[摘 要] 目的：构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒（DPM），探讨其对三阴性乳腺癌（TNBC）细胞4T1及其小鼠移植瘤的治疗效果。方法：通过物理吸附法制备 DPM 纳米颗粒，利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞，细胞实验分为对照组、超声辐照组（US组）、DPM治疗组（DPM组）和DPM治疗联合超声辐照组（DPM + US组），用CCK-8法检测细胞活性，免疫荧光法检测高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的表达，WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型，分为四组，处理同细胞实验，测量肿瘤体积，免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ（HIF-1ɑ）蛋白的表达，TUNEL法检测细胞凋亡，流式细胞术检测免疫细胞活化情况，对主要器官进行H-E染色，以评估纳米材料的体内安全性。结果：DPM呈梭形，平均粒径（268 ± 3.302）nm，电位（33.1 ± 0.87）mV。细胞实验中，DPM联合超声辐照可明显抑制4T1细胞的增殖（P < 0.001），提高4T1细胞中ROS水平（P < 0.001），诱导4T1细胞CRT表达上调（P < 0.001），HMGB1从细胞核中移至细胞质，激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加（均P < 0.001）]。体内实验中，DPM联合超声辐照可显著抑制4T1细胞移植瘤生长（P < 0.001）并促进免疫细胞表型转化（P < 0.001），抑制移植瘤组织中Ki-67、HIF-1α蛋白表达（均P < 0.01），谷胱甘肽（GSH）产生（P < 0.01），促进CRT、HMGB1蛋白表达、ROS产生（P < 0.001），对主要器官结构无明显影响。结论： DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长，诱导抗肿瘤免疫应答，且对主要器官无明显毒性。

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

This paper has summarized current studies on retinitis pigmentosa （RP） from two perspectives， which were disease mechanism insights from western medicine， and etiology， pathogenesis and therapeutic principles in traditional Chinese medicine （TCM）. From the perspective of western medicine， the understanding of RP has evolved from an early single-factor explanation focusing on pathogenic gene mutations to a more comprehensive， multifactorial model involving genetic abnormalities， photoreceptor cell degeneration， retinal pigment epithelium dysfunction， oxidative stress， inflammatory responses， microenvironmental imbalance， and vascular insufficiency. In TCM， RP is considered to be a disorder manifested in the eyes but rooted in dysfunction of the zang-fu （脏腑） organs. Its pathogenesis is primarily associated with congenital insufficiency， liver-kidney depletion， impaired spleen function of transportation and transformation， and stasis obstructing the meridians. The core pathological mechanism can be summarized as "deficiency complicated by stasis"， emphasizing holistic imbalance， dynamic disease progression， and syndrome differentiation and treatment. The differences and complementarities between the two medical systems in understanding disease progression are further discussed. RP is proposed to be more appropriately regarded as a complex disease characterized by long-term progression， stage-dependent evolution， and persistent decompensation. Western medicine contributes to elucidating the molecular mechanisms underlying RP and provides the foundation for targeted therapeutic interventions， whereas TCM offers a holistic perspective for understanding disease evolution through the assessment of overall functional status， disease-stage stratification， and long-term syndrome-based regulation.

This paper has summarized current studies on retinitis pigmentosa （RP） from two perspectives， which were disease mechanism insights from western medicine， and etiology， pathogenesis and therapeutic principles in traditional Chinese medicine （TCM）. From the perspective of western medicine， the understanding of RP has evolved from an early single-factor explanation focusing on pathogenic gene mutations to a more comprehensive， multifactorial model involving genetic abnormalities， photoreceptor cell degeneration， retinal pigment epithelium dysfunction， oxidative stress， inflammatory responses， microenvironmental imbalance， and vascular insufficiency. In TCM， RP is considered to be a disorder manifested in the eyes but rooted in dysfunction of the zang-fu （脏腑） organs. Its pathogenesis is primarily associated with congenital insufficiency， liver-kidney depletion， impaired spleen function of transportation and transformation， and stasis obstructing the meridians. The core pathological mechanism can be summarized as "deficiency complicated by stasis"， emphasizing holistic imbalance， dynamic disease progression， and syndrome differentiation and treatment. The differences and complementarities between the two medical systems in understanding disease progression are further discussed. RP is proposed to be more appropriately regarded as a complex disease characterized by long-term progression， stage-dependent evolution， and persistent decompensation. Western medicine contributes to elucidating the molecular mechanisms underlying RP and provides the foundation for targeted therapeutic interventions， whereas TCM offers a holistic perspective for understanding disease evolution through the assessment of overall functional status， disease-stage stratification， and long-term syndrome-based regulation.

ObjectiveTo observe the effect of rehabilitation robot training on abdominal muscles thickness and balance ability in children with hemiplegia. MethodsFrom October, 2024 to December, 2025, 58 children with hemiplegia were admitted to Beijing Bo'ai Hospital and randomly divided into control group (n = 29) and experimental group (n = 29). Both groups received conventional rehabilitation treatment, and the experimental group received rehabilitation robot training in addition, for four weeks. The thickness of bilateral external oblique, internal oblique and transversus abdominis, Berg Balance Scale (BBS) score, the time of Timed Up and Go Test (TUGT), the center of pressure (COP) ellipse area, and self-selected walking speed (SWS) and maximum walking speed (MWS) of 10-meter walk test were compared before and after training. ResultsThree cases dropped out in each group. After training, the thickness of the external oblique, internal oblique and transverse abdominis on the hemiplegic side increased significantly in the experimental group (|t| > 7.280, P < 0.001, Cohen's d = 1.43~2.01), and was better in the experimental group than in the control group (|t| > 2.895, P < 0.01, Cohen's d = 0.80~1.60); the BBS score increased in both groups (|t| > 6.667, P < 0.001, Cohen's d = 1.30~4.06), and was better in the experimental group than in the control group (t = -2.721, P < 0.01, Cohen's d = 0.75). The time of TUGT decreased in both groups (t > 5.790, P < 0.001, Cohen's d = 1.14~2.68), and was better in the experimental group than in the control group (t = 2.290, P < 0.05, Cohen's d = 0.63). The SWS and MWS increased in both groups (|Z| > 2.910, P < 0.01, r = 0.40~0.68), and were better in the experimental group than in the control group (|Z| > 2.912, P < 0.05, r = 0.40~0.45), and the differences remained significant after correction. ConclusionRehabilitation robot training can improve the thickness of external oblique, the internal oblique and transversus abdominis muscles on the hemiplegic side in children with hemiplegia, and improve their balance and walking functions.

Objective To analyze the global pattern, long-term trends, and regional and population heterogeneity in the burden of 375 diseases and injuries and 88 risk factors from 1990 to 2023 using data from the Global Burden of Disease Study 2023 (GBD 2023). Methods Publicly available GBD 2023 estimates were extracted for incidence, deaths, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs), and age-standardized rates at the global level and by socio-demographic index (SDI), GBD region, age group, and sex. Descriptive analysis, ranking comparison, stratified analysis, and trend analysis were performed, and 95% uncertainty interval was used to assess the stability of estimates. Results In 2023, non-communicable diseases were the leading contributor to global DALYs, accounting for 64.39% of DALYs across the three major disease and injury groups (communicable, maternal, neonatal, and nutritional diseases, non-communicable diseases, and injuries), and also had the highest age-standardized DALYs rate. From 1990 to 2023, age-standardized DALYs rates declined for three major disease and injury groups, with estimated annual percentage changes of −2.69%, −0.78%, and −1.47%, respectively. Cardiovascular diseases ranked first by both DALYs and deaths in 2023, whereas respiratory infections and tuberculosis ranked first by incidence. Non-communicable diseases were the leading cause of disease burden across all SDI strata. As the SDI level declined, the burden of communicable, maternal, neonatal, and nutritional diseases, as well as injuries, increased markedly. Behavioral and metabolic risks remained the main contributors to attributable deaths and DALYs. Conclusion From 1990 to 2023, the global burden of disease continues to shift toward non-communicable diseases; however, some regions still face a double burden of infectious, maternal and child, injury-related, and chronic diseases. Integrating deaths, DALYs, YLLs, YLDs, and risk-attributable burden helps identify priority areas for prevention and resource allocation across regions and populations.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

BACKGROUND:Osteoporotic vertebral fractures are the most common complication in patients with osteoporosis.As a new imaging technique,spine magnetic resonance imaging(MRI)is much more sensitive than X-ray film in the diagnosis of osteoporotic vertebral fractures.However,total spine MRI is costly and takes a long time to scan.Therefore,there is no consensus on whether all patients with osteoporotic vertebral fractures need to undergo total spine MRI scan and which patients need to undergo total spine MRI. OBJECTIVE:To analyze the distribution characteristics of vertebral fractures and explore their clinical significance by observing the whole spine MRI data of osteoporotic vertebral fractures patients. METHODS:Data of cases and MRI images of all patients diagnosed with fresh osteoporotic vertebral fractures who visited the Department of Orthopedics,Affiliated Hospital of Southwest Medical University from August 2018 to September 2022 were retrospectively analyzed.903 patients were included in the study based on inclusion and exclusion criteria.General information(age,gender,and body mass index),medical history characteristics(duration of illness,history of trauma surgery,percussion pain area,and pain score)were collected.The characteristics of vertebral fractures were analyzed through whole spine magnetic resonance imaging.Firstly,based on the number of vertebral fractures in patients,they were divided into the single vertebral fracture group(484 cases)and the multi-vertebral fracture group(419 cases),and the differences were analyzed between the two groups.Then,based on whether the farthest interval between the fractured vertebrae was greater than or equal to 5,the multi vertebral fracture group was further divided into two subgroups.Among them,Group A(the farthest interval between the fractured vertebrae was less than 5)contained 306 cases;Group B(with the farthest interval between fractured vertebral bodies greater than 5)included 113 cases.The differences were analyzed between two subgroups. RESULTS AND CONCLUSION:(1)Among 903 patients,419 patients(46.4%)had more than two fractured vertebrae.There were 654 patients(72.4%)with thoracolumbar fractures,and 54 patients(6%)with fractures in the thoracic plus lumbar region and the entire thoracic to lumbar region.In group B,96.5%of patients had multiregional percussion pain.(2)Compared with the patients in the single vertebral fracture group and the multi-vertebral fracture group,there were significant differences in bone mineral density,whether the medical history was greater than or equal to 1 month,the history of low energy injury,and the distribution and number of axial percussion pain areas in the spine during physical examination between the two groups(P<0.05).Age,gender,body mass index,whether there was underlying disease,pain visual analog scale score,whether there was a history of elderly thoracolumbar fracture,and whether there was a history of thoracolumbar surgery,and the number of fractured vertebrae had no statistical significance(P>0.05).(3)There were statistically significant differences between the Groups A and B in bone mineral density,the distribution and quantity of percussion pain area,and the history of low energy injury(P<0.05).There were no significant differences in age,gender,history of old fractures,visual analog scale score,body mass index,whether the medical history was longer than or equal to 1 month,history of underlying diseases,and history of thoracolumbar surgery between the two groups(P>0.05).(4)Patients with multiple low-energy trauma history,history of more than 1 month,multiple percussion pain,and the lower bone mineral density should be alert to the occurrence of multiple vertebral fracture and jump fracture.We recommend the whole spinal MRI for these patients.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

Objective: Based on spinopelvic parameters and biomechanical principles, the pedicle-facet joint (PFJ) morphological characteristics of isthmic and degenerative spondylolisthesis were analyzed, and the mechanism of their onset and progression was discussed. Methods: This retrospective cross-sectional study included 194 patients with L5 spondylolysis or L5–S1 low-grade isthmic spondylolisthesis (IS group), 172 patients with L4–5 degenerative spondylolisthesis (DS group), and 366 patients with nonlumbar spondylolysis (NL group). The spinopelvic parameters and PFJ morphological parameters of the patients were measured, the differences in these parameters among and within the 3 groups were compared, and the correlations were analyzed. Results: Sacral slope (SS) and lumbar lordosis (LL) were the highest in the IS group, the second highest in the DS group, and the lowest in the NL group. Among the 3 groups, the L4 facet joint angle (FJA) was the largest in the IS group, the second largest in the NL group, and the smallest in the DS group. The L4 pedicle-facet joint angle (PFA) was the largest in the DS group, the second largest in the IS group, and the smallest in the NL group. Pearson correlation analysis showed that within each group, SS and LL were negatively correlated with FJA and positively correlated with PFA. Conclusion This study found a correlation between the PFJ morphological characteristics of patients with lumbar spondylolisthesis and spinopelvic parameters, suggesting that the morphological characteristics of PFJs may be caused by varying stresses under different spinopelvic morphologies.