BACKGROUND:Troxerutin has been found to have a significant ameliorative effect on brain disorders,but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells. OBJECTIVE:To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats. METHODS:Fifty clean grade rats were randomized into healthy group,model group,and troxerutin+nuclear factor-κB agonist group,troxerutin group,and nuclear factor-κB inhibitor group.Except for the healthy group,all other groups were used to establish a rat model of cerebral infarction by arterial ligation.The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage.The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage+20 mg/kg RANK intraperitoneally.The troxerutin group was treated with 72 mg/kg troxerutin by gavage.The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram.Administration in each group was given once a day for 30 continuous days.Zea-longa was used to detect neurological damage in rats,hematoxylin-eosin staining was used to observe pathological changes,TUNEL was used to detect neuronal apoptosis,and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels,respectively. RESULTS AND CONCLUSION:Compared with the healthy group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65,nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group(P＜0.05).Compared with the model group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group(P＜0.05).Compared with the troxerutin+nuclear factor-κB agonist group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group(P＜0.05).In addition,there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group(P＞0.05).In the model group,there was a large number of cytoplasmic vacuolation,obvious edema and necrosis,and a large number of inflammatory cell infiltrations.In the troxerutin+nuclear factor-κB agonist,the swelling of brain tissue was reduced,and reticulate structures and condensed cells were reduced,still with some edema.In the troxerutin group and nuclear factor-κB inhibitor group,brain tissue swelling,neuronal edema degeneration,cytoplasmic vacuolation and neuronal nucleus consolidation were reduced,and the inflammatory cell infiltration was significantly decreased.To conclude,troxrutin can reduce the expression of neurological impairment,inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction,and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

ObjectiveTo explore the effects of compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata on the expression of type 2 innate lymphoid cells（ILC2s）-related factors in the lung of allergic rhinitis（AR）mice. MethodsAccording to the random number table method，fifty-four C57BL/6J mice were randomly divided into the following groups： Blank group，model group，Mahuang Fuzi Xixintang group，Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba and Asari Radix et Rhizoma group，Ephedrae Herba and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba group，Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group （6 mice in each group）. Except the blank group，the other groups were subjected to intraperitoneal injection of ovalbumin（OVA）and intranasal challenge to induce AR. After the AR model was established，the mice in the blank group and the model group were given 0.2 mL·d^-1 normal saline by gavage，while those in the Mahuang Fuzi Xixintang group（2.31 g·kg^-1），Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group（1.54 g·kg^-1）， Ephedrae Herba and Asari Radix et Rhizoma group（1.16 g·kg^-1）， Ephedrae Herba and Aconiti Lateralis Radix Praeparata group（1.93 g·kg^-1），Ephedrae Herba group（0.77 g·kg^-1），Aconiti Lateralis Radix Praeparata group（1.16 g·kg^-1），and Asari Radix et Rhizoma group（0.39 g·kg^-1）were given corresponding medicine by gavage，with the treatment lasting for 14 consecutive days. The survival state of mice in each group was observed， and the levels of serum immunoglobulins E（IgE）after intranasal challenge were measured by enzyme-linked immunosorbent assay（ELISA）. The pathological changes of nasal and lung tissues were observed by hematoxylin-eosin（HE）staining. The expression of ILC2s in lung tissue of mice was detected by immunofluorescence（IF）. The mRNA expression of GATA binding protein 3（GATA3），retinoic acid receptor-related orphan receptor-α（RORα）， and inhibitor of DNA binding 2（ID2）in the lung tissue of mice was detected by quantitative real-time polymerase chain reaction（real-time PCR）. The levels of IgE，interleukin（IL）-4，IL-5， and IL-13 in serum were detected by ELISA. ResultsCompared with the blank group，the model group had poor survival state of mice and significantly increased serum IgE level after intranasal challenge（p<0.01）. Additionally，the mice in the model group showed a large amount of neutrophil infiltration in the mucosa of the posterior turbinate， obvious nasal mucosal bleeding and purulent secretion，shed epithelium， thickened bronchial wall，obvious intravascular hyperemia and edema，diffusion and infiltration of a large number of inflammatory cells，seriously damaged alveolar structure，and local lung consolidation. The model group also exhibited significantly increased expression of ILC2s in the lung tissue（P<0.01），increased mRNA expression of GATA3 and RORα，decreased mRNA expression of ID2（P<0.05，P<0.01），and increased levels of serum IgE， IL-4，IL-5，and IL-13（P<0.05，P<0.01）. Compared with the model group，the Mahuang Fuzi Xixintang group and the other medicine treatment groups showed improved survival state of mice， significantly reduced inflammatory cell infiltration in the nasal and lung tissues，a small amount of nasal mucosal bleeding，trachea wall thinning，and no hyperemia，edema， and nasal secretions. Furthermore， the expression of ILC2s in lung tissue was significantly decreased（P<0.01）. The mRNA expression level of GATA3 was decreased（P<0.05），especially in the Aconiti Lateralis Radix Praeparata group（P<0.01）. The expression mRNA levels of RORα were decreased only in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group and the Ephedrae Herba group（P<0.05）. The levels of serum IgE were decreased（P<0.05）， and IL-5 levels were significantly decreased（P<0.01）. IL-4 levels were significantly decreased in the groups except the Aconiti Lateralis Radix Praeparata group（P<0.01），and the level of IL-13 in the Mahuang Fuzi Xixintang group was decreased（P<0.05）. The levels of IL-13 in were significantly decreased in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group， Ephedrae Herba group， Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group（P<0.01）. ConclusionDifferent compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata can reduce the inflammation of OVA-induced AR mice and has more advantages in reducing the secretion of IgE and IL-5. The compatibility of Ephedrae Herba and Aconiti Lateralis Radix Praeparata has the most advantage in reducing the mRNA expression of GATA3 and RORα to inhibit the expression of ILC2s and thus exert the anti-allergic effect，while the other compatibility has the extensive advantage in inhibiting the mRNA expression of GATA3.

ObjectiveTo explore the effects of compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata on the expression of type 2 innate lymphoid cells（ILC2s）-related factors in the lung of allergic rhinitis（AR）mice. MethodsAccording to the random number table method，fifty-four C57BL/6J mice were randomly divided into the following groups： Blank group，model group，Mahuang Fuzi Xixintang group，Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba and Asari Radix et Rhizoma group，Ephedrae Herba and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba group，Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group （6 mice in each group）. Except the blank group，the other groups were subjected to intraperitoneal injection of ovalbumin（OVA）and intranasal challenge to induce AR. After the AR model was established，the mice in the blank group and the model group were given 0.2 mL·d^-1 normal saline by gavage，while those in the Mahuang Fuzi Xixintang group（2.31 g·kg^-1），Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group（1.54 g·kg^-1）， Ephedrae Herba and Asari Radix et Rhizoma group（1.16 g·kg^-1）， Ephedrae Herba and Aconiti Lateralis Radix Praeparata group（1.93 g·kg^-1），Ephedrae Herba group（0.77 g·kg^-1），Aconiti Lateralis Radix Praeparata group（1.16 g·kg^-1），and Asari Radix et Rhizoma group（0.39 g·kg^-1）were given corresponding medicine by gavage，with the treatment lasting for 14 consecutive days. The survival state of mice in each group was observed， and the levels of serum immunoglobulins E（IgE）after intranasal challenge were measured by enzyme-linked immunosorbent assay（ELISA）. The pathological changes of nasal and lung tissues were observed by hematoxylin-eosin（HE）staining. The expression of ILC2s in lung tissue of mice was detected by immunofluorescence（IF）. The mRNA expression of GATA binding protein 3（GATA3），retinoic acid receptor-related orphan receptor-α（RORα）， and inhibitor of DNA binding 2（ID2）in the lung tissue of mice was detected by quantitative real-time polymerase chain reaction（real-time PCR）. The levels of IgE，interleukin（IL）-4，IL-5， and IL-13 in serum were detected by ELISA. ResultsCompared with the blank group，the model group had poor survival state of mice and significantly increased serum IgE level after intranasal challenge（p<0.01）. Additionally，the mice in the model group showed a large amount of neutrophil infiltration in the mucosa of the posterior turbinate， obvious nasal mucosal bleeding and purulent secretion，shed epithelium， thickened bronchial wall，obvious intravascular hyperemia and edema，diffusion and infiltration of a large number of inflammatory cells，seriously damaged alveolar structure，and local lung consolidation. The model group also exhibited significantly increased expression of ILC2s in the lung tissue（P<0.01），increased mRNA expression of GATA3 and RORα，decreased mRNA expression of ID2（P<0.05，P<0.01），and increased levels of serum IgE， IL-4，IL-5，and IL-13（P<0.05，P<0.01）. Compared with the model group，the Mahuang Fuzi Xixintang group and the other medicine treatment groups showed improved survival state of mice， significantly reduced inflammatory cell infiltration in the nasal and lung tissues，a small amount of nasal mucosal bleeding，trachea wall thinning，and no hyperemia，edema， and nasal secretions. Furthermore， the expression of ILC2s in lung tissue was significantly decreased（P<0.01）. The mRNA expression level of GATA3 was decreased（P<0.05），especially in the Aconiti Lateralis Radix Praeparata group（P<0.01）. The expression mRNA levels of RORα were decreased only in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group and the Ephedrae Herba group（P<0.05）. The levels of serum IgE were decreased（P<0.05）， and IL-5 levels were significantly decreased（P<0.01）. IL-4 levels were significantly decreased in the groups except the Aconiti Lateralis Radix Praeparata group（P<0.01），and the level of IL-13 in the Mahuang Fuzi Xixintang group was decreased（P<0.05）. The levels of IL-13 in were significantly decreased in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group， Ephedrae Herba group， Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group（P<0.01）. ConclusionDifferent compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata can reduce the inflammation of OVA-induced AR mice and has more advantages in reducing the secretion of IgE and IL-5. The compatibility of Ephedrae Herba and Aconiti Lateralis Radix Praeparata has the most advantage in reducing the mRNA expression of GATA3 and RORα to inhibit the expression of ILC2s and thus exert the anti-allergic effect，while the other compatibility has the extensive advantage in inhibiting the mRNA expression of GATA3.

Objective: To examine the association of joint effect of overweight and obesity with dyslipidemia on left ventricular hypertrophy (LVH) in children, so as to provide scientific evidence for the prevention of early cardiovascular damage in children. Methods: Data were obtained from the second followup crosssectional survey of Huantai Childhood Cardiovascular Health Cohort study in 2021, comprising 1 047 children aged 10-15 years with complete information. Based on overweight and obesity status and dyslipidemia status, all participants were divided into four groups:normal weight with normal lipid levels, normal weight with dyslipidemia, overweight and obesity with normal lipid levels, and overweight and obesity with dyslipidemia. Left ventricular mass index (LVMI) levels and prevalence of LVH across four groups were compared. Multivariate Logistic regression model was used to examine the association of joint effect of overweight and obesity with dyslipidemia on LVH in children. Results: There were significant differences in LVMI levels [(28.66±7.10, 29.63±4.71,31.49±5.86,32.65±4.80)g/m2.7] and prevalence of LVH (4.28%, 12.50%, 22.74%, 31.30%) across four groups (F/χ2=50.76, 90.92, P<0.05). After adjustment for confounding variables such as gender,age,screen time,sleep duration,fruit and vegetable intake,carbonated beverage consumption,physical activity and elevated blood pressure, compared to children with both normal weight and normal lipid levels, the risk of LVH in children with dyslipidemia alone increased (OR=3.27, 95%CI=1.57-6.82，P<0.05). Children with overweight and obesity alone also had a significantly increased risk of LVH (OR=6.33, 95%CI=3.76-10.66), and the highest risk was observed in those with both overweight and obesity with dyslipidemia (OR=9.66, 95%CI=5.35-17.43) (P<0.05). Conclusions The joint effect of overweight and obesity with dyslipidemia is positively correlated with LVH in children. To prevent LVH in children, both overweight and obesity with dyslipidemia should be paid attention to.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

Objective: To analyze the trajectory of dietary behaviors among middle school students in Jiading District, Shanghai, from 2021 to 2023, and longitudinally verify their association with anxiety and depression symptoms, aiming to provide scientific evidence for promoting the mental health of adolescents. Methods: The data were sourced from the National Monitoring and Intervention Project on Common Diseases and Health Impact Factors of students in Jiading District, Shanghai. A total of 1 217 middle school students who participated in at least two surveys from 2021 to 2023 were selected as the research objects, and group-based trajectory model was constructed to identify their dietary behavior scores trajectories. Modified Poisson regression was used to investigate the impact of dietary behavior scores trajectories on anxiety and depression, while Logistic regression was employed to explore the association between trajectories and changes in depression score levels. Results: The dietary behavior scores trajectories of middle school students were divided into three groups: Persistent Healthy Dietary Behavior (9.5%), Persistent Relatively Unhealthy Dietary Behavior (85.0%), and Persistent Very Unhealthy Dietary Behavior (5.5%). Students who perceived their academic performance as poor and whose parents had a cultural level of high school or below had a significantly lower proportion in the Persistent Healthy Dietary Behavior group compared to students with other characteristics ( χ 2=12.87, 8.69, 6.50, P <0.05). Compared with the Persistent Healthy Dietary Behavior group, the risk of anxiety symptoms in middle school students in the Persistent Very Unhealthy Dietary Behavior group was significantly increased ( aRR=3.04, 95%CI =1.15-8.02); Persistent Relatively Unhealthy Dietary Behavior and Persistent Very Unhealthy Dietary Behavior increased the risk of depressive symptoms ( aRR = 1.80 , 2.45, respectively), and were positively correlated with the increase in depression scores ( aOR =1.70, 2.24) ( P <0.05). Conclusions The dietary behavior of middle school students have not changed significantly in the past three years, with persistent unhealthy dietary behavior being the most common. Unhealthy dietary behaviors are positively correlated with the risk of anxiety and depressive symptoms and an increase in depression scores.

Objective: To analyze epidemiological trends and changing characteristics of syphilis among students in Yunnan Province from 2005 to 2023, so as to provide evidence for the comprehensive prevention and control of syphilis in schools. Methods: The case data of syphilis among students in Yunnan Province from 2005 to 2023 were obtained from the China Information System for Disease Control and Prevention. The Joinpoint regression model was used to conduct a time trend analysis of the reported incidence rate of syphilis. Results: From 2005 to 2023, a cumulative total of 3 191 cases of syphilis were reported in schools in Yunnan Province(1 248 male cases and 1 943 female cases). The reported incidence rate rose continuously from 0.17/100 000 in 2005 to 8.26/100 000 in 2023, with an average annual percent change (AAPC) of 24.89%( Z =13.18, P <0.01). The reported incidence rate was higher in female students than in male students ( χ 2=229.48, P <0.05). The incidence rates in the primary school, junior high school, senior high school and higher education were 0.21/100 000, 2.42/100 000, 4.45/100 000 and 6.29/100 000 respectively, and the difference was statistically significant (χ 2=3 432.84, P <0.05). The average annual growth rate was the highest in the junior high school stage(AAPC= 30.68% , Z =7.57, P <0.05),followed by the senior high school stage (AAPC=24.28%, Z = 5.70 , P <0.05).The reported incidence rate of primary and secondary syphilis increased from 0.12/100 000 in 2005 to 2.06/ 100 000 in 2023, with an AAPC of 16.86% ( Z = 4.57, P <0.05). Conclusions The overall reported incidence rate of syphilis among students in schools in Yunnan Province shows a sustained upward trend, with the most rapid annual increase observed in junior high schools. Schools should prioritize syphilis education and expand awareness campaigns to curb transmission.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption. Methods: Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells. Results: CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. In vitro experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in CckbrCKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erkuclear factor-kappa B (NF-κB) pathway. Conclusion Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.