Encephalomyocarditis virus(EMCV)is a zoonotic pathogen that causes encephalitis and myocarditis as its primary clinical manifestations.To explore effective preventive measures,this study utilized a Bac-to-Bac expression system to insert the EMCV P12A and 3C genes into the pFastBacDual shuttle vector,resulting in the generation of the recombinant baculovirus Ac-P12A-3C.This facilitated the large-scale expression and purification of EMCV virus-like particles(VLPs),which were correctly assembled into particles of approximately 30 nm in diameter,as ob-served by electron microscopy.Immunization and challenge experiments in mice demonstrated that these VLPs could effectively protect against EMCV infection,achieving a protection rate of 100％.Histopathological sections indicated that,compared to the PBS control group,the VLP immuniza-tion group exhibited significantly reduced tissue damage,along with a marked decrease in viral load within the tissues.In piglets,immunization with the VLPs elicited a robust humoral response,with neutralizing antibody titers reaching 1∶320 to 1∶640 after a second immunization,and no signifi-cant adverse reactions were observed throughout the immunization process.This study preliminarily explores the immunogenicity and safety of the VLP vaccine,laying the foundation for the development of a subunit vaccine based on EMCV VLPs and offering a new strategy for the prevention and control of encephalomyocarditis.

Encephalomyocarditis virus(EMCV)is a zoonotic pathogen that causes encephalitis and myocarditis as its primary clinical manifestations.To explore effective preventive measures,this study utilized a Bac-to-Bac expression system to insert the EMCV P12A and 3C genes into the pFastBacDual shuttle vector,resulting in the generation of the recombinant baculovirus Ac-P12A-3C.This facilitated the large-scale expression and purification of EMCV virus-like particles(VLPs),which were correctly assembled into particles of approximately 30 nm in diameter,as ob-served by electron microscopy.Immunization and challenge experiments in mice demonstrated that these VLPs could effectively protect against EMCV infection,achieving a protection rate of 100％.Histopathological sections indicated that,compared to the PBS control group,the VLP immuniza-tion group exhibited significantly reduced tissue damage,along with a marked decrease in viral load within the tissues.In piglets,immunization with the VLPs elicited a robust humoral response,with neutralizing antibody titers reaching 1∶320 to 1∶640 after a second immunization,and no signifi-cant adverse reactions were observed throughout the immunization process.This study preliminarily explores the immunogenicity and safety of the VLP vaccine,laying the foundation for the development of a subunit vaccine based on EMCV VLPs and offering a new strategy for the prevention and control of encephalomyocarditis.

Objective:To investigate the clinical value of AB classification combined with Arima classification for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCC).Methods:From July 2017 to December 2022, 76 cases of SESCC receiving endoscopic submucosal dissection and intra-epithelial papillary capillary loops (IPCL) AB classification as type B2 in Ningbo Medical Center Lihuili Hospital and Jiangsu Province Hospital of Chinese Medicine were included in the study. IPCL was reclassified according to Arima classification. The depth of infiltration determined by pathology was the gold standard. The sensitivity, the specificity, the positive predictive value and the negative predictive value of B2-Arima combined classification in predicting the invasion depth of SESCC were analyzed.Results:In the 76 cases of type B2 IPCL lesions, 31 cases (40.79%) were T1a-MM/T1b-SM1 SESCC. The sensitivity, the specificity, the positive predictive value, the negative predictive value and the diagnostic accuracy of type B2 IPCL to predict T1a-MM/T1b-SM1 SESCC were 70.45% (31/44), 79.64% (176/221), 40.79% (31/76), 93.12% (176/189), and 78.11% (207/265), respectively. After Arima classification, the above corresponding indicators of type B2-4ML and type B2-AVA-4M IPCL in predicting T1a-MM/T1b-SM1 SESCC were 61.36% (27/44), 88.24% (195/221), 50.94% (27/53), 91.98% (195/212), 83.77% (222/265) and 38.64% (17/44), 94.57% (209/221), 58.62% (17/29), 88.56% (209/236), 85.28% (226/265), respectively.Conclusion:B2 IPCL combined with Arima classification can improve the diagnostic accuracy of T1a-MM/T1b-SM1 ESSCC.

Objective:To systematically evaluate the effects of liver and kidney function on the occurrence of thrombocytopenia induced by linezolid and the population pharmacokinetic characteristics of linezolid, so as to provide guidance for the individualization of linezolid in patients with liver and renal insufficiency.Methods:Relevant databases at home and abroad have been searched up to November 2023. The literature about the influence of liver and kidney function on linezolid-induced thrombocytopenia were analyzed using the Rev Man 5.4 statistical software, and the effect sizes were odds ratio ( OR) and standardized mean difference ( SMD) with their 95% confidence interval ( CI) in the meta-analysis. The literature on population pharmacokinetic studies of linezolid were summarized and systematically reviewed. Results:A total of 32 literature were included in the meta-analysis, including 4 112 patients. Among them, 1 458 (35.5%) developed thrombocytopenia and 2 654 (64.5%) did not. The meta-analysis results showed that the risk of linezolid-induced thrombocytopenia in the renal insufficiency patients was higher than that in patients with normal renal function [47.9% (594/1 241) vs. 25.8% (493/1 912), OR=3.24, 95% CI: 2.31-4.53], and the lower baseline creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) were associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05); the risk of thrombocytopenia induced by linezolid in patients with liver dysfunction was higher than that in patients with normal liver function [47.6% (119/250) vs. 33.9% (360/1 061), OR=2.36, 95% CI: 1.73-3.22], and the higher baseline total bilirubin (TBil) was associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05). A total of 15 articles were included in the review of population pharmacokinetic study, 11 of which were based on self-built or publicly published population pharmacokinetic models and used Monte Carlo simulation to evaluate the efficacy and safety probabilities in different dosing regimens of linezolid. Among them, there were 5 and 2 articles optimized the dosing regimen of linezolid in patients with renal and liver insufficiency, respectively. Conclusions:Liver and renal insufficiency increases the risk of linezolid-induced thrombocytopenia, and baseline levels of Ccr, eGFR, and TBil can serve as sensitive indicators for predicting the risk. Patients with liver and renal insufficiency can use population pharmacokinetic models for an optimized linezolid regimen before treatment to reduce the risk of linezolid-induced thrombocytopenia.

Objective:To systematically evaluate the effects of liver and kidney function on the occurrence of thrombocytopenia induced by linezolid and the population pharmacokinetic characteristics of linezolid, so as to provide guidance for the individualization of linezolid in patients with liver and renal insufficiency.Methods:Relevant databases at home and abroad have been searched up to November 2023. The literature about the influence of liver and kidney function on linezolid-induced thrombocytopenia were analyzed using the Rev Man 5.4 statistical software, and the effect sizes were odds ratio ( OR) and standardized mean difference ( SMD) with their 95% confidence interval ( CI) in the meta-analysis. The literature on population pharmacokinetic studies of linezolid were summarized and systematically reviewed. Results:A total of 32 literature were included in the meta-analysis, including 4 112 patients. Among them, 1 458 (35.5%) developed thrombocytopenia and 2 654 (64.5%) did not. The meta-analysis results showed that the risk of linezolid-induced thrombocytopenia in the renal insufficiency patients was higher than that in patients with normal renal function [47.9% (594/1 241) vs. 25.8% (493/1 912), OR=3.24, 95% CI: 2.31-4.53], and the lower baseline creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) were associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05); the risk of thrombocytopenia induced by linezolid in patients with liver dysfunction was higher than that in patients with normal liver function [47.6% (119/250) vs. 33.9% (360/1 061), OR=2.36, 95% CI: 1.73-3.22], and the higher baseline total bilirubin (TBil) was associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05). A total of 15 articles were included in the review of population pharmacokinetic study, 11 of which were based on self-built or publicly published population pharmacokinetic models and used Monte Carlo simulation to evaluate the efficacy and safety probabilities in different dosing regimens of linezolid. Among them, there were 5 and 2 articles optimized the dosing regimen of linezolid in patients with renal and liver insufficiency, respectively. Conclusions:Liver and renal insufficiency increases the risk of linezolid-induced thrombocytopenia, and baseline levels of Ccr, eGFR, and TBil can serve as sensitive indicators for predicting the risk. Patients with liver and renal insufficiency can use population pharmacokinetic models for an optimized linezolid regimen before treatment to reduce the risk of linezolid-induced thrombocytopenia.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective To investigate the change situation of serum pepsinogen (PG) and gastrin-17(G-17) levels change in gastric cancer,and on this basis diagnostic significance of combined detection of carbohydrate antigen 72-4 (CA72-4) and 13C urea breath test (13C UBT) detection in early gastric cancer.Methods The enzyme-linked immunosorbent (ELISA) method was used to detect serum PG Ⅰ,PG Ⅱ and G-17 levels in healthy people,atrophic gastritis group and gastric cancer group.Firstly the changes of above three indicators were compared;then according to PG Ⅰ and G-17,the carcinoma group was divided into the group A,B,C and D,these four groups were detected the helicobacter pylori infection status by 13C UBT.Finally the CA72-4 levels were performed the statistics by using the tumor markers detection results.Results Serum PG Ⅰ level and PG Ⅰ/PG Ⅱ ratio in the control group,atrophic gastritis group and gastric cancer group was gradually declined,the difference was statistically significant (P＜0.05);serum G-17 level in the control group,atrophic gastritis group and gastric cancer group was gradually increased,the difference among 3 groups was statistically significant (P＜0.05);in early gastric cancer rate ratio among 4 groups,which in the group B was highest,the difference was statistically significant (P＜0.05);in the comparison of positive rates of 13 C UBT and CA72-4 level in early gastric cancer among 4 group,the 13 C UBT positive rate and CA72-4 level in the group B were higher than those in the group A,C and D,the differences were statistically significant (P＜0.05).Moreover the CA72-4 level in the group B had significant difference between early gastric cancer and advanced gastric cancer (P＜0.01).Conclusion Serum PG Ⅰ reduce and G-17 increase combined with CA72-4 high level and 13C UBT positive have an important forewarning value for the diagnosis of gastric cancer.

Objective To purify and rejuvenate the plant of Curcama kwangsiensis,improve the transplantation survival rate of cultivars,and make the convenience of storagement and management for the cultivars production.Methods The rhizome plantlet formation of C.kwangsiensis was induced by regulating both of macro-element and sucrose concentration in the MS culture medium.Results Both of them were very important influence factors on the rhizome plantlet formation of C.kwangsiensis.Media 1/2 MS and 6% sucrose were adaptable to the rhizome plantlet formation of C.kwangsiensis,had the best effects on the formation rate of the rhizome plantlet,diameter and direct transplanting rate of the rhizome plantlet.Both plantlet and root system development were stronger.Conclusion In the present research,it is successful in inducing the rhizome plantlet formation of C.kwangsiensis.