BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60％fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P＜0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P＜0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P＜0.05),Bcl-2/Bax ratio was significantly decreased(P＜0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P＜0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P＜0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P＜0.05),the protein expression of Caspase-3 was significantly decreased(P＜0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P＜0.05),but no significant changes were observed in the other indexes(P＞0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60％fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P＜0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P＜0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P＜0.05),Bcl-2/Bax ratio was significantly decreased(P＜0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P＜0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P＜0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P＜0.05),the protein expression of Caspase-3 was significantly decreased(P＜0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P＜0.05),but no significant changes were observed in the other indexes(P＞0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

ObjectiveTo investigate the material basis of the pathogenesis of cerebral ischemic injury with blood stasis and toxin syndrome and to explore the protective effects of Huayu Jiedu prescription （HYJDP） on neutrophil extracellular trap-related cell death （NETosis） in cerebral ischemic injury following acute cerebral infarction. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into six groups （n=12 per group）： sham operation （Sham） group， blood stasis and toxin model （Model） group， low-， medium-， and high-dose HYJDP groups （HYJDP-L， HYJDP-M， and HYJDP-H； 9， 18， and 36 g·kg^-1， respectively）， and butylphthalide （NBP） group （0.06 g·kg^-1）. Except for the Sham group， rats in all other groups were subjected to carrageenan/dry yeast combined with a modified intraluminal filament method to establish a focal cerebral ischemia model of the middle cerebral artery with blood stasis and toxin syndrome. Neurological function was evaluated at 24 h after modeling using the Zea-Longa neurological deficit score. Cerebral infarction rate was assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Pathological morphology of brain tissue was observed using hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of interleukin-8 （IL-8）， myeloperoxidase-DNA complexes （MPO-DNA）， and citrullinated histone H3 （CitH3）. Protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （p-Akt）， mammalian target of rapamycin （p-mTOR）， sequestosome 1 （p62）， and CitH3 in brain tissue was detected by Western blot. Immunofluorescence （IF） was used to detect the expression of neutrophil-specific marker Ly6G， CitH3， and neuron-specific nuclear protein （NeuN） in brain tissue. ResultsCompared with the Sham group， neurological deficit scores and cerebral infarction rates in the model group were significantly increased （P<0.01 for both）. HE staining showed varying degrees of neuronal degeneration and necrosis， characterized by blurred neuronal structures， nuclear pyknosis and fragmentation， cytoplasmic dissolution into a vacuolated reticular pattern， and mild glial cell proliferation. ELISA results showed that serum levels of IL-8， MPO-DNA， and CitH3 were significantly increased （P<0.01）. Western blot analysis demonstrated decreased expression of p-PI3K， p-Akt， p-mTOR， and p62， while CitH3 expression was significantly increased （P<0.01）. IF results showed an increased number of NETs⁺ cells and a significant decrease in NeuN⁺ cells （P<0.01）. Compared with the Model group， neurological deficit scores in the HYJDP-H group were significantly decreased （P<0.05）， and cerebral infarction rates in the HYJDP-H and NBP groups were significantly reduced （P<0.01）. HE staining showed that brain tissue damage was markedly alleviated in the HYJDP-H group. ELISA results showed that levels of IL-8， MPO-DNA， and CitH3 were significantly decreased in the HYJDP-M， HYJDP-H， and NBP groups （P<0.01）. Western blot analysis showed that expression of p-PI3K， p-Akt， p-mTOR， and p62 was significantly increased in the HYJDP-H and NBP groups， while CitH3 expression was significantly reduced in all drug intervention groups （P<0.01）. IF results showed that the number of NETs⁺ cells was significantly decreased and the number of NeuN⁺ cells was significantly increased in all drug intervention groups （P<0.01）. ConclusionNETs may be the material basis of the pathogenesis of cerebral ischemic injury characterized by blood stasis and toxin. HYJDP can regulate the PI3K/Akt/mTOR signaling pathway， reduce the release of pro-inflammatory mediators and NETosis-related products， alleviate cerebral ischemic injury caused by autophagy-dependent NETosis， and thereby exert a neuroprotective effect.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To explore the effectiveness of the cumulative sum (CUSUM) and the exponentially weighted moving average (EWMA) for early warning of influenza epidemic using two datasets of reported influenza cases and influenza-like illness (ILI) cases. Methods Using the reported cases of influenza and ILI in Daxing District, Beijing, from week 23 of 2018 to week 22 of 2024 as data sets, the CUSUM and EWMA models were established, respectively. The positive rate of influenza etiology was used as the ^“gold standard^”, and the Youden index was used as the evaluation index to compare the early warning effect of the two models under different data sets and different parameters. Results In CUSUM, the optimal Youden indices of the reported influenza cases set and the ILI cases set were 0.751 and 0.635, respectively. In EWMA, the optimal Youden indices of the reported influenza cases set and the ILI cases set were 0.544 and 0.464, respectively. The optimal EWMA and CUSUM models could both issue early warning signals in advance of the ^“gold standard^”. Conclusion In the influenza epidemic early warning in Daxing District, Beijing, the CUSUM model established with the reported cases of influenza can achieve good early warning effects, but the model parameters need to be dynamically adjusted according to the local epidemic characteristics.

ObjectiveTo investigate somatization symptoms in adolescents during frequent earthquakes in Hefei， and to explore their correlation with earthquake experiences. MethodsA cross-sectional survey was used to select 324 adolescents in Hefei as the survey objects. The self-rating scale of somatization symptoms （SSS） and the fatigue intensity scale （FIS） were used to evaluate the somatization symptoms and fatigue degree of middle school students， and multivariate Logistic regression analysis was used to explore the related factors of somatization symptoms and fatigue among middle school students. ResultsA total of 324 adolescents were included， and the overall detection rate of somatization symptoms was 6.5%， and the detection rate of moderate or above fatigue was 20.1%. The results of regression analysis showed that adolescents who were concerned about the earthquake for a longer time （≥1 h） had a higher risk of somatization symptoms （OR=5.430， 95%CI： 1.547-19.058）， and adolescents who received pre-earthquake training had a lower degree of fatigue （OR=0.535， 95%CI： 0.292-0.981） （P<0.05）. ConclusionDuring the frequent earthquakes， adolescents have more somatization symptoms and fatigue. Therefore， it is crucial to enhance health education， reduce the emphasis on event-related reports， and implement earthquake prevention and disaster reduction training to improve the physical and mental health of adolescents.

ObjectiveTo investigate the mechanisms of Runmu Dihuang decoction （RMDHD） in treating perimenopausal dry eye with liver-kidney Yin deficiency syndrome based on the silent information regulator 3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty female Sprague-Dawley rats were randomly divided into six groups （n=10 per group）： Sham operation group， model group， sodium hyaluronate eye drop group， and low-， medium-， and high-dose RMDHD groups （5.625， 11.25， 22.50 g·kg^-1）. Except for the sham operation group， all rats underwent bilateral ovariectomy and were administered 0.1% benzalkonium chloride eye drops combined with long-term chronic irritation to establish a perimenopausal dry eye model with liver-kidney Yin deficiency syndrome. Drug administration began in the 11th week after modeling and continued for 21 days. General conditions， screen-grip test scores， tear secretion volume， tear film breakup time （TFBUT）， and corneal fluorescein staining were recorded. Serum levels of reactive oxygen species （ROS）， follicle-stimulating hormone （FSH）， estradiol （E₂）， and progesterone （PROG） were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the lacrimal glands， corneas， and uteri were observed using hematoxylin-eosin （HE） staining. Protein expression levels of SIRT3， HIF-1α， phosphorylated NF-κB p65 （p-NF-κB p65）， and total NF-κB p65 in the lacrimal glands were detected by Western blot. The expression of inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the lacrimal glands was assessed by immunohistochemistry （IHC）. ResultsAfter model establishment， no significant differences were observed among the groups except the sham operation group. Compared with the sham operation group， the other groups exhibited slowed movement， dull responses， increased irritability， reduced body weight， elevated rectal temperature， decreased screen-grip test scores， reduced tear secretion， and significantly shortened TFBUT （P<0.05）. After treatment， compared with the model group， the sodium hyaluronate eye drop group and all RMDHD groups showed improved general conditions， significantly increased tear secretion （P<0.05）， prolonged TFBUT （P<0.05）， and elevated screen-grip test scores （P<0.05）. Serum ROS and FSH levels were significantly decreased， while E₂ and PROG levels were significantly increased （P<0.05）. Pathological damage to the cornea， lacrimal glands， and uterus was ameliorated. In addition， protein expression levels of SIRT3 and HIF-1α in the lacrimal glands were significantly upregulated （P<0.05）， whereas the expression of p-NF-κB p65， IL-1β， and TNF-α was significantly downregulated （P<0.05）. ConclusionRMDHD increases tear secretion and TFBUT， improves lacrimal gland and corneal injury， and alleviates dry eye symptoms in a perimenopausal dry eye rat model with liver-kidney Yin deficiency syndrome. The underlying mechanism may be related to regulation of the SIRT3/HIF-1α/NF-κB signaling pathway， inhibition of oxidative stress and inflammatory responses， and reduction of ocular surface tissue damage.

ObjectiveTo conduct a comparative quality analysis of Inulae Flos， fuzz of Inulae Flos and calyx of Inulae Flos， elucidating the scientific connotation of the "removing calyx" process in the traditional processing of Inulae Flos. MethodsInulae Flos decoction pieces were collected， and the fuzz and calyx of Inulae Flos were prepared according to the experiences of old medicine workers. Subsequently， according to the methods under the "Inulae Flos" item in the 2025 edition of the Pharmacopoeia of the People's Republic of China， the appearance characteristics and thin-layer chromatography（TLC） identification of these samples were tested， and the moisture content， total ash content， extract content were also measured. The characteristic fingerprint patterns of Inulae Flos and fuzz of Inulae Flos were established by high-performance liquid chromatography（HPLC）， followed by similarity evaluation， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA）. The contents of cryptochlorogenic acid， caffeic acid， 1，3-O-dicaffeoylqunic acid， 1，5-O-dicaffeoylqunic acid， and 1-O-acetyl britannilactone were determined to compare the quality differences of Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos. ResultsThe moisture content of Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos was all<10%. The determination results of total ash content were as follows：Calyx of Inulae Flos>Inulae Flos>fuzz of Inulae Flos， and the determination results of alcohol-soluble extract content were as follows：Fuzz of Inulae Flos>Inulae Flos>calyx of Inulae Flos. HPLC fingerprint patterns of Inulae Flos and fuzz of Inulae Flos were established， and 22 common peaks were identified. The similarity analysis and PCA showed that the overall quality of Inulae Flos and fuzz of Inulae Flos was similar， while the overall quality of calyx of Inulae Flos differed significantly from that of Inulae Flos and fuzz of Inulae Flos. PLS-DA results showed that Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos clustered into distinct groups， indicating significant differences among them. Cryptochlorogenic acid and caffeic acid had relatively high contents in calyx of Inulae Flos， the contents of 1，3-O-dicaffeoylqunic acid and 1，5-O-dicaffeoylqunic acid in Inulae Flos and fuzz of Inulae Flos were higher than those in calyx of Inulae Flos. The order of 1-O-acetyl britannilactone content was determined as follows：fuzz of Inulae Flos>Inulae Flos>calyx of Inulae Flos. ConclusionThe scientific nature of "Removing Calyx" process in the cleansing of Inulae Flos by old medicine workers is demonstrated by the resulting fuzz of Inulae Flos decoction pieces exhibiting enhanced cleanliness and higher content of the index component 1-O-acetyl britannilactone. This study provides a reference basis for further improving and enhancing the processing method and quality control standards of Inulae Flos.

Guishenwan （GSW）， originating from Jingyue Quanshu （Zhang Jingyue's Complete Works）， is a classic traditional Chinese medicine （TCM） formula with a history of over 400 years. Designed for kidney essence deficiency syndrome， it is clinically applied to treat diseases associated with essence-blood deficiency， such as ovarian insufficiency diseases in women， oligospermia-induced infertility in men， and lumbar disc herniation. Numerous studies have confirmed its significant efficacy and advantages in managing ovarian insufficiency diseases， including diminished ovarian reserve （DOR）， premature ovarian insufficiency （POI）， and premature ovarian failure （POF）. According to recent literature， the therapeutic mechanisms of GSW in treating ovarian insufficiency diseases involve regulating the hypothalamic-pituitary-ovarian axis （HPOA） function， ameliorating reproductive endocrine disorders， improving ovarian function， modulating relevant signaling pathways， and exerting immunoregulatory and anti-inflammatory effects. A review of GSW in clinical treatment revealed that clinical applications of GSW， particularly in combination with Western medicine， not only alleviate symptoms but also compensate for the limitations of hormone replacement therapy， thereby reducing recurrence， minimizing adverse reactions， and enhancing safety. This review aims to provide a scientific basis for the rational clinical use of GSW in ovarian insufficiency diseases， offer innovative TCM strategies for developing novel ovarian-protective drugs， promote the integration of TCM and Western medicine in reproductive medicine， and ultimately contribute a Chinese approach to global management of ovarian insufficiency diseases.

Macular hole is an age-related disorder defined by a full-thickness defect of the foveal retina and a profound loss of central vision. First described in the mid-19th century, its study has now extended across more than 150 years. Breakthroughs in science and technology—especially the relentless refinement of retinal imaging platforms—have progressively refined our understanding of the disease. Optical coherence tomography(OCT)in particular has revolutionized characterization of the condition. At the same time, the widespread adoption of macular hole surgery has not only driven deeper investigations into pathogenesis and pre-operative assessment but also facilitated the global dissemination of surgical expertise and a marked rise in anatomical success. This review synthesizes the multimodal imaging hallmarks of macular holes and highlights the remaining clinical challenges in the application of OCT technology.