ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P0.01） and increases in number of platform crossings （P0.05）， alternation rate （P0.01）， number of entries into the new arm （P0.05）， preference index （P0.01）， and discrimination index （P0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P0.05） and elevated levels of ACh and DA （P0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

Insomnia is a sleep disorder characterized by difficulty in falling asleep， sleep maintenance disorder and impaired daytime function. Its pathological mechanism involves multiple factors such as nerve excitability， circadian rhythm， cell apoptosis， oxidative stress injury. As a classical tyrosine kinase signaling pathway， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） triggers Akt phosphorylation cascade， inducing inflammatory response， apoptosis， autophagy， oxidative damage， nerve excitability， and circadian rhythm imbalance. Traditional Chinese medicine（TCM） can improve sleep by targeting the PI3K/Akt pathway. Based on this， this paper systematically reviews the research progress on the regulation of PI3K/Akt pathway by traditional Chinese medicine（TCM） for insomnia at home and abroad. These drugs can regulate neuronal excitability by regulating the PI3K/Akt pathway， affect the circadian rhythm， alleviate inflammation， apoptosis， autophagy and oxidative stress， and thus regulate sleep-wake. Furthermore， literature review indicates that the PI3K/Akt signaling pathway may represent a specific pathway underlying phlegm-turbidity disturbing the upper Jiao-type insomnia.

ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P<0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P<0.01） and increases in number of platform crossings （P<0.05）， alternation rate （P<0.01）， number of entries into the new arm （P<0.05）， preference index （P<0.01）， and discrimination index （P<0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P<0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P<0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P<0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P<0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P<0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P<0.05） and elevated levels of ACh and DA （P<0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

Insomnia is a sleep disorder characterized by difficulty in falling asleep， sleep maintenance disorder and impaired daytime function. Its pathological mechanism involves multiple factors such as nerve excitability， circadian rhythm， cell apoptosis， oxidative stress injury. As a classical tyrosine kinase signaling pathway， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） triggers Akt phosphorylation cascade， inducing inflammatory response， apoptosis， autophagy， oxidative damage， nerve excitability， and circadian rhythm imbalance. Traditional Chinese medicine（TCM） can improve sleep by targeting the PI3K/Akt pathway. Based on this， this paper systematically reviews the research progress on the regulation of PI3K/Akt pathway by traditional Chinese medicine（TCM） for insomnia at home and abroad. These drugs can regulate neuronal excitability by regulating the PI3K/Akt pathway， affect the circadian rhythm， alleviate inflammation， apoptosis， autophagy and oxidative stress， and thus regulate sleep-wake. Furthermore， literature review indicates that the PI3K/Akt signaling pathway may represent a specific pathway underlying phlegm-turbidity disturbing the upper Jiao-type insomnia.

ObjectiveTo investigate the therapeutic effect of Bazhen Lihe Kangxian prescription on rats with liver fibrosis induced by carbon tetrachloride （CCl₄）， and to explore its mechanism of action against liver fibrosis. MethodsA total of 50 male Sprague-Dawley rats were randomly divided into blank group， model group， silybin group （43.19 mg/kg）， and low-， middle-， and high-dose Bazhen Lihe Kangxian prescription groups （7.96， 15.93， and 31.86 g/kg， respectively）. Subcutaneous injection of 40% CCl₄-olive oil solution （twice a week for 8 consecutive weeks） was performed to establish a model of liver fibrosis. After successful modeling， the rats in the blank group and the model group were given normal saline by gavage， while those in the treatment groups were given the corresponding drug by gavage， once a day for 4 consecutive weeks. HE staining and Masson staining were used to observe liver histopathological changes； an automatic biochemical analyzer was used to measure the serum levels of albumin （Alb）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT）； ELISA was used to measure the serum levels of hyaluronic acid （HA）， collagen Ⅳ （Col-Ⅳ）， procollagen Ⅲ N-terminal peptide （PⅢNP）， and laminin （LN）； Western blotting was used to measure the protein expression levels of phosphoinositide 3-kinase （PI3K）， phosphorylated PI3K （p-PI3K）， protein kinase B （Akt）， phosphorylated Akt （p-Akt）， mammalian target of rapamycin （mTOR）， and phosphorylated mTOR （p-mTOR） in liver tissue； RT-qPCR was used to measure the mRNA expression levels of collagen Ⅰ （Col-Ⅰ） and α-smooth muscle actin （α-SMA） in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank group， the model group had disrupted hepatic lobular structure， disordered arrangement of hepatic cell cords， hepatocyte fatty degeneration， severe inflammatory cell infiltration， and deposition of massive blue collagen fibers， as well as significant increases in the levels of AST， ALT， HA， LN， Col‑Ⅳ， and PⅢNP and a significant reduction in the level of Alb （all P<0.01）. Compared with the model group， the silybin group and the three Bazhen Lihe Kangxian prescription groups had varying degrees of improvement in inflammatory cell infiltration， hepatocyte fatty degeneration， and collagen deposition in liver tissue， as well as significant reductions in the levels of AST， ALT， HA， LN， Col‑Ⅳ， and PⅢNP and a significant increase in the level of Alb （all P<0.01）. Compared with the blank group， the model group had significant increases in the protein expression levels of p‑PI3K/PI3K， p-Akt/Akt， and p‑mTOR/mTOR and the mRNA expression levels of Col-I and α-SMA in liver tissue （all P<0.01）； compared with the model group， the silybin group and the high- and middle-dose Bazhen Lihe Kangxian prescription groups had significant reductions in the protein expression levels of p-PI3K/PI3K （all P<0.01）， and the silybin group and the three Bazhen Lihe Kangxian prescription groups had significant reductions in the protein expression levels of p-Akt/Akt and p-mTOR/mTOR and the mRNA expression levels of Col-Ⅰ and α-SMA in liver tissue （all P<0.01）. ConclusionBazhen Lihe Kangxian prescription can improve CCl₄-induced liver fibrosis in rats and alleviate liver injury， possibly by inhibiting the PI3K/Akt/mTOR pathway.

Objective To examine resting-state whole-brain network connectivity in children with Chinese developmental dyslexia(DD)and typically developing(TD)children using functional near-infrared spectroscopy(fNIRS).Methods From November to December,2024,19 DD children aged six to twelve years in Children's Hospital of Fudan University were enrolled,along with 18 TD children matching age and sex.Regions of interest included frontal cortex(FC),temporal lobe(TL),occipital lobe(OL)and parietal lobe(PL).Resting-state data were acquired by fNIRS for five minutes in both groups.Functional connectivity strength was calculated at rest,and between-group differences in connectivity strength and brain networks were compared,based on the time series of oxyhe-moglobin concentration.Results The whole-brain functional connectivity strength was higher in DD group than in TD group(t=2.100,P<0.05).Connectivity between the right OL-right FC(t=2.426,P<0.05),right OL-left FC(t=2.483,P<0.05),right TL-right FC(t=2.568,P<0.05)and right TL-left FC(t=2.304,P<0.05)were stonger in DD group than in TD group.The major regions exhibiting differences of whole-brain connectivity between two groups were the right dorsolateral prefrontal cortex,right visual association cortex,right frontal cortex,left orbitofrontal cortex,left visual association cortex,left primary visual cortex and right primary motor cortex.Conclusion Children with DD exhibited significantly stronger connectivity in the right occipital and temporal lobes,as well as between these regions and the prefrontal cortex,suggesting possible right-hemispheric compensation for insufficiency in the left-hemisphere reading network.

Histone lactylation is a novel type of post-translational modification,where a lactate molecule covalently binds to the lysine residues of histones.This modification plays a key role in cellular metabolic reprogramming,particularly in digestive system tumorigenesis and progression.In recent years,the role of histone lactylation in various malignancies has been increasingly recognized,highlighting its broad impact on tumor biology and clinical potential.This article focused on the research progress of histone lactylation in digestive system cancers,specifically analyzing its mechanisms in major gastrointestinal cancers such as gastric cancer,liver cancer,and colon cancer.Studies have shown that lactylation modifies histone lysine residues directly,regulating tumor cell gene expression and chromatin conformation,thereby promoting tumor proliferation,invasion,and metastasis.Lactylation affects histone-DNA interactions,altering chromatin openness and enhancing the transcriptional activity of oncogenes.In addition,targeted therapies that modulate lactation levels or inhibit lactation-related enzymes,such as lactate dehydrogenase inhibitors,lactate production inhibitors,and specific histone lactonases,are effective in inhibiting tumorigenesis and progression and have demonstrated potential therapeutic efficacy in preclinical models.This article systematically summarized the mechanisms of histone lactylation in various types of gastrointestinal cancers,offering new research directions and theoretical support for targeted therapeutic strategies based on lactylation modification.

Objective To investigate the current status of pain crisis in patients with advanced colorectal cancer(CRC)and analyze its influencing factors.Methods A total of 186 patients with advanced CRC who were hospitalized in the Oncology Department,the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from June 2024 to March 2025 were selected as the subjects of the investigation.General information questionnaires numerical rating scale,distress tolerance scale,self-rating anxiety scale,self-rating depression scale and quality of life assessment scales were used for the investigation.Logistic regression was used to analyze the influencing factors of pain crisis in patients with advanced CRC.Results Among the 186 CRC patients,87 experienced pain crises,with an incidence rate of 46.8％.The results indicated that pain type,use of analgesics,traditional Chinese medicine adjuvant therapy,metastasis radiotherapy and chemotherapy,pain intensity and pain tolerance were important influencing factors for pain crises in advanced CRC patients.Conclusion The incidence of pain crisis in patients with advanced CRC is relatively high.Nursing staff should promptly identify patients with pain crisis and implement targeted intervention strategies for high-risk patients to reduce the risk of pain crisis.

Objective:To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.Methods:Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). Results:① PAH variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS variants. ② Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) were located in exons, with the main types of variants were missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants occurred in the PAH gene catalytic center region of PAH protein, while 19.74% (30/152) of variants involved non-coding sequences. ③The phenotypes of the 75 PAHD children were evenly distributed. The rescreening Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values ( P<0.001, P<0.001; P=0.004, P=0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types significantly affect the phenotype ( P=0.042, P=0.045). ④APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes ( κ=0.755, P<0.001). Conclusion:PAH variants were detected in the most of HPA children in Lianyungang area. The location and type of PAH variants were related to the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model predicted the phenotype was highly consistent with the actual phenotype.

ObjectiveTo observe the effect of Shenshu Fujian decoction on platelet-derived growth factor （PDGF）/naked cuticle homolog 2 （NKD2） /Wnt signaling pathway in rats with chronic renal failure （CRF）. MethodsSixty male SD rats were randomly divided into normal group， model group， Niaoduqing group （5 g·kg^-1）， low-dose Shenshu Fujian decoction group （5.5 g·kg^-1）， medium-dose Shenshu Fujian decoction group （11 g·kg^-1）， and high-dose Shenshu Fujian decoction group （22 g·kg^-1）， with 10 rats in each group. A CRF rat model was established by feeding a 0.5% adenine diet for 21 days. After successful modeling， intragastric administration was given once daily for 28 consecutive days. After treatment， the renal morphology of rats was observed. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Hematoxylin-eosin （HE） staining and Masson staining were used to detect renal histopathological changes， and collagen volume fraction （CVF） was calculated. Serum levels of inflammatory markers interleukin （IL）-1β and IL-6 were measured using enzyme-linked immunosorbent assay （ELISA）. The expressions of fibronectin 1 （FN1）， type Ⅰ collagen （ColⅠ）， α-smooth muscle actin （α-SMA）， platelet-derived growth factor receptor-β （PDGFR-β）， NKD2， dishevelled protein 2 （DVL2） and β-catenin in renal tissue were detected by immunohistochemistry and Western blot. ResultsCompared with the normal group， the model group showed significant renal pathological changes， a markedly increased kidney weight/body weight ratio （P<0.01）， significantly elevated CVF （P<0.01）， and notably increased serum levels of SCr， BUN， IL-1β， and IL-6 （P<0.01）. Expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were also significantly increased （P<0.01）. Compared with the model group， all treatment groups showed significantly decreased kidney weight/body weight ratios and CVF （P<0.01）， as well as markedly decreased serum SCr， BUN， IL-1β， and IL-6 levels. Protein expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were decreased， with more pronounced effects observed in the Niaoduqing， medium-dose， and high-dose Shenshu Fujian decoction groups （P<0.05， P<0.01）. ConclusionShenshu Fujian decoction improves renal function， reduces inflammation， and reverses renal fibrosis in CRF rats， possibly by downregulating the expression of PDGF/NKD2/Wnt signaling pathway-related proteins.