As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective:To investigate the CLEC3B protein of differentially expressed proteins(DEPs)in serum of normal persons and patients with sepsis,and explore the possibility that target C-type lectin domain family 3 member B(CLEC3B)protein was used as molecular markers of sepsis.Methods:Peripheral bloods of 10 healthy persons and 18 patients with sepsis were collected,and the data of peripheral serum proteins were collected by data independent acquisition(DIA)method.The data were uploaded to iDEP online platform to analyze the DEPs in peripheral blood of patients with sepsis.Bioinformatics analysis of these DEPs was conducted to screen out the key proteins of sepsis.Enzyme linked immunosorbent assay(ELISA)was used to verify and plot the receiver operating characteristic(ROC)curves of key proteins.Results:A total of 138 differentially expressed proteins(DEPs)were screened out by using proteomics analysis,of which 34 kinds of proteins were significantly down-regulated and 104 kinds of proteins were significantly up-regulated.DEPs mostly concentrated in cellular processes,biological regulation,biological process regulation,participating binding,catalytic activation,molecular function regulation,immune system,signal transduction and so on.A protein-protein interaction network was constructed by DEPs,which screened out the key protein CLEC3B.ELISA results showed that the CLEC3B protein concentration[(297.73±22.00)ng/mL]of patients in the sepsis group was significantly lower than that[(452.42±191.72)ng/mL]in the healthy group,and the difference was statistically significant(t=13.13,P=0.000).The area under curve(AUC)value of ROC curve,sensitivity and specificity of CLEC38 protein were respectively 0.998,97.73%and 100.0%.Conclusion:CLEC3B is significantly decreased in sepsis group,which sensitivity and specificity are high.It can be used as a potentially biological diagnostic biomarker of sepsis.

Objective:To screen key differentially expressed genes(DEGs)in dead mice with sepsis by spleen high-through-put sequencing combined with bioinformatics.Methods:①A mouse sepsis model was set up by intraperitoneal injection of lipopolysac-charide(LPS),a 7-day survival curve of mice was drawn,and the modeling doses of survival group and death group were screened out.②Expressions of TNF-α,IL-1β,IL-6 and IL-10 in peripheral blood of mice in control group,survival group and death group were verified by ELISA.③High-throughput sequencing was conducted on spleens of survival group and death group,and the key genes were screened by bioinformatics analysis of DEGs.④Expressions of key genes and proteins were detected by RT-PCR and Western blot.Results:①LPS dosage in survival group was 15 mg/kg(with a mortality of 30%),and LPS dosage in death group was 30 mg/kg(with a mortality of 80%).②Expression levels of IL-6,TNF-α and IL-1β in sepsis mice were significantly higher than those of control group,while expression level of IL-10 was decreased(P<0.05).Comparison of sepsis model groups showed that levels of pro-inflammatory factors in death group were higher than those in survival group,while level of IL-10 was lower than that in survival group(P<0.05).③A total of 2999 DEGs in survival group and death group were screened out by bioinformatics,among which 1185 genes were up-regulated and 1814 genes were down-regulated.Top 5 DEGs enrichment pathways were screened out:"hematopoietic cell lineage""primary immunodeficiency""African trypanosomiasis""leishmaniasis"and"B-cell receptor signaling pathway".Ifit1,Ifit3 and Mx1 were three key genes that were screened out.④Compared with survival group,expressions of genes and proteins of Ifit1,Ifit3 and Mx1 were down-regulated in spleen tissues of the death group(P<0.05).Conclusion:By high-throughput sequencing and bioinformatics,Ifit1,Ifit3 and Mx1 are screened out as key genes related to the death outcome of sepsis,which probably influence the outcome of sepsis through the immune mechanism related to virus infection.

Objective To investigate the importance of echoendoscope in identifying common bile duct lesions associated with portal hypertension in liver cirrhosis.Methods From November 2022 to January 2023,a group of 37 individuals suffering from liver cirrhosis,portal hypertension,esophageal,and gastric varices underwent echoendoscope analysis to assess the common bile duct wall's thickness,its width,and to examine its cavity's dimensions.Result The common bile duct's wall exhibited roughness with 97.3%(36/37),with an average thickness of 0.19 cm,a width of 0.47 cm,and flocculent deposits constituting 73.0%(27/37).The typical bile duct exhibited curvature in 13.5%(5/37).None of the patients experienced bleeding either during or following the echoendoscope examination.Conclusion The use of echoendoscope distinctly reveals cirrhosis-induced common bile duct and portal hypertension;a majority of cirrhosis and portal hypertension sufferers exhibit inflammation in the common bile duct;this technique is deemed safe for assessing esophageal and gastric varices in cirrhosis patients.

Purpose/Significance The load balancing scheduling method is proposed to shorten the waiting time and balance the load of each machine in additive manufacturing of customized medical devices.Method/Process By analyzing the influencing factors in the time dimension,the mathematical model of the two-objective multi-constraint optimization problem is established.The load balancing operator is introduced and the load balancing scheduling algorithm is used to solve the model.Result/Conclusion The load balancing scheduling method with load balancing operators is superior to other algorithms in terms of task waiting time and load balancing perform-ance,especially for large-scale tasks.This method can effectively shorten task waiting time and realize machine load balancing.

Diabetic ulcer (DU), one of the common and serious complications in patients with diabetes mellitus, often leads to infection, necrosis and amputation, and has a long and costly treatment period. Because of DU's unclear healing mechanism and the difficulty of delayed healing, its treatment and management have been a major challenge in clinical medicine. In recent years, the potential role of mitochondrial autophagy in DU has become a research hotspot with the in-depth study of mitochondrial autophagy mechanism. Previous studies have shown that mitochondrial autophagy is an important intracellular self-repair mechanism that plays a crucial role in maintaining cellular health and functional stability. During the development of DU, mitochondrial autophagy plays multiple roles in attenuating oxidative stress and inflammatory responses, maintaining mitochondrial functional homeostasis, influencing cell proliferation and repair capacity during DU healing, promoting DU healing, and enhancing antimicrobial capacity. In this paper, we illustrate the multiple roles played by mitochondrial autophagy in DU prevention and treatment, as well as the potential applications of mitochondrial autophagy in DU therapy. It is expected to provide a basis for the clinical application of mitochondrial autophagy in DU treatment, and provide more effective strategies and solutions for the treatment of DU.

Diabetic ulcer (DU), one of the common and serious complications in patients with diabetes mellitus, often leads to infection, necrosis and amputation, and has a long and costly treatment period. Because of DU's unclear healing mechanism and the difficulty of delayed healing, its treatment and management have been a major challenge in clinical medicine. In recent years, the potential role of mitochondrial autophagy in DU has become a research hotspot with the in-depth study of mitochondrial autophagy mechanism. Previous studies have shown that mitochondrial autophagy is an important intracellular self-repair mechanism that plays a crucial role in maintaining cellular health and functional stability. During the development of DU, mitochondrial autophagy plays multiple roles in attenuating oxidative stress and inflammatory responses, maintaining mitochondrial functional homeostasis, influencing cell proliferation and repair capacity during DU healing, promoting DU healing, and enhancing antimicrobial capacity. In this paper, we illustrate the multiple roles played by mitochondrial autophagy in DU prevention and treatment, as well as the potential applications of mitochondrial autophagy in DU therapy. It is expected to provide a basis for the clinical application of mitochondrial autophagy in DU treatment, and provide more effective strategies and solutions for the treatment of DU.

Objective To explore the value of multi-parameter spectral CT for differentiating grade G2-3 pancreatic neuroendocrine tumor(pNET)and pancreatic neuroendocrine carcinoma(pNEC).Methods Preoperative double-layer detector spectral CT(DLCT)data of 35 patients with pNET(pNET group,including 25 cases of G2 grade and 10 cases of G3 grade)and 17 patients with pNEC(pNEC group)were retrospectively analyzed.Conventional CT and spectral CT parameters were compared between groups,and those being significant different between groups according to univariate analysis were respectively incorporated into multivariate logistic regression to select the independent predictors for identifying grade G2-3 pNET and pNEC.Conventional CT model and spectral CT model were constructed,and the combined model was constructed based on the two.The efficacy of each model for distinguishing grade G2-3 pNET and pNEC was evaluated.Results CT values of lesions during venous phase(OR=0.939,P=0.025)and vascular invasion(OR=5.049,P=0.027)shown on conventional CT were both independent predictors,and conventional CT model was constructed,its area under the curve(AUC)for distinguishing grade G2-3 pNET and pNEC was 0.808.Normalized iodine concentration during venous phase(OR=0.603)and normalized effective atomic number during venous phase(OR=0.847)on spectral CT were both independent predictors(both P＜0.05),and spectral CT model was constructed.The AUC of spectral CT model was 0.894,higher than that of conventional CT model(Z=2.127,P=0.033).The AUC of combined model was 0.924,higher than that of conventional CT model(Z=2.302,P=0.021)but not significantly different with that of spectral CT model(Z=0.827,P=0.408).Conclusion Multi-parameter spectral CT could effectively differentiate grade G2-G3 grade pNET and pNEC.

Objective:To investigate the efficacy of endoscopic retrograde cholangiopancreatography in the treatment of Child-Pugh C cirrhosis complicated by obstructive jaundice and its effects on liver function and infection indexes.Methods:The clinical data of 86 patients with Child-Pugh C cirrhosis complicated by obstructive jaundice who received treatment in the Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, from June 2017 to June 2022 were retrospectively analyzed. These patients were divided into an observation group ( n = 56) and a control group ( n = 30) according to different treatment methods. Patients in the observation group underwent endoscopic retrograde cholangiopancreatography and those in the control group received conservative drug treatment. After 14 days of treatment, clinical efficacy was compared between the two groups. The changes in liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptide (GGT)] and infection indicators [white blood cell count (WBC), procalcitonin (PCT), and C-reactive protein (CRP)] were compared between the two groups before and after treatment. The incidence of postoperative complications was compared between the two groups. At 6 months after treatment, the prognosis was compared between the two groups. Results:The total response rate in the observation group was 98.21% (55/56), which was significantly higher than 60.00% (18/30) in the control group ( Z = 23.43, P < 0.001). Before treatment, serum ALT, AST, GGT levels in the control group were (294.53 ± 45.19) U/L, (286.62 ± 17.15) U/L, and (304.53 ± 12.34) U/L, respectively, and they were (96.25 ± 16.7) U/L, (113.25 ± 8.56) U/L, (122.25 ± 9.24) U/L after 14 days of treatment. Before treatment, serum ALT, AST, and GGT levels in the observation group were (352.36 ± 70.23) U/L, (303.31 ± 12.12) U/L, and (368.36 ± 10.23) U/L, respectively, and they were (108.65 ± 12.38) U/L, (95.65 ± 6.54) U/L, and (85.66 ± 7.28) U/L, respectively, after 14 days of treatment. After treatment, serum ALT, AST, and GGT levels in each group were significantly decreased compared with those before treatment (observation group t = 22.54, 49.54, 64.76; control group t = 25.57, 112.83, 168.48, all P < 0.05). After treatment, the amplitude of decrease in serum ALT, AST, and GGT levels in the observation group were significantly greater than those in the control group ( t = 2.27, 3.18, 4.61, all P < 0.05). After treatment, PCT, CRP, and WBC in each group were significantly decreased compared with those before treatment (observation group: t = 11.68, 11.46, 5.42, control group: t = 20.39, 18.69, 19.02, all P < 0.05). After treatment, the amplitude of decrease in serum PCT, CRP, and WBC in the observation group were significantly greater than those in the control group ( t = 5.14, 1.67, and 2.11, all P < 0.05). Within 14 days after treatment, there were two cases of acute pancreatitis, one case of hyperamylasemia, and one case of transient biliary bleeding in the observation group. There was one case of acute pancreatitis in the control group. The incidence of complications in the observation group was slightly, but not significantly, higher than that in the control group ( P > 0.05). After treatment, 12 patients (40.00%) in the control group experienced worsening jaundice, and additional endoscopic retrograde cholangiopancreatography salvage treatment was given. After treatment, total bilirubin level decreased by > 50%, reaching the standard of significant efficacy. At 6 months after treatment, stent obstruction occurred in two patients, which was effectively treated by replacement. There were no deaths in each group during the follow-up period. Conclusion:Implantation of a nasobiliary duct or a biliary duct stent during endoscopic retrograde cholangiopancreatography is more effective at treating yelloxemia in patients with Child-Pugh C cirrhosis complicated by obstructive jaundice than medication. The former method can effectively relieve obstructive jaundice, smooth drainage, improve liver function, reduce infection, and be relatively safe.

Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.
Humans ; Mitophagy ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Cell Line ; Autophagy ; Apoptosis ; Membrane Proteins ; Proto-Oncogene Proteins/genetics* ; Tumor Suppressor Proteins/pharmacology*