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The effect of orbital radiation therapy on thyroid-associated orbitopathy complicated with dysthyroid

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 359-364 doi: 10.1007/s11684-017-0528-5

摘要：

Thyroid-associated orbitopathy (TAO) is an inflammatory autoimmune disorder. The most serious complication of TAO is dysthyroid optic neuropathy (DON), which can lead to permanent vision loss because of volume expansion in the orbital apex. Orbital radiation therapy (ORT) is an anti-inflammatory treatment used in the treatment of active TAO. Clinical studies support radiotherapy as having a modest effect on DON, and early radiotherapy may protect against disease progression to DON. Current studies suggest that radiotherapy is generally safe. However, risks still exist in some cases. The possible effects of radiotherapy on TAO, especially complicated with DON, are reviewed. The effects of radiotherapy on DON are not completely known, and evidence from standardized, prospective, and multicenter clinical trials is still lacking.

关键词： thyroid-associated orbitopathy     dysthyroid optic neuropathy     orbital radiation therapy    

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Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 113-117 doi: 10.1007/s11684-014-0310-x

摘要：

Papillary thyroid carcinoma (PTC) is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was identified in Europeans by conducting a genome-wide association study, and a strong association signal with PTC was observed in rs944289 and NKX2-1 (located at the 14q13.3 locus), which was probably the genetic risk factor of PTC. This study aimed to examine the association of this gene with PTC in Chinese. A total of 354 patients with PTC and 360 healthy control subjects from the Han population of Northern China were recruited in the study. These individuals were genotyped to determine rs12589672, rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was obtained (C vs. T, P=0.027, OR=1.264, 95% CI=1.026-1.557; and C/C-C/T vs. T/T, P=0.034, OR=1.474, 95% CI=1.028-2.112). Conducting a subgroup analysis, we found a marginal difference in the allele frequency distribution of rs944289 (adjusted P=0.062) between the patients with PTC and multi-nodular goiter and the control subjects. We also observed an interaction (P=0.029; OR=2.578, 95% CI=1.104-6.023) between rs944289 and diabetes in patients with PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the Han population of Northern China, but no clear association was observed in either of the tag single nucleotide polymorphisms of NKX2-1.

关键词： NKX2-1     papillary thyroid carcinoma     the Han population of Northern China     association    

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甲状腺乳头状癌菌群失调及与肿瘤信号通路异常的相关性研究 Article

喻爽, 丁彦强, 王雪洁, Siu Kin Ng, 曹思婷, 刘伟鑫, 郭朱明, 谢宇彬, 洪澍彬, 许丽霞, 李晓星, 李杰, 吕伟明, 彭穗, 李延兵, 沈祖尧, 于君, 肖海鹏

《工程（英文）》 2023年 第28卷 第9期   页码 179-192 doi: 10.1016/j.eng.2023.01.007

摘要：

研究表明微生态失调在多种肿瘤的发生发展中起至关重要的作用。然而，对于甲状腺肿瘤中细菌是否参与肿瘤的发生仍不清楚。本研究中，我们旨在探索甲状腺组织中的菌群特征及其对甲状腺乳头状癌（PTC）的作用。我们同时对 340 例PTC和甲状腺良性结节 （BTN） 患者的肿瘤组织及其邻近正常组织进行菌群分析和转录组测序。在PTC、BTN及其邻近无肿瘤组织中鉴定出明显不同的菌群特征。我们通过免疫组化染色、细菌原位杂交和电镜观察验证了甲状腺组织内细菌的存在。与BTN相比，我们发现在PTC中有17个菌属存在显著丰度差异，其中PTC中富集菌Rhodococcus、Neisseria、Streptococcus、Halomonas和Devosia存在促癌作用；以及丰度降低的Amycolatopsis则可能有抑癌作用。这些丰度存在明显差异的细菌可以鉴别PTC组织（PTC-T）与BTN组织（BTN-T），曲线下面积（AUC）为81.66%。微生物网络分析表明，PTC组织内细菌间的相互关联性高于BTN组织。同时，在合并桥本甲状腺炎组织的PTC中发现与免疫相关的菌属（Erwinia、Bacillus 和 Acinetobacter）明显富集。此外，我们联合转录组测序分析提示PTC富集菌与肿瘤相关信号通路的关键基因如BRAF、KRAS、IRAK4、CTNNB1、PIK3CA、MAP3K7 和 EGFR存在正相关性。总的来说，我们的研究结果表明，甲状腺肿瘤组织内存在菌群失调，并可能通过肿瘤相关信号通路参与PTC的发生。

关键词： 甲状腺乳头状癌     甲状腺良性结节     细菌     转录组     桥本甲状腺炎    

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Analyses of levels of thyroid hormones and its receptor expression in puerperants and newborns from an

JU Ying, CHEN Lan, JIANG Qi, YANG Kedi, CHEN Xuemin, XU Guojian, LI Liping

《医学前沿（英文）》 2008年 第2卷 第3期   页码 276-282 doi: 10.1007/s11684-008-0052-8

摘要： In this study, the serum levels, including thyroid hormones free triiodothyronine (FT), free thyroxine(FT),thyroid stimulating hormone(TSH)among the subjects from the exposed group ( = 48) and the control group ( = 45) were detected by immuno radiometric assay (IRMA). The expression levels of TR?1, TR?1, TSHR mRNA in placentas and umbilical cords were detected by fluorescent quantitative real-time PCR (FQ-PCR). The correlations between the thyroid hormone levels in maternal serum and umbilical serum, and between the expression levels of its receptors mRNA in placentas and umbilical cords were determined. We found that the FT levels of both maternal serum and umbilical cord serum in the exposed group were lower than those in the control ( < 0.05). However, the increased TSH levels in the exposed group had statistically significance compared to those in the control group ( < 0.05). The TR?1 and TR?1 mRNA levels both in placentas and umbilical cords in the exposed group were lower than those in the control group ( < 0.05 and 0.01). However, the TSHR mRNA levels in the exposed group were significantly different compared to those in the control group ( < 0.01). The serum FT4 and TSH levels of parturient women were positively correlated with those of the newborns in both groups ( < 0.05 and 0.01). The mRNA levels of TR?1, TR?1 and TSHR in the placentas were positively correlated with those in umbilical cords in both groups ( < 0.01). The findings suggest that some environmental pollutants existing in the electronic waste (e-waste) dismantling region may affect the health of local parturient women and newborns, representing changes both in serum levels of thyroid hormones and in mRNA expression of its receptors.

关键词： control     immuno radiometric     FT     TSH     exposed    

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mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid

《医学前沿（英文）》 doi: 10.1007/s11684-023-0999-5

摘要： Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial–to–mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.

关键词： thyroid carcinoma     mesenchymal stem cell     extracellular vesicle     GTF2I     FAT1     CDK4    

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Crk-associated substrate, vascular smooth muscle and hypertension

TANG Dale

《医学前沿（英文）》 2008年 第2卷 第4期   页码 323-331 doi: 10.1007/s11684-008-0062-6

摘要： Hypertension is characterized by vascular smooth muscle constriction and vascular remodeling involving cell migration, hypertrophy and growth. Crk-associated substrate (CAS), the first discovered member of the adapter protein CAS family, has been shown to be a critical cellular component that regulates various smooth muscle functions. In this review, the molecular structure and protein interactions of the CAS family members are summarized. Evidence for the role of CAS in the regulation of vascular smooth muscle contractility is presented. Contraction stimulation induces CAS phosphorylation on Tyr-410 in arterial smooth muscle, creating the binding site for the Src homology (SH) 2/SH3 protein CrkII, which activates neuronal Wiskott-Aldrich syndrome protein (N-WASP)-mediated actin assembly and force development. The functions of CAS in cell migration, hypertrophy and growth are also summarized. Abelson tyrosine kinase (Abl), c-Src, focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (PYK2), protein tyrosine phosphatase-proline, glutamate, serine and threonine sequence protein (PTP-PEST) and SHP-2 have been documented to coordinate the phosphorylation and dephosphorylation of CAS. The downstream signaling partners of CAS in the context of cell motility, hypertrophy, survival and growth are also discussed. These new findings establish the important role of CAS in the modulation of vascular smooth muscle functions. Furthermore, the upstream regulators of CAS may be new biologic targets for the development of more effective and specific treatment of cardiovascular diseases such as hypertension.

关键词： Contraction stimulation     phosphatase-proline     molecular structure     discovered     hypertension    

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Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during

Wei Wang, Shuqin Jiang, Zhirui Cui, Xiangyang Luo, Lingli Shi, Heli Zheng

《医学前沿（英文）》 2018年 第12卷 第5期   页码 580-585 doi: 10.1007/s11684-017-0585-9

摘要：

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5–3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.

关键词： therapeutic     idiopathic short-stature children     free T4     the first year     recombinant human growth hormone    

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Atypical pituitary hormone–target tissue axis

《医学前沿（英文）》 2023年 第17卷 第1期   页码 1-17 doi: 10.1007/s11684-022-0973-7

摘要： A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an “atypical pituitary hormone–target tissue axis.” This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the “atypical pituitary hormone–target tissue axis” could enable the identification of novel therapeutic targets for metabolic diseases.

关键词： thyroid-stimulating hormone     follicle-stimulating hormone     luteinizing hormone     adrenocorticotrophic hormone     prolactin    

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Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

《医学前沿（英文）》 2022年 第16卷 第3期   页码 459-466 doi: 10.1007/s11684-021-0841-x

摘要： Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

关键词： Fanconi anemia     aplastic anemia     hematologic malignancy     germline predisposition    

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New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse

《医学前沿（英文）》 2022年 第16卷 第5期   页码 714-722 doi: 10.1007/s11684-021-0888-8

摘要： A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01–1.55) and 1.35 (95% CI 1.07–1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07–2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

关键词： metabolic dysfunction-associated fatty liver disease     non-alcoholic fatty liver disease     fibrosis score     brachial-ankle pulse wave velocity     albuminuria    

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Transparent exopolymer particles (TEPs)-associated protobiofilm: A neglected contributor to biofouling

《环境科学与工程前沿（英文）》 2021年 第15卷 第4期 doi: 10.1007/s11783-020-1361-7

摘要：

• Bacteria could easily and quickly attached onto TEP to form protobiofilms.

关键词： Transparent exopolymer particles (TEPs)     TEP-protobiofilm     Bacteria attachment     Biofouling of membrane    

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年 第17卷 第2期   页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug resistance    

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Risk factors for ventilator-associated pneumonia among patients undergoing major oncological surgery

null

《医学前沿（英文）》 2017年 第11卷 第2期   页码 239-246 doi: 10.1007/s11684-017-0509-8

摘要：

Patients undergoing major oncological surgery for head and neck cancer (SHNC) have a particularly high risk of nosocomial infections. We aimed to identify risk factors for ventilator-associated pneumonia (VAP) in patients undergoing SHNC. The study included 465 patients who underwent SHNC between June 2011 and June 2014. The rate of VAP, risk factors for VAP, and biological aspects of VAP were retrospectively evaluated. The incidence of VAP was 19.6% (n=95) in patients who required more than 48 h of mechanical ventilation. Staphylococcus (37.7%), Enterobacteriaceae (32.1%), Pseudomonas(20.8%), and Haemophilus (16.9%) were the major bacterial species that caused VAP. The independent risk factors for VAP were advanced age, current smoking status, chronic obstructive pulmonary disease, and a higher simplified acute physiology score system II upon admission. Tracheostomy was an independent protective factor for VAP. The median length of stay in the ICU for patients who did or did not develop VAP was 8.0 and 6.5 days, respectively (P=0.006). Mortality among patients who did or did not develop VAP was 16.8% and 8.4%, respectively (P<0.001). The potential economic impact of VAP was high because of the significantly extended duration of ventilation. A predictive regression model was developed with a sensitivity of 95.3% and a specificity of 69.4%. VAP is common in patients who are undergoing SHNC and who require more than 48 h of mechanical ventilation. Therefore, innovative preventive measures should be developed and applied in this high-risk population.

关键词： ventilator-associated pneumonia (VAP)     pneumonia     risk factors     surgery for head and neck cancer (SHNC)    

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Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy

Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie

《医学前沿（英文）》 2018年 第12卷 第6期   页码 667-677 doi: 10.1007/s11684-017-0583-y

摘要： Platelets have long been known to play critical roles in hemostasis by clumping and clotting blood vessel injuries. Recent experimental evidence strongly indicates that platelets can also interact with tumor cells by direct binding or secreting cytokines. For example, platelets have been shown to protect circulating cancer cells in blood circulation and to promote tumor metastasis. In-depth understanding of the role of platelets in cancer progression and metastasis provides promising approaches for platelet biomimetic drug delivery systems and functional platelet-targeting strategies for effective cancer treatment. This review highlights recent progresses in platelet membrane-based drug delivery and unique strategies that target tumor-associated platelets for cancer therapy. The paper also discusses future development opportunities and challenges encountered for clinical translation.

关键词： platelet-mimicking delivery systems     tumor-associated platelets     cancer therapy     EPR effect    

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Advances on immune-related adverse events associated with immune checkpoint inhibitors

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

《医学前沿（英文）》 2021年 第15卷 第1期   页码 33-42 doi: 10.1007/s11684-019-0735-3

摘要： Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

关键词： cancer     immunotherapy     immune checkpoint inhibitors     immune-related adverse events     review    

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标题 作者 时间 类型 操作

The effect of orbital radiation therapy on thyroid-associated orbitopathy complicated with dysthyroid

null

期刊论文

Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern

null

期刊论文

甲状腺乳头状癌菌群失调及与肿瘤信号通路异常的相关性研究

喻爽, 丁彦强, 王雪洁, Siu Kin Ng, 曹思婷, 刘伟鑫, 郭朱明, 谢宇彬, 洪澍彬, 许丽霞, 李晓星, 李杰, 吕伟明, 彭穗, 李延兵, 沈祖尧, 于君, 肖海鹏

期刊论文

Analyses of levels of thyroid hormones and its receptor expression in puerperants and newborns from an

JU Ying, CHEN Lan, JIANG Qi, YANG Kedi, CHEN Xuemin, XU Guojian, LI Liping

期刊论文

mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid

期刊论文

Crk-associated substrate, vascular smooth muscle and hypertension

TANG Dale

期刊论文

Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during

Wei Wang, Shuqin Jiang, Zhirui Cui, Xiangyang Luo, Lingli Shi, Heli Zheng

期刊论文

Atypical pituitary hormone–target tissue axis

期刊论文

Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

期刊论文

New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse

期刊论文

Transparent exopolymer particles (TEPs)-associated protobiofilm: A neglected contributor to biofouling

期刊论文

Progress and challenges in RET-targeted cancer therapy

期刊论文

Risk factors for ventilator-associated pneumonia among patients undergoing major oncological surgery

null

期刊论文

Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy

Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie

期刊论文

Advances on immune-related adverse events associated with immune checkpoint inhibitors

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

期刊论文