ObjectiveTo explore the potential mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of regulating mitochondrial autophagy via the PTEN-induced kinase 1 （PINK1）/E3 ubiquitin ligase （Parkin） pathway. MethodsMale SD rats were subjected to abdominal aortic constriction to establish the CHF model. Twenty-four successfully modeled rats were randomly divided into the model group， sacubitril/valsartan group， and low- and high-dose Shenqi Jianxin Formula groups， with 6 rats in each group. Six other rats were set as the sham surgery group， which were only separated the abdominal aorta and then closed the abdomen. Rats in the low-dose and high-dose Shenqi Jianxin Formula groups were given intragastric administration of Shenqi Jianxin Formula suspension at doses of 4.41 g/（kg·d） and 17.64 g/（kg·d）， respectively； the sacubitril/valsartan group received intragastric administration of sacubitril/valsartan sodium tablet suspension at 10 mg/（kg·d）； the sham surgery group and the model group were given normal saline at 10 ml/（kg·d） via intragastric gavage. The intervention lasted for 4 consecutive weeks. Cardiac function indices including left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were detected， and serum brain natriuretic peptide （BNP） content was measured. HE staining and Masson staining were used to observe myocardial histopathological changes. Transmission electron microscopy was employed to examine the ultrastructure of cardiac tissues. Quantitative real-time polymerase chain reaction （Rt-qPCR） was performed to determine the mRNA expressions of PINK1/Parkin pathway-related factors and autophagy-associated proteins including Beclin-1， p62， and microtubule-associated protein 1 light chain 3 （LC3） in myocardial tissues. ResultsCompared with the sham surgery group， the model group showed significant decreases in LVEF and LVFS levels， an increase in serum BNP content， down-regulated mRNA and protein expressions of PINK1， Parkin and Beclin-1 in cardiac tissues， up-regulated mRNA and protein expressions of p62， as well as significant reductions in LC3B mRNA expression， phosphorylated PTEN-induced kinase 1 （p-PINK1） and phosphorylated E3 ubiquitin ligase （p-Parkin） protein levels， and the ratio of microtubule-associated protein 1 light chain 3-Ⅱ to microtubule-associated protein 1 light chain 3-Ⅰ （LC3Ⅱ/LC3Ⅰ） （P＜0.05）. Pathological results revealed obvious myocardial cell edema， necrosis and degeneration， increased disorder of myocardial fiber arrangement， extensive inflammatory cell infiltration， moderate to severe mitochondrial swelling， a few mitochondrial vacuolar changes， and no obvious autophagy in the field of vision in the model group. Compared with the model group， all the above indicators were significantly improved in the high-dose Shenqi Jianxin Formula group and the sacubitril/valsartan group （P＜0.05）. Moreover， the improvement of each index in the high-dose Shenqi Jianxin Formula group was superior to that in the low-dose group （P＜0.05）. In the high-dose Shenqi Jianxin Formula group， myocardial myofibrils were arranged regularly with orderly orientation， the striated structure was clear， and necrotic cells significantly reduced. ConclusionShenqi Jianxin Formula can activate the PINK1/Parkin signaling pathway in myocardial tissues， enhance mitochondrial autophagy， and clear dysfunctional mitochondria， thereby improving cardiac function and delaying the progression of CHF.

ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

Abstract To achieve identification and intervention synergy with regards to critical windows for the prevention and control of childhood hypertension, the study adopts a life course perspective to systematically review the developmental pathways of childhood hypertension, identify key challenges facing current prevention and control efforts, and discuss monitoring and intervention strategies during critical windows of opportunity. By promoting continuous, multi setting screening and dynamic monitoring, improving measurement standardization and diagnostic feasibility, developing child specific risk assessment tools and strengthening coordinated interventions across families, schools, communities and individuals, the prevention of childhood hypertension can shift away from passive detection toward proactive risk management and primary prevention, thereby providing robust evidence and practical pathways to reduce the lifelong burden of cardiovascular disease.

Objective: To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions. Methods: In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension. Results: At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ). Conclusion The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.

Abstract The prevalence of hypertension in children and adolescents continues to rise with a trend toward earlier onset, presenting a phenomenon that cannot be fully explained by traditional risk factor frameworks. Circadian rhythm disruption, particularly the dual disturbance of dietary and sleep rhythms, has emerged as a novel risk factor and become a research hotspot. The review systematically summarizes the epidemiological associations, biological mechanisms, and intervention strategies regarding dietary rhythm, sleep rhythm, and their co exposure with blood pressure in children and adolescents. Future research needs to focus on Chinese pediatric populations through longitudinal cohort studies and randomized controlled trials to clarify causal relationships and regulatory mechanisms, thereby providing evidence based guidance for chronic disease prevention and control in children.

To analyze the disease burden of acute lymphoid leukemia(ALL) and its changing trends in China and globally from 1990 to 2021, aiming to provide a theoretical basis for disease prevention, treatment, and policy formulation.

Objective: To explore the association between vegetable intake with glucose and lipid metabolism levels among school aged children, so as to provide scientific basis for dietary intervention on children s metabolic health. Methods: Based on a natural population cohort in Jiulongpo District and Fengdu County of Chongqing, 2 133 school aged children aged 6-9 years were enrolled in the baseline survey in 2014, and 2 029 children completed the follow up in 2019. Questionnaire surveys were used to collect vegetable intake, general demographic and lifestyle data. Height, weight and waist circumference were measured, and glucose and lipid metabolism indicators such as fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (TC), low densith lipoprotein triglyceride (LDL-C), high densith lipoprotein triglyceride (HDL-C) were detected. Mann-Whitney U test and Kruskal-Wallis H test were used for intergroup comparisons in multivariate analysis, and mixed effects linear regression model was used to analyze the association between vegetable intake and glucose and lipid metabolism. Results: The levels of FBG, TG, TC, HDL-C and LDL-C at baseline and follow up were [4.09(3.90,4.48), 0.84(0.60,1.14), 3.49(3.09,3.91), 1.25(1.09,1.46), 1.69 ( 1.39 ,2.02)；4.31(4.00,4.64), 0.92(0.71,1.22), 3.49(3.12,3.87), 1.36(1.16,1.57), 1.77(1.51,2.06)] mmol/L, respectively. Among these indicators, FBG, TG, HDL-C and LDL-C all increased significantly ( Z =-12.08, -7.82, -9.82, -5.37, all P < 0.01 ). The detection rate of low HDL-C levels at follow up (13.11%) was significantly lower than that at baseline (18.10%) ( χ 2=19.57, P <0.05). At baseline, there were significant differences in FBG, TC, TG, HDL-C and LDL-C among children with different vegetable intake levels ( H =68.47, 30.16, 11.02, 13.27, 44.70); at followup, only HDL-C showed significant intergroup differences ( H =13.10)(all P <0.05). Mixed effects linear regression model showed that after adjusting for confounding factors, vegetable intake was significantly negatively correlated with blood glucose levels among school aged children ( β=-0.03, 95%CI = -0.05 to -0.01, P <0.01). Conclusion Higher vegetable intake can independently reduce the risk of abnormal blood glucose in school aged children, which is of great significance for maintaining glucose metabolic health.

Objective: To construct a risk prediction model for pediatric metabolic dysfunction associated steatotic liver disease (MASLD), so as to provide practical tool for the early identification of high risk children. Methods: A healthy cohort of children in Southwest China was established from January 2021 to April 2025. A nested case-control study design was used to include 507 cases MASLD group and 507 cases in non MASLD group. Data on physical measurements, blood biochemical parameters, and liver ultrasound indicators were collected. Conditional Logistic regression was used to analyze the relationship between individual variables and MASLD, Lasso regression was applied for multivariable screening, and a high risk prediction model was constructed and presented in the form of a nomogram. Internal validation was performed using 10 repeated ten fold cross validations to assess model discrimination, accuracy, sensitivity, and specificity. Results: Logistic regression analysis showed that MASLD was associated with central obesity ( OR=22.11, 95%CI =15.62-31.29), apolipoprotein B ( OR=30.24, 95%CI =12.42-73.63), increased hepatorenal echo ( OR=326.00, 95%CI =183.87-578.01), hepatomegaly ( OR=24.98, 95%CI =16.66-37.46) (all P <0.05). The Lasso regression jointly selected 6 key variables, including hepatorenal echo, central obesity, hepatomegaly, right liver lobe inclination, body mass index, and alanine amino transferase. The results of cross validation showed that the average area under the curve (AUC) was 0.999 5, the average accuracy was 98.74%, and the sensitivity and specificity were 98.21% and 99.22% respectively, indicating a good predictive effect of the model. Conclusion The risk prediction model for high risk MASLD among children based on ultrasound and clinical indicators has good prediction effect, which is helpful for the early identification and risk stratification of pediatric MASLD.