Early histological transformation of follicular lymphoma to diffuse large B-cell lymphoma indicating adverse survival: A population-based analysis and validation.

INTRODUCTION: The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts. METHODS: A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database. The Hematological Malignancy Research Network FL cohort and Aristotle study FL cohort were used to assess the external validity. RESULTS: Among 44,127 FL cases from the Surveillance, Epidemiology, and End Results database, 1311 cases were pathology-proven recorded to transform to diffuse large B-cell lymphoma. The cumulative rates of HT at 5, 10, and 15 years after FL diagnosis were estimated to be 1.19%, 2.93%, and 5.01%, respectively. Significantly worse overall survival and cancer-specific survival were exhibited in patients with HT than those without HT. Early HT (transformation of FL within 48 months after FL diagnosis [TOD48]) was an independent predictor for adverse overall survival of HT patients, regardless of treatment modalities before transformation. The adverse prognostic effect of TOD48 was validated in the Hematological Malignancy Research Network cohort and Aristotle study cohort. Older age (>75 years) and B symptoms within FL at diagnosis were the independent risk factors of TOD48. Furthermore, a novel prognostic model combining TOD48 with Follicular Lymphoma International Prognostic Index (TOD48-FLIPI) was constructed and validated for risk stratification. CONCLUSION: TOD48 was a risk indicator of HT, and the novel prognostic model "TOD48-FLIPI" for HT patients was proposed.

Diffuse large B-cell lymphoma with continuously elevated immunoglobulin M following treatment: a case report with pathologic, immunophenotypic, and molecular analyses.

A rare subtype of diffuse large B-cell lymphoma (DLBCL) has been reported to be accompanied by elevated immunoglobulin M (IgM) paraprotein in the serum at diagnosis, called as IgMs-DLBCL. The monoclonal IgM paraprotein disappears soon after treatment in most of these patients. Here, we described a DLBCL patient with continuously elevated IgM following therapy. A 59-year-old male was diagnosed with DLBCL (GCB subtype per Hans algorithm, stage IA) with involvement of the right cervical lymph node. After six cycles of immuno-chemotherapy with the R-CHOP regimen, complete metabolic remission was achieved, but an elevated level of serum IgM persisted. To investigate the origin of elevated IgM, pathologic, immunophenotypic, and molecular analyses of lymph node and bone marrow (BM) samples were performed pre- and post-treatment. BM infiltration of lymphoplasmacytic cells, and a typical immunophenotypic profile by flow cytometry supported the diagnosis of Waldenström macroglobulinemia (WM). The MCD subtype of DLBCL was identified by next-generation sequencing of the lymph node at initial diagnosis characterized by co-occurring point mutations in MYD88 L265P and CD79B. Additionally, two different dominant clonotypes of the immunoglobulin heavy chain (IGH) were detected in the lymph node and BM by IGH sequencing, which was IGHV 3-11*06/IGHJ 3*02 and IGHV 3-11*06/IGHJ 6*02, respectively, speculating to be two independent clonal origins. This study will provide a panoramic understanding of the origin or biological characteristics of DLBCL co-occurring with WM.

Bisabolane-type sesquiterpenoids and bacillibactin from the marine-derived fungus Aspergillus sydowii SCSIO 41041 and their enzyme inhibiting activity.

Twelve compounds, including eleven bisabolane-type sesquiterpenoids (1 - 11), and one bacillibactin (12) were identified from marine-derived fungus Aspergillus sydowii SCSIO 41041 isolated from Creseis acicula. The chemical structures were elucidated by the basis of spectroscopic evidences, including HRESIMS, NMR and optical rotation. Biologically, all compounds were evaluated for their acetyl cholin-esterase (AChE) enzyme, pancreatic lipase (PL) enzyme, neuraminidase (NA) and phosphodiesterase 4 (PDE4) inhibitory activities. Compound 12 displayed significant inhibitory activity against neuraminidase (NA) with an IC50 value of 24.0 µM, which was equivalent to the positive drug oseltamivir phosphate (IC50 value of 20.0 µM). And the NA inhibitory activity was confirmed by molecular docking analysis.

Nonmetric multidimensional scaling and probabilistic ecological risk assessment of trace metals in surface sediments of Daya Bay (China) using diffusive gradients in thin films.

This research is one main objective to assess combined toxicity of trace metal mixtures in aquatic biota in coastal sediments. Coastal sediments around the world are a major reservoir of trace metals from industrial wastewater discharge. Our case study site, Daya Bay in southern China, was selected because it has been under severe man-made impacts. Diffusive gradients in thin films (DGT) technique has proven to be a good method for measuring the bioavailability of trace metals. The bioavailability and distribution of trace metals in surface sediments were investigated along with their possible biological risks. The average bioavailable (DGT-labile) concentrations (µg/L) were 0.44 (V), 0.51 (Cr), 52.49 (Mn), 0.10 (Co), 1.36 (Ni), 0.74 (Cu), 14.53 (Zn), 0.97 (As), 0.14 (Se), 6.73 (Mo), 0.17 (Cd), 0.27 (Sb), 0.10 (W), and 1.32 (Pb). Nonmetric multidimensional scaling (NMS) is a robust multivariate ordination method that makes no assumptions about the distribution of the underlying data. NMS was used to explore that DGT-labile concentrations of trace metals were influenced by sediment properties. NMS results indicated that most DGT- labile trace metals influenced by sediment properties. Risk assessment of single trace metal toxicity revealed that risk quotient (RQ) values for Mn, Cu, Zn and Pb significantly exceeded 1, demonstrating that the toxic effects of these trace metals should be not ignored. The probabilistic ecological risk assessment for integral toxicity of one mixture of 14 trace metals revealed that Daya Bay surface sediments had a low probability (9.04 %) of adverse effects on aquatic biota.

Metal Biological Enrichment Capacities, Distribution Patterns, and Health Risk Implications in Sea Bass (Lateolabrax japonicus).

Seabass (Lateolabrax japonicus) is a major aquacultured fish species worldwide. The bioconcentration, bioaccumulation, and biomagnification of metals in water, sediments, and commercial feed were investigated in L. japonicus from an aquaculture pond in the Pearl River Delta of South China. Aluminum (Al), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), and lead (Pb) were determined in the dorsal muscle, viscera, backbone, gill, and stomach contents of L. japonicus. The gill and stomach contents had higher levels of bioconcentration of most metals than other parts of fish. Based on the bioaccumulation factor, the gill and backbone exhibited the highest accumulation of Zn, while the viscera had the highest capacity to accumulate Cu. The mean biomagnification factor values exceeded for As in dorsal muscle, for Cu in the viscera, for Cr and Pb in the gill, and for Al, Cr, Fe, Cu, and Pb in the stomach contents, indicating efficient bioaccumulation from commercial feed and their habitat. Non-metric multidimensional scaling analysis revealed two groups that resulted from the accumulation of metals in various parts of L. japonicus. Moreover, health risk assessment indicated that no notable adverse health effects occurred from the ingestion of L. japonicus.

Quantitative Proteomic Analysis Reveals the Key Molecular Events Driving Phaeocystis globosa Bloom and Dissipation.

Phaeocystis globosa is a marine-bloom-forming haptophyte with a polymorphic life cycle alternating between free-living cells and a colonial morphotype, that produces high biomass and impacts ecological structure and function. The mechanisms of P. globosa bloom formation have been extensively studied, and various environmental factors are believed to trigger these events. However, little is known about the intrinsic biological processes that drive the bloom process, and the mechanisms underlying P. globosa bloom formation remain enigmatic. Here, we investigated a P. globosa bloom occurring along the Chinese coast and compared the proteomes of in situ P. globosa colonies from bloom and dissipation phases using a tandem mass tag (TMT)-based quantitative proteomic approach. Among the 5540 proteins identified, 191 and 109 proteins displayed higher abundances in the bloom and dissipation phases, respectively. The levels of proteins involved in photosynthesis, pigment metabolism, nitrogen metabolism, and matrix substrate biosynthesis were distinctly different between these two phases. Ambient nitrate is a key trigger of P. globosa bloom formation, while the enhanced light harvest and multiple inorganic carbon-concentrating mechanisms support the prosperousness of colonies in the bloom phase. Additionally, colonies in the bloom phase have greater carbon fixation potential, with more carbon and energy being fixed and flowing toward the colonial matrix biosynthesis. Our study revealed the key biological processes underlying P. globosa blooms and provides new insights into the mechanisms behind bloom formation.

Risk assessment of heavy metal and pesticide mixtures in aquatic biota using the DGT technique in sediments.

Heavy metals and pesticides (HMPs) are common contaminants due to their extensive use worldwide. Diffusive gradients in thin films (DGT) are a good method for measuring the bioavailable concentration of pollutants. This study represents the first evaluation of HMP toxicity in aquatic biota using the DGT technique in sediments. Zhelin Bay was selected as the case study site because it has been contaminated by pollutants. Nonmetric multidimensional scaling (NMS) analysis reveals that a diverse range of pollutants (V, Cr, Ni, Cu, Zn, As, Se, InHg, Mo, Cd, Sb, W, Pb, CLP, PYR) are mainly influenced by sediment characteristics. Assessment of single HMP toxicity found that the risk quotient (RQ) values for Mn, Cu, inorganic Hg (InHg), chlorpyrifos (CLP) and diuron (DIU) are significantly higher than 1, indicating that the adverse effects of these single HMPs should not be ignored. The combined toxicity of HMP mixtures based on probabilistic ecotoxicological risk assessment shows that Zhelin Bay surface sediments had a medium probability (54.6%) of toxic effects to aquatic biota.

Micro-CT and SEM investigation of sound absorption structure and chambers in the otoliths of Giant Panda fish species - Chinese Bahaba (Bahaba taipingensis).

As a critically endangered (CR) fish species, Chinese Bahaba is a unique "Giant Panda" fish species in China and has been listed among the national first-class wildlife protection animals and China's top 10 genetic resources of aquatic products since 2021. This fish species is of high commercial value because its swim bladder is commonly used in traditional Chinese medicine. Its otoliths are the sensory organs immersed in the endolymph for maintaining its balance and hearing. However, rare information has been reported on the sound absorption structure and chambers of otoliths of such "Giant Panda" fish. The big "C" groove was found in the fish's front sagittal otolith with the crystal cluster in the back sagittal otolith, the former of which is a 3D layered structure, that is constructed by elongated prismatic crystals. Besides, there are numerous small holes and adhesion material in this 3D layered structure, where many chambers were also found, indicating that some specific sounds may be captured by this structure and these chambers may then amplify such sounds at a certain wavelength. This finding could be of great importance for protecting and conserving this critically endangered species.

Application of diffusive gradients in thin films to determine rare earth elements in surface sediments of Daya Bay, China: Occurrence, distribution and ecotoxicological risks.

Known as burgeoning contaminants, the bioavailability of rare earth elements (REEs) can be determined using diffusive gradients in thin films (DGT). As Daya Bay (South China) has been under serious anthropogenic influences, the present study examined the distribution of REEs in surface sediments and their possible ecological risks in the bay. The range of DGT-labile concentrations of REEs (∑REEs) was from 5.67 µg/L to 8.41 µg/L, with an average of 7.34 µg/L. Results of assessment of single REE toxicity revealed that the risk quotient (RQ) values of Y, Ce and Yb were >1, indicating that their potential negative impacts on the nearby environment. However, analysis of the integral toxicity of REE mixtures through assessment of probabilistic ecotoxicological risks showed that there was a negligibly low probability of toxicity of PRE surface sediments to aquatic organisms in the study area.

Appraising ecotoxicological risk of mercury species and their mixtures in sediments to aquatic biota using diffusive gradients in thin films (DGT).

Mercury (Hg) is a global, persistent and inevitable pollutant, the toxicity of which is mostly reflected in its species including inorganic Hg (InHg) and methyl mercury (MeHg). Using diffusive gradients in thin films (DGT) is deemed as a reliable technique to determine the bioavailability of pollutants. This study is the first attempt to assess the integrated toxicity of mercury species mixtures in sediments to the aquatic biota based on the DGT technique. In the course, the Daya Bay under serious anthropogenic influences was selected as the study case. The results showed that the DGT concentrations of InHg and MeHg were detected as 0.30-1.93 µg/L and 0.28-1.94 µg/L respectively in the surface sediments collected from the Daya Bay. In terms of the toxicity of single mercury species, the risk quotient (RQ) values of InHg and MeHg significantly exceeded 1, indicating that the adverse effects of InHg and MeHg should not be ignored. In terms of the integrated toxicity of mercury species mixtures, the probabilistic biological risk assessment results demonstrate that Daya Bay features low (3.32%) probability of toxic effects in its surface sediments to the aquatic biota.

Inferior survival and frequent hepatic dysfunction in non-Hodgkin's lymphoma patients with HBV infection: a systematic review and meta-analysis.

OBJECTIVES: No clear consensus has been reached about the clinical features in hepatitis B virus (HBV)-associated non-Hodgkin's lymphoma (NHL) patients. We performed a systematic review and meta-analysis to explore the clinical characteristics and prognosis of NHL patients with chronic HBV infection (HBsAg+). METHODS: Seven electronic databases were searched for relevant studies up to 31 January 2021. Hazard ratio (HR) or odds ratio (OR) corresponding to 95% confidence interval (CI) were calculated to estimate the outcomes. The primary outcome was survival outcome, including overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed in diffuse large B-cell lymphoma (DLBCL) patients. RESULTS: Twenty-three retrospective studies, comprising of 1202 HBsAg+ NHL patients and 4448 HBsAg- NHL patients, were included. Twenty-two studies were conducted on Chinese patients. Compared with HBsAg- NHL patients, significantly shorter OS (HR 1.68; 95% CI 1.48-1.91) and PFS (HR 1.80; 95% CI 1.20-2.71), lower rate of complete remission (OR 0.59, 95% CI 0.44-0.80) and higher frequency of hepatic dysfunction during chemotherapy (OR 3.46; 95% CI 2.61-4.57) were demonstrated in HBsAg+ NHL patients. Moreover, HBsAg+ patients were characterized by a younger age of disease onset, advanced disease stage, higher level of LDH and more frequent presence of B symptoms, and involvement of spleen and liver at diagnosis. Furthermore, subgroup analysis in DLBCL patients was also showed similar results. CONCLUSION: Our study implicated that NHL patients, especially DLBCL, with chronic HBV infection displayed inferior prognosis, higher incidence of hepatic dysfunction during chemotherapy and distinct clinical features.

Pharmacodynamic, pharmacokinetic, and phase 1a study of bisthianostat, a novel histone deacetylase inhibitor, for the treatment of relapsed or refractory multiple myeloma.

HDAC inhibitors (HDACis) have been intensively studied for their roles and potential as drug targets in T-cell lymphomas and other hematologic malignancies. Bisthianostat is a novel bisthiazole-based pan-HDACi evolved from natural HDACi largazole. Here, we report the preclinical study of bisthianostat alone and in combination with bortezomib in the treatment of multiple myeloma (MM), as well as preliminary first-in-human findings from an ongoing phase 1a study. Bisthianostat dose dependently induced acetylation of tubulin and H3 and increased PARP cleavage and apoptosis in RPMI-8226 cells. In RPMI-8226 and MM.1S cell xenograft mouse models, oral administration of bisthianostat (50, 75, 100 mg·kg-1·d-1, bid) for 18 days dose dependently inhibited tumor growth. Furthermore, bisthianostat in combination with bortezomib displayed synergistic antitumor effect against RPMI-8226 and MM.1S cell in vitro and in vivo. Preclinical pharmacokinetic study showed bisthianostat was quickly absorbed with moderate oral bioavailability (F% = 16.9%-35.5%). Bisthianostat tended to distribute in blood with Vss value of 0.31 L/kg. This distribution parameter might be beneficial to treat hematologic neoplasms such as MM with few side effects. In an ongoing phase 1a study, bisthianostat treatment was well tolerated and no grade 3/4 nonhematological adverse events (AEs) had occurred together with good pharmacokinetics profiles in eight patients with relapsed or refractory MM (R/R MM). The overall single-agent efficacy was modest, stable disease (SD) was identified in four (50%) patients at the end of first dosing cycle (day 28). These preliminary in-patient results suggest that bisthianostat is a promising HDACi drug with a comparable safety window in R/R MM, supporting for its further phase 1b clinical trial in combination with traditional MM therapies.

Polycyclic Aromatic Hydrocarbons (PAHs) in the intertidal sediments of Pearl River Estuary: Characterization, source diagnostics, and ecological risk assessment.

The surface intertidal sediments in the Pearl River Estuary of China were analyzed from multiple perspectives, including the distribution characteristics, potential sources, and biological risks of polycyclic aromatic hydrocarbons (PAHs). The average concentration of PAHs, ranging from 73.68 ng/g to 933.25 ng/g, was 346.78 ng/g. PAHs are mainly composed of the 2- and 3-ring PAHs, with naphthalene (Nap), phenanthrene (Phe), pyrene (Pyr), benzo(g,h, i) perylene (Dib), fluoranthene (Flua), and indeno (1,2,3-c,d) pyrene (Ind) as the dominant constituents. The principal component analysis combined with multiple linear regression showed that petroleum combustion and biomass/coal combustion have contributed 52.78% and 40.53%, respectively, to the PAHs in intertidal sediments of Pearl River Estuary. The occurrence of adverse biological effects as a result of PAH contamination in the intertidal sediments of Pearl River Estuary has increased by 8% based on the mean value of the probable effect quotient.

First attempt to assess ecotoxicological risk of fifteen rare earth elements and their mixtures in sediments with diffusive gradients in thin films.

Rare earth elements (REEs) are emerging contaminants due to their large scale of exploitation worldwide for using in the high-technology sector. Diffusive gradients in thin films (DGT) are a good method to measure the bioaccessibility of inorganic substances. This study is the first to evaluate the combined toxicity of REEs in sediments to aquatic biota using the DGT technique. The intertidal zone of the Pearl River Estuary (PRE) was selected as a case study, as the upper reaches of the Pearl River is a major REE reserve and production region. The DGT-labile measured concentrations of REEs (∑REEs) were found to range from 7.02-16.06 µg/L in intertidal surface sediments of the PRE. Assessment of single REE toxicity found that risk quotient (RQ) values for Y, Pr, Nd, Eu, Dy, Er, and Yb are significantly higher than 1, indicating that the adverse effects of these single REEs should be not ignored. The combined toxicity of REE mixtures based on probabilistic ecotoxicological risk assessment, shows that intertidal surface sediments of PRE had a low probability (3.72%) of toxic effects to aquatic biota.

[Characteristics, Source Analysis, and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) Pollution in Marine Organisms from Estuaries of Changhua River in Hainan Province].

To assess the contamination by polycyclic aromatic hydrocarbons (PAHs) in organisms in the estuary of Changhua River in Hainan, we determined the content of 16 priority PAHs by gas chromatography and mass spectrometry (GC-MS). The composition, source, and potential edible risk of PAHs were studied. The results showed that the total PAHs of demersal fish (wet weight, same below), crustaceans, and pelagic fish were 5.52-787.98, 12.18-154.64, and 10.20-199.79 ng·g-1, respectively, and the average contents were 83.21, 64.72, and 89.48 ng·g-1, respectively. There were some differences in the content of PAHs in various organisms. The average content followed the order of pelagic fish > demersal fish > crustaceans. Compared with other areas in the country and abroad, the content of marine organisms'PAHs in the estuary of the Changhua River was above the medium level. The result of isomer characteristic ratio showed that the PAHs of 33 organisms mainly came from the combustion sources (petroleum combustion and biomass combustion) and petroleum sources. Moreover, demersal fish were greatly affected by combustion sources, while pelagic fish were greatly affected by petroleum sources. Human risk assessment indicated that the content of benzopyrene (BaP) was within the limits set by the European Union. Most of the organisms in the estuary of Changhua River were within the safe range of consumption, but the long-term consumption of these seafoods may pose a potential health risk (1.0×10-5≤ILCR<1.0×10-4).

Bioaccessibility and human health implications of heavy metals in different trophic level marine organisms: A case study of the South China Sea.

This study investigated the total concentrations and bioaccessibility of heavy metals in edible tissues and trophic levels of 12 marine organism species in the South China Sea. The results were used to estimate health risks to humans. Of the heavy metals detected, nickel (Ni) was present at the highest concentrations, followed in descending, order by iron (Fe), zinc (Zn), manganese (Mn), chromium (Cr), copper (Cu), cadmium (Cd) and lead (Pb). Cd had the highest percentage bioaccessibility (61.91%). There were no correlations between log-transformed total metal concentrations and trophic level values, nor between log-transformed bioaccessibility metal concentrations and trophic level values. This indicates there is no biomagnification among these trace metals. The carcinogenic risk probabilities for Pb and Cr to urban and rural residents were below the acceptable level (< 1â€¯× 10-4). The target hazard quotient (THQ) value for each metal and the total THQ values for all metals studied indicated no significant risk of non-carcinogenic effects to urban and rural residents from consuming marine organisms from the South China Sea.

Non-metric multidimensional scaling and human risks of heavy metal concentrations in wild marine organisms from the Maowei Sea, the Beibu Gulf, South China Sea.

We investigated heavy metal concentrations in wild marine organisms from Maowei Sea, a significant gulf of low-latitude developing regions of the Beibu Gulf, South China Sea. Twenty species, comprising fish, cephalopods, and crustaceans were collected and analyzed for heavy metals. Heavy metal levels (mg/kg, wet weight) in the aquatic organism samples were: 0.003-1.800 for Cd, 0.02-0.14 for Pb, 0.10-0.63 for Cr, 0.20-77.50 for Cu, 9.50-64.60 for Zn, 0.006-0.066 for Hg, and 0.10-1.50 for As. Non-metric multidimensional scaling coupled with cluster analysis revealed two groupings that mainly resulted from different species of the metals in marine organisms. The highest concentrations of Cd, Pb, Cr, Ni, Cu, Zn, Hg, and As were found in species of cephalopods. Health risk assessment based on the target hazard quotients (THQ) and total THQ indicated no significant adverse health effects from consumption of marine organisms.

Nucleos(t)ide analogues for preventing HBV reactivation in immunosuppressed patients with hematological malignancies: a network meta-analysis.

BACKGROUND: We aimed to evaluate the efficacy of five oral nucleos(t)ide analogues (NAs), including lamivudine, entecavir, adefovir, telbivudine and tenofovir, for the prevention of hepatitis B virus (HBV) reactivation and HBV-related complications in chronic hepatitis B virus (CHB) infected patients with hematological malignancies receiving chemotherapy or hematopoietic stem cell transplantation (HSCT) by network meta-analysis. METHODS: The search identified 28 articles involving 5 different prophylactic regimens covering 1478 participants. RESULTS: Among five prophylactic regimes, tenofovir (predicted probability, 90%), was the most effective intervention followed by entecavir (88%) in preventing HBV reactivation. There was no significant difference between tenofovir and entecavir for preventing HBV reactivation. With regards to other outcomes, tenofovir and telbivudine was not included to evaluate due to lack of relevant studies. Entecavir was the most effective intervention in reducing the risk of HBV related hepatitis (100%), HBV related death (61%) and all other causes of hepatitis (98%). CONCLUSION: Tenofovir and entecavir might be the most potent regimes in prevention of HBV reactivation for CHB infected patients with hematological malignancies undergoing chemotherapy or HSCT.

Polycyclic aromatic hydrocarbons (PAHs) in wild marine organisms from South China Sea: Occurrence, sources, and human health implications.

Concentrations of 16 US EPA priority polycyclic aromatic hydrocarbons (PAHs) were measured in 15 marine wild organism species from South China Sea. The concentration (dry weight) of 16 PAHs ranged from 94.88 to 557.87ng/g, with a mean of 289.86ng/g. The concentrations of BaP in marine species were no detectable. The composition of PAHs was characterized by the 2- and 3-ring PAHs in marine species, and NA, PHE and FA were the dominant constituents. PAHs isomeric ratios indicated PAHs mainly originated from grass, wood and coal combustion, and petroleum. The human health risk assessment based on the excess cancer risk (ECR) suggested the probability of PAHs posing carcinogenic risk to human beings with consumption of marine organisms were negligible (probability<1×10-6).