BACKGROUND:One of the advantages of clear aligner treatment is molar distalization.However,tooth tilting movement and loss of anterior anchorage may occur during treatment.There are few studies on whether these problems can be improved by selecting clear aligners with different thicknesses and edges to improve the clinical treatment effect.OBJECTIVE:To analyze the control ability of clear aligners with different thickness and edges on the central incisor,lateral incisor,and second molar when pushing the maxillary second molar distally by three-dimensional finite element analysis.METHODS:Three-dimensional finite element analysis models of bilateral maxillary second molar distalization with clear aligner,maxillary dentition,periodontal ligament,and alveolar bone with different thicknesses and margins were established by Mimics,Geomagic Wrap,3-matic and SolidWorks software,respectively.There were 16 combinations of four thicknesses(0.4,0.5,0.625,and 0.75 mm)and four margins(scallop,straight,straight extension 2 mm and straight extension 4 mm).The data were imported into Ansys Workbench software for design and solution.The mean value,peak value and distribution of the periodontal ligament equivalent stress of the second molar,the equivalent stress and the maximum initial displacement of the second molar,and the control ability of each appliance on the second molar,central incisor,and lateral incisor were analyzed.RESULTS AND CONCLUSION:(1)The mean equivalent stress of periodontal ligament of the second molar,the equivalent stress of the second molar and the maximum initial displacement of the second molar increased with the extension of the appliance edge and the increase of the thickness of the appliance in the 16 groups of models.(2)When the thickness of appliances was the same,the maximum equivalent stress of the second molar in the linear appliance group was the highest,and the maximum equivalent stress of the second molar in the linear extended appliance group was greater than that in the scallop appliance group.When the edge of the appliance was the same,the periodontal ligament equivalent stress peak of the second molar increased with the increase of the thickness of the appliance.The equivalent stress distribution in the periodontal ligament of the second molar in the linear extendable appliance group was more uniform than that in the scallop appliance group and the linear appliance group.(3)When the thickness of the appliance was the same,the scallop-shaped appliance had the worst control on the second molar.When the edge of the appliance was the same,with the increase of the thickness of the appliance,the control of the second molar by the linear extender appliance was gradually stronger than that by the linear appliance.The control of the central incisor was stronger and more stable with the linear extended 2 mm appliance,while the control of the lateral incisor was stronger and more stable with the linear appliance.(4)The results showed that when using clear aligners to push molars distally,extending the edge of the appliance could improve the control of the molars and reduce the tilting movement of the teeth.The design of a straight extension margin of 2 mm for the central incisor and a straight edge for the lateral incisor can enhance the control of the anchorage incisor and reduce the labial inclination of the anterior teeth.

Objective To explore the pro-inflammation resolution and protective effects of reactive oxygen species (ROS)-responsive liposomes modified with a cardiac-targeted peptide and loaded with resolvin D1 (RvD1, C-LP-RvD1) on myocardial ischemia-reperfusion (MI/R) injury. Methods The C-LP-RvD1 nanoliposomes were constructed, characterized physically and chemically, and evaluated for in vitro release. Non-targeting peptide-modified drug-loaded liposomes (LP-RvD1) were served as controls. Apoptotic adult mouse cardiomyocytes (AMCMs) were used to verify in vitro targeted binding capacity of C-LP-RvD1. In MI/R mice models, the in vivo distribution and cardiac enrichment of C-LP-RvD1 were assessed. Levels of specialized pro-resolving mediator (SPM) and inflammatory factors in cardiac tissue homogenates and cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Cardiac function and fibrosis remodeling were evaluated via echocardiography and Masson staining four weeks after treatment. Biosafety was evaluated in healthy mice injected by C-LP-RvD1. Results The C-LP-RvD1 exhibited good nanoscale uniformity and stability, with ROS-triggered accelerated release characteristics. In vitro experiments showed that C-LP-RvD1 had higher binding capacity to apoptotic AMCMs than LP-RvD1, with significantly higher SPM levels (P＜0.01) and lower inflammatory factor levels (P＜0.05). In vivo experiments indicated enhanced cardiac enrichment of C-LP-RvD1 in MI/R injured hearts, with higher local myocardial SPM levels and lower inflammatory factor levels compared to LP-RvD1 (P＜0.05). Four weeks after treatment, compared with LP-RvD1, the C-LP-RvD1 mice group showed improved cardiac function indicators and reduced ventricular fibrosis remodeling ratio (P＜0.05). Safety evaluation revealed no significant systemic inflammation, immunogenicity, or coagulation abnormalities in healthy mice, with liver and kidney function and major organ histology showing no notable damage. Conclusions C-LP-RvD1 improves effective delivery of RvD1 to MI/R injured hearts through injury-targeted enrichment and ROS-responsive release, promoting inflammation resolution and suppressing excessive inflammation, thereby improving cardiac function and reducing adverse remodeling, with favorable biosafety.

With the widespread application of chemotherapy, immunotherapy, and targeted therapy, cardiotoxicity associated with anti-tumor treatment has gained increasing attention. Drug-induced cardiac injury can significantly impact patients’ quality of life and may even limit the overall efficacy of anti-tumor therapy. The underlying mechanisms include oxidative stress, inflammatory responses, mitochondrial dysfunction, apoptosis, and immune dysregulation. Owing to multitarget effects, low toxicity, and holistic regulatory properties, Chinese traditional medicines have demonstrated considerable potential in cardioprotection. This review summarizes the principal mechanisms of drug-induced myocardial injury related to anti-tumor therapy and highlights recent advances in the prevention and treatment of cardiotoxicity using Chinese medical formulae, such as compound danshen dripping pills, nuanxinkang, qili qiangxin capsules, and shengmai powder, as well as their bioactive constituents. The cardioprotective effects of these agents are discussed in terms of their antioxidative, anti-inflammatory, immunomodulatory, and mitochondrial-protective actions. Furthermore, it highlights certain traditional medicines that exhibit unique advantages in synergistic cardioprotective and anti-tumor therapy. Future efforts should focus on well-designed, systematic clinical studies to facilitate the translational application of integrated Chinese and Western medicine in cardio-oncology.

ObjectiveTo investigate the changes in chemical components of Gardeniae Fructus（GF） before and after being charred， providing data support for research on the material basis of GF Carbonisata（GFC）. MethodsUltra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Orbitrap MS/MS） was used to conduct a comprehensive analysis of the chemical components in GF and GFC under positive and negative ion modes with Compound Discoverer 3.3 software and online database. Then， principal component analysis and partial least squares-discriminant analysis in SIMCA14.1 software were used to analyze the MS data of each sample. Based on the principle of variable importance in the projection（VIP） value>1， differential secondary and primary metabolites before and after carbonization were screened. In addition， MetaboAnalyst website was used for pathway enrichment of Kyoto Encyclopedia of Genes and Genomes（KEGG）， so as to provide a reference for clarifying the processing mechanism. ResultsA total of 185 components were identified， including 96 secondary metabolites and 89 primary metabolites. These components were classified into nine categories， primarily including iridoid glycosides， flavonoids， and terpenoids， their fragmentation pathways were also analyzed. Simultaneously， multivariate statistical analysis was performed on the secondary and primary metabolites， identifying 70 and 59 differential metabolites， respectively. The secondary metabolites were enriched in two metabolic pathways， including C5-branched dibasic acid metabolism and flavonoid and flavonol biosynthesis， while the primary differential metabolites were enriched in seven pathways such as linoleic acid metabolism and tyrosine metabolism. ConclusionThe chemical components of GF change significantly after carbonization， with a significant decrease in the contents of iridoid glycosides and terpenoids such as hydroxyisogeniposide， crocin Ⅱ， crocetin， and jasminoside B. while the contents of 4-hydroxycoumarin， geniposidic acid， gentiopicroside， and gardenoside methyl ester increase significantly. This change is presumed to be associated with the enhanced cooling and hemostatic effects of the processed products. The identified key components provide a basis for elucidating the material basis underlying the efficacy changes before and after carbonization.

Objective: To understand the serum vitamin D and vitamin K 1 levels of children in the Qingdao area, so as to provide scientific grounds for appropriate vitamin supplementation. Methods: A total of 4 469 children aged 0-14 years old, who attended the children s healthcare outpatient clinics of a tertiary hospital in Qingdao, were enrolled in the current study between January 2023 and July 2024. The levels of vitamin D and vitamin K 1 were measured by liquid chromatography tandem mass spectrometry. The inter group differences were analyzed using Chi square test, Wilcoxon rank sum test, and Kruskal-Wallis H test. The correlation analysis of vitamin D and vitamin K 1 levels with age was performed using the Spearman correlation. Results: The serum vitamin D level among children was 28.72(22.67, 36.26)ng/mL. The vitamin D deficiency and insufficiency rates were 2.10% and 14.59 %, respectively. The serum 25-(OH)D 2 level was 0.29(0.14, 0.53)ng/mL, the serum 25-(OH)D 3 level was 27.99( 21.78 , 35.57)ng/mL and the serum vitamin K 1 level was 0.54(0.29, 1.04)ng/mL. The vitamin K 1 deficiency rate was 13.76%. Among different age stages, the serum vitamin D level was highest in infancy [37.45(30.39, 43.87)ng/mL] and lowest in school age children [22.39(18.00, 26.97)ng/mL]; the level of vitamin K 1 was highest in preschool children [0.79(0.41, 1.51) ng/mL] and lowest in school age children[0.45 (0.26, 0.76) ng/mL]; the serum vitamin D deficiency and insufficiency rates were highest in school age children (5.03% and 30.81%); the vitamin K 1 deficiency rate was highest in infancy (21.53%) ( H/χ 2=1 698.31, 253.70 , 137.85 , 583.79, 89.30, all P <0.05). Among different seasons, the serum vitamin D and vitamin K 1 levels were lowest in the winter [26.74(18.37, 35.86) and 0.50 (0.27, 0.94)ng/mL; H =50.71, 7.86]; the vitamin D deficiency and insufficiency rates were highest in the winter (5.41% and 24.80%; χ 2=59.93, 83.35) (all P <0.05). The serum vitamin D level had a moderate negative correlation with age ( r =-0.62), and there was a low positive correlation between the serum vitamin D and vitamin K 1 levels in infancy and early childhood ( r =0.21, 0.26) (all P <0.05). Conclusions The serum vitamin D and vitamin K 1 levels are lowest in school age children and in the winter, and the serum vitamin K 1 deficiency rate is highest in infancy. There is a need to focus on critical periods of infancy and school age, and strengthen interventions during the high risk winter season. The nutritional status of vitamin D and vitamin K 1 in children should be enhanced.

AIM:To analyze the influencing factors of postoperative malignant glaucoma(MG)in patients with primary angle-closure glaucoma(PACG)using logistic regression and decision tree models.METHODS:A retrospective study was conducted on PACG patients who underwent surgery at Eye Hospital of Handan City from March 2020 to March 2025. Patients were divided into two groups: the MG group, who developed MG within 6 mo postoperatively, and the non-MG group. Data were collected from the electronic medical record system. Univariate analysis was performed, followed by multivariate logistic regression to identify independent risk factors. A classification and regression tree model was constructed to visualize the hierarchical relationships among predictors. The predictive performance of the two models was evaluated and compared using receiver operating characteristic(ROC)curve analysis.RESULTS:Totally 182 cases(182 eyes)with PACG were enrolled in this study, including 91 cases(91 eyes)in the MG group and 91 cases(91 eyes)in the non-MG group. In the MG group, there were 53 males and 38 females; 69 cases were aged ≥60 y and 22 cases were aged <60 y. In the non-MG group, there were 47 males and 44 females; 33 cases were aged ≥60 y and 58 cases were aged <60 y. The non-MG group comprised 91 patients, including 47 males and 44 females. Among them, 33 cases were aged ≥60 y, and 58 cases were aged<60 y. The MG group had significantly higher proportions of patients aged ≥60 y, diabetes, moderate-stage PACG, persistent high intraocular pressure(IOP), complete anterior chamber angle closure, lens thickness <4.5 mm, axial length <22 mm, and severe postoperative inflammation compared to the non-MG group(all P<0.01). Multivariate Logistic regression identified the following as independent influencing factors for postoperative MG: age [OR (95%CI)=2.136(1.401-3.255)], PACG stage [OR (95%CI)=2.996(2.044-4.391)], IOP [OR (95%CI)=3.527(1.604-7.755)],anterior chamber angle [OR (95%CI)=4.826(2.498-9.324)], axial length [OR (95%CI)=5.125(1.265-20.771)], and severe postoperative inflammation [OR (95%CI)=2.338(1.478-3.699)](all P<0.05). The decision tree model selected six explanatory variables: age, PACG stage, IOP, anterior chamber angle status, axial length, and severe postoperative inflammation. Axial length was the primary splitting factor at the root node. The areas under the ROC curve(AUC)for the logistic regression and decision tree models were 0.913(0.863-0.950)and 0.921(0.872-0.956), respectively, with no significant difference between them(Z=0.561, P=0.575).CONCLUSION:Both the logistic regression and decision tree models effectively identify key influencing factors for postoperative MG in PACG patients, including age, PACG stage, IOP, anterior chamber angle status, axial length, and severe postoperative inflammation. The decision tree model offers an intuitive, visual representation of risk stratification, facilitating clinical decision-making. Both models are applicable for clinical risk assessment.

Objective To systematically analyze the spatiotemporal distribution characteristics and epidemiological trends of tracheal, bronchus, and lung cancer (TBL) disease burden attributed to air pollution globally and in China and the United States from 1990 to 2021, and to assess the patterns of disease burden changes from 2022 to 2031 based on predictive models, providing a scientific basis for formulating targeted TBL prevention and control strategies. Methods Based on the Global Burden of Disease (GBD) 2021 database, we analyzed the disease burden data of TBL attributed to air pollution globally and in China and the United States from 1990 to 2021. R Studio 4.3.2 software was used to analyze the corresponding trends and the Bayesian age-period-cohort (BAPC) prediction model was used to predict the status of the disease burden of TBL attributed to air pollution in the world and in China and the United States from 2022 to 2031. Results In 2021, China had the highest number of deaths and disability-adjusted life years attributed to air pollution (211 400 patients and 4.8947 million person-years), followed by the United States (6 000 patients and 124 300 person-years). The age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) of TBL due to air pollution in the world and in China and the United States showed a decreasing trend. From 1990 to 2021, the ASMR and ASDR of TBL in China due to air pollution were much higher than those in the United States and the global average. In terms of gender, from 1990 to 2021, the disease burden of male patients with TBL attributed to air pollution was much higher than that of female patients. The BAPC prediction model showed that from 2022 to 2031, the ASMR and ASDR of TBL attributed to air pollution showed an upward trend globally, while they showed a downward trend in China and the United States. Conclusion Over the past 30 years, the air pollution-related TBL disease burden in the world and in China and the United States has continued to decline, but China's disease burden is still significantly higher than the global average. The disease burden in men far exceeds that in women, with men and the population aged ≥50 years being high-risk groups. In the future, the global disease trend may reverse and rise, while China and the United States are expected to continuously decline. However, precise prevention and control for high-risk groups remains a key challenge.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

ObjectiveTo observe the effects of Xiaoyaosan on glucagon-like peptide-1 （GLP-1）/GLP-1 receptor （GLP-1r） and protein kinase A （PKA）/cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathways in the hippocampal CA1 region of rats under chronic restraint stress （CRS），and to explore the mechanism of this formula to alleviate anxiety and depression-like behaviors. Methods40 specific pathogen-free male Sprague-Dawley （SD） rats were randomly divided into normal，model，Xiaoyaosan，and fluoxetine groups，with 10 rats in each group. CRS was used to induce anxiety and depression-like behaviors. The rats in the Xiaoyaosan group were gavaged with aqueous solution of traditional Chinese medicine formula granules （7.36 g·kg^-1·d^-1），while those in the fluoxetine group were gavaged with aqueous solution of fluoxetine （2 mg·kg^-1·d^-1）. Body weight was measured on days 0，7，14，and 21 of the experiment. On days 0 and 22 of the experiment，the sucrose preference test （SPT），forced swimming test （FST），and open field test （OFT） were performed. The pathological morphology of the hippocampal CA1 region was observed by Nissl staining. The relative mRNA expression of post-synaptic density protein-95 （PSD95） and synapsin （SYP） was detected by reverse transcription quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blot were used to detect expression of proteins in the GLP-1/GLP-1r and PKA/CREB/BDNF pathways in the hippocampal CA1 region. ResultsAfter CRS modeling，compared with the normal group，the rats of the model group had anxiety and depression-like behavioral manifestations，neuronal damage in the hippocampal CA1 region，significantly downregulated expression of synaptic plasticity markers PSD95 and SYP genes （P<0.01），and inhibition of GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways （P<0.05，P<0.01）. Compared with the model group，the Xiaoyaosan group exhibited alleviated anxiety and depression-like behaviors，reduced neuronal damage in the hippocampal CA1 region， significantly increased expression of PSD95 and SYP genes （P<0.01），and the activation of the GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways （P<0.05，P<0.01）. ConclusionXiaoyaosan can alleviate anxiety and depression-like behaviors in CRS rats by improving synaptic plasticity in the hippocampal CA1 region. The mechanisms may be related to the activation of the GLP-1/GLP-1r pathway and its mediated PKA/CREB/BDNF signaling pathway by the formula.