Ageing microenvironment mediates lymphocyte carcinogenesis and lymphoma drug resistance: From mechanisms to clinical therapy (Review).

Cellular senescence has a complex role in lymphocyte carcinogenesis and drug resistance of lymphomas. Senescent lymphoma cells combine with immunocytes to create an ageing environment that can be reprogrammed with a senescence­associated secretory phenotype, which gradually promotes therapeutic resistance. Certain signalling pathways, such as the NF­κB, Wnt and PI3K/AKT/mTOR pathways, regulate the tumour ageing microenvironment and induce the proliferation and progression of lymphoma cells. Therefore, targeting senescence­related enzymes or their signal transduction pathways may overcome radiotherapy or chemotherapy resistance and enhance the efficacy of relapsed/refractory lymphoma treatments. Mechanisms underlying drug resistance in lymphomas are complex. The ageing microenvironment is a novel factor that contributes to drug resistance in lymphomas. In terms of clinical translation, some senolytics have been used in clinical trials on patients with relapsed or refractory lymphoma. Combining immunotherapy with epigenetic drugs may achieve better therapeutic effects; however, senescent cells exhibit considerable heterogeneity and lymphoma has several subtypes. Extensive research is necessary to achieve the practical application of senolytics in relapsed or refractory lymphomas. This review summarises the mechanisms of senescence­associated drug resistance in lymphoma, as well as emerging strategies using senolytics, to overcome therapeutic resistance in lymphoma.

Kidney collecting-duct-derived vasopressin is not essential for appropriate concentration or dilution of urine.

We previously showed that kidney collecting ducts make vasopressin. However, the physiologic role of collecting-duct-derived vasopressin is uncertain. We hypothesized that collecting-duct-derived vasopressin was required for appropriate concentration of urine. We developed a vasopressin conditional knockout mouse model wherein Cre recombinase expression induces deletion of Avp exon 1 in the distal nephron. We then used age-matched 8 - 12 week old Avp fl/fl;Ksp-Cre(-) (WT) and Avp fl/fl;Ksp-Cre(+) mice for all experiments. We collected urine, serum, and kidney lysates at baseline. We then challenged both WT and KO mice with 24 hour water restriction, water loading, and administration of the vasopressin type 2 receptor (V2R) agonist desmopressin (dDAVP) 1 µg/kg/ip) followed by V2R antagonist OPC-31260 (10 mg/kg/ip). We performed immunofluorescence and immunoblot analysis at baseline and confirmed vasopressin knockout in the collecting duct. We found that urinary osmolality (UOsm), plasma Na+, K+, Cl-, BUN, and copeptin were similar in WT vs KO mice at baseline. Immunoblots of vasopressin regulated proteins Na:K:2Cl cotransporter (NKCC2), Na:Cl cotransporter (NCC) and water channel aquaporin-2 (AQP2) showed no difference in expression or phosphorylation at baseline. Following 24 hour water restriction, WT and KO mice had no differences in UOsm, plasma Na+, K+, Cl-, BUN or copeptin. Additionally, there were no differences in the rate of urinary concentration or dilution as WT and KO mice UOsm was nearly identical after dDAVP and OPC-31260 administration. We conclude that collecting-duct-derived vasopressin is not essential to appropriately concentrate or dilute urine.

Effects of indoor air pollution from household solid fuel use on the risk of gastrointestinal and liver diseases in middle aged and elderly adults.

Solid fuels are widely used in China and increase the concentrations of indoor air pollutants. Nevertheless, there is limited longitudinal evidence linking solid fuel use and Gastrointestinal (GI) and liver diseases. This study aimed to prospectively investigate the association between household solid fuel use and the risk of GI and liver diseases in middle aged and elderly adults. This work was based on the China Health and Retirement Longitudinal Study (CHARLS). Longitudinal data incorporate with cross-sectional data were analyzed. Compared with individuals using clean fuel for cooking, solid fuel users were observed to have higher risk of GI diseases (OR in 2011, 2013, 2015, 2018 wave separately: 1.37, 95 % CI: 1.24-1.50, P < 0.001; 1.24, 95 % CI: 1.11-1.39, P < 0.001; 1.18, 95 % CI: 1.06-1.33, P < 0.001; 1.23, 95 % CI: 1.04-1.45, P < 0.05). The associations between solid fuel use and liver diseases were not significant in most of the groups. Participants transforming from solid to clean cooking fuels had lower risk of GI and liver diseases than persistent solid fuel users. Moreover, biomass cooking fuel users were at a significant higher risk of both liver and GI diseases compared with clean fuel users. Overall, household solid fuel use, especially for cooking, was related to higher risk of GI and liver diseases, while switching from solid to clean fuels could reduce this risk. Using biomass for cooking was identified to be more associated with the increasing risk of GI and liver diseases than cooking with coal.

Risk factors for diabetic retinopathy, diabetic macular edema, and sight-threatening diabetic retinopathy.

OBJECTIVE: To identify the risk factors for the development of diabetic retinopathy (DR), diabetic macular edema (DME), and sight threatening DR (STDR) based on a city-wide diabetes screening program. RESEARCH DESIGN AND METHODS: Diabetic patients were prospectively recruited between June 2016 and December 2022. All patients underwent dilated fundus photography centered on the disc and macula or macula spectral domain optical coherence tomography (SD-OCT) scan. Complete medical history was documented.Systematic examination, blood analysis, and urinalysis were performed. Multivariate logistic regression analysis adjusting for age and sex was conducted. RESULTS: Out of 7,274 diabetic patients, 6,840 had gradable images, among which 3,054 (42.0%) were graded as DR, 1153 (15.9%) as DME, and 1,500 (20.6%) as STDR. The factors associated with DR, DME, and STDR included younger age (odds ratio [OR]: 0.96, 0.97, and 0.96 respectively), lower BMI (OR: 0.97, 0.95, and 0.95 respectively), longer duration of diabetes (OR: 1.07, 1.03, and 1.05 respectively) and positive of urinary albumin (OR: 2.22, 2.56, and 2.88 respectively). Other associated factors included elevated blood urea nitrogen (OR: 1.22, 1.28, and 1.27 respectively), higher LDL-cholesterol, lower blood haemoglobin (OR: 0.98, 0.98, and 0.98), insulin intake, presence of diabetic foot pathologies and diabetic peripheral neuropathy. We also identified novel risk factors, including high serum potassium (OR: 1.37, 1.46, and 1.55 respectively), high serum sodium (OR: 1.02, 1.02, and 1.04 respectively). Better family income was a protective factor for DR, DME, and STDR. Alcohol consumption once a week was also identified as a protective factor for DR. CONCLUSIONS: This study revealed high serum sodium, high serum potassium, low blood haemoglobin, and the level of family income as novel associated factors for DR, which can help with DR monitoring and management.

Remnant cholesterol and risk of major adverse cardiovascular events: a systematic review and dose-response meta-analysis of cohort studies.

Emerging evidence indicates a significant role of remnant cholesterol in contributing to the residual risk associated with major adverse cardiovascular events (MACE). This study aims to evaluate the dose-response relationship between remnant cholesterol and the risk of MACE. PubMed, Embase and Cochrane databases were reviewed to identify cohort studies published in English up to 1 August 2023. Twenty-eight articles were selected. Pooled hazard ratios (HR) and their 95% confidence intervals (CIs) were calculated using fixed or random-effects models to evaluate the association between remnant cholesterol and the risk of MACE. The dose-response relationship between remnant cholesterol levels and the risk of MACE was analyzed using the linear model and restricted cubic spline regression models. For calculated remnant cholesterol levels, the pooled HR (95% CI) of MACE for per 1-SD increase was 1.13 (1.08, 1.17); HR (95% CI) for the second quartile (Q2), the third quartile (Q3) and the highest quartile (Q4) of remnant cholesterol levels were 1.14 (1.03, 1.25), 1.43 (1.23, 1.68) and 1.68 (1.44, 1.97), respectively, compared with the lowest quartile (Q1). For measured remnant cholesterol levels, the pooled HR (95% CI) of MACE per 1-SD increase was 1.67 (1.39, 2.01). The dose-response meta-analysis showed a dose-response relationship between remnant cholesterol levels and the risk of MACE, both on a linear trend (P < 0.0001) and a nonlinear trend (P < 0.0001). The risk of MACE is associated with increased levels of remnant cholesterol, and the dose-response relationship between remnant cholesterol levels and the risk of MACE showed both linear and nonlinear trends.

Oxidized low-density lipoprotein changes the inflammatory status and metabolomics profiles in human and mouse macrophages and microglia.

The conjunctiva of primary open angle glaucoma patients showed high level of oxidized low-density lipoprotein (ox-LDL), which is associated with the inflammatory response. Microglia and macrophages are the immune cells involved in retinal ganglion cell survival regulation; yet, their roles of the ox-LDL-induced inflammation in glaucoma remain elusive. Here we aimed to investigate the lipid uptake, inflammatory cytokine expression, and metabolomics profiles of human and murine-derived microglial and macrophage cell lines treated with ox-LDL. Under the same ox-LDL concentration, macrophages exhibited higher lipid uptake and expression of pro-inflammatory cytokines as compared to microglia. The ox-LDL increased the levels of fatty acid metabolites in macrophages and sphingomyelin metabolites in microglia. In summary, this study revealed the heterogeneity in the inflammatory capacity and metabolic profiles of macrophages and microglia under the stimulation of ox-LDL.

Rapid Sample Pretreatment Facilitating SERS Detection of Trace Weak Organic Acids/Bases in Simple Matrices.

Surface-enhanced Raman spectroscopy (SERS) is a powerful tool for highly sensitive qualitative and quantitative analyses of trace targets. However, sensitive SERS detection can only be facilitated with a suitable sample pretreatment in fields related to trace amounts for food safety and clinical diagnosis. Currently, the sample pretreatment for SERS detection is normally borrowed and improved from the ones in the lab, which yields a high recovery but is tedious and time-consuming. Rapid detection of trace targets in a complex environment is still a considerable issue for SERS detection. Herein, we proposed a liquid-liquid extraction method coupled with a back-extraction method for sample pretreatment based on the pH-sensitive reversible phase transition of the weak organic acids and bases, where the lowest detectable concentrations were identical before and after the pretreatment process. The sensitive (µg L-1 level) and rapid (within 5 min) SERS detection of either koumine, a weak base, or celastrol, a weak acid, was demonstrated in different drinking water samples and beverages. Furthermore, target generality was demonstrated for a variety of weak acids and bases (2 < pKa < 12), and the hydrophilicity/hydrophobicity of the target determines the pretreatment efficiency. Therefore, the LLE-BE coupled SERS was developed as an easy, rapid, and low-cost tool for the trace detection of the two types of targets in simple matrices, which paved the way toward trace targets in complex matrices.

A DNA circuit that records molecular events.

Characterizing the relative onset time, strength, and duration of molecular signals is critical for understanding the operation of signal transduction and genetic regulatory networks. However, detecting multiple such molecules as they are produced and then quickly consumed is challenging. A MER can encode information about transient molecular events as stable DNA sequences and are amenable to downstream sequencing or other analysis. Here, we report the development of a de novo molecular event recorder that processes information using a strand displacement reaction network and encodes the information using the primer exchange reaction, which can be decoded and quantified by DNA sequencing. The event recorder was able to classify the order at which different molecular signals appeared in time with 88% accuracy, the concentrations with 100% accuracy, and the duration with 75% accuracy. This simultaneous and highly programmable multiparameter recording could enable the large-scale deciphering of molecular events such as within dynamic reaction environments, living cells, or tissues.

Signaling Transduction Pathways and G-Protein-Coupled Receptors in Different Stages of the Embryonic Diapause Termination Process in Artemia.

Artemia is a widely distributed small aquatic crustacean, renowned for its ability to enter a state of embryonic diapause. The embryonic diapause termination (EDT) is closely linked to environmental cues, but the precise underlying mechanisms remain elusive. In this study, ATAC-seq and RNA-seq sequencing techniques were employed to explore the gene expression profiles in Artemia cysts 30 min after EDT. These profiles were compared with those during diapause and 5 h after EDT. The regulatory mechanisms governing the EDT process were analyzed through Gene Ontology (GO) enrichment analysis of differentially expressed genes. Furthermore, the active G-protein-coupled receptors (GPCRs) were identified through structural analysis. The results unveiled that the signaling transduction during EDT primarily hinges on GPCRs and the cell surface receptor signaling pathway, but distinct genes are involved across different stages. Hormone-mediated signaling pathways and the tachykinin receptor signaling pathway exhibited heightened activity in the '0-30 min' group, whereas the Wnt signaling pathway manifested its function solely in the '30 min-5 h' group. These results imply a complete divergence in the mechanisms of signal regulation during these two stages. Moreover, through structural analysis, five GPCRs operating at different stages of EDT were identified. These findings provide valuable insights into the signal regulation mechanisms governing Artemia diapause.

Clinicopathologic analysis of nodal T-follicular helper cell lymphomas, a multicenter retrospective study from China.

Background: Nodal T-follicular helper cell lymphomas (nTFHLs) represent a new family of peripheral T-cell lymphomas (PTCLs), and comparative studies of their constituents are rare. Methods: This study retrospectively enrolled 10 patients with nTFHL-F and 30 patients with nTFHL-NOS diagnosed between December 2017 and October 2023 at six large comprehensive tertiary hospitals; 188 patients with nTFHL-AI were diagnosed during the same period at the First Affiliated Hospital of Zhengzhou University for comparison. Results: Compared with nTFHL-AI, nTFHL-NOS patients exhibited better clinical manifestations, lower TFH expression levels, and a lower Ki-67 index. However, no differences in clinicopathological features were observed between nTFHL-F and nTFHL-AI patients as well as nTFHL-NOS patients. According to the survival analysis, the median OS for patients with nTFHL-NOS, nTFHL-AI, and nTFHL-F were 14.2 months, 10 months, and 5 months, respectively, whereas the median TTP were 14 months, 5 months, and 3 months, respectively. Statistical analysis revealed differences in TTP among the three subtypes(P=0.0173). Among the population of patients receiving CHOP-like induction therapy, there were significant differences in the OS and TTP among the nTFHL-NOS, nTFHL-AI, and nTFHL-F patients (P=0.0134, P=0.0205). Both the GDPT and C-PET regimens significantly improved the ORR, OS, and PFS in nTFHL patients. Conclusion: There are significant differences in the clinical manifestations, pathology, and survival outcomes among the three subtypes of nTFHLs. However, further research with a larger sample size, and involving clinical pathology and molecular genetics is needed to determine the distinctive biological characteristics of these tumors.

Profile of Lipoprotein Subclasses in Chinese Primary Open-Angle Glaucoma Patients.

To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG patients on intraocular pressure (IOP)-lowering treatment and 20 age-matched control subjects were recruited. Based on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), the study subjects were divided into elevated- and normal-level subgroups. The plasma lipoprotein, lipoprotein subclasses, and oxidized LDL (oxLDL) levels were quantitatively measured. The discrimination potential of the lipoproteins was evaluated using the area under the receiver operating characteristic curve (AUC), and their correlation with clinical parameters was also evaluated. Compared to the control subjects with elevated TC and/or LDL-C levels, the levels of TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL), LDL subclass LDL3 and small dense LDL (sdLDL), and oxLDL were significantly higher in POAG patients with elevated TC and/or LDL-C levels. No differences in any lipoproteins or the subclasses were found between the POAG patients and control subjects with normal TC and LDL-C levels. Moderate-to-good performance of TC, LDL-C, non-HDL, LDL3, sdLDL, and oxLDL was found in discriminating between the POAG patients and control subjects with elevated TC and/or LDL-C levels (AUC: 0.710-0.950). Significant negative correlations between LDL3 and sdLDL with retinal nerve fiber layer (RNFL) thickness in the superior quadrant and between LDL3 and average RNFL thickness were observed in POAG patients with elevated TC and/or LDL-C levels. This study revealed a significant elevation of plasma lipoproteins, especially the LDL subclasses, in POAG patients with elevated TC and/or LDL-C levels, providing insights on monitoring specific lipoproteins in POAG patients with elevated TC and/or LDL-C.

Reconstruction of Metabolic-Protein Interaction Integrated Network of Eriocheir sinensis and Analysis of Ecdysone Synthesis.

Integrated networks have become a new interest in genome-scale network research due to their ability to comprehensively reflect and analyze the molecular processes in cells. Currently, none of the integrated networks have been reported for higher organisms. Eriocheir sinensis is a typical aquatic animal that grows through ecdysis. Ecdysone has been identified to be a crucial regulator of ecdysis, but the influence factors and regulatory mechanisms of ecdysone synthesis in E. sinensis are still unclear. In this work, the genome-scale metabolic network and protein-protein interaction network of E. sinensis were integrated to reconstruct a metabolic-protein interaction integrated network (MPIN). The MPIN was used to analyze the influence factors of ecdysone synthesis through flux variation analysis. In total, 236 integrated reactions (IRs) were found to influence the ecdysone synthesis of which 16 IRs had a significant impact. These IRs constitute three ecdysone synthesis routes. It is found that there might be alternative pathways to obtain cholesterol for ecdysone synthesis in E. sinensis instead of absorbing it directly from the feeds. The MPIN reconstructed in this work is the first integrated network for higher organisms. The analysis based on the MPIN supplies important information for the mechanism analysis of ecdysone synthesis in E. sinensis.

Untargeted and Oxylipin-Targeted Metabolomics Study on the Plasma Samples of Primary Open-Angle Glaucoma Patients.

Purpose: to determine the metabolomics profiles in the plasma samples of primary open-angle glaucoma (POAG) patients. Methods: The plasma samples from 20 POAG patients under intraocular pressure (IOP)-lowering medication treatment and 20 control subjects were subjected to the untargeted metabolomics analysis, among which 10 POAG patients and 10 control subjects were further subjected to the oxylipin-targeted metabolomics analysis by liquid chromatography-mass spectrometry analysis. The prediction accuracy of the differentially abundant metabolites was assessed by the receiver operating characteristic curves. Pathway analysis and correlation analysis on the differentially abundant metabolites and clinical and biochemical parameters were also conducted. Results: Untargeted metabolomics profiling identified 33 differentially abundant metabolites in the POAG patients, in which the metabolism of linoleic acid, α-linolenic acid, phenylalanine, and tricarboxylic acid cycle were enriched. The correlation analysis indicated that the differentially abundant metabolites were associated with central corneal thickness, peripapillary retinal nerve fiber layer thickness, visual field defects, and lymphocytes. The oxylipin-targeted metabolomics analysis identified 15-keto-Prostaglandin F2 alpha, 13,14-Dihydro-15-keto-prostaglandin D2, 11-Dehydro-thromboxane B2, 8,9-Epoxyeicosatrienoic acid, and arachidonic acid to be significantly decreased in the POAG patients and enriched in the arachidonic acid (AA) pathway. Conclusions: This study revealed that the metabolites in the arachidonic acid metabolism pathway are differentially abundant, suggesting high IOP may not be the only detrimental factor for optic nerve cell damage in this group of POAG patients. Lipid metabolism instability-mediated alterations in oxylipins and AA pathways may be important in POAG, suggesting that oxidative stress and immune-related inflammation could be valuable directions for future therapeutic strategies.

Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury.

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI. In three population-based epidemiology cohorts, we found that CHIP was associated with a greater risk of incident AKI, which was more pronounced in patients with AKI requiring dialysis and in individuals with somatic mutations in genes other than DNMT3A, including mutations in TET2 and JAK2. Mendelian randomization analyses supported a causal role for CHIP in promoting AKI. Non-DNMT3A-CHIP was also associated with a nonresolving pattern of injury in patients with AKI. To gain mechanistic insight, we evaluated the role of Tet2-CHIP and Jak2V617F-CHIP in two mouse models of AKI. In both models, CHIP was associated with more severe AKI, greater renal proinflammatory macrophage infiltration and greater post-AKI kidney fibrosis. In summary, this work establishes CHIP as a genetic mechanism conferring impaired kidney function recovery after AKI via an aberrant inflammatory response mediated by renal macrophages.

The long-term release and particle fracture behaviors of nanoplastics retained in porous media: Effects of surfactants, natural organic matters, antibiotics, and bacteria.

The transport of nanoplastics (NPs) in porous media has received a lot of attention, but the studies on the long-term release of NPs retained in porous media and the particle fracture during this process are seriously lacking. For filling this deficiency, we examined the individual or synergistic effects of surfactants, natural organic matters (NOMs), antibiotics, and bacteria on the desorption, long-term release, and particle fracture behaviors of polystyrene NPs (PS-NPs) retained in porous media. It was found that the change in hydrophilicity of PS-NPs dominated the long-term release of PS-NPs retained in porous media when surfactants were present. In the single system of surfactants and the dual system of surfactants and NOMs, the release of PS-NPs were improved owing to the increasing hydrophilicity of PS-NPs, although cationic surfactants also reduced the electrostatic repulsion between PS-NPs and porous media. Increasing antibiotic concentration reduced the electrostatic repulsion between PS-NPs and porous media to inhibit the release of PS-NPs. When bacteria were present whether containing antibiotics or not, the effects on roughness of PS-NPs dominated the release of PS-NPs. The effects of surfactants and NOMs on the PS-NP desorption were similar with the long-term release, with changes in hydrophilicity dominating the process. Whereas the effects of antibiotics and bacteria on the PS-NP desorption were different with the long-term release. Surfactants and NOMs in the presence of surfactants inhibited the fracture of PS-NPs by increasing the hydrophilicity of PS-NPs brought about the coating of water molecules on PS-NPs for protection. Antibiotics had no significant effects on the fracture of PS-NPs due to unaltered vertical forces on PS-NPs and no protective effect. Bacteria in the presence or absence of antibiotics inhibited the fracture of PS-NPs by coating PS-NPs retained in porous media to protect PS-NPs from fracture.

The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma.

Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1ß (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1ß, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.

A real-world observation on thrombopoietic agents for patients with cancer treatment-induced thrombocytopenia in China: A multicenter, cross-sectional study.

BACKGROUND: Studies on various thrombopoietic agents for cancer treatment-induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens. METHODS: In this retrospective, cross-sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL-11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO-RA). The outcomes, compliance, and safety of different treatments were analyzed. RESULTS: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL-11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL-11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy-induced thrombocytopenia (CIT) than rhIL-11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 109/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO-RA alone than with rhTPO and rhIL-11. CONCLUSIONS: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL-11, rhTPO, and TPO-RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding. PLAIN LANGUAGE SUMMARY: To provide an overview of the outcome of cancer treatment-induced thrombocytopenia in China, our cross-sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL-11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL-11.

Residential energy transition and chronic respiratory diseases.

Obtaining clean energy is of prime importance for planetary health and sustainable development. We aimed to assess the association between residential energy transition and the risk of chronic respiratory diseases. Using data from the Global Health Observatory and Global Burden of Diseases, Injuries, and Risk Factors Study, we delineated the spatial distribution and temporal trends of the population using clean fuels for cooking at a global scale. In the China Health and Retirement Longitudinal Study, we performed rigorous and well-structured multistage analyses incorporating both cross-sectional and prospective data analyses to examine the associations between solid fuel use, residential energy transition, duration of solid fuel use, and the risk of chronic respiratory diseases. Despite great progress, huge disparities in access to clean energy persist globally. Residential energy transition was associated with a lower risk of chronic respiratory diseases. In the period of 2011-2013, compared with persistent solid fuel users, both participants who switched from solid to clean fuels (adjusted risk ratio [RR] 0.78, 95% confidence interval [CI] 0.62-0.98) and persistent clean fuel users (adjusted RR 0.71, 95% CI 0.57-0.89) had significantly lower risk of chronic respiratory diseases (p < 0.001 for trend). Consistent associations were observed in the period of 2011-2015 and 2011-2018. Household energy transition from solid to clean fuels could reduce the risk of chronic respiratory diseases. This is a valuable lesson for policy-makers and the general public to accelerate energy switching to alleviate the burden of chronic respiratory diseases and achieve health benefits, particularly in low- and middle-income countries.

Cytoplasmic retention of the DNA/RNA-binding protein FUS ameliorates organ fibrosis in mice.

Uncontrolled accumulation of extracellular matrix leads to tissue fibrosis and loss of organ function. We previously demonstrated in vitro that the DNA/RNA-binding protein fused in sarcoma (FUS) promotes fibrotic responses by translocating to the nucleus, where it initiates collagen gene transcription. However, it is still not known whether FUS is profibrotic in vivo and whether preventing its nuclear translocation might inhibit development of fibrosis following injury. We now demonstrate that levels of nuclear FUS are significantly increased in mouse models of kidney and liver fibrosis. To evaluate the direct role of FUS nuclear translocation in fibrosis, we used mice that carry a mutation in the FUS nuclear localization sequence (FUSR521G) and the cell-penetrating peptide CP-FUS-NLS that we previously showed inhibits FUS nuclear translocation in vitro. We provide evidence that FUSR521G mice or CP-FUS-NLS-treated mice showed reduced nuclear FUS and fibrosis following injury. Finally, differential gene expression analysis and immunohistochemistry of tissues from individuals with focal segmental glomerulosclerosis or nonalcoholic steatohepatitis revealed significant upregulation of FUS and/or collagen genes and FUS protein nuclear localization in diseased organs. These results demonstrate that injury-induced nuclear translocation of FUS contributes to fibrosis and highlight CP-FUS-NLS as a promising therapeutic option for organ fibrosis.

Evaluation of multiple organophosphate insecticide exposure in relation to altered thyroid hormones in NHANES 2007-2008 adult population.

The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are simultaneously exposed to a multitude of chemicals. This study aimed to evaluate the association between an individual and a mixture of OPI metabolites and changes in serum thyroid hormone (TH) concentrations. The analyzed data were 1,434 participants from the United States National Health and Nutrition Examination Surveys (NHANES) cycle 2007-2008. Generalized linear model (GLM) regression, weighted quantile sum (WQS), and adaptive least absolute shrinkage and selection operator (adaptive LASSO) regression were used to investigate the associations between urinary OPI metabolites and altered serum THs. In GLM, all of the five urinary OPI metabolites were inversely associated with free triiodothyronine (FT3) among the male subjects; meanwhile, higher thyroglobulin (Tg) was related to dimethylphosphate (DMP). Moreover, in WQS models, the metabolite mixture induced FT3 down-regulation (ß = -0.209 (95% CI: -0.310, -0.114)), and caused an increased Tg concentration (ß = 0.120 (95% CI: 0.024, 0.212)), however, any significant association was observed among female participants. Consistently, the weighted index and LASSO coefficient demonstrated dimethylthiophosphate (DMTP) as the strongest metabolite in the FT3 model (mean weight= 3.449e-01 and ß =-0.022, respectively), and dimethylphosphate (DMP) represented the highest association in the Tg model (mean weight= 9.873e-01 and ß =-0.020, respectively). Further research is required to confirm our results and investigate the clinical impacts of these disruptions.