Objective: To explore the efficacy of a novel injectable hydrogel (GelMA/P11/IL4@LIP) loaded with P11 bacteriophages and interleukin-4 (IL-4) liposomes (LIP) in preventing relapse after maxillary expansion in mice, providing experimental evidence for its clinical application. Methods: This study was approved by the experimental animal ethics committee of our hospital. First, 15 7-week-old C57BL/6 mice were used to establish a maxillary expansion model and divided into 5 groups (3 mice in each group): a control group, post expansion day 3 group (PED3 group), post expansion day 7 group (PED7 group), retention for 14 days group (RET group), and relapse for 7 days group (REL group). The mice in each group were sacrificed at their designated time points (day 0, 3, 7, 21, 28), and their maxilla and anterior cranial regions were collected. Bone parameters and the inter-crestal distance (ICD) of maxillary incisor mesial alveolar ridge were measured using micro-computed tomography (micro-CT). Histological staining was performed to evaluate bone formation and resorption, while immunohistochemistry (IHC) was performed for macrophage markers (CD86 and CD206), mesenchymal stem cell markers (glioma-associated oncogene homolog 1 [Gli1]), and osteogenic markers (Runt-related transcription factor 2 [Runx2] and Osterix [OSX]). Next, GelMA/P11/IL4@LIP was synthesized and administered to mouse models of maxillary expansion. A total of 24 7-week-old C57BL/6 mice were divided into 4 groups (6 mice in each group): a blank control group, GelMA group, GelMA/P11 group, and GelMA/P11/IL4@LIP group. All mice underwent palatal expansion. On PED7, the expanders of all 24 mice were cemented with resin to initiate the 14-day retention period. On day 1 of the retention phase, the mice in each group received injections of saline, GelMA, GelMA/P11, or GelMA/P11/IL4@LIP at the midpalatal suture. After the 14-day retention period, three mice in each group were randomly selected and sacrificed, while the other three had their expanders removed and underwent a 7-day relapse before being sacrificed on day 28 (REL). Micro-CT, histological staining, and IHC were performed to evaluate the preventive effect of GelMA/P11/IL4@LIP on post-expansion relapse. Results: The mice maxillary expansion model exhibited a decreased ICD at REL compared to RET in micro-CT analysis (P = 0.008). IHC analysis demonstrated prolonged M1 macrophage infiltration, scarce Gli1+ mesenchymal stem cells, and insufficient expression of osteogenic markers (RUNX2 and OSX) (P < 0.001). Compared to the blank control and GelMA groups, GelMA/P11/IL4@LIP hydrogel injection in the midpalatal suture led to increased ICD at REL, promoted the timely M2 polarization of macrophages, recruited Gli1+ mesenchymal stem cells, and upregulated the expression of RUNX2 and OSX (P < 0.05). Conclusion The mechanism of relapse after maxillary expansion involves the persistent infiltration of M1 macrophages, as well as the inadequate recruitment and insufficient osteogenic differentiation of MSCs in the midpalatal suture. The GelMA/P11/IL4@LIP composite enhanced orofacial mesenchymal stem cell recruitment and promoted the M2 polarization of macrophages, thereby enhancing osteogenesis in the midpalatal suture and preventing post-expansion relapse.

ObjectiveTo investigate whether anti-programmed death-1 （PD-1） monoclonal antibody can enhance the efficacy and safety of argon-helium cryoablation combined with targeted therapy in patients with unresectable hepatocellular carcinoma （uHCC） aged 60 years or older. MethodsA retrospective analysis was performed for the clinical data of 124 patients with advanced uHCC aged 60 years or older who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to September 2024. After propensity score matching， 57 patients received cryoablation combined with targeted therapy （double combination group）， while 57 received cryoablation combined with targeted therapy and anti-PD-1 monoclonal antibody （triple combination group）. The indicators for efficacy assessment included objective response rate （ORR）， disease control rate （DCR）， progression-free survival （PFS）， overall survival （OS）， and the incidence rate of adverse events. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. A Cox proportional-hazards regression model analysis was used to investigate the influencing factors for survival prognosis. ResultsThe triple combination group had a significantly higher ORR than the double combination group （59.6% vs 29.8%， χ²=9.083， P=0.003）， while there was no significant difference in DCR between the two groups （87.7% vs 77.2%， χ²=1.516， P=0.218）， and compared with the double combination group， the triple combination group had significantly longer median PFS （9.1 months vs 4.8 months， χ²=7.813， P=0.005） and median OS （26.1 months vs 13.6 months， χ²=14.199， P<0.001）. The multivariate Cox proportional-hazards regression model analysis showed that triple combination treatment was an independent influencing factor for PFS （hazard ratio ［HR］=0.52， 95% confidence interval ［CI］： 0.35 — 0.78， P=0.001） and OS （HR=0.32， 95%CI： 0.20 — 0.51， P<0.001）. There was no significant difference in the incidence rate of adverse events between the two groups （P>0.05）. ConclusionTriple combination treatment with argon-helium cryoablation， targeted therapy， and anti-PD-1 monoclonal antibody can significantly improve survival benefits in uHCC patients aged 60 years or older， with a controllable safety profile.

OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

In order to establish a competitive chemiluminescent enzyme-linked immunoassay for rapid and quantitative detection of Senecavirus A antibodies,the polystyrene plate was coated with inactivated Senecavirus A antigen,and the monoclonal antibodies against Senecavirus A VP2 and VP3 proteins labeled by horseradish peroxidase(HRP)were used as the competitive enzymic anti-bodies of the antibodies in the serum samples.The standard curve of the calibrator prepared by di-lution of positive serum was drawn to achieve quantitative detection.The successfully established SVA competitive CLEIA reported the result within 45 minutes.The maximum dilution of 1∶2 048 for calibrator serum was still detectable with no cross-reaction with the standard positive serum of other five kinds of virus antigens such as foot-and-mouth disease.The coefficient of variation within batches was less than 10％,and the coefficient of variation between batches was less than 15％,which showed good repeatability and stability.The positive and negative coincidence rates were 95.30％and 97.57％,respectively,and the total coincidence rate was 96.88％,showing high consistency.The SVA competitive CLEIA assay established in this study can be used for the rapid quantitative detection of Senecavirus A antibodies,filling the gap in the domestic rapid quantitative detection of SVA antibodies.

Acupuncture is considered both safe and effective for treating depression;however,its underlying mechanism remains incompletely understood.This article reviewed the mechanisms of acupuncture in depression from the perspective of brain network dynamics.It has been found abnormal alterations in the structural and functional brain networks,including the default mode network,cognitive control network,salience network and affective network in individuals with depression.Acupuncture has been shown to enhance the diffusion anisotropy value of white matter and repair the microstructure of white matter fiber bundles in key brain regions.It can also modulate the activation the functional brain networks,either globally or in specific network segments,improve functional connectivity within and between functional networks,regulate global transmission efficiency and connectivity patterns of functional networks,restore brain network interaction balance,regulate abnormal integration of functional networks,and improve emotional regulation ability and cognitive function,in order to alleviate the clinical symptoms of depression and serve as an effective antidepressant therapy,which can provide reference for the study of acupuncture intervention in the brain network mechanism of depression.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.

BACKGROUND:Activation of nuclear factor-κB/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling leads to endothelial dysfunction,oxidative stress,and plays a key role in the initiation of lipid metabolism disorders and arteriosclerosis.However,currenty,the effect of walnut oil and peanut oil on skeletal muscle inflammatory factors in arteriosclerotic rats remains unclear.OBJECTIVE:To discuss the effect and mechanism of walnut oil and peanut oil on atherosclerosis.METHODS:Forty 8-week-old SD male rats were randomly divided into normal control group(n=10)and high fat group(n=30)after 1 week of adaptive feeding.The atherosclerosis model was established by high-fat diet combined with vitamin D3 injection.The rats with successful modeling were randomly divided into model group(n=10),peanut oil group(n=8)and walnut oil group(n=8).The latter two groups were gavaged with peanut oil or walnut oil for 4 weeks(5 days/week,1.2 g/kg per day).After the intervention,ELISA was used to detect the related indexes of blood lipids in rats.The morphological changes of aorta were observed by hematoxylin-eosin staining.The RT-qPCR and western blot assay were used to detect nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,interleukin-18 mRNA and nuclear factor-κB,NLRP3,interleukin-1β protein expression levels in skeletal muscle.The protein expressions of nuclear factor-κB and NLRP3 were detected by immunofluorescence immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the aortic wall of rats in the model group was thickened,the damage and lipid precipitation were more serious,the blood lipid levels and arteriosclerosis index were significantly increased(P＜0.01).The mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18,and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly increased(P＜0.01).(2)Compared with model group,the vulnerable area of aortic tissue in peanut oil group and walnut oil group was significantly reduced,the levels of total cholesterol,triglyceride,low density lipoprotein cholesterol in serum,and atherosclerosis index were decreased(P＜0.01),and the mRNA expressions of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18 and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly decreased(P＜0.01 or P＜0.05).(3)Compared with peanut oil group,the serum total cholesterol,triglyceride,and low density lipoprotein cholesterol levels in walnut oil group were significantly decreased(P＜0.01 or P＜0.05),and the mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-18,and the protein levels of nuclear factor-κB,NLRP3,interleukin-1β decreased significantly in skeletal muscle(P＜0.01 or P＜0.05).It is concluded that both peanut oil and walnut oil have ameliorative effect on atherosclerotic damage,which may be related to nuclear factor-κB/NLRP3 signaling pathway,and walnut oil has better ameliorative effect than peanut oil.

BACKGROUND:Activation of nuclear factor-κB/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling leads to endothelial dysfunction,oxidative stress,and plays a key role in the initiation of lipid metabolism disorders and arteriosclerosis.However,currenty,the effect of walnut oil and peanut oil on skeletal muscle inflammatory factors in arteriosclerotic rats remains unclear.OBJECTIVE:To discuss the effect and mechanism of walnut oil and peanut oil on atherosclerosis.METHODS:Forty 8-week-old SD male rats were randomly divided into normal control group(n=10)and high fat group(n=30)after 1 week of adaptive feeding.The atherosclerosis model was established by high-fat diet combined with vitamin D3 injection.The rats with successful modeling were randomly divided into model group(n=10),peanut oil group(n=8)and walnut oil group(n=8).The latter two groups were gavaged with peanut oil or walnut oil for 4 weeks(5 days/week,1.2 g/kg per day).After the intervention,ELISA was used to detect the related indexes of blood lipids in rats.The morphological changes of aorta were observed by hematoxylin-eosin staining.The RT-qPCR and western blot assay were used to detect nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,interleukin-18 mRNA and nuclear factor-κB,NLRP3,interleukin-1β protein expression levels in skeletal muscle.The protein expressions of nuclear factor-κB and NLRP3 were detected by immunofluorescence immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the aortic wall of rats in the model group was thickened,the damage and lipid precipitation were more serious,the blood lipid levels and arteriosclerosis index were significantly increased(P＜0.01).The mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18,and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly increased(P＜0.01).(2)Compared with model group,the vulnerable area of aortic tissue in peanut oil group and walnut oil group was significantly reduced,the levels of total cholesterol,triglyceride,low density lipoprotein cholesterol in serum,and atherosclerosis index were decreased(P＜0.01),and the mRNA expressions of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18 and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly decreased(P＜0.01 or P＜0.05).(3)Compared with peanut oil group,the serum total cholesterol,triglyceride,and low density lipoprotein cholesterol levels in walnut oil group were significantly decreased(P＜0.01 or P＜0.05),and the mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-18,and the protein levels of nuclear factor-κB,NLRP3,interleukin-1β decreased significantly in skeletal muscle(P＜0.01 or P＜0.05).It is concluded that both peanut oil and walnut oil have ameliorative effect on atherosclerotic damage,which may be related to nuclear factor-κB/NLRP3 signaling pathway,and walnut oil has better ameliorative effect than peanut oil.

A 70-year-old female patient with tumor in the neck and body of the pancreas received 11 cycles of chemotherapy with paclitaxel and gemcitabine. Due to disease progression, she subsequently underwent chemotherapy of fluorouracil, calcium folinate, and irinotecan, combined with immunotherapy of serplulimab. After 28 days (only one session of immunotherapy), the patient developed drooping of the right upper eyelid and chest tightness, followed by pain in the middle and lower segments of the sternum and radiating pain to the throat, accompanied by speech difficulties, dysphagia, and chest tightness and wheezing. Laboratory tests indicated hypersensitive troponin T 0.551 μg/L, creatine kinase (CK) 3 426 U/L, CK-MB 176 μg/L, and myoglobin 1 702 μg/L. The imaging examination of head and neck ruled out intracranial lesions, while the electrocardiogram suggested myocardial damage. Immune-related myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) induced by serplulimab was considered. Immunotherapy was temporarily halted, and treatments with methyprednisolone and human immunoglobulin were administered. Sixteen days later, clinical symptoms of IM3OS in the patient were improved, with laboratory tests showing hypersensitive troponin I 0.075 μg/L, CK 216 U/L, CK-MB 58 μg/L, and myoglobin 273 μg/L. Upon follow-up, the patient switched to monotherapy with irinotecan alone or combined with raltitrexed for cancer treatment, clinical symptoms of IM3OS did not recur, and no abnormalities were observed in myocardial injury markers or muscle enzymes.