Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

In recent years, the rising prevalence of obesity and its associated metabolic syndromes has emerged as a critical global public health concern. Sustained weight loss exceeding 10% of total body weight has been shown to ameliorate obesity-related comorbidities, including type 2 diabetes mellitus, hypertension, and hepatic steatosis. Recently, the potential of brown adipose tissue (BAT) to improve metabolism has garnered significant attention. However, evidence regarding weight loss therapies that promote BAT activation remains limited in preclinical models and is even scarcer in clinical studies, partly due to the paucity of appropriate BAT assessment techniques. This review aims to explore the potential impact of various weight loss therapies on BAT, with the goal of providing novel insights and strategies for the treatment of obesity.

ObjectiveThis study aims to investigate the effect of Liuwei Dihuangwan on the autophagy function in the hippocampus of senescence-accelerated mouse prone 8 （SAMP8） by regulating the expression of glycoprotein non-metastatic melanoma protein B （GPNMB）. Furthermore， it is designed to explore the mechanism of the method of tonifying the kidneys and replenishing essence in the treatment of Alzheimer's disease （AD）. MethodsIn experiment 1， 24 5-month-old SAMP8 mice were randomly and equally divided into the model group， and the low-， middle- and high-dose（0.59，1.18，2.36 g·kg^-1） Liuwei Dihuangwan groups. At the same time， six 5-month-old senescence accelerated mouse resistant 1 （SAMR1） mice were used as the control group. The learning and memory ability was evaluated through novel object recognition experiment. Serum cortisol （Cort）， adrenocorticotropic hormone （ACTH） and urine 17-hydroxycorticosteroid （17-OHCS） levels were detected by enzyme-linked immunosorbent assay （ELISA）. The ultrastructure of hippocampal neurons was observed by transmission electron microscope （TEM）， and the expression levels of hippocampal GPNMB， a disintegrin and metalloproteinase 10 （ADAM10） and autophagy-related proteins were detected by Western blot. In experiment 2， 18 SAMP8 mice were randomly and equally divided into the model group， vector control group （Vector）， and GPNMB overexpression group （GPNMB^OE）. Lentiviral vectors were stereotactically injected into the brain （2 μL per side in the GPNMB^OE group）. Western blot was used to detect the expression of the above target proteins in the hippocampus； In Experiment 3， 24 SAMP8 mice were randomly and equally divided into the model group， Liuwei Dihuangwan group， Liuwei Dihuangwan+negative control （NC） group， and Liuwei Dihuangwan+GPNMB silencing group （shGPNMB）. Before drug treatment， the Liuwei Dihuangwan+NC group and the Liuwei Dihuangwan+shGPNMB group were injected with negative control and GPNMB silencing lentivirus， respectively. Western blot was used to detect the expression of the above target proteins in the hippocampus. ResultsThe novel object discrimination index of mice in the model group was significantly lower than that of mice in the control group （P<0.01）. The novel object discrimination index of mice in the medium- and high-dose Liuwei Dihuangwan groups was significantly higher than that of mice in the model group （P<0.01）. Aggregated autolysosomes were observed in the normal hippocampus tissue by TEM. In the model group， mitochondria were dominant， and no typical characteristic autophagosomes were observed. In the low- and medium-dose Liuwei Dihuangwan groups， a small number of autolysosomes and autophagosomes with double-membrane structures were observed. In the high-dose Liuwei Dihuangwan group， the number of autophagosomes and autolysosomes was greater than that in the low- and medium-dose groups. The results of ELISA and Western blot showed that compared with the control group， the levels of serum Cort， ACTH， and urine 17-OHCS in the model group were substantially increased， while the expression of hippocampal ADAM10， Beclin1， and microtubule associated-protein light chain 3-Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ） was significantly decreased. The expression of GPNMB and ubiquitin binding protein p62 was significantly increased （P<0.05， P<0.01）. Compared with the model group， the serum Cort and ACTH levels in the low-， medium-， and high-dose Liuwei Dihuangwan groups were significantly reduced， while only the urine 17-OHCS level in the high-dose group was significantly reduced. The hippocampal GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ expression levels in the medium-， and high-dose groups of Liuwei Dihuangwan were significantly increased compared to the model group， whereas the expression of p62 was significantly reduced （P<0.01）. The above indicators showed a progressive trend among the three groups. Compared with the model group， the GPNMB^OE group showed a significant increase in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ expression， and a significant decrease in p62 expression （P<0.01）. Compared with the model group， the expression of GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ in the hippocampus of the Liuwei Dihuangwan group significantly increased， while the expression of p62 significantly decreased （P<0.01）. Compared with the Liuwei Dihuangwan group， the Liuwei Dihuangwan+shGPNMB group showed a significant decrease in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ， and a significant increase in p62 expression （P<0.01）. ConclusionLiuwei Dihuangwan can enhance hippocampal autophagy function and improve AD by upregulating GPNMB expression.

BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

Objective To investigate the feasibility of parallel capillary bundle arrays for physiomimetic impedance modeling and establish a parametric quantification framework,thereby providing a customizable impedance characterization methodology for diverse in-vitro mock circulation researches.Methods Based on the parallel flow resistance and Poiseuille equation,a tube resistance element with multiple parallel-aligned capillary glass tubes was designed and fabricated.The resistance values of the capillary-bundle and a ball valve were measured through constant flow experiments analogous to electrical resistance measurement method.Moreover,a simple lumped-parameter mock circulation loop was constructed and the pressure and flow rate for each node of the loop were measured under different input flow waveforms.An 0D-Windkessel model corresponding to the experiment was developed.The impedance and compliance were adjusted to match the simulated and experimental pressure and flow waveforms.The accuracy of the capillary bundle impedance in pulsatile experiments was verified by using the computational resistance values.Results The constant-flow impedance calibration experiments revealed that the capillary bundle impedance remained unaffected by flow rate variations over a wide flow range.When the capillary bundle impedance was integrated into the pulsatile circulatory system and the same impedance value obtained from the constant-flow calibration was applied in the computational model,the resulting pressure and flow waveforms showed good agreement with those measured in the pulsatile experiments.However,when the ball valves with nominally identical impedance values were inserted in the pulsatile system,the calculated impedance exhibited a two-fold difference,and significant discrepancies were observed between the simulated and experimental terminal flow waveforms.Conclusions The capillary bundle impedance maintains a constant value regardless of flow rate variations.Once the calibrated resistance value is determined through constant flow experiments,it can be directly applied to pulsatile systems.This approach can provide quantitative pulsatile flow conditions for testing various medical devices.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective To investigate the clinicopathological parameters and risk factors of the patients with connective tissue disease-associated interstitial lung disease(CTD-ILD)complicated with Epstein-Barr virus(EBV)viraemia.Methods The CTD-ILD pa-tients admitted to Department of Respiratory and Critical Care Medicine,Nanjing Drum Tower Hospital from January 2023 to April 2024 were collected.Based on the detection results of EBV DNA,the patients were divided into the EBV DNA(+)group and EBV DNA(-)group.The clinicopathological parameters of the two groups were analyzed.Results Out of 162 CTD-ILD patients who underwent EBV DNA testing,a total of 28 were found to have EBV viraemia.The levels of serum albumin([32.7±4.1]g/L vs[34.8±3.8]g/L,t=2.559,P＜0.05),oxygenation index([268.5±94.0]mmHg vs[323.2±120.9]mmHg,t=2.062,P＜0.05),and percentages of predicted diffusing capacity for carbon monoxide([30.9±15.3]% vs[44.9±18.8]%,t=2.127,P＜0.05])in the EBV DNA(+)group were significantly lower than those in the EBV DNA(-)group,while the levels of lactate dehydrogenase(LDH,[369.1±206.2]U/L vs[298.8±128.7]U/L,t=2.335,P＜0.05)were significantly higher than that in the EBV DNA(-)group.The acute exacerbation of ILD in the EBV DNA(+)group was more common than that in the EBV DNA(-)group(P＜0.05).Multivariate Lo-gistic analysis showed that honeycombing and low oxygenation index were independent risk factors of CTD-ILD patients complicated with EBV viraemia.Conclusion The CTD-ILD patients complicated with EBV viraemia have poorer oxygenation and are more prone to suf-fer from acute exacerbation of ILD.Honeycombing in chest HRCT and low oxygenation index are independent risk factors of CTD-ILD patients complicated with EBV viraemia.

Objective To investigate the feasibility of parallel capillary bundle arrays for physiomimetic impedance modeling and establish a parametric quantification framework,thereby providing a customizable impedance characterization methodology for diverse in-vitro mock circulation researches.Methods Based on the parallel flow resistance and Poiseuille equation,a tube resistance element with multiple parallel-aligned capillary glass tubes was designed and fabricated.The resistance values of the capillary-bundle and a ball valve were measured through constant flow experiments analogous to electrical resistance measurement method.Moreover,a simple lumped-parameter mock circulation loop was constructed and the pressure and flow rate for each node of the loop were measured under different input flow waveforms.An 0D-Windkessel model corresponding to the experiment was developed.The impedance and compliance were adjusted to match the simulated and experimental pressure and flow waveforms.The accuracy of the capillary bundle impedance in pulsatile experiments was verified by using the computational resistance values.Results The constant-flow impedance calibration experiments revealed that the capillary bundle impedance remained unaffected by flow rate variations over a wide flow range.When the capillary bundle impedance was integrated into the pulsatile circulatory system and the same impedance value obtained from the constant-flow calibration was applied in the computational model,the resulting pressure and flow waveforms showed good agreement with those measured in the pulsatile experiments.However,when the ball valves with nominally identical impedance values were inserted in the pulsatile system,the calculated impedance exhibited a two-fold difference,and significant discrepancies were observed between the simulated and experimental terminal flow waveforms.Conclusions The capillary bundle impedance maintains a constant value regardless of flow rate variations.Once the calibrated resistance value is determined through constant flow experiments,it can be directly applied to pulsatile systems.This approach can provide quantitative pulsatile flow conditions for testing various medical devices.