ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

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.

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.

ObjectiveTo explore the effect of transcutaneous electrical acupoint stimulation （TEAS） on stress response in patients undergoing unilateral biportal endoscopy （UBE） and to identify optimal TEAS parameters. MethodsA total of 96 patients undergoing UBE were randomly grouped into total intravenous anesthesia （TIVA） group， acupuncture-assisted anesthesia with continuous waves （AACW） group， and acupuncture-assisted anesthesia with sparse-dense waves （AASDW） group， with 32 patients per group. All groups were given a standardized TIVA protocol. In the AACW group （100 Hz continuous wave stimulation） and the AASDW group （2/100 Hz sparse-dense wave stimulation）， TEAS intervention was applied to both bilateral Zusanli （ST36） and Sanyinjiao （SP6） 30 minutes before TIVA induction and continued until the end of the surgery. In the TIVA group， electrodes were only connected without electrical stimulation. The stress response indicators including cortisol （Cor） and adrenocorticotropic hormone （ACTH）， heart rate （HR）， mean arterial pressure （MAP）， and bispectral index （BIS） at before anesthesia induction （T0）， after tracheal intubation （T1）， during laminectomy （T2）， and 1 hour after surgery （T3） were compared across groups. The operation duration， anesthesia duration， extubation and recovery duration were recorded， as well as pain intensity including visual analogue scale （VAS）， and sedation level （by Ramsay sedation score） at 2， 6， 12 hours after surgery， and postoperative complications. ResultsThe AACW group and AASDW group had lower ACTH and COR levels at T1， T2 and T3， as well as lower HR and MAP levels at T1 and T2 than TIVA group， with AASDW group being lower than AACW group （P＜0.05）. At T3， the AASDW group had higher BIS than TIVA group and AACW group （P＜0.05）. No significant difference in operation duration was observed （P＞0.05）. The AACW group and AASDW group had shorter anesthesia， extubation and recovery duration than TIVA group， with AASDW group being the shortest （P＜0.05）. The VAS scores at 2 h， 6 h， and 12 h after surgery in the AACW and AASDW groups were lower than those in the TIVA group， with the AASDW group showing significantly lower scores than the AACW group （P＜0.05）. The Ramsay sedation scores in the AASDW group were lower than those in the AACW group at 2 h and 6 h after surgery （P＜0.05）. The total incidence of complications in the AASDW group was 6.25% （2/32）， significantly lower than 28.13% （9/32） in the TIVA group （P＜0.05）. ConclusionTEAS can effectively suppresses stress response in patients undergoing UBE， with the 2/100 Hz sparse-dense wave parameter being most effective， which can stabilize hemodynamics， accelerate recovery， improve postoperative sedation and analgesia quality， and reduces complications.

Drawing on the concepts of behavioural change taxonomies and theoretical coding schemes， this paper designs a theoretical model of "manipulative effect units" for manual medicine， establishing a logical framework that links "treatment objectives （theory-driven）-treatment techniques （precise implementation）-expected effects （immediate verification）". First， it analyses the methodological challenges faced by manual medicine as a complex intervention， reviewing the insights and limitations of existing research frameworks. It then focuses on the model's core concepts， theoretical architecture and multi-level coding system of "manipulative effect units"， illustrating its application logic using tuina for knee osteoarthritis as an example. Finally， it proposes a development pathway of "manipulative effect units" model in complex interventions based on consensus， technological integration and artificial intelligence. This model aims to provide a unified methodological foundation for the standardised description， reproducible research and identification of active components in manual interventions， thereby propelling manual medicine from empirical transmission towards a new phase guided by theory and evidence optimization.

ObjectiveTo develop a core outcome set for musculoskeletal pain （MKP-COS） and a specific outcome set for traditional Chinese medicine external treatment （MKP-SOS-ETCM）， providing a standardized basis for clinical research in musculoskeletal pain and serving as a reference for core outcome set （COS） development in related fields. MethodsExisting COS studies on musculoskeletal pain （MKP） were systematically searched， and core outcome indicators were extracted to form an initial item pool. The Delphi method was used， in which experts were invited to reach consensus on MKP-COS and MKP-SOS-ETCM. The inclusion criteria for consensus are set as an importance score of 7-9 points with ≥75% of experts reaching agreement. ResultsA total of 47 COS studies were included， and after discussion and consolidation， a preliminary item pool containing 34 outcome indicators was established. After three rounds of Delphi expert consensus， MKP-COS was identified， including five outcomes including pain， motor function， joint range of motion， activities of daily living， and adverse events/ adverse reactions； MKP-SOS-ETCM included six outcomes involving stiffness （including morning stiffness）， joint tenderness count， work status/ productivity， overall physician assessment， structural damage， and muscle strength. ConclusionThis study has established MKP-COS and MKP-SOS-ETCM， forming a dual-dimensional outcome assessment system integrating both disease commonality and intervention specificity.

ObjectiveTo develop a core outcome set for musculoskeletal pain （MKP-COS） and a specific outcome set for traditional Chinese medicine external treatment （MKP-SOS-ETCM）， providing a standardized basis for clinical research in musculoskeletal pain and serving as a reference for core outcome set （COS） development in related fields. MethodsExisting COS studies on musculoskeletal pain （MKP） were systematically searched， and core outcome indicators were extracted to form an initial item pool. The Delphi method was used， in which experts were invited to reach consensus on MKP-COS and MKP-SOS-ETCM. The inclusion criteria for consensus are set as an importance score of 7-9 points with ≥75% of experts reaching agreement. ResultsA total of 47 COS studies were included， and after discussion and consolidation， a preliminary item pool containing 34 outcome indicators was established. After three rounds of Delphi expert consensus， MKP-COS was identified， including five outcomes including pain， motor function， joint range of motion， activities of daily living， and adverse events/ adverse reactions； MKP-SOS-ETCM included six outcomes involving stiffness （including morning stiffness）， joint tenderness count， work status/ productivity， overall physician assessment， structural damage， and muscle strength. ConclusionThis study has established MKP-COS and MKP-SOS-ETCM， forming a dual-dimensional outcome assessment system integrating both disease commonality and intervention specificity.

Objective To explore the dominant views with positive results when performing echocardiography on common congenital heart disease (CHD) in children using the seven-step screening method for pediatric echocardiography. Methods The echocardiographic data of children with atrial septal defect, patent foramen ovale, ventricular septal defect, and patent ductus arteriosus were collected from September 2021 to February 2022. The disease type distribution, view distribution, and the dominant view distribution were analyzed. Dominant view referred to the view with a high ratio of positive result images per view to the total image in each disease. Results A total of 8 353 images of 1 633 children with common CHD were collected. There were 813 males and 820 females ageed 0-7 years, including 3 613 images in 701 patients with atrial septal defect, 1 178 images in 206 patients with patent foramen ovale, 2 857 images in 576 patients with ventricular septal defect, and 705 images in 150 patients with patent ductus arteriosus. The dominant views of atrial septal defect were subxiphoid 2-chamber view (92.96%), subxiphoid 4-chamber view (85.61%), parasternal 4-chamber view (62.07%), and parasternal short-axis view (38.50%). The dominant views of patent foramen ovale were subxiphoid 2-chamber view (82.69%) and subxiphoid 4-chamber view (65.41%). The dominant views of ventricular septal defect were parasternal 5-chamber view (79.73%), parasternal short-axis view (79.41%), parasternal 4-chamber view (58.18%), and parasternal long-axis view (51.11%). The dominant view of patent ductus arteriosus was parasternal short-axis view (98.80%). Conclusion The analysis of the lesion key areas of common CHD shows that there are 4 dominant views for atrial septal defect and ventricular septal defect, 2 for patent foramen ovale, and only 1 for patent ductus arteriosus. Clarifying the dominant views of common CHD is conducive to rapid and accurate diagnosis of diseases, clinical practice, teaching and scientific research.

[摘 要] 目的：探讨年轻乳腺癌独特的DNA甲基化特征，筛选与预后相关的甲基化位点，构建并验证预后预测模型，并通过多组学整合及关键蛋白验证评估其临床价值。方法：收集癌症基因组图谱（TCGA）数据库中的乳腺癌样本DNA甲基化及临床数据，筛选年轻乳腺癌特有的甲基化位点。采用随机森林、LASSO回归及单因素和多因素Cox比例风险回归分析构建预后模型。使用受试者工作特征（ROC）曲线、校准曲线和一致性指数（C-index）评估模型性能，并比较高、低风险组间的多组学特征差异，在独立队列中通过免疫组化法检测模型关键基因LAMA5的蛋白表达，分析其与预后的关系。结果：年轻乳腺癌相较于老年乳腺癌，在启动子区域（尤其是CpG岛）呈现显著低甲基化特征。通过多步骤差异分析获得3 489个年轻乳腺癌特有的甲基化位点，经Cox比例风险回归筛选出12个与总生存期（OS）独立相关的位点，其中启动子区、基因体区和基因间区位点各4个。基于筛选出的12个甲基化位点构建的预测模型，在TCGA训练集中显示出良好的区分度，高风险组总生存期显著更差（P = 0.002 5），5、8和10年OS预测曲线下面积（AUC）达0.88～0.94。多组学分析显示，高风险组丝裂原活化蛋白激酶（MAPK）信号通路激活，TP53基因突变频率更高，雌激素受体α蛋白表达较低。将TP53突变状态及雌激素受体1（ESR1）mRNA表达水平等关键多组学指标纳入模型，构建综合列线图，其预测效能进一步提升。组织芯片验证显示，模型关键基因LAMA5蛋白表达阴性患者的OS更差（P = 0.046），且富集于三阴性乳腺癌，与模型高风险组的临床病理特征一致。结论：整合启动子和非启动子区域信息的基于12个甲基化位点的模型可用于年轻乳腺癌患者的预后分层。联合年龄、TP53突变及ESR1 mRNA表达水平构建的综合列线图显示出较单一甲基化模型更高的预测效能。

BackgroundPatients with colorectal cancer are frequently comorbid with depression， which severely affects the quality of life and treatment compliance， while compromising the efficacy of anticancer treament and prognosis. Current therapeutic strategies still have notable limitations， particularly the lack of systematic and targeted synergistic regimens that integrate oncological management and anti-depressive intervention. It is of great clinical significance to explore a safe and effective new comprehensive intervention protocol and clarify its underlying mechanism of action. ObjectiveTo explore the effectiveness and safety of Shugan Yunpi Decoction in alleviating depressive and anxiety symptoms in colorectal cancer patients with depressive disorder through the PI3K-AKT signaling pathway， in order to provide references for the comprehensive treatment of colorectal cancer and depressive disorder. MethodsThis study was a randomized controlled trial. A total of 106 patients admitted to the Baoding No.1 Hospital of traditional Chinese medicine from November 2023 to July 2025 were enrolled， who met the diagnostic criteria for the Chinese protocol of diagnosis and treatment of colorectal cancer （2023 edition） and the diagnostic criteria for depressive disorder as specified in the Chinese Classification and Diagnostic Criteria of Mental Disease， third edition （CCMD-3）. Patients were divided into the study group and the control group using a random number table， with 53 cases in each group. The control group received conventional chemotherapy combined with traditional Chinese medicine five-element music therapy， while the study group received conventional chemotherapy combined with Shugan Yunpi Decoction therapy. Both groups were treated for 8 weeks. Depressive and anxiety symptoms were assessed using the Hamilton Depression Scale-17 item（HAMD-17） and Hamilton Anxiety Scale （HAMA）， respectively. Western blot protein immunoblotting was used to detect the expression levels of PI3K， AKT， and pAKT. Real-time fluorescence quantitative reverse transcription polymerase chain reaction （qRT-PCR） was used to detect the expression levels of PI3K mRNA and AKT mRNA. Adverse reactions were recorded using a self-designed adverse reaction record form. ResultsRepeated measures analysis of variance showed that the time effects （F=139.336， 234.747）， group effects （F=43.900， 101.266）， and time-group interaction effects （F=13.409， 43.216） for HAMD-17 and HAMA scores in both groups were statistically significant （P<0.01）. After 4 and 8 weeks of treatment， the HAMD-17 and HAMA scores in both groups were lower than those before treatment， with statistically significant differences （P<0.05）. HAMD-17 and HAMA scores in the study group were lower than those in the control group （P<0.05）. The time effects （F=571.356， 309.266， 414.492）， group effects （F=6.901， 26.361， 39.362）， and time-group interaction effects （F=18.592， 19.266， 33.484） for the protein expression levels of PI3K， AKT， and pAKT in both groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the protein expression levels of PI3K and pAKT in the study group were lower than those in the control group， while the AKT protein expression level was higher than that in the control group（P<0.01）. The time effects （F=338.555， 225.059）， group effects （F=5.429， 9.726）， and time-group interaction effects （F=12.953， 21.214） for PI3K mRNA and AKT mRNA expression levels in two groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the expression levels of PI3K mRNA and AKT mRNA in the study group were lower than those in the control group （P<0.05）. The incidence of adverse reactions in the study group was lower than that in the control group （χ²=4.810， P<0.05）. ConclusionShugan Yunpi Decoction may help to ameliorate depressive and anxiety symptoms in colorectal cancer patients with depressive disorder by regulating the PI3K-AKT signaling pathway， decreasing the levels of PI3K， pAKT， PI3K mRNA， and AKT mRNA， with a favorable safety profile. ［Funded by Baoding City Science and Technology Planning Project （number， 2341ZF291）］