Dynamic changes of peripheral inflammatory markers link with disease severity and predict short-term poor outcome of myasthenia gravis.

The relationship between peripheral inflammatory markers, their dynamic changes, and the disease severity of myasthenia gravis (MG) is still not fully understood. Besides, the possibility of using it to predict the short-term poor outcome of MG patients have not been demonstrated. This study aims to investigate the relationship between peripheral inflammatory markers and their dynamic changes with Myasthenia Gravis Foundation of America (MGFA) classification (primary outcome) and predict the short-term poor outcome (secondary outcome) in MG patients. The study retrospectively enrolled 154 MG patients from June 2016 to December 2021. The logistic regression was used to investigate the relationship of inflammatory markers with MGFA classification and determine the factors for model construction presented in a nomogram. Finally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were utilized to evaluate the incremental capacity. Logistic regression revealed significant associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI) and MGFA classification (p = 0.013, p = 0.032, p = 0.017, respectively). Incorporating dynamic changes of inflammatory markers into multivariable models improved their discriminatory capacity of disease severity, with significant improvements observed for NLR, systemic immune-inflammation index (SII) and AISI in NRI and IDI. Additionally, AISI was statistically associated with short-term poor outcome and a prediction model incorporating dynamic changes of inflammatory markers was constructed with the area under curve (AUC) of 0.953, presented in a nomograph. The inflammatory markers demonstrate significant associations with disease severity and AISI could be regarded as a possible and easily available predictive biomarker for short-term poor outcome in MG patients.

Possible sarcopenia and its risk factors in a home for seniors in Shanghai.

BACKGROUND AND OBJECTIVES: The Asian Working Group for Sarcopenia (AWGS) recommended various measures for identifying patients with possible sarcopenia in its 2019 consensus. The present survey aimed to assess older adults in a senior home to determine the prevalence and associated factors for possible sarcope-nia and to compare the differences between various assessment pathways based on AWGS 2019 criteria. METHODS AND STUDY DESIGN: This cross-sectional study examined 583 participants of a senior home. Patients with possible sarcopenia were determined through the following four pathways: [I] calf circumference (CC) + handgrip strength (HGS); [II] SARC-F+HGS; (III) SARC-CalF+HGS; and (IV) CC, SARC-F, and/or SARC-CalF+HGS. RESULTS: The four assessment pathways revealed a high prevalence of possible sarcopenia in the older adults in the senior home ([I]=50.6%; [II]=46.8%; [III]=48.2%; [IV]=65.9%). There is significant difference in prevalence between pathway IV and the other pathways (p<0.001). A multivariate analysis revealed that advanced age, risk of malnutrition, malnutrition, high level of care, an exercise frequency of <3 times per week, and osteoporosis were correlated with a higher risk of possible sarcopenia. By contrast, oral nutritional supplements (ONS) reduced the risk of possible sarcopenia. CONCLUSIONS: This survey reported a high prevalence of possible sarcopenia in the older adults of the senior home and determined the associated influencing factors. Furthermore, our findings suggested that pathway IV is the most suitable pathway for the examined older adults which enabled the detection and early intervention of more possible sarcopenia.

Malnutrition and its risk factors in a home for seniors in Shanghai.

BACKGROUND AND OBJECTIVES: Older adults residing in senior homes are at a high risk of malnutrition. In this study, we investigated the nutritional status of these individuals and factors associated with malnutrition in this population. METHODS AND STUDY DESIGN: This cross-sectional study (September 2020-January 2021) included a total of 583 older adults residing in a senior home in Shanghai (mean age, 85.0±6.6 years). The Mini Nutritional Assessment Short Form (MNA-SF) questionnaire was administered to assess the nutritional status of the participants. Patients with possible sarcopenia were identified according to the guidelines recommended by the Asian Working Group for Sarcopenia in its 2019 consensus (AWGS 2019). Moreover, the factors influencing malnutrition were determined through multivariate analyses. RESULTS: The likelihoods of having malnutrition and being at a risk of malnutrition were noted in 10.5% and 37.4% of the participants, respectively. In both male and female participants, handgrip strength (HGS) and calf circumference (CC) increased significantly with increasing scores on the aforementioned questionnaire (p<0.001). Among the participants, 44.6% had ≥3 chronic diseases and 48.2% used multiple medicines. Multivariate analyses revealed that dys-phagia (OR, 3.8; 95% CI, 1.7-8.5), possible sarcopenia (OR, 3.6; 95% CI, 2.2-5.6), and dementia (OR, 4.5; 95% CI, 2.8-7.0) were correlated with a relatively high prevalence of malnutrition/malnutrition risk. Exercise (at least thrice a week) reduced malnutrition risk. CONCLUSIONS: Malnutrition is common among older adults residing in senior homes; therefore, the associated factors must be identified, and appropriate interventions should be administered.

Abdominal visceral adiposity influences CD4+ T cell cytokine production in pregnancy.

Women with pre-gravid obesity are at risk for pregnancy complications. While the macrophage response of obese pregnant women categorized by body mass index (BMI) has been documented, the relationship between the peripheral CD4(+) T cell cytokine profile and body fat compartments during pregnancy is unknown. In this study, third trimester peripheral CD4(+) T cell cytokine profiles were measured in healthy pregnant women [n=35; pre-pregnancy BMI: 18.5-40]. CD4(+) T cells were isolated from peripheral blood mononuclear cells and stimulated to examine their capacity to generate cytokines. Between 1 and 3weeks postpartum, total body fat was determined by dual-energy X-ray absorptiometry and abdominal subcutaneous and visceral fat masses were determined by magnetic resonance imaging. Pearson's correlation was performed to assess relationships between cytokines and fat mass. Results showed that greater abdominal visceral fat mass was associated with a decrease in stimulated CD4(+) T cell cytokine expression. IFN-gamma, TNF-alpha, IL-12p70, IL-10 and IL-17A were inversely related to visceral fat mass. Chemokines CCL3 and IL-8 and growth factors G-CSF and FLT-3L were also inversely correlated. Additionally, total body fat mass was inversely correlated with FGF-2 while abdominal subcutaneous fat mass and BMI were unrelated to any CD4(+) T cell cytokine. In conclusion, lower responsiveness of CD4(+) T cell cytokines associated with abdominal visceral fat mass is a novel finding late in gestation.

Neuronal Intranuclear Inclusion Disease with NOTCH2NLC GGC Repeat Expansion: A Systematic Review and Challenges of Phenotypic Characterization.

Neuronal intranuclear inclusion disease (NIID) is a highly clinically heterogeneous neurodegenerative disorder primarily attributed to abnormal GGC repeat expansions in the NOTCH2NLC gene. This study aims to comprehensively explore its phenotypic characteristics and genotype-phenotype correlation. A literature search was conducted in PubMed, Embase, and the Cochrane Library from September 1, 2019, to December 31, 2022, encompassing reported NIID cases confirmed by pathogenic NOTCH2NLC mutations. Linear regressions and trend analyses were performed. Analyzing 635 cases from 85 included studies revealed that familial cases exhibited significantly larger GGC repeat expansions than sporadic cases (p < 0.001), and this frequency significantly increased with expanding GGC repeats (p trend < 0.001). Age at onset (AAO) showed a negative correlation with GGC repeat expansions (p < 0.001). The predominant initial symptoms included tremor (31.70%), cognitive impairment (14.12%), and muscle weakness (10.66%). The decreased or absent tendon reflex (DTR/ATR) emerged as a notable clinical indicator of NIID due to its high prevalence. U-fiber was observed in 79.11% of patients, particularly prominent in paroxysmal disease-dominant (87.50%) and dementia-dominant cases (81.08%). Peripheral neuropathy-dominant cases exhibited larger GGC repeat expansions (median = 123.00) and an earlier AAO (median = 33.00) than other phenotypes. Moreover, a significant genetic anticipation of 3.5 years was observed (p = 0.039). This study provides a comprehensive and up-to-date compilation of genotypic and phenotypic information on NIID since the identification of the causative gene NOTCH2NLC. We contribute a novel diagnostic framework for NIID to support clinical practice.

Comparison of the therapeutic effects of mesenchymal stem cells derived from human dental pulp (DP), adipose tissue (AD), placental amniotic membrane (PM), and umbilical cord (UC) on postmenopausal osteoporosis.

Background: Osteoporosis is a systemic bone disease characterized by bone loss and microstructural degeneration. Recent preclinical and clinical trials have further demonstrated that the transplantation of mesenchymal stem cells (MSCs) derived from human adipose tissue (AD), dental pulp (DP), placental amniotic membrane (AM), and umbilical cord (UC) tissues can serve as an effective form of cell therapy for osteoporosis. However, MSC-mediated osteoimmunology and the ability of these cells to regulate osteoclast-osteoblast differentiation varies markedly among different types of MSCs. Methods: In this study, we investigated whether transplanted allogeneic MSCs derived from AD, DP, AM, and UC tissues were able to prevent osteoporosis in an ovariectomy (OVX)-induced mouse model of osteoporosis. The homing and immunomodulatory ability of these cells as well as their effects on osteoblastogenesis and the maintenance of bone formation were compared for four types of MSCs to determine the ideal source of MSCs for the cell therapy-based treatment of OVX-induced osteoporosis. The bone formation and bone resorption ability of these four types of MSCs were analyzed using micro-computed tomography analyses and histological staining. In addition, cytokine array-based analyses of serological markers and bioluminescence imaging assays were employed to evaluate cell survival and homing efficiency. Immune regulation was determined by flow cytometer assay to reflect the mechanisms of osteoporosis treatment. Conclusion: These analyses demonstrated that MSCs isolated from different tissues have the capacity to treat osteoporosis when transplanted in vivo. Importantly, DP-MSCs infusion was able to maintain trabecular bone mass more efficiently with corresponding improvements in trabecular bone volume, mineral density, number, and separation. Among the tested MSC types, DP-MSCs were also found to exhibit greater immunoregulatory capabilities, regulating the Th17/Treg and M1/M2 ratios. These data thus suggest that DP-MSCs may represent an effective tool for the treatment of osteoporosis.

Systemic Inflammatory Response Index, a Potential Inflammatory Biomarker in Disease Severity of Myasthenia Gravis: A Pilot Retrospective Study.

Purpose: Myasthenia gravis (MG) is a chronic autoimmune disease caused by neuromuscular junction (NMJ) dysfunction. Our current understanding of MG's inflammatory component remains poor. The systemic inflammatory response index (SIRI) presents a promising yet unexplored biomarker for assessing MG severity. This study aimed to investigate the potential relationship between SIRI and MG disease severity. Patients and Methods: We conducted a retrospective analysis of clinical data from 171 MG patients admitted between January 2016 and June 2021. Patients with incomplete data, other autoimmune diseases, or comorbidities were excluded. Disease severity was evaluated using the Myasthenia Gravis Foundation of America (MGFA) classification and Myasthenia Gravis Activities of Daily Living (MG-ADL) on admission. The association between SIRI and disease severity was assessed through logistic regression analysis, along with receiver operating characteristic (ROC) curve and decision curve analysis (DCA) comparisons with established inflammation indicators. Results: After exclusion, 143 patients were analyzed in our study. SIRI levels significantly differed between patients with higher and lower disease severity (p < 0.001). Univariate logistic regression showed that SIRI had a significant effect on high disease severity (OR = 1.376, 95% CI 1.138-1.664, p = 0.001). This association remained significant even after adjusting for age, sex, disease duration, history of MG medication and thymoma (OR = 1.308, 95% CI 1.072-1.597, p = 0.008). Additionally, a positive correlation between SIRI and MG-ADL was observed (r = 0.232, p = 0.008). Significant interactions were observed between SIRI and immunosuppressor (p interaction = 0.001) and intravenous immunoglobulin (p interaction = 0.005). DCA demonstrated the superior net clinical benefit of SIRI compared to other markers when the threshold probability was around 0.2. Conclusion: Our findings indicate a strong independent association between SIRI and disease severity in MG, suggesting SIRI's potential as a valuable biomarker for MG with superior clinical benefit to currently utilized markers.

Identification of novel serum metabolic signatures to predict chronic kidney disease among Chinese elders using UPLC-Orbitrap-MS.

BACKGROUND: Chronic kidney disease (CKD) is a major public health concern. However, validated and broadly applicable biomarkers for early CKD diagnosis are currently not available. We aimed to identify serum metabolic signatures at an early stage of CKD to provide a reference for future investigations into the early diagnostic biomarkers. METHODS: Serum metabolites were extracted from 65 renal dysfunction (RD) patients and 121 healthy controls (discovery cohort: 12 RD patients and 55 health participants; validation cohort: 53 RD patients and 66 health participants). Metabolite extracts were analyzed by ultraperformance liquid chromatography coupled with quadrupole-electrostatic field orbital trap mass spectrometry (UPLC-QE-Orbitrap MS) for untargeted metabolomics. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was performed to detect different compounds between groups. Receiver operating characteristic (ROC) curve analysis was carried out to determine the diagnostic value of the validated differential metabolites between groups. We referred to the Kyoto Encyclopedia of Gene and Genomes (KEGG) to elucidate the metabolic pathways of the validated differential metabolites. RESULTS: A total of 22 and 23 metabolites had significantly different abundances in the discovery and validation cohort, respectively. Six of them (creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine) in the RD group was more abundant than that of the health group in both cohorts. The combination of the six validated differential metabolites were able to accurately detect RD (AUC 0.86). Three of the six metabolites are involved in the metabolism of arginine and proline. CONCLUSIONS: The present study highlights that creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine are metabolite indicators with potential predictive value for CKD.

Predictive value of neutrophil to apolipoprotein A1 ratio in patients with acute ischaemic stroke.

The neutrophil to apolipoprotein A1 ratio has emerged as a possible prognostic biomarker in different medical conditions. Nonetheless, the predictive potential of neutrophil to apolipoprotein A1 ratio in determining the 3-month prognosis of acute ischaemic stroke patients who undergo intravenous thrombolysis has yet to be fully acknowledged. In this study, 196 acute ischaemic stroke patients with recombinant tissue plasminogen activator and 133 healthy controls were included. Meanwhile, we incorporated a total of 386 non-thrombolytic acute ischaemic stroke patients. The acute ischaemic stroke patients with recombinant tissue plasminogen activator were divided into four groups based on quartiles of neutrophil to apolipoprotein A1 ratio. The association between neutrophil to apolipoprotein A1 ratio and the 3-month prognosis was evaluated through univariate and multivariate regression analyses. Additionally, subgroup analyses were conducted to investigate the predictive value of neutrophil to apolipoprotein A1 ratio in different patient populations. Adverse outcomes were defined as a modified Rankin Scale score of 3-6. The study findings revealed a significant association between elevated neutrophil to apolipoprotein A1 ratio levels and poor prognosis in acute ischaemic stroke patients. In the highest quartile of neutrophil to apolipoprotein A1 ratio levels (Q4), after controlling for age, gender, admission National Institutes of Health Stroke Scale score, blood urea nitrogen and stroke subtypes, the odds ratio for adverse outcomes at 3 months was 13.314 (95% confidence interval: 2.878-61.596, P = 0.001). An elevated neutrophil to apolipoprotein A1 ratio value was found to be associated with a poor prognosis in acute ischaemic stroke patients, regardless of whether they received recombinant tissue plasminogen activator treatment or not. The new model, which incorporating neutrophil to apolipoprotein A1 ratio into the conventional model, demonstrated a statistically significant improvement in discriminatory power and risk reclassification for 3-month poor outcomes in acute ischaemic stroke patients treated with recombinant tissue plasminogen activator. The new model exhibited a categorical net reclassification index (P = 0.035) of 12.9% and an integrated discrimination improvement (P = 0.013) of 5.2%. Subgroup analyses indicated that the predictive value of neutrophil to apolipoprotein A1 ratio differed across stroke subtypes. Neutrophil to apolipoprotein A1 ratio is a potential biomarker for predicting the prognosis of acute ischaemic stroke patients. The clinical implications of our findings are significant, as early identification and intervention in high-risk patients can improve their outcomes. However, further studies are required to validate our results and elucidate the underlying mechanisms of the association between neutrophil to apolipoprotein A1 ratio and poor prognosis in acute ischaemic stroke patients.

Docosahexaenoic and arachidonic acid levels in extremely low birth weight infants with prolonged exposure to intravenous lipids.

OBJECTIVE: To report changes in red blood cell long-chain polyunsaturated fatty acids levels in extremely low birth weight (ELBW) infants relative to duration of intravenous lipid emulsion. STUDY DESIGN: Serial blood samples were collected from 26 ELBW infants during the first 2 months of life in the neonatal intensive care unit using a prospective cohort study design. The primary outcome was the change in long-chain polyunsaturated fatty acids levels over the study period relative to a duration of intravenous lipid emulsion of either ≤ 28 days or >28 days. Secondary outcomes included parenteral and enteral nutritional exposures as well as prematurity-associated morbidities. Longitudinal regression estimated changes in fatty acid levels between the 2 exposure groups. RESULTS: Infants with >28 days intravenous lipid emulsion had 36 more days of intravenous lipid emulsion than did those with ≤ 28 days (P < .001). Docosahexaenoic acid significantly decreased over time in all infants and decreased significantly more in infants exposed to intravenous lipid emulsion for >28 days (P = .03). Arachidonic acid significantly decreased over the study period but the decrease was not related to intravenous lipid emulsion duration. Linoleic and α-linolenic acids had significantly larger increases over time in those with longer exposure to intravenous lipid emulsion (P < .01). CONCLUSION: Docosahexaenoic acid status of ELBW infants declined significantly in the first 2 months of life and the decline was significantly greater in those exposed to intravenous lipid emulsion >28 days compared with those exposed ≤ 28 days.

Effect of phenylephrine on alveolar fluid clearance in ventilator-induced lung injury.

OBJECTIVE: To investigate the effect of phenylephrine (an α-adrenergic agonist) on alveolar fluid clearance (AFC) in ventilator-induced lung injury and the possible mechanism involved. METHODS: A total of 170 male Wistar rats were randomly allocated into 17 groups (n=10) using random number tables. Short-term (40 minutes) mechanical ventilation with high tidal volume (HVT) was performed to induce lung injury, impair active Na+ transport and lung liquid clearance in the rats. Unventilated rats served as controls. To demonstrate the effect of phenylephrine on AFC, phenylephrine at different concentrations (1×10(-5), 1×10(-6), 1×10(-7), 1×10(-8), and 1×10(-9) mol/L) was injected into the alveolar space of the HVT ventilated rats. To identify the influence of adrenergic antagonists, Na(+) channel, and microtubular system on the effect of phenylephrine, phenylephrine at 1×10(-5) mol/L combined with prazosin (an α1-adrenergic antagonist, 1×10(-4) mol/L), yohimbine (an α2-adrenergic antagonist, 1×10(-4) mol/L), atenolol (a ß1- adrenergic antagonist, 1×10(-5) mol/L), ICI-118551 (an ß2-adrenergic antagonist, 1×10(-5) mol/L), amiloride (a Na+ channel blocker, 5×10(-4) mol/L), ouabain (a Na(+)/K(+)-ATPase blocker, 5×10(-4) mol/L), colchicine (a microtubular disrupting agent, 0.25 mg/100 g body weight), or ß-lumicolchicine (an isomer of colchicine, 0.25 mg/100 g body weight) were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes. AFC and total lung water content were measured. RESULTS: Basal AFC in control rats was (17.47±2.56)%/hour, which decreased to (9.64± 1.32)%/hour in HVT ventilated rats (P=0.003). The perfusion of phenylephrine at 1×10(-8), 1×10(-7), 1×10(-6), and 1×10(-5) mol/L significantly increased the AFC in HVT ventilated rats (all P<0.05). This effect of phenylephrine on AFC was suppressed by prazosin, atenolol, and ICI-118551 in HVT ventilated rats by 53%, 31%, and 37%, respectively (all P<0.05). The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain, respectively (both P<0.05). Colchicine significantly inhibited the effect of phenylephrine (P=0.031). CONCLUSION: Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the absorption of pulmonary edema.

CONUT can be a predictor of postoperative complications after laparoscopic-assisted radical gastrectomy for elderly gastric cancer patients.

Compared with young patients, elderly patients with gastric cancer usually have lower muscle mass, poorer nutritional status, lower immunity, and worse cardiopulmonary function. Therefore, how to improve the prognosis of elderly gastric cancer patients after laparoscopic-assisted radical gastrectomy is the focus and difficulty of clinician. The aim of our study was to investigate the risk factors for postoperative complications of these patients. The data of gastric cancer patients aged ≥ 60 years who underwent laparoscopic-assisted radical gastrectomy were analyzed. Univariate was used to determine the potential risk factors and then multivariate analyses was used to determine the independent risk factors for postoperative complications. Univariate analysis showed that age, preoperative red blood cell (RBC), preoperative albumin (ALB), preoperative C-reactive protein (CRP), preoperative hemoglobin (Hb), preoperative blood transfusion, preoperative lymphocytes, total cholesterol, CRP-to-ALB ratio, controlling nutritional status (CONUT) score, TNM stage were all the potential risk factors for postoperative complications. Binary logistic regression showed that CONUT, age and preoperative RBC were correlated with postoperative complications. For elderly gastric cancer patients after laparoscopic-assisted radical gastrectomy, CONUT, age and preoperative RBC were all the independent risk factors for overall postoperative complications and could be used as reliable indicators for judging the short-term prognosis.

Cellulose nanocrystal as an enhancing core for antitumor polymeric micelles to overcome biological barriers.

Polymeric micelles are extensively studied nanocarriers to improve the solubility, blood circulation, biodistribution, and adverse effects of chemotherapeutic drugs. However, the antitumor efficacy of polymeric micelles is often restricted due to multiple biological barriers, including blood fluid shear stress (FSS) and limited tumor penetration in vivo. Herein, cellulose nanocrystal (CNC) as a green material with rigidity and rod-shaped structure is developed to be an enhancing core for polymeric micelles to overcome these biological barriers. Doxorubicin (DOX) loaded methoxy poly (ethylene glycol)-block-poly (D, L-lactic acid) (mPEG-PLA, PP) ligated CNC nanoparticles (PPC/DOX NPs) are fabricated via one-pot synthesis. In comparison to the self-assembled DOX loaded mPEG-PLA micelles (PP/DOX NPs), PPC/DOX NPs exhibit remarkable improvements in FSS resistance, cellular internalization, blood circulation, tumor penetration, and antitumor efficacy owing to the unique rigidity and rod-shaped structure of CNC core. Moreover, PPC/DOX NPs present various advantages beyond DOX·HCl and CNC/DOX NPs. The superiority of PPC/DOX NPs in antitumor efficacy reveals the effectiveness of adopting CNC as the enhancing core for polymeric micelles, suggesting that CNC is a promising biomaterial in advancing nanomedicine.

Engineering the Intestinal Lymphatic Transport of Oral Nanoparticles to Educate Macrophages for Cancer Combined Immunotherapy.

The effectiveness of the commonly used therapy is low for treating triple-negative breast cancer (TNBC). Macrophages, accounting for up to 50% of the TNBC tumor mass, are involved in innate and adaptive immunity, which can serve as an effective weapon against TNBC via combined immunotherapy. Here, we engineered mannose and glycocholic acid-modified trimethyl chitosan (MTG) nanoparticles (NPs) encapsulating signal regulatory protein α (SIRPα) siRNA (siSIRPα, a macrophage checkpoint inhibitor) and mucin 1 (MUC1) pDNA (pMUC1, a therapeutic pDNA vaccine) (MTG/siSIRPα/pMUC1 NPs) for in situ educating macrophages via an oral route to exert the cooperative antitumor effects of siSIRPα and pMUC1. Orally delivered MTG-based NPs accumulated in the macrophages in lymph nodes and tumor tissues via the intestinal lymphatic transport pathway, leading to strong cellular immunity responses. Following the transfection of orally administered MTG/siSIRPα/pMUC1 NPs within the same macrophages, siSIRPα strengthened the pMUC1 vaccine-induced systemic cellular immunity, while pMUC1 enhanced siSIRPα-mediated macrophage phagocytosis, M1-phenotype polarization, and tumor microenvironment (TME) remodeling at the tumor sites, thereby inhibiting the growth and metastasis of TNBC. The simultaneous achievements of the mutual promotion of innate and adaptive immunity in the local TME and in the whole body suggested that MTG/siSIRPα/pMUC1 NPs would provide a promising paradigm for the combined immunotherapy of TNBC via oral delivery of genes.

Identification of key genes and pathways associated with diabetes of the exocrine pancreas.

This study aimed to identify potential essential genes and pathways in diabetes of the exocrine pancreas (DEP) and explore possible molecular mechanisms. The array dataset GSE76895 was downloaded from the Gene Expression Omnibus database. Pancreatic tissue samples from 20 Diabetes of the exocrine pancreas and 32 nondiabetic individuals were selected for analysis. GEO2R analyzed differentially expressed genes (DEGs) in the 2 groups. Gene ontology annotation, Kyoto Encyclopedia of Genes Genomes and Reactome pathway enrichment analyses and Gene Set Enrichment Analysis were performed in this study. Protein-protein interaction (PPI) networks were constructed using Cytoscape software, and core networks were identified using MCODE plugins. A total of 62 genes, including 59 up-regulated and 3 down-regulated genes, were differentially expressed in DEP samples compared with nondiabetic patients. PPI network with 53 nodes and 138 edges was established. HLA-DRA is identified as the central gene of the PPI network and maybe a marker gene for DEP. Furthermore, up-regulated DEGs are mainly enriched in pathways related to the immune system and infection. The results of this study suggest that HLA-DRA and immune system pathways may play essential roles in DEP.

Elevated Albumin to Globulin Ratio on Day 7 is Associated with Improved Function Outcomes in Acute Ischemic Stroke Patients with Intravenous Thrombolysis.

Background and Purpose: Albumin to globulin ratio (A/G) has been established as a representative biomarker for assessing inflammation and nutritional status. However, the prognostic value of A/G has rarely been reported in acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT). Methods: A total of 311 AIS patients who had undergone IVT and completed 3-month follow-up were retrospectively recruited in this study. Albumin (Alb), globulin (Glb) and A/G on admission, within 24 hours after IVT and on day 7 were recorded. Poor outcome was defined as death or major disability (modified Rankin Scale, 3-6) at 3 months. Results: Among the 311 cases, 260 patients had admission blood samples, 296 cases had blood samples within 24 hours after IVT and 126 cases had blood samples on day 7. The patients with and without available blood samples were well-balanced. During the first 24 h, we observed A/G to increase significantly compared with baseline whereas at day 7 it was almost back to baseline in patients with a poor outcome. Receiver operating characteristic (ROC) curves analysis showed that A/G had a better performance in discriminating patients at high risk and low risk of a poor outcome than either Alb or Glb alone and carried the highest predictive ability on day 7 (AUC = 0.807). Lower 7-day A/G was independently associated with a poor outcome (per-SD increase, OR = 0.182, 95% CI: 0.074-0.446). Conclusion: A/G is an important prognostic indicator for AIS outcomes and merits dynamic monitoring.

Admission Random Blood Glucose, Fasting Blood Glucose, Stress Hyperglycemia Ratio, and Functional Outcomes in Patients With Acute Ischemic Stroke Treated With Intravenous Thrombolysis.

BACKGROUND: Stress hyperglycemia ratio (SHR), calculated as glucose/glycated hemoglobin, has recently been developed for assessing stress hyperglycemia and could provide prognostic information for various diseases. However, calculating SHR using random blood glucose (RBG) drawn on admission or fasting blood glucose (FBG) could lead to different results. This study intends to evaluate the association between SHR and functional outcomes in patients with acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (r-tPA) intravenous thrombolysis. METHODS: Data from 230 patients with AIS following thrombolytic therapy with r-tPA in the Third Affiliated Hospital of Wenzhou Medical University from April 2016 to April 2019 were retrospectively reviewed. SHR1 was defined as [RBG (mmol/L)]/[HbA1c (%)] and SHR2 was defined as [FBG (mmol/L)]/[HbA1c (%)]. The outcomes included early neurological improvement (ENI), poor function defined as a modified Rankin Scale score (mRS) of 3-6, and all-cause death in 3 months. Multivariable logistic regression was performed to estimate the association between SHR and adverse outcomes. RESULTS: After adjustment for possible confounders, though patients with AIS with higher SHR1 tend to have a higher risk of poor outcome and death and unlikely to develop ENI, these did not reach the statistical significance. In contrast, SHR2 was independently associated with poor functional outcome (per 0.1-point increases: odds ratios (OR) = 1.383 95% CI [1.147-1.668]). Further adjusted for body mass index (BMI), triglyceride-glucose index (TyG), and diabetes slightly strengthen the association between SHR (both 1 and 2) and adverse outcomes. In subgroup analysis, elevated SHR1 is associated with poor functional outcomes (per 0.1-point increases: OR = 1.246 95% CI [1.041-1.492]) in non-diabetic individuals and the association between SHR2 and the poor outcomes was attenuated in non-cardioembolic AIS. CONCLUSION: SHR is expected to replace random or fasting glucose concentration as a novel generation of prognostic indicator and a potential therapeutic target.

The effect of influenza virus A on th1/th2 balance and alveolar fluid clearance in pregnant rats.

ABSTRACT Pregnant women are more prone to H1N1 infection and often with severe complications. The authors studied the influence of H1N1 infection on T-helper cell type 1/type 2 (Th1/Th2) balance and alveolar fluid clearance (AFC) in pregnant rats. The pregnant rats were infected intranasally with influenza virus. Peripheral blood interferon-γ (IFN-γ) and interleukin-4 (IL-4) were measured by enzyme-linked immunosorbent assay (ELISA) and AFC was estimated by albumin concentration in alveolar lavage. The ratio of IFN-γ/IL-4 in nonpregnant rats was 21 ± 7. There was significant increase in both cytokines in infected pregnant rats compared with noninfected counterparts, with dramatic reduction in IFN-γ/IL-4 ratio (8 ± 3) compared to that (15 ± 8) in normal pregnant group. AFC of normal nonpregnant rats was 17% ± 3% and H1N1 infection reduced it to 11% ± 2%. AFC of normal pregnant rats was 22% ± 2% and H1N1 infection reduced it to 10% ± 2%. Dexamethasone reversed AFC in both nonpregnant and pregnant groups (14% ± 4% and 13% ± 2%, respectively). These results show that influenza virus A infection leads to Th2-biased immunity and reduces AFC in normal rats, and further worsens these in pregnant rats. Dexamethasone reverses these effects in both pregnant and nonpregnant rats.

Stool Saponified Fatty Acid, Behavior, Growth, and Stool Characteristics in Infants Fed a High-OPO Formula: A Randomized, Double-Blind Clinical Trial.

Objective: 1,3-Dioleoyl-2-palmitoylglycerol (OPO) is an ideal structured triglyceride for infant formula, with a similar structure to human milk fat. We conducted this randomized, double-blind controlled, single-center trial to evaluate the effects of an OPO formula in infants. Study Design: One hundred seventy-four healthy term infants <14 days old were assigned to the standard formula-fed group (n = 55), high sn-2 palmitic acid (OPO) formula-fed infants (n = 58), and breastfed (BF) group (n = 61). The primary endpoint was the total saponified fatty acid content in feces at week 6 and week 12. Results: Infants from the OPO group had lower concentrations of fecal saponified fatty acids than those from the standard formula group (p < 0.0001) at week 6 and week 12. The frequencies of crying per day and per night of infants in the OPO group were significantly less than those of infants in the standard formula group (p < 0.0001). After 12 weeks of feeding, the length of infants was significantly higher in the OPO group than in the other two groups (p = 0.002). Infants in the OPO group had a significantly lower stool calcium concentration and a higher stool frequency per day than infants in the standard formula group. Conclusion: In summary, a high concentration of OPO in formula is beneficial to the growth and development of infants.

Effects of vermicompost fertilization on soil, tomato yield and quality in greenhouse.

The excessive use of chemical fertilizer on vegetables in protected facilities resulted in soil degradation, serious soil-borne diseases, and lower vegetable yield and quality. We examined the effects of vermicompost on soil nutrient, enzyme activities, microbial quantity, tomato growth, yield and quality in greenhouse. The results showed that both broadcast and furrow application of vermicompost improved soil environment, and significantly increased contents of soil organic matter and soil nutrients (nitrogen, phosphorus and potassium). Vermicompost application significantly increased sucrase and catalase activities, abundance of bacteria and actinomycetes, and decreased the abundance of fungi in the soil. Furrow application but not the broadcast application promoted the growth of tomato plants. The vermicompost promoted root activities and leaf photosynthesis, increased chlorophyll, nitrogen and potassium contents in leaves. Broadcast and furrow application of vermicompost significantly increased tomato yield by 22.7% and 32.6%, respectively. Furrow application increased the contents of soluble protein, soluble sugar, vitamin C and titratable acid by 66.1%, 11.0%, 122.6% and 29.9%, respectively, and decreased nitrate content in tomato fruits by 65.7%. However, broadcast application did not affect fruit quality.