Values of combined detection of polygene methylation in stool for the diagnosis of colorectal cancer and precancerous lesions / 肿瘤研究与临床

Objective:To investigate the methylation status of SDC2, PPP2R5C and ADHFE1 genes in stool and their values in the screening of colorectal cancer and precancerous lesions.Methods:From August 2020 to March 2021, 64 patients with colorectal cancer, 72 patients with adenoma, 33 patients with hyperplastic polyps and 59 healthy people were recruited from Qingdao Central Hospital Affiliated to Qingdao University, and the morning stool samples were collected from the research subjects. The genomic DNA was extracted and modified with sulfite. The methylation status of SDC2, PPP2R5C and ADHFE1 genes were detected by methylation specific polymerase chain reaction (MSP), and the fecal occult blood test (FOBT) was performed. Taking the pathological results as the gold standard, receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to compare the effect of combined detection of methylation of three genes and FOBT in predicting colorectal cancer and precancerous lesions. R-Studio software was used to construct a nomogram for the prediction of colorectal cancer with combined detection of gene methylation in stool and other clinical features, and the calibration and validation were performed.Results:The positive rates of combined detection of methylation of SDC2, PPP2R5C and ADHFE1 genes in stool were higher than those of FOBT in colorectal cancer+adenoma [74.3% (101/136) vs. 47.1% (64/136), χ2 = 23.20, P = 0.001], colorectal cancer [90.6% (58/64) vs. 70.3% (45/64), χ2 = 8.91, P = 0.003] and adenoma [59.7% (43/72) vs. 26.4% (19/72), χ2 = 14.43, P = 0.002]. There was no significant difference in the positive rates in hyperplastic polyps [21.2% (7/33) vs. 6.1% (2/33), χ2 = 0.12, P = 0.125] and healthy controls [10.2% (6/59) vs. 8.5% (5/59), χ2 = 4.01, P = 1.000]. The combined detection of gene methylation was better than FOBT in the prediction of colorectal cancer + adenoma [AUC: 0.85 (95% CI 0.80-0.91) vs. 0.71 (95% CI 0.64-0.78), P < 0.05], especially in the prediction of adenoma [AUC: 0.82 (95% CI 0.74-0.89) vs 0.64 (95% CI 0.57-0.69), P < 0.001]. The sensitivity and specificity of ADHFE1 gene methylation status in predicting colorectal cancer were high (90.6% and 96.6%). In colorectal cancer patients over 50 years old, the positive rate of combined detection of gene methylation was higher than that of FOBT [90.2% (55/61) vs. 68.9% (42/61), P < 0.05]. The nomogram calibration curve for predicting colorectal cancer constructed based on the combined detection of gene methylation and each clinical feature showed a high degree of concordance between the predicted and observed diagnostic performance of colorectal cancer. Conclusions:The methylation levels of SDC2, PPP2R5C AND ADHFE1 genes in stool are increased in patients with colorectal cancer or adenoma. The combined detection of gene methylation is expected to be a non-invasive method for the screening of colorectal cancer and precancerous lesions.

Pharmacoeconomic Systematic Review of Osimertinib for Advanced Non-small Cell Lung Cancer / 中国药房

OBJECTIVE：To s ystematically review the economics of osimertinib for advanced non-small cell lung cancer （NSCLC），and to provide the reference for clinical application and healthcare decision makers. METHODS ：Retrieved from PubMed，Embase，the Cochrane L ibrary，Health Technology Assessment ，CNKI，Wanfang database ，VIP，CBM，etc.， pharmacoeconomic studies on osimertinib in the treatment of advanced NSCLC were collected from the inception to Apr. 2020. After screening and extracting relevant data ，the quality of the included studies was evaluated by using the Quality of Health Economics Studies （QHES），and the economic research results of the included literatures were systematically evaluated by using descriptive analysis method. RESULTS & CONCLUSIONS ：A total of 10 studies from 7 different countries were included ；QHES scores of the included literatures were 73-93，with an average of 86.8，and the quality of the researches was generally high. All the 10 studies were cost-effectiveness analysis ，including 6 first-line treatment ，4 second-line treatment. Six studies reported the cost discount rate ；only one study used the cost of osimertinib after price reduction for evaluation and analysis. Compared with other epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKI），six studies from different countries showed that osimertinib as the first-line treatment drug had no cost-effectiveness advantage ；cost-effectiveness of second-line treatment of osimertinib was controversial ，compared to chemotherapy. For advanced NSCLC patients ，the second-line treatment of osimertinib after the national centralized negotiation of price reduction has a more cost-effectiveness advantage in China ’s medical service system，while the first-line treatment of osimertinib before price reduction does not have this advantage compared with other EGFR-TKI drugs.

The assessment of the left atrial myocardial fibrosis of atrial fibrillation with late Gadolinium enhancementMRI / 中华放射学杂志

Objective To investigate the clinical value of 2 dimension late Gadolinium enhancement MRI (LGE-MRI) technique for the evaluation of atrial myocardial fibrosis in patients with atrial fibrillation. Methods Forty-nine cases of atrial fibrillation in our hospital from March 2015 to December 2016 were retrospectively collected. The LGE-MR was acquired by the Siemens 3.0 T MR machine before the catheter ablation.The findings of LGE-MR were evaluated by two experienced doctors. The left atrium(LA)were manually segmented into 8 regions in axial view.All patients were classified into 4 stages based on the extent of enhancement, stage 0: absence of enhancement, stage Ⅰ: enhancement appeared in minimal two consecutive slices in single region,stageⅡ:enhancement in two regions,stageⅢ:enhancement in three or more regions. All electroanatomic maps were obtained after electrical conversion during catheter ablation. The Kappa test was used to assess the consistency of LGE-MRI left atrial myocardial fibrosis and CARTO system of the left atrial endocardial voltage reconstruction. Results Forty-nine cases of atrial fibrillation with LGE-MRI and CARTO were included. There were 17 cases of atrial fibrosis stage 0,10 cases of stageⅠ,11 cases of stageⅡ,11 cases of stageⅢaccording to LGE-MRI findings;There were 17 cases of atrial fibrosis stage 0,19 cases of stageⅠ,12 cases of stageⅡ,11 cases of stage Ⅲ with reference to CARTO findings. The diagnostic accuracy of the LGE-MRI atrial fibrosis was 81.6%(40/49),of which the correlation was good(Kappa= 0.751,P<0.001). Conclusions LGE-MRI can accurately assess the degree of left atrial myocardial fibrosis in patients with atrial fibrillation,help to select the proper candidate and strategy in catheter ablation.

Heparin-treated dendritic cells promote Th0 to Th1 differentiation via the Toll-like receptor 3 in peripheral blood monocytes of patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the mechanisms underlying the ability ofheparin-treated dendritic cells (DCs) to promote Th0 to Th1 differentiation in chronic hepatitis B (CHB).</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMCs) were isolated from CHB patients and cultured in RPMI-1640 with recombinant GM-CSF and IL-4 with or without heparin to obtain DCs for study. The levels of Toll-like receptors (TLRs) on the DCs were measured using FACS and qPCR techniques.DC subsets with high expression of TLRs were selected for analysis of functional changes by treatment with the corresponding TLR-siRNA. The CD4+ T cell subpopulation was purified from peripheral blood by Dynal immunomagnetic beads, and then the production of IL-12 by DCs in the presence of poly(I:C) or R848 and ofIFN and IL-4 by Th cells co-cultured with DCs was evaluated by ELISA. The t-test was used for statistical analysis.</p><p><b>RESULTS</b>TLR3 expression, and not expression of TLR 7 or TLR8,was significantly increased in heparin-treated DCs as compared to levels detected in the DCs without heparin treatment (t =2.849,P less than 0.05;t =3.027,P less than 0.05). The level of IL-12 produced by heparin-treated DCs stimulated with poly(I:C) was obviously higher than that produced by DCs without heparin treatment and stimulated with poly(I: C) (t =8.68,P less than 0.01) or with R848 (t =19.01,P less than 0.01). However, the IL-12 production by TLR3-siRNA transfected-DCs was significantly reduced (t =31.49, P less than 0.01).When Th cells from allogenic patients with CHB were co-cultured with the TLR3-siRNA transfectedDCs, the frequency ofCD4+ IFN+ cells was significantly reduced (1.64+/-0.57% vs.6.31+/-0.88%,P less than 0.01),as was the capability of Thl to generate IFNg (t =20.83,Pless than 0.01).</p><p><b>CONCLUSION</b>Heparin may have up-regulated the TLR3 expression level of DCs, and sequentially promoted Th0 to Th1 differentiation.</p>

Screening biomarkers in bone marrow supernatant of multiple myeloma by 2-DE and MALDI-TOF-MS / 中华检验医学杂志

Objective To analyze the differentially expressed proteins in bone marrow supernatants of multiple myeloma patients by using 2-DE and MALDI-TOF-MS,and search for the special protein markers for studying the mechanism of the development and diagnosis or differential diagnosis of multiple myeloma.Methods The bone marrow supernatant samples of fourteen multiple myeloma patients,five other hematologic malignancies and five normal controls were collected.After removing albumin and IgG,the proteins in the supernatants were separated by 2-DE.Three groups images were analyzed and compared by Imagemnster 2D platinum 5.0 analysis software.Differentially expressed proteins were selected if the protein spots intensity showed more than 3 fold increase or decrease among different groups.The identities of the differentially expressed proteins with good repeatibility were determined by PMF based on by MALDI-TOF-MS or MALDI-TOF-MS/MS and NCBInr database search.Results 2-DE maps of bone marrow supernatants of the three groups could be analyzed and compared by image analysis of software.Forty-seven and fifty-eight differentially expressed protein spots were detected in multiple myeloma samples compared with normal controls and other hematologic malignancies samples,respectively.Forty-one reproducible spots were analyzed and identified by mass spectrum.Compared with other hematologic malignancies and normal controls,five up-expressed proteins and three down-expressed proteins were identified in multiple myeloma samples.They includes immunoglobulin J chain κ and λ light chain,provirus ancestral Gag polyprotein,mature oxy-cope catalytic antibody with hapten for up-expressed proteins,and hemoglobin,haptoglobin Hp2,zinc-alPha-2-glycoprotein for down-expressed proteins.These differentially expressed proteins reflect the features of muhiple myeloma,and relate to the development,progression and therapy of multiple myeloma.Conclusions Eight differentially expressed proteins in bone marrow supernatants of multiple myeloma are identified by using 2-DE and MALDI-TOF-MS.These differentially expressed proteins could be useful in studying the mechanism of the development and progression of multiple myeloma,and in developing diagnosis and differential diagnosis of multiple myeloma.

Simultaneous Determination of 6 Antidepressants in Human Plasma by HPLC / 中国药房

OBJECTIVE:To establish a rapid and sensitive HPLC method for simultaneous determination of plasma concentrations of 6 antidepressants.METHODS:With diprozin as internal standard,the alkalized samples were extracted by liquid-liquid extraction and separated on a Phenomenex-C18 column using acetonitrile-0.05 mol?L-1 sodium dihydrogen phosphate(pH was adjusted to 2.5 by phosphoric acid) as mobile phase at a flow rate of 1.2 mL?min-1 by a gradient elution.The column temperature was set at 40℃.Venlafaxine was detected by fluorescence detection at an Ex wavelength of 276 nm and Em wavelength of 598 nm;doxepin,paroxetine,sertraline,fluoxetine and amitriptyline were detected at an UV detection wavelength of 200 nm.RESULTS:The linear ranges of venlafaxine,doxepin,paroxetine,sertraline,fluoxetine and amitriptyline were 5～1 000 ?g?L-1,40 ～200 ?g?L-1,20～800 ?g?L-1,40～1 000 ?g?L-1 and 10～400 ?g?L-1,respectively,with correlation coefficients ≥0.990 for all.Both the intra-day RSD and inter-day RSD were less than 15%;the extraction recovery rates were greater than 60% and methodological recovery were greater than 90% for all the samples.CONCLUSION:The method is simple,economical,rapid,accurate and sensitive,and it is applicable for the clinical monitoring of plasma drug concentrations as well as the analysis and pharmacokinetic study of toxic drugs.

Pancreatoduodenectomy for the treatment of chronic local pancreatitis in the head of pancreas / 中国普通外科杂志

Objective To evaluate the rationale of pancreatoduodenectomy for the treatment of chronic local pancreatitis in the head of pancreas.Methods Eleven patients underwent pancreatoduodenectomy for chronic local pancreatitis in the head of pancreas with 7 cases treated by Whipple′s operation and 4 by pylorus preserving pancreatoduodenectomy.Results Postoperative stress ulcer and wound infection occurred and were cured subsequently in one each.Postoperative follow up showed good quality of life in all the 11 patients.Conclusions Pancreatoduodenectomy is an effective cure for patients suffering from chronic local pancreatitis of the head of the pancreas refractory for conservative therapy.

Preparation and Clinical Application of Compound Fleroxacin Ear-drops / 中国药房

OBJECTIVE:To study the quality control,stability and therapeutic effect of compound fleroxacin ear-drops.ME_THODS:The content of fleroxacin in the ear-drops was determined by ultraviolet spectrophotometry.RESULTS:There was a good linearity in a range of concentrations from 2?g/ml to 12?g/ml,r=0.9 998,average rate of recovery was 100.38%,RSD=0.39%(n=6).The preparation showed stable quality and satisfactory effect.CONCLUSION:This ear-drops is simple in preparation,reliable in quality-control and effective in clinical use.

Effect of Dendritic Cells Loaded with Tumor Antigens on Antitumor Activity of Tumor-Infiltrating Lymphocytes from Hepatocellular Carcinoma in vitro / 中国肿瘤生物治疗杂志

Objective: To investigate the effects of dendritic cells(DCs) loaded with tumor antigens on the proliferation and antitumor activity of tumor-infiltrating lymphocytes(TILs) from hepatocellular carcinoma (HCC) in vitro . Methods:DCs derived from the peripheral blood of patients with HCC were loaded with autologous tumor lysate(Tuly) to generate DC-Tuly and then the DC-Tuly was co-cultured with autologous TILs in low concentration of IL-2. TILs were counted, and the phenotypes of DCs and TILs were assayed by FCM and the cytotoxicity of TILs was determined with LDH method. The concentration of cytokines in TILs culture supernatant such as IFN-? and TNF-? was detected by ELISA . Results: The expression levels of CD1a, CD80, CD83,CD86, CD40, HLA-DR molecules on the DC-Tuly are notably increased( P