1.Clinical Research and Basic Study on Effect of Huangqin Qingre Chubi Capsule (黄芩清热除痹胶囊) on Self-Perception of Patients and Immune Inflammation in Rheumatoid Arthritis
Fanfan WANG ; Jian LIU ; Qin ZHOU ; Jianting WEN ; Yue SUN ; Mingyu HE
Journal of Traditional Chinese Medicine 2026;67(5):544-556
ObjectiveTo evaluate the comprehensive intervention effects of Huangqin Qingre Chubi Capsule (黄芩清热除痹胶囊, HQC) on self-perception of patients (SPP) and immune inflammation in patients with rheumatoid arthritis (RA), and to explore its potential mechanisms. MethodsClinical data of 452 RA patients were retrospectively collected. Patients were divided into a control group (274 cases), treated with conventional western medicine, and an observation group (178 cases), treated with HQC for at least 2 weeks in addition to conventional western medicine. The treatment duration was 2 weeks for both groups. Propensity score matching (PSM) was performed at a ratio of 1∶1 to match patients between groups. SPP including the Chinese version of the short form-36 health survey (SF-36), self-rating anxiety scale (SAS), self-rating depression scale (SDS), visual analog scale (VAS), and Chinese patient-reported index for rheumatoid arthritis (CPRI-RA), as well as immune inflammatory indicators, including erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), interleukin-6 (IL-6), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), complement C3, and complement C4, were collected before and after treatment. Spearman correlation analysis was used to assess the relationships between SPP and immune inflammatory indicators. Logistic regression, association rule analysis, and mediation analysis were performed to evaluate the effects and potential pathways of HQC on SPP and immune inflammatory indicators. Network pharmacology was applied to identify the active components and core targets of HQC in the treatment of RA, followed by molecular docking verification. In cell experiments, cells were divided into normal group, model group, 20% medicated serum group, and 80 nmol/L control group. Human synovial fibroblasts (FLS) were cultured with complete medium in the normal group, while human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were cultured in the model group. In the 20% medicated serum group, RA-FLS were cultured with medium containing 20% HQC-medicated serum, and in the 80 nmol/L control group, RA-FLS were cultured with complete medium containing 80 nmol/L methotrexate suspension. After 48 h of culture, cell viability was detected by cell counting kit-8 (CCK-8) assay. Levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) in the cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Protein levels of matrix metalloproteinase 9 (MMP9), transcription factor AP-1 subunit (JUN), vascular endothelial growth factor A (VEGFA), and C-X-C motif chemokine ligand 8 (CXCL8) were detected by Western Blot, and cell migration ability was evaluated using Transwell assay. ResultsAfter PSM, 178 cases were included in each group. After treatment, SF-36 scores increased, while scores of SAS, SDS, VAS and CPRI-RA, levels of ESR, hs-CRP, IL-6, complement C3, and complement C4 levels decreased in both groups; IgG and IgM levels were also reduced in the observation group (P<0.05). Physical functioning (correlation coefficient -0.19, P<0.05) and social functioning (correlation coefficient -0.18, P<0.05) of SF-36 were negatively correlated with hs-CRP, while VAS score was positively correlated with hs-CRP (correlation coefficient 0.19, P<0.05). HQC showed high associations with improvements in multiple indicators of SPP and immune inflammatory, and acted as a protective factor for the improvement of several SPP; hs-CRP and ESR played partial mediating roles in the improvement of SPP induced by HQC (P<0.05). Network pharmacology analysis identified baicalein, quercetin, α1-sitosterol, β-sitosterol, stigmasterol, baicalin, and crocetin as the core active components, and JUN, IL-6, VEGFA, MMP9, IL-1β, and CXCL8 as the core targets. Molecular docking results showed strong binding affinities of quercetin with VEGFA, JUN, MMP9, IL-6, and IL-1β, of baicalin with VEGFA and MMP9, and of wogonin with CXCL8. Cell experiments demonstrated that HQC and methotrexate inhibited RA-FLS viability and migration, reduced levels of IL-1β, IL-6, and IL-8, decreased protein levels of MMP9, JUN, VEGFA, and CXCL8, and increased IL-10 levels (P<0.05). ConclusionHQC can improve SPP in RA by regulating immune inflammatory responses. Its mechanism may be related to multi-pathway and multi-target inhibition of synovial cell inflammation and migration.
2.Real-world study on the application and influencing factors of SGLT-2i in patients with heart failure with preserved ejection fraction
Tiantian CAI ; Junlong CHEN ; Yihang ZHANG ; Siyi HE ; Jian LIU ; Ruonan XIAO ; Shangjian LUO ; Lei GAO ; Dongying ZHANG
China Pharmacy 2026;37(8):1045-1049
OBJECTIVE To investigate the application and influencing factors of sodium-dependent glucose transporters 2 inhibitors(SGLT-2i) in patients with heart failure with preserved ejection fraction(HFpEF) in the real world. METHODS Data from 358 patients with HFpEF who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from May 2023 to May 2024 were retrospectively collected. The patients were divided into the SGLT-2i group and the non-SGLT-2i group based on whether they were prescribed SGLT-2i upon discharge. Baseline characteristics, comorbidities, and differences in drug treatment were compared between the two groups. Based on univariate analysis, multivariate Logistic regression analysis was performed to identify independent influencing factors of SGLT-2i use in patients with HFpEF, followed by further stratified analysis. RESULTS Among 358 HFpEF patients, the overall utilization rate of SGLT-2i was 33.5%. Combined with type 2 diabetes [OR=9.063,95%CI(4.924-16.679) ] , atrial fibrillation [OR=3.135,95%CI(1.590-6.178) ] , coronary artery heart disease [OR=1.888,95%CI(1.072-3.327) ] and the use of loop diuretics [OR=3.822, 95%CI (1.588-9.200) ] were all independent influencing factors for the use of SGLT-2i in patients with HFpEF ( P <0.05). The results of the stratified descriptive analysis were consistent with those of the multivariate analysis, showing a higher utilization rate of SGLT-2i among patients with concomitant T2DM,atrial fibrillation, coronary artery heart disease, and those receiving loop diuretics ( P <0.05); whereas the utilization rate of SGLT-2i was comparable across patients with different levels of renal function ( P >0.05). CONCLUSIONS In the real-world clinical practice, the utilization of SGLT-2i in patients with HFpEF remains suboptimal, and treatment coverage still needs to be improved. Their use of SGLT-2i is primarily influenced by the presence of type 2 diabetes, atrial fibrillation, coronary artery heart disease, and the use of loop diuretics.
3.Protocol for Chinese guidelines for perioperative airway management in thoracic surgery (2026 edition)
Xiuyi ZHI ; Lunxu LIU ; Jianxing HE ; Guowei CHE ; Jian HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):894-899
Driven by the widespread adoption of minimally invasive thoracic surgical techniques and the deepening integration of enhanced recovery after surgery (ERAS) protocols, evidence-based perioperative airway management has emerged as a pivotal determinant of surgical safety, pulmonary functional recovery, and long-term prognosis. Currently, substantial regional disparities in thoracic surgical expertise persist across China, manifesting as heterogeneity in preoperative assessment standardization, inconsistent airway preparation strategies, divergent approaches to complication prevention, and limited penetration of advanced anesthetic technologies. To promote the standardization of clinical practices in this domain among hospitals at all levels, a multidisciplinary expert consortium has initiated the development of the Chinese Guidelines for Perioperative Airway Management in Thoracic Surgery (2026 edition). This protocol systematically delineates the methodological framework and structural blueprint underpinning the guideline’s formulation. Compared to the 2020 edition, the updated guideline places specific emphasis on refining stratified criteria for preoperative cardiopulmonary reserve assessment, establishing standardized management pathways for non-intubated spontaneous-ventilation techniques, formulating individualized multimodal perioperative pulmonary rehabilitation regimens, and defining precise intervention workflows for persistent postoperative cough. Collectively, these measures aim to further reduce the baseline incidence of perioperative pulmonary complications and to provide robust support for the clinical translation of enhanced recovery principles within the field of thoracic surgery.
4.One Health theory and practice in China:history,present and future
Mu-xin CHEN ; Tian TIAN ; Yang HONG ; Jun-hu CHEN ; Jing-shu LIU ; Jian HE ; Xian-fa CHEN ; Qin LI ; Jin-xin ZHENG ; Tie-jian FENG ; Xiao-nong ZHOU
Chinese Journal of Zoonoses 2025;41(5):447-455
This paper summarizes the progress of theoretical research and practice of One Health in China,and discusses the paradigm of One Health governance to improve the prevention and control of infectious diseases in China and the world,and provide an example for the improvement of the public health system.In particular,China has long history to apply the concept of One Health in the national schistosomiasis control programmes and patriotic health campaigns,which were not only focusing on human health,but also emphasizing the sustainable development of animal health and ecological environment.At the same time,the application of tools such as system dynamics model,eDNA technology,One Health economic assessment and global One Health index(GOHI)in the field of disease control and environmental health provides technical support for the concept of One Health.Despite the challenges of practical application of these tools,the One Health concept will play a greater role in providing sustainable solutions for human-animal-environmental health by strengthening interdisciplinary collaboration,improving standardization protocols and promoting inter-national cooperation.
5.Vascularization characteristics of tissue-engineered oral mucosa equivalents
Lijuan SHI ; Jian WEI ; Xuan ZHANG ; Lingxiao HE ; Xiaoxi JIANG ; Minhai NIE ; Jiana CHEN ; Xuqian LIU
Chinese Journal of Tissue Engineering Research 2025;29(22):4748-4760
BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.
6.Sodium lactate modulates TLR4/NF-κB signaling pathway for treatment of right heart failure
Zhong-jian ZHANG ; Xiao-ying LUO ; Di QU ; Chun-liu QIAN ; Ting ZENG ; Zhi-ling HE ; Jia-jie LIAO ; Shuang LI
Chinese Pharmacological Bulletin 2025;41(10):1843-1849
Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P<0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P<0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.
7.Prospective study on the association between lifestyles and the risk of type 2 diabetes in adult residents
Meng-ru HE ; Xiao-li XU ; Gen-ming ZHAO ; Xing LIU ; Hui-lin XU ; Dan-dan HE ; Yu-ping CHENG ; Yong-gen JIANG ; Qian PENG ; Jian-hua SHI ; Xiao-hua LIU
Fudan University Journal of Medical Sciences 2025;52(5):647-656,685
Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.
8.Study on the efficacy and safety of Metformin hydrochloride enteric-coated capsules in patients with type 2 diabetes mellitus
Yiming WU ; Jian ZHANG ; Nan GU ; Qijuan DONG ; Ruiyun LIU ; Hong ZHANG ; Haixia LIU ; Yongcai ZHAO ; Lin CHENG ; Lianshan PU ; Fang BIAN ; Gang HE ; Quanmin LI ; Wei DU ; Zhaoling WANG ; Wei XU ; Liyong ZHONG ; Xiaohui GUO
Chinese Journal of Diabetes 2025;33(3):210-214
Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384~0.069)and PPS(-0.139,95%CI-0.390~0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.
9.Analysis of clinicopathological parameters and risk factors for the patients with connective tissue disease-associated interstitial lung disease complicated with EBV viraemia
Hanyi JIANG ; Tingting ZHAO ; Yonglong XIAO ; Jian HE ; Rongfeng QI ; Jin XU ; Yin LIU
Chinese Journal of Clinical Laboratory Science 2025;43(3):174-178
Objective To investigate the clinicopathological parameters and risk factors of the patients with connective tissue disease-associated interstitial lung disease(CTD-ILD)complicated with Epstein-Barr virus(EBV)viraemia.Methods The CTD-ILD pa-tients admitted to Department of Respiratory and Critical Care Medicine,Nanjing Drum Tower Hospital from January 2023 to April 2024 were collected.Based on the detection results of EBV DNA,the patients were divided into the EBV DNA(+)group and EBV DNA(-)group.The clinicopathological parameters of the two groups were analyzed.Results Out of 162 CTD-ILD patients who underwent EBV DNA testing,a total of 28 were found to have EBV viraemia.The levels of serum albumin([32.7±4.1]g/L vs[34.8±3.8]g/L,t=2.559,P<0.05),oxygenation index([268.5±94.0]mmHg vs[323.2±120.9]mmHg,t=2.062,P<0.05),and percentages of predicted diffusing capacity for carbon monoxide([30.9±15.3]% vs[44.9±18.8]%,t=2.127,P<0.05])in the EBV DNA(+)group were significantly lower than those in the EBV DNA(-)group,while the levels of lactate dehydrogenase(LDH,[369.1±206.2]U/L vs[298.8±128.7]U/L,t=2.335,P<0.05)were significantly higher than that in the EBV DNA(-)group.The acute exacerbation of ILD in the EBV DNA(+)group was more common than that in the EBV DNA(-)group(P<0.05).Multivariate Lo-gistic analysis showed that honeycombing and low oxygenation index were independent risk factors of CTD-ILD patients complicated with EBV viraemia.Conclusion The CTD-ILD patients complicated with EBV viraemia have poorer oxygenation and are more prone to suf-fer from acute exacerbation of ILD.Honeycombing in chest HRCT and low oxygenation index are independent risk factors of CTD-ILD patients complicated with EBV viraemia.
10.Application of Auto-prescription combined with low-dose contrast and iterative reconstruction algorithm in the CT angiography of thoracodorsal artery
Jian HE ; Yijun LIU ; Wei WEI ; Mengting HU ; Jingyi ZHANG ; Qiye CHENG ; Deshuo DONG ; Zhiming MA ; Changyu DU
Journal of Practical Radiology 2025;41(5):861-865
Objective To explore the application value of Auto-prescription combined with low-dose contrast and adaptive statisti-cal iterative reconstruction-Veo(ASIR-V)algorithm in the computed tomography angiography(CTA)of thoracodorsal artery(TDA).Methods A total of 100 patients who underwent TDA CTA examination were prospectively selected.A tube voltage of 120 kVp and contrast agent of 1.5 mL/kg were used for group A(50 cases),and images were reconstructed with 40% post-set ASIR-V.The Auto-prescription for tube voltage and contrast agent of 1.2 mL/kg were used for group B(50 cases),while images were reconstruc-ted with 40%,60%,and 80% post-set ASIR-V,labeled as subgroups B1 to B3.The objective and subjective evaluation results of the images were compared between and within groups.Results Group A had an effective dose(ED)of 2.98(2.65,4.03)mSv,while group B had an ED of 1.92(1.44,3.33)mSv.The iodine intake in group B was lower than that in group A,and the CT value of the axillary artery in group B was significantly higher than that in group A(P<0.001).With the increased of ASIR-V level in group B,the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the images gradually increased(P<0.05).In terms of subjec-tive scores on axial images,both subgroups B2 and B3 were superior to group A(P<0.001);with the increased of ASIR-V level in group B,subjective scores of axial images increased first and then decreased,among which subjective score of subgroup B2 was the highest and the differences were statistically significant(P<0.001).In terms of subjective scores on three-dimensional image quality,subgroups B1 to B3 were superior to group A(P<0.001).Conclusion The use of Auto-prescription combined with low-dose con-trast and 60% ASIR-V can significantly optimize the display of TDA,and reduce the radiation dose and contrast agent dose to a certain extent.

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