ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

AIM: To evaluate the efficacy and safety of 3% diquafosol sodium eye drops in children wearing orthokeratology lenses and with dry eye disease(DED)or at risk of DED.METHODS: Randomized controlled trials. Children with DED or at risk of DED were randomly assigned in a 1:1 ratio to receive either 3% diquafosol sodium eye drops 6 times daily or a blank control at Chongqing Aier Children's Eye Hospital from November 2023 to November 2024. The primary endpoint was the change in the Dry Eye Questionnaire-5(DEQ-5)score from baseline at 12 wk. Secondary assessments included non-invasive breakup time(NIBUT), tear meniscus height, Schirmer's test, corneal fluorescein staining score, and axial length.RESULTS: A total of 80 participants(80 eyes)were enrolled(40 in each group), the average age of the participants was 11.11±1.88 years, with 43 females(54%)and 37 males(46%), and all completed the trial. After 12 wk, the DEQ-5 scores for the diquafosol sodium group and the blank control group were 1.88±2.02 and 2.88±2.79, respectively(P=0.079). The diquafosol sodium group demonstrated a significant improvement in DEQ-5 dryness symptom scores(-0.33±0.66 vs. 0.05±0.81, P=0.023)and NIBUT(6.18±3.73 vs. -1.09±4.40 s, P<0.001)at 12 wk. Additionally, the diquafosol sodium group showed no axial length elongation, in contrast to the blank control group, which exhibited elongation(0.00±0.08 vs. 0.05±0.10 mm, P=0.013). No other significant differences were found in the secondary endpoints. No adverse events occurred during the trial.CONCLUSION: Although no statistically significant improvements were noted in the overall DEQ-5 scores, the 3% diquafosol sodium eye drops significantly improved dryness symptoms and NIBUT when compared to the blank control group.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

Objective To analyze the case data of farmers' foodborne disease surveillance reports in Guizhou Province from 2022 to 2024, and to provide reference for the precise prevention and control of foodborne diseases among farmers in Guizhou Province. Methods Case data of foodborne disease surveillance reports of farmers were systematically collected from 2022 to 2024 in Guizhou Province. Descriptive epidemiological methods were used to analyze the temporal, geographical, and demographic distribution of foodborne diseases among farmers, along with their primary clinical symptoms and pathogen detection results. Results From 2022 to 2024, a total of 22,882 cases of foodborne diseases were reported among farmers in Guizhou Province. The majority of clinical symptoms (97.81%) were related to the digestive system, with summer being the peak season. While females outnumbered males, the gender difference was statistically insignificant (P >0.05). The 36-55 age group accounted for the highest proportion (38.83%), with Zunyi City (34.89%) and Qiandongnan Prefecture (23.21%) reporting the most cases. Fungal products were the most frequently reported suspected food items (26.96%), and home-made preparation was the primary processing method (58.63%). A total of 1 210 fecal samples were collected through active monitoring with an overall detection rate of 13.22%. Norovirus showed the highest detection rate (9.92%, 120/1 210). Statistically significant differences were observed among different seasons, age groups, regions, types and processing methods of suspected food exposure, and pathogen detection rates (P <0.001). Conclusion Foodborne disease prevention and control among farmers in Guizhou Province should focus on the risks of wild mushroom poisoning in summer and homemade foods, and continuously improve farmers' awareness of the dangers of foodborne diseases and food safety.

ObjectiveTo investigate the association of hepatic steatosis with the level of viral replication and the progression of hepatic fibrosis in patients with chronic hepatitis B （CHB） through a real-world study， and to determine the independent influencing factors for hepatic fibrosis. MethodsA total of 887 CHB patients who attended the outpatient service and inpatient ward of Hepatology in The First Affiliated Hospital of Dalian Medical University from July 2021 to March 2025 were enrolled as subjects， and according to the presence or absence of metabolic dysfunction-associated steatotic liver disease （MASLD）， they were divided into CHB group with 560 patients and CHB+MASLD group with 327 patients. The association between hepatic steatosis and HBV load in CHB patients was analyzed， as well as the impact of varying degrees of hepatic steatosis on hepatic fibrosis. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Spearman correlation analysis was performed； a Logistic regression analysis was used to investigate influencing factors. ResultsThe patients enrolled received antiviral therapy according to viral load； of all patients， 275 （31%） received nucleos（t）ide analogue combined with pegylated interferon-α， 532 （60%） received nucleos（t）ide analogue monotherapy， and 80 （9%） did not receive antiviral therapy. A total of 44 patients （5.0%） who were receiving PEG-IFN-α therapy and had marked thrombocytopenia were excluded， and finally 843 patients were included for comparison of aspartate aminotransferase-to-platelet ratio index （APRI） and fibrosis-4 index （FIB-4）. Compared with the CHB group， the CHB+MASLD group had a significantly higher proportion of male patients （χ²=5.917， P<0.05） and a significant increase in CAP value （t=21.646， P<0.05）. The median values of liver function parameters for the population enrolled were within the normal range， and no significant inflammatory activity was observed. The virological analysis showed that compared with the CHB group， the CHB+MASLD group had significantly lower serum level of pregenomic RNA （Z=-2.894， P<0.05） and HBeAg positivity rate （χ²=8.725， P<0.05）， and CAP was significantly negatively correlated with pgRNA （r=-0.117， P<0.05）. In the HBeAg-negative subgroup， compared with the CHB group， the CHB+MASLD group had a significantly lower level of hepatitis B surface antigen （Z=-0.765， P<0.05）； in the HBeAg-positive subgroup， the CHB+MASLD group had a significantly higher level of HBV DNA than the CHB group （Z=-2.509， P<0.05）. The analysis of hepatic fibrosis showed that the CHB+MASLD group had significantly lower values of APRI （Z=-3.418， P<0.05） and FIB-4 （Z=-6.237， P<0.05）. Compared with the CHB group， the CHB+MASLD S1 group had a significantly higher proportion of patients without fibrosis and a significantly lower proportion patients with liver cirrhosis （χ²=7.935， P<0.05）； in the CHB+MASLD S2 group， there was no significant difference in the proportion of patients with different fibrosis stages； the CHB+MASLD S3 group had a significantly lower proportion of patients without fibrosis and a significantly higher proportion of patients with early-stage fibrosis （χ²=9.101， P<0.05）. The Logistic regression analysis showed that an increase in CAP （odds ratio ［OR］=1.08， 95% confidence interval ［CI］： 1.03 — 1.13， P<0.05）， an increase in age （OR=1.02， 95%CI： 1.01 — 1.04， P<0.05）， male sex （OR=1.77， 95%CI： 1.19 — 2.64， P<0.05）， an increase in HBV DNA （OR=1.35， 95%CI： 1.15 — 1.57， P<0.001）， an increase in aspartate aminotransferase （OR=1.02， 95%CI： 1.01 — 1.03， P<0.001）， and an increase in gamma-glutamyl transpeptidase （OR=1.00， 95%CI： 1.00 — 1.01， P=0.028） were independent influencing factors for hepatic fibrosis. The risk of hepatic fibrosis in S3 patients was higher than that in patients without steatosis （OR=5.05， 95%CI： 2.48 — 10.29， P<0.001）. ConclusionThere is a lower level of HBV replication in CHB patients comorbid with MASLD. Hepatic steatosis is associated with HBV-related virological markers and the progression of hepatic fibrosis， and severe fatty liver disease may promote the progression of hepatic fibrosis in CHB patients.

ObjectiveTo develop and preliminarily validate a prediction model for brace treatment failure risk in patients with adolescent idiopathic scoliosis (AIS), based on information obtained before brace treatment and during initial brace fitting. MethodsA total of 191 patients with AIS who initiated thoracolumbosacral orthosis treatment at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March, 2015 to August, 2024 and had determinable outcomes were retrospectively included. Patients were divided according to a prespecified scheme into a training set (n = 133) and a validation set (n = 58). Brace treatment failure was defined as progression of the major-curve Cobb angle by ≥ 5° from baseline during follow-up or at brace weaning, or a final major-curve Cobb angle > 45°. Logistic regression, random forest, support vector machine with radial basis function kernel, and extreme gradient boosting (XGBoost) models were developed using routinely available clinical and radiographic variables before brace treatment and during initial brace fitting. Stratified five-fold cross-validation was used for hyperparameter tuning in the training set. Model performance was evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), Brier score, calibration curves, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) was used to interpret the main explanatory model. ResultsIn cross-validation of the training set, both random forest and XGBoost showed good discriminative performance, with cross-validation-AUC values of 0.871 and 0.880, respectively. In the validation set, the AUC values of random forest and XGBoost were 0.888 and 0.899, the AUPRC values were 0.678 and 0.830, and the Brier scores were 0.086 and 0.076, respectively. Random forest was selected as the primary model for interpretation, with a calibration intercept of 0.091 and a calibration slope of 0.995. SHAP analysis indicated that the in-brace correction rate and the major-curve Cobb angle measured in the brace contributed most to the model predictions. ConclusionThe random forest model developed using routinely available pretreatment and initial-fitting variables shows preliminary predictive value for brace treatment failure risk in AIS, and may provide quantitative support for follow-up scheduling, brace-fit reassessment and early adherence-oriented management.

Objective: To analyze the effects of health literacy on overweight and obesity among primary school students and their parents in terms of salt, oil and sugar reduction (referred to as the "three reductions"), so as to provide a theoretical basis for the development of obesity control measures. Methods: From March to April 2024, a total of 1 022 fourthgrade primary school students and 913 parents were surveyed in 24 classes in six counties in Shandong Province using multistage cluster random sampling, and physical measurements of primary school students were conducted. Pearsons correlation analysis and ordered multivariate Logistic regression were used to investigate the associations between health literacy of primary school students and their parents with overweight and obesity among children. Results: The detection rates of overweight and obesity primary school students in Shandong Province were 14.87% and 24.66%, respectively, with significant sex difference in obesity rate (29.46% for boys and 19.76% for girls) (χ2=12.93, P<0.01). In addition to students reducing oil scores, parental reducing salt,reducing oil,reducing sugar, comprehensive health literacy scores and students reducing salt,reducing sugar and comprehensive health literacy scores showed a negative relationship with students overweight and obesity (r=-0.10, -0.08, -0.07, -0.10, -0.04, -0.07, -0.03, P<0.05). The overweight and obesity rates among primary school students with high parental reducing salt,reducing oil,reducing sugar and composite health literacy scores were lower (OR=0.69, 0.69, 0.71, 0.63, P<0.05); and the overweight and obesity rate among students with high parental and low parental and high and low parental health literacy scores were lower (OR=0.68, 0.57, P<0.05). Conclusion Improving health literacy regarding "three reductions" for parents and children, especially parents, can effectively reduce the risk of childhood overweight and obesity.

ObjectiveTo explore the optimal construction method and the biological basis for establishing a mouse model of ischemic heart disease（IHD） with Qi and Yin deficiency syndrome by intraperitoneal injection of isoproterenol（ISO）. MethodsA total of 144 male C57BL/6J mice were randomly assigned into three normal groups and nine model groups according to body mass， with 12 mice in each group. The model groups 1， 4， and 7 were administered ISO via intraperitoneal injection at a dose of 5 mg·kg^-1·d^-1 for four consecutive days， the model groups 2， 5， and 8 received ISO at a dose of 10 mg·kg^-1·d^-1 for seven consecutive days， while the model groups 3， 6， and 9 were given ISO at a dose of 15 mg·kg^-1·d^-1 for 14 consecutive days. The normal groups were administered an equivalent volume of normal saline via intraperitoneal injection. After the modeling process， body mass， 24-hour food and water intake， grip strength， and spontaneous activity of the mice were measured. Cardiac function was assessed using echocardiography， the serum levels of norepinephrine（NE）， cyclic adenosine monophosphate（cAMP）， and cyclic guanosine monophosphate（cGMP） were determined via enzyme-linked immunosorbent assay（ELISA）. The content of adenosine triphosphate（ATP） in myocardial tissue was measured by biochemical analysis， while histopathological changes in myocardial tissue were observed via hematoxylin-eosin（HE） staining. An orthogonal experimental design was applied for intuitive analysis and variance analysis to screen the optimal modeling conditions of the mouse model of IHD with Qi and Yin deficiency syndrome. A data-dependent acquisition（DDA） proteomic technique was employed to quantitatively detect differentially expressed proteins in myocardial tissue between the optimal model group and the normal group. And bioinformatics analysis was conducted to explore the potential biological mechanisms underlying the Qi and Yin deficiency model of IHD. ResultsOrthogonal results showed that the injection cycle had a great influence on model establishment， and the optimal modeling condition was identified as intraperitoneal injection of ISO at 15 mg·kg^-1·d^-1 for 14 consecutive days. Under this condition， compared with the normal group， the model group demonstrated significant reductions in body mass， food intake， water intake， grip strength， total distance and average speed of exercise， ejection fraction（EF）， fractional shortening（FS）， serum levels of NE and cGMP， and myocardial ATP content（P<0.01）， while immobility time， cAMP level， and the cAMP/cGMP value were significantly increased（P<0.05， P<0.01）. HE staining results revealed that myocardial tissue in the model group had disordered cell arrangement， inflammatory cell infiltration， myocardial fiber rupture， and fibrous tissue proliferation. Proteomic analysis identified 141 differentially expressed proteins in the model group compared with the normal group， with 52 up-regulated and 89 down-regulated. Gene Ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis indicated that the cellular components（CC） were mainly related to mitochondria and the inner mitochondrial membrane， the biological processes（BP） were associated with complement activation， platelet activation， and responses to metal ions， suggesting that the potential functional pathways involved the complement and coagulation cascade， as well as porphyrin metabolism. ConclusionContinuous intraperitoneal injection of ISO at a dose of 15 mg·kg^-1 for 14 days successfully establishes a mouse model of IHD with Qi and Yin deficiency syndrome， and the underlying mechanisms may be related to the regulation of iron ions by complement C3， C5 and Cp， and plays a role in the regulation through the BP of complement activation， platelet activation， and responses to metal ions， and the signaling pathways of the complement and coagulation cascade and porphyrin metabolism.

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 explore the optimal construction method and the biological basis for establishing a mouse model of ischemic heart disease（IHD） with Qi and Yin deficiency syndrome by intraperitoneal injection of isoproterenol（ISO）. MethodsA total of 144 male C57BL/6J mice were randomly assigned into three normal groups and nine model groups according to body mass， with 12 mice in each group. The model groups 1， 4， and 7 were administered ISO via intraperitoneal injection at a dose of 5 mg·kg^-1·d^-1 for four consecutive days， the model groups 2， 5， and 8 received ISO at a dose of 10 mg·kg^-1·d^-1 for seven consecutive days， while the model groups 3， 6， and 9 were given ISO at a dose of 15 mg·kg^-1·d^-1 for 14 consecutive days. The normal groups were administered an equivalent volume of normal saline via intraperitoneal injection. After the modeling process， body mass， 24-hour food and water intake， grip strength， and spontaneous activity of the mice were measured. Cardiac function was assessed using echocardiography， the serum levels of norepinephrine（NE）， cyclic adenosine monophosphate（cAMP）， and cyclic guanosine monophosphate（cGMP） were determined via enzyme-linked immunosorbent assay（ELISA）. The content of adenosine triphosphate（ATP） in myocardial tissue was measured by biochemical analysis， while histopathological changes in myocardial tissue were observed via hematoxylin-eosin（HE） staining. An orthogonal experimental design was applied for intuitive analysis and variance analysis to screen the optimal modeling conditions of the mouse model of IHD with Qi and Yin deficiency syndrome. A data-dependent acquisition（DDA） proteomic technique was employed to quantitatively detect differentially expressed proteins in myocardial tissue between the optimal model group and the normal group. And bioinformatics analysis was conducted to explore the potential biological mechanisms underlying the Qi and Yin deficiency model of IHD. ResultsOrthogonal results showed that the injection cycle had a great influence on model establishment， and the optimal modeling condition was identified as intraperitoneal injection of ISO at 15 mg·kg^-1·d^-1 for 14 consecutive days. Under this condition， compared with the normal group， the model group demonstrated significant reductions in body mass， food intake， water intake， grip strength， total distance and average speed of exercise， ejection fraction（EF）， fractional shortening（FS）， serum levels of NE and cGMP， and myocardial ATP content（P<0.01）， while immobility time， cAMP level， and the cAMP/cGMP value were significantly increased（P<0.05， P<0.01）. HE staining results revealed that myocardial tissue in the model group had disordered cell arrangement， inflammatory cell infiltration， myocardial fiber rupture， and fibrous tissue proliferation. Proteomic analysis identified 141 differentially expressed proteins in the model group compared with the normal group， with 52 up-regulated and 89 down-regulated. Gene Ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis indicated that the cellular components（CC） were mainly related to mitochondria and the inner mitochondrial membrane， the biological processes（BP） were associated with complement activation， platelet activation， and responses to metal ions， suggesting that the potential functional pathways involved the complement and coagulation cascade， as well as porphyrin metabolism. ConclusionContinuous intraperitoneal injection of ISO at a dose of 15 mg·kg^-1 for 14 days successfully establishes a mouse model of IHD with Qi and Yin deficiency syndrome， and the underlying mechanisms may be related to the regulation of iron ions by complement C3， C5 and Cp， and plays a role in the regulation through the BP of complement activation， platelet activation， and responses to metal ions， and the signaling pathways of the complement and coagulation cascade and porphyrin metabolism.