ObjectiveTo observe the clinical efficacy and possible mechanisms of Xianglian Huazhuo Granules （香连化浊颗粒， XHG） in the treatment of chronic atrophic gastritis with intestinal metaplasia. MethodsA total of 140 patients with chronic atrophic gastritis and intestinal metaplasia were randomly divided into a treatment group and a control group， with 70 cases in each group. The treatment group received 12.5 g of XHG orally， twice daily. The control group received 12.5 g of placebo orally， twice daily. Both groups were treated for 6 months. The traditional Chinese medicine （TCM） symptom scores， pathological types， serum tumor markers of the digestive system， and serum bile acids （TBA）， interleukin-23 （IL-23）， and Dickkopf-related protein 1 （DKK-1） levels were observed before and after treatment. Safety indicators and adverse events were recorded. After treatment， TCM syndrome efficacy and pathological types were evaluated， and patients were followed up for 18 months with gastric endoscopy and pathological results， which were compared with the results after treatment finished. ResultsTwo patients dropped out in the control group， and a total of 168 cases were included in the final analysis， 70 in the treatment group and 68 in the control group. The treatment group showed a significant reduction in TCM symptom scores， serum TBA， IL-23， and DKK-1 levels， and a significant increase in alpha-fetoprotein （AFP）， carbohydrate antigen 125 （CA125）， carbohydrate antigen 199 （CA199） levels； in the control group， carcinoembryonic antigen （CEA）， CA125， CA199 levels significantly increased （P＜0.05 or P＜0.01）； and carbohydrate antigen 242 （CA242） level in both the treatment group and the control group decreased significantly （P＜0.01）. The treatment group had lower TCM symptom scores and lower levels of serum TBA， IL-23， and DKK-1 compared to the control group （P＜0.05）. The effective rate for TCM syndrome efficacy in the treatment group was 80.00% （56/70）， significantly higher than the 20.59% （14/68） in the control group （P < 0.05）. The effective rate for pathological classification in the treatment group was 72.73% （8/11） for mixed intestinal metaplasia， significantly better than 46.15% （6/13） in the control group （P＜0.05）. No adverse events were reported in either group. Among 40 patients who had a follow-up endoscopy after one year， 21 were from the treatment group， of whom 11 showed reduced intestinal metaplasia， 9 showed no significant changes， and 1 had worsened； while 19 patients in the control group had 4 with reduced intestinal metaplasia， 13 with no significant changes， and 2 with worsened conditions. No cancer was detected in either group. The treatment group showed significantly better improvement in intestinal metaplasia on follow-up gastric endoscopy pathology than the control group （P＜0.05）. ConclusionXHG can significantly improve the clinical symptoms in patients with chronic atrophic gastritis and intestinal metaplasia and reduce the degree of mixed intestinal metaplasia. The mechanism may involve lowering serum TBA， DKK-1， and IL-23 levles， thus delaying the progression from inflammation to cancer.

ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Objective: To understand the latent categories of sleep disturbances among children and adolescents with neurodevelopmental disorders (NDDs) in Tianjin and their relationship with behavioral and social issues, so as to provide a basis for preventing and improving sleep disturbances in the population. Methods: From September 2021 to June 2024, 272 children and adolescents aged 2-23 years with neurodevelopmental disorders were recruited from special education schools and designated rehabilitation institutions in Tianjin. Sleep disturbances were assessed using the Children s Sleep Habits Questionnaire (CSHQ). Behavioral and social issues and severity were evaluated using the Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS). Latent class analysis (LCA) was employed to categorize the subjects into different sleep disturbances categories. Cochran- Armitage test was used to analyze the trend of detection rate of sleep disturbances in different age groups. Spearman rank correlation was used to analyze the correlation between the scores of each scale. The generalized linear model was used to analyze the influence of CARS and ABC scale scores. Covariance analysis was used to examine differences in behavioral and social issues among the different categories. Results: Among 272 survey respondents, a total of 197(72.4%) children and adolescents with NDDs were identified with sleep disturbances. The detection rates of sleep disturbances were 88.9% for those aged 2-6 years, 70.6% for aged 7-12, 66.7% for aged 13-18 and 50.0% for 19-23 years old, which was decreased across age group ( Z =3.58, P <0.01). There was a positive correlation between the total CSHQ score and the total ABC score ( r=0.16, P =0.01). The generalized linear model analysis showed that after adjusting age, gender, parents education level and family monthly income, bedtime habit ( β =3.60) and sleeping latency disorder ( β =3.36) were positively correlated with CARS scores, while the bedtime habit ( β =16.73) and waking up at night ( β =17.46) were positively correlated with ABC scores ( P <0.05). LCA revealed that sleep disturbances in children and adolescents with NDDs could be classified into four categories. The covariance analysis results showed that there were statistically significant differences in the average scores of CSHQ (70.84±9.05, 50.96±6.64, 50.33±5.82, 43.84±5.44) and ABC (49.44± 39.34 , 53.04±39.75, 63.51±40.31, 38.14±34.23) among different categories of all partipants ( F=92.09, 3.95, P <0.05). Conclusion Sleep disturbances in children and adolescents with NDDs are severe and exhibit distinct categorical characteristics.

Animal experiments are an essential component of life sciences and medical research. However, the external validity and reliability of individual animal studies are frequently challenged by inherent limitations such as small sample sizes, high design heterogeneity, and poor reproducibility, which impede the effective translation of research findings into clinical practice. Systematic reviews and meta-analysis represent a key methodology for integrating existing evidence and enhancing the robustness of conclusions. Currently, however, the application of systematic reviews and meta-analysis in the field of animal experiments lacks standardized guidelines for their conduct and reporting, resulting in inconsistent quality and, to some extent, diminishing their evidence value. To address this issue, this paper aims to systematically delineate the reporting process for systematic reviews and meta-analysis of animal experiments and to propose a set of standardized recommendations that are both scientific and practical. The article's scope encompasses the entire process, from the preliminary preparatory phase [including formulating the population， intervention， comparison and outcome （PICO） question, assessing feasibility, and protocol pre-registration] to the key writing points for each section of the main report. In the core methods section, the paper elaborates on how to implement literature searches, establish eligibility criteria, perform data extraction, and assess the risk of bias, based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis （PRISMA) statement, in conjunction with relevant guidelines and tools such as Animal Research： Reporting of in Vivo Experiments （ARRIVE) and a risk of bias assessment tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). For the presentation of results, strategies are proposed for clear and transparent display using flow diagrams and tables of characteristics. The discussion section places particular emphasis on how to scientifically interpret pooled effects, thoroughly analyze sources of heterogeneity, evaluate the impact of publication bias, and cautiously discuss the validity and limitations of extrapolating findings from animal studies to clinical settings. Furthermore, this paper recommends adopting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to comprehensively grade the quality of evidence. Through a modular analysis of the entire reporting process, this paper aims to provide researchers in the field with a clear and practical guide, thereby promoting the standardized development of systematic reviews and meta-analysis of animal experiments and enhancing their application value in scientific decision-making and translational medicine.

Objective To investigate the differences in radiation dose during chest CT examinations among children of different age groups and establish dose estimation regression models. Methods Chest CT data from 135 children aged 4 to 15 years were retrospectively collected from the First Affiliated Hospital of Soochow University between January 2022 and December 2023. The children were divided into three age groups: 4-5 years, 6-10 years and 11-15 years. CT scanning parameters (tube voltage, tube current, scan range) and dosimetry parameters including volume CT dose index (CTDI_vol) dose length product (DLP), and size-specific dose estimate (SSDE) were recorded. The Kruskal-Wallis test was used to compare intergroup differences. A Pearson correlation analysis was performed to assess the relationship between age and dose indicators. Both linear and nonlinear regression models were constructed. Results Age showed a weak positive correlation with CTDI_vol (r = 0.27), a moderate positive correlation with DLP (r = 0.60), and a moderate negative correlation with SSDE (r = −0.55). Linear regression analysis revealed that DLP increased with age (y = 117.85 + 9.81x, R² = 0.36), while SSDE decreased with age (y = 12.4 − 0.18x, R² = 0.32). Using orthogonal distance regression, the goodness-of-fit of the nonlinear models for DLP and SSDE significantly improved (R² = 0.99 and 0.94, respectively). Conclusion In pediatric chest CT dose assessment, CTDI_vol underestimates radiation dose compared to SSDE and fails to account for patient body size. The dose estimation models constructed with orthogonal distance regression outperform those established using the least squares method, demonstrating higher fitting accuracy, and can serve as a reference for personalized dose management in pediatric CT examinations.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

Nano-drug delivery systems offer significant benefits, including high specific surface area, structural and functional diversity, and surface modifiability. When formulated as inhalable nano-formulation, these can not only enable precise pulmonary drug delivery but also improve pulmonary bioavailability and enhance thera-peutic efficacy. Currently, there are four types of inhalable nano-formulations for the treatment of respiratory diseases. Inhalable liquid preparations exhibit facile manufactur-ability and broad applicability yet demonstrate compromised stability during aerosolization. Through structure optimization, surface modification, dispersion medium optimization and device improvement, the atomization stability of nano-drug has been enhanced. Pressurized metered-dose inhalers loaded with nano-drugs face technical challenges: conventional propellants may dissolve nano-carriers, whereas co-solvents like ethanol compromise delivery efficiency. Thus, it is necessary to develop novel propellants that provide thermodynamic stability and optimal delivery performance. Nano-drug formulations in dry powder inhalers exhibit relatively favorable physical stability, however, pulmonary delivery efficiency and nanoparticles integrity during processing remain problematic. Pulmonary delivery efficiency can be improved by employing strategies such as blending excipients to promote the re-dispersibility of nanoparticle agglomerates, optimizing the design of microcarrier, and innovating preparation processes. In contrast, soft mist inhalers are an ideal option for pulmonary delivery of nano-drugs owing to their gentle and efficient atomization properties to maintain nano-drug integrity. This review summarizes the inhalable nano-formulations and focuses on challenges and proposed strategies encoun-tered in integrating nano-drug delivery systems and inhalation drug delivery systems. It aims to provide references for the future development of inhalable nano-formulations.
Administration, Inhalation ; Humans ; Drug Delivery Systems/methods* ; Nanoparticles ; Dry Powder Inhalers ; Nanoparticle Drug Delivery System ; Drug Compounding ; Metered Dose Inhalers ; Drug Carriers

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

ObjectiveTo investigate the mechanism of Buzhong Yiqitang in ameliorating ferroptosis in autoimmune thyroiditis （AIT） mice based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/peroxisome proliferator-activated receptor γ （PPARγ）/glutathione peroxidase 4 （GPX4） pathway. Method120 SPF-grade 7-8-week-old NOD.H-2^h4 mice were randomly divided into control group， model group， low-， medium-， and high-dose Buzhong Yiqitang groups， and western medicine group， with 20 mice in each group. Except for the control group， all mice were fed with classic high-iodine water （0.05% NaI） to induce AIT models after 8 weeks. The low-， medium-， and high-dose Buzhong Yiqitang groups were administered 4.78， 9.56， 19.12 g·kg^-1 of Buzhong Yiqitang， respectively， via gavage. The western medicine group was given 3.033×10^-5 g·kg^-1 selenium yeast tablet suspension via gavage， while the control and model groups were given an equal volume of distilled water via gavage. After 8 weeks of continuous treatment， samples were collected. The pathological morphology of mouse thyroid tissue was observed through hematoxylin-eosin （HE） staining，the content of serumantithyroid peroxidase autoantibody（TPOAb）and anti-thyroglobulin antibodies（TGAb）was measured by enzyme-linked immunosorbent assay （ELISA），the kit was used to detect the levels of superoxide dismutase （SOD）， and malondialdehyde （MDA） in mouse serum. Immunofluorescence was used to detect the localized expression of GPX4 in thyroid tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of Nrf2， PPARγ， solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， lysolipid lecithin acyltransferase 3 （LPCAT3）， and GPX4 mRNA in thyroid tissue. Western blot was used to detect the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， LPCAT3， and GPX4 proteins in thyroid tissue. ResultCompared with control group， model group under light microscopy showed significant lymphocyte infiltration in the thyroid tissue， significantly increased levels of TGAb and TPOAb in serum （P<0.01）， significantly increased MDA levels and decreased SOD levels in serum （P<0.01）， significantly decreased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4 （P<0.01） in thyroid tissue， while the expression of LPCAT3 was significantly increased （P<0.01）. Compared with model group， the Buzhong Yiqitang groups and the western medication group under light microscopy showed lymphocyte infiltration in the thyroid tissue of was decreased， significantly decreased levels of TPOAb and TGAb in serum （P<0.05，P<0.01）， decreased MDA levels and increased SOD levels in serum（P<0.05，P<0.01），significantly increased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4， while the expression of LPCAT3 was significantly decreased （P<0.05，P<0.01） in the thyroid tissue. Compared with western medication group， Buzhong Yiqitang groups showed significant overall trends in the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， GPX4， and LPCAT3 （P<0.05，P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and its mechanism of action may be related to the regulation of Nrf2/PPARγ/GPX4 to inhibit ferroptosis.