In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

Sarcopenia is a systemic skeletal muscle disease characterized by the gradual decline of muscle mass，strength，and function，and its occurrence and development are related to multiple factors，involving several signaling pathways. Among them，the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway，as a key pathway regulating cellular growth，survival，and metabolism，plays an important role in the formation and development of sarcopenia. Its abnormal activation or deactivation may lead to an imbalance in muscle protein metabolism，resulting in muscle atrophy and reduction. Modern medicine is still in the exploratory stage of treatment for sarcopenia. Traditional Chinese medicine （TCM），with its multi-pathway and multi-target characteristics，has shown increasing advantages in the prevention and treatment of sarcopenia. In recent years，various monomers， extracts，and compound formulas of TCM have been proven to effectively prevent and treat sarcopenia by promoting muscle cell protein synthesis，reducing protein degradation，inhibiting cell apoptosis and inflammatory response，and improving mitochondrial function. This paper reviewed the improvement effects of TCM on sarcopenia based on the PI3K/Akt pathway and explored its specific action mechanisms， aiming to provide new insights for the treatment of sarcopenia with TCM.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

AIM:To automatically identify and quantitatively assess myopia-related fundus structural changes by combining non-mydriatic color fundus photography with an artificial intelligence(AI)-powered quantitative fundus analysis system and to further analyze the correlations between these fundus parameters and spherical equivalent(SE), axial length(AL), and age, providing the objective basis for monitoring myopia progression and supporting the formulation of personalized myopia prevention and control strategies. METHODS:A cross-sectional study was conducted enrolling myopic patients aged 18-50 y who underwent myopia screening from March 2023 to December 2023. Patients were stratified into three groups based on SE: the -3.00 D

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Objective This study aimed to investigate the seasonal variation of mosquitoes in Yantai, Shandong Province, and provide a scientific basis for mosquito and mosquito-borne disease control. Methods From March to November for each of the years between 2020 and 2023, adult mosquitoes were collected from different habitats, including parks, hospitals, urban residential areas, rural households and livestock sheds, in 13 counties of Yantai City using a mosquito trap lamp method, among which, female mosquitoes were separated and identified, and the numbers were counted. We used the circular distribution method to analyze the temporal distribution characteristics of mosquito density. Results The γ values obtained for mosquitoes in Yantai from 2020 to 2023, the distribution of mosquitoes in different habitats, and dominant mosquito species in different months showed strong seasonality, with values ranging from 0.7461 to 0.8531(P ＜ 0.05). The peak period of seasonal variation in mosquitoes occurred from June 28thto September 13th, with August 5thbeing identified as the peak day. The peak periods of seasonal variation in mosquitoes in residential areas, parks, hospitals, peasant households, and animals sheds were observed from June 24thto September 14th, June 25thto September 10th, June 22ndto September 12th, July 1stto September 9th, and July 2ndto September 17th, respectively, with corresponding peak days on August 4th,3rd, 2nd, 5th, and 9th, respectively. The peak periods of Culex pipiens pallens, Aedes albopictus, and Anopheles sinensis were from June 26thto September 11th, June 28thto September 17th, and July 12thto September 17th, respectively, with corresponding peak days on August 3rd,7th, and 14th, respectively. Conclusions Our findings in this study revealed that the peak of mosquito activity in Yantai was concentrated in early August, with a peak period extending from June 28thto September 13th, and there were differences between different habitats(with peak periods for rural households and livestock sheds occurring later than those in residential areas, parks, and hospitals). Moreover, with respect to the mosquito species, populations of Cx. pipiens pallens and Ae. albopictus peaked earlier than those of An. sinensis. Based on these findings, we recommend that city-wide mosquito control work should commence in late June, and include appropriate early prevention and control measures for key habitats, such as livestock sheds, and dominant mosquito species, such as Cx. pipiens pallens, to minimize the density of mosquito vectors and the risk of disease transmission.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective: To examine the effects of combined aerobic and resistance exercise on health related physical fitness (HPF) and depressive symptoms among senior high school freshmen, and to examine whether HPF mediates the relationship between exercise intervention and depressive symptoms, so as to provide a scientific basis for the coordinated promotion of mental health and physical fitness in schools. Methods: In March 2022, 190 senior high school freshmen from a secondary school of Suzhou in Anhui Province were selected by the random cluster sampling method and randomly assigned to an intervention group ( n = 99) and a control group ( n =91). The control group maintained routine activities, while the intervention group underwent a 10 week combined aerobic and resistance exercise program, three sessions per week, 40 minutes per session. Height, weight, standing long jump, sit ups, 20 m shuttle run, and sit and reach were measured before and after the intervention. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CES-D). Analysis of covariance (ANCOVA), Mann-Whitney U test, and Wilcoxon test were employed to compare outcomes before and after the intervention, and mediation analysis was conducted. Results: After controlling for pre test scores, ANCOVA results showed that compared with the control group, the intervention group demonstrated the following post intervention changes: a lower body mass index of 0.1 kg/m 2 among girls; higher standing long jump (13.2 cm for boys, 7.4 cm for girls), higher sit ups (5.5 reps for boys, 3.7 reps for girls), higher 20 m shuttle run (7.4 times for boys, 5.1 times for girls), and higher sit and reach (3.2 cm for boys, 0.4 cm for girls) ( F =17.88-84.44); and lower CES-D scores (5.5 for boys, 4.0 for girls) ( Z =-2.51, -2.06) (all P <0.05). The indirect effect of HPF in the relationship between combined aerobic and resistance exercise and depressive symptoms was -2.11, supporting a partial mediation effect ( P < 0.01 ). Conclusions Combined aerobic and resistance exercise improves HPF and alleviates depressive symptoms to varying degrees among senior high school freshmen. HPF served as a partial mediator through which exercise intervention reduces depressive symptoms.