ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

AIM: To observe the changes of retinal nerve fiber layer(RNFL)thickness and radial peripheral capillary(RPC)density in patients with unilateral branch retinal vein occlusion(BRVO), and further analyze the correlation between RPC density and RNFL thickness.METHODS: Observational study. Totally 37 patients with unilateral BRVO diagnosed at the ophthalmology department of First Hospital of Qinhuangdao from October 2020 to January 2022 were selected, the 37 affected eyes were the unilateral BRVO group, and 37 fellow healthy eyes were the contralateral unaffected group, and 35 healthy individuals(35 right eyes were selected)without ocular diseases during the same period were selected as the normal control group. The best corrected visual acuity, intraocular pressure, anterior segment, fundus and optical coherence tomography angiography(OCTA)were examined in both eyes of all BRVO patients and healthy individuals. The central macular thickness(CMT), the RNFL thickness, and the optic disc-AV crossing distance(DAVD)were measured by built-in software of the OCTA equipment. The optimized U-net algorithm was used to eliminate the large blood vessels, and then the RPC density was calculated. The CMT, RNFL thickness and RPC density were compared among the three groups. And the correlations of the RPC density with the CMT, RNFL thickness, and the DAVD were investigated.RESULTS: Compared with the contralateral unaffected group and the normal control group, the CMT and the RNFL thickness were significantly thickened in the unilateral BRVO group(all P<0.05); there were no statistical differences in the CMT and the RNFL thickness between the contralateral unaffected group and the normal control group(all P>0.05). The RPC density in the unilateral BRVO group increased compared with the contralateral unaffected group and decreased compared with the normal control group, but there was no statistically difference(all P>0.05). However, the RPC density in the contralateral unaffected group decreased compared with the normal control group(P<0.05). The RPC density in the unilateral BRVO group was not correlated with the CMT(P=0.960), but positively correlated with the RNFL thickness(r=0.401, P=0.014)and negatively correlated with the DAVD(r=-0.339, P=0.040).CONCLUSION: The RNFL thickened significantly and the RPC density did not change significantly in the optic disc area of BRVO patients. The RPC density is positively correlated with the RNFL thickness, indicating that the RNFL thickness can be used as a monitoring indicator to analyze and study the damage degree of the RPC density.

Parkinson's disease（PD） is the second most common neurodegenerative disease in the world， which seriously affects the lives of patients. With the acceleration of aging process， the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However， the pathogenesis of PD is still unclear. According to reports， the brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra， which is closely related to neurophysiological processes such as neurogenesis， synaptic plasticity， neuroinflammation， and oxidative stress. It plays an important role in the occurrence and development of PD. At present， the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms， but with the increase of dose， the adverse reactions are significantly enhanced. Traditional Chinese medicine（TCM） has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food， economy， minor adverse reactions and multi-target action. Therefore， this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas， extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad， so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.

Polymer magnetic microspheres are a new type of composite functional materials,which have the advantages of stable structure,diverse modification methods,and magnetic response.These characteristics make polymer magnetic microspheres have the advantages of high sensitivity,high-specificity and fast response when detecting logo carriers or modified materials,and shows great application prospects in the fields of biomedicine and medical diagnosis.In this review,the basic properties of polymer magnetic microspheres were summarized,the research progresses of magnetic microspheres in the fields of biomedicine and medical diagnosis were emphatically introduced,and the improvement of preparation methods and development trends in the future were prospected.

Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Objective:To investigate the efficacy of antiviral therapy and influencing factors of hepatitis B surface antigen(HBsAg) negative conversion for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) in children.Methods:The clinical data of 38 children with CHB who received antiviral treatment in Children's Hospital Affiliated to Xi'an Jiaotong University from January 2019 to August 2024 were collected.All patients were treated with interferon alpha monotherapy or combined with nucleoside analogues for 48 weeks.The patients were divided into HBsAg negative group and HBsAg non-negative group according to the therapeutic results at 48 weeks.Multivariate Logistic regression were used to identify influencing factors of HBsAg negative conversion at 48 weeks.The receiver operator characteristic（ROC）curve was used to analyze the predictive value of each factor to HBsAg negative conversion.Results:The alanine aminotransferase normalization rate，hepatitis B virus DNA negative rate，HBeAg negative rate and HBsAg negative rate were 76.3%，94.7%，39.5% and 47.4%，respectively at 48 weeks.There were 18 cases in HBsAg negative group and 20 cases in HBsAg non-negative group.There were statistical significant differences in age and HBsAg decline level at 12 and 24 weeks of antiviral treatment between HBsAg negative group and HBsAg non-negative group（ P<0.05）.Multivariate Logistic regression analysis showed that age and HBsAg decline level at 12 and 24 weeks of antiviral treatment were independent predictors of HBsAg negative conversion at 48 weeks（ OR=0.664，95% CI 0.473-0.932， P=0.018； OR=8.719，95% CI 1.920-39.604， P=0.005； OR=6.182，95% CI 2.083-18.347， P=0.001）.The area under the curve of age and HBsAg decline level at 12 and 24 weeks were 0.737（95% CI 0.576-0.899， P=0.012），0.847（95% CI 0.725-0.969， P<0.001）and 0.939（95% CI 0.811-0.991， P<0.001），respectively.When the age was less than 4.625 years，the sensitivity，specificity，positive predictive value and negative predictive value of HBsAg negative conversion at 48 weeks were 83.3%，65.0%，68.2% and 81.3%，respectively.A decrease in HBsAg level of >1.07 lg IU/mL at 12 weeks of treatment had a sensitivity，specificity，positive predictive value，and negative predictive value of 72.2%，90.0%，86.7%，and 78.3%，respectively，for predicting HBsAg seroclearance at 48 weeks.A reduction in HBsAg of >1.92 lg IU/mL at 24 weeks of treatment showed a sensitivity，specificity，positive predictive value，and negative predictive value of 83.3%，90.0%，88.2%，and 85.7%，respectively，in predicting HBsAg seroclearance at 48 weeks. Conclusion:The children with CHB have a higher rate of HBsAg negative conversion after antiviral therapy at 48 weeks.Age and HBsAg decline level at 12 and 24 weeks of antiviral treatment can serve as early predictors for HBsAg negative conversion in children with CHB.

Objective To analyze the distribution of serum food specific immunoglobulin(Ig)E and IgG antibodies in patients with adverse food reactions in Qingdao area.Methods The specific IgE test results of 4 199 patients with suspected food allergy and the specific IgG test results of 741 patients with food intoler-ance were collected from the Affiliated Hospital of Qingdao University from 2012 to 2022.A total of 4 199 pa-tients with suspected food allergy(2 308 males and 1 891 females)were enrolled in this study.According to the age,the patients were divided into infancy(＜1 year old)205 cases,early childhood(1-＜3 years old)1009 cases,childhood(3-＜14 years old)1 946 cases,adolescence(14-＜18 years old)99 cases,youth(18-＜40 years old)554 cases,middle age(40-＜65 years old)329 cases and old age(≥65 years old)57 cases.A to-tal of 741 patients with food intolerance(469 males and 272 females)were enrolled in this study.According to the age,the patients were divided into 81 cases in infancy(＜1 year old),298 cases in early childhood(1-＜3 years old)and 362 cases in childhood(3-＜14 years old).Enzyme-linked immunosorbent assay was used to detect the positive rates of IgE and IgG antibodies in serum of patients,and the positive rates of IgE and IgG antibodies in patients with different gender and age were compared.Results Egg white and cow's milk were the most sensitive foods in infants and young children.The positive rate of specific IgE antibody decreased gradually with the increase of age,and increased slightly in old age.The positive rate of specific IgE antibody in shrimp and crab increased first and then decreased with age,and it was higher in young and middle age.The tolerance of infants and children to meat and crustaceans was relatively strong,and the positive rate of food specific IgG to fish was higher than that to meat(P＜0.05).The positive rate of tomato-specific IgG was the highest in infancy and gradually decreased with age(P＜0.05).Conclusion With the increase of age and the change of dietary structure,the positive rate of food specific IgG antibody may change significantly.Clinicians should accurately grasp the epidemiological characteristics of food adverse reactions in this area,and adjust and optimize the diet structure of patients to make correct diagnosis and treatment.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To observe the value of Node-RADS based on dynamic contrast-enhanced MRI(DCE-MRI)for assessing axillary lymph node metastasis of breast cancer.Methods A total of 308 patients with breast cancer were retrospectively enrolled and divided into metastasis group(n=153)and non-metastasis group(n=155)based on the presence of axillary lymph node metastasis or not.Two radiologists independently scored the axillary lymph nodes shown on DCE-MRI according to Node-RADS criteria.Inter-observer scores was assessed using Kappa test.Taken pathological result as the gold standard,receiver operating characteristic curves were plotted,and the area under the curve(AUC)was calculated to evaluate the efficacy of Node-RADS scores for diagnosing axillary lymph node metastasis.Results Good inter-observer consistency of Node-RADS scores was observed.When Node-RADS score＞2,the highest AUC of 2 radiologists was 0.928 and 0.921,respectively,being not significantly different(P＞0.05).Conclusion Node-RADS based on DCE-MRI had good efficacy for evaluating axillary lymph node metastasis of breast cancer.Node-RADS score higher than 2 strongly indicated possibility of lymph node metastasis.

Stroke associated with infective endocarditis is rare and has a high mortality rate.Lack of clinical understanding can easily lead to misdiagnosis,and delayed treatment can lead to poor prognosis.This article reports a case of infective endocarditis complicated with severe mixed stroke,in order to improve clinicians'attention to the diagnosis and treatment of such diseases.