after ASCT. The measured parameters were prolonged isolated thrombocytopenia (PIT), secondary failure of platelet recovery (SFPR) and other calculated response index. Patients with platelet count (PC) ≤ 50×109/L were treated with TPORA, namely with either eltrombopag (Elt), hetrombopag (Het), or avatrobopag (Ava). RESULTS: The group of 20 patients, who received TPORA administration for their thrombocytopenia after ASCT, had a median age of 50 years (ranging between 17 and 60 years). The median administration time of TPORA application was 48 days (ranging from 7 to 451 days); an overall response rate (ORR) was 85% with no response in 15% of patients, while with complete response (CR) in 70% of patients and partial response (PR) in 15% of patients. The median platelet count was 19 × 109/L before TPORA treatment and increased to 87×109)/L after the treatment. The TPORA treatment was safe as only 4 patients (20%) displayed a mild transaminase elevation. No other reported side effects occurred, such as thrombosis, joint pain, diarrhea, and myelofibrosis. It was demonstrated that the short response time to TPORA treatment correlated to the fast platelet recovery, when the number of megakaryocytes in the bone marrow smear exceeded 35/4.5 cm2 under a low magnification of 100 times (p = 0.015). CONCLUSION: TPORA therapy for thrombocytopenia occurring after the radiotherapy/ chemotherapy-conditioned ASCT was well tolerated and effective for platelets recovery.

Single-cell RNA sequencing reveals the dynamics of hepatic non-parenchymal cells in autoprotection against acetaminophen-induced hepatotoxicity.

Gaining a better understanding of autoprotection against drug-induced liver injury (DILI) may provide new strategies for its prevention and therapy. However, little is known about the underlying mechanisms of this phenomenon. We used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells (NPCs) in autoprotection against DILI, using acetaminophen (APAP) as a model drug. Autoprotection was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice, followed by a higher dose in a secondary challenge. NPC subsets and dynamic changes were identified in the APAP (hepatotoxicity-sensitive) and APAP-resistant (hepatotoxicity-resistant) groups. A chemokine (C-C motif) ligand 2+ endothelial cell subset almost disappeared in the APAP-resistant group, and an R-spondin 3+ endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP autoprotection. Moreover, the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of inflammation. DC-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant group. In addition, the natural killer cell subsets NK-3 and NK-4 and the Sca-1-CD62L+ natural killer T cell subset may promote autoprotection through interferon-γ-dependent pathways. Furthermore, macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP hepatotoxicity. Overall, this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.

Laser capture microdissection for biomedical research: towards high-throughput, multi-omics, and single-cell resolution.

Spatial omics technologies have become powerful methods to provide valuable insights into cells and tissues within a complex context, significantly enhancing our understanding of the intricate and multifaceted biological system. With an increasing focus on spatial heterogeneity, there is a growing need for unbiased, spatially resolved omics technologies. Laser capture microdissection (LCM) is a cutting-edge method for acquiring spatial information that can quickly collect regions of interest (ROIs) from heterogeneous tissues, with resolutions ranging from single cells to cell populations. Thus, LCM has been widely used for studying the cellular and molecular mechanisms of diseases. This review focuses on the differences among four types of commonly used LCM technologies and their applications in omics and disease research. Key attributes of application cases are also highlighted, such as throughput and spatial resolution. In addition, we comprehensively discuss the existing challenges and the great potential of LCM in biomedical research, disease diagnosis, and targeted therapy from the perspective of high-throughput, multi-omics, and single-cell resolution.

Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway.

BACKGROUND: Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. METHODS: The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. RESULTS: We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo . CONCLUSION: Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Outcomes of patients with hematological malignancies who undergo unrelated donor hematopoietic stem cell transplantation with ATG-Fresenius versus ATG-Genzyme.

To compare the outcomes of patients with hematological malignancies who received ATG-Fresenius (ATG-F) 20 mg/kg versus those who received ATG-Genzyme (ATG-G) 10 mg/kg in an unrelated donor hematopoietic stem cell transplantation (HSCT) procedure, a total of 186 patients who underwent their first allogeneic HSCT with an unrelated donor were retrospectively analyzed. One hundred and seven patients received ATG-F, and seventy-nine patients received ATG-G. Multivariate analysis showed that the type of ATG preparation had no effect on neutrophil engraftment (P = 0.61), cumulative incidence of relapse (P = 0.092), nonrelapse mortality (P = 0.44), grade II-IV acute graft-versus-host disease (GVHD) (P = 0.47), chronic GVHD (P = 0.29), overall survival (P = 0.795), recurrence-free survival (P = 0.945) or GVHD-free relapse-free survival (P = 0.082). ATG-G was associated with a lower risk of extensive chronic GVHD and a higher risk of cytomegaloviremia (P = 0.01 and HR = 0.41, P < 0.001 and HR = 4.244, respectively). The results of this study suggest that the preparation of rabbit ATG used for unrelated HSCT should be selected based on the incidence of extensive chronic GVHD of each center, and the posttransplant management strategy should be adjusted according to the ATG preparation.

Distinct diurnal chemical compositions and formation processes of individual organic-containing particles in Beijing winter.

Organic aerosols (OA) are major components of fine particulate matter, yet their formation mechanism remains unclear, especially in polluted environments. In this study, we investigated the diurnal chemical compositions and formation processes of OA in carbonaceous particles during winter in Beijing using aerosol time-of-flight mass spectrometry. We found that 84.5% of the measured carbonaceous particles underwent aging processes, characterized by larger diameter and more secondary species compared to fresh carbonaceous particles, and presented different chemical compositions of OA in the daytime and nighttime. During the day, under high O3 concentrations, organosulfates and oligomers existed in the aged carbonaceous particles, which were mixed with a higher signal of nitrate compared with sulfate. At night, under high relative humidity, distinct spectral signatures of hydroxymethanesulfonate and organic nitrogen compounds, and minor signals of other hydroxyalkylsulfonates and high molecular weight organic compounds were present in the aged carbonaceous particles, which were mixed with a higher signal of sulfate compared with nitrate. Our results indicated that photochemistry contributed to OA formation in the daytime, while aqueous chemistry played an important role in OA formation in the nighttime. The findings can help improve the performance of air quality and climate models on OA simulation.

The Novel Prognostic Index Model of Combining Circulating Tumor DNA and PINK-E Predicts the Clinical Outcomes for Newly Diagnosed Extranodal NK/T-cell Lymphoma.

Extranodal NK/T-cell lymphoma (ENKTL) is a highly aggressive and heterogeneous disease with poor clinical outcome. Our previous work had demonstrated that circulating tumor DNA (ctDNA) analyses were feasible in ENKTL, and dynamic tracing of ctDNA could be used to monitor the disease status. However, the prognostic value of ctDNA in ENKTL has not been fully investigated. Patients with newly diagnosed ENKTL from February 2017 to December 2021 (n = 70) were enrolled. The pretreatment ctDNA concentration (hGE/mL) was measured. The prognostic value of ctDNA, international prognostic index (IPI), Korean prognostic index (KPI), PINK-E, and the combination of PINK-E and ctDNA (PINK-EC) were investigated in our cohort. The IPI and PINK-E risk categories had a significant difference in progression-free survival (PFS) and overall survival (OS) between the low-risk and intermediate-risk groups. The KPI risk category had a difference in PFS and OS between the intermediate-risk and high-risk groups. Furthermore, integrating ctDNA into the PINK-E model could overcome the shortcomings of other prognostic models, which could significantly distinguish the different-risk groups. Overall, our results demonstrated that PINK-EC showed a superior prognostic prediction value and stability compared with IPI, KPI, and PINK-E. The integration of molecular features of the tumor into classic risk categories might better characterize a high-risk group where novel treatment approaches are most needed.

[Research progress in pharmacological effectsand mechanism of Fel Ursi against cardiovascular and cerebrovascular diseases].

Fel Ursi is a dried product obtained from the gallbladder of Ursidae animals, such as Selenarctos thibetanus or Ursus arctos, through gallbladder surgery for bile drainage. It is one of the rare animal medicinal materials in China and is known for its therapeutic effects, including clearing heat, removing toxins, extinguishing wind, relieving spasms, clearing the liver, and improving vision. Research has also found that Fel Ursi has pharmacological effects against cardiovascular and cerebrovascular diseases, such as anti-inflammatory, anti-apoptotic, and antioxidant stress properties. Recently, numerous studies have confirmed the close relationship between cardiovascular and cerebrovascular diseases and the gut microbiota as well as gut metabolites. Fel Ursi contains bile acid components that may have bidirectional regulatory effects on the gut microbiota and gut metabolites. This aspect could represent a potential therapeutic pathway for Fel Ursi in the treatment of cardiovascular and cerebrovascular diseases. This article comprehensively summarized relevant literature in China and abroad, reviewed the research progress on the pharmacological effects of Fel Ursi against cardiovascular and cerebrovascular diseases, and explored the impact of Fel Ursi on gut microbiota and gut metabolites, thereby aiming to provide references for further in-depth research and clinical application of Fel Ursi.

Analysis of the Efficacy and Safety of Avatrombopag Combined With MSCs for the Treatment of Thrombocytopenia After Allogeneic Hematopoietic Stem Cell Transplantation.

Platelet graft failure (PGF) is a frequent and serious complication after Allogeneic hematopoietic stem cell transplantation (allo-HSCT) and lacks effective treatment strategies, which could affect the prognosis of patients and even cause death. The exact underlying mechanism of PGF remains unclear, and lacks standard treatment. Here, we conduct a retrospective study to evaluate the efficacy and safety of avatrombopag combined with mesenchymal stem cells (MSCs) in 16 patients with thrombocytopenia after allo-HSCT. Patients were administered the following treatment regimen: 20 mg/d avatrombopag; if the PLT count was less than 50×10^9/L for at least 2 weeks, the dose was increased to 40 mg/d; if the PLT count was 200-400×10^9/L, the dose was reduced; and if the PLT count was greater than 400×10^9/L, avatrombopag was terminated. Umbilical cord MSCs (1×10^6 cells/kg) infusion was performed every week for 4-6 weeks. Among the 16 patients, 13 patients (81.3%) achieved a complete response (CR), 2 patients (12.5%) got a partial response (PR), and 1 patient (6.3%) had no response (NR). The median time to obtain CR was 32 (7-426) days after treatment with avatrombopag combined with umbilical cord MSCs. The time to reach 20×10^9/L≤ PLT <50×10^9/L in the 2 patients with PR was 52 and 230 days after treatment, respectively. One patient had a severe pulmonary infection and died of cytomegalovirus pneumonia. Overall, our results indicated that combination of avatrombopag with MSCs can promote platelet recovery after transplantation, thereby improving the survival rate of patients and improving the quality of life of patients after transplantation, and providing a new method and strategy for the treatment of thrombocytopenia after allo-HSCT.

Unbalanced emission reductions and adverse meteorological conditions facilitate the formation of secondary pollutants during the COVID-19 lockdown in Beijing.

During the coronavirus disease 2019 (COVID-19) lockdown in 2020, severe haze pollution occurred in the North China Plain despite the significant reduction in anthropogenic emissions, providing a natural experiment to explore the response of haze pollution to the reduction of human activities. Here, we study the characteristics and causes of haze pollution during the COVID-19 outbreak based on comprehensive field measurements in Beijing during January and February 2020. After excluding the Spring Festival period affected by fireworks activities, we found the ozone concentrations and the proportion of sulfate and nitrate in PM2.5 increased during the COVID-19 lockdown compared with the period before the lockdown, and sulfate played a more important role. Heterogeneous chemistry and photochemistry dominate the formation of sulfate and nitrate during the whole campaign, respectively, and the heterogeneous formation of nitrate at night was enhanced during the lockdown. The coeffects of more reductions in NOx than VOCs, weakened titration of NO, and increased temperature during the lockdown led to the increase in ozone concentrations, thereby promoting atmospheric oxidation capacity and photochemistry. In addition, the increase in relative humidity during the lockdown facilitated heterogeneous chemistry. Our results indicate that unbalanced emission reductions and adverse meteorological conditions induce the formation of secondary pollutants during the COVID-19 lockdown haze, and the formulation of effective coordinated emission-reduction control measures for PM2.5 and ozone pollution is needed in the future, especially the balanced control of NOx and VOCs.

Predictive value of the ratio of venoarterial PCO2 to arteriovenous O2 content difference for organ injury in patients with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is a common but severe disease with high mortality. Organ injury is the primary risk factor for death in SAP patients. The purpose of this study was to explore the predictive value of the ratio of venoarterial PCO2 to arteriovenous O2 content difference [P(cv-a)CO2/C(a-cv)O2] for organ injury in patients with SAP to provide evidence for further clinical intervention. METHODS: We retrospectively collected data from 108 patients with SAP admitted to Huzhou Central Hospital between January 2018 and January 2021. Forty-five patients who experienced organ injury were defined as the organ injury group, and 63 patients without organ injury were defined as the control group. The differences in P(cv-a)CO2/C(a-cv)O2, lactate, hematocrit (HCT), Acute Physiology and Chronic Health Evaluation (APACHE II) scores, and Ranson scores between the two groups were analyzed, and a receiver operating characteristic curve (ROC) was used to analyze the value of P(cv-a)CO2/C(a-cv)O2 in the prediction of organ injury in SAP patients. RESULTS: At admission, the organ injury group demonstrated significantly higher Ranson scores and APACHE II scores than the control group (Ranson scores: 6.09±1.35 vs. 3.97±2.02, respectively, P=0.000; APACHE II scores: 11.64±2.91 vs. 10.08±2.91, respectively, P=0.007). The value of P(cv-a)CO2/C(a-cv)O2 was also elevated compared to the control group (1.47±0.41 vs. 1.09±0.33, respectively, P=0.000) as was the level of lactate (3.33±0.86 vs. 2.56±0.70 mmol/L, respectively, P=0.000). There was no significant difference in HCT between the two groups at admission (44.47%±6.29% vs. 44.53%±5.75%, respectively, P=0.957). The Ranson score, APACHE II score, P(cv-a)CO2/C(a-cv)O2 and lactate levels were all significant predictors of organ injury in patients with SAP. The area under the curve of P(cv-a)CO2/C(a-cv)O2 was 0.733 (0.637-0.829), P=0.000. CONCLUSIONS: P(cv-a)CO2/C(a-cv)O2 is a potential predictor of organ injury in patients with SAP.

[Phenotypic and genotypic analysis of a pedigree affected with hereditary protein C deficiency].

OBJECTIVE: To analyze the phenotype and genetic variant in a pedigree affected with inherited protein C (PC) deficiency. METHODS: The proband and her family members (7 individuals from 3 generations) were tested for plasma protein C activity (PC:A), protein C antigen (PC:Ag) content and other coagulation indicators. All of the 9 exons and flanking sequences of the proband's PROC gene were amplified by PCR and sequenced. Suspected variants were verified by reverse sequencing of the proband and her family members. Bioinformatic software was used to analyze the pathogenicity and conservation of the variant site. Swiss-PdbViewer was used to analyze the three-dimensional model and the interaction with the mutant amino acid. RESULTS: The PC:A and PC:Ag of the proband, her grandmother, father and elder brother were decreased to 55%, 52%, 48%, 51% and 53%, 55%, 50%, 56%, respectively. Genetic analysis showed that the four individuals have all carried heterozygous c.1318C>T (p.Arg398Cys) missense mutation in exon 9 of the PROC gene. The score of MutationTaster was 0.991, PROVEAN was -3.72, and FATHMM was -2.49, all predicted it to be a harmful mutation. Phylogenetic analysis also showed that Arg398 was weakly conservative among homologous species. Protein model analysis showed that, in the wild type, Arg398 can form a hydrogen bond with Glu341 and Lys395 respectively, when it was mutated to Cys398, the hydrogen bond with Glu341 disappears and an additional hydrogen bond was formed with Lys395, which has changed the spatial structure of the protein. CONCLUSION: The heterozygous missense mutation c.1318C>T (p.Arg398Cys) of the PROC gene probably underlay the decreased PC:A and PC:Ag in this pedigree.

Serum Inflammatory Factor Profiles in the Pathogenesis of High-Altitude Polycythemia and Mechanisms of Acclimation to High Altitudes.

High-altitude polycythemia (HAPC) is a common aspect of chronic mountain sickness (CMS) caused by hypoxia and is the main cause of other symptoms associated with CMS. However, its pathogenesis and the mechanisms of high-altitude acclimation have not been fully elucidated. Exposure to high altitude is associated with elevated inflammatory mediators. In this study, the subjects were recruited and placed into a plain control (PC) group, plateau control (PUC) group, early HAPC (eHAPC) group, or a confirmed HAPC (cHAPC) group. Serum samples were collected, and inflammatory factors were measured by a novel antibody array methodology. The serum levels of interleukin-2 (IL-2), interleukin-3 (IL-3), and macrophage chemoattractant protein-1 (MCP-1) in the eHAPC group and the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, tumor necrosis factor-alpha (TNF-alpha), MCP-1, and interleukin-16 (IL-16) in the cHAPC group were higher than those in the PUC group. More interestingly, the expression of IL-1 beta, IL-2, IL-3, TNF-alpha, MCP-1, and IL-16 in the PUC group showed a remarkable lower value than that in the PC group. These results suggest that these six factors might be involved in the pathogenesis of HAPC as well as acclimation to high altitudes. Altered inflammatory factors might be new biomarkers for HAPC and for high-altitude acclimation.

Surface-enhanced Raman scattering for mixing state characterization of individual fine particles during a haze episode in Beijing, China.

The nondestructive characterization of the mixing state of individual fine particles using the traditional single particle analysis technique remains a challenge. In this study, fine particles were collected during haze events under different pollution levels from September 5 to 11 2017 in Beijing, China. A nondestructive surface-enhanced Raman scattering (SERS) technique was employed to investigate the morphology, chemical composition, and mixing state of the multiple components in the individual fine particles. Optical image and SERS spectral analysis results show that soot existing in the form of opaque material was predominant during clear periods (PM2.5 ≤ 75 µg/m3). During polluted periods (PM2.5 > 75 µg/m3), opaque particles mixed with transparent particles (nitrates and sulfates) were generally observed. Direct classical least squares analysis further identified the relative abundances of the three major components of the single particles: soot (69.18%), nitrates (28.71%), and sulfates (2.11%). A negative correlation was observed between the abundance of soot and the mass concentration of PM2.5. Furthermore, mapping analysis revealed that on hazy days, PM2.5 existed as a core-shell structure with soot surrounded by nitrates and sulfates. This mixing state analysis method for individual PM2.5 particles provides information regarding chemical composition and haze formation mechanisms, and has the potential to facilitate the formulation of haze prevention and control policies.

Stronger secondary pollution processes despite decrease in gaseous precursors: A comparative analysis of summer 2020 and 2019 in Beijing.

To control the spread of COVID-19, China implemented a series of lockdowns, limiting various offline interactions. This provided an opportunity to study the response of air quality to emissions control. By comparing the characteristics of pollution in the summers of 2019 and 2020, we found a significant decrease in gaseous pollutants in 2020. However, particle pollution in the summer of 2020 was more severe; PM2.5 levels increased from 35.8 to 44.7 µg m-3, and PM10 increased from 51.4 to 69.0 µg m-3 from 2019 to 2020. The higher PM10 was caused by two sandstorm events on May 11 and June 3, 2020, while the higher PM2.5 was the result of enhanced secondary formation processes indicated by the higher sulfate oxidation rate (SOR) and nitrate oxidation rate (NOR) in 2020. Higher SOR and NOR were attributed mainly to higher relative humidity and stronger oxidizing capacity. Analysis of PMx distribution showed that severe haze occurred when particles within Bin2 (size ranging 1-2.5 µm) dominated. SO42-(1/2.5) and SO42-(2.5/10) remained stable under different periods at 0.5 and 0.8, respectively, indicating that SO42- existed mainly in smaller particles. Decreases in NO3-(1/2.5) and increases in NO3-(2.5/10) from clean to polluted conditions, similar to the variations in PMx distribution, suggest that NO3- played a role in the worsening of pollution. O3 concentrations were higher in 2020 (108.6 µg m-3) than in 2019 (96.8 µg m-3). Marked decreases in fresh NO alleviated the titration of O3. Furthermore, the oxidation reaction of NO2 that produces NO3- was dominant over the photochemical reaction of NO2 that produces O3, making NO2 less important for O3 pollution. In comparison, a lower VOC/NOx ratio (less than 10) meant that Beijing is a VOC-limited area; this indicates that in order to alleviate O3 pollution in Beijing, emissions of VOCs should be controlled.

Tandem autologous hematopoietic stem cell transplantation for treatment of adult T-cell lymphoblastic lymphoma: a multiple center prospective study in China.

T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and lacks of a standard treatment regimen. In this study, we assessed the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) strategy for adult T-LBL and evaluated prognostic factors affecting survival. 181 Newly-diagnosed adult T-LBL patients were enrolled, 89 patients were treated with chemotherapy alone, 46 patients were allocated to single auto-HSCT group, 46 patients were treated with tandem auto-HSCT. The median follow-up time was 37 months, the 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (26.5% vs 53.1% and 54.8%). The 3-year PFS and OS rate of the tandem auto-HSCT group (73.5% and 76.3%) were significantly higher than those of the single auto-HSCT group (46.9% and 58.3%) and the chemotherapy group (45.1% and 57.1%). In the tandem auto-HSCT group, age and disease status after the first transplantation impacted the OS and PFS. Multivariate analysis identified that disease status after the first transplantation was the only independent prognostic factor for patients treated with tandem-HSCT. In addition, diagnostic models of the initial CD8+CD28+/CD8+CD28- T cell ratio in predicting the disease status were found to be significant. Taken together, tandem auto-HSCT can be considered an optimal strategy for adult T-LBL patients (ChiCTR-ONN-16008480).

Aqueous degradation of artificial sweeteners saccharin and neotame by metal organic framework material.

The artificial sweeteners (ASs) saccharin (SAC) and neotame (NEO) are widely used across the globe and are considered as emerging contaminants in surface, ground, and drinking waters. To degrade SAC and NEO, the metal organic framework material Co-based bio-MOF-11 was prepared by hydrothermal reaction and used with peroxymonosulfate (PMS) activator. The effects of the initial concentration of SAC and NEO, bio-MOF-11-Co dosage, PMS concentration, initial pH, temperature, and competitive anions were determined. The results revealed that bio-MOF-11-Co effectively catalyzed the degradation of SAC and NEO and possessed good stability and recycling efficiency. The degradation reaction was effective from pH 3.6-9.8 and followed quasi-first-order kinetics with degradation rate constants of 0.001-0.013 min-1 for SAC and 0.03-0.52 min-1 for NEO. Increased temperature was conducive to the degradation of both artificial sweeteners. The presence of Cl- inhibited the degradation of SAC and NEO, while the presence of CO32- promoted their degradation. Electron paramagnetic resonance (EPR) and free radical quenching demonstrated that the primary free radicals were sulfate radicals ( [Formula: see text] ) and hydroxyl radicals (HO). The change of cobalt oxidation state and electron transfer in bio-MOF-11-Co mainly induces the production of [Formula: see text] . A plausible mechanism for degradation is [Formula: see text] and HO attack on CS bonds, NS bonds, and benzene rings.

Plasmacytoid Dendritic Cell Infiltration in Acute Myeloid Leukemia.

INTRODUCTION: Increasing evidence has demonstrated that plasmacytoid dendritic cells (PDCs) in the tumor microenvironment (TME) play an important role in tumorigenesis and progression. PDC infiltration has been found in certain malignancies such as classic Hodgkin's lymphoma and chronic myelomonocytic leukemia. Our previous work reported that PDC infiltration could occur in acute myeloid leukemia (AML), but the clinical significance of PDC in AML has not been thoroughly investigated. PATIENTS AND METHODS: Here, we evaluated the clinical significance of PDC to AML transition in a leukemia microenvironment. The frequency of PDCs in 80 acute myelomonocytic leukemia (AML-M4) and 83 acute monocytic leukemia (AML-M5) patients was determined by flow cytometry. RESULTS: We found 62 cases with PDC infiltration. These patients showed higher numbers of bone marrow blasts, higher mean Hb concentration, and required more cycles of chemotherapy before achieving complete remission (CR), but had lower white blood cell and platelet counts compared to patients without PDC infiltration. Drug sensitivity analysis showed that patients with PDC infiltration had lower sensitivity to standard chemotherapy regimens. Kaplan-Meier survival curves demonstrated that patients with PDC infiltration had a shorter overall survival (OS) time and progression-free survival time. DISCUSSION: These results suggested that PDC infiltration can be used for risk stratification of AML-M4/M5, and PDCs may transdifferentiate into leukemia in an AML microenvironment.