ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription （YJTL） in the treatment of intrauterine adhesion （IUA） from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Keap1/Nrf2/HO-1） signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group （n=8） and a modeling group （n=40）. An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling， the remaining 32 rats were randomly divided into a model group， a low-dose YJTL group （YJTL-L）， a high-dose YJTL group （YJTL-H）， and a Progynova group. Rats in the normal and model groups were administered purified water （15 mL·kg^-1） by gavage daily， while rats in the YJTL-L， YJTL-H， and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg^-1 and Progynova at 2.06 × 10^-4 g·kg^-1， respectively， for 14 consecutive days. The general condition， uterine morphology， and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin （HE） staining. Serum levels of reactive oxygen species （ROS） and glutathione peroxidase （GSH-Px） were measured by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of Keap1， Nrf2， and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence （IF） was used to assess the distribution of Nrf2 and HO-1， as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group， rats in the model group exhibited poor mental status and reduced mobility， markedly edematous and tortuous uterine morphology， decreased gland number， and inflammatory reactions in the endometrium， along with an increased uterine organ index （P<0.05）. Serum ROS levels were significantly increased （P<0.05）， while serum GSH-Px levels were significantly decreased （P<0.05）. In endometrial tissue， Keap1 protein expression was increased （P<0.05）， whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed， accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group， all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced （P<0.05）， serum GSH-Px levels were increased （P<0.05）， Keap1 protein expression in endometrial tissue was decreased， and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner （P<0.05）. Notably， significant nuclear translocation of Nrf2 was observed， with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

ObjectiveCell adhesion is a critical process that regulates cellular physiological functions. Quantitative characterization of adhesion dynamics is essential for elucidating the intrinsic mechanical mechanisms underlying cellular activities. Although atomic force microscopy-based single-cell force spectroscopy is widely used for single-cell adhesion measurements, it requires complex chemical modifications for preparation of live-cell probes, leading to limitations such as cumbersome operation, low throughput, and potential impacts on cell viability. Fluidic force microscopy, which combines atomic force microscopy with microfluidic probes, is a technique allowing the operation of force-controlled nanopipettes in aqueous environments. By applying negative or positive pressure via a pressure controller, a single living cell can be captured onto or released from the cantilever under physiological conditions. This procedure offers a simple workflow and high assay throughput for single-cell adhesion measurements without the need for chemical functionalization. In this study, fluidic force microscopy-based single-cell force spectroscopy was adopted to achieve long-term quantitative characterization of single-cell adhesion dynamics in a simpler and more efficient manner, comparing the dynamic differences in adhesion establishment between two cell lines with different differentiation levels. MethodsHEK 293T and hTERT RPE-1 cells were non-invasively captured on the cantilever of a fluidic force microscope via its integrated microfluidic system during 40 h of adhesion culture. Cell-substrate detachment assays were performed, and force-distance curves were recorded to extract key mechanical adhesion parameters, including adhesion force, adhesion energy, and maximum detachment distance. These measurements were combined with real-time monitoring of cell spreading area to systematically characterize the dynamic evolution of single-cell adhesion. ResultshTERT RPE-1 cells rapidly entered a stable adhesion phase within 1 h after seeding, with both area-normalized adhesion force and area-normalized adhesion energy reaching peak values. In contrast, HEK 293T cells required 4 h to achieve stable adhesion. Subsequently, the adhesion force, adhesion energy and maximum detachment distance of hTERT RPE-1 and HEK 293T cells stabilized at approximately 240 nN vs. 30 nN, 2.2 pJ vs. 0.12 pJ and 6 μm vs. 4 μm, respectively. hTERT RPE-1 cells reached the peak of area-normalized adhesion parameters earlier than HEK 293T cells, with their peak area-normalized adhesion force and area-normalized adhesion energy being substantially elevated relative to HEK 293T cells. HEK 293T cells presented stronger linear correlations among adhesion energy, maximum detachment distance and adhesion force compared with hTERT RPE-1 cells. For both cell lines, cell spreading area exhibited a weak correlation with adhesion force. Whereas the area-normalized adhesion parameters of HEK 293T cells remained relatively constant throughout the adhesion process, hTERT RPE-1 cells exhibited elevated values in the early phase, followed by a gradual decline. These results indicated distinct dynamic adhesion patterns between the two cell types, with hTERT RPE-1 cells exhibiting stronger adhesion strength and higher adhesion efficiency. ConclusionIn this study, fluidic force microscopy-based single-cell force spectroscopy was successfully applied to perform long-term in situ quantitative measurement of the adhesion dynamics in single adherent cells. The approach revealed divergent adhesion patterns between HEK 293T and hTERT RPE-1 cells, suggesting a close association between cell differentiation and adhesion behaviors. These findings provide quantitative mechanical evidence for further understanding the underlying mechanisms of cell adhesion.

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*

The neurophysiological mechanisms by which exercise improves cognitive function have not been fully elucidated. A comprehensive and systematic review of current domestic and international neurophysiological evidence on exercise improving cognitive function was conducted from multiple perspectives. At the molecular level, exercise promotes nerve cell regeneration and synaptogenesis and maintains cellular development and homeostasis through the modulation of a variety of neurotrophic factors, receptor activity, neuropeptides, and monoamine neurotransmitters, and by decreasing the levels of inflammatory factors and other modulators of neuroplasticity. At the cellular level, exercise enhances neural activation and control and improves brain structure through nerve regeneration, synaptogenesis, improved glial cell function and angiogenesis. At the structural level of the brain, exercise promotes cognitive function by affecting white and gray matter volumes, neural activation and brain region connectivity, as well as increasing cerebral blood flow. This review elucidates how exercise improves the internal environment at the molecular level, promotes cell regeneration and functional differentiation, and enhances the brain structure and neural efficiency. It provides a comprehensive, multi-dimensional explanation of the neurophysiological mechanisms through which exercise promotes cognitive function.
Animals ; Humans ; Brain/physiology* ; Cognition/physiology* ; Exercise/physiology* ; Nerve Regeneration/physiology* ; Neuronal Plasticity/physiology*

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

Amid the global wave of digital economy, China's medical artificial intelligence applications are rapidly advancing through technological innovation and policy support, while facing multifaceted evaluation and regulatory challenges. The dynamic algorithm evolution undermines the consistency of assessment criteria, multimodal systems lack unified evaluation metrics, and conflicts persist between data sharing and privacy protection. To address these issues, the China National Health Development Research Center has established a value assessment framework for artificial intelligence medical technologies, formulated the country's first technical guideline for clinical evaluation, and validated their practicality through scenario-based pilot studies. Furthermore, this paper proposes introducing a "regulatory sandbox" model to test technical compliance in controlled environments, thereby balancing innovation incentives with risk governance.
Artificial Intelligence/legislation & jurisprudence* ; China ; Humans ; Algorithms

OBJECTIVE: To investigate effectiveness of simplified all-arthroscopic Broström technique in treatment of chronic lateral ankle instability in adolescents. METHODS: A clinical data of 21 adolescent patients with chronic lateral ankle instability, who met the selection criteria and were admitted between June 2023 and May 2024, was retrospectively analyzed. There were 18 males and 3 females with an average age of 16.0 years (range, 13-18 years). There were 9 cases of left ankle joint injury and 12 cases of right ankle joint injury. Anterior talofibular ligament (ATFL) injury was diagnosed by arthroscopy in all patients. There were 11 cases of cartilage injury, 5 cases of avulsion fractures, and 6 cases of ankle impingement syndrome. The time from first sprain to operation ranged from 3-60 months (mean, 12.0 months). The ATFL was repaired and the ankle joint stability was restored by simplified all-arthroscopic Broström technique. Visual analogue scale (VAS) score, Tegner score, American Orthopaedic Foot and Ankle Society (AOFAS) score, Karlsson ankle function scale (KAFS) score, Foot and Ankle Outcome Score (FAOS) were used to evaluate ankle pain and function. MRI was used to evaluate the ligament healing. RESULTS: All patients were followed up 8-15 months (mean, 12.6 months). After operation, 1 patient suffered from superficial peroneal nerve injury, 1 patient developed anterior scar impingement on the ankle, 2 patients had superficial wound infection, and 1 patient suffered from sprain again. The VAS score, Tenger score, AOFAS score, KAFS score, and FAOS score significantly improved when compared with the preoperative scores ( P<0.05). MRI examination showed the ligament healing and good tension. CONCLUSION For adolescent patients with chronic lateral ankle instability, using simplified all-arthroscopic Broström technique to repair ATFL can effectively alleviate ankle pain, improve stability, and achieve good effectiveness.
Humans ; Joint Instability/surgery* ; Male ; Adolescent ; Female ; Arthroscopy/methods* ; Ankle Joint/physiopathology* ; Retrospective Studies ; Ankle Injuries/surgery* ; Lateral Ligament, Ankle/injuries* ; Treatment Outcome ; Chronic Disease ; Range of Motion, Articular