Potential causal and temporal relationship between plasma triglyceride levels and circulating leukocyte.

BACKGROUND: Circulating triglyceride (TG) and leukocytes, the main components of the vascular system, may impact each other and co-fuel atherosclerosis. While the causal relationship between plasma TG levels and leukocyte counts remains unclear. METHODS: Bidirectional mendelian randomisation (MR) analysis was conducted to investigate the potential causal relationship between TG levels and the counts of leukocytes and their subtypes. A cross-lagged panel model (CLPM) using a longitudinal healthy screening data (13,389 adults with an follow-up of 4 years) was fitted to examine the temporal relationship between them. RESULTS: Genetically predicted plasma TG levels were positively associated with total leukocyte counts (TLC) [ß(se)=0.195(0.01)], lymphocyte counts (LC) [ß(se)=0.196(0.019)], and neutrophill counts (NC) [ß(se)=0.086(0.01)], which remained significant after adjusting for several confounders. Inversely, the genetically predicted TLC [ß(se)=0.033(0.008)], LC [ß(se)=0.053(0.008)], and NC [ß(se)=0.034(0.008)] were positively associated with plasma TG levels. However, when all three of them were put into the MR model adjusted for each other, only LC was significantly associated with TG levels. There was no association between genetically predicted TG levels and monocyte counts (MC), basophil counts, and eosinophill counts. The results of CLPM showed that the temporal effect of elevated TLC, MC, LC, and NC on plasma TG levels were stronger than the inverse effect. CONCLUSION: Our findings suggesting a causal associations of plasma TG levels with TLC, LC, and NC. In turn, LC was positively associated with plasma TG levels. Additionally, elevated circulating LC may precede high plasma TG levels.

Nisin A elevates adenosine to achieve anti-inflammatory activity.

Inflammation is a ubiquitous physiological status that exists during the occurrence, development and prognosis of numerous diseases. Clinical anti-inflammatory drugs mainly include antibiotics, antivirals, non-steroids and corticosteroids, and the treatments are often accompanied by side effects, including nausea, abdominal pain, allergy, nerve injury and organ dysfunction. Current studies have focused on continuously exploring efficient anti-inflammatory natural components with high biosafety, while nisin, a natural bioactive anti-microbial peptide produced by Lactococcus, has been reported to have anti-inflammatory activity via its superior anti-bacterial abilities. Several recent studies have focused on the potent direct anti-inflammation of nisin, whereas its effects and the corresponding mechanism still remain unclear. The cellular and Caenorhabditis elegans (C. elegans) models were constructed in this study to evaluate the anti-inflammatory effects of nisin A both in vitro and in vivo, while the inflammatory mechanism was further uncovered based on omics analysis. This study reveals the direct anti-inflammatory activity of nisin A and elucidates the regulatory actions of nisin A on adenosine, followed by alteration of the sphingolipid signaling pathway and purine metabolism, enhancing the deep understanding of nisin A with its anti-inflammatory capacity, providing new ideas for future nisin A-based anti-inflammatory strategies.

Construction of an endoplasmic reticulum stress and cuproptosis -related lncRNAs signature in chemosensitivity in hepatocellular carcinoma by comprehensive bioinformatics analysis.

Endoplasmic reticulum stress (ERS) and cuproptosis have remarkable effects on hepatocellular carcinoma (HCC) leading to a poor prognosis. The current study aimed to explore credible signature for predicting the prognosis of HCC based on ERS and cuproptosis-related lncRNAs. In our study, clinical and transcriptomic profiles of HCC patients were obtained from the Cancer Genome Atlas (TCGA) database. An ERS and cuproptosis-related lncRNA prognostic signature, including NRAV, SNHG3, LINC00839 and AC004687.1, was determined by correlation tests, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) methods. Survival and predictive value were evaluated using Kaplan-Meier and receiver operating characteristic (ROC) curves, while calibration and nomograms curves were developed. Besides the enrichment analyses for ERS and cuproptosis-related lncRNAs, mutational status and immune status were assessed with TMB and ESTIMATE. Additionally, consensus cluster analysis was employed to compare cancer subtype differences, while drug sensitivity and immunologic efficacy were evaluated for further exploration. qRT-PCR and CCK-8 were utilized to verify the alteration of the prognostic lncRNAs expression and proliferation in vitro. High-risk groups exhibited poorer prognosis. The signature exhibited robust predictive value as an independent prognostic indicator and showed significant correlation with clinicopathological features. In the enriched analysis, biological membrane pathways were enriched. Low-risk patients had lower TMB and higher immune status. A cluster analysis revealed that cluster 2 had the best clinical immunological efficacy and most active immune function. In brief, our constructed signature with ERS and cuproptosis-related lncRNAs was associated survival outcomes of HCC, and can be used to predict the clinical classification and curative effect.

The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.

ABSTRACT: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-ß-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.

Endocytosis: the match point of nanoparticle-based cancer therapy.

Nanomedicine has inspired a ground-breaking strategy for cancer therapy. By intelligently assembling diverse moieties to form nanoparticles, numerous functionalities such as controlled release, synergistic efficiency, and in situ killing can be achieved. The emerging nanoparticles have been designed with elevated targeting efficiency as targeting cancer cells is the primary requirement for nanoparticles. However, effective targeting does not guarantee therapeutic effects as endocytosis is a prerequisite for nanoparticles to exert effects. The recent decade has witnessed the rapid development of endocytosis-oriented nanoparticles, and this review subtly analyzes, categorizes, and exemplifies these nanoparticles according to their biological internalization patterns, and the correlation between the endocytosis mechanism and the property of nanoparticles is bridged. Based on the interdisciplinary vision, the present challenges and future perspectives of nanoparticle design for successful endocytosis are discussed, highlighting the potential strategies for the future development of endocytosis-oriented nanoparticles, thus facilitating the endocytosis-oriented strategy from bench to bedside. The undeniable fact is that endocytosis-oriented nanoparticles will definitely bring new blood to the next generation of advanced cancer therapies.

Effects of Latilactobacillus sakei LZ217 on Gastric Mucosal Colonization, Metabolic Interference, and Urease Expression in Helicobacter pylori Infection.

Emerging evidence suggests differential antagonism of lactic acid-producing bacteria (LAB) to Helicobacter pylori, posing challenges to human health and food safety due to unclear mechanisms. This study assessed 21 LAB strains from various sources on H. pylori growth, urease activity, and coaggregation. Composite scoring revealed that Latilactobacillus sakei LZ217, derived from fresh milk, demonstrates strong inhibitory effects on both H. pylori growth and urease activity. L. sakei LZ217 significantly reduced H. pylori adherence of gastric cells in vitro, with inhibition ratios of 47.62%. Furthermore, in vivo results showed that L. sakei LZ217 alleviated H. pylori-induced gastric mucosa damage and inflammation in mice. Metabolomic exploration revealed metabolic perturbations in H. pylori induced by L. sakei LZ217, including reduced amino acid levels (e.g., isoleucine, leucine, glutamate, aspartate, and phenylalanine) and impaired carbohydrate and nucleotide synthesis, contributing to the suppression of ureA (28.30%), ureE (84.88%), and ureF (59.59%) expressions in H. pylori. This study underscores the efficacy of LAB against H. pylori and highlights metabolic pathways as promising targets for future interventions against H. pylori growth and colonization.

Relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D in patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. METHODS: A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. RESULTS: Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P < 0.001) and BMI (OR = 1.04, p = 0.007) were independent predictors of NAFLD in patients with T2DM. CONCLUSIONS: This study revealed the correlation between serum 25(OH)D levels and NAFLD in patients with T2DM. We also demonstrated that serum 25(OH)D levels were negatively correlated with FLI/FIB-4 levels in patients with T2DM with NAFLD, suggesting that vitamin D deficiency may promote hepatic fibrosis progression in T2DM with NAFLD.

How does ferrocene correlate with ferroptosis? Multiple approaches to explore ferrocene-appended GPX4 inhibitors as anticancer agents.

Ferroptosis has emerged as a form of programmed cell death and exhibits remarkable promise for anticancer therapy. However, it is challenging to discover ferroptosis inducers with new chemotypes and high ferroptosis-inducing potency. Herein, we report a new series of ferrocenyl-appended GPX4 inhibitors rationally designed in a "one stone kills two birds" strategy. Ferroptosis selectivity assays, GPX4 inhibitory activity and CETSA experiments validated the inhibition of novel compounds on GPX4. In particular, the ROS-related bioactivity assays highlighted the ROS-inducing ability of 17 at the molecular level and their ferroptosis enhancement at the cellular level. These data confirmed the dual role of ferrocene as both the bioisostere motif maintaining the inhibition capacity of certain molecules with GPX4 and also as the ROS producer to enhance the vulnerability to ferroptosis of cancer cells, thereby attenuating tumor growth in vivo. This proof-of-concept study of ferrocenyl-appended ferroptosis inducers via rational design may not only advance the development of ferroptosis-based anticancer treatment, but also illuminate the multiple roles of the ferrocenyl component, thus opening the way to novel bioorganometallics for potential disease therapies.

Metabolism of quercitrin in the colon and its beneficial regulatory effects on gut microbiota.

BACKGROUND: Quercitrin is a dietary flavonoid widely found in plants with various physiological activities. However, whether quercitrin alters gut microbiota in vivo is not well understood. The aim of this study was to investigate metabolism of quercitrin in the colon and its regulation on gut microbiota in mice. RESULTS: Herein, 22 flavonoids related to quercitrin metabolism were identified based on ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Gas chromatography and 16S rDNA gene sequencing were used to investigate short-chain fatty acid (SCFA) content and diversity of composition of gut microbiota, respectively. The results showed that quercitrin significantly alters the beta-diversity of the gut microbiota, probiotics such as Akkermansia and Lactococcus were significantly increased, and the production of propanoate, isovalerate and hexanoate of the quercitrin group were enhanced significantly. The Spearman's association analysis provided evidence that Gardnerella and Akkermansia have obvious correlations with most of quercitrin metabolites and SCFAs. CONCLUSION: Quercitrin and its metabolites in the colon altered the structure of the mice gut microbiota and increased the content of SCFAs. Our experiments provide valuable insights into quercitrin research and application. © 2024 Society of Chemical Industry.

Glutathione-activated biotin-targeted dual-modal imaging probe with improved PDT/PTT synergistic therapy.

BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

Potential effects of aerosol generation and transmission during bedside endoscope cleaning.

Airborne transmission is among the most frequent types of nosocomial infection. Recent years have witnessed frequent outbreaks of airborne diseases, such as severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome (MERS) in 2012, and coronavirus disease 2019 (COVID-19), with the latter being on the rampage since the end of 2019 and bringing the effect of aerosols on health back to the fore (Gralton et al., 2011; Wang et al., 2021). An increasing number of studies have shown that certain highly transmissible pathogens can maintain long-term stability and efficiently spread through aerosols (Leung, 2021; Lv et al., 2021). As reported previously, influenza viruses that can spread efficiently through aerosols remain stable for a longer period compared to those that cannot. The World Health Organization (WHO) has stated that aerosol-generating procedures (AGPs) play an important role in aerosol transmission in hospitals (Calderwood et al., 2021). AGPs, referring to medical procedures that produce aerosols, including dental procedures, endotracheal intubation, sputum aspiration, and laparoscopic surgeries, have been reported to be significantly associated with an increased risk of nosocomial infection among medical personnel (Hamilton, 2021).

Effects of Maternal Diet on Infant Health: A Review Based on Entero-Mammary Pathway of Intestinal Microbiota.

SCOPE: The microbes in breast milk are critical for the early establishment of infant gut microbiota and have important implications for infant health. Breast milk microbes primarily derive from the migration of maternal intestinal microbiota. This review suggests that the regulation of maternal diet on gut microbiota may be an effective strategy to improve infant health. METHODS AND RESULTS: This article reviews the impact of breast milk microbiota on infant development and intestinal health. The close relationship between the microbiota in the maternal gut and breast through the entero-mammary pathway is discussed. Based on the effect of diet on gut microbiota, it is proposed that changing the maternal dietary structure is a new strategy for regulating breast milk microbiota and infant intestinal microbiota, which would have a positive impact on infant health. CONCLUSION: Breast milk microbes have beneficial effects on infant development and regulation of the immune system. The mother's gut and breast can undergo certain bacterial migration through the entero-mammary pathway. Research has shown that intervening in a mother's diet during breastfeeding can affect the composition of the mother's gut microbiota, thereby regulating the microbiota of breast milk and infant intestines, and is closely related to infant health.

Immunocyte membrane-derived biomimetic nano-drug delivery system: a pioneering platform for tumour immunotherapy.

Tumor immunotherapy characterized by its high specificity and minimal side effects has achieved revolutionary progress in the field of cancer treatment. However, the complex mechanisms of tumor immune microenvironment (TIME) and the individual variability of patients' immune system still present significant challenges to its clinical application. Immunocyte membrane-coated nanocarrier systems, as an innovative biomimetic drug delivery platform, exhibit remarkable advantages in tumor immunotherapy due to their high targeting capability, good biocompatibility and low immunogenicity. In this review we summarize the latest research advances in biomimetic delivery systems based on immune cells for tumor immunotherapy. We outline the existing methods of tumor immunotherapy including immune checkpoint therapy, adoptive cell transfer therapy and cancer vaccines etc. with a focus on the application of various immunocyte membranes in tumor immunotherapy and their prospects and challenges in drug delivery and immune modulation. We look forward to further exploring the application of biomimetic delivery systems based on immunocyte membrane-coated nanoparticles, aiming to provide a new framework for the clinical treatment of tumor immunity.

Hypolipidemic effect of polysaccharide from Sargassum fusiforme and its ultrasonic degraded polysaccharide on zebrafish fed high-fat diet.

Sargassum fusiforme is a brown seaweed that grows abundantly along the rocky coastlines of Asian countries. The polysaccharides derived from Sargassum fusiforme (SFPS) have received much interest due to their various bioactivities, such as hypolipidemic, hypoglycemic, and antioxidant activities. In this study, we extracted and purified SFPS, and obtained the ultrasonic degradation product (SFPSUD). The lipid regulatory effects of SFPS and SFPSUD were investigated in a zebrafish model fed a high-fat diet. The results showed that SFPS significantly decreased the levels of total cholesterol (TC) and triglycerides (TG), and increased the activities of lipoprotein lipase (LPL) and hepatic lipase (HL). SFPSUD was more effective than the SFPS in reducing the TC and TG levels in zebrafish, as well as increasing the LPL and HL activities. Histopathological observations of zebrafish livers showed that SFPSUD significantly improved lipid metabolism disorder in the hepatocytes. The possible lipid-lowering mechanism in zebrafish associated with SFPS and SFPSUD may involve acceleration of the lipid metabolism rate by increasing the activities of LPL and HL. Thus, SFPSUD could be tested as a highly effective hypolipidemic drug. Our results suggest that SFPS and SFPSUD have potential uses as functional foods for the prevention and treatment of hyperlipidemia. Ultrasound can be effectively applied to degrade SFPS to improve its physicochemical properties and bioactivities.

Dress me an outfit: advanced probiotics hybrid systems for intelligent IBD therapy.

Inflammation bowel disease (IBD) has emerged as a public health challenge worldwide; with high incidence and rapid prevalence, it has troubled billions of people and further induced multitudinous systemic complications. Recent decade has witnessed the vigorous application of food-borne probiotics for IBD therapy; however, the complicated and changeable environments of digestive tract have forced probiotics to face multiple in vivo pressures, consequently causing unsatisfied prophylactic or therapeutic efficacy attributed to off-targeted arrival, damaged viability, insufficient colonization efficiency, etc. Fortunately, arisen hybrid technology has provided versatile breakthroughs for the targeted transplantation of probiotics. By ingeniously modifying probiotics to form probiotics hybrid systems (PHS), the biological behaviors of probiotics in vivo could be mediated, the interactions between probiotics with intestinal components can be facilitated, and diverse advanced probiotic-based therapies for IBD challenge can be developed, which attribute to the intelligent response to microenvironment of PHS, and intelligent design of PHS for multiple functions combination. In this review, various PHS were categorized and their intestinal behaviors were elucidated systematically, their therapeutic effects and intrinsic mechanism were further analyzed. Besides, shortages of present PHS and the corresponding solutions have been discussed, based on which the future perspectives of this field have also been proposed. The undeniable fact is that PHS show an incomparable future to bring the next generation of advanced food science.

Dressing probiotics with versatile outfits would impart them with extended functions, including elevated targeted efficiency to the nidi, controlled in situ release, enhance intestinal colonization, comprehensive microecology regulation, and so on. In this article, we systematically analyzed and categorized PHS for intelligent IBD therapy published in recent decade, and discussed their pros and cons to further raise the future orientation for PHS development.

Distribution and spread of tigecycline resistance gene tet(X4) in Escherichia coli from different sources.

Tigecycline serves as a last-resort antimicrobial agent against severe infections caused by multidrug-resistant bacteria. Tet(X) and its numerous variants encoding flavin-dependent monooxygenase can confer resistance to tigecycline, with tet(X4) being the most prevalent variant. This study aims to investigate the prevalence and characterize tigecycline resistance gene tet(X) in E. coli isolates from various origins in Yangzhou, China, to provide insights into tet(X) dissemination in this region. In 2022, we tested the presence of tet(X) in 618 E. coli isolates collected from diverse sources, including patients, pig-related samples, chicken-related samples, and vegetables in Yangzhou, China. The antimicrobial susceptibility of tet(X)-positive E. coli isolates was conducted using the agar dilution method or the broth microdilution method. Whole genome sequencing was performed on tet(X)-positive strains using Illumina and Oxford Nanopore platforms. Four isolates from pig or pork samples carried tet(X4) and exhibited resistance to multiple antimicrobial agents, including tigecycline. They were classified as ST542, ST10, ST761, and ST48, respectively. The tet(X4) gene was located on IncFIA8-IncHI1/ST17 (n=2), IncFIA18-IncFIB(K)-IncX1 (n=1), and IncX1 (n=1) plasmids, respectively. These tet(X4)-carrying plasmids exhibited high similarity to other tet(X4)-bearing plasmids with the same incompatible types found in diverse sources in China. They shared related genetic environments of tet(X4) associated with ISCR2, as observed in the first identified tet(X4)-bearing plasmid p47EC. In conclusion, although a low prevalence (0.65%) of tet(X) in E. coli strains was observed in this study, the horizontal transfer of tet(X4) among E. coli isolates mediated by pandemic plasmids and the mobile element ISCR2 raises great concerns. Thus, heightened surveillance and immediate action are imperative to curb this clinically significant resistance gene and preserve the efficacy of tigecycline.

Exopolysaccharide from Lacticaseibacillus paracasei alleviates gastritis in Helicobacter pylori-infected mice by regulating gastric microbiota.

Introduction: Many probiotics have the ability to produce extracellular polysaccharides (EPS). EPS derived from these probiotics has been confirmed to regulate the host intestinal microecological balance and alleviate the symptoms of diseases caused by gastrointestinal microecological imbalance. Results: Lactic acid bacteria (LAB) strain with good exopolysaccharide (EPS) producing ability, namely, Lacticaseibacillus paracasei ZFM54 (L. paracasei ZFM54) was screened. The fermentation conditions of L. paracasei ZFM54 for EPS production were optimized. The EPS54 was characterized by chemical component and monosaccharide composition determination, UV, FT-IR and NMR spectra analysis. Cango red, SEM, AFM and XRD analysis were conducted to characterize the structure of EPS54. The EPS54 effectively reduced the colonization of Helicobacter pylori to AGS cells and recovered the cell morphology. EPS54 could also effectively alleviate the gastritis in the H. pylori-infected mice by down-regulating the mRNA expression levels of pro-inflammatory cytokines IL-6, IL-8, IL-1ß and TNF-α and up-regulating the mRNA expression of inflammatory cytokine IL-10 in gastric cells. EPS54 was also found to be able to positively regulate the structure of gastric microbiota. Conclusion: The EPS 54 from L. paracasei ZFM54 can alleviate gastritis in H. pylori-infected mice by modulating the gastric microbiota.

Safety of Tonsillectomy and/or Adenoidectomy in Pediatric Patients with Prolonged Activated Partial Thromboplastin Time and Factor XII Deficiency.

Objective: To evaluate the safety and feasibility of tonsillectomy and/or adenoidectomy (T&A) in pediatric patients with prolonged activated partial thromboplastin time (APTT) and coagulation factor deficiency. Methods: A prospective study was admitted to the children undergoing T&A at our institution between October 2019 and January 2020, specifically focusing on preoperative coagulation function. Within this group, we identified 5 patients exhibiting prolonged APTT and coagulation factor deficiencies, constituting the experimental group, and 10 patients matched by gender and age with normal blood coagulation function were selected as the control group. Comparative analyses between the two groups were conducted, focusing on surgical duration, intraoperative bleeding volume, duration of hospital stay, and postoperative complications such as active bleeding across the groups. At the six-month postoperative mark, a reassessment of coagulation functions and factor assays was conducted within the experimental group. Results: No statistically significant differences were discovered in terms of surgical duration or bleeding volume when comparing the experimental subgroups with their respective control counterparts. Furthermore, there were no incidences of postoperative active bleeding observed in any of the groups. Notably, postoperative APTT values (32.7 ± 1.7s) exhibited a significant disparity compared to preoperative levels (43.7 ± 1.8s, p < 0.01). Coagulation factors demonstrated normalization, evidenced by a significant difference in postoperative Factor XII levels (40.2 ± 5.4%) compared to preoperative levels (63.1 ± 5.9%, p < 0.01). Conclusion: Prolonged APTT with FXII factor deficiency does not show a significant bleeding tendency and is not a contraindication for T&A surgery. Post T&A surgery, children with abnormal coagulation function and deficient clotting factors show significant improvement compared to pre-surgery. It is important to consider that chronic inflammation in adenoids and tonsils may contribute to the prolongation of APTT and the manifestation of Factor XII deficiency.

Rh(III)-catalyzed atroposelective C-H alkynylation of 1-aryl isoquinolines with hypervalent iodine-alkyne reagents.

An efficient Rh(III)-catalyzed enantioselective C-H alkynylation of isoquinolines is disclosed. The C-H alkynylation of 1-aryl isoquinolines with hypervalent iodine-alkyne reagents proceeded in DMA at room temperature in the presence of 2.5 mol% chiral SCpRh(III) complex along with 20 mol% AgSbF6, providing axially chiral alkynylated 1-aryl isoquinolines in excellent yields (up to 93%) and enantioselectivity (up to 95% ee). The diverse transformations of the product further enhance the potential utility of this reaction.

First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial.

Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.