Peripheral blood eosinophils: an important reference for radiologists to distinguish between pulmonary paragonimiasis and tuberculous pleurisy in children.

OBJECTIVE: In this study, we examined the value of chest CT signs combined with peripheral blood eosinophil percentage in differentiating between pulmonary paragonimiasis and tuberculous pleurisy in children. METHODS: Patients with pulmonary paragonimiasis and tuberculous pleurisy were retrospectively enrolled from January 2019 to April 2023 at the Kunming Third People's Hospital and Lincang People's Hospital. There were 69 patients with pulmonary paragonimiasis (paragonimiasis group) and 89 patients with tuberculous pleurisy (tuberculosis group). Clinical symptoms, chest CT imaging findings, and laboratory test results were analyzed. Using binary logistic regression, an imaging model of CT signs and a combined model of CT signs and eosinophils were developed to calculate and compare the differential diagnostic performance of the two models. RESULTS: CT signs were used to establish the imaging model, and the receiver operating characteristic (ROC) curve was plotted. The area under the curve (AUC) was 0.856 (95% CI: 0.799-0.913), the sensitivity was 66.7%, and the specificity was 88.9%. The combined model was established using the CT signs and eosinophil percentage, and the ROC was plotted. The AUC curve was 0.950 (95% CI: 0.919-0.980), the sensitivity was 89.9%, and the specificity was 90.1%. The differential diagnostic efficiency of the combined model was higher than that of the imaging model, and the difference in AUC was statistically significant. CONCLUSION: The combined model has a higher differential diagnosis efficiency than the imaging model in the differentiation of pulmonary paragonimiasis and tuberculous pleurisy in children. The presence of a tunnel sign on chest CT, the absence of pulmonary nodules, and an elevated percentage of peripheral blood eosinophils are indicative of pulmonary paragonimiasis in children.

Clinical application of dual-layer spectral CT multi-parameter feature to predict microvascular invasion in hepatocellular carcinoma.

OBJECTIVE: This study aimed to investigate the feasibility of using dual-layer spectral CT multi-parameter feature to predict microvascular invasion of hepatocellular carcinoma. METHODS: This retrospective study enrolled 50 HCC patients who underwent multiphase contrast-enhanced spectral CT studies preoperatively. Combined clinical data, radiological features with spectral CT quantitative parameter were constructed to predict MVI. ROC was applied to identify potential predictors of MVI. The CT values obtained by simulating the conventional CT scans with 70 keV images were compared with those obtained with 40 keV images. RESULTS: 50 hepatocellular carcinomas were detected with 30 lesions (Group A) with microvascular invasion and 20 (Group B) without. There were significant differences in AFP,tumer size, IC, NIC,slope and effective atomic number in AP and ICrr in VP between Group A ((1000(10.875,1000),4.360±0.3105, 1.7750 (1.5350,1.8825) mg/ml, 0.1785 (0.1621,0.2124), 2.0362±0.2108,8.0960±0.1043,0.2830±0.0777) and Group B (4.750(3.325,20.425),3.190±0.2979,1.4700 (1.4500,1.5775) mg/ml, 0.1441 (0.1373,0.1490),1.8601±0.1595, 7.8105±0.7830 and 0.2228±0.0612) (all p < 0.05). Using 0.1586 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.875 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.625 with CT value at 70 keV and improved to 0.843 at 40 keV. CONCLUSION: Dual-layer spectral CT provides additional quantitative parameters than conventional CT to enhance the differentiation between hepatocellular carcinoma with and without microvascular invasion. Especially, the normalized iodine concentration (NIC) in arterial phase has the greatest potential application value in determining whether microvascular invasion exists, and can offer an important reference for clinical treatment plan and prognosis assessment.

Genome-wide association analysis and transgenic characterization for amylose content regulating gene in tuber of Dioscorea zingiberensis.

BACKGROUND: Amylose, a prebiotic found in yams is known to be beneficial for the gut microflora and is particularly advantageous for diabetic patients' diet. However, the genetic machinery underlying amylose production remains elusive. A comprehensive characterization of the genetic basis of amylose content in yam tubers is a prerequisite for accelerating the genetic engineering of yams with respect to amylose content variation. RESULTS: To uncover the genetic variants underlying variation in amylose content, we evaluated amylose content in freshly harvested tubers from 150 accessions of Dioscorea zingibensis. With 30,000 high-quality single nucleotide polymorphisms (SNP), we performed a genome-wide association analysis (GWAS). The population structure analysis classified the D. zingiberensis accessions into three groups. A total of 115 significant loci were detected on four chromosomes. Of these, 112 significant SNPs (log10(p) = 5, q-value < 0.004) were clustered in a narrow window on the chromosome 6 (chr6). The peak SNP at the position 75,609,202 on chr6 could explain 63.15% of amylose variation in the population and fell into the first exon of the ADP-glucose pyrophosphorylase (AGPase) small subunit gene, causing a non-synonymous modification of the resulting protein sequence. Allele segregation analysis showed that accessions with the rare G allele had a higher amylose content than those harboring the common A allele. However, AGPase, a key enzyme precursor of amylose biosynthesis, was not expressed differentially between accessions with A and G alleles. Overexpression of the two variants of AGPase in Arabidopsis thaliana resulted in a significantly higher amylose content in lines transformed with the AGPase-G allele. CONCLUSIONS: Overall, this study showed that a major genetic variant in AGPase probably enhances the enzyme activity leading to high amylose content in D. zingiberensis tuber. The results provide valuable insights for the development of amylose-enriched genotypes.

Association between elevated preoperative red cell distribution width and mortality after brain tumor craniotomy.

BACKGROUND: Red cell distribution width (RDW) has been recognized as a potential inflammatory biomarker, with elevated levels associated with adverse outcomes in various diseases. However, its role in predicting outcomes after brain tumor craniotomy remains unclear. We aimed to assess whether preoperative RDW influences mortality and postoperative complications in patients undergoing brain tumor craniotomy. METHODS: This retrospective cohort study analyzed serum RDW levels in patients undergoing brain tumor craniotomy at West China Hospital. RDW was evaluated in two forms: RDW-CV and RDW-SD, and was categorized into four quartiles for analysis by using logistic regression and multivariate analysis to adjust for confounding. RESULTS: The study encompassed 10,978 patients undergoing brain tumor craniotomy. our analysis revealed no significant difference in 30-day mortality across various RDW-CV levels. However, we observed a dose-response relationship with preoperative RDW-CV levels in assessing long-term mortality risks. Specifically, patients with RDW-CV levels of 12.6-13.2% (HR 1.04, 95% CI 1.01-1.18), 13.2-13.9% (HR 1.12, 95% CI 1.04-1.26), and > 13.9% (HR 1.34, 95% CI 1.18-1.51) exhibited a significantly higher hazard of long-term mortality compared to those with RDW-CV < 12.6%. When preoperative RDW-CV was analyzed as a continuous variable, for each 10% increase in RDW-CV, the adjusted OR of long-term mortality was 1.09 (95% CI 1.05-1.13). we also observed significant associations between preoperative higher RDW-CV levels and certain postoperative complications including acute kidney injury (OR 1.46, 95% CI: 1.10-1.94), pneumonia infection (OR 1.19 95% CI: 1.05-1.36), myocardial infarction (OR 1.32, 95% CI: 1.05-1.66), readmission (OR 1.15, 95% CI: 1.01-1.30), and a prolonged length of hospital stay (OR 1.11, 95% CI: 1.02-1.21). For RDW-SD levels, there was no significant correlation for short-term mortality, long-term mortality, and postoperative complications. CONCLUSIONS: Our study showed elevated preoperative RDW-CV is significantly associated with increased long-term mortality and multiple postoperative complications, but no such association is observed with RDW-SD. These findings show the prognostic importance of RDW-CV, reinforcing its potential as a valuable tool for risk stratification in the preoperative evaluation of brain tumor craniotomy patients.

Effect of Lycium barbarum polysaccharide on osteoblast proliferation and differentiation in postmenopausal osteoporosis.

OBJECTIVE: We aimed to investigate the effect of Lycium barbarum polysaccharide (LBP) on the proliferation and differentiation of osteoblasts in postmenopausal individuals with osteoporosis using in vitro cell experiments. METHODS: We assessed the effect of long-term LBP consumption on the intestinal metabolites of individuals using a simulation of the human intestinal microbiota ecosystem. We also tested the capacity of LBP in proliferating MC3T3-E1 cells using the cell counting kit-8 (CCK-8) method and analyzed the effect of intestinal metabolites on the osteogenic differentiation of MC3T3-E1 cells by testing bone metabolism viability with relevant indicators. RESULTS: The level of short-chain fatty acids (SCFAs) significantly increased (p < 0.05), and the concentrations of acetic acid, propionic acid, and butyric acid all showed an upward trend after the treatment using LBP. At appropriate concentrations, the fermentation supernatant can enhance osteoblast proliferation by significantly increasing the active expression of bone-alkaline phosphatase (B-ALP) and osteocalcin (OCN) in osteoblasts (p < 0.05). CONCLUSION: By modulating the metabolites of intestinal microbiota, production of SCFAs, the prebiotic properties of LBP can enhance osteoblast differentiation through in vitro simulation experiment and cell-based assay.

Association of persistent postoperative hyperglycemia with mortality after elective craniotomy.

OBJECTIVE: The influence of persistent postoperative hyperglycemia after craniotomy has not yet been explored. This study aimed to investigate the hypothesis that persistent postoperative hyperglycemia is associated with mortality in patients undergoing an elective craniotomy. METHODS: This study included adult patients (age ≥ 18 years) undergoing an elective craniotomy between January 2011 and March 2021 at the West China Hospital, Sichuan University. Peak daily blood glucose values measured within the first 7 days after craniotomy were collected. Persistent hyperglycemia was defined by two or more consecutive serum glucose levels of mild, moderate, or severe hyperglycemia. Normoglycemia, mild hyperglycemia, moderate hyperglycemia, and severe hyperglycemia were defined as glucose values of ≤ 6.1 mmol/L, > 6.1 and ≤ 7.8 mmol/L, > 7.8 and ≤ 10.0 mmol/L, and > 10.0 mmol/L, respectively. RESULTS: This study included 14,907 patients undergoing an elective craniotomy. In the multivariable analysis, both moderate (adjusted OR 3.76, 95% CI 2.68-5.27) and severe (adjusted OR 3.82, 95% CI 2.54-5.76) persistent hyperglycemia in patients were associated with higher 30-day mortality compared with normoglycemia. However, this association was not observed in patients with mild hyperglycemia (adjusted OR 1.32, 95% CI 0.93-1.88). Interestingly, this association was observed regardless of whether patients had preoperative hyperglycemia. There was no interaction between moderate or severe hyperglycemia and preexisting diabetes (p for interaction = 0.65). When postoperative peak blood glucose values within the first 7 days after craniotomy were evaluated as a continuous variable, for each 1-mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.17 (95% CI 1.14-1.21). Postoperative blood glucose (area under the curve [AUC] = 0.78) was superior to preoperative blood glucose (AUC = 0.65; p < 0.001) for predicting mortality. Moderate and severe persistent hyperglycemia in patients were associated with an increased risk of deep venous thrombosis (adjusted OR 3.20, 95% CI 2.31-4.42), pneumonia (adjusted OR 2.77, 95% CI 2.40-3.21), myocardial infarction (adjusted OR 4.38, 95% CI 3.41-5.61), and prolonged hospital stays (adjusted OR 1.43, 95% CI 1.29-1.59). CONCLUSIONS: In patients undergoing an elective craniotomy, moderate and severe persistent postoperative hyperglycemia were associated with an increased risk of mortality compared with normoglycemia, regardless of preoperative hyperglycemia.

Enhanced interactions among gut mycobiomes with the deterioration of glycemic control.

BACKGROUND: The gut mycobiome is closely linked to health and disease; however, its role in the progression of type 2 diabetes mellitus (T2DM) remains obscure. Here, a multi-omics approach was employed to explore the role of intestinal fungi in the deterioration of glycemic control. METHODS: 350 participants without hypoglycemic therapies were invited for a standard oral glucose tolerance test to determine their status of glycemic control. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping array, and plasma metabolites were measured with untargeted liquid chromatography mass spectrometry. FINDINGS: The richness of fungi was higher, whereas its dissimilarity was markedly lower, in participants with T2DM. Moreover, the diversity and composition of fungi were closely associated with insulin sensitivity and pancreatic ß-cell functions. With the exacerbation of glycemic control, the co-occurrence network among fungus taxa became increasingly complex, and the complexity of the interaction network was inversely associated with insulin sensitivity. Mendelian randomization analysis further demonstrated that the Archaeorhizomycetes class, Fusarium genus, and Neoascochyta genus were causally linked to impaired glucose metabolism. Furthermore, integrative analysis with metabolomics showed that increased 4-hydroxy-2-oxoglutaric acid, ketoleucine, lysophosphatidylcholine (20:3/0:0), and N-lactoyl-phenylalanine, but decreased lysophosphatidylcholine (O-18:2), functioned as key molecules linking the adverse effect of Fusarium genus on insulin sensitivity. CONCLUSIONS: Our study uncovers a strong association between disturbance in gut fungi and the progression of T2DM and highlights the potential of targeting the gut mycobiome for the management of T2DM. FUNDINGS: This study was supported by MOST and NSFC of China.

Characterization of the complete mitochondrial genome of Ergasilus anchoratus Markevich, 1946 (Ergasilidae) and phylogeny of Copepoda.

The mitochondrial (mt) genome can provide data for phylogenetic analyses and evolutionary biology. Herein, we sequenced and annotated the complete mt genome of Ergasilus anchoratus. This mt genome was 13852 bp long and comprised 13 protein-coding genes (PCGs), 22 tRNAs and 2 rRNAs. All PCGs used the standard ATN start codons and complete TAA/TAG termination codons. A majority of tRNA genes exhibited standard cloverleaf secondary structures, with the exception of one tRNA that lacked the TψC arm (trnC), and three tRNAs that lacked the DHU arm (trnR, trnS1 and trnS2). Phylogenetic analyses conducted using Bayesian inference (BI) and maximum likelihood (ML) methods both supported Ergasilidae as a monophyletic family forming a sister group to Lernaea cyprinacea and Paracyclopina nana. It also supported the monophyly of orders Calanoida, Cyclopoida, and Siphonostomatoida; and the monophyly of families Harpacticidae, Ergasilidae, Diaptomidae, and Calanidae. The gene orders of E. anchoratus and Sinergasilus undulatus were identical, which represents the first instance of two identical gene orders in copepods. More mt genomes are needed to better understand the phylogenetic relationships within Copepoda in the future.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Multicomponent Reductive Coupling for Selective Access to Functional γ-Lactams by a Single-Atom Cobalt Catalyst.

Despite their significant importance to numerous fields, the difficulties in direct and diverse synthesis of α-hydroxy-γ-lactams pose substantial obstacles to their practical applications. Here, we designed a nitrogen and TiO2 co-doped graphitic carbon-supported material with atomically dispersed cobalt sites (CoSA-N/NC-TiO2), which was successfully applied as a multifunctional catalyst to establish a general method for direct construction of α-hydroxy-γ-lactams from cheap and abundant nitro(hetero)arenes, aldehydes, and H2O with alkynoates. The striking features of operational simplicity, broad substrate and functionality compatibility (>100 examples), high step and atom efficiency, good selectivity, and exceptional catalyst reusability highlight the practicality of this new catalytic transformation. Mechanistic studies reveal that the active CoN4 species and the dopants exhibit a synergistic effect on the formation of key acid-masked nitrones; their subsequent nucleophilic addition to the alkynoates followed by successive reduction, alkenyl hydration, and intramolecular ester ammonolysis delivers the desired products. In this work, the concept of reduction interruption leading to new reaction route will open a door to further develop useful transformations by rational catalyst design.

Molecular phylogeny of the family Rhabdiasidae (Nematoda: Rhabditida), with morphology, genetic characterization and mitochondrial genomes of Rhabdias kafunata and R. bufonis.

BACKGROUND: The family Rhabdiasidae (Nematoda: Rhabditida) is a globally distributed group of nematode parasites, with over 110 species parasitic mainly in amphibians and reptiles. However, the systematic position of the family Rhabdiasidae in the order Rhabditida remains unsolved, and the evolutionary relationships among its genera are still unclear. Moreover, the present knowledge of the mitochondrial genomes of rhabdiasids remains limited. METHODS: Two rhabdiasid species: Rhabdias kafunata Sata, Takeuchi & Nakano, 2020 and R. bufonis (Schrank, 1788) collected from the Asiatic toad Bufo gargarizans Cantor (Amphibia: Anura) in China, were identified based on morphology (light and scanning electron microscopy) and molecular characterization (sequencing of the nuclear 28S and ITS regions and mitochondrial cox1 and 12S genes). The complete mitochondrial genomes of R. kafunata and R. bufonis were also sequenced and annotated for the first time. Moreover, phylogenetic analyses based on the amino acid sequences of 12 protein-coding genes (PCGs) of the mitochondrial genomes were performed to clarify the systematic position of the family Rhabdiasidae in the order Rhabditida using maximum likelihood (ML) and Bayesian inference (BI). The phylogenetic analyses based on the 28S + ITS sequences, were also inferred to assess the evolutionary relationships among the genera within Rhabdiasidae. RESULTS: The detailed morphology of the cephalic structures, vulva and eggs in R. kafunata and R. bufonis was revealed using scanning electron microscopy (SEM) for the first time. The characterization of 28S and ITS regions of R. kafunata was reported for the first time. The mitogenomes of R. kafunata and R. bufonis are 15,437 bp and 15,128 bp long, respectively, and both contain 36 genes, including 12 PCGs (missing atp8). Comparative mitogenomics revealed that the gene arrangement of R. kafunata and R. bufonis is different from all of the currently available mitogenomes of nematodes. Phylogenetic analyses based on the ITS + 28S data showed Neoentomelas and Kurilonema as sister lineages, and supported the monophyly of Entomelas, Pneumonema, Serpentirhabdias and Rhabdias. Mitochondrial phylogenomic results supported Rhabdiasidae as a member of the superfamily Rhabditoidea in the suborder Rhabditina, and its occurrance as sister to the family Rhabditidae. CONCLUSIONS: The complete mitochondrial genome of R. kafunata and R. bufonis were reported for the first time, and two new gene arrangements of mitogenomes in Nematoda were revealed. Mitogenomic phylogenetic results indicated that the family Rhabdiasidae is a member of Rhabditoidea in Rhabditina, and is closely related to Rhabditidae. Molecular phylogenies based on the ITS + 28S sequence data supported the validity of Kurilonema, and showed that Kurilonema is sister to Neoentomelas. The present phylogenetic results also indicated that the ancestors of rhabdiasids seem to have initially infected reptiles, then spreading to amphibians.

Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia.

Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.

Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis.

Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodontal pathogen Porphyromonas gingivalis (Pg) aggravates intestinal inflammation and Th17/Treg cell imbalance in a gut microbiota-dependent manner. Specifically, metagenomic and metabolomic analyses shows that oral administration of Pg increases levels of the Bacteroides phylum but decreases levels of the Firmicutes, Verrucomicrobia, and Actinobacteria phyla. Nevertheless, it suppresses the linoleic acid (LA) pathway in the gut microbiota, which was the target metabolite that determines the degree of inflammation and functions as an aryl hydrocarbon receptor (AHR) ligand to suppress Th17 differentiation while promoting Treg cell differentiation via the phosphorylation of Stat1 at Ser727. Therapeutically restoring LA levels in colitis mice challenged with Pg exerts anti-colitis effects by decreasing the Th17/Treg cell ratio in an AHR-dependent manner. Our study suggests that Pg aggravates colitis via a gut microbiota-LA metabolism-Th17/Treg cell balance axis, providing a potential therapeutically modifiable target for IBD patients with periodontitis.

Reduction-Specified Coupling Reactions of Nitroarenes by Heterogeneous Cobalt Catalysis.

The in-depth study on reduction-specified coupling reactions of the nitroarenes by heterogeneous cobalt catalysis opens a door for diversified syntheses of functional N-containing molecules. Guided by the structure-function relationship of heterogeneous materials, rational design of nano-catalysts can effectively regulate the routes of organic reactions. Precise transformation of the intermediates generated during the nitroarene reduction with a suitable nano-catalyst is a promising way to develop new tandem reactions, and to synthesize structurally novel compounds that are of difficult access with the conventional approaches.

Therapeutic challenges in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Compared to our knowledge of B-cell tumors, our understanding of T-cell leukemia and lymphoma remains less advanced, and a significant number of patients are diagnosed with advanced stages of the disease. Unfortunately, the development of drug resistance in tumors leads to relapsed or refractory peripheral T-Cell Lymphomas (r/r PTCL), resulting in highly unsatisfactory treatment outcomes for these patients. This review provides an overview of potential mechanisms contributing to PTCL treatment resistance, encompassing aspects such as tumor heterogeneity, tumor microenvironment, and abnormal signaling pathways in PTCL development. The existing drugs aimed at overcoming PTCL resistance and their potential resistance mechanisms are also discussed. Furthermore, a summary of ongoing clinical trials related to PTCL is presented, with the aim of aiding clinicians in making informed treatment decisions.

Efficacy and Safety of Once-Weekly Insulin Regimes on Glycemic Control for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

BACKGROUND: Randomized controlled trials have found that once-weekly insulin resulted in greater glycemic control compared to once-daily insulin in patients with type 2 diabetes. However, no direct comparisons have been made between different types of once-weekly insulin thus far. This systematic review and network meta-analysis aimed to evaluate the effect of the two most advanced once-weekly insulin analogues, namely insulin icodec and insulin Fc, in patients with type 2 diabetes. METHODS: We conducted a thorough search in the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published from the beginning to October 10, 2023, with no language limitations. Our aim was to conduct a systematic review of randomized controlled trials that investigated the effectiveness and safety of once-weekly insulin in individuals with type 2 diabetes. Our primary outcome was to evaluate excellent glycemic control, defined as patients achieving glycated hemoglobin levels below 7%. RESULTS: We identified a total of 7 trials involving 2829 patients. The results showed that once-weekly insulin icodec is more effective than once-weekly insulin Fc (RR 1.59 [95% CI 1.08-2.38]), once-daily degludec (RR 1.43 [95% CI 1.14-1.83]), and once-daily glargine (RR 1.15 [95% CI 1.00-1.41]). Moreover, the incidence of severe hypoglycemia was lower with once-weekly insulin icodec compared to once-daily degludec (RR 0.00016 [95% CI 0 to 0.41]). However, no significant difference in the incidence of severe hypoglycemia was observed between once-weekly insulin icodec and once-daily glargine (RR 0.39 [95% CI 0.03 to 4.83]). CONCLUSIONS: In patients with type 2 diabetes, once-weekly insulin icodec achieved superior glycemic control compared to once-weekly insulin Fc, with no significant difference in the occurrence of hypoglycemia. The ranking probability results have shown that one weekly icodec seems to be the preferred option in patients with type 2 diabetes. TRIAL REGISTRATION: PROSPERO Identifier: CRD42023470894.

GCY-20 signaling controls suppression of Caenorhabditis elegans egg laying by moderate cold.

Organisms sensing environmental cues and internal states and integrating the sensory information to control fecundity are essential for survival and proliferation. The present study finds that a moderate cold temperature of 11°C reduces egg laying in Caenorhabditis elegans. ASEL and AWC neurons sense the cold via GCY-20 signaling and act antagonistically on egg laying through the ASEL and AWC/AIA/HSN circuits. Upon cold stimulation, ASEL and AWC release glutamate to activate and inhibit AIA interneurons by acting on highly and lowly sensitive ionotropic GLR-2 and GLC-3 receptors, respectively. AIA inhibits HSN motor neuron activity via acetylcholinergic ACR-14 receptor signaling and suppresses egg laying. Thus, ASEL and AWC initiate and reduce the cold suppression of egg laying. ASEL's action on AIA and egg laying dominates AWC's action. The biased opposite actions of these neurons on egg laying provide animals with a precise adaptation of reproductive behavior to environmental temperatures.

Chronic Intermittent Hypobaric Hypoxia Reduces Hypothalamic N-Methyl-d-Aspartate Receptor Activity and Sympathetic Outflow in Spontaneously Hypertensive Rats.

Guo, Xinqi, Hongyu Ma, Ziye Cui, Qiyue Zhao, Ying Zhang, Lu Jia, Liping Zhang, Hui Guo, Xiangjian Zhang, Yi Zhang, Yue Guan, and Huijie Ma. Chronic intermittent hypobaric hypoxia reduces hypothalamic N-Methyl-d-Aspartate Receptor activity and sympathetic outflow in spontaneously hypertensive rats. High Alt Med Biol. 25:77-88, 2024. Objective: This study aims to determine the role of hypothalamic renin-angiotensin system (RAS) in the antihypertensive effect of chronic intermittent hypobaric hypoxia (CIHH). Methods: Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) received 35 days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h/day. The levels of RAS, blood pressure, and N-methyl-d-aspartate receptor (NMDAR) activities of hypothalamic paraventricular nucleus (PVN) presympathetic neurons from each group of rats were determined. Results: The systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure (MAP) of SHRs significantly decreased from the third week of CIHH treatment. This blood pressure reduction effect could be maintained for at least 2 weeks after stopping the CIHH treatment. CIHH treatment also attenuated the decrease in MAP and renal sympathetic nerve activity induced by hexamethonium administration in SHRs, but not in WKY rats. Furthermore, CIHH reversed the increase in serum angiotensin (Ang)II concentration and the expression of PVN angiotensin-converting enzyme (ACE) and AngII type 1 (AT1) receptors, as well as the decrease in serum Ang1-7 concentration and the expression of PVN ACE2 and Mas receptors in SHRs. In addition, the administration of CIHH resulted in a reduction in the frequency of miniature excitatory postsynaptic currents and amplitude of NMDAR current in PVN presympathetic neurons of SHRs, which means that CIHH decreased the pre- and postsynaptic NMDAR activity of PVN presympathetic neurons in SHRs. However, pretreatment with A779 (a Mas receptor blocker) or AngII abrogated the above effects. Meanwhile, Ang1-7 pretreatment mimicked the CIHH effect on pre- and postsynaptic NMDAR activity of presympathetic neurons in SHRs. Conclusions: Our data indicate that CIHH reduces pre- and postsynaptic NMDAR activity of PVN presympathetic neurons, sympathetic outflow, and blood pressure by decreasing the activity of the ACE/AngII/AT1 axis and increasing the activity of ACE2/Ang1-7/Mas axis in the hypothalamus in hypertension.

Association between postoperative changes in natremia and outcomes in patients undergoing elective craniotomy.

Postoperative dysnatremias, characterized by imbalances in serum sodium levels, have been linked to increased resource utilization and mortality in surgical and intensive care patients. The management of dysnatremias may involve medical interventions based on changes in sodium levels. In this study, we aimed to investigate the impact of postoperative changes in natremia on outcomes specifically in patients undergoing craniotomy.We conducted a retrospective analysis of patient records from the Department of Neurosurgery at West China Hospital, Sichuan University, covering the period from January 2011 to March 2021. We compared the highest and lowest sodium values in the first 14 postoperative days with the baseline values to define four categories for analysis: no change < 5 mmol/L; decrease > 5 mmol/L; increase > 5 mmol/L; both increase and decrease > 5 mmol/L. The primary outcome measure was 30-day mortality.A total of 12,713 patients were included in the study, and the overall postoperative mortality rate at 30 days was 2.1% (264 patients). The increase in sodium levels carried a particularly high risk, with a tenfold increase (OR 10.21; 95% CI 7.25-14.39) compared to patients with minimal or no change. Decreases in sodium levels were associated with an increase in mortality (OR 1.60; 95% CI 1.11-2.23).Moreover, the study revealed that postoperative sodium decrease was correlated with various complications, such as deep venous thrombosis, pneumonia, intracranial infection, urinary infection, seizures, myocardial infarction, and prolonged hospital length of stay. On the other hand, postoperative sodium increases were associated with acute kidney injury, deep venous thrombosis, pneumonia, intracranial infection, urinary infection, surgical site infection, seizures, myocardial infarction, and prolonged hospital length of stay.Changes in postoperative sodium levels were associated with increased complications, prolonged length of hospital stay, and 30-day mortality. Moreover, the severity of sodium change values correlated with higher mortality rates.