1.Clinical significance of Endoglin in prostate cancer research
Hui YANG ; Hongyi ZHANG ; Huafeng LI ; Ganggang ZHAO
International Journal of Laboratory Medicine 2024;45(15):1887-1890
Prostate cancer is one of the most common malignant tumors in male genitourinary system,and it is one of the main causes of male death in Europe and America.The incidence of prostate cancer in our coun-try is increasing,the key of treatment of prostate cancer is early diagnosis and early treatment.Endoglin also known as endothelial glycoprotein,is the most reliable marker of endothelial cell proliferation,which is over-expressed in neovascularization.Soluble Endoglin was found in the serum of tumor patients,which can be used as an auxiliary diagnosis.Inhibition of Endoglin receptor can inhibit the formation of tumor blood vessels,which provides a basis for targeted therapy.Microvessel density marked by Endoglin is of great significance in the clinical and pathological grading of solid tumors and can be used to evaluate the prognosis.This article re-views the role of Endoglin in the pathogenesis,diagnosis,treatment and prognosis of prostate cancer.
2.Discussion on the Pathogenesis and Microcosmic Syndrome Differentiation of Spasmolytic Polypeptide Expressing Metaplasia Based on the Theory of"Spleen Deficiency and Evil Stagnation"
Xinlong LI ; Siyi LI ; Penhui YANG ; Quiyue LI ; Huafeng PAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(5):1104-1110
Gastric Precancerous Lesions(GPL)have the risk of developing gastric cancer,and Spasmolytic Polypeptide Expressing Metaplasia(SPEM)is the initial step of GPL,which has the risk of malignant progression to gastric precancerous lesions.Currently,the exploration of the pathogenesis during this metaplasia stage remains incomplete.Traditional Chinese Medicine(TCM),relying on its solid theoretical foundation and abundant resources of Chinese medicinal materials,possesses unique advantages in the prevention and treatment of GPL.Based on the theory of"spleen deficiency and evil stagnation",we conducts microcosmic syndrome differentiation analysis from the pathophysiological state,markers,and signal pathways of the disease,and proposes to invigorate the spleen and remove blood stasis.The detoxification method is used for treatment,and its feasibility is analyzed in combination with the literature,in order to provide new ideas and strategies for the TCM treatment of SPEM.
3.Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
ZOU HAI ; ZHANG MENGYU ; YANG XUE ; SHOU HUAFENG ; CHEN ZHENGLIN ; ZHU QUANFENG ; LUO TING ; MOU XIAOZHOU ; CHEN XIAOYI
Journal of Zhejiang University. Science. B 2024;25(9):756-772
Doxorubicin(DOX)is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors;however,its clinical application is limited by significant cardiotoxicity.Cynaroside(Cyn)is a flavonoid glycoside distributed in honeysuckle,with confirmed potential biological functions in regulating inflammation,pyroptosis,and oxidative stress.Herein,the effects of Cyn were evaluated in a DOX-induced cardiotoxicity(DIC)mouse model,which was established by intraperitoneal injections of DOX(5 mg/kg)once a week for three weeks.The mice in the treatment group received dexrazoxane,MCC950,and Cyn every two days.Blood biochemistry,histopathology,immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment.The results demonstrated the significant benefits of Cyn treatment in mitigating DIC;it could effectively alleviate oxidative stress to a certain extent,maintain the equilibrium of cell apoptosis,and enhance the cardiac function of mice.These effects were realized via regulating the transcription levels of pyroptosis-related genes,such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,and gasdermin D(GSDMD).Mechanistically,for DOX-induced myocardial injury,Cyn could significantly modulate the expression of pivotal genes,including adenosine monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),sirtuin 3(SIRT3),and nuclear factor erythroid 2-related factor 2(Nrf2).We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway,which plays a central role in preventing DOX-induced cardiomyocyte injury.In conclusion,the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.
4.Effect of fibrinogen on the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus
Zhijie JIAN ; Xiangrui QIAO ; Haibo LI ; Guolin YAO ; Huafeng GUO ; Hui LIU ; Yue WU ; Jian YANG ; Lele CHENG
Chinese Journal of Arteriosclerosis 2024;32(5):410-414
Aim To investigate the relationship between fibrinogen(FIB)and the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus(T2DM).Methods Hospitalized T2DM patients who underwent two or more coronary CT angiography(CCTA)examinations in the First Affiliated Hospital of Xi'an Jiaotong U-niversity from January 2015 to December 2020 were included.The subjects were divided into high FIB and low FIB groups according to the median of FIB.The differences in the progression of coronary plaque stenosis rate and other clini-cal characteristics were compared between the two groups,and the relationship between FIB level and the progression of coronary plaque stenosis rate was analyzed by Spearman's correlation analysis and Logistic regression.Results A total of 145 patients were included,73 in the high FIB group and 72 in the low FIB group at baseline,with a median follow-up time of 25(18,40)months between CCTA.The age,proportion of women,and the progression of coronary plaque ste-nosis rate were higher in the high FIB group than those in the low FIB group,and the differences were statistically signifi-cant(P<0.05).FIB level was positively correlated with the change in coronary plaque stenosis rate(r2=0.308,P<0.001).Multivariate Logistic regression analysis showed that FIB level was a risk factor for the progression of coronary plaque stenosis rate in patients with T2DM(OR=5.25,95%CI:1.97~14.02,P<0.001),after adjusting for age,sex and other clinical risk factors.Conclusion High baseline FIB level is an independent risk factor for the progression of coronary plaque stenosis rate in patients with T2DM,and monitoring FIB level is beneficial to cardiovascular risk stratifica-tion in patients with T2DM.
5.The Inheritance of Chinese Narrative Medicine Practice to the Traditional Chinese Medicine’s Life Wisdom
Xiaolin YANG ; Zhiting LIU ; Huafeng WANG
Chinese Medical Ethics 2023;36(11):1180-1186
Starting from the inheritance and development of Chinese philosophy of life and Traditional Chinese Medicine (TCM) wisdom through the Chinese narrative medicine practice, this paper discussed the inheritance and correspondence relationship between the text reading ability in Chinese narrative medicine practice and the "four diagnostic" in TCM wisdom, narrative regulation and the "mind-body philosophy" in TCM, as well as the narrative wisdom and the "Tao produces one" in the Chinese philosophy of life. By analyzing the stories of contemporary doctors’ practice of narrative wisdom, this paper clarified that the Chinese narrative medicine system is a new model of medical education and clinical practice constructed by absorbing the essence elements of Chinese traditional life wisdom and TCM culture, and integrating the concept of western narrative medicine. It advocated for Chinese scholars to actively build the discipline of "narrative traditional Chinese medicine", constantly translate and introduce the achievements to foreign countries, and create a good narrative ecology of TCM.
6.Comprehensive evaluation of salt-alkali tolerance of rice germplasms at germination and seedling stages and analysis of salt-tolerant genes.
Pingyong SUN ; Wuhan ZHANG ; Fu SHU ; Qiang HE ; Li ZHANG ; Zhuhong YANG ; Zhirong PENG ; Yun XIE ; Huafeng DENG
Chinese Journal of Biotechnology 2022;38(1):252-263
Cultivating salt-alkali tolerant rice varieties is one of the important ways to meet the increasing food demand of growing global population. In this study, twenty-one rice germplasms with different salt-alkali tolerance were treated with six salt-alkali concentrations at germination and seedling stages. The germination potential, germination rate, shoot length, root length, root number, fresh weight of shoot and seedlings were measured. The average value of salt damage rate was used to evaluate the salt-alkali tolerance. As the salt-alkali concentration increases, the inhibition on seed germination and growth became more obvious. Upon treatment with 1% NaCl plus 0.25% NaHCO3, the salt damage rate of germination rate has the largest variation, ranging from 0% to 89.80%. The salt damage rate of each trait shows a similar trend at all concentrations. Four germplasm resources with strong salt-alkali tolerance (Dajiugu, Nippobare, Mowanggu and 02428) and 7 sensitive germplasms were screened. The salt-tolerant gene sequence of 4 salt-alkali tolerant varieties and 3 sensitive germplasms were analyzed. OSHAL3 and OsRR22 were identical among the 7 germplasms, but SKC1 and DST showed clear variations between the salt-alkali tolerant and sensitive germplasms. Besides the salt-alkali tolerant germplasm resources, this study can also serve as a reference for mining of genes involved in salt-alkali tolerance and breeding of salt-alkali tolerant rice varieties.
Alkalies
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Germination
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Oryza/genetics*
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Plant Breeding
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Seedlings/genetics*
7.Ectopic replantation of forearm, wrist and palm in a destructive injury of a young child: A case report
Chenguang LIU ; Shuqiang XIE ; Huafeng ZHANG ; Ruifu YANG ; Zhaosen WU ; Qiqiang DONG ; Dahai YIN ; Weiqiang LIU ; Peng WANG ; Jianxi HOU
Chinese Journal of Microsurgery 2022;45(5):585-587
Reports a case admitted in the Ward I of Department of Surgery of Zhengzhou Renji Hospital in June 2017. A young child who suffered destructive injury of left forearm, wrist and palm with severed 3rd-5th fingers. Tendon and neurovascular repairs of forearm, wrist and palm were performed with pedicled abdomina flap and the 3rd-5th fingers ectopic replantation in Phase I surgery. In the Phase II surgery, the abdomina flap division was carried out. The replantation of severed fingers after ectopic replantation and the reconstruction of foot defect with free anterolateral thigh flap(ALTF) were carried out in Phase III surgery. In Phase IV surgery, fingers functional reconstruction and foot flap thinning were performed. Four years after surgery, the thumb oppositions to middle, ring and little fingers could be completed, with slightly limitations. The appearance and texture of transferred foot flap were good, and the child could walk and run almost normally.
8.Real-world outcomes of niraparib treatment in patients with ovarian cancer: the first observational multicenter study in China
Jin LI ; Jianhua YANG ; Huafeng SHOU ; Lin ZHANG ; Xiaohong HUANG ; Xuedong TANG ; Fei ZHENG ; Fang LIU ; Xiaohua WU
Journal of Gynecologic Oncology 2022;33(S1):S11-
Objective:
The objective of this study was to present the real-world patients’ portrait, and the results of niraparib treatment in China.
Methods:
This study included 142 patients treated with niraparib from 8 hospitals in China between December 2018 and September 2021. Patients’ characteristics were summarized. The efficacy and safety in first-line maintenance (1L-M), platinum-sensitive recurrence maintenance (PSR-M), and treatment for ovarian cancer were evaluated. Survival outcomes and the factors influencing progression-free survival (PFS) were estimated.
Results:
The 93 patients received Niraparib as 1L-M, 31 as PSR-M and 18 as salvage. BRCA status was wild type or unknown in 87.3% of patients. With a median follow-up time of 8.7 months, the median PFS (mPFS) for 1L-M has not yet been reached, and the mPFS for PSR-M and salvage therapy was 10.5 and 5.7 months, respectively. Responses to last chemotherapy and cancer antigen 125 value before taking niraparib were 2 important factors affecting PFS among 1L and PSR patients. The 12.7% (18/142) of patients experienced grade ≥3 hematologic adverse events and 23.2% experienced dose adjustment. It was noteworthy that when the interval of chemotherapy and niraparib <21 days, the incidence of grade ≥3 adverse events increased significantly (p=0.0355).
Conclusion
Generally, niraparib was effective and well tolerated, which was consistent with the results of prospective trials. However, in real world, it was more inclined to use niraparib in late-line treatment without genetic testing.
9.The texture analysis of MRI diffusion-weighted imaging for predicting prognosis of neonatal hypoglycemic encephalopathy
Ruizhu WANG ; Yanli XI ; Huafeng XU ; Ming YANG ; Xin WANG ; Feng YANG ; Yunsu ZOU ; Yaojin SUN
Chinese Journal of General Practitioners 2022;21(4):367-375
Objective:To investigate the prognostic value of texture analysis of MRI diffusion weighted imaging (DWI) for neonatal hypoglycemic encephalopathy (HE).Methods:The clinical data and MRI data of 119 patients with neonatal HE admitted to Children′s Hospital of Nanjing Medical University from July 2013 to September 2020 were retrospectively analyzed. The children were followed up to 7—8 months and scored by Bayley scales of infant and toddler development. According to the overall development index, the children were divided into three groups: normal group (≥85, group A, n=42), mild developmental retardation group (70-84, group B, n=46) and developmental retardation group (≤69, group C, n= 31). The whole brain region (except sulcus and cisterna) was delineated as region of interest (ROI) by LIFEx 3.4 software in MRI apparent diffusion coefficient images. A total of 37 parameters were calculated automatically by the software, The clinical data, including gender, gestational age, age at MRI scan, birth weight, mode of delivery, history of asphyxia at birth, maternal preeclampsia or diabetes, minimum blood glucose, duration of hypoglycemia, neonatal behavioral neurological assessment (NBNA), presence or absence of polycythemia); the texture parameters, including histogram, volume, gray level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), neighborhood gray tone difference matrix (NGTDM), gray level size zone matrix (GLSZM), in the three groups were analyzed; and the diagnostic efficacy of clinical parameters and texture parameters was analyzed. Multivariate Logistic regression was used to analyze statistically significant clinical parameters and texture parameters, and receiver operating characteristic curve (ROC) was used to evaluate the prognostic efficacy of these parameter for neonatal HE. Results:There were no significant differences in gender, gestational age, age at MRI scan, delivery mode and blood glucose minimum among the three groups ( P>0.05). There were significant differences in birth weight [(3 150±130)g, (3 020±220)g, (2 880±140)g, F=-0.31, P=0.015], history of suffocation (10 cases, 18 cases, 20 cases, P=0.001), history of maternal diabetes or preeclampsia (14 cases, 29 cases, 21 cases, P=0.002), blood glucose duration [(5.0±0.2)d, (8.0±0.4)d, (14.0±1.7)d, F=-3.09, P=0.030] and NBNA scores (32.0±3.2, 28.0±2.6, 22.0±1.9, F=-4.21, P=0.010) among three groups. There were significant differences in kurtosis and entropy of histogram (2.57±1.12, 3.66±0.98, 4.23±0.37, F=3.54, P=0.010;5.89±1.09, 7.67±2.12, 8.92±1.62, F=-4.42, P=0.020); energy, contrast and dissimilarity of GLCM (0.48±0.01, 0.36±0.02, 0.23±0.01, F=-3.12, P=0.001;2 419±21, 3 354±31, 4 313±26, F=-4.16, P=0.020;126±14, 153±23, 344±43, F=-3.50, P<0.001); long run emphasis of GLRLM (0.78±0.15, 1.12±0.12, 1.76±0.31, F=-4.13, P=0.006), run length non-uniformity and run percentage (71.7±13.9, 96.6±10.7, 104.1±13.5, F=-0.98, P=0.001;0.91±0.05, 0.84±0.21, 0.72±0.17, F=2.97, P=0.010); coarseness and busyness of NGTDM [0.09±0.01, 0.13±0.03, 0.26±0.07, F=-1.95, P=0.003;0.16(0.04, 4.14), 0.32(0.05, 9.84), 0.45(0.15, 10.14), H=-3.24, P=0.030], short-zone emphasis and short-zone high gray length emphasis of GLSZM (4.74±0.45, 3.44±1.03, 1.88±0.67, F=-3.14, P=0.040; 278 963±239, 164 607±544, 111 653±618, F=-3.84, P=0.001) among three groups. Multivariate Logistic regression showed that duration of hypoglycemia, NBNA score, energy, kurtosis, run percentage and short zone effect were independent risk factors for poor prognosis of neonatal HE ( OR=7.43, 4.09, 1.10, 2.11, 1.36, 1.68, P=0.002, 0.027, 0.001, 0.006, 0.007, 0.010, respectively). ROC curve showed that for combined hypoglycemic duration, NBNA and texture parameters, the area under the curve (AUC) was the highest (AUC=0.94, P<0.001). Conclusion:Texture analysis of the MRI diffusion weighted imaging can predict the prognosis of neonatal hypoglycemic encephalopathy at an early stage, which has better prediction efficiency when combined with clinical features.
10.Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer.
Junru FENG ; Hui LU ; Wenhao MA ; Wenjing TIAN ; Zhuan LU ; Hongying YANG ; Yongping CAI ; Pengfei CAI ; Yuchen SUN ; Zilong ZHOU ; Jiaqian FENG ; Jiazhong DENG ; Ying SHU ; Kun QU ; Weidong JIA ; Ping GAO ; Huafeng ZHANG
Protein & Cell 2022;13(11):825-841
Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals
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Antineoplastic Agents/therapeutic use*
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Carcinoma, Hepatocellular/metabolism*
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Cell Line, Tumor
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Clustered Regularly Interspaced Short Palindromic Repeats
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Genome
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Humans
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Liver Neoplasms/metabolism*
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Metformin/therapeutic use*
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Mice
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Phosphorylation
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Synthetic Lethal Mutations
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Transcription Factors/metabolism*
;
rac GTP-Binding Proteins/metabolism*

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