1.Application of Proton Density Fat Fraction of Magnetic Resonance Imaging in Evaluation of Thigh Skeletal Muscle in Healthy People
Yiou WANG ; Xinru ZHANG ; Qingling YU ; Kexin JIANG ; Qianyi QIU ; Yi YANG ; Xiaodong ZHANG
Chinese Journal of Medical Imaging 2024;32(10):1051-1057
Purpose To explore the ability of proton density fat fraction(PDFF)and decay constant T2* values in MRI to reflect skeletal muscle aging.Materials and Methods 3T MRI data of skeletal muscle in the middle thigh of 211 healthy adults from the Third Affiliated Hospital of Southern Medical University from August to December 2023 were prospectively collected.Gender,age,height,weight and body mass index(BMI)were recorded.PDFF value and T2* value of thigh skeletal muscle were measured at post-processing workstation,and statistical differences among different age,gender and BMI groups were analyzed.The correlation between PDFF value and T2* value of thigh skeletal muscle and age and BMI was analyzed.Results There were statistically significant differences in PDFF values of thigh skeletal muscle among different age groups(H=18.476-85.619,all P<0.01).There were significantly differences in T2*values of the left and right quadriceps muscles,hamstrings and adductors among different age groups(H=13.342-47.566,all P<0.05).There were statistically significant differences in the PDFF values of right quadriceps,left and right hamstring,adductor and sartor muscles between male and female groups(Z=-4.929--1.626,all P<0.05),while there were statistically significant differences in T2* values of left sartor muscle(Z=-2.971,P=0.003).There was no statistical significance in PDFF value of skeletal muscle of thigh in different BMI groups(P>0.05),but there were statistically significant differences in T2* value of left and right quadriceps muscle,hamstring muscle and adductor muscle(H=9.542-24.495,all P<0.05).There was a moderate positive correlation between age and PDFF value of thigh skeletal muscle(r=0.635,P<0.01),but a slight negative correlation with T2* value of left and right quadriceps,hamstring and sarcoleus(r=-0.451--0.189,all P<0.01).There was a slight positive correlation between BMI and T2* values of thigh skeletal muscle(r=0.317,P<0.01).There was a moderate negative correlation between the PDFF value and T2* value of all thigh skeletal muscles(r=-0.749--0.624,P<0.01).The PDFF and T2* values of the front and back thigh muscles(quadriceps,hamstring)were most significantly correlated with age and BMI.Conclusion PDFF based on MRI can reflect the age-related changes in the microenvironment of thigh skeletal muscle,and is a potential imaging biological marker for accurate and non-invasive quantitative evaluation of thigh skeletal muscle aging.
2.Adrenal pheochromocytoma impacts three main pathways:cysteine-methionine,pyrimidine,and tyrosine metabolism
LAI CHONG ; YANG QINGLING ; ZHANG YUNUO ; GONG RENJIE ; WANG MAJIE ; LI JIANKANG ; LAI MAODE ; SUN QINGRONG
Journal of Zhejiang University. Science. B 2024;25(5):410-421
Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.
3.Activin and Hepatocyte Growth Factor Promotes Colorectal Cancer Stemness and Metastasis through FOXM1/SOX2/CXCR4Signaling
Hong PENG ; Ting YE ; Lei DENG ; Xiaofang YANG ; Qingling LI ; Jin TONG ; Jinjun GUO
Gut and Liver 2024;18(3):476-488
Background/Aims:
Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear.
Methods:
In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored.
Results:
Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133 + subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells.Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis.
Conclusions
Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.
4.Value of serum chitinase-3-like protein 1 in predicting the risk of decompensation events in patients with liver cirrhosis
Hang YANG ; Lili ZHAO ; Ping HAN ; Qingling CHEN ; Jun WEN ; Jie LIU ; Xiaojing CHENG ; Jia LI
Journal of Clinical Hepatology 2023;39(7):1578-1585
Objective To investigate the value of serum chitinase-3-like protein 1 (CHI3L1) in predicting the risk of decompensation events in patients with liver cirrhosis, since prediction of decompensation events and adoption of active preventive measures are the key to improving the survival time of patients with liver cirrhosis. Methods A case-control study was conducted for 305 patients with liver cirrhosis who were diagnosed and treated in Tianjin Second People's Hospital from January 2019 to May 2021, among whom there were 200 patients with compensated liver cirrhosis and 105 patients with decompensated liver cirrhosis at baseline. According to whether decompensation events occurred within 1 year, the 305 patients with liver cirrhosis were divided into decompensation group with 79 patients and non-decompensation group with 226 patients; according to whether decompensation events occurred for the first time within 1 year, the 200 patients with compensated liver cirrhosis were divided into first-time decompensation group with 43 patients and non-first-time decompensation group with 157 patients. The independent samples t -test or the Mann-Whitney U test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test or the chi-square test was used for comparison of categorical data between groups. The binary logistic regression analysis was used to investigate the association between each variable and decompensation events; the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to investigate the value of each variable in predicting decompensation events, and the maximum value of Youden index was used to determine the optimal cut-off value. Results The patients who experienced decompensation events within 1 year had a significantly higher baseline serum level of CHI3L1 than those who did not experience such events [243.00 (136.00-372.00) ng/mL vs 117.50 (67.75-205.25) ng/mL, U =4720.500, P < 0.001], and the patients who experienced decompensation events for the first time within 1 year had a significantly higher baseline serum level of CHI3L1 than those who did not experience such events [227.98 (110.00-314.00) ng/mL vs 90.00 (58.00-168.50) ng/mL, U =1 681.500, P < 0.001]. Patients with cirrhosis with higher baseline CHI3L1 levels had an increased risk of decompensation events within 1 year ( OR =1.004, 95% CI : 1.002-1.006, P < 0.001); Patients with compensated cirrhosis with higher baseline serum CHI3L1 levels had an increased risk of first decompensated event within 1 year ( OR =1.006, 95% CI : 1.003-1.008, P < 0.001). The baseline serum level of CHI3L1 had an AUC of 0.751 in predicting the risk of first-time decompensation events, with a sensitivity of 90.7% and a specificity of 55.4% at the optimal cut-off value of 95.5 ng/mL. The predictive model based on the combination of serum CHI3L1 level and Child-Pugh class had an AUC of 0.809, with a sensitivity of 72.1% and a specificity of 77.1% at the maximum value of Youden index. Conclusion Serum CHI3L1 level can be used as an effective predictive factor for the risk of first-time decompensation events in patients with compensated liver cirrhosis, and its combination with Child-Pugh class shows a higher predictive value.
5.MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axis via downregulating PTEN.
Ke WEI ; Jiwen SHI ; Yuhan XIAO ; Wenrui WANG ; Qingling YANG ; Changjie CHEN
Journal of Southern Medical University 2023;43(7):1081-1092
OBJECTIVE:
To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects.
METHODS:
Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice.
RESULTS:
Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis.
CONCLUSION
Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.
Humans
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Animals
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Mice
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MicroRNAs/metabolism*
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Cell Line, Tumor
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Cell Proliferation/physiology*
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Mice, Nude
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Cell Movement/physiology*
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Colorectal Neoplasms/pathology*
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Luciferases/metabolism*
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Gene Expression Regulation, Neoplastic
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PTEN Phosphohydrolase/metabolism*
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Chemokine CXCL12/metabolism*
6.Eligibility of C-BIOPRED severe asthma cohort for type-2 biologic therapies.
Zhenan DENG ; Meiling JIN ; Changxing OU ; Wei JIANG ; Jianping ZHAO ; Xiaoxia LIU ; Shenghua SUN ; Huaping TANG ; Bei HE ; Shaoxi CAI ; Ping CHEN ; Penghui WU ; Yujing LIU ; Jian KANG ; Yunhui ZHANG ; Mao HUANG ; Jinfu XU ; Kewu HUANG ; Qiang LI ; Xiangyan ZHANG ; Xiuhua FU ; Changzheng WANG ; Huahao SHEN ; Lei ZHU ; Guochao SHI ; Zhongmin QIU ; Zhongguang WEN ; Xiaoyang WEI ; Wei GU ; Chunhua WEI ; Guangfa WANG ; Ping CHEN ; Lixin XIE ; Jiangtao LIN ; Yuling TANG ; Zhihai HAN ; Kian Fan CHUNG ; Qingling ZHANG ; Nanshan ZHONG
Chinese Medical Journal 2023;136(2):230-232
7.Mechanism of Chaihu Shugansan in Treatment of Functional Dyspepsia in Rats Based on Mitophagy and Pink1/Parkin Signaling Pathway
Xiangxiang WANG ; Yujiao WANG ; Li LI ; Qingling JIA ; Kailin JIANG ; Keming YANG ; Jianghong LING
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(2):45-51
ObjectiveTo investigate the mechanism of Chaihu Shugansan in the treatment of functional dyspepsia in rats based on mitophagy and PTEN-induced kinase 1 (Pink1)/E3 ubiquitin ligase (Parkin). signaling pathway. MethodAccording to the principle of random grouping, 40 SD rats were assigned into a normal group, a model group, a Chaihu Shugansan group, and a positive drug (domperidone) group, with 10 rats in each group. The rats in other groups except the normal group received tail-clamping stimulation to replicate the model of functional dyspepsia. After each time of stimulation, the rats in the normal, model, Chaihu Shugansan, and positive drug groups were administrated with normal saline, normal saline, Chaihu Shugansan (4.8 g·kg-1), and an aqueous solution of domperidone (4.5 mg·kg-1), respectively. After 28 days of modeling, the gastric emptying rate and the small intestine propulsion rate of the rats in each group were measured and the tissue samples were collected. Hematoxylin-eosin (HE) staining was employed for observation of damage in gastric antrum tissue, and transmission electron microscopy (TEM) for ultrastructural observation of gastric interstitial cells of Cajal (ICCs). Immunofluorescence co-localization was adopted to observe the expression of cytochrome c oxidase (COX Ⅳ) and Parkin. Western blot was employed to determine the expression levels of microtubule-associated protein 1, light chain 3 (LC3), and the mitophagy-associated proteins prohibitin2 (PHB2), Pink1, Parkin, and ubiquitin-specific protease 30 (USP30). ResultCompared with the normal group, the modeling decreased the gastric emptying rate and the small intestine propulsion rate (P<0.05). Compared with the model group, Chaihu Shugansan increased the gastric emptying rate and the small intestine propulsion rate (P<0.05). The results of TEM showed that Chaihu Shugansan reduced the swelling degree of mitochondria in gastric antrum tissue. Compared with the normal group, the modeling increased the fluorescence intensity of Parkin in mitochondria (P<0.01), while such increase can be alleviated by Chaihu Shugansan (P<0.01). Western blotting results showed that compared with the normal group, the modeling up-regulated the protein levels of LC3, Pink1, Parkin, and PHB2 (P<0.05, P<0.01) and down-regulated the protein level of USP30 (P<0.01). Compared with the model group, Chaihu Shugansan down-regulated the protein levels of LC3, Pink1, Parkin, and PHB2 (P<0.05, P<0.01) and up-regulated the protein level of USP30 (P<0.01). ConclusionChaihu Shugansan may treat functional dyspepsia by blocking the Pink1/Parkin signaling pathway to inhibit excessive mitochondrial autophagy in ICCs.
8.Comparative study of white matter diffusion properties in vulnerable and resistant individuals to continuous attention after short term sleep deprivation
Chen WANG ; Lin WU ; Xing TANG ; Xiuhua LYU ; Junqiang ZHU ; Qingling YANG ; Peng FANG ; Ziliang XU ; Yongqiang XU ; Leilei LI ; Yuanqiang ZHU ; Minwen ZHENG
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(4):326-332
Objective:To investigate the differences of white matter diffusion properties between vulnerable and resistant individuals to continuous attention after sleep deprivation.Methods:According to the psychomotor vigilance test performance before and after sleep deprivation, the participants were divided into the vulnerable group( n=24) and resistant group( n=25). All participants underwent diffusion tensor imaging (DTI) scans.Tract based spatial statistics(TBSS) was used to compare fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity(AD), radial diffusivity(RD) maps between the two groups.Spearman correlation analysis was conducted by SPSS 24.0 to investigate the relationships between the altered DTI metrics and PVT task performance. Results:(1) Compared with resistant group, FA value of vulnerable group decreased in the body of corpus callosum(x, y, z=-8, 9, 25, t=-7.855), right superior longitudinal fasciculus(x, y, z=-39, -7, 26, t=-6.252), bilateral anterior limb of internal capsule(x, y, z=-13, 8, 13, t=-5.235; x, y, z=12, 8, 3, t=-5.024) and right posterior thalamic radiation(x, y, z=-26, -56, 17, t=-5.469)(TFCE corrected, P<0.05, cluster size≥50 voxel). (2) Compared with resistant group, MD value of vulnerable group increased in the body of corpus callosum(x, y, z=-3, -6, 26, t=7.613), right superior longitudinal fasciculus(x, y, z=-31, -19, 38, t=5.314), bilateral anterior limb of internal capsule(x, y, z=-16, 7, 8, t=6.898; x, y, z=15, 5, 7, t=6.652), splenium of corpus callosum(x, y, z=27, -53, 17, t=6.541), and AD value increased in the right superior longitudinal fasciculus(x, y, z=-33, -19, 39, t=4.892), splenium of corpus callosum(x, y, z=-22, -49, 21, t=5.450), genu of corpus callosum(x, y, z=4, 26, 0, t=4.332), as well as RD value increased in the right superior corona radiata(x, y, z=-17, 1, 33, t=7.558), body of corpus callosum(x, y, z=4, -8, 26, t=6.699), right anterior limb of internal capsule(x, y, z=-12, 7, 3, t=5.212) (TFCE corrected, P<0.05, cluster size≥50 voxel). (3) Correlational analysis revealed that the negative correlations were found between PVT task performance and the FA value in the right superior longitudinal fasciculus( r=-0.492, P<0.001), right anterior limb of internal capsule( r=-0.510, P<0.001), right posterior thalamic radiation( r=-0.502, P<0.001) and body of corpus callosum( r=-0.464, P<0.001). The positive correlations were found between PVT task performance and the MD value in the body of corpus callosum( r=0.500, P<0.001), right superior longitudinal fasciculus( r=0.499, P<0.001), splenium of corpus callosum( r=0.462, P<0.001), right anterior limb of internal capsule( r=0.471, P<0.001), and AD value in right superior longitudinal fasciculus( r=0.643, P<0.001), as well as RD value in right superior corona radiate( r=0.498, P<0.001) (Bonferroni corrected, P<0.003). Conclusion:Differences in the microstructural characteristics of white matter fiber tracts in specific brain regions may constitute the potential neuropathological basis for the phenotypes of vulnerable and resistant individuals to continuous attention after sleep deprivation.
9.Application of staged rehabilitation training in ICU patients receiving mechanical ventilation under the framework of quantitative assessment strategy
Qingling WANG ; Jingyu HE ; Xiaolong YANG ; Lanlan LIU ; Xin GUO
Chinese Journal of Modern Nursing 2021;27(18):2442-2448
Objective:To explore the effects of staged rehabilitation training on the dyspnea, motor function, and lung function of mechanically ventilated patients with severe pneumonia in ICU under the framework of a quantitative assessment strategy, and provide a scientific basis for clinical work.Methods:Totally 104 mechanically ventilated patients with severe pneumonia in ICU at Xuanwu Hospital, Capital Medical University from April 2018 to April 2020 were selected by the convenient sampling method, and divided into the control group and the observation group according to the random number table, with 52 patients in each group. Patients in the control group received conventional rehabilitation training, while patients in the observation group underwent staged rehabilitation training under the framework of quantitative assessment strategy on the basis of the training provided to the control group. The incidence of complications, mechanical ventilation time, ICU stay time, compliance time of adequate enteral nutrition, and nursing satisfaction were compared between the two groups of patients. The dyspnea scores, Medical Research Council (MRC) score, motor function, and lung function [peak respiratory flow (PEF) , forced expiratory volume in 1 s (FEV 1) , FEV 1/forced vital capacity (FVC) ] of the two groups were compared when they were admitted into the ICU, transferred from the ICU, and discharged from the hospital. Results:The mechanical ventilation time, ICU stay time, and compliance time of adequate enteral nutrition in the observation group were shorter than those in the control group, and the differences were statistically significant ( P<0.01) . The PEF, FEV 1, FEV 1/FVC, and motor function in the observation group were higher than those in the control group, and the MRC score was lower than that in the control group, with statistically significant differences ( P<0.05) . The incidence of complications in the observation group was 9.62% (5/52) , which was lower than 25.00% (13/52) in the control group, and the difference was statistically significant ( P<0.05) . The nursing satisfaction in the observation group was higher than that in the control group, and the difference was statistically significant ( P<0.01) . Conclusions:In the management of mechanically ventilated patients with severe pneumonia in the ICU, staged rehabilitation training under the framework of quantitative assessment strategies can reduce the symptoms of dyspnea, improve lung function, enhance mobility, and reduce the risk of complications through targeted and standardized training, which also helps to speed up disease recovery.
10.Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis
Zheng LIU ; Jianjun CHEN ; Lei CHENG ; Huabin LI ; Shixi LIU ; Hongfei LOU ; Jianbo SHI ; Ying SUN ; Dehui WANG ; Chengshuo WANG ; Xiangdong WANG ; Yongxiang WEI ; Weiping WEN ; Pingchang YANG ; Qintai YANG ; Gehua ZHANG ; Yuan ZHANG ; Changqing ZHAO ; Dongdong ZHU ; Li ZHU ; Fenghong CHEN ; Yi DONG ; Qingling FU ; Jingyun LI ; Yanqing LI ; Chengyao LIU ; Feng LIU ; Meiping LU ; Yifan MENG ; Jichao SHA ; Wenyu SHE ; Lili SHI ; Kuiji WANG ; Jinmei XUE ; Luoying YANG ; Min YIN ; Lichuan ZHANG ; Ming ZHENG ; Bing ZHOU ; Luo ZHANG
Allergy, Asthma & Immunology Research 2020;12(2):176-237
The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult
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Asian Continental Ancestry Group
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Biomarkers
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China
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Consensus
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Diagnosis
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Diagnosis, Differential
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Drug Therapy
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Eosinophils
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Epidemiology
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Epigenomics
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Genetics
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Humans
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Hypersensitivity
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Inflammation
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International Agencies
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Medical Staff
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Neck
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Phenotype
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Precision Medicine

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