Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection.

Objective To explore the utility of comprehensive geriatric assessment (CGA) in screening risk factors for osteosarcopenia (OS) among older adults (≥80 years old) and to evaluate the therapeutic efficacy of CGA-guided integrated interventions for OS. Methods A total of 420 patients aged ≥80 years, recruited from the Department of Geriatrics, General Practice of The Affiliated Jiangyin Hospital of Nantong University, and community health centers from January 2022 to October 2024, were enrolled. Participants were classified into OS (n＝139) and non-OS (n＝281) groups based on diagnostic criteria. CGA was utilized to compare differences in general characteristics, laboratory indicators, comorbidities between groups. Binary logistic regression analysis identified independent risk and protective factors. Subsequently, 40 OS patients were randomly assigned to an intervention group (n＝20) receiving integrated interventions including nutritional support, exercise training, and psychological management or a control group (n＝20, receiving routine care). Appendicular skeletal muscle mass index (ASMI), grip strength, gait speed, and bone mineral density (BMD) T-score were compared between groups after 3 months. Results The prevalence of OS in this cohort was 33.1%. Compared to the non-OS group, the OS group exhibited significant differences in age, body mass index (BMI), smoking history, comorbidity index, concomitant medication, cognitive impairment, visual and hearing impairment, sleep disorders, depression, marital status, social participation, activities of daily living, nutritional risk, total cholesterol, uric acid, and constipation (P＜0.05). Logistic regression analysis identified age and comorbidity index as significant risk factors for OS, while BMI, married status, total cholesterol, and activities of daily living (assisted and independent) served as protective factors. The intervention group demonstrated significant improvements in grip strength, gait speed, BMD T-score, and male ASMI compared to controls (P＜0.05). Conclusions CGA demonstrates clinical utility in systematically identifying risk factors for OS in the old population. Multimodal interventions guided by CGA effectively improve musculoskeletal function in elderly OS patients.

Objective: To investigate the iodine nutrition status of children in water borne iodine excess areas in Hebei Province, so as to provide references for scientific prevention and control of water borne iodine excess hazards. Methods: From March to September each year during 2018 to 2023, a cross sectional survey was conducted in 39 water borne iodine excess counties (measured in 2017) from 5 cities (Cangzhou, Hengshui, Xingtai, Handan and Langfang) in Hebei Province. The survey included the detection of iodine content in residents drinking water, the measurement of thyroid volume in children aged 6-12, the detection of salt iodine and urinary iodine. The iodine nutrition status and water iodine distribution of 6-12 year-old children were evaluated from different perspectives such as years, gender, and age. Kruskal-Wallis H- test, Mann-Whitney U test and Chi square test were used for group comparison. Results: A total of 38 755 children were surveyed from 2018 to 2023, and 1 270 drinking water samples were tested across the province. The mass volume concentration of iodine in water showed a decreasing trend over the years ( Z= -30.87, P <0.01). Among 38 470 salt samples monitored from children s home, 24 790 were not non iodized salt, with a non iodized salt rate of 64.44%. A total of 31 989 urine samples were collected from children aged 8-10 years, with the median urine iodine was 245.94 μg/L. Comparing the results of urinary iodine in children from different years, the median urinary iodine from 2018 to 2023 were 328.0, 339.3, 267.8, 279.1, 291.3, 186.5 μg/L, respectively, with statistically significant differences ( H= 4 138.40 , P <0.01). Further pairwise comparisons showed that the median urinary iodine of children in 2023 was lower than in all other years ( Z =-51.59 to -11.41, all P <0.01). Among children aged 6-12 years, 1 150 cases of goiter were detected and the rate of goiter was 3.0%; and the goiter rates in boys and girls were 2.8% and 3.1%, with no significant difference between the sexes ( χ 2= 2.76, P >0.05). There were significant differences in the rate of goiter among different years and ages ( χ 2=324.02, 191.61, both P <0.05). Conclusions With the progress of water reform in water borne iodine excess areas of Hebei Province, children s iodine nutrition has reduced from excessive state to suitable state. It is necessary to continue to expand the coverage of water based iodine reduction projects, and strengthen the monitoring of iodine nutrition status of key populations in water borne iodine excess areas.

ObjectiveTo investigate the efficacy and safety of N-acetylcysteine （NAC） in the treatment of severe alcoholic hepatitis （SAH）， and to provide a basis for clinical medication for SAH. MethodsA prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of >32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018， and these patients were divided into NAC group with 84 patients and control group with 86 patients. NAC （8 g/day， 28 days） was assessed in terms of its safety in SAH patients， its impact on 28-day biochemical parameters， and its role in improving 28- and 180-day survival rates. A further analysis was performed to investigate the effect of NAC on the 28- and 180-day survival rates of SAH patients with acute-on-chronic liver failure （ACLF-SAH patients） and those without acute-on-chronic liver failure （non-ACLF-SAH patients）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors. ResultsNo serious adverse events were observed during NAC treatment， suggesting that NAC had a good safety profile. Compared with the control group， NAC did not significantly improve the 28-day biochemical parameters （all P>0.05） and survival rate of SAH patients （P=0.081）， but it could improve the 180-day survival rate of SAH patients （67.4% vs 81.0%， χ²=4.280， P=0.039）. NAC did not improve the 28- and 180-day survival rates of ACLF-SAH patients （both P>0.05）； NAC did not improve the 28-day survival rate of non-ACLF-SAH patients （P>0.05）， but it could improve the 180-day survival rate of these patients （68.4% vs 88.9%， χ²=4.883， P=0.027）. The multivariate Cox regression survival analysis showed that NAC treatment （hazard ratio ［HR］=2.530， 95% confidence interval ［CI］： 1.334‍ ‍— 4.796， P=0.004，）， Maddrey discriminant function score （HR=3.852， 95%CI： 2.032 — 7.304， P<0.001）， and serum sodium level （HR=1.948， 95%CI： 1.079‍ ‍—‍ ‍3.517， P=0.027） were independent influencing factors for 180-day survival rate in SAH patients. ConclusionNAC has a good safety profile in the treatment of SAH and can improve the 180-day survival rate of SAH patients， and in particular， non-ACLF-SAH patients can benefit from NAC treatment in terms of middle- and long-term survival rates.

ObjectiveTo reveal the molecular mechanism of Angong Niuhuangwan（AGNH） in improving traumatic brain injury（TBI） based on single cell sequencing. MethodSeventy-five male SD rats were randomly divided into the sham group， model group， piracetam group（3.6 g·kg^-1）， AGNH low- and high-dose groups（0.09， 0.27 g·kg^-1）， with 15 rats in each group. In addition to the sham group， the other 4 groups used the modified Feeney free-fall impact method to prepare TBI model， and the drugs were administered by gavage immediately after modeling， 24 hours later， the modified neurological deficit score（mNSS） was performed， and brain tissue was isolated to determine the degree of cerebral edema. Hematoxylin-eosin（HE） staining was used to observe the injury degree in the cortex， CA1 region and CA3 region of brain tissue. The expression levels of cyclooxygenase-2（COX-2）， interferon regulatory factor 1（IRF1）， Janus kinase 2（JAK2） and suppressor of cytokine signaling 3（SOCS3） were observed by immunofluorescence（IF） staining. The levels of interleukin（IL）-6， IL-18， IL-1β， IL-17A， tumor necrosis factor-α（TNF-α）， Caspase-1 and nucleotide binding oligomerization domain（NOD）-like receptor heat protein domain associated protein 3（NLRP3） inflammasome were determined by enzyme-linked immunosorbent assay（ELISA）. The regulation of AGNH on each cell population was analyzed by single cell sequencing， and differentially expressed genes were analyzed by Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG）， which led to construct microglia differentially expressed gene network to search for the key targets， and validated by ELISA and IF. ResultCompared with the sham group， the mNSS and brain water content were significantly increased in the model group（P<0.01）. Compared with the model group， mNSS and brain water content in the low and high dose AGNH groups were decreased（P<0.05，P<0.01）. HE staining results showed that compared with the sham group， the cells in the cerebral cortex and hippocampus of rats in the model group were seriously lost， and the cells were arranged loosely（P<0.01）. Compared with the model group， AGNH could significantly increase the density of neurons in the CA1 and CA3 regions of the cerebral cortex and hippocampus， making the arrangement more compact， as well as improved cell morphology（P<0.05，P<0.01）. ELISA and IF staining showed that AGNH could reduce the levels of Caspase-1， IL-17A， TNF-α， NLRP3 and COX-2 in brain tissue of TBI rats（P<0.05， P<0.01）. A total of 13 cell subsets were identified by single cell sequencing， among which microglia played an important role in neuroimmunity. The results of GO enrichment analysis of differentially expressed genes in microglia showed that AGNH improved TBI in response to inflammation and TNF-α. KEGG enriched IL-17 signaling pathway， TNF signaling pathway， Toll-like receptor signaling pathway， etc. The results of network analysis showed that the key targets of AGNH in regulating TBI might be IL-6， IL-1β， JAK2， SOCS3， IRF1. IF and ELISA verification results showed that compared with the sham group， SOCS3 expression in microglia was decreased in the model group， and the expressions of IL-6， IL-1β， JAK2 and IRF1 were increased（P<0.01）. Compared with the model group， AGNH could increase the expression of SOCS3， decrease the expression of IL-6， IL-1β， JAK2， IRF1 （P<0.05， P<0.01）. ConclusionAGNH can reduce the degree of brain edema and brain injury， decrease the expression of inflammatory factors， and inhibit the expression of NLRP3 and its downstream Caspase-1 in TBI rats， which may act on the targets of IL-6， IL-1β， JAK2， IRF1 and SOCS3 in microglia.

ObjectiveTo investigate whether elemene（ELE） enhances the anti-glioma efficacy of cabazitaxel（CTX）， and prepare a double-targeted cationic liposome（LIP） co-loaded with ELE/CTX for the treatment of glioma， and to achieve the effect of increasing the efficacy and reducing the adverse reactions. Pharmacodynamic tests in vitro were performed to explore the advantages and mechanism of its preparation. MethodELE/CTX@LIP was prepared by high speed shear combined with probe ultrasound， the particle size and potential were characterized by nano-particle size potentiometer， and high performance liquid chromatography（HPLC） was used to determine the encapsulation efficiency and drug loading capacity of CTX/ELE. The cytotoxicity of ELE/CTX in vitro was detected by cell proliferation and activity assay（CCK8）. JMP Pro 16 software was used to optimize the process parameters of ELE/CTX@LIP based on encapsulation efficiency. The optimal cationic material type， content and ratio were screened by in vitro cytotoxicity and in vitro cell uptake， on this basis， the dual-targeted cationic liposome T7/arginine glycine aspartate tripeptide sequence（T7/cRGD）-ELE/CTX@CLIP was prepared， the stability of morphology and particle size were characterized， and the effect of T7/cRGD-ELE/CTX@CLIP on the apoptosis inducing ability and cell cycle regulation ability of glioma cells was analyzed by cell cycle and apoptosis. ResultELE/CTX showed stronger anti-glioma activity on C6 and RG2 cells. The results of in vitro cytotoxicity and in vitro cell uptake showed that the amount of cationic material was 0.10% of the total content. The optimum ratio of T7， cRGD and phospholipids was 1∶1∶50. T7/cRGD-ELE/CTX@CLIP［1，2-dilinoleyloxy-3-dimethylaminopropane（Dlin-MC3-DMA）］ and T7/cRGD-ELE/CTX@CLIP［1，2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000（DMG-PEG2000）］ showed multi-level spherical nanostructures with particle sizes of 146.0， 111.3 nm， respectively， and were stable in serum. In vitro cytotoxicity results showed that T7/cRGD-ELE/CTX@CLIP had higher cytotoxicity to glioma cells than single-targeted liposomes or dual-targeted non-cationic liposomes. T7/crGD-ELE/CTX@CLIP affected the apoptosis and cycle of glioma cells， the results showed that ELE/CTX combined with liposomes could more effectively activate the apoptosis channel and inhibit the proliferation of glioma cells， and the use of T7/cRGD short peptide and cation modification enhanced the ability of apoptosis induction. ELE/CTX could effectively block glioma cell cycle at G₂/M phase， and the effect was enhanced after T7/cRGD targeted modification. ConclusionELE can enhance the anti-glioma effect of CTX. The preparation parameters of ELE/CTX@LIP are stable and feasible. Combined with the in vitro efficacy test， the anti-glioma mechanism of T7/cRGD-ELE/CTX@CLIP is preliminarily revealed.

Objective·To investigate the effect of Astragali Radix on T lymphocyte subsets and cytokine expression in Hashimoto's thyroiditis patients with normal thyroid function.Methods·A total of 120 Hashimoto's thyroiditis patients with normal thyroid function and complete data were selected from January 2020 to December 2020 in Jinshan Branch of Shanghai Sixth People's Hospital.The patients were randomly divided into intervention group(n=60)and control group(n=60)by the method of random number table.The treatment plan of the control group was iodine appropriate state diet,and the intervention group was combined with oral Astragali Radix solution(150 mL per time,twice/d)on the basis of the treatment of the control group.The two groups were treated for 6 months.The changes in peripheral blood serum T lymphocyte subsets(CD3+,CD4+,CD8+,and CD4+/CD8+),cytokines[interleukin-2(IL-2),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)],hypersensitive C-reactive protein(hs-CRP),erythrocyte sedimentation rate(ESR),thyroid function,autoantibody,liver and kidney function,and other biochemical indexes were compared before and after treatment between the two groups.Adverse reactions were observed during the treatment.The factors influencing the change amplitude of thyroid peroxidase antibody(TPOAb)were analyzed by multifactor linear regression.Results·Finally,118 patients,with 59 cases in each group,were included in the study.After 6 months of treatment,the intervention group showed significant improvements in the proportions of CD4+ T cells,the ratio of CD4+/CD8+,and the levels of IL-2,TNF-α,IL-10,hs-CRP,ESR,TPOAb,and thyroglobulin antibody(TGAb)compared to the values before treatment and in the control group(P<0.05).There were no statistically significant differences on the above indicators before and after treatment in the control group(P>0.05).No serious adverse reactions were observed in the intervention group.Multiple linear regression analysis results showed that the use of Astragali Radix,increase of CD4+ level,increase of CD4+/CD8+ ratio,and decrease of hs-CRP level were influencing factors for the decrease of TPOAb level(β=-0.393,P=0.029;β=-0.513,P=0.010;β=-0.351,P= 0.035;β=0.434,P=0.023).Conclusion·Astragali Radix can improve the levels of CD4+ T cells,CD4+/CD8+ratio,IL-2,TNF-α,IL-6,and IL-10 in Hashimoto's thyroiditis patients with normal thyroid function,and it is safe to use.

Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.

BACKGROUND:In recent years,the demand for in vitro maturation of immature oocytes has increased.Oocyte maturation is affected by many factors,among which the selection of medium is particularly important,and there is currently no unified plan. OBJECTIVE:To compare the in vitro maturation of germinal vesicle stage oocytes with different maturation media and to investigate its effects on oocyte quality and developmental potential. METHODS:Germinal vesicle oocytes were matured in G-1TM PLUS medium,CZB medium and M16 medium,and mature oocytes in vivo were used as control group to compare in vitro fertilization and early embryo development among various groups.The immunofluorescence method was used to evaluate mitochondrial function in mature oocytes of each group.Calcium oscillation was detected by confocal microscopy real-time imaging system. RESULTS AND CONCLUSION:(1)There was no significant difference in the first polar body ejection rate among the three groups(P>0.05).(2)The rate of in vitro fertilization was higher in the G-1TM PLUS group(52.86±11.24)%than that in the M16 group(37.76±6.70)%and the CZB group(30.62±5.51)%.The blastocyst rate was lower in the CZB group(36.23±6.63)%than that in the control group(78.16±4.17)%,G-1TM PLUS group(55.75±7.63)%and M16 group(53.36±6.33)%.(3)Compared with the control group,the length-to-width ratio of the spindle in the CZB group increased(P<0.005).(4)The mitochondrial function of the CZB group was worse than that of the control group,G-1TM PLUS group and M16 group,and abnormal mitochondrial agglutination occurred in the CZB group.(5)The frequency of calcium oscillations in the CZB and M16 groups was significantly higher than that in the G1 and control groups.In conclusion,during in vitro maturation of mouse oocytes,in vitro maturation rate was not significantly different among G-1TM PLUS,CZB and M16 media,but the G-1TM PLUS medium had a higher rate of fertilization and blastocyst formation.