Objective: To analyze the heterogeneity of mobile phone dependence development trajectory in middle school students and its association with loneliness and selfcontrol ability, so as to provide reference for the prevention of mobile phone dependence in middle school students. Methods: A total of 941 grade 1 students from 4 public middle schools in Xiangxi Autonomous Prefecture, Hunan Province were selected for the followup survey by random cluster sampling from October 2023 to April 2024 and October 2024. Mobile Phone Addiction Index (MPAI), University of California, Los Angeles Loneliness Scale-20 (UCLA-20) and Selfcontrol Scales (SCS) were used for questionnaire survey. The heterogeneity of the developmental trajectory of middle school students mobile phone dependence was analyzed by the latent growth curve model (LGMM), and the influencing factors of the developmental trajectory of middle school students mobile phone dependence were explored by multiple Logistic regression analysis. Results: The development trajectory of middle school students mobile phone dependence could be divided into four categories: C1 "low risk slow decline group (n=438,44.6%)", C2 "medium risk slow rise group (n=272,29.7%)", C3 "high risk rapid decline group (n=73,8.6%)" and C4 "high risk rapid rise group (n=158,17.1%)". There were significant differences in the distribution of mobile phone dependence development track heterogeneity subgroups among sex, only child, lodging, and leftbehind students (χ2=117.79, 44.88, 37.09, 130.50, P <0.01). The results of the multinomial Logistic regression model analysis showed that, with C1 group as the reference, C2, C3, and C4 were positively correlated with students loneliness [OR(95%CI)=1.04 (1.02-1.06), 1.11(1.08-1.14), 1.12(1.09-1.14)]; C2 and C4 groups were negatively correlated with students selfcontrol [OR(95%CI)=0.97(0.96-0.99), 0.95(0.93-0.97)] (P<0.01). Conclusions The development trajectory of mobile phone dependence among middle school students is heterogeneous. Reducing the loneliness of individuals and cultivating good selfcontrol ability are helpful to alleviate mobile phone dependence behavior among middle school students.

OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease， acute myocardial ischemia model， hyperlipidemia model， blood stasis model， and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high， medium， and low doses （0.6， 1.2 and 2.4 g/kg） on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase （LDH）， creatine kinase-MB （CK- MB）]， oxidative stress factors [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）]， inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， intercellular adhesion molecule-1 （ICAM-1）]， myocardial infarction percentage， serum lipid indexes [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， platelet aggregation function 话：022-84845240。E-mail：jiangx@tjipr.com [maximum aggregation rate （MAR）]， and thrombus formation indexes [thrombosis time， thrombus mass， thrombus protein content， plasminogen activator inhibitor-1 （PAI-1）， and tissue-type plasminogen activator （t-PA）] were evaluated in the rat models. RESULTS In myocardial ischemia tests， Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB， LDH， MDA， GSH， IL-6， TNF-α， IL- 1β， and MCP-1 in serum （P＜0.05 or P＜0.01）. In hyperlipidemia tests， high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC， LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests， different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats （P＜0.01）. In artery thrombosis tests， high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation （P＜ 0.01）， significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum （P＜0.01）. CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions， including anti-myocardial ischemia， lipid-lowering， and anti-thrombotic effects.

Patent foramen ovale(PFO)is a common congenital heart disease.The clinical manifestations of PFO are heterogeneous,which can easily lead to missed diagnosis and misdiagnosis.In recent years,people found PFO is related to a variety of nervous system diseases such as TIA,migraines,dizziness,syncope,seizures.This paper reviews the relationship between PFO and nervous system paroxysmal disease and its possible mechanism.This review aims to improve clinicians'understanding of PFO and provide ideas for the diagnosis and treatment of PFO.

Objective We aimed to compared matrix metalloproteinase-13 (MMP-13) and transforming growth factor-β1 (TGF-β1) in synovial fluid,the phosphorylation level of Smad3 in articular cartilage (P-Smad3),and their correlation with traditional Chinese medicine (TCM) patterns in patients with knee osteoarthritis (KOA) of liver-kidney deficiency pattern and pattern of intermingled phlegm and blood stasis.Methods Using a cross-sectional field investigation method,KOA patients hospitalized in the Orthopedics Department of Dongzhimen Hospital,Beijing University of Chinese Medicine from September 2019 to February 2023 were collected. A total of 112 KOA patients were included,among which 63 cases were diagnosed with liver-kidney deficiency pattern,and 49 cases were diagnosed with pattern of intermingled phlegm and blood stasis. The intensity of knee pain,function,and X-ray imaging result were quantified using the Visual Analogue Scale (VAS),Lysholm Knee Scoring Scale,and Kellgren-Lawrence (K-L) Grading Scale,respectively. The TCM pattern was identified and quantified using a TCM Pattern Scoring Scale. Immunohistochemistry was used to determine the phosphorylation characteristics of Smad3 in articular cartilage,and ELISA was used to measure the contents of MMP-13 and TGF-β1 in synovial fluid. The level characteristics and their correlation with the degree of syndrome were analyzed.Results (i) There was no statistically significant difference in VAS scores,Lysholm scores,and K-L grades between KOA patients with different TCM patterns. (ii) Compared with KOA patients with pattern of intermingled phlegm and blood stasis,patients with pattern of liver-kidney deficiency had higher levels of MMP-13 in synovial fluid and lower levels of TGF-β1 in synovial fluid (P<0.05). (iii) In KOA patients with liver-kidney deficiency pattern,there was a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.292,P=0.020),while there was a negative correlation between the level of TGF-β1 in synovial fluid and the score of TCM pattern (r=-0.781,P<0.001). In KOA patients with pattern of intermingled phlegm and blood stasis,there was also a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.936,P<0.001). (iv) The mean optical density value of P-Smad3 in articular cartilage was lower in KOA patients with liver-kidney deficiency pattern than in pattern of intermingled phlegm and blood stasis (P<0.05).Conclusion KOA patients with liver-kidney deficiency pattern or pattern of intermingled phlegm and blood stasis have different levels of TGF-β1 and MMP-13 in synovial fluid,as well as varying degrees of Smad3 phosphorylation in articular cartilage,which is consistent with the analysis of etiology and pathogenesis under different patterns. The levels of TGF-β1 and MMP-13 in synovial fluid of patients with liver-kidney deficiency pattern can reflect the severity of the pattern to a certain extent,and the mechanism may be related to the inhibition of the activation level of the TGF-β/Smad signaling pathway. This study enriches the research content of the material basis of TCM patterns.

Objective: To analyze the developmental trajectories of middle school students loneliness and social support, as well as to explore the interaction between loneliness and social support, so as to provide the evidence based support for the mental health development of adolescents. Methods: A total of 989 first year students from four public middle schools in Xiangxi Tujia and Miao Autonomous Prefecture, Hunan Province were selected for three follow up surveys by a cluster random sampling method (T1:March 2023, T2:June 2023, T3:December 2023). The UCLA Loneliness Scale-20 (ULS-20) and Social Support Scale for University Students (SSSUS) were employed for questionnaire data collection. The growth mixture modeling was utilized to test the developmental trajectories of loneliness and social support among middle school students, while the cross lagged analysis was performed to investigate their mutual influence. Results: The scores for loneliness and social support in T1, T2 and T3 were (43.1±5.8, 42.5± 6.8 , 42.0±6.9; 55.9±12.0, 60.7±15.7, 60.4±16.7), respectively. Correlational analysis revealed a significant negative correlation between loneliness levels (T1, T2, T3) and social support (T1, T2, T3) ( r =-0.47 to -0.36, P <0.01). Growth mixture modeling indicated a linear declining trend of middle school students loneliness, and the developmental trajectory of social support showed a linear increasing trend, with significant individual differences in initial levels and rates of change ( P <0.05). Cross lagged analyses revealed that loneliness levels at T1 negatively predicted social support scores at T2 ( β =-0.16), and loneliness levels at T2 negatively predicted social support scores at T3 ( β =-0.12) ( P <0.05). Additionally, prior loneliness positively predicted its subsequent levels, with path coefficients of 0.58 and 0.47, respectively ( P <0.05). Social support scores at T1 negatively predicted loneliness levels at T2 ( β =-0.10), while scores at T2 negatively predicted loneliness levels at T3 ( β =-0.15) ( P <0.05). Prior loneliness also positively predicted its subsequent levels, with path coefficients of 0.43 and 0.44, respectively ( P <0.05). Conclusion The developmental trajectory of middle school students loneliness demonstrates a decreasing trend, while that of social support exhibits a linear increasing trend, indicating a longitudinal causal relationship between loneliness and social support.

Hyaluronic acid is widely used in biomaterials, cosmetics, clinical medicine and other fields due to its good biocompatibility, degradability, hydrophilicity, tumor targeting, viscosity and other characteristics. Pharmacodynamic activities of natural small molecular products which derived from traditional Chinese medicine (TCM) are significant, but their low solubility and poor targeting limit the clinical application. Based on supramolecular properties of hyaluronic acid, in this review, numerous studies were reviewed on the improvement of solubility, bioavailability, targeting and suitable dosage forms of small molecular compounds in TCM by domestic and foreign scholars using hyaluronic acid as carrier. It provides new ideas and inspirations for exploring the potential application value of small molecule compounds in TCM and even for the research and development of new drugs.

OBJECTIVE To study the metabolites of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats and to investigate its metabolic regularity. METHODS In vitro incubation system of liver microsomes of rats was built. The jolkinolide A，jolkinolide B ，17-hydroxyl jolkinolide A and 17-hydroxyl jolkinolide B were added into incubation system of liver microsomes in rats activated by reduced nicotinamide adenine dinucleotide phosphate ，incubated at 37 ℃ for 30 min，and then terminated the reaction with acetonitrile. Taking the negative group （adding acetonitrile firstly and then starting incubation for 30 min）as the reference，the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used ；Anaylyst®TF 1.7.1、PeakView® 2.2，MetabolitePilot 1.5 and MasterView 1.2 software were used to speculate and identify the fragmentation law of mass spectrometry and metabolites. RESULTS Four diterpenoids were easy to lose neutral fragments such as H 2O and CO in secondary mass spectrometry. Jolkinolide A and 17-hydroxyl jolkinolide A showed similar metabolism pathway ，including dihydroxylation，dehydrogenation，and monohydroxylation ；six and five metabolites were identified respectively. Jolkinolide B and 17-hydroxyl jolkinolide B showed similar metabolism pathway ，including monohydroxylation ，hydration and isomerization. Five metabolites were identified. CONCLUSIONS Both jolkinolide A and 17-hydroxyl jolkinolide A produce the metabolites of hydroxylation and dehydrogenation in liver microsomes of rats ；both jolkinolide B and 17-hydroxyl jolkinolide B produce the metabolites of hydroxylation ，hydration and isomerization in liver microsomes of rats. The metabolites of four diterpenoids are phase Ⅰ metabolites.

【Objective】 To establish an indirect ELISA method for detecting IgG, IgM and IgA antibodies against Hepatitis E virus (HEV). 【Methods】 Tn-5 cells were infected with recombinant HEV baculovirus, and HEV-like particles (VLP) were collected and purified for coating antigen. The reaction conditions and methodology of indirect ELISA method were established and evaluated. The prevalence of HEV antibody among blood donors in Xishuangbanna were detected. 【Results】 The collected and purified VLP showed HEV antigenicity. The positive rates of anti-HEV IgG, IgM and IgA in blood donors in Xishuangbanna Prefecture were 18%(90/500), 5.6%(28/500) and 2.6%(13/500), respectively. The recent HEV infection rate was 1.8 % (9/500), and the seroprevalence of hepatitis E was 19.8% (99/500). Of the 13 anti-HEV IgA positive samples, 2 were both anti-HEV IgG and IgM negative. 【Conclusion】 HEV antibody positive is common among blood donors in Xishuangbanna, some of which are recent infections, posing a threat to the safety of blood transfusion. HEV IgA antibody indirect ELISA combined with human HEV IgM antibody detection can improve the detection rate of recent HEV infection.

The goal of the present study was to determine the effectiveness and safety of hemoperfusion (HP) in beagle dogs with chronic kidney disease (CKD). The experimental protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Institute of Pharmaceutical Research New Drug Evaluation Research (IACUC2019071501). Twelve CKD model beagles were randomly divided into two groups: a low-frequency treatment group (n = 6) and a high-frequency treatment group (n = 6). The dogs in the high- and low-frequency groups received HP treatment every 3 days and once per week, respectively, for two treatments, with each session lasting 2 h. The test results showed that high-frequency HP treatment significantly decreased the accumulation of toxins in the CKD beagles. Hematology, coagulation function, electrolytes and liver function indicated that the HP treatment was safe. The body index effects were consistent between the low- and high-frequency treatment groups. Therefore, HP treatment once every 3 days was safe at the animal level. Multiple HP treatments every 3 days were more conducive than weekly treatments to the removal of uremic toxins with better prognosis and had no associated safety hazards.

Objective:To analyze the epidemiological characteristics of human brucellosis (HB), evolution and origin feature of Brucella strains in Tongliao city, Inner Mongolia Autonomous Region during 2004-2018, and to provide evidence for strategy development against the disease. Methods:Data from the reports on HB in Tongliao during 2004-2018 were extracted from the China Information System for Disease Control and Prevention before being analyzed with software Excel 2016. Epidemiologic feature was described, using the number of cases, constituent ratio and related rates. Conventional biotypes methods were used for identification of species/biovars strains while species of six Brucella strains were further verified by AMOS-PCR. Cluster analyze on six Brucella strains were performed with Bio-Numerics 5.0 software and for examining and revealing the genetic characteristics of the related strains. Results:During 2004-2018, a total of 16 704 HB cases were reported, with the incidence rate as 35.41/100 000. The incidence rates appeared as 110.51/100 000 in Jarud Banner and 67.84/100 000 in Kulun flag, which were both higher than the other areas. Most of the cases were reported in the 40 -54 year olds, which accounted for 48.75% (8 143/16 704). The number of HB in farmers appeared as 14 873, which counted for 89.04% (14 873/16 704) of all the cases. Male to female ratio of incidence was 2.40∶1. Most of the reported cases appeared between March to May, which accounted for 56.30% (9 405/16 704). Peak of the disease was seen in April. Using the conventional identification method, results showed that the available six strains all belonged to B. melitensis, including three of them as B. melitensis bv.1 and others three strains as B. melitensis bv. 3. Results from the amplified AMOS-PCR showed that all the strains were B. melitensis. The six strains clustered in two MLVA-11 genotypes (111 and 116) and all belonged to the Eastern Mediterranean lineage. Based on the MLVA-16 cluster analysis, results suggested that strains from this study were having close genetic relationship with B. melitensis strains that were from Jilin and Heilongjiang provinces. Conclusions:Human brucellosis identified in Tongliao area was with greater risk in spreading the disease to the vicinity. Our findings indicated that the programs on detection and control of the disease should be strengthened.