Lysine malonylation of DgnsLIPID TRANSFER PROTEIN1 at the K81 site improves cold resistance in chrysanthemum.

Lysine malonylation (Kmal) is a recently discovered posttranslational modification, and its role in the response to abiotic stress has not been reported in plants. In this study, we isolated a nonspecific lipid transfer protein, DgnsLTP1, from chrysanthemum (Dendranthema grandiflorum var. Jinba). Overexpression and CRISPR-Cas9-mediated gene editing of DgnsLTP1 demonstrated that the protein endows chrysanthemum with cold tolerance. Yeast 2-hybrid, bimolecular fluorescence complementation, luciferase complementation imaging, and coimmunoprecipitation experimental results showed that DgnsLTP1 interacts with a plasma membrane intrinsic protein (PIP) DgPIP. Overexpressing DgPIP boosted the expression of DgGPX (glutathione peroxidase), increased the activity of GPX, and decreased the accumulation of reactive oxygen species (ROS), thereby enhancing the low-temperature stress tolerance of chrysanthemum, while the CRISPR-Cas9-mediated mutant dgpip inhibited this process. Transgenic analyses in chrysanthemum showed that DgnsLTP1 improves the cold resistance of chrysanthemum in a DgPIP-dependent manner. Moreover, Kmal of DgnsLTP1 at the K81 site prevented the degradation of DgPIP in Nicotiana benthamiana and chrysanthemum, further promoted DgGPX expression, enhanced GPX activity, and scavenged excess ROS produced by cold stress, thereby further enhancing the cold resistance of chrysanthemum.

Association of Valproic Acid and Its Main Metabolites' Plasma Concentrations with Clinical Outcomes among Epilepsy Patients: A 10-Year Retrospective Study Based on Therapeutic Drug Monitoring.

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 µg/mL) is inadequate for predicting clinical outcomes. Additionally, the relationship between VPA metabolites and clinical outcomes remains unclear. In this retrospective study, 485 Chinese Southern Han epilepsy patients receiving VPA monotherapy were analyzed after reaching steady-state levels. Plasma concentrations of VPA and its five main metabolites were determined by liquid chromatography-mass spectrometry (LC-MS). We assessed the relevance of the recommended therapeutic VPA range for clinical outcomes and explored the association between VPA/metabolites levels and treatment efficacy/adverse effects. Vitro experiments were conducted to assess 4-ene-VPA hepatotoxicity. The therapeutic range of VPA exhibited no significant correlation with clinical outcomes, and plasma concentrations of VPA failed to serve as predictive indicators for treatment response/adverse effects. Treatment responders had higher 2-PGA concentrations (median, 26.39 ng/mL versus 13.68 ng/mL), with a threshold of 36.5 ng/mL for optimal epilepsy treatment. Patients with abnormal liver function had a higher 4-ene-VPA median concentration (6.41 µg/mL versus 4.83 µg/mL), and the ratio of 4-ene-VPA to VPA better predicted VPA-induced hepatotoxicity (area under the curve, 0.718) than 4-ene-VPA concentration. Vitro experiments revealed that 4-ene-VPA was more hepatotoxic than VPA in HepaRG and L02 cell lines. Total plasma VPA concentration does not serve as a predictor of clinical outcomes. 2-PGA concentrations may be associated with efficacy, whereas the ratio of 4-ene-VPA to VPA may be considered a better biomarker (threshold 10.03%) for VPA-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This was the first and largest observational cohort in China to explore the relationship between patients' parent and metabolites concentrations of VPA and clinical outcomes during the maintenance of VPA monotherapy in epileptic patients. This study provided feasible references of VPA for epilepsy clinical treatment with a larger sample of patients compared with previous studies for a more definitive conclusion based on real-world situations. We found two potential biomarkers in predicting efficacy and liver injury, respectively. This breakthrough has the potential to assist in the rational use of VPA.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

Sodium thiosulfate: A donor or carrier signaling molecule for hydrogen sulfide?

Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H2S), emerging findings suggest that it is the executive signaling molecule for H2S and that its effects may not be dependent on H2S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms in vivo. We also discussed the interplay of sodium thiosulfate and H2S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future.

Fabrication of a Terbium-Functionalized Cadmium Organic Framework with Proper Energy Levels as a Ratiometric Probe of an Anthrax Biomarker.

Anthrax bacillus is a very dangerous zoonotic pathogen that seriously endangers public health. Rapid and accurate qualitative and quantitative detection of its biomarkers, 2,6-dipicolinic acid (DPA), is crucial for the prevention and treatment of this pathogenic bacterium. In this work, a novel Cd-based MOF (TTCA-Cd) has been synthesized from a polycarboxylate ligand, [1,1':2',1″-terphenyl]-4,4',4″,5'-tetracarboxylic acid (H4TTCA), and further doped with Tb(III), forming a dual-emission lanthanide-functionalized MOF hybrid (TTCA-Cd@Tb). TTCA-Cd@Tb can be developed as a high-performance ratiometric fluorescent sensor toward DPA with a very low detection limit of 7.14 nM and high selectivity in a wide detection range of 0-200 µM, demonstrating a big advancement and providing a new option for the detection of DPA.

Post-traumatic hyperoxia after pediatric TBI.

OBJECTIVE: Hyperoxia has been suggested as a mechanism for secondary injury following adult traumatic brain injury (TBI), but its effects have not been well described in pediatric patients. METHODS: Pediatric (≤18yo) TBI patients were identified in a prospective institutional registry from October 2008 to April 2022. The first, highest, and the Area Under the Curve (AUC) PaO2 in the first 24 hours were collected and calculated for each patient from arterial blood gas reports after admission to the ICU. Neurological outcome after 6 months was measured using dichotomized modified Rankin Scale (mRS) and Glasgow Outcome Scale - Extended (GOS-E). Multivariable logistic regression models were used to determine if the three measurements for hyperoxia predicted an unfavorable outcome after controlling for well-established clinical and imaging predictors of outcome. RESULTS: We identified 98 pediatric patients with severe accidental TBI during the study period. Hyperoxia (PaO2 > 300 mmHg) occurred in 33% of the patients. The presence of elevated PaO2 values, determined by all three evaluations of hyperoxia, was not associated with unfavorable outcome after 6 months. CONCLUSION: Utilizing multiple methods to assess exposure, hyperoxia was present in a substantial number of patients with severe TBI but was not associated with an unfavorable outcome.

Personalized, parcel-guided non-invasive transcranial magnetic stimulation for the treatment of post-concussive syndrome: safety and proof of concept.

OBJECTIVE: To determine the safety and proof of concept of a parcel-guided, repetitive Transcranial Magnetic Stimulation (rTMS) in patients who develop a heterogeneous array of symptoms, known collectively as post-concussive syndrome (PCS), following traumatic brain injury (TBI). METHODS: We performed a retrospective review of off-label, individualized, parcel-guided rTMS in 19 patients from December 2020 to May 2023. Patients had at least one instance of mild, moderate, or severe TBI and developed symptoms not present prior to injury. rTMS targets were identified based on machine learning connectomic software using functional connectivity anomaly matrices compared to healthy controls. EuroQol (EQ-5D), as a measurement of quality of life, and additional questionnaires dependent on individual's symptoms were submitted prior to, after, and during follow-up from rTMS. RESULTS: Nineteen patients showed improvement in EQ-5D and Rivermead Post Concussion Symptoms Questionnaires - 3 after treatment and follow-up. For nine patients who developed depression, five (55%) attained response and remission based on the Beck Depression Inventory after treatment. Eight of ten patients with anxiety had a clinically significant reduction in Generalized Anxiety Disorder-7 scores during follow-up. CONCLUSION: Parcel-guided rTMS is safe and may be effective in reducing PCS symptoms following TBI and should incite further controlled studies.

ACBP4-WRKY70-RAP2.12 module positively regulates submergence-induced hypoxia response in Arabidopsis thaliana.

ACYL-CoA-BINDING PROTEINs (ACBPs) play crucial regulatory roles during plant response to hypoxia, but their molecular mechanisms remain poorly understood. Our study reveals that ACBP4 serves as a positive regulator of the plant hypoxia response by interacting with WRKY70, influencing its nucleocytoplasmic shuttling in Arabidopsis thaliana. Furthermore, we demonstrate the direct binding of WRKY70 to the ACBP4 promoter, resulting in its upregulation and suggesting a positive feedback loop. Additionally, we pinpointed a phosphorylation site at Ser638 of ACBP4, which enhances submergence tolerance, potentially by facilitating WRKY70's nuclear shuttling. Surprisingly, a natural variation in this phosphorylation site of ACBP4 allowed A. thaliana to adapt to humid conditions during its historical demographic expansion. We further observed that both phosphorylated ACBP4 and oleoyl-CoA can impede the interaction between ACBP4 and WRKY70, thus promoting WRKY70's nuclear translocation. Finally, we found that the overexpression of orthologous BnaC5.ACBP4 and BnaA7.WRKY70 in Brassica napus increases submergence tolerance, indicating their functional similarity across genera. In summary, our research not only sheds light on the functional significance of the ACBP4 gene in hypoxia response, but also underscores its potential utility in breeding flooding-tolerant oilseed rape varieties.

Comparison of immediate vs. delayed guided tissue regeneration in Infrabony defect of second molars after adjacent third molar extraction: a retrospective study.

BACKGROUND: The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making. METHODS: D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn's test or the Bonferroni test for pairwise comparisons. RESULTS: A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p < 0.001) and the delayed GTR group (2.98 ± 1.08 mm vs. 0.68 ± 1.03 mm, p < 0.001) compared to the control group. CONCLUSION: GTR can effectively improve d-M2 infrabony defects when the third molar is removed, whether simultaneously or delayed. Patients may experience less discomfort with immediate GTR treatment as it requires only one surgery.

Incremental Effect of Mitral Regurgitation on Left Atrial Dysfunction and Atrioventricular Interaction in Hypertensive Patients by MRI.

BACKGROUND: Mitral regurgitation may occur when hypertension causes left ventricular (LV) and left atrial (LA) remodeling. However, its role in LA function in hypertensive patients remains unclear. PURPOSE: To explore how mitral regurgitation affects LA function in hypertension and to investigate atrioventricular interaction in hypertensive patients with mitral regurgitation. STUDY TYPE: Retrospective. POPULATION: A total of 193 hypertensive cases and 64 controls. FIELD STRENGTH/SEQUENCE: A 3.0 T/balanced steady-state free precession. ASSESSMENT: LA volume (LAV), LA strain (reservoir, conduit, and active), LA ejection fraction, and LV strain (global peak longitudinal [GLS], circumferential [GCS], and radial strain [GRS]) were evaluated and compared among groups. Regurgitant fraction (RF) was evaluated in regurgitation patients and used to subdivide patients into mild (RF: 0%-30%), moderate (RF: 30%-50%), and severe (RF: >50%) regurgitation categories. STATISTICAL TESTS: One-way analysis of variance, Spearman and Pearson's correlation coefficients (r), and multivariable linear regression analysis. A P value <0.05 was considered statistically significant. RESULTS: Hypertensive patients without mitral regurgitation showed significantly impaired LA reservoir and conduit functions and significantly decreased LV GLS but preserved pump function and LAV compared to controls (P = 0.193-1.0). Hypertensive cases with mild regurgitation (N = 22) had significantly enlarged LAV and further reduced LA reservoir function, while the group with moderate regurgitation (N = 20) showed significantly reduced LA pump function, further impaired conduit function, and significantly reduced LV strain. The severe regurgitation (N = 13) group demonstrated significantly more severely impaired LA and LV functions and LAV enlargement. Multivariable linear regression showed that regurgitation degree, GRS, GCS, and GLS were independently correlated with the LA reservoir, conduit, and active strain in hypertensive patients with mitral regurgitation. DATA CONCLUSION: Mitral regurgitation may exacerbate LA and LV impairment in hypertension. Regurgitation degree, LV GRS, GCS, and GLS were independent determinants of the LA strain in hypertensive patients with mitral regurgitation, which demonstrated atrioventricular interaction. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 3.

Additional Impact of Aortic Regurgitation on Left Ventricular Strain and Remodeling in Essential Hypertension Patients Evaluated Using MRI.

BACKGROUND: Understanding the impact of aortic regurgitation (AR) on hypertensive patients' hearts is important. PURPOSE: To assess left ventricular (LV) strain and structure in hypertensive patients and investigate the relationship with AR severity. STUDY TYPE: Retrospective. POPULATION: 263 hypertensive patients (99 with AR) and 62 controls, with cardiac MRI data. FIELD STRENGTH/SEQUENCE: Balanced steady-state free precession (bSSFP) sequence at 3.0T. ASSESSMENT: AR was classified as mild, moderate, or severe based on echocardiographic findings. LV geometry was classified as normal, concentric remodeling, eccentric hypertrophy, or concentric hypertrophy based on MRI assessment of LV mass/volume ratio and LV Mass index (LVMI). LV global radial peak strain (GRPS), global circumferential peak strain (GCPS), and global longitudinal peak strain (GLPS) were obtained by post-processing bSSFP cine datasets using commercial software. STATISTICAL TESTS: ANOVA, Kruskal-Wallis test, Spearman's correlation coefficients (r), chi-square test, and multivariable linear regression analysis. A P value <0.05 was considered statistically significant. RESULTS: Hypertensive patients with AR had significantly lower LV myocardial strain and higher LVMI than the group without AR (GRPS 26.25 ± 12.23 vs. 34.53 ± 9.85, GCPS -17.4 ± 5.84 vs. -20.57 ± 3.57, GLPS -9.86 ± 4.08 vs. -12.95 ± 2.94, LVMI 90.56 ± 38.56 vs.58.84 ± 17.55). Of the 99 patients with AR, 56 had mild AR, 26 had moderate AR and 17 had severe AR. The degree of AR was significantly negatively correlated to the absolute values of LV GRPS, GCPS and GLPS (r = -0.284 - -0.416). LV eccentric hypertrophy increased significantly with AR severity (no AR 21.3%, mild AR 42.9%, moderate AR 73.1%, severe AR 82.4%). In multivariable analysis, the degree of AR was an independent factor affecting LV global strain and LVMI even after considering confounding factors (ß values for global myocardial strain were -0.431 to -0.484, for LVMI was 0.646). DATA CONCLUSION: Increasing AR severity leads to decreased cardiac function and worse ventricular geometric phenotypes in hypertensive patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Significant CT dose reduction of 2-[18F]FDG PET/CT in pretreatment pediatric lymphoma without compromising the diagnostic and staging efficacy.

OBJECTIVES: To compare the diagnostic and staging efficacy of PET/diagnostic-level CT (PET/DxCT) and PET/low-dose CT (PET/LDCT) in pretreatment pediatric lymphoma patients and to estimate the reduction of the CT effective dose in the PET/CT scan. METHODS: One hundred and five pediatric patients who underwent total-body PET/CT examination were enrolled and divided into the DxCT group (n = 47) and LDCT group (n = 58) according to their dose levels. The sensitivity, specificity, PPV, and NPV of PET/DxCT and PET/LDCT for detecting the involvement of lymph node, spleen, bone marrow, and other extranodal organs in pretreatment lymphoma were compared. ROC analysis was performed to evaluate the integral efficiency. The staging accuracies based on PET/DxCT and PET/LDCT were also evaluated. Dosimetry was calculated for DxCT and LDCT, and the reduction in the effective dose was estimated. RESULTS: In the diagnosis of nodal, splenic, bone marrow, and other extranodal involvement, the differences in sensitivity, specificity, PPV, and NPV between PET/LDCT and PET/DxCT were not significant (all p values ∈ [0.332, 1.000]). Both modalities had accuracies above 90% and the ROC analysis indicated good or high efficiency in diagnosing all patterns of lymphoma involvement. PET/LDCT and PET/DxCT each had a staging accuracy of 89.7% and 89.4%, respectively. LDCT had a comparable image quality score with DxCT, with a significant increase in noise (p < 0.001) and a 66.1% reduction in effective dose. CONCLUSIONS: PET/LDCT allowed for a 66.1% CT effective dose reduction compared to PET/DxCT in pediatric lymphoma patients without compromising the diagnostic and staging efficacy. KEY POINTS: • Pediatric lymphoma patients can benefit from a reduced effective dose of PET/CT. • This retrospective study showed that the diagnostic and staging efficacies of PET/low-dose CT are comparable to those of PET/diagnostic-level CT, both with satisfactory efficiency in diagnosing all patterns of lymphoma involvement. • PET/low-dose CT allowed for a 66.1% CT effective dose reduction compared to PET/diagnostic-level CT.

Blue-Emitting Zero-Dimensional Inorganic-Organic Hybrids Constructed from Beta-Diketonate Ligands and Bulky Organic Cations.

Two zero-dimensional inorganic-organic hybrids, namely, [C4mim][Cd(TCDPPA)3] (1) and [C4mpy][Cd(TCDPPA)3] (2), where (TCDPPA)- = 2,2,2-trichloro-N-(di(pyrrolidin-1-yl)phosphoryl)acetamide, (C4mim)+ = 1-butyl-3-methylimidazolium, and (C4mpy)+ = 1-butyl-4-methylpyridinium, have been synthesized via metathesis reactions and characterized systematically. These ionic cadmium-containing inorganic-organic hybrid compounds are assembled from a bulky organic cation and a complex anion constructed from the chelation of three TCDPPA ligands to one cadmium ion. These compounds possess wide band gaps and emit in the deep-blue region intensely with a quantum yield as high as 34.04%. The success of this work provides a new method for the design and fabrication of high-efficiency blue-emitting materials.

Safety and clinical outcomes in endovascular treatment for symptomatic cerebral venous thrombosis: a single-center experience with meta-analysis.

The role of mechanical thrombectomy (MT) in cerebral venous sinus thrombosis (CVT) is ambiguous. This study aims to share our experience with MT in CVT, supplemented by a meta-analysis on this treatment. All patients who had MT for CVT at our institution, between 2016 and 2021, were retrospectively reviewed for treatment indications, the technique used, success and complication rates, and clinical outcomes. A meta-analysis was performed for clinical and safety outcomes from published literature with > 10 patients. A total of 15 patients were included in this study. All had a venous hemorrhage or deteriorating despite anticoagulation. MT was performed using aspiration (with wide bore catheters) in 7 patients: aspiration with stent retriever in 5 and transjugular Fogarty-balloon thrombectomy in 3 patients. Adjunctive intra-sinus thrombolysis (IST) was used in 4 cases and venoplasty in 3. Technical success (restoring antegrade venous flow on arterial injection) was 100% with no procedure-related major complication. The direct transjugular approach was cheaper and faster. At 3-month follow-up, 86% of patients had good outcomes (MRS < 2). Meta-analysis of clinical and safety outcomes from 22 and 20 studies, respectively, demonstrated a positive association between MT and good outcomes as well as no significant association with hazardous periprocedural events. EVT via mechanical means for CVT is feasible in our series and meta-analysis. From our experience, trans-jugular Fogarty balloon embolectomy seems to be a potential cost-saving option, at least in a certain part of the world.

Effect of maternal age on foetal chromosomal defects: an investigation based on non-invasive prenatal testing.

BACKGROUND: This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in the prenatal screening of foetal aneuploidy-associated diseases at different gestational ages. METHODS: Briefly, cell-free foetal DNAs were extracted from plasma first, followed by DNA sequencing and bioinformatics analyses for chromosome aneuploidy (T21, T18, and T13), sex chromosome aneuploidy (SCA), and microdeletion/microduplication. Subsequently, the positive results were subject to karyotype analyses. RESULTS: The pregnant women included in this study were divided into six groups, and the results, such as chromosome diagnoses, and clinical phenotypes, were collected for data analyses. According to the results of the data analysis, the positivity rates of foetal chromosomal abnormalities in pregnant women under 20, 20-24, 25-29, 30-34, 35-39, and >40 years old were 0%, 0.17%, 0.25%, 0.27%, 0.60%, and 1.66%, respectively. The positive predictive value (PPV) in the 20-24 years group was 41.67%, that in the 25-29 years group was 62.5%, that in the 30-34 years group was 66.67%, that in the 35-39 years group was 90.74%, and that in the >40 years group was 90.32%. CONCLUSION: Overall, NIPT detection in elderly pregnant women has excellent clinical application value in reducing the incidence of either birth defects or abortion caused by invasive chromosome examination.

It is critical to diagnose foetal chromosome aneuploidy in time through prenatal screening to prevent birth defects. This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in prenatal screening of foetal aneuploidy-associated diseases at different gestational ages. A retrospective analysis based on NIPT screening data at a medical laboratory was performed. The results showed that the total positivity rate and total positive predictive value of trisomy 21, trisomy 18, and trisomy 13 in older pregnant women (≥35 years old) were significantly higher than those in younger pregnant women, and there was an increasing trend with increasing maternal ages. This study indicated that NIPT detection in elderly pregnant women has an excellent application value in clinical practice to reduce the incidence of birth defects and abortion caused by invasive chromosome examination.

[Epidemiological Analysis of Carbapenem-Resistant Enterobacteriaceae Strains in the Clinical Specimens of a Hospital].

Objective: To analyze the detection rate, in vitro susceptibility to antibiotics, and carbapenemase types of carbapenem-resistant Enterobacteriaceae (CRE) strains in the clinical samples of a hospital and to provide support for the prevention, control and treatment of CRE-related infections. Methods: Clinical specimens were examined according to the operating procedures of bacteriological tests. Species identification and in vitro drug susceptibility testing were performed on the isolated strains. Carbapenemase inhibitor enhancement testing, which combined the use of 3-aminobenzeneboronic acid and ethylenediaminetetraacetic acid, was conducted to identify the types of carbapenemase in the CRE strains. Results: In 2021, 2215 CRE strains were isolated from 157196 clinical samples collected in this hospital, presenting a detection rate of 1.4% (2215/157196). A total of 1134 non-repetitive strains of CRE were isolated from 903 patients. The main sources of samples were respiratory tract (494/1134, 43.6%), secretion (191/1134, 16.8%) and blood (173/1134, 15.3%) samples. The cases with the same CRE strain isolated from the samples of two, three and four sites accounted for 12.5%, 4.9%, and 1.1%, respectively. The most common species was Klebsiella pneumoniae (883/1134, 77.9%), followed by Enterobacter cloacae complex (107/1134, 9.4%) and Escherichia coli (96/1134, 8.5%). The rates of resistance to polymyxin B and tigecycline of different species of CRE strains were not significantly different ( P<0.05). Serine carbapenemase-producing strains, metallo-ß-lactamase-producing strains, and those producing both enzymes accounted for 82.6% (809/979), 17.2% (168/979), and 0.2% (2/979), respectively. Conclusion: CRE strains are frequently isolated from samples collected from the respiratory tract, secretion, and blood. The most common strain is serine carbapenemase-producing K. pneumoniae, which has a high resistance rate to various antimicrobial drugs, and risk factors of its associated infections deserve more attention.

[Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology].

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

Kindlin-2 protects pancreatic ß cells through inhibiting NLRP3 inflammasome activation in diabetic mice.

Diabetes mellitus has been a major public health problem worldwide, characterized by insulin resistance and dysfunction of ß-cells. A previous study showed that Kindlin-2 loss in ß-cells dramatically reduces insulin secretion and decreases ß-cell mass, resulting in severe diabetes-like phenotypes. It suggests that Kindlin-2 in ß-cells play an important role in regulating glucose homeostasis. However, the effect of Kindlin-2 on the function of ß-cells under chronic hyperglycemia in diabetes has not been explored. Here we report that Kindlin-2 overexpression ameliorates diabetes and improves insulin secretion in mice induced by streptozocin. In contrast, Kindlin-2 insufficiency exacerbates diabetes and promotes ß-cells dysfunction and inflammation in ß-cells induced by a high-fat diet (HFD). In vitro, Kindlin-2 overexpression prevented high-glucose (HG)-induced dysfunction in ß-cells. Kindlin-2 overexpression also decreased the expression of pro-inflammatory cytokines and NLRP3 inflammasome expression in ß-cells exposed to HG. Furthermore, the loss of Kindlin-2 aggravates the expression of inflammatory cytokines and NLRP3 induced by HG in ß-cells. Collectively, we demonstrate that Kindlin-2 protects against diabetes by inhibiting NLRP3 inflammasome activation.

The prognostic value of end-of-treatment FDG-PET/CT in diffuse large B cell lymphoma: comparison of visual Deauville criteria and a lesion-to-liver SUVmax ratio-based evaluation system.

PURPOSE: The aim of this study was to determine a better criterion for end-of-treatment PET (EoT-PET) assessment and prognostic evaluation of patients with diffuse large B cell lymphoma (DLBCL). METHOD: EoT-PET scans were assessed using the visual Deauville 5-point scale (5PS) and LLR, the maximum standard uptake value ratio between the lesion and the liver. The cutoff value of LLR was obtained by receiver operator characteristic curve analysis. Patient outcomes were compared using Kaplan-Meier survival analysis. Prognostic indexes of different criteria were compared. Multivariate Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Four hundred forty-nine newly diagnosed DLBCL patients who received rituximab-based immunochemotherapy were included, and the median follow-up duration was 41.4 months. Patients with Deauville score (DS) 4 displayed significantly longer PFS and OS compared with patients with DS 5 (both p < 0.001), and they had significantly shorter PFS (p < 0.01) but similar OS (p = 0.057) compared with patients with DS 1-3. The differences in PFS and OS between groups were all significant whether positive EoT-PET was defined as DS 4-5 or DS 5 (all p < 0.001). The optimal cutoff of LLR was 1.83, and both PFS and OS were significantly different between EoT-PET-positive and EoT-PET-negative patients as defined by the cutoff (both p < 0.001). LLR-based criterion displayed higher specificity, positive predictive value, and accuracy than 5PS-based criterion in the prediction of disease progression and death events. In the multivariate analysis, positive EoT-PET (as defined by LLR) was related to unfavorable PFS and OS (both p < 0.001). Additional treatment was not correlated with outcomes of EoT-PET-negative patients either defined by LLR or 5PS or EoT-PET-positive patients classified by 5PS, but it was the only beneficial factor for OS (p < 0.05) in EoT-PET-positive patients with LLR ≥ 1.83. CONCLUSION: The optimal cutoff of LLR may be superior to Deauville criteria in identifying low-risk DLBCL patients with negative EoT-PET after the first-line immunochemotherapy and sparing them the cost and toxicity of additional treatment.

Causal relationship between genetically predicted depression and cancer risk: a two-sample bi-directional mendelian randomization.

BACKGROUND: Depression has been reported to be associated with some types of cancer in observational studies. However, the direction and magnitude of the causal relationships between depression and different types of cancer remain unclear. METHODS: We performed the two-sample bi-directional mendelian randomization with the publicly available GWAS summary statistics to investigate the causal relationship between the genetically predicted depression and the risk of multiple types of cancers, including ovarian cancer, breast cancer, lung cancer, glioma, pancreatic cancer, lymphoma, colorectal cancer, thyroid cancer, bladder cancer, and kidney cancer. The total sample size varies from 504,034 to 729,150. Causal estimate was calculated by inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the causal relationship. RESULTS: After correction for heterogeneity and horizontal pleiotropy, we only detected suggestive evidence for the causality of genetically predicted depression on breast cancer (OR = 1.09, 95% CI: 1.03-1.15, P = 0.0022). The causal effect of depression on breast cancer was consistent in direction and magnitude in the sensitivity analysis. No evidence of causal effects of depression on other types of cancer and reverse causality was detected. CONCLUSIONS: The result of this study suggests a causative effect of genetically predicted depression on specific type of cancer. Our findings emphasize the importance of depression in the prevention and treatment of breast cancer.