1.Clinical Characteristics and Influencing Factors of Rheumatoid Arthritis in Patients with Cold Dampness Obstruction Syndrome
Yanyu CHEN ; Yanqi LI ; Longxiao LIU ; Liubo ZHANG ; Tianyi LAN ; Nan ZHANG ; Cheng XIAO ; Yuan XU ; Qingwen TAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):140-146
ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis (RA) in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information, clinical data, laboratory test results, and traditional Chinese medicine (TCM) symptom information were collected for syndrome differentiation, on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study, including 88 (34.1%) patients with cold dampness obstruction syndrome, 53 (20.5%) patients with dampness and heat obstruction syndrome, 31 (12.0%) patients with wind dampness obstruction syndrome, 29 (11.2%) patients with liver-kidney deficiency syndrome, 19 (7.4%) patients with Qi-blood deficiency syndrome, 14 (5.4%) patients with phlegm-stasis obstruction syndrome, 15 (5.8%) patients with stasis obstructing collateral syndrome and 9 (3.5%) patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever, 28-tender joint count (TJC28), and 28-joint disease activity score (DAS28)-C-reactive protein (CRP) and higher central sensitization, cold feeling of joints, fear of wind and cold, cold limbs, and abdominal distention than the group of other syndromes (P<0.05). The binary logistic regression analysis showed that central sensitization (OR 5.749, 95%CI 2.116-15.616, P<0.001) and DAS28-CRP (OR 0.600, 95% CI 0.418-0.862, P=0.006) were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization, cold feeling of joints, abdominal distension and may be a clinical syndrome associated with central sensitization.
2.Effect of hip abductor muscle exercise on three-dimensional gait and collapse rate in patients with non-traumatic femoral head necrosis
Yingjia YUAN ; Yanzi YI ; Jin LI ; Ke WANG ; Yu WANG ; Tianye LIN ; Qingwen ZHANG ; Wei HE ; Qiushi WEI
Chinese Journal of Tissue Engineering Research 2025;29(33):7211-7216
BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P>0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P>0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P<0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P<0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P>0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P<0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P<0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P>0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P<0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P<0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P<0.05),and that in the hip abductor muscle exercise group(22%)was significantly lower than that in the control group(45%).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.
3.Association of Obesity Phenotypes With Cognitive Impairment and Genetic Stratification Analysis in Older Chinese Adults
Xin CHEN ; Haiyu YAN ; Qingwen ZHAO ; Nan YANG ; Bin XU ; Jiaqiang LIAO ; Xia JIANG ; Jiayuan LI
Journal of Sichuan University (Medical Sciences) 2025;56(4):956-963
Objective To evaluate the association of different obesity phenotypes and their components with the risk of cognitive impairment in older Chinese adults,and to assess the association between obesity and cognitive impairment in different cognition-related genetic backgrounds.Methods A cross-sectional study based on the West China Health and Aging Cohort was conducted.Logistic regression was applied to estimate the association of obesity phenotypes and components with cognitive impairment in older Chinese adults stratified by APOE gene and polygenic risk scores.Results A total of 7 316 participants were enrolled,of whom 1 820 had cognitive impairment.Weight gains were associated with a reduced risk of cognitive impairment(odds ratio[OR]=0.96,95%CI,0.95-0.97).Being overweight with a normal waist-to-hip ratio was a protective factor for cognition(OR=0.74,95%CI,0.61-0.90),whereas the coexistence of elevated waist-to-hip ratio and overweight did not increase the risk of cognitive impairment.Sarcopenia was associated with an elevated risk of cognitive impairment.This association was found in both overweight(OR=2.03,95%CI,1.71-2.41)and non-overweight older adults(OR=1.86,95%CI,1.58-2.20),and was significant across all polygenic risk score strata.Conclusion Increasing body mass may serve as a key protective factor against cognitive decline in older adults.Having sarcopenia and obesity is associated with an elevated risk of cognitive impairment,independent of genetic susceptibility.
4.Evaluation of Gradient-Variant Quantum Dot Fluorescence Technology for Rapid Detection of Brucella
Jiquan LI ; Xintong WANG ; Jianling WANG ; Shengnan TIAN ; Cunzhe ZHAO ; Xiaochen WANG ; Wenxiu JIAN ; Shengyu LI ; Qingwen ZHANG ; Lei ZHOU
Journal of Sichuan University (Medical Sciences) 2025;56(5):1208-1214
Objective To establish a brucellosis monitoring and testing technique applicable for the rapid field screening of natural epidemic diseases.Methods A rapid testing technique for Brucella was developed based on a double-antibody sandwich testing model using gradient-variant quantum dots as fluorescent tracers.The sensitivity,linearity,precision,and specificity of the technique were evaluated using suspensions of standard Brucella strains.Methodological comparisons across different sample types were conducted to assess the consistency of the test results.Results The gradient-variant quantum dots detection method was evaluated with standard Brucella strains,exhibiting a sensitivity of 1×103 CFU/mL and a linear correlation coefficient(r)of 0.994(95%CI,0.933-1.055).The maximum coefficient of variation was 12.94%in repeated tests,showing good specificity.A comparative assessment of 305 clinical samples was conducted using the Brucella gradient-variant quantum dots detection method,the Rose Bengal plate agglutination test(RBT),and the serum agglutination test(SAT),yielding a Kappa value of 0.95,indicating almost perfect agreement.Additionally,a comparative assessment of 110 environmental samples collected on-site was conducted using the Brucella gradient-variant quantum dots detection method and quantitative real-time PCR(qPCR).The Kappa values for aerosol collection fluid,surface wipes,and wool samples were all above 0.83,demonstrating near-perfect agreement.For fecal and soil samples,the Kappa values were above 0.62,indicating substantial agreement.Conclusion The Brucella detection method based on gradient-variant quantum dots technology is simple and can be conducted rapidly.The detection method demonstrates high sensitivity,linearity,precision,and specificity.It shows consistent performance in clinical sample testing.It is well-suited for field rapid screening of natural epidemic diseases in field settings and shows good application prospects in the monitoring,prevention,and rapid detection of zoonotic diseases.
5.Different exercise modalities promote functional recovery after peripheral nerve injury
Xiaoxuan ZHAO ; Shuaiyi LIU ; Qi LI ; Zheng XING ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(6):1248-1256
BACKGROUND:Exercise as a form of active rehabilitation can improve the dysfunction caused by peripheral nerve injury,and different exercise modalities target different lesion sites and recovery mechanisms. OBJECTIVE:To comprehensively analyze the application and mechanisms of different exercise modalities in functional recovery from peripheral nerve injury. METHODS:A computerized search was conducted in PubMed and CNKI databases for relevant literature published before January 2024.The search terms used were"peripheral nerve injury,spinal cord,exercise,cerebral cortex,muscle atrophy,mirror therapy,blood flow restriction training"in both English and Chinese.Finally,77 articles were included for review. RESULTS AND CONCLUSION:Peripheral nerve injury can cause systemic pathological changes such as skeletal muscle atrophy,corresponding spinal cord segmental lesions,and sensorimotor cortex remodeling.Aerobic exercise can improve dysfunction by enhancing the immune response,promoting glial cell polarization,and promoting the release of nerve growth factor.Blood flow restriction exercise can regulate the secretion of muscle growth factor,promote muscle growth and enhance muscle strength.Mirror movement has a good effect in activating the cerebral cortex and reducing cortical remodeling.Different exercise modalities have potential benefits in functional recovery after peripheral nerve injury;however,there are still some problems and challenges,such as the choice of exercise modalities,the control of exercise intensity and frequency,and the detailed analysis of mechanisms.
6.Causal relationship between 91 inflammatory proteins and cervical disc degeneration
Shuaiyi LIU ; Xiaoxuan ZHAO ; Qi LI ; Zheng XING ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(17):3732-3740
BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran's Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.
7.Electromyographic biofeedback therapy and motor function recovery after spinal cord injury
Jiajia LIANG ; Jiaojiao SUN ; Wenjie LIU ; Zheng XING ; Qi LI ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(14):3002-3010
BACKGROUND:Electromyographic biofeedback therapy has demonstrated unique advantages of non-invasive,real-time feedback,personalized treatment and promotion of neuroplasticity,and can promote the recovery of motor function in patients with spinal cord injury.OBJECTIVE:To review the current application status and therapeutic effects of electromyographic biofeedback combined with exercise therapy,robotic exoskeletons,and virtual reality technology in the recovery of motor function after spinal cord injury.METHODS:Relevant literature was retrieved from CNKI and PubMed databases up to May 2024.The search terms included"spinal cord injury,EMG biofeedback,physical therapy,robotic exoskeleton,VR,motor function,exercise"in both English and Chinese.Finally,71 articles were included for review.RESULTS AND CONCLUSION:Mechanisms by which electromyographic biofeedback therapy promotes spinal cord injury rehabilitation include promoting neural plasticity changes,strengthening neuromuscular connections and improving movement patterns.Electromyographic biofeedback,as an emerging tool for treating spinal cord injury,is often used in conjunction with other therapeutic methods,including exercise therapy,robotic exoskeletons,and VR,to promote the recovery of motor function after spinal cord injury.The effectiveness of combination therapy has been significantly improved.However,there are still some problems and challenges,such as the lack of detailed analysis of the mechanism,the lack of large-scale trials that provide strong evidence for combined efficacy,and the limited adaptability of the technology.Future research can focus on these aspects:to improve the personalization and accuracy of electromyographic biofeedback;to develop new rehabilitation equipment and expand the application areas of electromyographic biofeedback combined with more advanced technologies or engineering equipment;to apply electromyographic biofeedback to gait training systems,respiratory training systems,and limb-linkage rehabilitation systems,so as to improve the accuracy of the feedback and the effect of personalized treatment plans.At the same time,the ease of use and comfort of the equipment will be improved.
8.Causal relationship between 91 inflammatory proteins and cervical disc degeneration
Shuaiyi LIU ; Xiaoxuan ZHAO ; Qi LI ; Zheng XING ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(17):3732-3740
BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran's Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.
9.Electromyographic biofeedback therapy and motor function recovery after spinal cord injury
Jiajia LIANG ; Jiaojiao SUN ; Wenjie LIU ; Zheng XING ; Qi LI ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(14):3002-3010
BACKGROUND:Electromyographic biofeedback therapy has demonstrated unique advantages of non-invasive,real-time feedback,personalized treatment and promotion of neuroplasticity,and can promote the recovery of motor function in patients with spinal cord injury.OBJECTIVE:To review the current application status and therapeutic effects of electromyographic biofeedback combined with exercise therapy,robotic exoskeletons,and virtual reality technology in the recovery of motor function after spinal cord injury.METHODS:Relevant literature was retrieved from CNKI and PubMed databases up to May 2024.The search terms included"spinal cord injury,EMG biofeedback,physical therapy,robotic exoskeleton,VR,motor function,exercise"in both English and Chinese.Finally,71 articles were included for review.RESULTS AND CONCLUSION:Mechanisms by which electromyographic biofeedback therapy promotes spinal cord injury rehabilitation include promoting neural plasticity changes,strengthening neuromuscular connections and improving movement patterns.Electromyographic biofeedback,as an emerging tool for treating spinal cord injury,is often used in conjunction with other therapeutic methods,including exercise therapy,robotic exoskeletons,and VR,to promote the recovery of motor function after spinal cord injury.The effectiveness of combination therapy has been significantly improved.However,there are still some problems and challenges,such as the lack of detailed analysis of the mechanism,the lack of large-scale trials that provide strong evidence for combined efficacy,and the limited adaptability of the technology.Future research can focus on these aspects:to improve the personalization and accuracy of electromyographic biofeedback;to develop new rehabilitation equipment and expand the application areas of electromyographic biofeedback combined with more advanced technologies or engineering equipment;to apply electromyographic biofeedback to gait training systems,respiratory training systems,and limb-linkage rehabilitation systems,so as to improve the accuracy of the feedback and the effect of personalized treatment plans.At the same time,the ease of use and comfort of the equipment will be improved.
10.Regulatory role of miR-351-5p in lipopolysaccharide-induced ferroptosis of cardiomyocytes
Mengru ZHANG ; Yanfen PENG ; Qingwen LI ; Lishan FU ; Qingsen RAN ; Dan-dan LI ; Baolin LI
Chinese Journal of Pathophysiology 2025;41(6):1162-1169
AIM:This study aims to investigate the role of ferroptosis in the myocardium of mice with lipopoly-saccharide(LPS)-induced sepsis and in the injury of H9c2 rat cardiomyocytes,and to explore the regulatory function of microRNA-351-5p(miR-351-5p)in this context.METHODS:An in vivo model of sepsis-induced cardiomyopathy was established in mice through intraperitoneal injection of LPS.Twenty-four mice were randomly divided into negative control(NC)group,LPS group,and LPS+ferroptosis inhibitor ferrostatin-1(Fer-1)group.Hematoxylin-eosin(HE)staining was conducted to assess cardiac injury,and plasma levels of creatine kinase(CK)and lactate dehydrogenase(LDH)were also measured.Additionally,the levels of Fe2+and malondialdehyde(MDA)in plasma were quantified,and the mRNA levels of acyl-CoA synthetase long chain family member 4(ACSL4)and prostaglandin-endperoxide synthase 2(PTGS2)were de-tected by RT-qPCR.In vitro,H9c2 cardiomyocytes were stimulated with LPS to create cellular models,followed by treat-ment with Fer-1,inhibitor NC,or miR-351-5p inhibitor.Cell viability was evaluated using CCK8 assay,intracellular re-active oxygen species(ROS)were measured by flow cytometry,intracellular Fe2+levels were assessed using a fluorescence probe,and the protein expression of glutathione peroxidase 4(GPX4)and ACSL4 was analyzed by Western blot.The MDA and reduced glutathione(GSH)levels were measured using commercial kits.MicroRNA(miRNA)sequencing was performed on the LPS-stimulated H9c2 cardiomyocyte models,with differential miRNAs identified and subsequently vali-dated using RT-qPCR.RESULTS:The mice in LPS group exhibited significant myocardial tissue dysregulation com-pared with NC group,with enlarged space,increased plasma CK and LDH levels(P<0.05),elevated Fe2+and MDA levels in myocardial tissues(P<0.05),and increased mRNA levels of ACSL4 and PTGS2(P<0.05).In contrast,the mice in LPS+Fer-1 group demonstrated improved myocardial tissue structure,reduced space,decreased plasma CK and LDH levels(P<0.05),and lower Fe2+and MDA levels in myocardial tissues(P<0.05),along with decreased mRNA level of PTGS2(P<0.05).In H9c2 cardiomyocytes,cell viability,intracellular GSH level,and GPX4 protein level were significantly reduced in LPS group compared with NC group(P<0.05),while ROS,MDA,Fe2+,and ACSL4 protein levels were elevated(P<0.05).The cells in LPS+Fer-1 group showed increased viability,intracellular GSH level,and GPX4 protein level compared with LPS group(P<0.05),alongside reduced ROS,MDA,Fe2+,and ACSL4 levels(P<0.05).miRNA sequencing revealed a significant decrease in several miRNAs,with miR-351-5p showing the most pro-nounced reduction.In LPS+miR-351 inhibitor group,H9c2 cell viability significantly declined(P<0.05),and the levels of GSH and GPX4 were notably lowered(P<0.05),while ROS,MDA,Fe2+and ACSL4 protein levels were significantly elevated(P<0.05).However,in LPS+miR-351 inhibitor+Fer-1 group,the cell viability increased(P<0.05),and the GSH level rose significantly(P<0.05),with corresponding decreases in intracellular ROS,Fe2+and ACSL4 protein levels(P<0.05).CONCLUSION:Inhibition of ferroptosis attenuated sepsis-induced myocardial injury,and inhibition of miR-351-5p promotes sepsis-induced ferroptosis of H9c2 cardiomyocytes.

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