ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

BACKGROUND: The benefits of ideal cardiovascular-health metrics (ICVHMs) in patients with renal insufficiency remain unclear. This study aimed to investigate the associations between ICVHM and prognosis in a renal insufficiency population. METHODS: The trial enrolled 29,682 participants from the US National Health and Nutrition Examination Survey (NHANES), 2007-2018, with mortality follow-up through December 31, 2019. Participants were divided into three groups based on estimated glomerular filtration rates. Cardiovascular health was assessed using new "Life's Essential 8" metrics. Cox regression analyses based on NHANES data were used to determine the associations between ICVHMs and cardiovascular mortality in patients with renal insufficiency. RESULTS: During a mean follow-up of 6.58 years, ideal cardiovascular health (hazard ratio [HR] = 0.42; 95% confidence interval [CI]; 0.25-0.70) and ideal health behavior (HR = 0.53; 95% CI; 0.39-0.73) reduced cardiovascular mortality in participants with renal insufficiency. For each one ICVHM increment, a 25% reduction in cardiovascular mortality was recorded (95% CI; 0.69-0.82). When compared with participants with normal renal function, for those with mild renal insufficiency, the HR for cardiovascular mortality gradually decreased from 1.47 (95% CI; 0.85-2.52) in those who had ≤1 ICVHMs to 0.30 (95% CI; 0.12-0.77) in participants who had >6 ICVHMs. CONCLUSIONS From an ICVHM perspective, enhanced cardiovascular benefits were observed in individuals with renal insufficiency, coupled with a reduced risk of all-cause mortality. Furthermore, when compared with individuals with normal renal function, increased ICVHMs can mitigate adverse risks associated with renal impairment.
Humans ; Male ; Female ; Nutrition Surveys ; Middle Aged ; Renal Insufficiency/physiopathology* ; Aged ; Prognosis ; Adult ; Cardiovascular Diseases/mortality* ; Glomerular Filtration Rate/physiology* ; Proportional Hazards Models

OBJECTIVES: This study aimed to investigate the potential mediating role of plasma phosphorylated tau217 (p-tau217) in the association between periodontitis and mild cognitive impairment (MCI). METHODS: In this case-control study, patients diagnosed with MCI in the Neurology Department of the First Affiliated Hospital of Shandong Second Medical University from November 2023 to May 2024 were selected as the case group (MCI group). Cognitively normal (CN) volunteers, matched for age and education level and recruited from the physical examination center during the same period, served as the control group (CN group). The general demographic data of the study participants were collected. The Beijing versions of the Montreal Cognitive Assessment (MoCA), clinical dementia rating (CDR), and activities of daily living scale (ADL) were used to assess neuropsychological functions. Clinical periodontal examinations were conducted, the periodontal inflamed surface area (PISA) was calculated, and the periodontitis stage was determined in accordance with the 2018 classification. Fasting elbow venous blood samples were collected in the morning, and blood biochemical indicators were measured. Plasma p-tau217 levels were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using t-test, Mann-Whitney U test, chi-square test, partial correlation analysis, multivariate Logistic regression analysis, multiple linear regression analysis, restricted cubic spline (RCS) regression analysis, and mediation effect analysis. RESULTS: Among the 192 participants, 96 belong to the MCI group and 96 to the CN group. The prevalence of periodontitis was 63.5% in the MCI group and 43.8% in the CN group, with a statistically significant difference (χ²=7.561, P=0.006). The plasma p-tau217 levels in the MCI group were significantly higher than those in the CN group [7.00 (4.27-9.65) ng/mL versus 2.02 (0.80-3.81) ng/mL, Z=-8.108, P<0.001]. Partial correlation analysis revealed that plasma p-tau217 levels were positively correlated with all the clinical periodontal indices (all P<0.001). After adjustments for baseline covariates, multivariate Logistic regression indicated that periodontitis was an independent risk factor for MCI. Patients with periodontitis had a 1.977-fold higher MCI risk than those without periodontitis (OR=1.977, 95%CI: 1.088-3.594, P=0.025). Moreover, the MCI risk for stage Ⅰ/Ⅱ periodontitis and stage Ⅲ/Ⅳ periodontitis was 1.878 times (OR=1.878, 95%CI: 1.029-3.425, P=0.040) and 2.625 times (OR=2.625, 95%CI: 1.073-6.246, P=0.035) higher than that for patients without periodontitis, respectively. Trend test showed that the MCI risk increased with periodontitis severity (P_trend=0.016). After adjustments for baseline covariates, multiple linear regression analysis showed that periodontitis was an independent risk factor for increased plasma p-tau217 levels (β=3.309, 95%CI: 2.363-4.254, P<0.001). Compared with patients without periodontitis, those with stage Ⅰ/Ⅱ periodontitis (β=1.838, 95%CI: 0.869-2.806, P<0.001) and stage Ⅲ/Ⅳ periodontitis (β=5.539, 95%CI: 4.442-6.636, P<0.001) had significantly higher plasma p-tau217 levels. In addition, trend test indicated that plasma p-tau217 levels increased with periodontitis severity (P_trend<0.001). After adjustments for baseline covariates, RCS regression analysis further revealed that PISA had a positive linear dose-response relationship with MCI risk (P_overall=0.002, P_nonlinear=0.344) and plasma p-tau217 levels (P_overall<0.001, P_nonlinear=0.140). After adjustments for baseline covariates, mediation analysis showed that plasma p-tau217 mediated the association between periodontitis and MCI, with a mediation proportion of 13.99% (95% Bootstrap CI: 0.38%-49.39%, P=0.038). CONCLUSIONS Periodontitis was independently positively associated with MCI risk, and plasma p-tau217 plays a mediating role in this association.
Humans ; Cognitive Dysfunction/complications* ; tau Proteins/blood* ; Periodontitis/complications* ; Case-Control Studies ; Male ; Female ; Phosphorylation ; Aged ; Middle Aged ; Activities of Daily Living