ObjectiveBlood-Heat syndrome is a core syndrome of Traditional Chinese Medicine (TCM) in Henoch-Schönlein purpura nephritis (HSPN), yet its biological basis remains unclear. This study aimed to systematically elucidate the scientific basis of Blood-Heat syndrome within the context of HSPN and to identify its objective biomarkers using a multidimensional biological approach.MethodsIn the clinical research part, we divided it into a discovery cohort and a validation cohort. The discovery cohort employed Data-Independent Acquisition (DIA) proteomics technology to analyze serum samples from HSPN patients with Blood-Heat syndrome (n = 15), those without Blood-Heat syndrome (non-Blood-Heat, n = 30), and healthy controls (n = 30). The findings were then validated through ELISA in both the discovery cohort and an independent validation cohort (n = 30 for blood heat syndrome, n = 30 for non-blood heat syndrome). In the basic research component, we established a rat model combining HSPN with Blood-Heat syndrome to replicate the clinical findings.ResultsProteomic analysis identified 87 specific differentially expressed proteins (DEPs) associated with Blood-Heat syndrome. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed significant enrichment in the sphingolipid signaling pathway (P = 0.02). We further identified a panel of nine core biomarkers (AHSG, HRG, KNG1, HP, AZGP1, PTX3, MAPK1, A1BG, and COL1A1), which demonstrated excellent diagnostic performance in distinguishing between healthy control group and blood-heat syndrome, as well as between blood-heat syndrome and non-blood-heat syndrome (with AUC values all ≥0.7). ELISA validation showed that, compared to the healthy control group and non-Blood-Heat group, the levels of AHSG, HRG, and KNG1 were significantly downregulated in the Blood-Heat group, while the other six markers were significantly upregulated (P < 0.01 for all). This trend was fully replicated in the HSPN Blood-Heat syndrome rat model.ConclusionBased on multidimensional evidence from clinical proteomics and animal model replication, this study suggests that Blood-Heat syndrome in the context of HSPN has a reproducible molecular phenotype. The functional enrichment of its differential proteins involves the sphingolipid signaling pathway, accompanied by an enhanced inflammatory background represented by ERK2 upregulation. Based on these findings, we propose a core scientific hypothesis of “Blood-Heat-related stress—sphingolipid signaling-associated alterations—ERK2-mediated inflammatory amplification,” providing a direction for future mechanistic validation and targeted intervention research.

Immunoglobulin A vasculitis nephritis (IgAVN) is the most common secondary glomerular disease in children, and the severity of renal involvement is a critical determinant of long-term prognosis. Although renal biopsy remains the gold standard for pathological diagnosis, its invasive nature and delayed indication limit its utility for early monitoring. With the advancement of precision medicine, identifying non-invasive and sensitive biomarkers has become an urgent clinical need. In recent years, beyond classical immune-inflammatory indicators, the application of high-throughput technologies such as genomics, proteomics, and metabolomics has provided a new dimension for the systematic characterization of the IgAVN molecular landscape. This review summarizes the current status of research on IgAVN biomarkers, focusing on the latest breakthroughs ranging from core immune molecules like Gd-IgA1 to multi-omics “fingerprints.” Furthermore, it critically analyzes the challenges currently faced in the clinical translation of these findings, aiming to provide a theoretical basis for establishing an early warning system and personalized diagnosis and treatment strategies for IgAVN.

To investigate the efficacy and safety of Telitacicept (RC18) in children with Henoch-Schönlein Purpura Nephritis (HSPN). A prospective self-controlled study enrolled HSPN children from the First Affiliated Hospital of Henan University of Chinese Medicine from December 2023 to January 2025. Clinical and laboratory indices and adverse reactions were recorded during 1–4 months of follow-up. Primary study endpoint was 24 h UTP, and the secondary study endpoints included urinary RBC count, renal function (BUN, UA, Scr, eGFR) and safety. Exploratory analysis included dynamic changes in lymphocytes, BAFF, APRIL and Gd-IgA1. Twenty-one patients were enrolled. After Telitacicept treatment, the 24 h UTP response rate was 100

CD163 is a surface marker expressed by M2c macrophages. This study aims to evaluate the level of urinary soluble CD163 (u-sCD163) in children with IgA vasculitis with nephritis (IgAVN) and its potential diagnostic value. U-sCD163 was analyzed in 73 children with IgAVN who underwent a kidney biopsy, 37 children with IgA nephropathy and 50 normal controls. CD163 expression was analyzed by immunohistochemistry. Correlation analyses and inter-group comparison were performed to assess the association between u-sCD163 levels and clinicopathological features of IgAVN. The comparison of u-sCD163 levels before and after treatment was conducted. The level of u-sCD163 was significantly higher in children with IgAVN than healthy controls. Compared with grade II IgAVN subjects, u-sCD163 level was significantly elevated in grade III–IV subjects. There was no difference in u-sCD163 level between IgAVN and IgA nephropathy groups. There was no difference in serum CD163 level among different groups. In the IgAVN group, abundant CD163-positive cells were observed in glomeruli showing endocapillary proliferation, especially in areas of thrombosis and fibrinoid necrosis. In contrast, CD163-positive cells were scarce within cellular crescents, but increased in fibrocellular crescents. Levels of u-sCD163 showed a significant positive correlation with proportions of endocapillary proliferation, and moderately correlated with proteinuria, CD163 score of glomerular area, and weakly correlated with proportions of cellular crescents, D-dimer and fibrin degradation products (FDP). The level of u-sCD163 decreased significantly after treatment. U-sCD163 emerges as a promising marker associated with endocapillary proliferation and coagulation in pediatric patients with IgAVN.

Mycoplasma pneumoniae (MP) is a leading cause of pediatric community-acquired pneumonia, with clinical manifestations ranging from self-limiting disease to severe refractory pneumonia and long-term pulmonary sequelae. Three interrelated, partially overlapping yet still contested processes can explain the core pathogenic mechanisms of MP pneumonia (MPP). In the acute phase, immune dysregulation is characterized by excessive cytokine release and abnormal activation of innate and adaptive immune cells; however, the origin and regulation of this excessive inflammation remain controversial. During the immune evasion phase, MP employs multiple escape strategies, including adhesion proteins, CARDS toxins, and genomic plasticity, to circumvent host defenses, establish persistent infections, and further leave hidden dangers for acute phase inflammatory dysregulation and chronic phase structural remodeling. However, the exact molecular mediators remain unclear. Macrolide antibiotics remain the primary clinical treatment; however, therapeutic limitations persist owing to increasing drug resistance and the lack of immunopathological interventions. In the migration phase, sustained immune activation and abnormal repair processes persist even after pathogen clearance, resulting in chronic lung injury and fibrosis, with underlying immunological mechanisms still poorly understood. This review synthesizes current insights into immune dysregulation across the acute-to-chronic spectrum of MPP, identifies unresolved immunopathological bottlenecks, and highlights translational opportunities for immune-targeted interventions beyond antibiotics.

Crescent formation is common in pediatric IgA vasculitis nephritis (IgAVN), but its clinicopathological correlates and the significance of crescent burden and activity remain unclear. We retrospectively analyzed 1,280 children with biopsy-proven IgAVN and available crescent assessment who were hospitalized at the Department of Pediatric Nephrology, The First Affiliated Hospital of Henan University of Chinese Medicine, between January 2013 and January 2021. Patients were classified by the presence or absence of crescents on kidney biopsy. Univariable and sequential multivariable logistic regression analyses were performed, with additional stratified, post hoc, and sensitivity analyses for crescent burden and active crescents. Crescent formation was identified in 903/1,280 children (70.5

IgA vasculitis (IgAV) is the most common systemic small-vessel vasculitis in childhood, with an annual incidence of 3 to 26.7 per 100,000 children. Although it is predominantly sporadic, its 1.9% familial clustering rate and significant tendency for sibling comorbidity suggest a non-random pathogenesis. Multicohort GWAS data confirm that HLA-DRB1*01 and HLA-DRB1*11 are common genetic risk loci across ethnic groups. Furthermore, the core pathogenic molecule, galactose-deficient IgA1 (Gd-IgA1), exhibits a heritability of up to 64% in affected families, constituting the intrinsic basis for sibling concordance. Regarding the triggering mechanism, approximately 75% of IgAV cases are preceded by upper respiratory or gastrointestinal prodromal infections; the cross-transmission of streptococci and viruses within the family environment provides the external trigger for sibling-to-sibling transmission. Clinical phenotypes show that familial cases exhibit high consistency in the pattern of target organ involvement, and the renal involvement in the index case has significant predictive value for stratifying sibling risk. This article proposes potential mechanisms underlying the synchronized onset of disease and the formation of phenotypic mirroring among siblings, aiming to establish a clinical system for early warning and precise intervention based on family history.

Background: Crescent is a key pathological factor affecting the treatment in IgA vasculitis nephritis (IgAVN). The proportion of the crescent from 0 to 50% is broad in grade Ⅲ IgAVN. The present study aimed to analyze the clinicopathological features and outcomes of different proportions and types of crescent in grade Ⅲ IgAVN patients. Methods From January 2020 to December 2024, 442 patients with grade Ⅲ IgAVN were enrolled in this retrospective study. The patients were divided into two groups on the basis of crescent proportion: < 25% and 25%≤crescent<50%. According to the crescent type, the patients were divided into three groups: acute, subacute and chronic crescent groups. The clinicopathological features and outcome were compared among groups. Results Compared with crescent <25% group，urinary occult blood, proteinuria, urinary N-acetyl-beta-D-glucosaminidase (NAG), blood urea nitrogen (BUN), tubulointerstium injury rate and tubulointerstium injury scores all increased significantly, and estimated glomerular filtration rate (eGFR) decreased siginificantly in 25%≤crescent<50% group. Compared with acute crescent group, percentage of crescent, tubulointerstium injury rate and scores increased, eGFR and percentage of endocapillary proliferation decreased in subacute group, but proteinuria, urinary NAG and BUN were no difference between acute and subacute groups. Compared with acute and subacute groups, proteinuria in the chronic crescent group decreased significantly and chronic tubulointerstium score increased significantly. Follow up for 1 to 4 years, patients with 25%≤crescent<50% had higher incidence of end-stage renal disease (ESRD) than crescent<25% group, and patients in subacute and chronic crescent groups had higher incidence of ESRD than acute crescent group. Conclusions Different proportions and types of crescent in patients with grade Ⅲ IgAVN had different clinicopathological features and outcomes. It is necessary to refine and score the proportion and type of crescents in pathological diagnosis of IgAVN patients.

Glutamine (Gln) has been implicated as a potential protective factor against allergic rhinitis (AR), with supplementation studies suggesting improved patient prognosis. However, the precise relationship between circulating Gln levels and AR risk remains unclear. To address this, we employed bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between Gln and AR. Genome-wide association study (GWAS) summary statistics for AR (FinnGen dataset finn-b-ALLERGY_RHINITIS; 217,914 samples; 16,380,461 single nucleotide polymorphisms [SNPs]) and circulating Gln levels (met-d-Gln; 114,750 samples; 12,321,875 SNPs) were obtained from the Integrative Epidemiology Unit Open GWAS database. MR analyses were performed, primarily using the inverse variance weighted (IVW; fixed-effects) method. Sensitivity analyses included the weighted median, simple median, MR-Egger, and maximum likelihood methods. Robustness of the MR findings was further assessed via heterogeneity tests, horizontal pleiotropy evaluation (MR-Egger intercept test), and leave-one-out (LOO) analysis. Additionally, phenotypic association scanning was conducted for both AR and Gln. Forward MR (Gln→AR) revealed a significant negative causal association, identifying Gln as a protective factor for AR (IVW OR < 1; P < .05). Reverse MR (AR→Gln) showed no causal effect ( P > .05). Sensitivity analyses confirmed reliability: no significant heterogeneity (Q_ P > .05) or horizontal pleiotropy ( P > .05) was detected in either direction, and LOO analysis supported result stability. Phenotypic scanning corroborated Gln as a protective factor against AR (OR = 0.874, 95% CI = 0.77047–0.99093, P = .036). Our study suggests that Gln is a protective factor against AR and that AR is not causally associated with Gln.

Pediatric lupus nephritis(LN)is a challenging and severe condition in pediatrics.Traditional Chinese medicine(TCM)has shown significant advantages in improving immune disorders,reducing recurrence rates,and mitigating the toxic side effects of Western medications.However,it faces challenges such as the lack of a unified TCM syndrome differentiation system,insufficient standardization of dynamic syndrome differentiation,an incomplete efficacy evaluation system,and a lack of precise intervention methods.This study focuses on the clinical advantages of TCM.On 1 September 2024,the 35th Clinical Advantage Disease Series Salon was held in Zhengzhou,discussing the advantages of TCM and integrated Chinese-Western medicine in treating pediatric LN.Experts in TCM and integrated Chinese-Western medicine,along with interdisciplinary researchers,conducted extensive and in-depth discussions.They proposed specific recommendations for TCM and integrated Chinese-Western medicine in treating pediatric LN and reached a consensus.Based on this,the study analyzes the challenges in treating pediatric LN from the perspective of its development patterns,and summarizes three key areas and six research directions to highlight the advantages of TCM and integrated Chinese-Western medicine in treating pediatric LN.It focuses on three key areas:The construction of a TCM system for pediatric LN,the prevention and treatment of complications,and chronic disease management.And it proposes six research directions:(1)Constructing a syndrome differentiation system for pediatric LN;(2)Formulating TCM and integrated Chinese-Western medicine guidelines for pediatric LN;(3)Researching the mechanisms of enhancing efficacy and reducing toxicity in integrated Chinese-Western medicine for pediatric LN;(4)Preventing and treating complications in pediatric LN;(5)Developing and researching TCM regimens for preventing and treating the recurrence of pediatric LN;(6)Strategies for the full-cycle chronic disease management of pediatric LN.Finally,the study summarizes and generalizes the technological layout and research directions for pediatric LN.Therefore,based on the series of salons on traditional Chinese medicine advantages for children LN diseases,this paper puts forward a research paradigm of scientific and technological breakthroughs for children LN,in order to provide reference for the construction and research direction of children LN diagnosis and treatment system with traditional Chinese medicine characteristics.

Glucocorticoid-induced osteoporosis(GIOP) is a serious metabolic bone disease caused by long-term application of glucocorticoids(GCs). Traditional Chinese medicine(TCM) has unique advantages in improving bone microstructure and antagonizing hormone toxicity. This paper systematically reviews the theoretical research, clinical application, and basic research progress of TCM intervention in GIOP. In terms of theoretical research, the theory of &quot;kidney governing bone and generating marrow&quot; indicates that the kidney is closely related to bone development, revealing that core pathogenesis of GIOP is Yin-Yang disharmony, which can be discussed using the theories of &quot;Yin fire&quot;, &quot;ministerial fire&quot;, and &quot;Yang pathogen damaging Yin&quot;. Thus, regulating Yin and Yang is the basic principle to treat GIOP. In terms of clinical application, effective empirical prescriptions(such as Bushen Zhuanggu Decoction, Bushen Jiangu Decoction, and Zibu Ganshen Formula) and Chinese patent medicines(Gushukang Capsules, Hugu Capsules, Xianling Gubao Capsules, etc.) can effectively increase bone mineral density(BMD) and improve calcium and phosphorus metabolism. The combination of traditional Chinese and western medicine can reduce the risk of fracture and play an anti-GIOP role. In terms of basic research, it has been clarified that active ingredients of TCM(such as fraxetin, ginsenoside Rg_1, and salidroside) reduce bone loss and promote bone formation by inhibiting oxidative stress, ferroptosis, and other pathways, effectively improving bone homeostasis. Additionally, classical prescriptions(Modified Yiguan Decoction, Modified Qing'e Pills, Zuogui Pills, etc.) and Chinese patent medicines(Gushukang Granules, Lurong Jiangu Dropping Pills, Gubao Capsules, etc.) can improve bone marrow microcirculation, promote osteoblast differentiation, and inhibit bone cell apoptosis through multiple pathways, multiple targets, and multiple mechanisms. Through the above three aspects, the TCM research status on GIOP is elucidated in the expectation of providing reference for its diagnosis and treatment using traditional Chinese and western medicine treatment programs.

Mycoplasma pneumoniae pneumonia (MPP) is a common type of pneumonia among school-aged children and adolescents. Jinzhen Oral Liquid (JZOL) and Azithromycin (AZ) are commonly used treatments in traditional Chinese medicine (TCM) and Western medicine, respectively. There are several clinical and basic research reports on their solo effect against MPP, enabling their combined treatment to become possible. However, the mechanisms and specific pharmacodynamics of their combined therapy remain unclear. In this study, we conducted a mechanistic analysis of the combination of JZOL and AZ based on network target, elucidating their modular network regulatory mechanisms. The modular mechanisms involve four modules, including hormone response, cell differentiation and migration, signal transduction, oxygen and hypoxia response, centered by TNF signaling pathway-mediated regulation. Under the instruction of computational analysis, we conducted a randomized, double-blind, three-armed, parallel-controlled, multicenter clinical study of different doses of JZOL combined with AZ for the treatment of MPP in children. The objective of clinical research is to evaluate the synergistic effect of different doses of JZOL combined with AZ in the treatment of children with MPP, shortening the course of disease and improving prognosis, while observing the safety of clinical application. At the study endpoint, the median time to clinical recovery showed statistically significant differences (The double-dose group lasts for 5 days, the regular-dose group lasts for 6 days, and the placebo group lasts for 8 days), which were also observed between groups for time to complete fever remission, time to relief of cough/phlegm, effective rate of chest X-ray improvement, and rate of healing of TCM symptoms. Different doses of JZOL combined with AZ have shown the effects of shortening the course of the disease, relieving the symptoms, and improving the prognosis. The research program composed of computational prediction and clinical trials can significantly accelerate the research and development process and identify more effective treatment with good safety, which is worthy of clinical promotion. Chinese Clinical Trial Registry ChiCTR1800019007

Background:Xiao'er Fengre Qing Oral Liquid (XFQOL) is developed based on the classical traditional Chinese medicinal formula Yinqiao Powder. Compared to the original formulation, XFQOL exhibits enhanced heat-clearing, detoxification, and fever reduction, which can effectively address the common complications associated with influenza in children and is well-suited for pediatric use. However, there is currently a lack of high-quality evidence from clinical trials to support its efficacy and safety in clinical applications. Objective:This study aimed to investigate the efficacy and safety of XFQOL compared with Oseltamivir in pediatric influenza. Methods:A multicenter, block-randomized, double-blind, double-dummy, positive-drug-controlled, non-Inferiority clinical trial design was conducted. The study plans to enroll 420 pediatric participants, with 210 in each group. The experimental group will receive XFQOL with an Oseltamivir granules placebo, and the control group will receive Oseltamivir granules with a XFQOL placebo for 5 days, followed by a 2-day post-treatment observation. The primary endpoint was clinical recovery time, while secondary endpoints included complete fever resolution time, the area under the curve (AUC) of Canadian Acute Respiratory Illness and Flu Scale (CARIFS) symptom dimension Score over time, Traditional Chinese Medicine (TCM) syndrome efficacy, disappearance rates for individual symptoms, incidences of complications and severe and critical influenza, the usage of acetaminophen, and viral negative conversion rate. Safety evaluation focused on adverse events (AE) and adverse drug reactions (ADR). Results:A total of 418 participants were included in the Full Analysis Set, with 208 in the experimental group and 210 in the control group. Baseline characteristics were comparable between the groups. The median time to clinical recovery was 3 days for both groups, with a hazard ratio and its 95% confidence interval (experimental group/control group) of 1.115 (95% CI: 0.912-1.363). Non-inferiority testing demonstrated that the experimental group was not inferior to the control group. Subgroup analyses (positive for RT-PCR influenza, positive for RT-PCR influenza A, positive for RT-PCR influenza B) yielded results consistent with the primary endpoint. The median time to complete fever resolution was 32 h in both groups, with no statistically significant difference (P = 0.407). There were no statistically significant differences in the AUC of CARIFS symptom scores over time between the groups (P = 0.211). No significant differences were observed between the groups in the efficacy rates of TCM syndromes of Wind-Heat Invading the Defense Syndrome (P = 0.076) and Fright-complicated Syndrome (P = 0.168); however, significant differences were found in Phlegm-complicated Syndrome (P = 0.008) and Food-stagnation-complicated Syndrome (P = 0.024). The disappearance rates for individual symptoms, such as red and swollen pharynx, cough, copious sputum or audible phlegm sounds in the throat, and lack of appetite, showed statistically significant differences between the groups (P < 0.05), while no significant differences were observed for other symptoms. No statistically significant differences were observed between the experimental and control groups in the incidence of complications and severe and critical influenza, the usage of acetaminophen, and viral negative conversion rate (P > 0.05). The incidence rates of AE (P = 0.885) and ADR (P = 0.685) were comparable between the two groups, with no statistically significant differences observed. Conclusion:The efficacy of XFQOL in treating pediatric influenza (Wind-Heat Invading the Defense Syndrome) is non-inferior to Oseltamivir with respect to clinical recovery time. Additionally, its effectiveness in terms of fever reduction, symptom alleviation, incidences of complications and severe and critical influenza, the usage of acetaminophen, and viral negative conversion rate is comparable to that of Oseltamivir. Furthermore, it demonstrates good safety, suggesting its potential for clinical application. Clinical Trial Registration:clinicaltrials.gov, identifier ChiCTR2300076191.

The purpose of this study was to investigate the age and gender characteristics of 24-h urinary protein/creatinine ratio (24hUPCR) and urinary microalbumin/creatinine ratio (UMACR) among Chinese children and other related factors, and to establish preliminary reference ranges. A total of 200 healthy children aged 2–15 years were enrolled. We divided the subjects into twelve groups according to age. Kruskal–Wallis one-way ANOVA test and Spearman correlation analysis were used to compare 24hUPCR and UMACR with other variables and 95

Chronic rhinitis and its associated persistent nasal obstruction and mouth breathing are core factors leading to the development of characteristic “rhinitis face” or “adenoid facies” in children and adolescents. This review elucidates the diverse clinical manifestations of “rhinitis face,” including: persistent open-mouth posture; abnormal patterns of facial skeletal growth, such as midface hypoplasia and increased lower anterior facial height resulting in “long face syndrome”; alterations in jaw morphology and position, including maxillary constriction, high-arched palate, and mandibular retrognathia or posterior-inferior rotation; and various dentoalveolar malocclusions, such as proclined maxillary incisors, lip incompetence, narrow dental arches, and open bite. Additionally, these include characteristic periorbital skin changes, such as “allergic shiners” (dark circles under the eyes due to venous stasis or pigmentation), Dennie-Morgan lines (infraorbital folds associated with atopy), and, in some patients, eyelash trichomegaly (increased eyelash growth) potentially due to chronic inflammation. The nose may also exhibit a transverse nasal crease (the “allergic salute” sign) from repetitive rubbing. This paper delves into its pathophysiological mechanisms, emphasizing that mouth breathing patterns triggered by chronic nasal airway obstruction are the initiating factor. This alters the equilibrium of orofacial muscle forces, interferes with normal tongue posture and function, and affects the normal growth trajectory of the maxillofacial skeleton. Combined with local inflammatory responses and mechanical stimuli, these factors collectively contribute to the development of these complex facial characteristics. Clinical assessment requires a comprehensive approach including medical history, detailed physical examination, and various ancillary investigations such as nasal endoscopy, imaging studies (x-ray, CT, CBCT), cephalometric analysis, nasal patency tests, and allergen testing. “Rhinitis face” not only affects aesthetics but can also lead to severe maxillofacial skeletal deformities, dental malocclusions, temporomandibular joint dysfunction, and sleep-disordered breathing. It can also profoundly impact respiratory physiology, exercise tolerance, speech clarity, psychological well-being, and quality of life. Its long-term effects can persist into adulthood, although skeletal adaptive changes diminish after growth cessation. Regarding gender differences in its prevalence, existing data suggest that upstream factors (such as obstructive sleep apnea) may have a higher prevalence in males, and the impact of mouth breathing on facial morphology might exhibit sex-specific differences. However, the overall sex ratio for “rhinitis face” remains inconclusive. Concerning the notion that rhinitis causes enlarged eyes, there is currently no scientific evidence to support an actual increase in eyeball size. The perception of “larger eyes” is more likely a visual contrast effect due to allergic shiners, Dennie-Morgan lines, and possible mild eyelid edema. Regarding public opinions about finding “rhinitis face in girls” attractive, this review emphasizes the lack of scientific basis for such views, which are more likely subjective perceptions or cultural phenomena. Medically, “rhinitis face” is considered a pathological condition requiring active intervention. Management strategies for affected children emphasize a multidisciplinary approach, including early diagnosis and active treatment of the primary nasal pathology (e.g., allergic rhinitis, adenoidal hypertrophy), correction of improper mouth breathing habits through methods like orofacial myofunctional therapy, and, when necessary, intervention by orthodontists or maxillofacial surgeons (e.g., rapid maxillary expansion, fixed orthodontic treatment). This review aims to provide clinicians with a comprehensive understanding of “rhinitis face” to facilitate its early recognition, standardized diagnosis and treatment, and comprehensive management.

Background: This study aims to investigate whether immune dysregulation and gut microbiome alteration are exacerbated in atopic dermatitis (AD) with food allergy (ADFA) and potential treatment strategies. Methods: Total 159 children with AD (tAD) were divided into two groups: AD without-food allergy (ADNFA) and with food allergy (ADFA); 100 children without AD were included as control. Eosinophil counts and total serum IgE levels were measured by routine methods, serum food-specific IgE levels by quantitative fluorescence immunoassay, and serum cytokine levels by multi-microsphere flow immunofluorescence. The intestinal microbiota was evaluated in fecal specimens using metagenomic sequencing. A novel ADFA mouse model was generated to evaluate whether probiotic candidates identified from human fecal samples contributed to the improvement in ADFA pathology. Results: The levels of eosinophils, IgE, IL-2, TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, IL-12P70 and IFN-α were elevated in tAD compared to normal controls. Compared with ADNFA, the levels of eosinophils, IgE and IL-5 were persistently increased, while IFN-γ was decreased, the species of Lactococcus lactis (L. lactis) was reduced in ADFA. Compared with AD, the ADFA model had more severe skin lesions on the back and significantly higher serum OVA-specific IgE, IL-4 and IL-5. Following oral administration of L. lactis ( L. lactis 1.1936+1.3992), skin lesions in ADFA mice was significantly improved. The levels of OVA-specific IgE, IL-4 and IL-5 decreased in a dose-dependent manner. Conclusions: Food allergy aggravates immune dysregulation and gut microbiome dysbiosis in children with AD. L. lactis could be a candidate probiotic for the treatment of ADFA.

The comparison between traditional Chinese medicine Jinzhen Oral Liquid (JZOL) and western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This head to head randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1 and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels was the key mechanism of action. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial Trial registration: Chinese Clinical Trial Registry: ChiCTR2000034703 ### Clinical Protocols ### Funding Statement This study was funded by the National Key Research and Development Program of the Ministry of Science and Technology of China in 2018, "Research on Modernization of TCM" project, "Demonstration Study on Evidence-based Evaluation and Effect mechanism of Ten Chinese patent Medicines and Classic famous prescriptions in the Treatment of Major Diseases after marketed" (2018YFC1707400 and 2018YFC17074101). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committee of Dongzhimen Hospital gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data collected in this study are available to researchers through QinHua Fan (18810604390@163.com). Data requests will be reviewed and approved on the basis of scientific merit, and with a signed data access and sharing agreement. These data will be available for a minimum of 5 years after publication. * AB : acute bronchitis CAM : Complementary and Alternative Medicine TCM : Traditional Chinese medicine JZOL : Jinzhen Oral Liquid AHCHOS : Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution AUC : Area Under Curve HR : hazard ratio ITT : intention-to-treat FAS : full analysis set KEGG : Kyoto Encyclopedia of Genes and Genomes GO : Gene Ontology AEs : adverse events ADRs : adverse drug reactions Th : T-helper IFN : interferon TNF : tumor necrosis factor LPS : lipopolysaccharide Poly (I:C) : polyinosinic acid-polycytidylic acid PPI : permeability index BALF : bronchoalveolar lavage fluid PGE2 : prostaglandin E2 BK : bradykinin.

Background Qingre huazhuo tang (QRHZT) is a traditional Chinese medicine decoction that has been used clinically by traditional Chinese medicine masters for more than 50 years with good results. However, its mechanism is unknown, and further elucidation is necessary. Aim of the study To verify the mechanism by which QRHZT regulates IgA nephropathy through immune checkpoints and ferroptosis by combining network pharmacology, single-cell sequencing and experimental studies. Materials and methods The single-cell sequencing data obtained from podocytes of immunoglobulin A (IgA) nephropathy (IgAN) patients were screened, and the QRHZT target information was obtained from the ETCM database. Moreover, the KEGG, GSEA, immune checkpoint and ferroptosis data were analyzed and plotted using R language. Finally, the relevant immune checkpoint and ferroptosis targets were validated experimentally. Results QRHZT can regulate IgAN through the immune checkpoints FIT, FTH1, AKR1C3, and IL6 and the ferroptosis-related genes PVR and IFNG. Conclusion QRHZT has the potential to regulate IgAN, and omics strategies combined with network pharmacology is a feasible method for exploring the mechanisms of traditional Chinese medicines.

Background: Most studies explored the possible effects of caffeine on asthma and its symptoms in children, but the results were inconsistent. Few studies have investigated the association between caffeine and fractional exhaled nitric oxide (FENO). Therefore, we explored the association between caffeine intake and FENO in pediatric asthma patients by utilizing data from NHANES. Methods: A total of 928 asthmatic children were enrolled in our study after screening NHANES participants from 2007 to 2012. Linear regression model and XGBoost model were used to assess the potential association between caffeine intake and FENO in asthmatic children. Linear or nonlinear association was further confirmed with generalized additive model and piecewise linear regression model. We also executed stratified analyses to identify specific populations. Results: Multivariate linear regression models showed a negative correlation of caffeine intake with FENO in asthmatic children. Simultaneously, for each unit increase in caffeine intake (mg) FENO decreased by a certain amount, with 0.03 (-0.04,-0.02) ppb for model 1 which adjusted no covariates, 0.03 (-0.04,-0.01) ppb for model 2 which adjusted for sex, age, ethnicity, educational background, family income, and 0.03 (-0.05,-0.01) ppb for model 3 adjusted for BMI, waist, TC, TG, HDL based on model 2. Furthermore, we applied the XGBoost model of machine learning to assess the relative importance of chosen variables, and identified vitamin C, iron, caffeine intake, vitamin B12 and vitamin D as the five most significant variables for FENO. And the generalized additive model and the piecewise linear regression model further verified this linear and inverse association. Conclusion: Our study elucidated the linear and inverse relationship between caffeine intake and FENO in pediatric asthma patients, suggesting a potential immunological role of caffeine intake in asthmatic children. These findings pave the way for further research on the role of caffeine in the pathogenesis and treatment of asthma, and underscore the importance of recognizing the immunological implications of caffeine in asthma management.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.