Parkinson's disease （PD） is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra， abnormal aggregation of alpha-Synuclein （α-Syn）， and the formation of Lewy bodies. However， the exact mechanisms remain unclear. In recent years， the PD incidence has gradually increased， while current treatment methods are limited to symptom alleviation， incapable of halting disease progression， and prone to adverse effects， thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is closely related to oxidative stress， neuroinflammation， apoptosis， ferroptosis， and mitochondrial dysfunction， playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine （TCM） can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages， such as multiple targets， multiple pathways， and fewer adverse reactions， TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD， while summarizing the latest research on PD intervention by TCM monomers， active ingredients， and compounds， as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway， aiming to provide a reference for clinical medicine development to prevent and treat PD.

OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

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.

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

BACKGROUND: Parental myopia is an important risk factor for myopia in Chinese children and adolescents. This study aimed to assess the influence of parental myopia and the severity of myopia on offspring and to evaluate whether adopting healthy lifestyles can mitigate the effects of parental myopia on offspring. METHODS: This cross-sectional study analyzed data from children and adolescents aged 6-17 years with complete vision assessments and parental history of myopia from six provinces in China during 2013-2014. Parental demographic information, children's outdoor activity time, sleep time, and sedentary time were collected via questionnaire. Parental myopia was classified as no myopia, paternal myopia, maternal myopia, and both. The offspring were categorized into 10 groups based on parental myopia prescription. Associations of the above factors with myopia in children and adolescents were evaluated by logistic regression analysis. RESULTS: Among 40,864 children and adolescents (50.3% boys and 49.7% girls), 22,537 (55.2%) were diagnosed with myopia. In comparison to offspring devoid of parental myopia, children with one parent affected by myopia exhibited odds ratio (OR) of 1.75 (95% confidence interval [CI]: 1.62-1.88) for myopia, while those with both parents affected showed OR of 2.27 (95% CI: 2.02-2.55) after adjusted for lifestyle factors. The likelihood of myopia in offspring increased with increasing severity of parental myopia, with a 3.08-fold increase in risk observed when both parents presented high myopia. Nonetheless, children adhering to two or more healthy lifestyle factors demonstrated a diminished risk of myopia compared with those with fewer than two lifestyle factors, especially among offspring of non-myopic or mildly myopic parents. CONCLUSIONS Parental myopia has a dose-dependent association with their offspring. Healthy lifestyles may reduce the impact of parental factors on myopia in offspring. The observed associations suggest that although the genetic burden of parental myopia cannot be ignored, healthy lifestyles and nurturing are also very important.
Humans ; Myopia/epidemiology* ; Child ; Male ; Female ; Adolescent ; Cross-Sectional Studies ; China/epidemiology* ; Parents ; Surveys and Questionnaires ; Risk Factors

ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea （PD） in both traditional Chinese medicine （TCM） and western medicine， providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine. MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed， CNKI， and Wanfang Data. According to the diagnostic criteria of TCM and western medicine， the modeling methods in the literature were summarized， evaluated for strengths and weaknesses， and systematically assessed for clinical concordance rates to identify suitable reference models. ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine， respectively. Commonly used modeling methods included estrogen administration， physical stimulation， and surgical intervention， with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate. ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation， but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover， except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome， no animal models for other TCM syndromes have been reported， which limits comprehensive TCM research on this disease to a certain extent.

ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea （PD） in both traditional Chinese medicine （TCM） and western medicine， providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine. MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed， CNKI， and Wanfang Data. According to the diagnostic criteria of TCM and western medicine， the modeling methods in the literature were summarized， evaluated for strengths and weaknesses， and systematically assessed for clinical concordance rates to identify suitable reference models. ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine， respectively. Commonly used modeling methods included estrogen administration， physical stimulation， and surgical intervention， with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate. ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation， but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover， except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome， no animal models for other TCM syndromes have been reported， which limits comprehensive TCM research on this disease to a certain extent.

Metaflammation is a crucial mechanism in the onset and advancement of metabolic disorders, primarily defined by the activation of immune cells and increased concentrations of pro-inflammatory substances. The function of brain-derived neurotrophic factor (BDNF) in modulating immune and metabolic processes has garnered heightened interest, as BDNF suppresses glial cell activation and orchestrates inflammatory responses in the central nervous system via its receptor tyrosine kinase receptor B (TrkB), while also diminishing local inflammation in peripheral tissues by influencing macrophage polarization. Exercise, as a non-pharmacological intervention, is extensively employed to enhance metabolic disorders. A crucial mechanism underlying its efficacy is the significant induction of BDNF expression in central (hypothalamus, hippocampus, prefrontal cortex, and brainstem) and peripheral (liver, adipose tissue, intestines, and skeletal muscle) tissues and organs. This induction subsequently regulates inflammatory responses, ameliorates metabolic conditions, and decelerates disease progression. Consequently, BDNF is considered a pivotal molecule in the motor-metabolic regulation axis. Despite prior suggestions that BDNF may have a role in the regulation of exercise-induced inflammation, systematic data remains inadequate. Since that time, the field continues to lack structured descriptions and conversations pertinent to it. As exercise physiology research has advanced, the academic community has increasingly recognized that exercise is a multifaceted activity regulated by various systems, with its effects contingent upon the interplay of elements such as type, intensity, and frequency of exercise. Consequently, it is imperative to transcend the prior study paradigm that concentrated solely on localized effects and singular mechanisms and transition towards a comprehensive understanding of the systemic advantages of exercise. A multitude of investigations has validated that exercise confers health advantages for individuals with metabolic disorders, encompassing youngsters, adolescents, middle-aged individuals, and older persons, and typically enhances health via BDNF secretion. However, exercise is a double-edged sword; the relationship between exercise and health is not linearly positive. Insufficient exercise is ineffective, while excessive exercise can be detrimental to health. Consequently, it is crucial to scientifically develop exercise prescriptions, define appropriate exercise loads, and optimize health benefits to regulate bodily metabolism. BDNF mitigates metaflammation via many pathways during exercise. Initially, BDNF suppresses pro-inflammatory factors and facilitates the production of anti-inflammatory factors by modulating bidirectional transmission between neural and immune cells, therefore diminishing the inflammatory response. Secondly, exercise stimulates the PI3K/Akt, AMPK, and other signaling pathways via BDNF, enhancing insulin sensitivity, reducing lipotoxicity, and fostering mitochondrial production, so further optimizing the body’s metabolic condition. Moreover, exercise-induced BDNF contributes to the attenuation of systemic inflammation by collaborating with several organs, enhancing hepatic antioxidant capacity, regulating immunological response, and optimizing “gut-brain” axis functionality. These processes underscore the efficacy of exercise as a non-pharmacological intervention for enhancing anti-inflammatory and metabolic health. Despite substantial experimental evidence demonstrating the efficacy of exercise in mitigating inflammation and enhancing BDNF levels, numerous limitations persist in the existing studies. Primarily, the majority of studies have concentrated on molecular biology and lack causal experimental evidence that explicitly confirms BDNF as a crucial mediator in the exercise regulation of metaflammation. Furthermore, the outcomes of current molecular investigations are inadequately applicable to clinical practice, and a definitive pathway of “exercise-BDNF-metaflammation” remains unestablished. Moreover, the existing research methodology, reliant on animal models or limited human subject samples, constrains the broad dissemination of the findings. Future research should progressively transition from investigating isolated and localized pathways to a comprehensive multilevel and multidimensional framework that incorporates systems biology and exercise physiology. Practically, there is an immediate necessity to undertake extensive, double-blind, randomized controlled longitudinal human studies utilizing multi-omics technologies (e.g., transcriptomics, proteomics, and metabolomics) to investigate the principal signaling pathways of BDNF-mediated metaflammation and to elucidate the causal relationships and molecular mechanisms involved. Establishing a more comprehensive scientific evidence system aims to furnish a robust theoretical framework and practical guidance for the mechanistic interpretation, clinical application, and pharmaceutical development of exercise in the prevention and treatment of metabolic diseases.

OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.