BACKGROUND:Bone remodeling is the biological basis of orthodontic tooth movement.Type 2 diabetes mellitus leads to metabolic changes in the jaw and alveolar bone,so it is hypothesized that tooth mobility characteristics may be altered in a high-sugar environment.OBJECTIVE:To explore the impact of type 2 diabetes mellitus on orthodontic tooth movement in rats within one tooth movement cycle.METHODS:Seventy-two Sprague-Dawley rats were selected.Forty rats were randomly chosen and fed with a high-fat diet to construct a type 2 diabetes mellitus model.Thirty-two rats that were successfully modeled were randomly divided into a type 2 diabetes mellitus group(n=16)and a diabetic orthodontic group(n=16).The remaining 32 rats were randomly divided into a control group(n=16)and an orthodontic group(n=16).The rats in the orthodontic group and the diabetic orthodontic group were equipped with nickel-titanium coil spring orthodontic force application devices to move the unilateral maxillary first molars mesially with a force of 50 g.The rats were anesthetized and sacrificed on the 3rd,7th,14th,and 21st days after orthodontic treatment,and Micro-CT was used to measure the mesial displacement of the first molars and detect the changes in the bone microstructure parameters on the tension side.RESULTS AND CONCLUSION:There were significant differences in the tooth movement distances among the four groups of rats on the 3rd,7th,14th,and 21st days of orthodontic treatment(P＜0.05).There were significant differences in bone mineral density,bone volume fraction and trabecular bone separation on the tension side among the four groups on the 7th,14th,and 21st days of orthodontic treatment(P＜0.05).There were differences in the trabecular thickness among the four groups on the 3rd and 14th days of orthodontic treatment(P＜0.05).The diabetic orthodontic group had the smallest tension-side alveolar bone mineral density,bone volume fraction,and trabecular thickness,and the largest tooth movement distance and trabecular separation on the 21st day of orthodontic treatment.The above results indicate that type 2 diabetes mellitus adversely affects bone microstructural parameters on the tension side in orthodontic tooth movement in rats,suggesting the occurrence of an osteoporotic state.

BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

BACKGROUND:Multistimuli-responsive hydrogels have received extensive attention in the field of bone tissue engineering due to their special responsive capabilities and diverse functions.OBJECTIVE:To review the application of multistimuli-responsive hydrogels in bone damage repair,and explore their research and development ideas and future development directions.METHODS:Relevant literature was retrieved from PubMed,Web of Science,and WanFang databases.English search terms included"hydrogels,bone defect,bone repair,bone healing,bone tissue engineering,degenerative joint diseases,osteoarthritis,Cartilage."Chinese search terms were"multistimuli-responsive hydrogels,smart hydrogels,bone damage repair,bone tissue engineering."The search time limit was from database inception to August 2024.A total of 83 articles were included in the review.RESULTS AND CONCLUSION:Multistimuli-responsive hydrogels can react to various levels of physical,chemical,and biological stimuli,while exerting inherent functions such as swelling,deformation,degradation,and other special functions endowed by materials,making them highly potential in addressing clinical problems in bone damage repair.However,in practical applications,how to ensure that these materials maintain stability and durability in the complex biological environment and can be degraded in a controllable and harmless manner when needed is an urgent problem to be solved.

BACKGROUND:The surgical treatment of severe lumbar fractures is mainly based on posterior short-segment fixation,and different pedicle screw fixation methods have differences in biomechanical properties.OBJECTIVE:To simulate three different screw fixation techniques in the treatment of severe L1 vertebral fractures using three-dimensional finite element technology,and to compare and analyze the biomechanical characteristics of the upper and lower intervertebral discs,fractured vertebrae,and internal fixation devices during the simulated spinal movement.METHODS:A three-dimensional model of the T11-L3 spine was established to simulate severely unstable fracture of the lumbar 1 vertebral body using the designed three pedicle screw fixation methods:Model A with 4 traditional pedicle screws(2 in each T12 and L2),model B with 4 Universal Spine System pedicle screws(2 in each T12 and L2),and Model C were bilateral intermediate fixation with 6 pedicle screws(2 in each of T12,L1,and L2).Restraint and load were applied to simulate the maximum stress and maximum displacement of the internal fixation,the displacement of the L1 vertebral body,and stress on the intervertebral discs superior and inferior to the injured vertebra during the anterior flexion,posterior extension,left-sided bending,right-sided bending and left-right rotation of the lumbar spine.RESULTS AND CONCLUSION:(1)The maximum displacement and motion range of the lumbar 1 vertebra with Model C in flexion and extension,left bending,right bending,left rotation,and right rotation were lowest in the tested motion states;the maximum stress of the screws and connecting rods was the smallest;and the maximum stress of intervertebral discs superior and inferior to the injured vertebra was the smallest.This was followed by the Model B,while the maximum displacement and motion range of the lumbar 1 vertebra and the stress and displacement of the screw connecting rod in the Model A were highest,but it showed the worst biomechanical stability and was more prone to adjacent segment degeneration.(2)These results show that bilateral intermediate fixation with six pedicle screws during the treatment of severe lumbar fractures is more dispersed in internal fixator stress and exhibits the least displacement and motion range of the vertebral pedicle screws and rods compared with four universal spinal system pedicle screws and four traditional pedicle screws.Thus,it can effectively reduce the occurrence of internal fixation failure and the adjacent segment degeneration.

BACKGROUND:Exercise is an effective way to improve microvascular function in patients with type 2 diabetes.In recent years,exercise has been used as an intervention therapy for microvascular dysfunction in patients with type 2 diabetes.However,few studies have systematically explored the influence of factors,such as"exercise type,exercise intensity and amount of exercise,"on microvascular function in patients.To some extent,this limits the formulation of precise exercise prescriptions to improve microvascular dysfunction in patients with type 2 diabetes and the comparison of study results.OBJECTIVE:To investigate the effects of exercise type,intensity,frequency and amount of exercise on microvascular function in patients with type 2 diabetes mellitus,and to make suggestions on exercise prescription.METHODS:The first author used computer to search the studies on the improvement of microvascular function in type 2 diabetes patients involving exercise in CNKI,WanFang,PubMed and other databases.The search terms were"diabetes mellitus,type 2 diabetes mellitus,microcirculation,microvascular reactivity,microvessels,capillaries,vasodilation,blood perfusion volume,endothelial cells,shear stress,exercise,aerobic exercise,resistance exercise,high-intensity exercise"in Chinese and English.The articles were screened by a quick glance at the article titles and abstracts to exclude those that were not closely related to the topic,and finally 60 articles were included for review.RESULTS AND CONCLUSION:(1)Exercise is an effective way to improve microvascular function in patients with type 2 diabetes.Aerobic exercise lasting 12-24 weeks,3-5 times/week,exercise time＞30 minutes and intensity between 40％and 59％reserve oxygen intake can significantly improve microvascular function in patients with type 2 diabetes.On the basis of aerobic exercise,systemic resistance exercise 2-3 times a week(50％-85％1RM,every other day)or pressure resistance exercise can obtain better intervention effects.(2)In addition,exercise can improve microvascular function in patients with type 2 diabetes in a"dose-effect"manner,and patients can get better results from the intervention by increasing the amount of exercise,while maintaining safety.(3)The mechanism of exercise improving microvascular function in patients with type 2 diabetes is mainly related to promoting the release of nitric oxide and vascular endothelial growth factor from endothelial cells and inhibiting the release of endothelin1.

Objective:To investigate the diagnostic consistency of extrauterine growth restriction (EUGR) assessed by the Fenton 2013 preterm growth charts (Fenton 2013) and the growth charts by International Fetal and Newborn Growth Consortium for the 21st Century (IG-21).Methods:This multicenter retrospective cohort study included 5 591 preterm infants with a gestational age (GA) at birth of less than 32 weeks admitted to 19 member hospitals of the Neonatal Perinatal Collaborative Network of Suxinyun from January 1 st, 2019, to December 31 st, 2024. Clinical data including baseline characteristics, complications, feeding practices and anthropometrics were processed and analyzed. EUGR was assessed using both the Fenton 2013 and the IG-21. A decrease in weight Z-score at discharge compared to admission by more than 1 was defined as longitudinal EUGR, and discharge weight below the P10 for the corresponding corrected GA was defined as cross-sectional EUGR. Diagnostic consistency was assessed using the Kappa coefficient between the 2 standards, and diagnostic performance of the 2 standards was compared using the McNemar test. Risk factors for EUGR under different definitions were analyzed using univariate analysis and multivariate Logistic regression analysis. Results:A total of 5 591 preterm infants were included, with a GA at birth of (29.7±1.6) weeks and a birth weight of (1 360±315) g and at discharge with a corrected GA of (36.3±2.0) weeks and weight of (2 246±370) g. Detection rates of cross-sectional and longitudinal EUGR diagnosed by Fenton 2013 were both higher than those by IG-21 (37.0% (2 214/5 991) vs. 23.7% (1 324/5 591), 61.1% (3 662/5 991) vs. 30.7% (1 714/5 591), χ2=326.77 and 1 358.05, both P<0.001). Using Fenton 2013 as a reference, IG-21 demonstrated superior diagnostic value and consistency in identifying cross-sectional EUGR compared with longitudinal EUGR (sensitivity of 100.0% (3 377/3 377) vs. 99.6% (1 922/1 929), specificity of 59.8% (1 324/2 214) vs. 46.6% (1 707/3 662), positive predictive value of 79.1% (3 377/4 267) vs. 49.6% (1 922/3 877), negative predictive value of 100.0% (1 324/1 324) vs. 99.6% (1 707/1 714), accuracy of 84.1% (4 701/5 591) vs. 64.9% (3 629/5 591), and Kappa 0.64 vs. 0.37, all P<0.001). In multivariate Logistic regression models, risk factors common to EUGR across both standards included smaller GA at birth, lower birth weight, boy, early-onset sepsis, late-onset sepsis and the elder age at full enteral feeding (all P<0.05). Hemodynamically significant patent ductus arteriosus remained an independent risk factor for longitudinal EUGR regardless of whether by the Fenton 2013 or IG-21 standard (adjust odds ratio ( aOR) =1.25 and 1.27, 95% CI 1.09-1.42 and 1.11-1.45). In addition, under the IG-21 standard, severe bronchopulmonary dysplasia was an independent risk factor for cross-sectional EUGR ( aOR=1.54, 95% CI 1.00-2.38), while severe necrotizing enterocolitis was an independent risk factor for longitudinal EUGR ( aOR=2.18, 95% CI 1.01-4.73). Conclusions:IG-21 showed lower detection rates of both cross-sectional and longitudinal EUGR than Fenton 2013, suggesting greater clinical applicability of IG-21 by reducing overdiagnosis while maintaining sensitivity for predicting complications. Across both standards, cross-sectional EUGR facilitates early identification of growth restriction, whereas longitudinal EUGR better tracks dynamic growth patterns and complications of preterm infants.

Pancreatic neuroendocrine neoplasms represent a highly heterogeneous group of malignancies exhibiting a broad spectrum of biological behaviors ranging from indolent to highly aggressive. The formulation of therapeutic strategies requires a comprehensive consideration of patient condition and tumor biological characteristics. Neoadjuvant therapy has demonstrated promising efficacy in tumor downstaging,enhancing R0 resection rates,and improving prognoses across various solid tumors,yet its application in pancreatic neuroendocrine neoplasms remains underexplored with limited clinical evidence. This review systematically examines critical issues in neoadjuvant management of pancreatic neuroendocrine neoplasms based on contemporary guidelines and emerging literature,encompassing patient selection criteria,regimen optimization,response evaluation,and optimal surgical timing. Current challenges persist in standardizing neoadjuvant approaches,necessitating multicenter prospective studies to establish high-level evidence. Future advancements in artificial intelligence and precision medicine hold potential to revolutionize personalized therapeutic paradigms,ultimately improving patient survival outcomes.

ObjectiveTo investigate the effects of Yishen Juanbi pills （YSJB）-containing bone marrow fluid on the migration and differentiation phenotypes of CD4⁺T lymphocytes based on the stromal cell-derived factor-1/chemokine receptor 4 （SDF-1/CXCR4） signaling pathway. MethodsPrimary CD4⁺T lymphocytes were isolated from mice using magnetic bead separation and identified for purity by flow cytometry. A CD4⁺T lymphocyte culture system was then established to observe the effects of SDF-1 on CD4⁺T-cell migration and differentiation. On this basis， the experimental groups included the Sham group， the ovariectomy （OVX） group， the Sham+collagen-induced arthritis （CIA） group， the OVX+CIA group， the Sham+CIA+YSJB group （2.16 g·kg^-1）， the OVX+CIA+YSJB group （2.16 g·kg^-1）， and the OVX+CIA+methotrexate （MTX） group （1.5 mg·kg^-1）. Bone marrow fluid from each group was prepared according to previous methods and added to the CD4⁺ T-cell culture system at 5% （v/v）. Transwell assays were used to examine CD4⁺T-cell migration in each group. Real-time PCR was used to measure the mRNA expression levels of interleukin （IL）-17， tumor necrosis factor-α （TNF-α）， retinoic-acid-related orphan receptor γt （RORγt）， IL-10， transforming growth factor-β （TGF-β）， forkhead box P3 （FoxP3）， CXCR4， phosphoinositide 3-kinase （PI3K）， and protein kinase B （Akt）. Western blot was used to detect the expression of helper T （Th）17/regulatory T （Treg） cell signature factors （RORγt， FoxP3）， CXCR4， PI3K， phosphorylated （p）-PI3K， Akt， and p-Akt. In a separate set of experiments， cells were divided into the Sham group， OVX+CIA group， OVX+CIA+CXCR4 antagonist AMD3100 group， and OVX+CIA+YSJB+AMD3100 group to observe changes in the above indicators following AMD3100 intervention. ResultsCompared with the Sham group， the number of migrated cells in the lower chamber was significantly increased in the Sham+CIA and OVX+CIA groups （P<0.05， P<0.01）. The mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was significantly upregulated， whereas FoxP3， IL-10， and TGF-β mRNA expression was significantly decreased （P<0.05， P<0.01）. Protein expression of RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt was significantly increased， while FoxP3 protein expression was markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA group， the OVX+CIA+YSJB group and OVX+CIA+MTX group showed significantly reduced migration （P<0.05）， mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was also significantly decreased， while FoxP3， IL-10， and TGF-β mRNA expression was significantly increased （P<0.05， P<0.01）. RORγt protein expression was significantly downregulated， and FoxP3 protein expression markedly upregulated （P<0.05）. In the OVX+CIA+YSJB group， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was significantly decreased （P<0.05）. Compared with the OVX+CIA group， RORγt， CXCR4， PI3K， and Akt mRNA expression in CD4⁺T cells was significantly decreased in the OVX+CIA+AMD3100 group and the OVX+CIA+YSJB+AMD3100 group， while FoxP3 mRNA and protein expression was significantly upregulated （P<0.05， P<0.01）. RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was also markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA+AMD3100 group， the OVX+CIA+YSJB+AMD3100 group showed significantly decreased RORγt and Akt mRNA expression （P<0.05） and significantly lower p-Akt/Akt protein expression （P<0.05）. ConclusionYSJB-containing bone marrow fluid suppresses CD4⁺T-cell migration and regulates Th17/Treg balance by downregulating Th17-associated signature factors and upregulating Treg-associated signature factors through inhibition of the SDF-1/CXCR4 signaling pathway and PI3K/Akt signaling pathway. The SDF-1/CXCR4 signaling pathway is one of the targets through which YSJB inhibits CD4⁺T-cell differentiation.

In the context of the digital-intelligent era of traditional Chinese medicine （TCM）， the lack of clinical thinking is a pressing issue that limits the overall effectiveness of TCM and talent cultivation. The "disease-pulse-syndrome-treatment differentiation" thinking model， originally developed by ZHANG Zhongjing in the Treatise on Cold Damage and Miscellaneous Diseases （Shang Han Za Bing Lun）， has served as a guideline and paradigm followed by generations of medical practitioners. This study aims to construct a digitalized "disease-pulse-syndrome-treatment differentiation" thinking system， develop a digital assessment system， and implement it for practical application. The goal is to recommend a digitalized assessment model for TCM and provide a reference for the integrated innovation of talent cultivation in medicine， education， and research. First， based on the complex diagnostic and treatment framework of the Treatise on Cold Damage Diseases （Shang Han Lun）， the research team previously established a "process" + "result" thinking model that included four processes and ten steps. This study integrates knowledge unit theory and digital technology to create a digital system for "disease-pulse-syndrome-treatment differentiation" with a dual-control model of "process control" and "result control". The system consists of 46 items across three categories： knowledge body （W=20%）， knowledge element （W=30%）， and knowledge element associations （W=50%）. Second， a mixed-methods research design was employed， combining qualitative and quantitative approaches. The Delphi method was used to establish hierarchical levels and screen items， while the analytic hierarchy process （AHP） was used to assign weights. Expert surveys were conducted to reach a consensus and further validate the rationale and necessity of the system. Finally， based on the system architecture and integrating key computer technologies， a digital assessment system for "disease-pulse-syndrome-treatment differentiation" was developed. The Treatise on Cold Damage Diseases （Shang Han Lun） was used as a case study to validate the system's feasibility. Statistical results showed that the difficulty level of the assessment question bank was moderate （DL ranging from 0.65 to 0.89）， with good discrimination （D>0.4）， and reasonable reliability and validity （Cronbach's α=0.84， KMO=0.72， Bartlett's test P<0.01）. The system can perform process-oriented evaluations of candidates' thinking in "disease-pulse-syndrome-treatment differentiation" and effectively achieve the goal of clinical thinking assessment through a combination of "process control" and "result control". The examination system offers three major advantages. It standardizes， objectifies， and streamlines the assessment of thought processes， facilitates the organic transformation of TCM education from outcome-based education to thinking-based education， and from exam-oriented education to competency-oriented education， and promotes the practical transformation of TCM assessments from qualitative to quantitative evaluation， as well as from theory to practice. In summary， this system not only represents a technological upgrade to traditional examinations but also empowers the cultivation and assessment of clinical talent in the digital-intelligent era， demonstrating broad application prospects.

Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.