COVID-19 caused by SARS-CoV-2 infection poses a great threat to the lives of people around the world and has become a major global public health challenge. The innate immune system is the body's first line of defense against viral invasion and plays an important role in the development of COVID-19. As the main immune cells in the innate immune system, monocyte macrophages have pattern recognition receptors on their surface that recognize SARS-CoV-2 singlestranded RNA and damage associated molecular patterns(DAMPs) and induce antiviral innate immune responses. However,SARS-CoV-2 has a strong immune escape ability and can rapidly expand and replicate in host cells and induce host cell death, which further induces an inflammatory response and exacerbates COVID-19. Studies have shown that macrophage infiltration-induced hyperinflammatory responses(i.e., cytokine storms) are an important lethal mechanism of COVID-19,and that during SARS-CoV-2 infection, the over-activation of glycolysis is an important metabolic mechanism for viral immune escape and inflammatory response. This paper reviews the related research progress of glucose metabolism in the innate immune response against SARS-CoV-2.

Objective To explore the effect of stress hyperglycemia (SHG) on new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI). Methods A total of 1 321 patients with non-diabetic AMI who were admitted to the hospital from February 2024 to February 2025 were retrospectively selected. The occurrence of SHG was assessed according to the blood glucose level at admission. All patients received standard treatment after admission. The occurrence of NOAF during hospitalization was recorded. According to the presence or absence of NOAF occurrence, the patients were classified into NOAF group (n=118) and no-NOAF group (n=1,203). The clinical data of the two groups were collected and compared. Multivariate logistic regression analysis was applied to analyze the factors influencing the occurrence of NOAF in AMI patients. Results Among the 1 321 patients, 369 cases (27.93%) had SHG according to their blood glucose test at admission. After the completion of hospitalization, 118 of the 1321 patients developed NOAF, with an incidence rate of 8.93%. Multivariate logistic regression analysis revealed that SHG (OR=2.776, 95%CI: 1.384-5.567), smoking history (OR=2.680, 95%CI: 1.457-4.931), Killip grading at admission (OR=2.779, 95%CI: 1.361-5.671), Gensini score (OR=1.119, 95%CI: 1.038-1.205), time from onset to revascularization (OR=1.114, 95%CI: 0.973-1.275), and NT-proBNP (OR=1.123, 95%CI: 1.049-1.203) were independent influencing factors of NOAF in patients with AMI (P<0.05). Conclusion SHG, smoking history, Killip grading at admission, Gensini score, NT-proBNP, and time from onset to revascularization may influence the occurrence of NOAF in AMI patients during hospitalization, which should be given high attention.

Objective:To investigate the efficacy and mechanism of canagliflozin (Cana) in the treatment of high glucose-induced human podocyte (HPC) injury.Methods:The HPCs were divided into 5 groups: normal glucose group (NG group), mannitol group (MA group), high glucose group (HG group), Cana low dose (0.3 μmol/L) group and Cana high dose (1.0 μmol/L) group. Western blotting was used to examine the protein expressions of membrane-associated guanylate kinase inverted-2 (MAGI2), podocyte-associated protein nephrin, sodium-glucose transporter 2 (SGLT2), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis- associated speck-like protein containing a CARD (ASC), and cleaved-caspase1 in podocytes. Phalloidin staining of F-actin in podocytes was used to observe cytoskeletal injury. Intracellular reactive oxygen species (ROS) level of HPC was detected by the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe. Levels of interleukin (IL)-18 and IL-1β in culture medium of podocytes were detected by enzyme-linked immunosorbent assay (ELISA).Results:(1) Compared with the NG group, the protein expressions of MAGI2 and nephrin decreased (both P<0.01), the protein expression of SGLT2 increased ( P<0.01), the changes of cell morphology and cytoskeleton remodeling were obvious, intracellular ROS level increased ( P<0.01), while NLRP3, ASC and cleaved-caspase1 protein expressions decreased in the HG group (all P<0.01). The results of ELISA showed that IL-18 and IL-1β concentrations were higher in the HG group (both P<0.05). (2) Compared with the HG group, in the Cana groups, MAGI2 and nephrin expressions up-regulated (both P<0.01), the changes of cell morphology and cytoskeleton remodeling were alleviated. Meanwhile the Cana groups showed decreased SGLT2 expression ( P<0.05), lower ROS level, down- regulated NLRP3, ASC, cleaved-caspase1 expressions (all P<0.01), and decreased concentrations of IL-18 and IL-1β in culture medium of podocytes (both P<0.05). Conclusion:Cana can improve high glucose-induced injury and inflammation in human podocyte, possibly due to the repression of the ROS/NLRP3 signaling pathway.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective:To investigate the impact of the progesterone concentration on human chorionic gonadotropin (hCG) trigger day in fresh cycles versus thawed transfer cycles (the freeze-all strategy) with an antagonist protocol, and to compare the differences in clinical outcomes.Methods:This retrospective cohort study included a total of 2 165 cycles conducted at Henan Provincial People′s Hospital with cleavage-stage embryo (at least one top-quality) transfer between January 2017 and December 2023, with serum progesterone levels on hCG trigger day all≤6.34 nmol/L (i.e. 2 ng/ml). Multivariate logsitic regression analysis and curve fitting were performed based on different serum progesterone levels on hCG trigger day [≤3.17 nmol/L (i.e. 1 ng/ml) or 1-2 ng/ml].Results:Multivariate regression analysis, by using cycle type (either fresh or frozen-thawed cycle) as the exposure variable, showed that the clinical pregnancy rate (≤1 ng/ml: OR=0.93, 95% CI: 0.75-1.14; 1-2 ng/ml: OR=1.05, 95% CI: 0.58-1.87) and live birth rate (≤1 ng/ml: OR=0.90, 95% CI: 0.71-1.13; 1-2 ng/ml: OR=1.53, 95% CI: 0.79-3.00) had no statistically significant differences in group of progesterone concentration ≤1 ng/ml or in group of 1-2 ng/ml. Using serum progesterone levels on hCG trigger day as a continuous variable for curve fitting analysis, the clinical pregnancy rate in fresh or thawed cycles showed no significant changes with increasing progesterone levels. Conclusions:In the antagonist protocol with cleavage-stage embryo transfer (at least one top-quality), when the serum progesterone level on hCG day is ≤2 ng/ml, there are no significant differences in clinical outcomes between thawed cycles and fresh cycles, including clinical pregnancy rate and live birth rate. Transferred in fresh cycles or choosing the freeze-all strategy could be selected based on the actual situation of the patients.

BACKGROUND: Previous studies have shown that lymph node metastasis only occurs in some mixed ground-glass nodules (mGGNs) which the pathological results were invasive adenocarcinoma (IAC). However, the presence of lymph node metastasis leads to the upgrading of tumor-node-metastasis (TNM) stage and worse prognosis of the patients, so it is important to perform the necessary evaluation before surgery to guide the operation method of lymph node. The aim of this study was to find suitable clinical and radiological indicators to distinguish whether mGGNs with pathology as IAC is accompanied by lymph node metastasis, and to construct a prediction model for lymph node metastasis. METHODS: From January 2014 to October 2019, the patients with resected IAC appearing as mGGNs in computed tomography (CT) scan were reviewed. All the lesions were divided into two groups (with lymph node metastasis or not) according to their lymph node status. Lasso regression model analysis by applying R software was used to evaluate the relationship between clinical and radiological parameters and lymph node metastasis of mGGNs. RESULTS: A total of 883 mGGNs patients were enroled in this study, among which, 12 (1.36%) showed lymph node metastasis. Lasso regression model analysis of clinical imaging information in mGGNs with lymph node metastasis showed that previous history of malignancy, mean density, mean density of solid components, burr sign and percentage of solid components were informative. Prediction model for lymph node metastasis in mGGNs was developed based on the results of Lasso regression model with area under curve=0.899. CONCLUSIONS Clinical information combined with CT imaging information can predict lymph node metastasis in mGGNs.
Humans ; Lymphatic Metastasis ; Lung Neoplasms ; Adenocarcinoma ; Lymph Nodes ; Social Group

Objective To investigate the changes and formation mechanism of plasma endothelial microparticles (EMPs) in patients with acute pancreatitis (AP). Methods Blood samples were collected from 60 patients with AP who were treated in The First Affiliated Hospital of Anhui Medical University from August 2020 to June 2021, and these patients were divided into mild acute pancreatitis (MAP) group with 23 patients, moderate-severe acute pancreatitis (MSAP) group with 23 patients, and severe acute pancreatitis (SAP) group with 14 patients; 20 individuals who underwent physical examination were enrolled as control group.Differential centrifugation was used to obtain platelet-poor plasma, flow cytometry was used to measure the level of CD31 + CD41 - EMPs, and ELISA was used to measure the levels of endothelin-1(ET-1), von Willebrand factor (vWF), nitric oxide (NO), and vascular cell adhesion molecule-1(VCAM-1).HUVECs were stimulated by the plasma of AP patients, and then flow cytometry and qRT-PCR were used to measure the changes in EMPs, reactive oxygen species (ROS), and mitochondrial membrane potential and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1(ICAM-1), VCAM-1, NADPH oxidase, and P-selectin.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups and within each group.The chi-square test was used for comparison of categorical data between groups, and the Pearson correlation test was used for correlation analysis. Results Compared with the control group, the MAP, MSAP, and SAP groups had a significant increase in the level of EMPs (all P < 0.05).Compared with the MAP and MSAP groups, the SAP group had a significant increase in the level of EMPs (both P < 0.05).In the patients with AP, the level of EMPs was negatively correlated with Acute Physiology and Chronic Health Evaluation Ⅱ score, Bedside Index for Severity in Acute Pancreatitis, Ranson score, CT score, and C-reactive protein ( r =0.686 2, 0.777 3, 0.713 8, 0.771 8, and 0.473 9, all P < 0.01).Compared with the control group, the MAP, MSAP, and SAP groups had significant increases in the levels of ET-1, vWF, and VCAM-1 and a significant reduction in the level of NO (all P < 0.05).Compared with the control group, the MSAP and SAP groups had the plasma that promoted the release of a large amount of EMPs (both P < 0.05).Compared with the control group, all the other groups, except the MAP group in terms of VCAM-1 and eNOS, had significant increases in the mRNA expression levels of eNOS, iNOS, ICAM-1, P-selectin, VCAM-1, and NADPH oxidase (all P < 0.05).Compared with the HC group, the MAP, MSAP, and SAP groups and the LPS group had a significant increase in the level of ROS and a significant reduction in mitochondrial membrane potential in HUVECs (all P < 0.05). Conclusion There is a significant increase in the plasma level of EMPs in AP patients, which is correlated with the severity of pancreatitis.Meanwhile, the plasma of AP patients can promote the formation of EMPs in HUVECs in vitro, which may be associated with cell oxidative injury.

Objective:To explore the clinical characteristics of elderly patients with type 2 diabetes mellitus (T2DM) complicated with coronary atherosclerotic heart disease (CHD) and analyze the risk factors of CHD in patients with T2DM.Methods:Using the method of retrospective cohort study, 406 elderly male patients with T2DM (≥75 years old) admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University from January 2017 to January 2020 were selected and divided into T2DM without CHD group (165 cases) and T2DM with CHD group (241 cases). The clinical characteristics in elderly patients with T2DM complicated with CHD and risk factors for CHD were analyzed.Results:The age ((86.78±5.35 )years old), course of T2DM((12.32±0.46) years), fasting blood glucose(FPG)((7.64±2.81) mmol/L), hemoglobin a1c (HbA1c)((7.59±1.21)%), the proportion of hypertension(84.65%(204/241)), D-dimer((0.50±0.13) mg/L), the incidence of thromboembolic events(46.06%(111/241)), blood serum creatinine ((94.81±12.70) μmol/L), urea nitrogen((8.31±4.46) mmol/L), uric acid((376.44±116.01) μmol/L) in T2DM with CHD group were higher than those in T2DM without CHD((78.51±4.81)years old, (10.66±0.67)years, (6.84±2.19) mmol/L, (7.02±2.15)%, 63.03%(104/165), (0.21±0.04 ) mg/L, 13.33%(22/165), (83.01±14.40) μmol/L, (6.79±2.89) mmol/L, (333.56±95.15) μmol/L ), and the differences were statistically significant( t=15.908, t=2.042, t=3.055, t=3.088, χ 2=23.828, t=5.059, χ 2=42.098, t=2.401, t=4.188, t=4.075; all P<0.05). The total bilirubin(TBil)(8.80(6.60, 11.60) μmol/L), glomerular filtration rate(GFR)((76.49±29.80) mL/(min·1.75 m 2)) in T2DM with CHD group were lower than those in T2DM without CHD group (11.25(8.23, 15.28) μmol/L, (91.81±28.31) mL/(min·1.75 m 2)), the differences were statistically significant( Z=2.304, t=5.126; all P<0.001). The total cholesterol((3.84±0.85) mmol/L), low-density lipoprotein cholesterol(LDL-C)((2.12±0.68 ) mmol/L) in T2DM with CHD group were lower than those in T2DM without CHD group((4.10±1.00) mmol/L, (2.45±0.85) mmol/L), the differences were statistically significant( t=2.828, 4.156; all P<0.05). The rate of starting lipid-lowering and stable plaque treatment in T2DM with CHD group (82.57%(199/261))was higher than that in T2DM without CHD group(42.42%(70/165)), and the difference was statistically significant (χ 2=70.614, P<0.001). Influenced by lipid-lowering therapy, the total cholesterol and LDL-C in T2DM patients with CHD were significantly decreased.Logistic regression analysis showed that age elevated( OR 1.346, 95% CI 1.263-1.434, P<0.001), elevated hemoglobin a1c concentration( OR 1.427, 95% CI 1.140-1.785, P=0.002), complicated with hypertension( OR 3.534, 95% CI 1.684-7.418, P=0.001), elevated D-dimer concentration( OR 3.969, 95% CI 1.227-12.841, P=0.021)and elevated uric acid concentration( OR 1.005, 95% CI 1.001-1.008, P=0.006)were independent risk factors for CHD in elderly male patients with T2DM. Conclusion:Elderly patients with T2DM complicated with CHD are more likely to be in hypercoagulable state, more likely to have thromboembolic events, and more obvious renal function damage.Poor fasting blood glucose control and decreased total bilirubin concentration are the influencing factors of CHD in elderly male patients with T2DM.Age elevated, elevated hemoglobin a1c concentration, complicated with hypertension, elevated D-dimer concentration and elevated uric acid concentration are independent risk factors for CHD in elderly male patients with T2DM.

Objective:To study the complications of irreversible electroporation (nano-knife) ablation on locally advanced pancreatic cancer, and to analyse the causes of complications and related treatment.Methods:The clinical data of 36 patients with locally advanced pancreatic cancer treated with nano-knife ablation at the Fifth Affiliated Hospital of Zhengzhou University from January 2016 to March 2019 were studied retrospectively. The types and incidence of postoperative complications were analyzed. The complications were classified according to the Clavien-Dindo classification, and the severity of the complications was evaluated.Results:There were 15 patients (41.7%) who developed various degrees of complications, including splenic infarction, atrial fibrillation, portal vein thrombosis, pancreatic fistula, pseudoaneurysm, gastrointestinal bleeding, liver abscess and severe pancreatitis. Among them, 6 patients (16.7%) had grade III complication or above. Three (8.3%) patients with grade Ⅲ complications died of upper gastrointestinal bleeding 3 months after operation.Conclusions:Various complications might occur after nano-knife ablation, with postoperative gastrointestinal and abdominal bleeding being the main complications which resulted in death. Measures which can effectively reduce occurrence of complications need to be studied.