Immune characteristics and clinical significance of peripheral blood lymphocytes in breast cancer.

BACKGROUND: In the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape. METHODS: The primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients. RESULTS: Our analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy. CONCLUSIONS: These results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.

Effects of intravenous administration of magnesium sulfate in propofol-based sedation for ERCP in elderly patients: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Propofol-based sedations are widely used in elderly patients for endoscopic retrograde cholangiopancreatography (ERCP) procedure, but respiratory depression and cardiovascular adverse events commonly occur. Magnesium administered intravenously can alleviate pain and decrease propofol requirements during surgery. We hypothesized that intravenous magnesium was used as adjuvant to propofol might be beneficial in elderly patients undergoing ERCP procedures. METHODS: Eighty patients aged from 65 to 79 years who were scheduled for ERCP were enrolled. All patients were intravenously administered 0.1 µg/kg sufentanil as premedication. The patients were randomized to receive either intravenous magnesium sulfate 40 mg/kg (group M, n = 40) or the same volume of normal saline (group N, n = 40) over 15 min before the start of sedation. Intraoperative sedation was provided by propofol. Total propofol requirement during ERCP was the primary outcome. RESULTS: The total propofol consumption were reduced by 21.4% in the group M compared with the group N (151.2 ± 53.3 mg vs. 192.3 ± 72.1 mg, P = 0.001). The incidences of respiratory depression episodes and involuntary movement were less in the group M than those in the group N (0/40 vs. 6/40, P = 0.011; 4/40 vs. 11/40, P = 0.045; respectively). In the group M, the patients experienced less pain than those in the group N at 30 min after the procedure (1 [0-1] vs. 2 [1-2], P < 0.001). Correspondingly, the patients' satisfaction was clearly higher in the group M (P = 0.005). There was a tendency towards lower intraoperative heart rate and mean arterial pressure in group M. CONCLUSIONS: A single bolus of 40 mg/kg of intravenous magnesium can significantly reduce propofol consumption during ERCP, with higher sedation success and lower adverse events. TRIAL REGISTRATION: ID UMIN000044737. Registered 02/07/2021.

Role of miR-5010-3p in predicting the prognosis of hepatocellular carcinoma. / MiR-5010-3p在预测肝细胞癌预后中的作用（英文）.

OBJECTIVES: Numerous miRNAs have been found to be abnormally expressed in hepatocellular carcinoma (HCC). However, clinical significance of miR-5010-3p in HCC is not elucidated. This study aims to explore the prognostic value and role of miR-5010-3p in HCC. METHODS: The differential gene expression analysis of miR-5010-3p in HCC was performed based on the Cancer Genome Atlas (TCGA) database. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of miR-5010-3p expression level for HCC prognosis. The Kaplan-Meier, Cox univariate, and Cox multivariate analysis were used to predict its role in the prognosis of HCC. The downstream target genes were predicted. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to predict the potential functional pathways they may participate in. Finally, methyl thiazolyl tetrazolium (MTT) assay and 5-ethyl-2'-deoxyuridine (EDU) incorporation experiment were carried out to prove its effect on proliferation. RESULTS: The expression of miR-5010-3p was associated with histological grade (P=0.019), vascular invasion degree (P=0.049), TP53 level (P=0.004), and alpha fetoprotein (AFP) level (P=0.012). A moderate ability to distinguish between tumor and paracancerous tissues of miR-5010-3p in HCC was perceived by ROC curve (AUC: 0.712, 95% CI 0.649 to 0.776). High expression of miR-5010-3p was associated with shorter overall survival (OS) (P=0.003). The results of functional enrichment analysis showed that miR-5010-3p was related to the tumorigenesis process. In vitro experiments verified that miR-5010-3p promoted the proliferation of hepatocellular carcinoma cells. CONCLUSIONS: MiR-5010-3p promotes the proliferation of liver cancer cells, and its high expression is associated with poor prognosis, which may be a potential prognostic marker.

Individualized Whole Course Nutrition Management for Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) is the most common toxicity associated with radiotherapy for nasopharyngeal carcinoma (NPC). Patients with RIOM become malnourished, which can affect the delivery and dose of radiotherapy. The value of personalizing nutrition recommendations for cancer prevention and management is increasingly recognized. To investigate the effect of individualized whole course nutrition management on nutritional status and the incidence and severity of RIOM in NPCs. METHODS: This retrospective study included 77 patients who were provided individualized whole course nutrition management during radiotherapy (RT) and a 1-month follow-up. Seventy-one patients were included in the control group. RESULTS: During radiotherapy, severity of RIOM was significantly lower in the intervention group. There were statistically significant differences in oral mucosa recovery time and nutritional status between the two groups (p < 0.05). CONCLUSIONS: Individualized whole course nutrition management had the potential to maintain nutritional status and decrease the adverse effects of radiotherapy in NPCs.

Inhibitor of apoptosis-stimulating p53 protein protects against inflammatory bowel disease in mice models by inhibiting the nuclear factor kappa B signaling.

Drugs and therapies available for the treatment of inflammatory bowel disease (IBD) are not satisfactory. Our previous study has established the inhibitor of apoptosis-stimulating p53 protein (iASPP) as an oncogenic regulator in colorectal cancer by forming a regulatory axis or feedback loop with miR-124, p53, or p63. As iASPP could target and inhibit nuclear factor kappa B (NF-κB) activation, in this study the role and mechanism of iASPP in IBD was investigated. The aberrant up-regulation of iASPP in IBD was subsequently confirmed, based on online data sets, clinical sample examinations and 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis mice models. TNBS or DSS stimulation successfully induced colon shortness, body weight loss, mice colon oxidative stress and inflammation. In both types of colitis mice models, iASPP over-expression improved, whereas iASPP knockdown aggravated TNBS or DSS stimulation-caused colon shortness, body weight loss and mice colon oxidative stress and inflammation. Meanwhile, in both types of colitis mice models, iASPP over-expression inhibited p65 phosphorylation and decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, C-X-C motif chemokine ligand (CXCL)1 and CXCL2 in mice colons, whereas iASPP knockdown exerted opposite effects.

Exogenous NADPH ameliorates myocardial ischemia-reperfusion injury in rats through activating AMPK/mTOR pathway.

Our previous study shows that nicotinamide adenine dinucleotide phosphate (NADPH) plays an important role in protecting against cerebral ischemia injury. In this study we investigated whether NADPH exerted cardioprotection against myocardial ischemia/reperfusion (I/R) injury. To induce myocardial I/R injury, rats were subjected to ligation of the left anterior descending branch of coronary artery for 30 min followed by reperfusion for 2 h. At the onset of reperfusion, NADPH (4, 8, 16 mg· kg-1· d-1, iv) was administered to the rats. We found that NADPH concentrations in plasma and heart were significantly increased at 4 h after intravenous administration. Exogenous NADPH (8-16 mg/kg) significantly decreased myocardial infarct size and reduced serum levels of lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I). Exogenous NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and caspase-3. In addition, exogenous NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. We conducted in vitro experiments in neonatal rat cardiomyocytes (NRCM) subjected to oxygen-glucose deprivation/restoration (OGD/R). Pretreatment with NADPH (60, 500 nM) significantly rescued the cell viability and inhibited OGD/R-induced apoptosis. Pretreatment with NADPH significantly increased the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in OGD/R-treated NRCM. Compound C, an AMPK inhibitor, abolished NADPH-induced AMPK phosphorylation and cardioprotection in OGD/R-treated NRCM. In conclusion, exogenous NADPH exerts cardioprotection against myocardial I/R injury through the activation of AMPK/mTOR pathway and inhibiting mitochondrial damage and cardiomyocyte apoptosis. NADPH may be a potential candidate for the prevention and treatment of myocardial ischemic diseases.

LongShengZhi Capsule reduces carrageenan-induced thrombosis by reducing activation of platelets and endothelial cells.

Formation of thrombosis is associated with activation of platelets and endothelial cells. The effect of LongShengZhi Capsule (LSZ), a traditional Chinese medicine used for treatment of vascular diseases, on thrombosis was investigated in this study. BALB/c mice were induced thrombosis by injection of carrageenan while receiving pre or simultaneous LSZ treatment. We also compared the therapeutic effects of LSZ and clopidogrel on formed thrombi. LSZ inhibited carrageenan-induced thrombi in mouse tissue vessels. In addition, LSZ but not clopidogrel reduced formed thrombi with a short time window. The reduction of thrombi by LSZ was associated with reduced serum P-selectin, reduced expression of TNF-α and P-selectin and activated matrix metalloproteinase 2 expression in tissues. In vitro, LSZ decreased thrombin-induced human platelet clot retraction which was associated with inactivation of AKT and ERK1/2. LSZ also reduced adhesion of platelets or THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein or lipopolysaccharide. The anti-adherent actions of LSZ was attributed to reduction of oxidative stress, expression of platelet receptors (P2Y12, PAR4 and CD36) and AKT activity in platelets. LSZ also reduced adhesion molecules or tissue factor but activated tissue factor pathway inhibitor expression in HUVECs. Taken together, our study demonstrates the antithrombotic properties of LSZ by reducing activation of platelets and endothelial cells, and suggests its potential application in clinics.

LongShengZhi Capsule Reduces Established Atherosclerotic Lesions in apoE-Deficient Mice by Ameliorating Hepatic Lipid Metabolism and Inhibiting Inflammation.

Disorders of lipid metabolism and inflammation play an important role in atherosclerosis. LongShengZhi (LSZ) capsule, a Chinese herbal medicine, has been used for treatment of patients with vascular diseases for many years. In this article, we determined the effect of LSZ on the progression of established atherosclerotic lesions in apoE-deficient (apoE) mice. ApoE mice were prefed high-fat diet (HFD) for 8 weeks to induce atherosclerosis, then started with LSZ treatment contained in HFD for 10 weeks. Although LSZ had little effect on HFD-induced hypercholesterolemia, it substantially reduced en face and sinus aortic lesions. The reduction of lesions was associated with reduced macrophage/foam cell accumulation by activating ABCA1/ABCG1 expression. LSZ maintained the integrity of arterial wall by increasing collagen or smooth muscle cell content and inhibiting cell apoptosis. LSZ also attenuated HFD-induced fatty liver by down-regulating expression of lipogenic and cholesterol synthetic genes while activating expression of triglyceride catabolism genes. Moreover, LSZ demonstrated potent anti-inflammatory effects. In vivo, LSZ reduced serum TNF-α levels, infiltration of neutrophils, Kupffer cells, and expression of inflammatory cytokines in the liver. In vitro, it inhibited lipopolysaccharide or palmitate-induced expression of inflammatory cytokines in macrophages. Therefore, LSZ reduces atherosclerosis by ameliorating hepatic lipid metabolism and inhibiting inflammation.

NaoXinTong Capsule Inhibits Carrageenan-Induced Thrombosis in Mice.

Formation of thrombosis is mainly associated with dysfunctions of endothelial cells. NaoXinTong capsule (NXT), a traditional Chinese medicine, has been demonstrated multiple protective effects on vascular systems. However, it is unknown the effect of NXT on thrombosis. In this study, we determined whether NXT can inhibit carrageenan-induced thrombosis and the underlying mechanisms. Two days after carrageenan injection, severe thrombi were found in blood vessels of mouse tail and liver. By contrast, thrombi were substantially reduced by NXT treatment, and the reduction was associated with reduced serum tumor necrosis factor α and P-selectin levels. In vitro, NXT reduced lipopolysaccharide-activated adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) by inhibiting expression of adhesion molecules and interleukin 6, and reducing production of mitochondrial superoxide that is related to activation of antioxidant enzymes expression. NXT also reduced oxidized low-density lipoprotein-activated adhesion of platelets to HUVECs. In addition, NXT protected HUVECs against clopidogrel-induced cell death by inhibiting expression of tumor necrosis factor-like cytokine 1A and activating expression of vascular endothelial growth factor α. Taken together, our study indicates the potential application of NXT in antithrombosis by multiple antithrombotic functions.

Jasmonic acid deficiency leads to scattered floret opening time in cytoplasmic male sterile rice Zhenshan 97A.

Cytoplasmic male sterile (CMS) rice has been widely used for hybrid rice seed production in China. However, CMS rice suffers from undesirable flowering habits including scattered floret opening time (FOT), which causes different FOTs among parental rice plants and greatly reduces hybrid rice seed production. Little is known about the mechanism of scattered FOT in CMS rice. Our results demonstrate that scattered FOT in CMS rice Zhenshan 97A (ZS97A) resulted from the lack of a driving force to open florets, which was directly caused by retarded lodicule expansion. Our results indicate that retarded lodicule expansion in ZS97A was caused by reduced water accumulation due to retarded accumulation of osmotic regulation substances (ORSs). Further, the retardation in accumulation of ORSs and water were caused by jasmonic acid (JA) deficiency, resulting from down-regulation of OsAOC expression. Applying JA restored scattered FOT in ZS97A by promoting ORS and water accumulation, and inducing the expansion of the lodicules. Taken together, JA deficiency inhibited lodicule expansion by retarding the accumulation of ORSs and water, leading to scattered FOT in CMS rice ZS97A.

The long non-coding RNA NEAT1 interacted with miR-101 modulates breast cancer growth by targeting EZH2.

Nuclear enriched abundant transcript 1 (NEAT1), an important cancer-associated long non-coding RNA (lncRNA), contributes to the development and progression of several cancers. An increased expression of NEAT1 was observed in cancers including bladder cancer, lung cancer and breast cancer (BC). However, the exact effect of NEAT1 in BC progression and the underlying molecular mechanisms are still unknown up to now. Here, we investigated the detailed role of NEAT1 in human BC cell lines and clinical tumor samples in order to validate the function of this molecule. In our research, lncRNA-NEAT1 was specifically upregulated in BC cell lines and promoted BC cell growth through targeting miR-101. Knockdown of NEAT1 inhibited the proliferation and DNA synthesis of human BC cell in vitro. In addition, the regulation of EZH2 by miR-101 was required in NEAT1 induced BC cell growth. These findings indicated that NEAT1 might suppress the tumor growth via miR-101 dependent EZH2 regulation. Taken together, our data indicated that NEAT1 might be an oncogenic lncRNA that promoted proliferation of BC and could be regarded as a therapeutic target in human BC.

Prognostic values of Ki-67 in neoadjuvant setting for breast cancer: a systematic review and meta-analysis.

AIM: To assess the prognostic values of Ki-67 in neoadjuvant setting for breast cancer patients. METHODS: PubMed and EMBASE were searched. Revman software was used to conduct random-effect model meta-analysis. RESULTS: 49 studies (14,076 patients) were included. High Ki-67 before and after neoadjuvant chemotherapy were associated with worse overall survival (OS; before: hazard ratio [HR]: 2.29; 95% CI: 1.42-3.69; after: HR: 2.24; 95% CI: 1.82-2.75) and disease-free survival (DFS; before: HR: 1.54; 95% CI: 1.23-1.95; after: HR: 2.08; 95% CI: 1.83-2.37). Low/no reduction or increase might be associated with worse DFS (HR: 2.13; 95% CI: 1.51-3.02) and OS. CONCLUSION: Ki-67 before and after neoadjuvant chemotherapy, as well as the change could predict the prognosis for breast cancer patients.

Establishment of a ternary network system for evaluating the antioxidant fraction of Danhong injection.

Oxidative stress plays a crucial role in numerous cardiovascular diseases. As an effective therapy, Danhong injection (DHI) is considered to act through an antioxidant mechanism for the treatment of cardiovascular disease. In our study, we focused on the potential contribution of the antioxidant capacity of DHI fractions (Frs) and established an innovative screening method based on a 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay. A ternary network evaluation system, which was constructed based on the radical scavenging activity, the area under the activity-concentration curve and the solid content of the fractions, was implemented to select the fractions that posed the greatest antioxidant effect. As a result, Frs 5-7 and Frs 17-19 were shown to exhibit superior antioxidant activity according to the regression area of the ternary network, which was >0.5. Furthermore, the active fractions were characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry combined with nuclear magnetic resonance. This study provided an effective method for the comprehensive evaluation of the antioxidant effect of DHI fractions. Copyright © 2016 John Wiley & Sons, Ltd.

Citicoline protects brain against closed head injury in rats through suppressing oxidative stress and calpain over-activation.

Citicoline, a natural compound that functions as an intermediate in the biosynthesis of cell membrane phospholipids, is essential for membrane integrity and repair. It has been reported to protect brain against trauma. This study was designed to investigate the protective effects of citicoline on closed head injury (CHI) in rats. Citicoline (250 mg/kg i.v. 30 min and 4 h after CHI) lessened body weight loss, and improved neurological functions significantly at 7 days after CHI. It markedly lowered brain edema and blood-brain barrier permeability, enhanced the activities of superoxide dismutase and the levels of glutathione, reduced the levels of malondialdehyde and lactic acid. Moreover, citicoline suppressed the activities of calpain, and enhanced the levels of calpastatin, myelin basic protein and αII-spectrin in traumatic tissue 24 h after CHI. Also, it attenuated the axonal and myelin sheath damage in corpus callosum and the neuronal cell death in hippocampal CA1 and CA3 subfields 7 days after CHI. These data demonstrate the protection of citicoline against white matter and grey matter damage due to CHI through suppressing oxidative stress and calpain over-activation, providing additional support to the application of citicoline for the treatment of traumatic brain injury.

New species, new records and common species of Pluteussect.Celluloderma from northern China.

Wood-rotting fungi are organisms that can decompose wood substrates and extract nutrients from them to support their growth. They play a crucial role in the material cycle of forest ecosystems. The genus Pluteus plays a significant role in wood decomposition. In this study, the morphology and molecular systematics of the sect. Celluloderma of the genus Pluteus were carried out. Pluteusbrunneodiscus was identified as a new species, along with the discovery of two new records, P.cystidiosus and P.chrysophlebius, and a common species, P.romellii. Pluteusbrunneodiscus is characterized by the brown center of the pileus that transitions to white towards the margins, with the surface cracking to form irregular granules. It is typically found in Populus forests growing on decomposing twigs or wood chips. Line drawings, color photographs, and phylogenetic analyses of related species within the genus Pluteus accompany the descriptions of these four species. The analyses are based on ITS + TEF1-α sequence data. Finally, a key for the twenty species within the sect. Celluloderma of the genus Pluteus, which has been documented in China, is provided.

In vivo activity of dihydroartemisinin against Schistosoma mansoni schistosomula in mice.

Dihydroartemisinin, an anti-malarial agent, has been shown to exhibit activity against Schistosoma japonicum and S. mansoni. The purpose of the present study was to investigate the in vivo activity of dihydroartemisinin against juvenile S. mansoni and the changes to the genital system among worms surviving drug treatment. Mice were infected with 200 S. mansoni cercariae each and randomly assigned to groups. Dihydroartemisinin at a single oral dose of 300 mg/kg was given to mice on Days 14 or 16, 18, 20, 21, 22, 24, 26 or 28 post-infection, to assess the efficacy of dihydroartemisinin against juvenile S. mansoni. Mice were treated with dihydroartemisinin using various protocols with the total drug dose of 900 mg/kg, to investigate the efficacy of dihydroartemisinin against the schistosomula of S. mansoni. In addition, changes to the genital system among worms surviving dihydroartemisinin treatment, were recorded. An oral dose of dihydroartemisinin of 300 mg/kg was given to mice on Days 14, 16, 18, 20, 21, 22, 24, 26 or 28 days post-infection; this resulted in a 65.0-82.4% reduction in total worm burden and a 70.9-83.0% female worm burden. Better results were seen when treatment was given 20-24 days post-infection. Administration of multiple-dose and low-oral-dose dihydroarteminisinin (at doses of 90, 180, 300 and 450 mg/kg) at different times, reduced total worm burdens by 88.7-99.1% and female worm burdens by 93.2-99.5%. The egg tubercles in mice livers were significantly reduced following treatment; in some mice no egg tubercles were found. These findings indicate dihydroartemisinin exhibits high in vivo activity against the schistosomula of S. mansoni. It causes damage to the genital system of worms, influences the development of of S. mansoni worms, reduces the oviposition of surviving worms and enhances the formation of granulomas around tissue-trapped eggs, thereby reducing damage to the infected mammalian host.

Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis.

More clinical evidence is needed regarding the relative priority of treatments for brain metastases (BMs) from EGFR/ALK-negative/unselected non-small cell lung cancer (NSCLC). PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov databases were searched. Overall survival (OS), central nervous system progression-free survival (CNS-PFS), and objective response rate (ORR) were selected for Bayesian network meta-analyses. We included 25 eligible randomized control trials (RCTs) involving 3,054 patients, investigating nine kinds of treatments for newly diagnosed BMs and seven kinds of treatments for previously treated BMs. For newly diagnosed BMs, adding chemotherapy, EGFR-TKIs, and other innovative systemic agents (temozolomide, nitroglycerin, endostar, enzastaurin, and veliparib) to radiotherapy did not significantly prolong OS than radiotherapy alone; whereas radiotherapy + nitroglycerin showed significantly better CNS-PFS and ORR. Surgery could significantly prolong OS (hazard ratios [HR]: 0.52, 95% credible intervals: 0.41-0.67) and CNS-PFS (HR: 0.32, 95% confidence interval: 0.18-0.59) compared with radiotherapy alone. For previously treated BMs, pembrolizumab + chemotherapy, nivolumab + ipilimumab, and cemiplimab significantly prolonged OS than chemotherapy alone. Pembrolizumab + chemotherapy also showed better CNS-PFS and ORR than chemotherapy. In summary, immune checkpoint inhibitor (ICI)-based therapies, especially ICI-combined therapies, showed promising efficacies for previously treated BMs from EGFR/ALK-negative/unselected NSCLC. The value of surgery should also be emphasized. The result should be further confirmed by RCTs.

Analysis of nutritional risk, skeletal muscle depletion, and lipid metabolism phenotype in acute radiation enteritis.

BACKGROUND: Radiation enteritis, which often occurs during radiation-induced acute intestinal symptoms (RIAIS), is the most common and important complication during radiotherapy for cervical cancer. RIAIS caused by abdominal and pelvic radiotherapy will affect nutrient intake, digestion, absorption, and metabolism, leading to malnutrition or poorer nutritional status. In patients with malignant tumors, malnutrition can adversely affect the curative effect and response of radiotherapy by reducing radiosensitivity, affecting the precision of radiotherapy placement and increasing the incidence of radiotherapy-related adverse reactions. AIM: To analyze nutritional risk, skeletal muscle depletion, and lipid metabolism phenotype in acute radiation enteritis. METHODS: Fifty patients with cervical cancer received external beam radiotherapy, and 15 patients received brachytherapy after external beam radiotherapy. Body weight, body composition parameters, nutritional risk screening (NRS) 2002 score, and blood biochemical indices of patients with cervical cancer during periradiation were tested by a one-way repeated measures analysis of variance. Metabolomics analysis was used to identify characteristic lipid metabolism pathways. Clinical factors that affect linoleic acid changes were screened using the generalized evaluation equation. RESULTS: Among the 50 patients, 37 had RIAIS, including 34 patients with grade 1-2 RIAIS and 3 patients with grade 3 RIAIS. The NRS 2002 score of patients who underwent cervical cancer radiotherapy continued to increase during the periradiation period, and 42 patients who underwent cancer radiotherapy had nutritional deficits (NRS 2002 score ≥ 3 points) at the end of radiotherapy. Correlation analyses revealed that body weight and body mass index changes were closely associated with body fat content (R2 = 0.64/0.51). The results of the univariate analysis showed that radiotherapy time, percentage reduction of serum albumin, and percentage reduction of serum prealbumin were the key factors affecting skeletal muscle exhaustion (P < 0.05). Metabolomic analysis of fecal supernatants of cervical cancer patients during the periradiation period revealed the involvement of linoleic acid, cholic acid, arachidonic acid, and N-acetyl-L-benzene alanine in the metabolic pathway of linoleic acid. CONCLUSION: Cervical cancer radiotherapy patients faced nutritional risks, decreased serum albumin synthesis, and increased risk of skeletal muscle exhaustion. Linoleic acid was a biomarker of high nutritional risk.

Preparation and Quality Evaluation of Honokiol Nanoparticles Using a New Polysaccharide Polymer as its Carrier.

OBJECTIVE: To improve the solubility of Honokiol (HNK), Honokiol nanoparticles (HNK-NPs) were prepared using a new biodegradable polysaccharide polymer as its carrier. METHODS: HNK-NPs were prepared by hydrophilic polymer coagulation method, and the processing parameters were optimized according to average particle size and PDI by a single factor experiment. The morphology of the optimized nanoparticles was investigated by TEM, and the in vitro release was carried out to evaluate the optimized HNK-NPs. RESULTS: The encapsulation efficiency and drug loading of the HNK-NPs were 77.75 ± 2.63% and 13.46 ± 0.39%, respectively. The obtained nanoparticles of HNK-NPs were spherical-like under the electron microscope with a mean particle size of 198.50 ± 0.01 nm and a Zeta potential of -52.60 ± 1.00 mV. The in vitro release results showed that the cumulative release rates of nanoparticles were 48.28 ± 9.80% and 81.12 ± 4.35% within 2 h and 8 h, respectively, showing a stable release behavior. The average particle size and PDI of HNK-NPs solution prepared by the hydrophilic polymer condensation method had no obvious change at 72h. CONCLUSION: HNK-NPs were successfully prepared by the phase separation method. This new polysaccharide polymer should be an ideal carrier to help improve the solubility of HNK.

The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure.

Introduction: Multiple organ dysfunction syndrome (MODS) is common in patients with sepsistic admitted to an intensive care unit (ICU) and greatly increases mortality. Pancreatic stone protein/regenerating protein (PSP/Reg) is a type of C-type lectin protein that is overexpressed during sepsis. This study aimed to evaluate the potential involvement of PSP/Reg in MODS development in patients with sepsis. Materials and methods: The relationship between circulating PSP/Reg levels, patient prognosis, and progression to MODS was analyzed in patients with sepsis admitted to the ICU of a general tertiary hospital. Furthermore, to examine the potential involvement of PSP/Reg in sepsis-induced MODS, a septic mouse model was established per the cecal ligation and puncture procedure, randomized into three groups, and subjected to a caudal vein injection of recombinant PSP/Reg at two different doses and phosphate-buffered saline. Survival analyses and disease severity scoring were performed to evaluate the survival status of the mice; enzyme-linked immunosorbent assays were performed to detect the levels of inflammatory factors and organ-damage markers in murine peripheral blood; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to measure apoptosis levels in lung, heart, liver, and kidney tissue sections and to visualize the degree of organ damage in the mouse model; myeloperoxidase activity assay, immunofluorescence staining, and flow cytometry were performed to detect neutrophil infiltration levels in vital murine organs and the activation indexes of neutrophils. Results and discussion: Our findings indicated that Circulating PSP/Reg levels were correlated with patient prognosis and sequential organ failure assessment scores. Furthermore, PSP/Reg administration increased disease severity scores, shortened survival time, increased the TUNEL-positive staining rate, and increased the levels of inflammatory factors, organ-damage markers, and neutrophil infiltration in the organs. Neutrophils can be activated by PSP/Reg to an inflammatory state, both in vivo and in vitro, which is characterized by the increased levels of intercellular adhesion molecule 1 and CD29. Conclusion: Patient prognosis and progression to MODS can be visualized by monitoring PSP/Reg levels upon ICU admission. Additionally, PSP/Reg administration in animal models exacerbates the inflammatory response and severity of multiorgan damage, which may be accomplished by promoting the inflammatory state of neutrophils.