1.Reactive and Enzyme-activated Probe Strategies for Imaging Acute Kidney Injury
Ru-Long CHEN ; Ting-Fei XIE ; Jin-Xin ZHANG ; Jia-Ting CHEN ; Jie LI ; Peng-Fei ZHANG ; Ji-Hong CHEN ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(6):1622-1637
Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.
2.Mechanism of interleukin-9-induced osteoclast differentiation in bone erosion of cystic echinococcosis
Journal of Regional Anatomy and Operative Surgery 2025;34(6):489-493
Objective To investigate the role of interleukin-9(IL-9)in the invasive growth of bone cystic tissue with cystic echinococcosis and its molecular mechanisms.Methods Paraffin sections of bone cystic tissues from 8 patients with cystic echinococcosis were collected,and paraffin sections of affected knee joint tissues from 8 patients with osteoarthritis were selected as controls.qPCR was used to detect the expression levels of IL-9 mRNA in bone cystic tissues and osteoarthritis bone tissues.RAW264.7 cells were divided into the Undifferentia-tion group(Group 1),the MCSF group(Group 2),the MCSF+RANKL group(Group 3),the MCSF+RANKL+echinococcosis antigen B group(Group 4),and the MCSF+RANKL+IL-9 group(Group 5).qPCR was used to detect the expression levels of TRAP and cathepsin K mRNA in cells of each group.Western blot was used to detect the expression levels of p-p65,p65,nuclear factor of activated T-cells 1(NFATc1),phosphorylated signal transducer and activator of transcription 3(p-STAT3),signal transducer and activator of transcription 3(STAT3),phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)and extracellular signal-regulated kinase 1/2(ERK1/2)in cells of each group.Results The expression level of IL-9 mRNA was higher in bone cystic tissues than that in osteoarthritis bone tissues(P<0.05).Compared with Group 1,the expression levels of TRAP and cathepsin K mRNA in Group 2,Group 3,Group 4 and Group 5 were significantly increased(P<0.05),as well as the levels of p-p65,p-STAT3 and p-ERK1/2,and the expression levels of NFATc1(P<0.05);Compared with Group 3,the above indexes in Group 5 were all increased(P<0.05).Conclusion The expression level of IL-9 is up-regulated in bone cystic tissues,and it enhances the induction of osteoclast differentiation by up-regulating the nuclear factor-κB(NF-κB)/STAT3/ERK1/2 signaling pathway,which may play an important role in bone erosion of bone echinococcosis.
3.Prospective analysis of autophagy in prostate cancer cells based on gene expression databases and investigation of the C-Met regulatory mechanism
Ru ZHANG ; Yongqiang XIE ; Qiang ZHAO ; Keqiang CHAI ; Yulin LIU
Immunological Journal 2025;41(10):750-761
Objective To investigate the prognostic value of mitochondrial autophagy-related genes(MRGs)in prostate cancer(PCa),and to reveal their regulatory relationship with interstitial epidermal transforming factor(C-Met)based on the Gene Expression Database(GEO).Methods Single-cell RNA sequencing(scRNA-seq)data of three PCa samples were obtained from the GSE153892 dataset of GEO,and MRGs were collected from the Genecards database and previous literature.The scRNA-seq data were processed and analyzed using the Seurat software package,including quality control,gene expression screening,cell type annotation,differentially expressed genes(DEGs)identification,and intersection analysis with MRGs.The transcriptome data of PCa and control samples were downloaded from the Cancer Genome Atlas Database(TCGA)-PRAD cohort,and differential expression analysis and copy number variation analysis were conducted.The non-negative matrix factorization algorithm is adopted to conduct cluster analysis on PCa samples to identify different PCa subtypes.A prognostic risk model based on intersection genes was constructed,and the predictive ability of the model was analyzed through Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic(ROC)curve analysis.Conduct independent prognostic analysis,construct a nomogram model based on risk scores and clinical characteristics,and evaluate its ability to predict patient survival rates.The possibility of immune infiltration and tumor immune escape in PCa samples was evaluated by using the single-sample Gene Set Enrichment analysis(ssGSEA)algorithm and the TIDE database.The relationship between intersection genes and C-Met expression was analyzed using Pearson correlation analysis.Results scRNA-seq data analysis identified five cell types including B lymphocytes,epithelial cells,monocytes,natural killer cells and T lymphocytes,and discovered the intersection genes that were highly expressed in different cell types.Through differential expression analysis,genes significantly related to the prognosis of PCa patients were screened out,and a prognostic risk model was constructed.Six genes such as ADH5 and CAT were retained through LASSO analysis.A diagnostic model was constructed and grouped.There was a significant difference in survival time between the two groups in the internal test set(P<0.05).ROC curve evaluation showed that the model had a good predictive ability for 1-,3-,and 5-year survival rates.The external test set verified that there was a statistically significant difference in the expression of intersection genes(P<0.05).Independent prognostic analysis identified T stage and risk score as independent prognostic factors.A nomogram model was constructed.Calibration curve and ROC curve analyses showed that the predictive ability of this model was superior to that of the simple risk model.ssGSEA analysis revealed differences in the abundance of immune cell inflammation and immune function scores between the two groups.Most immune cells,immune function,and risk scores were related to the modeling genes.There were significant differences in TIDE scores and multiple immune checkpoints between the high-risk and low-risk groups(P<0.05).BCAT2,DCXR,OGT and FUS were positively correlated with the expression of C-Met,while ADH5 and CAT were negatively correlated with the expression of C-Met(P<0.05).Conclusion The prognostic risk model based on intersection genes can effectively predict the prognosis of patients with PCa,and the risk score and T stage are independent prognostic factors for PCa.The correlation analysis of intersection genes and C-Met expression provides a new idea for the targeted therapy of PCa.
4.Efficacy of free medial sural artery perforator flap transplantation in repairing electrical burn wounds on hands and feet
Weidong ZHANG ; Wei ZHANG ; Gang YU ; Lan CHEN ; Xiang GONG ; Weiguo XIE ; Tianfeng RU
Chinese Journal of Burns 2025;41(4):386-393
Objective:To explore the efficacy of free medial sural artery perforator flap transplantation in repairing electrical burn wounds on hands and feet.Methods:This study was a retrospective observational study. From November 2017 to September 2023, 21 male patients aged 28-51 years with electrical burns on hands and feet who met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital. There were 23 wounds, of which 14 were on the hand and 9 on the foot; 9 were associated with exposed tendon injury, 6 were associated with bone exposure or necrosis, and 8 were associated with joint injury. The wound area after debridement was 4.0 cm×2.5 cm-14.0 cm×10.0 cm. For 2 relatively wide wounds and 2 adjacent fingers/toes wounds, the lobulated flaps centered on 2 medial sural artery perforators were designed and incised for repair. For other wounds, medial sural artery perforator flaps were designed and incised. The flap area was 5.0 cm×3.0 cm-16.0 cm×11.0 cm. The arteriovenous vessels of flap were anastomosed end-to-end with the arteriovenous vessels of the recipient area; the cutaneous nerves of 10 flaps were anastomosed with the nerves in hand wound, and the sural nerve bundle was cut to repair one digital nerve defect. The donor site wound was closed with tension-relieving sutures. Postoperative flap survival and wound healing at donor site were recorded. During follow-up, subsequent flap revision was recorded, the texture and appearance of the flap, as well as the scarring and functional recovery of the donor area of the lower leg, were observed. At the last follow-up, the recovery of hand flap sensation was observed, the satisfaction of patients with the treatment effect of each operation was investigated by using Likert scale, the hand function of the affected hand in patients with hand wounds was evaluated by using the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association, and the weight-bearing walking ability of the affected foot in patients with foot wounds was evaluated by Holden walking ability grading.Results:There was a slight necrosis at the distal end of one flap after surgery, which healed after dressing change. All 23 flaps survived. The sutures of the two donor areas were poorly healed due to high local tension, and the second sutures were performed after debridement and drainage, and the healing was good. The wounds of the remaining 21 donor sites healed well. Follow-up of 6-26 months after surgery showed that 3 flaps were slightly bloated, and the appearance was improved after flap reconstruction; the other flaps did not undergo subsequent revision. All flaps were soft and similar to the surrounding tissue morphology. Linear scar remained in the donor site of the lower leg, and walking function was normal. At the last follow-up, the protective sensation of the hand flap was restored; the patients were very satisfied with the results of 21 surgeries and were relatively satisfied with the results of 2 surgeries. Among the 14 patients with hand wounds, the affected hand function was rated as excellent in 10 cases, very good in 3 cases, and acceptable in one case, and the weight-bearing walking ability of the affected foot in 7 patients with foot wounds was all rated as grade Ⅴ.Conclusions:The medial sural artery perforator flap has the advantages of reliable blood supply, appropriate thickness and smoothness, and can be lobulated or cut according to the shape of the wound. The flap demonstrates superior aesthetic and functional restoration in repairing electrical burn wounds on hands and feet, achieving high patient satisfaction with the surgical treatment effect.
5.Prospective analysis of autophagy in prostate cancer cells based on gene expression databases and investigation of the C-Met regulatory mechanism
Ru ZHANG ; Yongqiang XIE ; Qiang ZHAO ; Keqiang CHAI ; Yulin LIU
Immunological Journal 2025;41(10):750-761
Objective To investigate the prognostic value of mitochondrial autophagy-related genes(MRGs)in prostate cancer(PCa),and to reveal their regulatory relationship with interstitial epidermal transforming factor(C-Met)based on the Gene Expression Database(GEO).Methods Single-cell RNA sequencing(scRNA-seq)data of three PCa samples were obtained from the GSE153892 dataset of GEO,and MRGs were collected from the Genecards database and previous literature.The scRNA-seq data were processed and analyzed using the Seurat software package,including quality control,gene expression screening,cell type annotation,differentially expressed genes(DEGs)identification,and intersection analysis with MRGs.The transcriptome data of PCa and control samples were downloaded from the Cancer Genome Atlas Database(TCGA)-PRAD cohort,and differential expression analysis and copy number variation analysis were conducted.The non-negative matrix factorization algorithm is adopted to conduct cluster analysis on PCa samples to identify different PCa subtypes.A prognostic risk model based on intersection genes was constructed,and the predictive ability of the model was analyzed through Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic(ROC)curve analysis.Conduct independent prognostic analysis,construct a nomogram model based on risk scores and clinical characteristics,and evaluate its ability to predict patient survival rates.The possibility of immune infiltration and tumor immune escape in PCa samples was evaluated by using the single-sample Gene Set Enrichment analysis(ssGSEA)algorithm and the TIDE database.The relationship between intersection genes and C-Met expression was analyzed using Pearson correlation analysis.Results scRNA-seq data analysis identified five cell types including B lymphocytes,epithelial cells,monocytes,natural killer cells and T lymphocytes,and discovered the intersection genes that were highly expressed in different cell types.Through differential expression analysis,genes significantly related to the prognosis of PCa patients were screened out,and a prognostic risk model was constructed.Six genes such as ADH5 and CAT were retained through LASSO analysis.A diagnostic model was constructed and grouped.There was a significant difference in survival time between the two groups in the internal test set(P<0.05).ROC curve evaluation showed that the model had a good predictive ability for 1-,3-,and 5-year survival rates.The external test set verified that there was a statistically significant difference in the expression of intersection genes(P<0.05).Independent prognostic analysis identified T stage and risk score as independent prognostic factors.A nomogram model was constructed.Calibration curve and ROC curve analyses showed that the predictive ability of this model was superior to that of the simple risk model.ssGSEA analysis revealed differences in the abundance of immune cell inflammation and immune function scores between the two groups.Most immune cells,immune function,and risk scores were related to the modeling genes.There were significant differences in TIDE scores and multiple immune checkpoints between the high-risk and low-risk groups(P<0.05).BCAT2,DCXR,OGT and FUS were positively correlated with the expression of C-Met,while ADH5 and CAT were negatively correlated with the expression of C-Met(P<0.05).Conclusion The prognostic risk model based on intersection genes can effectively predict the prognosis of patients with PCa,and the risk score and T stage are independent prognostic factors for PCa.The correlation analysis of intersection genes and C-Met expression provides a new idea for the targeted therapy of PCa.
6.Mechanism of interleukin-9-induced osteoclast differentiation in bone erosion of cystic echinococcosis
Journal of Regional Anatomy and Operative Surgery 2025;34(6):489-493
Objective To investigate the role of interleukin-9(IL-9)in the invasive growth of bone cystic tissue with cystic echinococcosis and its molecular mechanisms.Methods Paraffin sections of bone cystic tissues from 8 patients with cystic echinococcosis were collected,and paraffin sections of affected knee joint tissues from 8 patients with osteoarthritis were selected as controls.qPCR was used to detect the expression levels of IL-9 mRNA in bone cystic tissues and osteoarthritis bone tissues.RAW264.7 cells were divided into the Undifferentia-tion group(Group 1),the MCSF group(Group 2),the MCSF+RANKL group(Group 3),the MCSF+RANKL+echinococcosis antigen B group(Group 4),and the MCSF+RANKL+IL-9 group(Group 5).qPCR was used to detect the expression levels of TRAP and cathepsin K mRNA in cells of each group.Western blot was used to detect the expression levels of p-p65,p65,nuclear factor of activated T-cells 1(NFATc1),phosphorylated signal transducer and activator of transcription 3(p-STAT3),signal transducer and activator of transcription 3(STAT3),phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)and extracellular signal-regulated kinase 1/2(ERK1/2)in cells of each group.Results The expression level of IL-9 mRNA was higher in bone cystic tissues than that in osteoarthritis bone tissues(P<0.05).Compared with Group 1,the expression levels of TRAP and cathepsin K mRNA in Group 2,Group 3,Group 4 and Group 5 were significantly increased(P<0.05),as well as the levels of p-p65,p-STAT3 and p-ERK1/2,and the expression levels of NFATc1(P<0.05);Compared with Group 3,the above indexes in Group 5 were all increased(P<0.05).Conclusion The expression level of IL-9 is up-regulated in bone cystic tissues,and it enhances the induction of osteoclast differentiation by up-regulating the nuclear factor-κB(NF-κB)/STAT3/ERK1/2 signaling pathway,which may play an important role in bone erosion of bone echinococcosis.
7.Discussion on the Treatment of Knee Osteoarthritis with Sanbi Decoction from the Theory of"Bone,Tendon and Muscle"
Zhengyu YANG ; Hailong WANG ; Ru WANG ; Xinliang LYU ; Mingming XIE ; Lijuan YANG ; Hongyu HOU ; Xue CHEN ; Xintong MA ; Guohua LI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):182-186
Knee osteoarthritis is a common joint disease within osteoarthritis,characterized by pain,swelling,and limited functionality as the main clinical manifestations.In severe cases,it affects daily life and falls under the category of"impediment syndrome"or"bone impediment"in TCM.The author believes that the theory of"bones,tendons,and muscles"is closely related to this disease.Treatment should focus on simultaneously nourishing the liver,spleen and kidneys,considering tendons,bones and muscles,while also dispelling wind,cold and dampness.The clinical application of Sanbi Decoction has shown good efficacy,and this discussion aimed to provide ideas for the diagnosis and treatment of knee osteoarthritis.
8.Mechanism of action of hesperidin and its derivatives in the management of spinal cord injury: a review
Zhourui YANG ; Yaoqin RU ; Yaoyao AN ; Hongru XIE ; Guohui HAI ; Qin ZHANG
Chinese Journal of Trauma 2025;41(5):510-516
Spinal cord injury is a central nervous system disorder caused by direct or indirect trauma to the spinal cord, with an increasing incidence year by year. Neuroinflammation, oxidative stress, and local edema following spinal cord injury can lead to motor, sensory and cognitive impairment in patients, resulting in an extremely high disability rate. Conventional treatments primarily involve surgery combined with pharmacotherapy, yet clinical outcomes remain unsatisfactory. Hesperidin, a citrus-derived flavonoid and its derivatives (neohesperidin, hesperetin, etc.) exhibit anti-inflammatory, antioxidant, anti-apoptotic, and pyroptosis-inhibitory properties. When used in the management of spinal cord injury, they can effectively improve post-injury motor dysfunction. However, hesperidin and its derivatives still face problems such as poor blood-brain-spinal cord barrier penetration and incomplete understanding of their key mechanisms, limiting the efficacy of monotherapy with hesperidin and its derivatives in the management of spinal cord injurg. To this end, the authors reviewed the research progress on mechanism of action of hesperidin and its derivatives in the management of spinal cord injury, aiming to provide a reference for its future research and clinical application.
9.Construction of a risk prediction model of hyperuricemia for community-dwelling residents
Cong XIE ; Jinxiu ZHANG ; Jinli RU
Chinese Journal of General Practitioners 2025;24(3):308-314
Objective:To construct a risk prediction model of hyperuricemia (HUA) for community-dwelling residents.Methods:This cross-sectional study was conducted from March to November 2020. A total of 1 967 residents in the Nanzhai community of Taiyuan city were selected by stratified sampling method as study subjects, among whom 1 555 (80%) subjects served as the training set and the remaining 412 (20%) as the validation set. Blood uric acid was measured in all subjects and level>420 mmol/L was defined as HUA. The risk factors of HUA were determined with multivariate logistic regression analysis, and a risk prediction model was constructed. The Hosmer-Lemeshow goodness-of-fit test and the receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the model.Results:Among the 1 555 residents in the training set, HUA was detected in 285 cases (18.3%). The detection rate in men was significantly higher than that in women [29.8% (220/739) vs. 8.0% (65/816), χ 2=123.17, P<0.05]. Compared to non-HUA group, the waist circumference and BMI, and the proportion of smoking, drinking, staying up late, and prevalence of hypertension and dyslipidemia were significant higher in HUA group. There was significant difference in the frequency of drinking tea, coffee, milk, and eating fruits, as well as the amount of beverages consumed between the two groups ( P<0.05). Multivariate logistic regression analysis showed that high BMI ( OR=1.132, 95 %CI:1.070-1.197, P<0.001), coffee consumption ( OR=1.337, 95 %CI:1.027-1.742, P=0.032), and dyslipidemia ( OR=1.479, 95 %CI:1.049-2.086, P=0.025) were risk factors of HUA, while female sex ( OR=0.213, 95 %CI:0.146-0.390, P<0.001) was protective factor of HUA. When all factors were included in the logistic regression model, gender, BMI, coffee consumption, beverage intake, sodium salt intake, sleep quality, and dyslipidemia ( OR=0.213, 1.113, 1.353, 0.788, 1.320, 0.788, 1.651) were important components of the HUA prediction model. By substituting the constant, these factors, and the regression coefficients into the logistic regression equation, the Logit(P) formula was obtained: Logit(P)=-1.530-1.547×gender+0.107×BMI+0.303×coffee consumption frequency-0.238×sodium salt intake+0.278×beverage intake-0.238×sleep quality+0.502×dyslipidemia. The ROC curve showed an area under the curve ( AUC) of 0.750. The Hosmer-Lemeshow goodness-of-fit test: P=0.632, indicating a satisfactory fit. When the formula was applied to the validation set for internal validation, the AUC was 0.745. Conclusion:The occurrence of HUA is influenced by multiple factors. The prediction model constructed in this study has good prediction performance,which may be used to predict the risk of HUA in primary care settings for community-dwelling residents.
10.Brief Discussion on the General Requirements of Quality Management System of In Vitro Diagnostic Reagents Developed by Medical Institutions.
Chinese Journal of Medical Instrumentation 2025;49(2):219-223
On March 19, 2021, the National Medical Products Administration(NMPA) issued the Regulations on the Supervision and Administration of Medical Devices (Order No. 739 of the State Council of the People's Republic of China), which clearly stipulated in Article 53 the basic definition and scope of use of in vitro diagnostic reagents developed by medical institutions. It also pointed out that the relevant administrative measures shall be formulated by the Drug Regulatory Department of the State Council in conjunction with the Health Department of the State Council. This initiative marks the re-incorporation of in vitro diagnostic reagents developed by medical institutions into China's regulatory system. This study reviewed the development of regulatory policies for self-developed in vitro diagnostic reagents at home and abroad, combined with the Key Points of On-site Verification of Self-developed In Vitro Diagnostic Reagents in Shanghai Medical Institutions issued by the Shanghai Municipal Drug Administration, in conjunction with the Shanghai Municipal Health Commission, and the specific verification work of pre-record evaluation, and sorted out the general requirements for the quality management system of self-developed in vitro diagnostic reagents. The purpose is to provide some references for the further development of this pilot work and its nationwide promotion.
China
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Quality Control
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Indicators and Reagents/standards*
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Reagent Kits, Diagnostic/standards*

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