Acute carotid stenting versus non-stenting treatment of acute ischemic stroke due to tandem lesions: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of acute carotid stenting (ACS) in comparison to non-stenting interventions for patients experiencing acute ischemic stroke (AIS) caused by tandem lesions (TL). METHODS: A systematic review of literature from PubMed, Embase, and Cochrane databases was conducted to identify relevant studies published up to October 10, 2023. The comparison between ACS and no stenting in patients with TL undergoing endovascular therapy (EVT) focused on outcomes, such as 90-day modified Rankin Scale (mRS) score, successful recanalization, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: The final analysis encompassed a total of 3,187 patients from 21 studies, with 1,786 patients classified as ACS patients and 1,401 as non-stent patients. The overall treatment effect favored the ACS group, as evidenced by their association with improved functional independence at 90 days (mRS 0-2) [relative risk (RR) = 1.18; 95% confidence interval (CI) 1.05-1.34; P < 0.05; I2 = 44%] and a higher rate of successful recanalization [modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b/3] (RR = 1.16; 95% CI 1.09-1.25; P < 0.05; I2 = 40%). The risk of sICH was not significantly different between the two groups (RR = 1.28; 95% CI 0.98-1.68; P > 0.05; I2 = 0%). Additionally, there was no significant difference in 90-day mortality between the two groups (RR = 0.78; 95% CI 0.58-1.07; P > 0.05; I2 = 45%). CONCLUSION: Among TL patients undergoing EVT, ACS may be associated with better functional outcomes at 90 days compared with no stenting.

Gut microbial metabolites SCFAs and chronic kidney disease.

The global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD's development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies.

Endovascular therapy versus medical management for acute ischemic stroke with large infarct core: Systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the efficacy and safety of endovascular therapy (EVT) versus best medical management (BMM) in patients with acute ischemic stroke (AIS) with large infarct core. METHODS: We searched Pubmed, Embase and Cochrane Central Register of Controlled Trials for published randomized clinical trials (RCTs) from inception to February 18, 2023. We defined patients with large core infarcts as having an Alberta Stroke Program early computed tomography score (ASPECTS) of 3-5. The primary outcome was functional independence, defined as a score of 0-2 on the modified Rankin scale (mRS) at 90 days. Secondary outcome was independent ambulation defined as mRS 0-3 at 90 days. Safety outcomes were mortality at 90 days, symptomatic intracranial hemorrhage (sICH) and any intracranial hemorrhage (ICH). RESULTS: The overall treatment effect was more favourable to EVT group. EVT was significantly correlated with improvement of functional independence at 90 days (mRS 0-2) (RR = 2.40; 95 % CI, 1.82-3.16; P < 0.01; I2 = 0 %) and independent ambulation (mRS 0-3) (RR = 1,78; 95 % CI, 1.28-2.48; P < 0.01; I2 = 58 %) at 90 days. 90-day mortality was not significantly different between the two groups(RR = 0.95; 95 % CI, 0.78-1.16; P > 0.05; I2 = 0 %). The risk of sICH and any ICH was higher in EVT group than in BMM group. CONCLUSION: Compared with BMM, EVT may improve functional outcomes in patients with ASPECTS 3-5, despite being associated with an increased risk of sICH and any ICH.

Short-term prognostic models for severe acute kidney injury patients receiving prolonged intermittent renal replacement therapy based on machine learning.

BACKGROUND: As an effective measurement for severe acute kidney injury (AKI), the prolonged intermittent renal replacement therapy (PIRRT) received attention. Also, machine learning has advanced and been applied to medicine. This study aimed to establish short-term prognosis prediction models for severe AKI patients who received PIRRT by machine learning. METHODS: The hospitalized AKI patients who received PIRRT were assigned to this retrospective case-control study. They were grouped based on survival situation and renal recovery status. To screen the correlation, Pearson's correlation coefficient, partial ETA square, and chi-square test were applied, eight machine learning models were used for training. RESULTS: Among 493 subjects, the mortality rate was 51.93% and the kidney recovery rate was 30.43% at 30 days post-discharge, respectively. The indices related to survival were Sodium, Total protein, Lactate dehydrogenase (LDH), Phosphorus, Thrombin time, Liver cirrhosis, chronic kidney disease stage, number of vital organ injuries, and AKI stage, while Sodium, Total protein, LDH, Phosphorus, Thrombin time, Diabetes, peripherally inserted central catheter and AKI stage were selected to predict the 30-day renal recovery. Naive Bayes has a good performance in the prediction model for survival, Random Forest has a good performance in 30-day renal recovery prediction model, while for 90-day renal recovery prediction model, it's K-Nearest Neighbor. CONCLUSIONS: Machine learning can not only screen out indicators influencing prognosis of AKI patients receiving PIRRT, but also establish prediction models to optimize the risk assessment of these people. Moreover, attention should be paid to serum electrolytes to improve prognosis.

Regulation of Ethanol Assimilation for Efficient Accumulation of Squalene in Saccharomyces cerevisiae.

Squalene is a triterpene that can be obtained from fish and plant oils. It is important in cosmetics and vaccines and is a precursor for many high-value terpenes and steroids. In order to increase squalene accumulation, the mevalonate pathway was systematically enhanced. Accumulation of squalene tended to increase when ethanol was added as a carbon source during fermentation, but a high concentration of ethanol affected both the strain growth and accumulation of products. By overexpressing the key trehalose synthesis gene TPS1 and the heat shock protein gene HSP104, the content of trehalose by Saccharomyces cerevisiae (S. cerevisiae) was enhanced, and stress caused by ethanol was relieved. The OD600 value of the modified S. cerevisiae strain was increased by 80.2%, its ethanol tolerance was increased to 30 g/L, and it retained excellent activity with 50 g/L ethanol. After optimizing the fermentation conditions, the squalene titer in a 5 L bioreactor reached 27.3 g/L and the squalene content was 650 mg/g dry cell weight, the highest squalene production parameters reported to date for a microorganism.

Impact of the degree of worsening renal function and B-type natriuretic peptide on the prognosis of patients with acute heart failure.

Background: The impact of the degree of worsening renal function (WRF) and B-type natriuretic peptide (BNP) on the prognosis of patients with acute heart failure (AHF) is still debatable. The present study investigated the influence of different degrees of WRF and BNP levels at discharge on 1-year all-cause mortality in AHF. Methods: Hospitalized AHF patients diagnosed with acute new-onset/worsening of chronic heart failure (HF) between January 2015 and December 2019 were included in this study. Patients were assigned into high and low BNP groups based on the median BNP level at discharge (464 pg/ml). According to serum creatinine (Scr) levels, WRF was divided into non-severe WRF (nsWRF) (Scr increased ≥0.3 mg/dl and <0.5 mg/dl) and severe WRF (sWRF) (Scr increased ≥0.5 mg/dl); non-WRF (nWRF) was defined as Scr increased of <0.3 mg/dl). Multivariable cox regression was used to evaluate the association of low BNP value and different degrees of WRF with a all-cause death, as well as testing for an interaction between the two. Results: Among 440 patients in the high BNP group, there was a significant difference in WRF on mortality (nWRF vs. nsWRF vs. sWRF: 22% vs. 23.8% vs. 58.8%, P < 0.001). Yet, mortality did not significantly differ across the WRF subgroups in the low BNP group (nWRF vs. nsWRF vs. sWRF: 9.1% vs. 6.1% vs. 15.2%, P = 0.489). In multivariate Cox regression analysis, low BNP group at discharge (HR, 0.265; 95%CI, 0.162-0.434; P < 0.001) and sWRF (HR, 2.838; 95%CI, 1.756-4.589; P < 0.001) were independent predictors of 1-year mortality in AHF.There was a significant interaction between low BNP group and sWRF(HR, 0.225; 95%CI, 0.055-0.918; P < 0.05). Conclusions: nsWRF does not increase the 1-year mortality in AHF patients, whereas sWRF does. A low BNP value at discharge is associated with better long-term outcomes and mitigates the adverse effects of sWRF on prognosis.

Reengineering of 7-dehydrocholesterol biosynthesis in Saccharomyces cerevisiae using combined pathway and organelle strategies.

7-Dehydrocholesterol (7-DHC) is a widely used sterol and a precursor of several costly steroidal drugs. In this study, 7-DHC biosynthesis pathway was constructed and modified in Saccharomyces cerevisiae. Firstly, the biosynthesis pathway was constructed by knocking out the competitive pathway genes ERG5 and ERG6 and integrating two DHCR24 copies from Gallus gallus at both sites. Then, 7-DHC titer was improved by knocking out MOT3, which encoded a transcriptional repressor for the 7-DHC biosynthesis pathway. Next, by knocking out NEM1 and PAH1, 7-DHC accumulation was improved, and genes upregulation was verified by quantitative PCR (qPCR). Additionally, tHMG1, IDI1, ERG2, ERG3, DHCR24, POS5, and CTT1 integration into multi-copy sites was used to convert precursors to 7-DHC, and increase metabolic flux. Finally, qPCR confirmed the significant up-regulation of key genes transcriptional levels. In a 96 h shaker flask fermentation, the 7-DHC titer was 649.5 mg/L by de novo synthesis. In a 5 L bioreactor, the 7-DHC titer was 2.0 g/L, which was the highest 7-DHC titer reported to date. Our study is of great significance for the industrial production of 7-DHC and steroid development for medical settings.

Heart Rate Measurement Based on 3D Central Difference Convolution with Attention Mechanism.

Remote photoplethysmography (rPPG) is a video-based non-contact heart rate measurement technology. It is a fact that most existing rPPG methods fail to deal with the spatiotemporal features of the video, which is significant for the extraction of the rPPG signal. In this paper, we propose a 3D central difference convolutional network (CDCA-rPPGNet) to measure heart rate, with an attention mechanism to combine spatial and temporal features. First, we crop and stitch the region of interest together through facial landmarks. Next, the high-quality regions of interest are fed to CDCA-rPPGNet based on a central difference convolution, which can enhance the spatiotemporal representation and capture rich relevant time contexts by collecting time difference information. In addition, we integrate the attention module into the neural network, aiming to strengthen the ability of the neural network to extract video channels and spatial features, so as to obtain more accurate rPPG signals. In summary, the three main contributions of this paper are as follows: (1) the proposed network base on central difference convolution could better capture the subtle color changes to recover the rPPG signals; (2) the proposed ROI extraction method provides high-quality input to the network; (3) the attention module is used to strengthen the ability of the network to extract features. Extensive experiments are conducted on two public datasets-the PURE dataset and the UBFC-rPPG dataset. In terms of the experiment results, our proposed method achieves 0.46 MAE (bpm), 0.90 RMSE (bpm) and 0.99 R value of Pearson's correlation coefficient on the PURE dataset, and 0.60 MAE (bpm), 1.38 RMSE (bpm) and 0.99 R value of Pearson's correlation coefficient on the UBFC dataset, which proves the effectiveness of our proposed approach.

Bone marrow mesenchymal stem cell exosomes suppress phosphate-induced aortic calcification via SIRT6-HMGB1 deacetylation.

BACKGROUND: Vascular calcification associated with chronic kidney disease (CKD) can increase the risk of mortality. Elevated serum levels of high mobility group box 1 (HMGB1) promotes vascular calcification in CKD via the Wnt/ß-catenin pathway. Sirtuin 6 (SIRT6) prevents fibrosis in CKD by blocking the expression of ß-catenin target genes through deacetylation. This study aimed to investigate whether the inhibition of vascular calcification by bone marrow mesenchymal stem cell (BMSC)-derived exosomes is related to SIRT6 activity and assess the regulatory relationship between HMGB1 and SIRT6. METHODS: CKD characteristics, osteogenic markers, calcium deposition, and the differential expression of HMGB1 and SIRT6 have been measured in a 5/6 nephrectomized mouse CKD model fed a high-phosphate diet to induce aortic calcification. In vitro assays were also performed to validate the in vivo findings. RESULTS: High phosphate promotes the translocation of HMGB1 from the nucleus to the cytosol and induces the expression of Runx2, osteopontin, and Msx2. However, BMSC-derived exosomes were found to alleviate CKD-related fibrosis and the induction of osteogenic genes although less significantly when SIRT6 expression is suppressed. SIRT6 was found to modulate the cytosol translocation of HMGB1 by deacetylation in vascular smooth muscle cells. CONCLUSION: Our results indicate that BMSC-derived exosomes inhibit high phosphate-induced aortic calcification and ameliorate renal function via the SIRT6-HMGB1 deacetylation pathway.

Short-term prognosis and influencing factors of patients with acute kidney injury treated with prolonged intermittent renal replacement therapy.

BACKGROUND: Studies assessing prognosis after prolonged intermittent renal replacement therapy (PIRRT) for acute kidney injury (AKI) are scarce. AIM: To assess the impact of PIRRT on AKI and factors associated with short-term prognosis. METHODS: In this retrospective nested case-control study, AKI patients administered PIRRT in Shanghai General Hospital from 01/2012 to 10/2018 were assigned to the 30-day survivor and death groups. Surviving patients were further divided into the kidney recovery and non-recovery groups at 30 and 90 days post-discharge, respectively. Propensity score matching was performed. RESULTS: Totally 576 patients were included in the non-matched study population, mortality and kidney recovery rates were 51.7% and 33.4%, respectively. After propensity score matching, there were 250 patients in each of the death and survival groups. Low PIRRT frequency (OR = 2.165, 95% CI = 1.178-3.978), infection (OR = 0.447, 95% CI = 0.251-0.795), number of damaged vital organs (OR = 0.478, 95% CI = 0.346-0.661), sodium (OR = 0.958, 95% CI = 0.928-0.988), total protein (OR = 1.047, 95% CI = 1.022-1.072), pre-dialysis thrombin time (TT; OR = 0.959, 95% CI = 0.936-0.983), pre-discharge glomerular filtration rate (GFR; OR = 1.024, 95% CI = 1.017-1.031) and admission ward [reference: renal ward; intensive care unit (OR = 0.042, 95% CI = 0.008-0.211); surgery (OR = 0.092, 95% CI = 0.018-0.465); medical (OR = 0.049, 95% C% CI = 0.009-0.259); other (OR = 0.097, 95% CI = 0.016-0.572)] independently predicted 30-day mortality. Peripherally inserted central catheter (OR = 13.970, 95% CI = 1.439-135.589), urea nitrogen (OR = 0.961, 95% CI = 0.933-0.990) and pre-discharge GFR (OR = 1.102, 95% CI = 1.067-1.137) independently predicted 30-day kidney recovery. Pre-dialysis Scr (OR = 0.997, 95% CI = 0.995-0.999), urea nitrogen (OR = 0.948, 95% CI = 0.912-0.986) and pre-discharge GFR (OR = 1.137 95% CI = 1.088-1.189) independently predicted 90-day kidney recovery. CONCLUSIONS: PIRRT improves survival and kidney function recovery in AKI patients. In patients with previous GFR ≥ 30 mL/(min-1.73 m2 ) and no prior maintenance dialysis, PIRRT at 3-5 sessions/week might be appropriate.

Dietary Plant Lectins Appear to Be Transported from the Gut to Gain Access to and Alter Dopaminergic Neurons of Caenorhabditis elegans, a Potential Etiology of Parkinson's Disease.

Lectins from dietary plants have been shown to enhance drug absorption in the gastrointestinal tract of rats, be transported trans-synaptically as shown by tracing of axonal and dendritic paths, and enhance gene delivery. Other carbohydrate-binding protein toxins are known to traverse the gut intact in dogs. Post-feeding rhodamine- or TRITC-tagged dietary lectins, the lectins were tracked from gut to dopaminergic neurons (DAergic-N) in transgenic Caenorhabditis elegans (C. elegans) [egIs1(Pdat-1:GFP)] where the mutant has the green fluorescent protein (GFP) gene fused to a dopamine transport protein gene labeling DAergic-N. The lectins were supplemented along with the food organism Escherichia coli (OP50). Among nine tested rhodamine/TRITC-tagged lectins, four, including Phaseolus vulgaris erythroagglutinin (PHA-E), Bandeiraea simplicifolia (BS-I), Dolichos biflorus agglutinin (DBA), and Arachis hypogaea agglutinin (PNA), appeared to be transported from gut to the GFP-DAergic-N. Griffonia Simplicifolia and PHA-E, reduced the number of GFP-DAergic-N, suggesting a toxic activity. PHA-E, BS-I, Pisum sativum (PSA), and Triticum vulgaris agglutinin (Succinylated) reduced fluorescent intensity of GFP-DAergic-N. PHA-E, PSA, Concanavalin A, and Triticum vulgaris agglutinin decreased the size of GFP-DAergic-N, while BS-I increased neuron size. These observations suggest that dietary plant lectins are transported to and affect DAergic-N in C. elegans, which support Braak and Hawkes' hypothesis, suggesting one alternate potential dietary etiology of Parkinson's disease (PD). A recent Danish study showed that vagotomy resulted in 40% lower incidence of PD over 20 years. Differences in inherited sugar structures of gut and neuronal cell surfaces may make some individuals more susceptible in this conceptual disease etiology model.

Prowashonupana barley dietary fibre reduces body fat and increases insulin sensitivity in Caenorhabditis elegans model.

Prowashonupana barley (PWB) is high in ß-glucan with moderate content of resistant starch. PWB reduced intestinal fat deposition (IFD) in wild type Caenorhabditis elegans (C. elegans, N2), and in sir-2.1 or daf-16 null mutants, and sustained a surrogate marker of lifespan, pharyngeal pumping rate (PPR), in N2, sir-2.1, daf-16, or daf-16/daf-2 mutants. Hyperglycaemia (2% glucose) reversed or reduced the PWB effect on IFD in N2 or daf-16/daf-2 mutants with a sustained PPR. mRNA expression of cpt-1, cpt-2, ckr-1, and gcy-8 were dose-dependently reduced in N2 or daf-16 mutants, elevated in daf-16/daf-2 mutants with reduction in cpt-1, and unchanged in sir-2.1 mutants. mRNA expressions were increased by hyperglycaemia in N2 or daf-16/daf-2 mutants, while reduced in sir-2.1 or daf-16 mutants. The effects of PWB in the C. elegans model appeared to be primarily mediated via sir-2.1, daf-16, and daf-16/daf-2. These data suggest that PWB and ß-glucans may benefit hyperglycaemia-impaired lipid metabolism.

Distinct mutations in MLH1 and MSH2 genes in hereditary non-polyposis colorectal cancer (HNPCC) families from China.

Hereditary non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inheritance syndrome. HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions. Our study aimed to identify the patterns of hMSH2 and hMLH1 mutations in Chinese HNPCC patients. Ninety-eight unrelated families from China meeting Amsterdam or Bethesda criteria were included in our study. Germline mutations in MLH1 and MSH2 genes, located in the exons and the splice-site junctions, were screened in the 98 probands by direct sequencing. Eleven mutations were found in ten patients (11%), with six in MLH1 (54.5%) and five in MSH2 (45.5%) genes. One patient had mutations in both MLH1 and MSH2 genes. Three novel mutations in MLH1 gene (c.157_160delGAGG, c.2157dupT and c.-64G>T) were found for the first time, and one suspected hotspot in MSH2 (c.1168C>T) was revealed.

Racial differences in MLH1 and MSH2 mutation: an analysis of yellow race and white race based on the InSiGHT database.

MLH1 and MSH2 mutations underlie 90% of hereditary nonpolyposis colorectal cancer (HNPCC) mutations. The International Society of Gastrointestinal Hereditary Tumors (InSiGHT) has established an international database of mutations associated with HNPCC. Based on the InSiGHT database and the original references that reported the mutations, we analyzed the distributions of MLH1 and MSH2 mutations in yellow race and white race respectively and compared them subsequently. We found: (1) the distributions of mutation individuals in exon 1, 17 and 19 of MLH1 gene and in exon 2 of MSH2 gene showed significant differences between the two race groups (p < 0.05); (2) the distributions of mutation types in exon 2, 7 and 18 of MLH1 and exon 10 and 16 of MSH2 showed significant differences (p < 0.05); and (3) three mutations (c.649C > T, c.1625A > T and c.1721T > C) in MLH1 and five mutations (c.23C > T, c.187dupG, c.505A > G, c.1168C > T and c.2211-6T > C) in MSH2 have much higher frequency in yellow race than those in white race. Furthermore, three mutations (c.1453G > C, c.1742C > T and c.1758dupC) in MLH1 and two mutations (c.1255C > A and c.1886A > G) in MSH2 were only found in yellow race, which implies that specific mutations in yellow race need more attention when screening mutations in these two genes.