ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

Objective To explore the longitudinal associations of body roundness index (BRI), visceral adiposity index (VAI), and metabolic score for visceral fat (METS-VF) with the risk of new-onset atrial fibrillation (AF). Methods This study included participants from the UK Biobank who were free of AF or pregnancy at baseline and completed the first and second assessments of BRI, VAI, and METS-VF. The changes in BRI, VAI, and METS-VF were classified using K-means clustering analyses, and the cumulative adiposity indices were also calculated. The primary outcome was new-onset AF. Three Cox regression models were employed to investigate the longitudinal associations of the BRI, VAI, and METS-VF changes with the risk of incident new-onset AF. The results were presented as hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Restricted cubic spline analyses were performed to explore potential non-linear associations between baseline or cumulative adiposity indices and the risk of new-onset AF. C-index analyses were conducted to evaluate the predictive value of BRI, VAI, and METS-VF for new-onset AF. Subgroup analyses were performed according to age, gender, race, smoking status, alcohol consumption, and physical activity. Polygenic risk scores were applied to account for genetic susceptibility and investigate potential interactions between adiposity indices and genetic risk. Univariate linear regression analyses were performed to evaluate the relationships of cumulative adiposity indices and magnetic resonance imaging and dual X-ray absorptiometry parameters, including visceral adipose tissue (VAT) volume, VAT mass, trunk fat volume, and trunk fat mass. We further applied the eXtreme Gradient Boosting (XGBoost) algorithm, with the feature importance being measured to evaluate the predictive value of each adiposity index for imaging parameters. Mendelian randomization analysis was further conducted to investigate the potential causal relationship between trunk fat mass and AF. Results A total of 12 776 participants were included. Over a median follow-up of 9.60 years, 761 (5.96%) new-onset AF events were recorded. Participants were divided into four classes based on the changes in adiposity indices. In the fully adjusted model, compared to participants in Class 1 of BRI, those in Class 3 (HR＝1.30, 95%CI 1.04-1.63, P＝0.023) and Class 4 (HR＝2.17, 95%CI 1.61-2.93, P＜0.001) were associated with significantly higher risks of new-onset AF. Regarding METS-VF, participants in Class 4 of METS-VF also demonstrated a significantly higher risk of new-onset AF compared to those in Class 1 (HR＝1.66, 95%CI 1.15-2.39, P＝0.007). However, no significant association was observed between different classes of VAI and the risk of new-onset AF. For every 1 standard deviation increase in cumulative BRI, VAI, and METS-VF, the fully adjusted HRs of new-onset AF were 1.23 (95%CI 1.13-1.35), 1.02 (95%CI 0.94-1.10), and 1.23 (95%CI 1.12-1.35), respectively. Cumulative adiposity indices (BRI, VAI, and METS-VF) were divided into quartiles. Using the first quartile as reference, participants in the highest quartiles of BRI (HR＝1.40, 95%CI 1.10-1.79, P＝0.007) and METS-VF (HR＝1.44, 95%CI 1.13-1.83, P＝0.003) both exerted a significantly higher risk of new-onset AF. Regarding VAI, no significant association was observed (HR＝1.00, 95%CI 0.81-1.23, P＝0.988). Restricted cubic spline analyses revealed non-linear relationships between cumulative BRI, baseline/cumulative VAI, and baseline/cumulative METS-VF with new-onset AF risk (all P_overall＜0.05, P_non-linear＜0.05). In the C-index analysis, BRI demonstrated the highest predictive performance for new-onset AF, followed by METS-VF and VAI. Subgroup analysis indicated a stronger association between METS-VF and the risk of new-onset AF amongst participants younger than 60 years (P_interaction＝0.008). Polygenic risk score analysis stratified by genetic risk demonstrated a synergistic effect between BRI and genetic risk with new-onset AF, with the overall risk of new-onset AF increasing as both BRI and genetic risk increased. Linear regression analysis revealed a positive correlation between cumulative BRI with VAT volume, VAT mass, trunk fat volume, and trunk fat mass. The feature importance plot derived from the XGBoost algorithm indicated that cumulative BRI had the greatest predictive value on VAT volume, VAT mass, trunk fat volume, and trunk fat mass. Mendelian randomization analysis confirmed a significant causal relationship between trunk fat mass and AF. Conclusions There are significant non-linear associations between BRI, METS-VF, and VAI with new-onset AF. Higher BRI and METS-VF are significantly associated with a higher risk of new-onset AF, whereas no significant association is observed for the VAI. BRI exhibits a positive correlation with VAT and trunk fat, and demonstrates superior performance in predicting new-onset AF compared to VAI and METS-VF. Monitoring and managing BRI may be important in the early detection and intervention of AF.

OBJECTIVE: To observe the effects of Xingnao Kaiqiao acupuncture technique (for regaining consciousness and opening orifice) on methylation of N6-methyladenosine (m6A), and key methyltransferases and demethylases, so as to clarify the mechanism of acupuncture on cerebral ischemia-reperfusion injury (CIRI). METHODS: Of 68 male Sprague-Dawley rats of SPF grade, 15 rats were randomly selected as a sham-operation group, and the remaining rats were subjected to the model of middle cerebral artery occlusion using the suture ligation. CIRI was induced by ischemia for 2 h followed by reperfusion. Rats that failed to modeling or died were excluded. The rest 45 rats were randomly divided into three groups, i.e. model group, acupuncture group, and non-point acupuncture group, with 15 rats in each group. The rats in the acupuncture group were treated with acupuncture at bilateral "Neiguan" (PC6) and "Shuigou" (GV26). In the non-point acupuncture group, acupuncture was delivered at three non-points, located 3 mm below the bilateral midaxillary line and 3 mm lateral to the tip of the coccyx. One intervention was operated in these two acupuncture groups and the needles were retained for 30 min. Before modeling start and 2 h after ischemia, a laser speckle flowmeter was used to monitor the cerebral blood perfusion. In 2 h of ischemia and 24 h of reperfusion, the neurological behavioral score was evaluated. The volume of rat cerebral infarction was determined by triphenyltetrazolium chloride (TTC) staining, and the level of m6A methylation in ischemic cortical area was detected by Dot blot, and the protein and mRNA expression of the demethylase i.e. fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and key methyltransferases, i.e. methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms' tumor 1-associated protein (WTAP) in ischemic cortical area were detected by Western blot and real-time PCR. RESULTS: Cerebral blood perfusion decreased by>70% after 2 h ischemia. Compared with the sham-operation group, the neurobehavioral score and the percentage of cerebral infarction volume increased in the model group (P<0.01); the level of m6A methylation in the ischemic cortical area increased (P<0.01), the protein and mRNA expression of FTO decreased (P<0.01), and that of ALKBH5, METTL3, and METTL14 increased (P<0.01, P<0.05) in the model group. When compared with the model group and the non-point acupuncture group, the acupuncture group showed a decrease in the neurobehavioral score and the percentage of cerebral infarction volume (P<0.01), the level of m6A methylation in the ischemic cortical area was reduced (P<0.01, P<0.05), and the protein and mRNA expression of FTO was elevated (P<0.01). CONCLUSION Xingnao Kaiqiao acupuncture technique presents its protective effect on the brain in the rats with CIRI, which is related to up-regulating the expression of FTO and modulating m6A methylation.
Animals ; Rats, Sprague-Dawley ; Male ; Acupuncture Therapy ; Reperfusion Injury/genetics* ; Rats ; Brain Ischemia/genetics* ; Humans ; Adenosine/metabolism* ; Methylation ; Acupuncture Points ; Cerebral Cortex/metabolism*

Objective A scoping review of studies on symptom clusters in patients with chronic heart failure(CHF)was conducted to provide reference for the treatment and management of CHF.Methods According to reporting framework of scoping review put forward by Arksey,the related literatures of Cochrane Library,CINAHL,Web of Science,PubMed,Embase,Wanfang Data Knowledge Service Platform,SinoMed,CNKI and VIP from January 2014 to July 2024 were searched,and the contents of the literatures were screened,extracted and analyzed.Results Ten articles were included,involving many symptom clusters,mainly including mood,ischemia,congestion,digestive tract and fatigue.Symptom group assessment tool mainly adopted Chinese version of Memorial symptom assessment scale-heart failure.Conclusion There are various types of symptom clusters in CHF patients,and they show dynamic changes in each disease stage.It is still necessary to strengthen the research on the evaluation tools,occurrence principles and standardized naming of symptom clusters.Medical staff can give first-class care to the main symptom clusters in each period,formulate personalized nursing intervention measures in advance,and improve the efficiency of symptom management in clinical nursing.

Objective Based on the traditional Chinese medicine theory of"simultaneous regulation of the liver and kidney,"this study integrated network pharmacology prediction,molecular docking,and animal experimental validation to analyze the multi-target regulatory network of Duzhong Xionghua(the male flower of Eucommia ulmoides)-Sanqi Hua(Sanchi flower)herb pair(hereinafter called"herb pair")in modulating glucolipid metabolic disorders in type 2 diabetes mellitus(T2DM),thereby elucidating its underlying molecular mechanism.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,and Wanfang Data were used to obtain the active ingredients of the male flower of Eucommia ulmoides and Sanchi flower.PubChem Compound,SwissTargetPrediction,and SuperPred were used to screen and predict the targets of the drugs;The Human Gene Database,The Online Mendelian Inheritance in Man,and Therapeutic Target Database were used to screen the key gene targets of T2DM.A"component-target-pathway"network diagram was constructed using Cytoscape software,and Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were employed to identify the functions of the relevant target genes and pathways.Molecular docking was used to verify the binding activities of the core components and the key targets.For animal experiments,spontaneous T2DM model mice were used,in which the normal group consisted of six mice(wild type)from the same litter,and the 24 successfully modeled mice were randomly divided into model,metformin(0.26 g/kg),high-dose herb pair(2.6 g/kg),and low-dose herb pair groups(1.3 g/kg)according to the blood glucose levels and body weights,with six mice per group.The drugs were administered by gavage daily for six consecutive weeks.The body weight and fasting blood glucose(FBG)levels were measured weekly,and an oral glucose tolerance test was performed in the fifth week.At the end of drug administration,body weight,naso-anal length,liver and bilateral epididymal adipose mass were measured;pathological changes in the liver were observed using HE staining;serum levels of aspartate transaminase(AST),alanine amino-transferase(ALT),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected using colorimetric assay;and liver tissue phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway protein expressions were determined using Western blotting.Results Network pharmacology screening identified 38 active components and 669 potential targets of the herb pair.Intersection analysis with 1,275 T2DM-related targets yielded 185 common targets.Protein-protein interaction network analysis and pathway enrichment revealed the PI3K/AKT signaling pathway as a key mechanism.Molecular docking confirmed the strong binding affinity of the core components to key targets such as AKT1,suggesting that the herb pair may activate the PI3K/AKT pathway and inhibit GSK-3β activity via beta-sitosterol etc.Animal experiments demonstrated that,compared with the model group,the metformin group exhibited reduced FBG,AST,and ALT levels(P<0.01),but failed to improve body weight,Lee's index,or epididymal fat coefficient.Both herb pair doses significantly lowered Lee's index,hepatic index,and the epididymal fat coefficient(P<0.01),with the low-dose herb pair group showing attenuated body weight gain in mice.In contrast,the high-dose herb pair group exhibited decreased FBG,improved glucose tolerance,reduced TC,TG,and LDL-C levels,and increased HDL-C level(all P<0.01).HE staining revealed that all metformin and the herb pair markedly restored hepatic structure and alleviated steatosis in model mice,with more pronounced effects in the high-dose group than in the low-dose group.Western blotting result indicated that in the low-dose herb pair group,phospho-PI3K(p-PI3K),AKT,and phospho-GSK-3β(p-GSK-3β)protein expressions significantly increased(P<0.05 or P<0.01),whereas GSK-3β decreased(P<0.05).The high-dose group exhibited enhanced PI3K,p-PI3K,AKT,phospho-AKT,and p-GSK-3β protein expressions(all P<0.01),accompanied by reduced GSK-3β expression(P<0.01).Conclusion The male flower of Eucommia ulmoides-Sanchi flower herb pair may ameliorate T2DM-related glucolipid metabolic disorders by modulating the PI3K/AKT/GSK-3β pathway.

Objective To analyze the 18F-fluorodeoxyglucose(18F-FDG)PET/CT manifestations of autoimmune pancreatitis(AIP)and to explore the diagnostic value of 18F-FDG PET/CT in AIP.Methods Twenty-three patients with suspected AIP who underwent 18F-FDG PET/CT were retrospectively analyzed.Eleven patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria(ICDC)of AIP published by the International Pancreatic Disease Association.The detection rate and diagnostic sensitivity of 18F-FDG PET/CT for pancreatic enlargement,duct stenosis,duct dilation,pseudocapsules,and extrapancreatic involvement were analyzed,along with the 18F-FDG PET/CT manifestations of AIP.Results The 18F-FDG PET/CT manifestations of 11 patients with AIP:9 patients(81.82%)showed diffuse pancreatic enlargement,and 2 patients(18.18%)had local pancreatic head enlargement.And metabolism showed diffuse or localized increase.The maximum standardized uptake value(SUVmax)for the early PET/CT was 1.7-9.1(4.52±1.92),and for the delayed PET/CT,it was 2.6-9.8(5.25±1.98),with a statistically signifi-cant difference between the two phases SUVmax(t=-7.627,P<0.001).Two patients showed duct stenosis,six had distal duct dilation,and three exhibited pseudocapsule formation.Extrapancreatic involvement occurred in ten patients(90.91%),including sclerosing cholangitis,bile duct dilation inside and outside the liver,gallbladder changes,lymph node involvement,salivary gland involvement,prostate involvement,retroperitoneal fibrosis,pulmonary lesions,arteritis,and granulomatous tissue formation,etc.Among them,the same patient may present with multiple manifestations of extrapancreatic involvement.Among the 11 patients,eight were diagnosed as AIP,two as pancreatic cancer,and one as acute pancreatitis by 18F-FDG PET/CT.The diagnostic sensitivity was 72.73%.Conclusion The 18F-FDG PET/CT of AIP demonstrates specificity in anatomical morphology and metabolic changes and can better display extrapancreatic involvement,which has unique clinical value in AIP imaging diagnosis.

Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95％reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.

Objective:To investigate the effects of a visual feedback electromyography-driven exoskeleton on patients with hand injuries and to compare its efficacy with conventional rehabilitation treatment.Method:Patients who met the inclusion and exclusion criteria were randomly divided into two groups,with 15 patients in the experimental group and 15 in the control group.The control group underwent a 4-week con-ventional rehabilitation program,which included occupational therapy,muscle strength training,and range of motion exercises.The experimental group received the same conventional rehabilitation alongside training with the visual feedback electro-myography-driven exoskeleton.All participants were evaluated for grip strength,pinch strength,Purdue Pegboard results,and DASH questionnaire scores before and after treatment.Statistical analyses were performed to compare intra-group and inter-group differences.Result:After 4 weeks of rehabilitation,both groups showed significant differences in grip strength,pinch strength,Purdue Pegboard scores,and DASH questionnaire scores compared to baseline(P＜0.05).Between-group comparisons showed no significant difference in the post-treatment grip weight ratio(P＞0.05),while all other indicators demonstrated significant differences(P＜0.05).Conclusion:Following 4 weeks of rehabilitation,both groups showed improvements in muscle strength,hand dex-terity,and activities of daily living in the upper limbs.However,the functional level of patients in the experimen-tal group was superior to that of the control group,indicating that task-oriented rehabilitation using a visual feed-back electromyography-driven exoskeleton significantly promotes functional recovery in patients with hand trauma.

Objectives:To investigate the correlation between resting heart rate(RHR)and atherosclerotic cardiovascular disease(ASCVD)and all-cause death in young and middle-aged people.Methods:A prospective cohort study was conducted enrolling 72 642 young and middle-aged participants(aged<60 years),who participated in the medical examination of the Kailuan Study from June 2006 to October 2007.According to the quartile of the RHR level,the participants were divided into Q1 group(<67 beats/min,n=14 381),Q2 group(67-70 beats/min,n=15 815),Q3 group(71-75 beats/min,n=15 876),Q4 group(76-80 beats/min,n=13 933)and Q5 group(>80 beats/min,n=12 637).Cox proportional hazard regression model was used to analyze the effect of RHR on ASCVD and all-cause death.The dose-response relationship between RHR and the risk of ASCVD and all-cause death was investigated using a restricted cubic spline regression model.Results:During a mean follow-up of(10.0±4.85)years,2 898 patients(3.99%)developed ASCVD.Multivariate Cox regression analysis showed that after adjusting for confounding factors,the risk of RHR and ASCVD in group Q5 increased by 20%compared with group Q1(HR=1.20,95%CI:1.06-1.35,P<0.05).There was no significant risk in groups Q2 to Q4 compared to Q1 group(all P>0.05).In addition,the risk of ASCVD increased by 4%for every 10 beats/min increase in RHR(HR=1.04,95%CI:1.01-1.07,P=0.009).During the follow-up period of(10.2±4.82)years,all-cause death occurred in 2 175 participants(2.99%).The results showed that compared with Q1 group,the risk of all-cause death in Q3 to Q5 groups increased by 33%(HR=1.33,95%CI:1.15-1.54,P<0.001),33%(HR=1.33,95%CI:1.14-1.54,P<0.001),and 78%(HR=1.78,95%CI:1.54-2.05,P<0.001)respectively,and there was no statistical significance between group Q2 and group Q1.The risk of all-cause death increased by 15%for every 10 beats/min increase in RHR(HR=1.15,95%CI:1.11-1.19,P<0.001).Restricted cubic spline analysis showed that RHR was linearly correlated with risk of ASCVD(Poverall=0.022,Pnon-linear=0.617),and the risk of ASCVD increased significantly with RHR>72 beats/min.RHR was linearly associated with the risk of all-cause death(Poverall<0.001,Pnon-linear=0.212),and the risk of all-cause death was significantly increased with RHR>72 betas/min.Conclusions:Higher RHR is associated with an increased risk of ASCVD and all-cause mortality in young and middle-aged individuals.

Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95％reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.