Network of depressive symptoms before and after a diagnosis of chronic kidney disease.

OBJECTIVE: A diagnosis of chronic kidney disease (CKD) may increase the risk for depression. The network perspective focuses on dynamic relationships among individual symptoms, which could advance our understanding of the development of depression during the transition to a diagnosis of CKD. The aim of this study was to use network analysis to examine the longitudinal associations of depressive symptoms from before to after a diagnosis of CKD. METHOD: The analytic sample included 1,386 participants from the Chinese Health and Retirement Longitudinal Study. Participants were aged 45 years or older and reported a doctor's diagnosis of CKD in any wave of interviews between 2011 and 2018. Depressive symptoms were measured by the 10-item version of the Center for Epidemiological Studies Depression. Cross-lagged panel network analysis was conducted to examine relationships between symptoms at three time points: prediagnosis; onset of diagnosis, and postdiagnosis). RESULTS: After controlling for other symptoms and covariates, feeling unable to get going and less happiness at prediagnosis were the most predictive of other symptoms at the diagnosis of CKD. Feeling effortful to do everything and depressed mood at the diagnosis of CKD were the most predictive of other symptoms at postdiagnosis. CONCLUSIONS: Fatigue (i.e., feeling unable to get going, feeling effortful to do everything), less happiness, and depressed mood were central symptoms during the transition to a diagnosis of CKD. These findings highlight the benefits of identifying and managing these central symptoms to reduce the risk of activating other depressive symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Extracellular vesicle-packaged ILK from mesothelial cells promotes fibroblast activation in peritoneal fibrosis.

Progressive peritoneal fibrosis and the loss of peritoneal function often emerged in patients undergoing long-term peritoneal dialysis (PD), resulting in PD therapy failure. Varieties of cell-cell communications among peritoneal cells play a significant role in peritoneal fibrogenesis. Extracellular vesicles (EVs) have been confirmed to involve in intercellular communication by transmitting proteins, nucleic acids or lipids. However, their roles and functional mechanisms in peritoneal fibrosis remain to be determined. Using integrative analysis of EV proteomics and single-cell RNA sequencing, we characterized the EVs isolated from PD patient's effluent and revealed that mesothelial cells are the main source of EVs in PD effluent. We demonstrated that transforming growth factor-ß1 (TGF-ß1) can substitute for PD fluid to stimulate mesothelial cells releasing EVs, which in turn promoted fibroblast activation and peritoneal fibrogenesis. Blockade of EVs secretion by GW4869 or Rab27a knockdown markedly suppressed PD-induced fibroblast activation and peritoneal fibrosis. Mechanistically, injured mesothelial cells produced EVs containing high level of integrin-linked kinase (ILK), which was delivered to fibroblast and activated them via p38 MAPK signalling pathway. Clinically, the expression of ILK was up-regulated in fibrotic peritoneum of patients undergoing long-term PD. The percentage of ILK positive EVs in PD effluent correlated with peritoneal dysfunction and the degree of peritoneal damage. Our study highlights that peritoneal EVs mediate communications between mesothelial cells and fibroblasts to initiate peritoneal fibrogenesis. Targeting EVs or ILK could provide a novel therapeutic strategy to combat peritoneal fibrosis.

Characterization of bone marrow heterogeneity in NK-AML (M4/M5) based on single-cell RNA sequencing.

Normal karyotype acute myeloid leukemia (NK-AML) is a heterogeneous hematological malignancy that contains a minor population of self-renewing leukemia stem cells (LSCs), which complicate efforts to achieve long-term survival. We performed single-cell RNA sequencing to profile 39,288 cells from 6 bone marrow (BM) aspirates including 5 NK-AML (M4/M5) patients and 1 healthy donor. The single-cell transcriptome atlas and gene expression characteristics of each cell population in NK-AML (M4/M5) and healthy BM were obtained. In addition, we identified a distinct LSC-like cluster with possible biomarkers in NK-AML (M4/M5) and verified 6 genes using qRT‒PCR and bioinformatic analyses. In conclusion, we utilized single-cell technologies to provide an atlas of NK-AML (M4/M5) cell heterogeneity, composition, and biomarkers with implications for precision medicine and targeted therapies.

Antitumor activity of recombinant oncolytic vaccinia virus with human IL2.

The tumor microenvironment is highly immunosuppressive. The genetically modified oncolytic vaccinia virus (OVV) is a promising vector for cancer immunotherapy. The aim of the present study was to assess the antitumor effects of human interleukin-2 (hIL2)-armed OVV in vitro. The hIL2 gene was inserted into a thymidine kinase and the viral growth factor double deleted oncolytic VV (VVDD) to generate recombinant hIL2-armed OVV (rVVDD-hIL2). Viral replication capacity in A549 cells was quantified by plaque titration on CV-1 cells. Production of hIL2 in cancer cells infected by rVVDD-hIL2 was measured by enzyme-linked immunosorbent assay. Finally, 3-(4,5-dimethylthiazol-2-yl)-5-(3-arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was performed to assess the antitumor effects of rVVDD-hIL2. The results showed that rVVDD-hIL2 viral particles expressed increasing levels of hIL2 in human and murine cancer cell lines with growing multiplicities of infection (MOIs). The insertion of the hIL2 gene did not impair the replication capacity of VV, and the rVVDD-hIL2 virus killed cancer cells efficaciously. The lytic effects of the recombinant oncolytic virus on tumor cells increased with the growing MOIs. In conclusion, these findings suggest that hIL2-armed VVDD effectively infects and lyses tumor cells, with high expression of hIL2.

Landscape of T Cells in NK-AML(M4/M5) Revealed by Single-Cell Sequencing.

Normal karyotype acute myeloid leukemia (NK-AML) is a highly heterogeneous malignancy that resides within a complex immune microenvironment, complicating efforts to reveal the interaction between leukemia cells and immune cells. Understanding tumor-infiltrating T cells is crucial to the advancement of immune therapies and the improvement of the prognosis for NK-AML patients. We performed single-cell RNA sequencing on bone marrow cells from 5 NK-AML (M4/M5) patients and 1 normal donor and paired single-cell T cell receptor (TCR) sequencing on single T cells. As a result, we identified 8 T cell clusters based on the gene expression characteristics of each subset in NK-AML and described their developmental trajectories. In NK-AML patients, specific clusters, such as mucosal-associated invariant T cells (MAITs), were preferentially enriched and potentially clonally expanded. These transcriptome and TCR data analyses provide valuable insights and rich resources for understanding the immune environment of NK-AML.

Clinical Significance of Decreased GPX1 Expression in Patients with Acute Myeloid Leukaemia (Non-M3).

OBJECTIVE: To determine the expression levels of GPX1, SOCS5 and IL7 and their clinical significance in patients with acute myeloid leukaemia (AML). STUDY DESIGN: A case-control study. PLACE AND DURATION OF STUDY: Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China, from January 2013 to November 2020. METHODOLOGY: Based on the bioinformatics analysis, the expression levels of GPX1, SOCS5 and IL7 in the bone marrow of 64 AML patients (non-M3) and 32 healthy individuals were evaluated by real-time PCR. Correlation between GPX1 expression and the clinical characteristics, response to induced chemotherapy, and survival time of AML patients were analysed as the outcome measure. RESULTS: GPX1 was significantly downregulated in AML patients, which helped in distinguishing AML patients from normal controls. The area under the curve (AUC) of the receiver operator characteristic (ROC) was 0.741 (p <0.001). Additionally, GPX1 expression was correlated with gender (r = -0.250, p = 0.045), FAB classification (r = -0.332,  p = 0.004), and chemotherapy response (r = 0.366, p = 0.003). AML patients with high GPX1 expression levels had a lower rate of remission (p = 0.021) and poor long-term survival (p = 0.036) than those with low GPX1 expression levels. CONCLUSION: Low GPX1 expression in AML patients may be closely associated with the pathogenesis and chemoresistance of AML. Key Words: Acute myeloid leukaemia, Clinical outcome, Gene expression, GPX1.

Development, Reliability, and Validity of the Home Blood Pressure Monitoring Adherence Scale for Patients with Chronic Kidney Disease.

BACKGROUND: Home blood pressure monitoring helps patients with chronic kidney disease to improve blood pressure control and can predict cardiovascular events, renal function progress, and risk of death. Few instruments are available to assess patient adherence to home blood pressure monitoring. OBJECTIVE: The aim of the study was to develop an instrument to evaluate home blood pressure monitoring adherence in patients with chronic kidney disease and test its reliability and validity. METHODS: An item pool was formed for the Home Blood Pressure Monitoring Adherence Scale by literature review. Patients with chronic kidney disease (n = 436) were surveyed to assess item selection and examine item reliability and validity. Scale reliability was evaluated using internal, split-half, and test-retest reliability, while validity was assessed according to content, construct, and criterion validity. RESULTS: The scale comprising eight items was formed from the item pool and item selection. Cronbach's α was 0.906, split-half reliability was 0.947, and test-retest reliability was 0.716. Item-level and scale-level (both universal agreement and average) content validity indices were 1.00. According to the Self-Efficacy for Managing Chronic Disease 6-item Scale, criterion validity for our scale was 0.251. Exploratory factor analysis extracted one factor and the cumulative variance contribution rate was 61.568%. Confirmatory factor analysis showed the model fit well (Χ 2=50.125, df=17, Χ 2 /df=2.949, root mean square error of approximation=0.095, confirmatory fit index=0.970). CONCLUSION: The scale has good reliability and validity for patients with chronic kidney disease, representing an efficient instrument for clinical assessment of home blood pressure monitoring adherence.

Influence of Monomer Ratios on Molecular Weight Properties and Dispersing Effectiveness in Polycarboxylate Superplasticizers.

A series of polycarboxylate superplasticizer (PCE) polymers were synthesized from acrylic acid (AA) and isoprenyloxy polyethylene glycol ether (IPEG) at the mole ratios of 3.0, 4.2, 5.0 and 6.0. In this study, the molecular weight properties of PCE polymers were recorded by size exclusion chromatography with the time interval of 1 h. Mini slump test was used to detect the dispersing effectiveness of PCE polymer in cement paste. The results indicated that the reaction rate of monomers, conversion of 52IPEG macromonomer and molecular weight of PCE polymers increased with the general adding ratio of AA to IPEG macromonomers while the side chain density of PCE polymers decreased. PCE polymers possessed molecular weight around 30,000 g/mol with low side chain density, and long main chain length presented high initial dispersing effectiveness at the low dosage around 0.12%. The majority of effective PCE polymers were formed during the adding period of acrylic acid in the first 3 h.

Rhabdomyolysis during myelosuppression in a patient with central nervous system leukemia: A case report.

RATIONALE: Rhabdomyolysis is a potentially life-threatening syndrome and is a rare complication in patients with acute leukemia. PATIENT'S CONCERNS: A 20-year-old male was admitted to our hospital due to skin ecchymosis in his trunk and lower limbs for 10 days. DIAGNOSES: Based on the precise diagnosis of leukemia, namely cell morphology, immunology, cytogenetics, and molecular biological typing (MICM), the patient was diagnosed with acute T-lymphocytic leukemia (T-ALL). INTERVENTIONS: The patient received hyper-Cyclophosphamide, Vincristine,Adriamycin, Dexamethasone (hyper-CVAD) regimen chemotherapy (methotrexate, pirarubicin, vincristine and dexamethasone alternating with methotrexate and cytarabine) for 3 courses of chemotherapy. After 3 months of treatment, the patient developed intermittent pain, blurred vision, and inarticulate speech. Therefore, the patient was considered as central nervous system leukemia (CNSL) and immediately received 2 courses of chemotherapy with hyper-CVAD-B combined with polyethylene glycol conjugated asparaginase (PEG-ASP). OUTCOMES: On the seventh day after the completion of chemotherapy, the patient was diagnosed with rhabdomyolysis because he complained of perianal pain and hematuria, and his creatine kinase (CK) increased suddenly to 3136 U/L. Finally, the patient died despite all kinds of active rescue. LESSONS: Rhabdomyolysis may occur after chemotherapy of leukemia. When patients developed hematuria, muscle weakness, or even asymptomatic elevation of CK levels, physicians should pay attention to the occurrence of rhabdomyolysis and take active hydration treatment.

Ethambutol and isoniazid induced severe neurotoxicity in a patient undergoing continuous ambulatory peritoneal dialysis.

Ethambutol (EMB) and isoniazid (INH) are the first-line antituberculosis (anti-TB) drugs. However, their neurotoxicity could cause adverse effect and the patients with end-stage renal disease are especially vulnerable due to the reduction in renal drug clearance. Here, we report a 36-year-old man receiving peritoneal dialysis developed progressive paralysis in lower extremities, vision loss and hoarseness 4 months after anti-TB treatment with INH, EMB and rifapentine because of concomitant pulmonary tuberculosis. A diagnosis of EMB/INH-induced peripheral neuropathy, retrobulbar neuritis and laryngoparalysis was made. The patient's neuropathy gradually improved 2 years after discontinuation of EMB/INH. Since EMB and INH may cause simultaneously severe and complex multineuropathy in dialysis patients, their adverse effects should be closely supervised in dialysis patients.

The diagnostic value of serum creatinine and cystatin c in evaluating glomerular filtration rate in patients with chronic kidney disease: a systematic literature review and meta-analysis.

BACKGROUND: Serum biomarkers, such as serum creatinine (SCr) and serum cystatin C (SCysC), have been widely used to evaluate renal function in patients who have chronic kidney disease (CKD). OBJECTIVE: This article aims to assess the value of determining SCr and SCysC levels in patients that have long-term kidney disease. Approaches: MEDLINE, EmBase, the Cochrane Library and other databases were searched using both MeSH terms and text words to collect research that assessed the diagnostic value of using SCr and SCysC to evaluate Glomerular Filtration Rate (GFR) in patients with CKD. Data were converted into fourfold tables. Summary Receiver Operating Characteristic Curves and meta-analyses were accomplished via Meta-Disc version 1.4. RESULTS: In total, 21 relevant articles involving 3112 study subjects were included in our review. Results showed that the collective sensitivity for SCr and SCysC was 0.77 (95% CI: 0.69-0.84) and 0.87 (95% CI: 0.82-0.91), respectively. The pooled specificity for SCr and SCysC was 0.91 (95% CI: 0.86-0.94) and 0.87 (95% CI: 0.82-0.91), respectively. Subgroup analyses demonstrated that when GFR cut-off values are set to 60 (ml/min/1.73 m2), the pooled sensitivity is 0.94 (95% CI: 0.90-0.96) for SCysC and 0.75 (95% CI: 0.68-0.82) for SCr. CONCLUSIONS: The diagnostical accuracy for impaired kidney function favors SCysC. Confidence intervals for the pooled sensitivity and specificity for SCr and SCysC overlap. However, SCysC is more sensitive for estimating GFR than SCr when GFR cut-off values are set to 60 (ml/min/1.73 m2).

Performances and working mechanism of a novel polycarboxylate superplasticizer synthesized through changing molecular topological structure.

A novel star-shaped polycarboxylate superplasticizer (SPCE) was synthesized through a simple two-step method. 1H Nuclear Magnetic Resonance (1H NMR) and Infrared Spectroscopy (IR) measurements were used for structural characterization. SPCE and comb-shaped polycarboxylate superplasticizer (CPCE) with same molecular weights were designed and synthesized. The cement paste containing SPCE exhibited better fluidity, fluidity retention, water reduction, 25% lower saturated dosage of PCE, 10% longer setting time, lower hydration heat, more delayed hydration heat evolution and lower amount of hydration products at early ages. Furthermore, the adsorption behavior of SPCE and CPCE in cement pastes and the zeta potential were investigated, and then the working mechanism of SPCE was theoretically explained. It is interesting that changing topological structure from comb-shape to star-shape can achieve the optimization of dispersion effect, and further improve the working effectiveness. The aims of this study are to provide a new avenue to synthesize superplasticizer with novel structure achieving the chemical diversity of superplasticizer structure, and to verify the contribution of optimizing molecular shape. This new type of superplasticizer can be used as a rheology modifying agent in fresh cement-based materials.

Prognostic value of nighttime blood pressure load in Chinese patients with nondialysis chronic kidney disease.

The prognostic value of nighttime blood pressure (BP) load in patients with chronic kidney disease (CKD) remains unknown. The prognostic value of nighttime BP load in a cohort of Chinese patients with nondialysis CKD was investigated. The authors monitored ambulatory BP and followed health outcomes in 588 Chinese CKD patients. Multivariable-adjusted Cox regression analyses indicated that nighttime BP load was a significant risk factor for all clinical outcomes in CKD patients, even when adjusted for clinic BP. Tertile 3 of systolic BP load (vs tertile 1) was associated with an increased risk of renal events (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.12-4.38) and cardiovascular events (HR, 5.34; 95% CI, 1.58-18.04); tertile 3 of diastolic BP load (vs tertile 1) was associated with an increased risk of all-cause mortality (HR, 6.73; 95% CI, 1.79-25.20), cardiovascular mortality (HR, 7.18; 95% CI, 1.47-35.03), renal events (HR, 2.40; 95% CI, 1.17-4.92), and cardiovascular events (HR, 5.87; 95% CI, 1.97-17.52). Higher nighttime BP load, especially nighttime diastolic BP load, was associated with a poorer prognosis in Chinese nondialysis CKD patients.

Preparation, Characterization and Performances of Powdered Polycarboxylate Superplasticizer with Bulk Polymerization.

A polycarboxylate superplasticizer (PCE) was synthesized in a non-solvent system with bulk polymerization and then was pulverized into powdered form to achieve a rapid transportation and convenient preparation. PCE synthesized by using isopentenyl polyethylene glycol (TPEG) or isobutenyl polyethylene glycol (IPEG) as a macromonomer exhibited the best fluidities and retaining properties at 80 °C and 75 °C, respectively. Besides, azobisisobutyronitrile (AIBN) was suitable as an initiator, and the fumaric acid was suitable as the third monomer. The test results of ¹H nuclear magnetic resonance (¹H NMR) confirmed the occurrences of polymerization, and the measurement results of molecular weight and distribution showed that PCE molecular weight characteristics were in accordance with their fluidity properties in cement paste. The application performances in cement showed that PCEs with the best paste fluidity retentions had the longest final setting time and the shortest setting time interval, and the PCEs with good fluidity properties can obviously delay the hydration process and lower the hydration heat. Accordingly, this is a novel, energy-saving and economical method to prepare powdered PCE in the field of concrete admixtures.