This study investigates the molecular complexities of non-alcoholic fatty liver disease (NAFLD)-induced brain dysfunction, with a focus on the liver-intestine-brain axis and potential therapeutic interventions. The main objectives include understanding critical microbiota shifts in NAFLD, exploring altered metabolites, and identifying key regulatory molecules influencing brain function. The methods employed encompassed 16S ribosomal RNA (rRNA) sequencing to scrutinize stool microbiota in NAFLD patients and healthy individuals, non-targeted metabolomics using LC-MS to uncover elevated levels of deoxycholic acid (DCA) in NAFLD mice, and single-cell RNA sequencing (scRNA-seq) to pinpoint the pivotal gene Hpgd in microglial cells and its downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Behavioral changes and brain function were assessed in NAFLD mice with and without Fecal microbiota transplantation (FMT) treatment, utilizing various assays and analyses. The results revealed significant differences in microbiota composition, with increased levels of Bacteroides in NAFLD patients. Additionally, elevated DCA levels were observed in NAFLD mice, and FMT treatment demonstrated efficacy in ameliorating liver function and brain dysfunction. Hpgd inhibition by DCA activated the JAK2/STAT3 pathway in microglial cells, leading to inflammatory activation, inhibition of mitochondrial autophagy, induction of neuronal apoptosis, and reduction in neuronal action potentials. This study elucidates the intricate molecular mechanisms underlying the liver-gut-brain axis in NAFLD, and the identification of increased DCA and the impact of JAK2/STAT3 signaling on microglial cells highlight potential therapeutic targets for addressing NAFLD-induced brain dysfunction.

This study investigates the molecular complexities of non-alcoholic fatty liver disease(NAFLD)-induced brain dysfunction,with a focus on the liver-intestine-brain axis and potential therapeutic interventions.The main objectives include understanding critical microbiota shifts in NAFLD,exploring altered me-tabolites,and identifying key regulatory molecules influencing brain function.The methods employed encompassed 16S ribosomal RNA(rRNA)sequencing to scrutinize stool microbiota in NAFLD patients and healthy individuals,non-targeted metabolomics using LC-MS to uncover elevated levels of deoxycholic acid(DCA)in NAFLD mice,and single-cell RNA sequencing(scRNA-seq)to pinpoint the pivotal gene Hpgd in microglial cells and its downstream Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.Behavioral changes and brain function were assessed in NAFLD mice with and without fecal microbiota transplantation(FMT)treatment,utilizing various assays and analyses.The results revealed significant differences in microbiota composition,with increased levels of Bacter-oides in NAFLD patients.Additionally,elevated DCA levels were observed in NAFLD mice,and FMT treatment demonstrated efficacy in ameliorating liver function and brain dysfunction.Hpgd inhibition by DCA activated the JAK2/STAT3 pathway in microglial cells,leading to inflammatory activation,inhibition of mitochondrial autophagy,induction of neuronal apoptosis,and reduction in neuronal action poten-tials.This study elucidates the intricate molecular mechanisms underlying the liver-gut-brain axis in NAFLD,and the identification of increased DCA and the impact of JAK2/STAT3 signaling on microglial cells highlight potential therapeutic targets for addressing NAFLD-induced brain dysfunction.

Allergic rhinitis （AR） is one of the most common chronic non-infectious inflammatory diseases in children. Traditional Chinese medicine （TCM） employs a comprehensive therapeutic system integrating treatment by stages and syndrome differentiation and treatment， demonstrating significant advantages in the management of pediatric AR. This article systematically reviews the clinical treatment methods and underlying mechanisms of TCM for pediatric AR in recent years. It is found that internal therapies （such as herbal formulas or Chinese patent medicines like Xiaoqinglong decoction， Yiqi tuomin decoction）， external therapies （including intradermal needles， acupoint application， tuina， and herbal nasal therapy）， as well as combined internal and external approaches （oral herbs combined with acupoint application）， have demonstrated significant effects in alleviating clinical symptoms， improving immune indicators， and reducing recurrence rates in children with AR. The underlying mechanisms are primarily associated with the regulation of signaling pathways such as Toll-like receptor/nuclear factor-kappa B and mitogen-activated protein kinase， thereby modulating immune balance， suppressing inflammatory responses， inhibiting pyroptosis， reducing mucus secretion， and promoting nasal mucosal repair.

Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.

Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective To investigate the incidence of central obesity and characteristics and changing trend of macronutrient energy supply in adult residents of Chongqing, and to analyze the relationship between carbohydrate energy supply and central obesity. Methods Using the longitudinal tracking data of China Health and Nutrition Survey project, combined with China food composition table , the energy and nutrient intake and macronutrient energy supply ratio were calculated. The association between carbohydrate energy supply and central obesity was analyzed by multi-level statistical model. Results In 2011, 2015 and 2018, the carbohydrate supply ratio of adult residents in Chongqing was 43.02%, 46.52%, and 46.07%, respectively, and the difference was statistically significant (F=18.699, P<0.001). The overweight rates in 2011, 2015, and 2018 were 29.2%, 36.7%, and 37.8%, while the obesity rates were 12.2%, 13.5%, and 19.5%, respectively, with statistically significant differences (χ²=41.416, P<0.001). The central obesity rates were 51.5%, 57.2%, and 62.8%, respectively (χ²=21.008, P<0.001). The carbohydrate supply ratio was positively correlated with waist circumference. Compared to the population with a carbohydrate to energy ratio of <55%, the risk of central obesity in the population with a carbohydrate to energy ratio of ≥ 65% was 1.63 times higher. Conclusion The ratio of carbohydrate to energy supply of adult residents in Chongqing has slightly increased. Rates of overweight, obesity and central obesity are on the rise. A high carbohydrate to energy supply ratio may be a risk factor for central obesity.

Objective To investigate the effect of the 5-HT1A receptor antagonist on synaptic plasticity in flurane-induced cognitive dys-function in aged rats.Methods Thirty 18-month-old Sprague-Dawley rats were randomly divided into control,model,and drug groups.The model group inhaled a 50%oxygen gas mixture(2 L/min)and 2%sevoflurane and were then treated with 5μL 0.9%NaCl;the drug group inhaled a 50%oxygen mixture(2 L/min)and 2%sevoflurane for 4 h and then the 5-HT1A receptor antagonist(3μg)was injected into the left ventricles of the rats;and the control group inhaled a 50%oxygen mixture(2 L/min)for 4 h.The water maze method was used to assess the learning memory of the rats and histopathological changes in the rat hippocampus were examined by HE staining.Nissl and Golgi staining were used to identify any changes to the neurons and synapses in hippocampal tissue.The MeCP2,p250GAP,PSD-95,GAP-43,and Syn expression levels were determined by immunofluorescence assay and the PKA,CREB1,and BDNFmRNA levels were determined using real-time PCR.Western blotting was performed to determine the PKA,CREB1,p-CREB1,and BDNF expression levels.Results The water maze data showed that the escape latency was significantly prolonged in the model group compared to the control group and,after treatment with the 5-HT1A receptor antagonist,the escape latency significantly decreased in the drug group compared to that of the model group(P<0.05).Moreover,the number of platform crossings was significantly lower in the model group than in the control group,but the number of platform crossings in the drug group was significantly higher than that in the model group(P<0.05).Compared to the control group,the hippocampal neurons in the model group had irregular morphology,loosely arranged and enlarged sur-rounding tissue gaps,deeply stained nuclei,a reduced number of Nissl bodies in the neurons,and a significantly reduced dendritic spine density and number of branches.After treatment with the 5-HT1A receptor antagonist,the hippocampal neurons in the drug group had a regular morphology,relatively complete structure,uniform arrangement,increased numbers of Nissl bodies in the neurons,and a signifi-cantly increased dendritic spine density and number of dendritic branches.Compared to the control group,MeCP2,PSD-95,GAP-43,Syn,PKA,CREB1,p-CREB1,and BDNF expression levels significantly decreased and p250GAP expression significantly increased in the rat brain tissue from the model group(P<0.05),but the PKA,CREB1,and BDNF mRNA levels significantly decreased(P<0.05).Furthermore,compared to the model group,the MeCP2,PSD-95,GAP-43,Syn,PKA,CREB1,p-CREB1,and BDNF expres-sion levels significantly increased along with the PKA,CREB1,and BDNF mRNA levels(P<0.05)in the drug group.However,the p250GAP protein expression level significantly decreased(P<0.05).Conclusion The 5-HT1A receptor antagonist improves learning memory in rats with sevoflurane-induced cognitive dysfunction.Specifically,it enhances PSD-95,GAP-43,and Syn expression levels,pro-motes synaptic remodeling,and protects rat hippocampal neuronal cells by activating the CREB/BDNF pathway.

Objective To investigate the mechanism of cartilage injury and inflammation in the WHBE rabbit KOA model and the effect of platelet-rich fibrin releasates(PRFr)treatment on the KOA process,we established a WHBE rabbit KOA model by excision of medial collateral and partial patellar ligaments and administered a PRFr solution.Methods Twenty-four WHBE rabbits were randomly divided into three groups:normal control(NC)group(n=6),model(KOA)group(n=12),and cure(PRFr)group(n=6).KOA and PRFr groups were injected with 0.5 mL saline and PRFr into both joint cavities on 7 and 14 postoperative days,respectively.At 4 and 8 weeks of modeling,the knee joint grade scoring,X-ray imaging,and gross scoring were performed.Serum levels of IL-1β,TNF-α,and MMP-13 were measured by ELISA.At 4 weeks,6 animals in the KOA group were euthanized,and at 8 weeks,the remaining animals in each group were euthanized.Pathological sections were prepared after decalcification,and then HE,toluidine blue,and safranin O-fast green staining and immunohistochemical analysis of TGF-β,BMP3,and NF-κB were conducted.Results The Lequesne MG behavioral score,Mankin's score,and Pelletier score of WHBE rabbits after the operation were significantly increased compared with the NC group(P＜0.01).Pathological observations revealed surface defects of the cartilage and partial loss of chondrocytes.These result indicated that the KOA model was established successfully.In KOA rabbits,knee joint swelling,joint pain stimulation,and movement limitation were obvious.X-rays showed a high-density soft tissue shadow,indicating more joint effusion and a rough articular surface in general.After PRFr treatment,the serum levels of proinflammatory factors IL-1β,TNF-α,and MMP-13 in KOA model rabbits were significantly reversed(P＜0.05,P＜0.01).Additionally,the cartilage surface became smooth,and most chondrocytes were neatly distributed.Expression levels of TGF-β,BMP3,and NF-κB induced by KOA were also significantly decreased(P＜0.01).Conclusions We successfully established a KOA model in WHBE rabbits,and PRFr improved the cartilage injury and inflammation of the WHBE rabbit KOA model through TGF-β/BMP and NF-κB pathways.