Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.

Objective To evaluate the predictive value of neutrophil/high-density lipoprotein cholesterol ratio(NHR)combined with monocyte/lymphocyte ratio(MLR)for early rebleeding after endoscopic treatment in patients with cirrhosis complicated by acute esophagogastric variceal bleeding(AEVB).Methods A total of 228 patients with cirrhosis complicated by AEVB were included in this study.According to the occurrence of early rebleeding,patients were divided into the rebleeding group(96 cases)and the non-rebleeding group(132 cases).General information and laboratory indicators of both groups were collected,and the End-Stage Liver Disease(MELD)score,Child-Turcotte-Pugh(CTP)score,Fibrosis-4(FIB-4)index,NHR,and MLR were calculated.Logistic regression analysis was used to identify the risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.A nomogram model based on NHR and MLR was constructed to predict the risk of early rebleeding.The predictive performance and goodness of fit of the model were evaluated using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI).Results Compared with the non-rebleeding group,systolic blood pressure,platelet count(PLT),albumin/globulin ratio(A/G)and low-density lipoprotein cholesterol(LDL-C)were decreased in the rebleeding group,while total bile acids(TBA),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),activated partial thromboplastin time(APTT),thrombin time(TT),international normalized ratio(INR),Fibrosis-4(FIB-4),NHR,MLR,MELD score and CTP score were increased(P＜0.05).NHR was positively correlated with AST,TBIL and INR(P＜0.05).MLR was negatively correlated with PLT,and positively correlated with AST,TBIL and FIB-4(P＜0.05).Logistic regression analysis results showed that prolonged TT,elevated NHR and MLR were independent risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.The nomogram model based on NHR and MLR to predict early rebleeding had an area under the curve of 0.810(95%CI:0.754-0.866).The Hosmer-Lemeshow test suggested that the model fit well.IDI and NRI analyse showed that the combination of NHR and MLR had better predictive value for the early rebleeding than that of MELD score and CTP score.Conclusion NHR and MLR are effective indicators for predicting early rebleeding after endoscopic treatment in patients with cirrhosis complicated by AEVB.They are helpful in the early identification of high-risk patients and provide a reference for clinical intervention.

Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2～6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7～9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.

Objective To evaluate the predictive value of neutrophil/high-density lipoprotein cholesterol ratio(NHR)combined with monocyte/lymphocyte ratio(MLR)for early rebleeding after endoscopic treatment in patients with cirrhosis complicated by acute esophagogastric variceal bleeding(AEVB).Methods A total of 228 patients with cirrhosis complicated by AEVB were included in this study.According to the occurrence of early rebleeding,patients were divided into the rebleeding group(96 cases)and the non-rebleeding group(132 cases).General information and laboratory indicators of both groups were collected,and the End-Stage Liver Disease(MELD)score,Child-Turcotte-Pugh(CTP)score,Fibrosis-4(FIB-4)index,NHR,and MLR were calculated.Logistic regression analysis was used to identify the risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.A nomogram model based on NHR and MLR was constructed to predict the risk of early rebleeding.The predictive performance and goodness of fit of the model were evaluated using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI).Results Compared with the non-rebleeding group,systolic blood pressure,platelet count(PLT),albumin/globulin ratio(A/G)and low-density lipoprotein cholesterol(LDL-C)were decreased in the rebleeding group,while total bile acids(TBA),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),activated partial thromboplastin time(APTT),thrombin time(TT),international normalized ratio(INR),Fibrosis-4(FIB-4),NHR,MLR,MELD score and CTP score were increased(P＜0.05).NHR was positively correlated with AST,TBIL and INR(P＜0.05).MLR was negatively correlated with PLT,and positively correlated with AST,TBIL and FIB-4(P＜0.05).Logistic regression analysis results showed that prolonged TT,elevated NHR and MLR were independent risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.The nomogram model based on NHR and MLR to predict early rebleeding had an area under the curve of 0.810(95%CI:0.754-0.866).The Hosmer-Lemeshow test suggested that the model fit well.IDI and NRI analyse showed that the combination of NHR and MLR had better predictive value for the early rebleeding than that of MELD score and CTP score.Conclusion NHR and MLR are effective indicators for predicting early rebleeding after endoscopic treatment in patients with cirrhosis complicated by AEVB.They are helpful in the early identification of high-risk patients and provide a reference for clinical intervention.

Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2～6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7～9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.

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Objective:To analyze the prevalence of human respiratory syncytial virus（RSV）and the evolutionary characteristics of the adhesion glycoprotein（G）gene in Xi'an from 2023 to 2024.Methods:Respiratory specimens were collected from patients with acute respiratory infections in Xi'an between October 2023 to October 2024. RSV nucleic acid screening was performed using real-time fluorescence quantitative PCR；full-length G gene sequencing was conducted on nucleic acid-positive specimens. Genotyping characterization of the obtained sequences was performed using Nextclade v3.10.0 software.Results:A total of 2 548 respiratory tract infection samples were collected，with 104 cases（4.08%，104/2 548）testing positive for RSV. The highest RSV positivity rate was observed in children aged ≤1 year（12.24%，18/147），and significant difference in positivity rates were found among age groups（χ 2=37.868， P<0.001）. Since October 2023，RSV has seen an epidemic peak during January to February 2024，and gradually declined thereafter，with no positive cases from May to September 2024. Among the 43 RSV-positive samples，12 strains were identified as subtype A（all genotype A.D.3），and 31 strains were subtype B（14 genotype B.D.4.1.1 and 17 genotype B.D.E.1）. Conclusion:From October 2023 to October 2024，RSV had an epidemic peak in January and February in Xi＇an，with subtype B being the predominant circulating type.

Objective:To analyze the prevalence of human respiratory syncytial virus（RSV）and the evolutionary characteristics of the adhesion glycoprotein（G）gene in Xi'an from 2023 to 2024.Methods:Respiratory specimens were collected from patients with acute respiratory infections in Xi'an between October 2023 to October 2024. RSV nucleic acid screening was performed using real-time fluorescence quantitative PCR；full-length G gene sequencing was conducted on nucleic acid-positive specimens. Genotyping characterization of the obtained sequences was performed using Nextclade v3.10.0 software.Results:A total of 2 548 respiratory tract infection samples were collected，with 104 cases（4.08%，104/2 548）testing positive for RSV. The highest RSV positivity rate was observed in children aged ≤1 year（12.24%，18/147），and significant difference in positivity rates were found among age groups（χ 2=37.868， P<0.001）. Since October 2023，RSV has seen an epidemic peak during January to February 2024，and gradually declined thereafter，with no positive cases from May to September 2024. Among the 43 RSV-positive samples，12 strains were identified as subtype A（all genotype A.D.3），and 31 strains were subtype B（14 genotype B.D.4.1.1 and 17 genotype B.D.E.1）. Conclusion:From October 2023 to October 2024，RSV had an epidemic peak in January and February in Xi＇an，with subtype B being the predominant circulating type.

With the continuous development of messenger RNA (mRNA) technology, mRNA-based drugs have shown broad application prospects in recent years. Since mRNA is easy to be degraded and difficult to enter cells directly, the mRNA delivery vectors have always been one of the focuses in the development of mRNA-based drugs. Although lipid nanoparticles (LNPs) have been widely used for the delivery of mRNA, they tend to accumulate in the liver, and repeated administration can easily induce inflammatory response which leads to tissue damage. Compared with LNPs, virus-like particles (VLPs) have the advantages of high biocompatibility and safety, being expected to offer new solutions for mRNA delivery. Based on the practical application requirements, this review summarized the research progress in VLPs according to the mRNA delivery steps: particle assembly, delivery into cells, and intracellular release. We hope to provide a basis and design ideas for the development of new VLPs as delivery vectors, promote the application of VLPs in mRNA delivery, and provide new possibilities for the research and application of mRNA-based therapeutics.
RNA, Messenger/administration & dosage* ; Humans ; Nanoparticles/chemistry* ; Genetic Vectors ; Lipids/chemistry* ; Drug Delivery Systems/methods* ; Virion ; Animals ; Gene Transfer Techniques ; Liposomes

Objective:To investigate the expression levels, correlation, and diagnostic efficacy of peripheral blood CD8 +T lymphocyte subsets and different immune checkpoint markers in patients with Brucellosis. Method:A case-control study was conducted on 32 patients with acute phase brucellosis (27 males and 5 females, aged 36 (30, 43) years), 38 patients with chronic phase brucellosis (30 males and 8 females, aged 40 (32, 48) years), and 30 healthy controls (24 males and 6 females, aged 39 (32, 46) years), who underwent physical examination at Xinjiang Uygur Autonomous Region People′s Hospital from February 1, 2021 to December 31, 2023. All subjects had fasting blood sampling once in the morning. Flow cytometry was used to detect the proportion of peripheral blood lymphocyte subsets, the expression levels of CD8 +T lymphocyte surface programmed cell death receptor-1 (PD-1), T lymphocyte immunoglobulin receptor with Ig and ITIM domains (TIGIT), T cell immunoglobulin and mucin domain containing protein 3 (TIM-3), perforin and granzyme B. The changes in these indicators during the acute and chronic phases of the disease were observed, and correlation analysis was performed using Spearman′s method. Receiver Operating Characteristic Curve (ROC) analysis is used to evaluate the diagnostic value of immunological indicators with differences in acute and chronic brucellosis. Results:CD3 +T lymphocyte in the chronic group (70.71%±8.78%) is significantly lower than that in the healthy control group (74.65%±7.31%) ( P<0.05), and CD4 +T lymphocyte in the acute phase group (39.52%±5.85%) is also lower than that in the healthy control group (45.10%±5.18%) ( P<0.01); while CD8 +T lymphocyte in the acute group (31.73%±5.87%) is significantly higher than that in the chronic phase group (26.75%±4.71%) ( P<0.001). There was a statistically significant difference ( P<0.001) in CD8+CD28 -T lymphocyte among the acute group (69.85% (58.62%, 78.55%)), chronic group (86.46% (73.30%, 92.52%)) and healthy control group (25.39% (20.60%,32.90%)), when compared pairwise. The expression levels of immune checkpoint PD-1, TIGIT, and TIM-3 on the surface of CD8 +T lymphocytes were higher in both the acute and chronic groups than in the healthy control group ( P<0.001). The expression level of perforin secreted by CD8 +T lymphocytes in the acute and chronic groups was lower than that in the healthy control group ( P<0.05), while the expression level of granzyme B in the acute and chronic groups was higher than that in the healthy control group ( P<0.01). The proportion of CD8 +CD28 -T lymphocytes in brucellosis patients was positively correlated with the expression levels of TIGIT and TIM-3 ( r=0.624, 0.406, P<0.001). The ROC curve combined with the proportion of CD8 +CD28 -T lymphocytes and the proportion of TIGIT on the surface of CD8 +T lymphocytes can distinguish acute and chronic brucellosis. The Area Under Curve (AUC) is 0.973, which has certain implications for clinical differentiation of patients with acute and chronic diseases. Conclusion:The CD8 +T lymphocyte subsets in patients with brucellosis exhibit dynamic changes, accompanied by changes in relevant immune checkpoint molecules, and can regulate the activation and inhibition of the immune status of brucellosis patients. The synergistic effect of CD8 +CD28 -T cells and TIGIT/TIM-3 may be a key mechanism of driving chronicity, and their combined diagnosis can serve as a clinical staging marker.