Low albumin combined with low-molecular-weight heparin as risk factors for liver injury using azvudine: Evidence from an analysis of COVID-19 patients in a national prospective pharmacovigilance database.

OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.

UPLC-MS based plasma metabolomics and lipidomics reveal alterations associated with IgG4-related disease.

OBJECTIVE: The pathogenesis of IgG4-related disease (IgG4-RD) remains unclear. Metabolomic profiling of IgG4-RD patients offers an opportunity to identify novel pathophysiological targets and biomarkers. This study aims to identify potential plasma biomarkers associated with IgG4-RD. METHODS: Thirty newly diagnosed IgG4-RD patients, age-matched healthy controls and post-treated IgG4-RD patients were enrolled. Patients' clinical data, laboratory parameters and plasma were collected. Plasma was measured for ultraperformance liquid chromatography-tandem mass spectrometry based metabolomics and lipidomics profiling. Multivariate and univariate statistical analyses were conducted to identify potential biomarkers. The receiver operating characteristic and the correlations between biomarkers and clinical parameters were investigated. RESULTS: The plasma metabolites are altered among healthy controls, newly diagnosed IgG4-RD and post-treated IgG4-RD groups. Of the identified features, eight metabolites were significantly perturbed in the IgG4-RD group, including glyceric acid 1,3-biphosphate (1,3-BPG), uridine triphosphate (UTP), uridine diphosphate glucose (UDP-Glc) or uridine diphosphate galactose (UDP-Gal), lysophospholipids, linoleic acid derivatives and ceramides. Receiver operating characteristic analysis indicated that UTP, UDP-Glc/UDP-Gal and LysoPC (18:1) had high sensitivity and specificity in diagnosis of IgG4-RD. A Pearson correlation analysis showed that 1,3-BPG and UTP were strongly correlated with clinical parameters. CONCLUSION: IgG4-RD patients have a unique plasma metabolomic profile compared with healthy controls. Our study suggested that metabolomic profiling may provide important insights into pathophysiology and testable biomarkers for diagnosis of IgG4-RD.

miR-4443 targets TRIM14 to suppress metastasis and energy metabolism of papillary thyroid carcinoma (PTC) in vitro.

Tripartite motif-containing protein 14 (TRIM14) is a tumor-promoter in papillary thyroid carcinoma (PTC). We found that miR-4443 expression was significantly downregulated in PTC tumor tissue, and was negatively associated with TRIM14. This study was designed to investigate the relationship between miR-4443 and TRIM14 on metastasis and energy metabolism in PTC and the underlying mechanisms. To this end, human PTC cells (SW1736 and MZ-CRC-1) were transfected with a miR-4443 mimic or miR-4443 inhibitor + siRNA-TRIM14, and then dual-luciferase assay, Transwell, Seahorse, and western blot analyses were performed to assess the function of miR-4443 and the underlying mechanism. We found that ectopic expression of miR-4443 inhibited PTC cell migration, invasion, ATP production, and aerobic glycolysis, while inhibition of miR-4443 had the opposite effect. miR-4443 directly targeted TRIM14 and reduced both TRIM14 mRNA and protein levels. Silencing TRIM14 significantly reversed miR-4443 inhibition-induced PTC cell migration, invasion, ATP production, aerobic glycolysis, and phosphorylation of the transcription factor STAT3. These findings suggest that miR-4443 is a tumor suppressor in PTC and inhibits metastasis and energy metabolism via the suppression of TRIM14 signaling.

The composition of bacteria in gut and beebread of stingless bees (Apidae: Meliponini) from tropics Yunnan, China.

Stingless bees are the main pollinators in tropical and subtropical regions. However, there are only a few studies on the structure and composition of bacteria in the gut and beebread of stingless bees, especially in China. To address this shortage of information, we characterized the microbiota of three common species of stingless bees (Lepidotrigona terminata, Lepidotrigona ventralis and Tetragonula pagdeni) and beebread samples of T. pagdeni. The results showed that the gut of stingless bees contained a set of dominant bacteria, including Acetobacter-like, Snodgrassella, Lactobacillus, Psychrobacter, Pseudomonas, Bifidobacterium and other species. The gut microbiota structures of the three stingless bees were different, and the abundances of bacterial species in the gut varied between communities of the same bee species. The reasons for this are manifold and may include food preference, age and genetic differences. In addition, the abundances of Lactobacillus, Carnimonas, Escherichia-Shigella, Acinetobacter and other species were high in the beebread of stingless bees. In conclusion, our findings reveal the bacteria composition and structure of the gut and beebread of stingless bees in China and deepen our understanding of the dominant bacteria of the gut and beebread of stingless bees.

Iguratimod treatment reduces disease activity in early primary Sjögren's syndrome: An open-label pilot study.

OBJECTIVES: To evaluate the efficacy and safety of iguratimod in patients with early primary Sjögren's syndrome (pSS). METHODS: Twenty-seven disease-modifying antirheumatic drug-naive female patients met the revised American-European Consensus Group criteria for pSS were enrolled in this open-label pilot study. Patients were treated with iguratimod 25 mg twice a day for 24 weeks. The disease activity was assessed with European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at 12 and 24 weeks. Salivary and lacrimal gland function, laboratory, and subjective variables were also assessed. Generalized estimating equations were used to analyze parameters over time. RESULTS: ESSDAI (median, 5 versus 2 versus 2, p < .01), IgG (median, 26.6 versus 22.4 versus 21.4 g/L, p < .01) and rheumatoid factor (median, 119.9 versus 94.1 versus 83.8 lU/mL, p < .01) levels decreased significantly during iguratimod treatment. ESSPRI, salivary and lacrimal gland function, fatigue and health-related quality of life did not change during treatment. One patient experienced thrombocytopenia, and no other serious adverse effects were observed. CONCLUSION: In this study, iguratimod treatment is safe and effective for improving disease activity and laboratory parameters in early pSS patients.

Complement C1q synergizes with PTX3 in promoting NLRP3 inflammasome over-activation and pyroptosis in rheumatoid arthritis.

Excessive inflammatory cytokines play crucial roles in the pathogenesis of rheumatoid arthritis (RA), however, the underlying mechanism remains unclear. In this study, we demonstrated that pentaxin 3 (PTX3), an essential component of innate immunity, was elevated in RA and preferentially bound to CD14+ monocytes. C1q promoted the binding and resulted in increased cell proliferation, activation and caspase-1-related late apoptotic cells (7-AAD+annexin V+), as well as enhanced release of inflammatory cytokines including TNF-α, IL-1ß and IL-6. Serum from RA patients, compared with healthy controls, induced gasdermin D (GSDMD)-dependent pyroptosis in monocytes, and this ability was associated with disease activity. Moreover, PTX3 synergized with C1q to promote pyroptosis in RA-serum pre-incubated monocytes by coordinately enhancing NLRP3 inflammasome over-activation and inducing GSDMD cleavage, cell swelling with large bubbles, caspase-1-dependent cell death and inflammatory cytokine release including IL-6. On the other hand, IL-6 promoted PTX3 plus C1q-induced pyroptosis in both normal and RA serum pre-incubated monocytes. These findings collectively implicated an important role of IL-6 in driving PTX3 plus C1q-mediated pyroptosis in RA and shed lights on a potential new treatment strategy targeting pyroptosis-mediated persistent inflammatory cytokine release.

Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis.

OBJECTIVE: Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS: We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay. RESULTS: We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen. CONCLUSIONS: These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.

Antibiotic prophylaxis in perioperative period of percutaneous nephrolithotomy: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To explore the efficacy of antibiotic prophylaxis in perioperative period of percutaneous nephrolithotomy (PCNL) by conducting a systematic review and meta-analysis. MATERIALS AND METHODS: A systematic literature search using Pubmed, Embase, and the Chinese SinoMed, CNKI, WanFang and VIP databases was performed to find comparative studies on the efficacy of different antibiotic prophylaxis strategies in PCNL for preventing postoperative sepsis. The last search was conducted on 21 April 2019. All selected articles were reviewed independently by two, and in case of discordance, three reviewers. Summarized unadjusted odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to assess the efficacy of different antibiotic prophylaxis strategies. RESULTS: Thirteen independent studies comprising up to 1549 individuals were included. Compared with single dose before anesthesia, preoperative prophylactic antibiotics significantly reduced postoperative sepsis (OR 0.31, 95% CI 0.20-0.50; P < 0.00001) and fever (OR 0.26, 95% CI 0.14-0.48; P < 0.0001). But no remarkable difference in sepsis risk between patients with and without postoperative prophylactic antibiotics was detected (RR 1.19, 95% CI 0.72-1.97; P = 0.49). And patients receiving postoperative prophylactic antibiotics were at a significantly high risk of fever (OR 1.88, 95% CI 1.01-3.05; P = 0.05). Compared with single dose before anesthesia, preoperative prophylactic antibiotics significantly reduced positive pelvic urine (RR 0.22, 95% CI 0.09-0.54; P = 0.0009) and stone cultures (RR 0.40, 95% CI 0.25-0.64; P = 0.0001). CONCLUSIONS: The conclusion is drawn that preoperative prophylactic antibiotics indeed lowered the risk of postoperative sepsis and fever, whereas its postoperative use seems unnecessary. Besides, preoperative prophylactic antibiotics reduced positive pelvic urine and stone cultures significantly, which are a risk factor for sepsis. In our meta-analysis, the efficacy of different types of antibiotics and different courses of preoperative antibiotics could not be assessed. To verify the correctness of these conclusions, randomized controlled trials with a larger sample size and more rigorous study design are required.

A simple risk score model for predicting contrast-induced nephropathy after coronary angiography in patients with diabetes.

BACKGROUND: Contrast-induced nephropathy (CIN) is a common complication in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) and associated with poor outcome. Some previous studies have already set up models to predict CIN, but there is no model for patients with diabetes mellitus (DM) especially. Therefore, we aim to develop and validate a simple risk score for predicting the risk of CIN in patients with DM undergoing CAG/PCI. METHODS: A total of 1157 consecutive patients with DM undergoing CAG/PCI were randomly assigned to a development cohort (n = 771) and a validation cohort (n = 386). The primary endpoint was CIN, which was defined as an absolute increase in serum creatinine (SCr) by 0.5 mg/dL from the baseline within 48-72 h after contrast exposure. The independent predictors for CIN were identified by multivariate logistic regression, and the discrimination and calibration of the risk score were assessed by ROC curve and Hosmer-Lemeshow test, respectively. RESULTS: The overall incidence of CIN was 45 (3.9%). The new simple risk score (Chen score), which included four independent variables (age > 75 years, acute myocardial infarction, SCr > 1.5 mg/dL, the use of intra-aortic balloon pump), exhibited a similar discrimination and predictive ability on CIN (AUC 0.813, 0.843, 0.796, P > 0.05, respectively), mortality (AUC 0.735, 0.771, 0.826, respectively) and MACEs when being compared with the classical Mehran or ACEF risk score. CONCLUSION: Our data suggest that the new simple risk score might be a good tool for predicting CIN in patients with DM undergoing CAG/PCI.

Clinical Implications of Contrast-Induced Nephropathy in Patients Without Baseline Renal Dysfunction Undergoing Coronary Angiography.

BACKGROUND: The clinical implications of different definitions of contrast-induced nephropathy (CIN) in patients without baseline renal dysfunction are not well defined. METHODS: Consecutive patients at a single centre without baseline renal dysfunction (estimated glomerular filtration rate, eGFR≥60ml/min/1.73m2) undergoing coronary angiography or percutaneous coronary intervention (PCI), were systematically evaluated for long-term risk of mortality following CIN using two broad definitions: an absolute increase from baseline in serum creatinine (SCr) ≥0.3mg/dl (mild to severe absolute CIN) and a relative increase from baseline of 25% (mild to severe relative CIN) within 72hours. RESULT: Of 2,823 subjects alive before discharge following coronary angiography there were 320 episodes of mild to severe relative CIN (11.3%) and 125 of mild to severe absolute CIN (4.4%). During a median follow-up of 2.3years, 73 patients (3.2%) died. After adjustment for confounders, mild to severe absolute CIN was associated with an adjusted hazard ratio (HR) (95% confidence interval) for all-cause mortality of 3.31 (1.74-6.30) (p<0.0001) and relative CIN with an adjusted HR of 1.92 (1.09, 3.38) (p=0.024). The risk of mortality rose with severity of CIN. Two commonly used definitions of CIN combining absolute and relative terms (increase ≥ 0.3mg/dl or 50%, and ≥ 0.5mg/dl or 25% from the baseline) confirmed these results. CONCLUSION: Among patients without baseline renal dysfunction undergoing coronary angiography, the incidence of CIN can range widely depending on definition. Absolute CIN is less common than relative CIN. Regardless of definition, CIN is associated with a markedly increased risk of long-term mortality. This finding requires confirmation in multicentre studies.

Safe Hydration to Prevent Contrast-Induced Acute Kidney Injury and Worsening Heart Failure in Patients with Renal Insufficiency and Heart Failure Undergoing Coronary Angiography or Percutaneous Coronary Intervention.

An optimal hydration volume (HV) that prevents contrast-induced acute kidney injury (CI-AKI) in patients with renal insufficiency and heart failure (HF) at a high risk of worsening HF (WHF) has not been determined. We aimed to determine a safe HV that prevents CI-AKI and WHF following coronary angiography (CAG) or percutaneous coronary intervention (PCI) in patients with renal insufficiency and HF. We recruited 1,307 patients with renal insufficiency and HF and investigated the relationships between the peri-procedural HV/weight (HV/W) ratio, and the risks of CI-AKI and WHF following CAG or PCI. Higher HV/W quartiles were associated with higher CI-AKI rates (Q1: 6.2%, Q2: 9.1%, Q3: 12.5%, and Q4: 18.7%; P < 0.001) and a greater likelihood of WHF (Q1: 2.2%, Q2: 2.7%, Q3: 4.9%, and Q4: 11.7%; P < 0.001). The multivariate analyses indicated that excessively high HV/W ratios were associated with moderately increased risks of CI-AKI (Q4 versus Q1: adjusted odds ratio [OR] 2.16, 95% confidence interval [CI] 1.17-4.00) and WHF (Q4 versus Q1: adjusted OR 3.09, 95% CI 1.21-7.88). The multivariate Cox regression analysis indicated that a higher HV/W ratio was associated with significantly increased long-term mortality (Q2 versus Q1: adjusted hazard ratio [HR] 2.36; Q3 versus Q1: adjusted HR 2.85; Q4 versus Q1: adjusted HR 2.94; all P < 0.05). In conclusion, an excessively high HV/W might be associated with a moderately increased risk of CI-AKI, WHF, and long-term mortality in patients with renal insufficiency and HF.

[Clinicopathologic features of testicular seminoma with syncytiotrophoblastic cells: Analysis of 3 cases and review of the literature].

OBJECTIVE: To investigate the clinical and histopathologic features of testicular seminoma with syncytoplasmic trophoblastic components. METHODS: Using light microscopic staining, we analyzed the clinical and histopathologic characteristics, diagnosis, differential diagnosis and prognosis of 3 cases of testicular seminoma with syncytoplasmic trophoblastic components, and reviewed the relevant literature. RESULTS: All the 3 cases were typical seminoma with syncytiotrophoblastic giant cells. Immunohistochemistry showed strong expressions of CD117 OCT-4, SALL4 and PLAP in diffuse tumor cells, and that of hCG in syncytiotrophoblastic cells. Continuous monitoring and consultation exhibited normal levels of serum ß-hCG in all the cases after postoperative chemotherapy. CONCLUSIONS: Testicular seminoma with syncytiotrophoblastic giant cells and increased serum ß-hCG is a rare subtype, which occurs mostly in young people, sensitive to chemotherapy postoperatively and with a relatively good prognosis.

[Clinicopathological characterization of non-Hodgkin lymphoma of the prostate].

OBJECTIVE: To study the clinicopathological characteristics of non-Hodgkin lymphoma (NHL) of the prostate. METHODS: We collected the clinical data on 6 cases of NHL of the prostate pathologically confirmed between 2001 and 2017. The patients were aged 49－76 (median 62) years old, with the main clinical manifestations of painless swelling of the prostate and lower urinary tract obstruction. We analyzed the clinical features and the results of histological detection, immunohistochemical staining and B-cell gene rearrangement assay, and explored the clinicopathological characteristics and differential diagnosis of the disease based on the relevant literature. RESULTS: Histological detection revealed diffuse large B-cell lymphoma (DLBCL) in 4 cases (66.7%), B-lymphoblastic lymphoma (B-LBL) in 1 (16.7%), and Burkitt lymphoma (BL) in another (16.7%). DLBCL was histologically characterized by diffuse oval or round medium-to-large-sized lyphoid cells with an infiltrative growth pattern, B-LBL by monotonous small-to-medium-sized lymphoid cells with prominet mitosis and apoptosis, and BL by diffuse and monotonous medium-sized neoplastic cells with round or oval nuclei, an infiltrative growth pattern, scanty cytoplasm and visible mitosis. One of the DLBCL patients received 5 doses of R-CHOP chemotherapy and has been followed up to the present time, while the other 3 were lost to follow-up; the B-LBL patient died at 1 month after diagnosis; and the BL patient gave up treatment. CONCLUSIONS: Non-Hodgkin's lymphoma of the prostate mostly presents as diffuse large B-cell lymphoma, and its diagnosis depends on immunohistochemistry and related molecular detection as well as its clinical and histopathological manifestations.

[Primary testicular diffuse large B-cell lymphoma: A clinicopathological analysis].

OBJECTIVE: To investigate the clinicopathological features, immunophenotype and treatment of primary testicular diffuse large B-cell lymphoma (DLBCL). METHODS: We retrospectively analyzed the pathomorphological characteristics and immunohistochemical markers of 23 cases of primary testicular DLBCL as well as their clinicopathological features with a review of the relevant literature. The patients were aged 48－76 (mean 61.4) years, 82.6% over 50 years, and all clinically presented with painless progressive unilateral testicular swelling, 9 cases in the left and the other 14 in the right testis. RESULTS: Histologically, the lymphomas were composed of large atypical cells with prominent karyokinesis and diffusely infiltrated the testicular parenchyma. The neoplastic cells were positive for B-cell markers. Five of the patients were followed up for 2 to 32 months, of whom 4 survived and 1 died at 9 months. CONCLUSIONS: Primary testicular DLBCL is a rare tumor with an invasive biological behavior, mostly found in elderly males and easily misdiagnosed or missed in diagnosis. Histopathology plays a key role and immunohistochemical markers are of high value in the definite diagnosis and differential diagnosis of the tumor.

Mnn10 Maintains Pathogenicity in Candida albicans by Extending α-1,6-Mannose Backbone to Evade Host Dectin-1 Mediated Antifungal Immunity.

The cell wall is a dynamic structure that is important for the pathogenicity of Candida albicans. Mannan, which is located in the outermost layer of the cell wall, has been shown to contribute to the pathogenesis of C. albicans, however, the molecular mechanism by which this occurs remains unclear. Here we identified a novel α-1,6-mannosyltransferase encoded by MNN10 in C. albicans. We found that Mnn10 is required for cell wall α-1,6-mannose backbone biosynthesis and polysaccharides organization. Deletion of MNN10 resulted in significant attenuation of the pathogenesis of C. albicans in a murine systemic candidiasis model. Inhibition of α-1,6-mannose backbone extension did not, however, impact the invasive ability of C. albicans in vitro. Notably, mnn10 mutant restored the invasive capacity in athymic nude mice, which further supports the notion of an enhanced host antifungal defense related to this backbone change. Mnn10 mutant induced enhanced Th1 and Th17 cell mediated antifungal immunity, and resulted in enhanced recruitment of neutrophils and monocytes for pathogen clearance in vivo. We also demonstrated that MNN10 could unmask the surface ß-(1,3)-glucan, a crucial pathogen-associated molecular pattern (PAMP) of C. albicans recognized by host Dectin-1. Our results demonstrate that mnn10 mutant could stimulate an enhanced Dectin-1 dependent immune response of macrophages in vitro, including the activation of nuclear factor-κB, mitogen-activated protein kinase pathways, and secretion of specific cytokines such as TNF-α, IL-6, IL-1ß and IL-12p40. In summary, our study indicated that α-1,6-mannose backbone is critical for the pathogenesis of C. albicans via shielding ß-glucan from recognition by host Dectin-1 mediated immune recognition. Moreover, our work suggests that inhibition of α-1,6-mannose extension by Mnn10 may represent a novel modality to reduce the pathogenicity of C. albicans.

DUSP1 and KCNJ2 mRNA upregulation can serve as a biomarker of mechanical asphyxia-induced death in cardiac tissue.

The incidence of death by asphyxia is second to the incidence of death by mechanical injury; however, death by mechanical asphyxia may be difficult to prove in court, particularly in cases in which corpses do not exhibit obvious signs of asphyxia. To identify a credible biomarker of asphyxia, we first examined the expression levels of 47,000 mRNAs in human cardiac tissue specimens from individuals who died of mechanical asphyxia and compared the expression levels with the levels of the corresponding mRNAs in specimens from individuals who died of craniocerebral injury using microarray. We selected 119 differentially expressed mRNAs, examined the expression levels of these mRNAs in 44 human cardiac tissue specimens of individuals who died of mechanical asphyxia, craniocerebral injury, hemorrhagic shock, or other causes. That the expression of dual-specificity phosphatase 1 (DUSP1) and potassium voltage-gated channel subfamily J member 2 (KCNJ2) was upregulated in human cardiac tissues from the mechanical asphyxia group compared with control tissues, regardless of age, environmental temperature, and postmortem interval (PMI), indicating that DUSP1 and KCNJ2 may be associated with mechanical asphyxia-induced death and can thus serve as useful biomarkers of death by mechanical asphyxia.

Safe Hydration Volume to Prevent Contrast-induced Acute Kidney Injury and Worsening Heart Failure in Patients With Heart Failure and Preserved Ejection Fraction After Cardiac Catheterization.

Few studies have investigated the efficacy and safety of hydration to prevent contrast-induced acute kidney injury (CI-AKI) and worsening heart failure (WHF) after cardiac catheterization in heart failure and preserved ejection fraction (HFpEF; HF and EF ≥50%) patients. We recruited 1206 patients with HFpEF undergoing cardiac catheterization with periprocedural hydration volume/weight (HV/W) ratio data and investigated the relationship between hydration volumes and risk of CI-AKI and WHF. Incidence of CI-AKI was not significantly reduced in individuals with higher HV/W [quartile (Q) 1, Q2, Q3, and Q4: 9.7%, 10.2%, 12.7%, and 12.2%, respectively; P = 0.219]. Multivariate analysis indicated that higher HV/W ratios were not associated with decreased CI-AKI risks [Q2 vs. Q1: odds ratio (OR), 0.95; Q3 vs. Q1: OR, 1.07; Q4 vs. Q1: OR, 0.92; all P > 0.05]. According to multivariate analysis, higher HV/W significantly increased the WHF risk (Q4 vs. Q1: adjusted OR, 8.13 and 95% confidence interval, 1.03-64.02; P = 0.047). CI-AKI and WHF were associated with a significantly increased risk of long-term mortality (mean follow-up, 2.33 years). For HFpEF patients, an excessively high hydration volume might not be associated with lower risk of CI-AKI but may increase the risk of postprocedure WHF.

Phytochemical and cytotoxic studies on the roots of Euphorbia fischeriana.

With the aim of supporting the folk applications of Euphorbia fischeriana, a phytochemical study was performed, which led to the discovery of 9 compounds, including three new ones (1-3) and six known ones (4-9). Their structures were determined by 1D, 2D NMR, and HRESIMS analysis. In the cytotoxic assays on Hep-3B cell line, 2 showed stronger inhibitory effects (IC50 8.1µmol/L) than that of positive control, and 1, 8 and 9 also gave inhibitory effects in a certain degree with IC50 values of 12.5, 12.0 and 18.7µmol/L, respectively. While on A549, the cytotoxic activities of 1 (IC50 11.9µmol/L) and 8 (IC50 9.4µmol/L) were superior to that of 5-Fu, and those of 4 and 9 were moderate with IC50 values of 28.2 and 29.8µmol/L, respectively. In addition, both petroleum ether and dichloromethane extracts showed cytotoxic activities with different degree, while n-butanol extracts had no effect. The results clarified that the low-polarity fractions of E. fischeriana, including triterpenoids, abietane and tigliane-type diterpenoids might be the potential bioactive ingredients which will exert strong antitumor effects.

Aggressive hydraTion in patients with ST-Elevation Myocardial infarction undergoing Primary percutaneous coronary intervention to prevenT contrast-induced nephropathy (ATTEMPT): Study design and protocol for the randomized, controlled trial, the ATTEMPT, RESCIND 1 (First study for REduction of contraSt-induCed nephropathy followINg carDiac catheterization) trial.

Adequate hydration is recommended for acute ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) to prevent contrast-induced nephropathy (CIN). However, the optimal hydration regimen has not been well established in these high-risk patients. The objective of this study is to evaluate the efficacy of a preprocedural loading dose plus postprocedural aggressive hydration with normal saline guided by the left ventricular end-diastolic pressure (LVEDP) compared with general hydration for CIN prevention. The ATTEMPT study is a multicenter, open-label, investigator-driven, randomized controlled trial in China. Approximately 560 patients with STEMI undergoing primary PCI will be randomized (1:1) to receive either periprocedural general hydration (control group) or aggressive hydration (treatment group). Patients in the control group receive periprocedural general hydration with ≤500 mL normal saline (within 6 hours) at a normal rate (0.5 or 1 mL/kg · h). Patients in the treatment group receive a preprocedural loading dose (125/250 mL) of normal saline within 30 minutes and intravenous hydration at a normal rate until LVEDP is available, followed by postprocedural aggressive hydration guided by LVEDP for 4 hours and then continuous intravascular hydration at the normal rate until 24 hours after PCI. The primary end point is CIN, defined as a >25% or 0.5-mg/dL increase in serum creatinine from baseline during the first 48 to 72 hours after procedure. The ATTEMPT study has the potential to identify optimal hydration regimens for STEMI patients undergoing PCI.