1.Comparision of Mutational Spectrum between Elderly and Young Adults with Acute Myeloid Leukemia Based on Next Generation Sequencing.
Wei-Min WANG ; Ya-Fei LI ; Ling SUN ; Zhong-Xing JIANG ; Ding-Ming WAN ; Jie MA ; Si-Lin GAN ; Fang WANG ; Wei-Jie CAO ; Hui SUN
Journal of Experimental Hematology 2020;28(1):12-17
OBJECTIVE:
To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS).
METHODS:
The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (<60 years old) were compared.
RESULTS:
The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ=7.180, P=0.007) and (20.0% vs 6.7%) ( χ=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ=16.653, P=0.000) and (23.6% vs 8.7%)(χ=9.041, P=0.003) respectively.
CONCLUSION
The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.
2.Potential mechanism of Huangqin decoction for the treatment of ulcerative colitis based on network pharmacology
Hong-xin SONG ; Xu-ran MA ; Dun-fang WANG ; Yan-li WANG ; Di-xin ZOU ; Jin-xue MIAO ; Han WANG ; Wei-peng YANG
Acta Pharmaceutica Sinica 2020;55(2):247-255
To study the mechanism of Huangqin decoction (HQT) in the treatment of ulcerative colitis (UC) by using network pharmacology, chemical components and targets related to the four herbs of Chinese meteria medical in HQT were searched through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) to construct the interaction network diagram of the target point of the compounds. The UC-related targets were screened through OMIM, TTD, and GeneCard databases. The compound-target network was constructed using Cytoseape_v3.7.1 software; based on the STRING database, a target interaction network for HQT for UC was constructed, and the core target of HQT for UC was selected based on topological parameters. GO (gene ontology) biological process enrichment analysis and KEGG (KEGG pathway analysis) pathway annotation analysis were performed on the disease and drug intersection targets using the R package clusterprofile version 3.12.0 in Bioconductor. The HQT compound-UC target network contains 128 compounds and corresponding targets 141. The core targets are AKTI, IL6, PTGS2, IL10, IL1
3.Electroacupuncture combined with lifestyle control on obese nonalcoholic fatty liver disease: a randomized controlled trial.
Can DONG ; Cai-Rong ZHANG ; Bo-Yu XUE ; Wei-Feng MIU ; Nan-Yuan FANG ; Kang LI ; Zeng-Jian OU ; Yu-Qi XU
Chinese Acupuncture & Moxibustion 2020;40(2):129-134
OBJECTIVE:
To observe the effect of electroacupuncture (EA) combined with lifestyle control on hepatic fat status, hepatic enzymology, glycolipid metabolism and anthropological parameters in patients with obese nonalcoholic fatty liver disease(NAFLD).
METHODS:
A total of 90 patients with obese NAFLD were randomized into an observation group (45 cases, 4 cases dropped off) and a control group (45 cases, 1 case dropped off). Lifestyle control was implemented in the control group. On the basis of the treatment in the control group, acupuncture was applied at Zhongwan (CV 12), Quchi (LI 11), Shuifen (CV 9), Huaroumen (ST 24), Daheng (SP 15), Guanyuan (CV 4), Qihai (CV 6), etc. EA was provided at Huaroumen (ST 24) and Daheng (SP 15) with dilatational wave, 2 Hz/100 Hz in frequency, 30 min each time, once every other day, 3 times a week. The treatment for 12 weeks was required in both of the two groups. Hepatic fat status [controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)], hepatic enzymology [alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT)], glycolipid metabolism and insulin sensitivity [fasting plasma glucose (FPG), fasting serum lisulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)] and anthropological parameters [body weight (BW), body mass index (BMI), fat percentage (FP), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR)] in the two groups were observed before and after treatment.
RESULTS:
①Compared before treatment, hepatic CAP, LSM, serum ALT, AST and GGT after treatment were obviously reduced in the two groups (<0.05, <0.01). After treatment, CAP and ALT in the observation group were lower than the control group (<0.05). ②Compared before treatment, FINS, HOMA-IR, LDL-C, TC and TG after treatment were obviously reduced in the two groups (<0.05, <0.01),while the levels of HDL-C were increased (<0.05). Compared before treatment, FPG after treatment in the observation group was reduced (<0.05). Compared with the control group, FINS, HOMA-IR, TC and TG in the observation group were lower than those in the control group after treatment (<0.05). ③Compared before treatment, BW BMI, FP, WC, HC, WHR after treatment were obviously reduced in the two groups (<0.01). After treatment, WC and WHR in the observation group were lower than the control group (<0.05).
CONCLUSION
Electroacupuncture combined with lifestyle control can effectively treat obese nonalcoholic fatty liver disease, and present better therapeutic effect on hepatic fat status, glycolipid metabolism, insulin resistance, WC and WHR.
4.Management of corona virus disease-19 (COVID-19): the Zhejiang experience.
Kaijin XU ; Hongliu CAI ; Yihong SHEN ; Qin NI ; Yu CHEN ; Shaohua HU ; Jianping LI ; Huafen WANG ; Liang YU ; He HUANG ; Yunqing QIU ; Guoqing WEI ; Qiang FANG ; Jianying ZHOU ; Jifang SHENG ; Tingbo LIANG ; Lanjuan LI
Journal of Zhejiang University. Medical sciences 2020;49(1):0-0
The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance"strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance"strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as and . Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.
5. Calcifying fibrous tumor: a clinicopathological analysis of 32 cases
Lei ZHANG ; Jianguo WEI ; Sangao FANG ; Rongkui LUO ; Ziguang XU ; Dujuan LI ; Lingfei KONG
Chinese Journal of Pathology 2020;49(2):129-133
Objective:
To investigate the clinicopathological characteristics, histogenesis, immunophenotypes, molecular genetic characteristics, diagnosis and differential diagnosis of calcifying fibrous tumors (CFT).
Methods:
A total of 32 cases of CFT (22 cases from Henan Provincial People′s Hospital and 10 cases from PLA Army Medical Center) diagnosed between June 2009 and February 2019 were reviewed. The clinical and pathologic data were analyzed.
Results:
There were 12 male and 20 female patients, aged from 15 to 63 years (mean 40.8 years). Eleven cases occurred in stomach, four cases in retroperitoneum, four cases in ovary, two cases in scrotum, two cases in mediastinum, two cases in head and neck, one case each in thoracic cavity, lung, adrenal gland, kidney, sigmoid colon, epididymis and mesosalpinx. All the tumors were solid masses with clear boundaries. The maximal dimension of the tumors ranged from 0.6 to 10.0 cm. Microscopically, there was hypocellular stromal sclerosis and wavy storiform coarse collagen with superimposed scattered or patchy lymphocytes and plasma cells; calcification or gravel formation were also detected. Immunohistochemistry showed that spindle cells were positive for vimentin and some were positive for CD34; and they were negative for calponin, SMA, desmin, S-100 protein, SOX10, STAT6, β-catenin, ALK, CD117, DOG1, CKpan, and EMA. No ALK rearrangement was detected by FISH in all cases. No C-KIT and PDGFRA mutation was detected in all the tested 11 cases of stomach, four cases of retroperitoneal and one case of sigmoid colon CFT. MDM2 was not amplified by FISH in all four tested cases of retroperitoneal CFT.
Conclusions
CFT is a rare benign tumor of fibroblastic cell origin. The diagnosis mainly depends on histomorphologic analysis and immunophenotyping. CFT should be differentiated from other benign and malignant spindle cell mesenchymal tumors.
6.Analysis of the setup errors and residual errors for ExacTrac X-ray image-guidance system for radiotherapy of somal tumors
Yanxin ZHANG ; Hao FANG ; Bing CHEN ; Wei ZHANG ; Shirui QIN ; Qian WANG ; Cheng CHEN ; Hongju LI ; Guishan FU ; Jianrong DAI
Chinese Journal of Radiological Medicine and Protection 2019;39(2):95-100
Objective To retrospectively analyze the setup error in radiotherapy of somal tumors and body metastases using the ExacTrac X-ray portal image,and to evaluate the feasibility and effectiveness of 6D setup error correction in body radiotherapy.Methods The translational and rotational setup errors were calculated by registering the bony structures on the ExacTrac X-setup images to that of the digitally reconstructed setup images,and the corresponding residual errors were calculated together.Results The translational and rotational setup errors in the x (left-right),y (superior-inferior),z (anterior-posterior) and Rx (sagittal),Ry (transverse),Rz (coronal) directions were(2.27±2.02) mm,(4.49±2.52) mm,(2.27± 1.37) mm and (1.02 ± 0.73) °,(0.67 ± 0.68) °,(0.76 ± 0.84) °,respectively.The residual translational and rotational setup errors in the x(r),y(r),z(r) and Rx(r),Ry(r),Rz(r) directions were(0.27±0.48)mm,(0.37±0.45)mm,(0.22±0.30)mm and (0.17±0.33)°,(0.14±0.34)°,(0.16± 0.28) ° respectively.Conclusions Besides the translational setup errors,a certain amount of rotational setup errors exist in radiotherapy of somal tumors and body metastases.By using the 6D setup error correction of the ExacTrac system,a translational less than 0.4 mm and rotational setup errors less than 0.2° could be achieved.
7.Experts consensus on the management of delirium in critically ill patients
Bo TANG ; Xiaoting WANG ; Wenjin CHEN ; Shihong ZHU ; Yangong CHAO ; Bo ZHU ; Wei HE ; Bin WANG ; Fangfang CAO ; Yijun LIU ; Xiaojing FAN ; Hong YANG ; Qianghong XU ; Heng ZHANG ; Ruichen GONG ; Wenzhao CHAI ; Hongmin ZHANG ; Guangzhi SHI ; Lihong LI ; Qibing HUANG ; Lina ZHANG ; Wanhong YIN ; Xiuling SHANG ; Xiaomeng WANG ; Fang TIAN ; Lixia LIU ; Ran ZHU ; Jun WU ; Yaqiu WU ; Chunling LI ; Yuan ZONG ; Juntao HU ; Jiao LIU ; Qian ZHAI ; Lijing DENG ; Yiyun DENG ; Dawei LIU
Chinese Journal of Internal Medicine 2019;58(2):108-118
To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.
8.Screening and intervention of resistant hypertension in the community
Xiaoling XU ; Wei YU ; Jing YAN ; Fang DING ; Shiyun HU ; Li YANG
Chinese Journal of General Practitioners 2019;18(1):47-51
Objective To assess the screening and intervention techniques for resistant hypertension in the community.Methods Random sampling method was used to recruit 1 171 hypertensive patients from two communities in Hangzhou and Zhuji cities of Zhejiang province form October 2015 to september 2016.Among them,97 patients with resistant hypertension were identified with the Three-steps-flow screening method and the individualized intervention was given.The standardized treatment and lifestyle changes were compared before and after intervention.Results Among 97 patients with resistant hypertension,7 cases of pseudo resistant hypertension were detected;there were 2 cases with thyroid disease history,48 cases with snoring history and 1 case with sleep apnea syndrome.The life style intervention and standardized medication guidance were given to 90 patients with resistant hypertension according to the individual risk factors.After one year of intervention,the results showed that the rate of normalized blood pressure was 83.5% (75/90) and the rate of standardized medication increased from 14.4%(13/90) to 90.0% (81/90),the rate of medication compliance increased from 46.7%(42/90) to 95.6%(86/90),the blood pressure control rate increased from 12.2%(11/90) to 77.8%(70/90),and the average systolic blood pressure and diastolic blood pressure levels were decreased by 20.4 mmHg (1 mmHg=0.133 kPa) and 15.5 mmHg.The life style of patients with resistant hypertension was remarkably changed,56.7%(51/90) of patients took exercise regularly,high salt/high calorie diet decreased from 37.8%(34/90) to 11.1%(10/90),the proportion of the obese went down to 16.7%(15/90).Conclusion With the application of resistant hypertension screening and intervention,there are remarkable improvement in blood pressure control and life style changes for patients with resistant hypertension in the community.
9.MicroRNA-206 Reduces Osteosarcoma Cell Malignancy In Vitro by Targeting the PAX3-MET Axis
Fang Biao ZHAN ; Xian Wei ZHANG ; Shi Long FENG ; Jun CHENG ; You ZHANG ; Bo LI ; Li Zhong XIE ; Qian Rong DENG
Yonsei Medical Journal 2019;60(2):163-173
PURPOSE: This study was undertaken to explore how miR-206 represses osteosarcoma (OS) development. MATERIALS AND METHODS: Expression levels of miR-206, PAX3, and MET mRNA were explored in paired OS and adjacent tissue specimens. A patient-derived OS cell line was established. miR-206 overexpression and knockdown were achieved by lentiviral transduction. PAX3 and MET overexpression were achieved by plasmid transfection. Treatment with hepatocyte growth factor (HGF) was utilized to activate c-Met receptor. Associations between miR-206 and PAX3 or MET mRNA in OS cells were verified by AGO2-RNA immunoprecipitation assay and miRNA pulldown assay. OS cell malignancy was evaluated in vitro by cell proliferation, metastasis, and apoptosis assays. PAX3 and MET gene expression in OS cells was assayed by RT-qPCR and Western blot. Activation of PI3K-AKT and MAPK-ERK in OS cells were assayed by evaluating Akt1 Ser473 phosphorylation and total threonine phosphorylation of Erk1/2, respectively. RESULTS: Expression levels of miR-206 were significantly decreased in OS tissue specimens, compared to adjacent counterparts, and were inversely correlated with expression of PAX3 and MET mRNA. miR-206 directly interacted with PAX3 and MET mRNA in OS cells. miR-206 overexpression significantly reduced PAX3 and MET gene expression in OS cells in vitro, resulting in significant decreases in Akt1 and Erk1/2 activation, cell proliferation, and metastasis, as well as increases in cell apoptosis, while miR-206 knockdown showed the opposite effects. The effects of miR-206 overexpression on OS cells were reversed by PAX3 or MET overexpression, but only partially attenuated by HGF treatment. CONCLUSION: miR-206 reduces OS cell malignancy in vitro by targeting PAX3 and MET gene expression.
Apoptosis
;
Blotting, Western
;
Cell Line
;
Cell Proliferation
;
Gene Expression
;
Hepatocyte Growth Factor
;
Immunoprecipitation
;
In Vitro Techniques
;
MicroRNAs
;
Neoplasm Metastasis
;
Osteosarcoma
;
Phosphorylation
;
Plasmids
;
RNA, Messenger
;
Threonine
;
Transfection
10.The levels of serum MCP-1 and IL-6 in patients with acute pancreatitis and its clinical significance
Jing HU ; Shaohua SUN ; Zhaohui PAN ; Xiaogao LI ; Fang WEI ; Li ZHANG
International Journal of Laboratory Medicine 2019;40(4):399-402
Objective To explore the dynamic changes of serum monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in patients with acute pancreatitis (AP) and its clinical significance.Methods A total of 103patients with AP admitted to our hospital from June 2016to December 2017were selected, which were divided into mild AP (MAP group, n=62) and severe AP (SAP group, n=41) according to the condition of disease.The levels of serum MCP-1and IL-6at 1st, 3rd, 7th day after admission were determined by the radioimmunoassay.At the same time, a total of 40healthy volunteers as control group were randomly selected.The predictive value of serum MCP-1and IL-6on for AP was analyzed.Results The serum MCP-1, IL-6level and APACHEⅡscore of MAP group and SAP group at 1st day were higher than those of control group (P<0.05) .The serum MCP-1, IL-6level and APACHEⅡscore of MAP group and SAP group at 3rd, 7th day were higher than those at 1st, and which at 7th were lower than those at 3rd (P<0.05) .The serum MCP-1, IL-6level and APACHEⅡscore of SAP group at 1st, 3rd, 7th were higher than those of MAP group (P<0.05) .Among patients with AP, serum MCP-1and IL-6were positively associated with APACHEⅡscore (P<0.05) .The best cutoff value of serum MCP-1for AP was 31.6pg/mL, and the area under ROC curve was 0.852, and the sensitivity and specificity was 0.87and 0.82respectively, and the accuracy was 0.85.The best cutoff value of serum IL-6for AP was 35.9ng/L, and the area under ROC curve was 0.876, and the sensitivity and specificity were 0.91and 0.85respectively, and the accuracy was 0.87.Conclusion The serum MCP-1and IL-6of patients with AP abnormal changes, which were closely related to the severity and prognosis.Early detection of MCP-1and IL-6can help to judge condition and evaluate prognosis.

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