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 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.

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.

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.

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 develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Objective:To evaluate the role of tubulin tyrosin ligase like-6 (TTLL6)-mediated microtubule polyglutamylation and Spastin(a microtubule cleaving protein)-induced excessive microtubule cleavage in the developmental impairment of dendritic spines in neonatal mice following repeated sevoflurane anesthesia, by utilizing TTLL6 conditional knockout mice.Methods:Fifty SPF female TTLL6 brain tissue-specific knockout (TTLL6 CKO: Camk2-Cre + ; TTLL6 f/f) and fifty control (TTLL6 CON: TTLL6 f/f) mice with C57BL/6J background, aged 6 days old were selected.TTLL6 CKO mice were divided into TTLL6 CON control group and TTLL6 CON sevoflurane group, and TTLL6 CKO mice were divided into TTLL6 CKO control group and TTLL6 CKO sevoflurane group, with 25 mice in each group by random block method.Mice in the sevoflurane groups were exposed to 3% sevoflurane with 60% O 2 for 2 hours daily on postnatal days 6, 8, and 10.The mice in control groups received only 60% O 2 under the same condition.The polyGlu-Tubulin and postsynaptic density 95(PSD95) protein expression were detected using Western blot. The expressions of TTLL6, Spastin, and α-Tubulin were assessed via immunofluorescence.Golgi staining and electron microscopy were employed to observe the density of hippocampal dendritic spines and synaptic conditions. The Morris water maze test was used to evaluate spatial memory capabilities. Statistical analysis was performed using GraphPad Prism 8.0 software. Results:(1) Behavioral results showed significant time and group interactions among the four groups in terms of latency to find the platform ( F=8.22, P<0.001).Mice in the TTLL6 CON sevoflurane group had a significantly longer escape latency on days 3-7 compared with the TTLL6 CON control group (all P<0.05), while there was no significant difference between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group (all P>0.05). The number of platform crossings differed significantly among the four groups ( H=11.95, P=0.007).The TTLL6 CON sevoflurane group had significantly fewer crossing times than the TTLL6 CON control group ( P<0.05), but no significant difference was observed between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group ( P>0.05). (2) Golgi staining and electron microscopy results revealed significant differences in dendritic spine density and synapse number among the four groups( F=29.00, 41.94, both P<0.001). The dendritic spine density ((5.83±0.40)/10 μm) and the number of synapses ((3.67±0.58)/10 μm) in the TTLL6 CON sevoflurane group were both significantly lower than those in the TTLL6 CON control group ((12.87±1.70)/10 μm, (9.33±0.57)/10 μm)(both P<0.05). In contrast, there was no statistically significant difference between the TTLL6 CKO sevoflurane group and TTLL6 CKO control group (both P>0.05). (3) Immunofluorescence results showed significant differences in the percentage of TTLL6 and Spastin and α-Tubulin co-expressed positive cells in the CA3 region of the hippocampus among the four groups of mice ( F=215.20, 26.08, both P<0.001). The percentage of TTLL6 and Spastin and α-Tubulin co-expressed positive cells in the TTLL6 CON sevoflurane group ((16.75±1.81) %, (47.98±8.42) %) were significantly higher than those in the TTLL6 CON control group ((2.44±0.58) %, (20.07±4.54) %)(both P<0.05), while there was no statistically significant difference between the TTLL6 CKO sevoflurane group and TTLL6 CKO control group ( P>0.05). (4) Western blot results indicated significant differences in the expression of polyGlu-Tubulin and PSD95 proteins in the hippocampal tissue among the four groups of mice ( F=19.66, 8.57, both P<0.001). The TTLL6 CON sevoflurane group had higher polyGlu-Tubulin expression (0.86±0.19) and lower PSD95 expression (0.61±0.13) compared to the TTLL6 CON control group (0.51±0.11, 1.01±0.07) (both P<0.05).However, there was no significant difference between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group ( P>0.05). Conclusion:The mechanism underlying long-term cognitive impairment in developing brain of neonatal mice caused by repeated sevoflurane anesthesia may relate to the upregulation of TTLL6-induced microtubule polyglutamylation and accelerated Spastin-mediated microtubule severing, which ultimately leads to abnormal dendritic spine development.

Objective:To investigate and analyze the thyroid examination results and influencing factors of interventional radiation workers in Tianjin.Methods:In February 2023, A convenient sampling method was used to select the staff engaged in interventional radiation work in an occupational health inspection institution in Tianjin from 2020 to 2022 as the study object. After excluding the incomplete data, 1080 people were included, and 363 medical staff with non-radiological work during the same period were included as the control group. To analyze the individual doses and occupational health examination data of interventional radiation workers, and to analyze the possible influencing factors of thyroid abnormalities.Results:The cumulative dose M ( Q1, Q3) of interventional radiation workers was 1.039 (0.528, 1.905) mSv. The levels of FT 3 and FT 4 in the intervention group were higher than those in the control group, while TSH levels were lower than those in the control group ( Z=4.84、6.03、-5.82, P<0.05). The levels of FT 3 and FT 4 in female interventional radiation workers were lower than those in males, while the levels of TSH were higher than those in males ( Z= -17.54、-6.65、3.61, P<0.05). There were statistically significant differences in FT 3 levels among different ages, differen tradiation exposure years, different initial age of exposure to radiation, and different cumulative doses ( H=47.22、11.33、16.70, Z=-2.48, P<0.05). There were statistically significant differences in thyroid ultrasound abnormalities among different genders, different ages, different initial age of exposure to radiation, and different cumulative doses ( χ2=28.02、61.12、17.87、11.30, P<0.05). The results of logistic regression analysis showed that the influencing factors of FT 3 distributed in the low-level group were female ( OR=10.53, 95% CI: 7.66-14.47, P<0.05), and age 40-49, ≥50 years old ( OR=2.40, 95% CI: 1.12-5.14 OR=3.79, 95% CI: 1.59-9.03, P<0.05). The influencing factors of thyroid ultrasound abnormalities were female ( OR=1.92, 95% CI: 1.48-2.50, P<0.05) and age ≥50 years old ( OR=3.93, 95% CI: 1.91-8.09, P<0.05) . Conclusion:Long term low dose ionizing radiation has a certain effect on FT 3, FT 4 and TSH levels of interventional radiation workers. Gender and increased age are possible influencing factors of the decreased FT 3 levels and thyroid ultrasound abnormalities.