Discussion on the Authenticity Verification Method in the Verification of Medical Device Registration Quality Management System / 中国医疗器械杂志

Authenticity verification is a very important aspect of medical device registration quality management system verification of medical device. How to verify the authenticity of samples is a problem worth discussing. This study analyzes the methods of authenticity verification from the aspects of product retention sample, registration inspection report, traceability of records, hardware facilities and equipment. In order to provide reference for relevant supervisors and inspectors in the verification of registration quality management system.

Transcriptome Analysis of Inhibitory Effect of Astaxanthin Against HepG2 Cell Lines / 肿瘤防治研究

Objective To investigate the gene expression differences of hepatocellular carcinoma (HCC) cells treated with astaxanthin and to analyze its biological information. Methods After treated with astaxanthin, the total RNA of HCC cells was extracted with TRIzol reagent. Illumina TruseqTM RNA sample Prep Kit was used for RNA-seq library construction and sequencing. We analyzed the differentially-expressed genes and function enrichments. Results Transcriptomic analysis showed that there were 39 642 566 and 497 155 920 reads in the control group and treatment group, respectively; the proportion of clean reads obtained by filtration were 94.89% and 93.56%, respectively. A total of 77 344 transcripts were detected, with 4 997 genes with significant differences in expression, among which 1 564 genes were up-regulated and 3 433 genes were down-regulated. Conclusions Astaxanthin may participate in several biological processes and signaling pathways of tumors. Significant repression of translation process by astaxanthin may result in the growth inhibition of HCC.

Expression and clinical significance of mismatch repair gene in colorectal cancer / 中国肿瘤临床

Objective: To investigate the expression and clinical significance of mismatch repair genes (MMR) MLH1, MSH2, MSH6, and PMS2 in colorectal carcinoma. Methods: Colorectal cancer tissues, collected from 607 patients enrolled in Sichuan Provincial People's Hospital from January 2015 to September 2016, were assigned into two groups based on whether the samples were positive or nega-tive for MMR expression to determine the relationship between MMR expression and clinicopathology. We then evaluated the diag-nostic value of MMR expression in the screening of Lynch syndrome and sporadic colorectal cancer. Results: The deletion rate of MMR protein was 35.58%. No statistically significant difference in age, sex, tumor size, P53, CD34, and D2-40 expression was detected be-tween the negative group with MMR protein deficiency and the positive group with normal expression (P>0.05). Differences in tumor location, differentiation, TNM stage, lymph node metastasis, and VEGF and Ki-67 expression between the two groups were statistically significant (P<0.05). The combined detection of MLH1, MSH2, PSM2, and MSH6 proteins may serve as a simple and economical meth-od for screening patients with Lynch syndrome. Conclusions: The risk of colorectal cancer can be reduced by MMR detection of surgi-cal specimens from colorectal cancer patients, screening of patients with Lynch syndrome and their family members, and assisting with proper management and intervention.

Expression of human leukocyte antigen-G in esophageal squamous cell carcinoma and its significance / 肿瘤研究与临床

Objective To investigate the expression of human leukocyte antigen-G(HLA-G)in patients with primary esophageal squamous cell carcinoma(ESCC)and its significance in the diagnosis and prognosis of ESCC.Methods Immunohistochemical SP method was used to detect the expression of HLA-G in 121 patients with primary ESCC admitted to Sichuan Provincial People's Hospital from January 2013 to January 2018.The relationship between expression of HLA-G and clinicopathological parameters and host immune response was compared by χ 2test and analysis of variance.Kaplan-Meier method was used for survival analysis,and Cox regression model was used for multivariate analysis.Results The expression rate of HLA-G in patients with primary ESCC was 90.9％(110/121).The expression of HLA-G had relationship with tissue differentiation(χ2= 41.695,P = 0.001),the depth of tumor invasion(χ 2= 120.432,P= 0.001),lymph node metastasis(χ2=6.297,P =0.043),clinical TNM stage(χ2=110.394,P = 0.001),and there was a statistically significant difference in host immune response among patients with different HLA-G expression levels(F = 3.190,P = 0.048).The survival rate of HLA-G-negative patients was significantly higher than that of HLA-G-positive patients [72.7％(8/11)vs.33.9％(20/59)],and the difference was statistically significant(χ2= 10.036,P = 0.001).The expression of HLA-G and TNM stage were independent factors affecting the prognosis of patients with primary ESCC(HR= 2.99,95％CI 1.52-5.88,P= 0.002; HR= 1.95,95％CI 1.47-3.13,P = 0.049).Conclusion HLA-G is highly expressed in ESCC tissues,and HLA-G expression is associated with the prognosis of patients with ESCC.

Research progress of static magnetic field targeting drug delivery system in tumor diagnosis and therapy / 国际生物医学工程杂志

Chemotherapy is one of the traditional tumors treatment solutions.Chemotherapy has the feature of tissue non-specificity,which can cause side effects on normal cells while inhibiting tumor cell growth.Magnetic targeting drug delivery system (MTDDS) employs biocompatible and stable magnetic nanoparticles (MNP) as drug carries to transport and accumulate anticancer drugs to the specific tumor tissues under the guidance of external magnetic field.This technology not only improves the efficiency of drug delivery and antitumor activity,but also reduces the drug dosage and side effects.The properties of drug-loaded MNPs and the applied external magnetic field are the main factors that affecting the MNPs targeting to the tumor tissues.The effectiveness of the targeted delivery of the drug-loaded magnetic nanoparticles mainly depends on the form and strength of the magnetic field at the target site.That is,whether there is sufficient strength to attract and retain NMPs,and to promote antitumor drug release at the tumor region.In this paper,the research progress of static magnetic field targeting drug delivery system in tumor diagnosis and therapy was summarized,which can provide some basic information for the relative scientific researches.

Malaria endemic situation and comprehensive prevention and control mea-sures in Caoxian County / 中国血吸虫病防治杂志

Objective To understand the malaria endemic characteristics and control measures in Caoxian County,Shan?dong Province,so as to summarize the experiences of malaria elimination. Methods The data of malaria endemic situation and control measures in Caoxian County from 1953 to 2014 were collected and descriptively analyzed,and the control effectiveness was evaluated. Results The incidence of malaria reduced from 13.25%in 1970 to 0.33%in 1983,and no malaria case was found in 1986. The goal of basic malaria elimination was achieved. The sporadic malaria infections were found from 2006 to 2010,and three imported malaria cases were found in Caoxian County from 2011 to 2014. Conclusion The effect of compre?hensive prevention and control measures taken in Caoxian County is significant,and the goal of malaria elimination has been reached. The imported malaria and secondary cases are future focuses of malaria control work.

Clinical effect of artificial liver support system on serum hs -CRP level in patients with hepatic failure / 临床肝胆病杂志

Objective To evaluate the clinical effect of artificial liver support system (ALSS)on serum high -sensitivity C -reactive pro-tein (hs -CRP)level and investigate the influence of the change in hs -CRP level on clinical prognosis among patients with hepatic failure. Methods Patients were recruited into three groups:group one included 60 patients who received ALSS due to hepatic failure;group two in-cluded 37 patients with hepatic failure without ALSS treatment;and group three included 37 patients with chronic hepatitis B.The serum levels of hs -CRP were measured in groups two and three,and in group one before and after ALSS treatment.Comparison of continuous data between groups was made by t test,and comparison of categorical data was made by chi -square test.Results The levels of hs -CRP in group one before treatment and in groups two and three were 12.89 ±9.39,12.22 ±9.73,and 2.83 ±6.79,respectively.No significant difference in hs -CRP level between group one and group two was observed (P >0.05).However,the hs -CRP level in group three was significantly different from those in group one and group two (P <0.001 ).The improvement rate in group one after ALSS treatment (78.3%)was significantly higher compared with that in group two (54.05%)(χ2 =6.315,P <0.05).ALSS treatment (t =5.179,P <0.05).ALSS treatment was selectively effective in a subgroup of patients and greatly decreased the hs -CRP level in these patients (t =5.344,P =0.000),resulting in a significant difference from the patients who were unresponsive to ALSS treatment (t =2.368,P =0.038).Conclusion Artificial liver support system can decrease the hs -CRP level in patients with hepatic failure.Serum level of hs -CRP can be used as a clinical indicator of disease progression and predict the clinical outcomes of ALSS in patients with hepatic failure.

The heterogenous expression and signiifcance of multidrug resistance-associated proteins in primary tumors and metastatic lymph nodes in patients with esophageal squamous cell carcinoma / 中国癌症杂志

Background and purpose: Postoperative chemotherapy targets the metastatic cancer in the remaining lymph nodes, but the heterogeneity in multidrug resistance (MDR) of metastatic cancer cells is a main factor affecting chemotherapeutic efficacy. Recent studies only examined the primary lesion of esophageal squamous cell carcinoma(ESCC). There is no report about heterogeneity between the primary tumor and metastases lymph node. The purpose of this study was to explore the heterogenous expression and clinical signiifcance of multidrug resistance (MDR) associated proteins in primary tumors and metastatic lymph nodes in patients with thoracic ESCC. Methods:The expressions of lung cancer associated resistance protein (LRP), P-glycoprotein (P-gp), topoisomeraseⅡ(TOPO-Ⅱ), thymidylate synthase (TS), glutathione S-transferase-π (GST-π) were examined by immunohistochemistry in primary lesions and corresponding metastatic lymph nodes in 54 patients with thoracic ESCC. The differences between expression of primary lesions and matched metastatic lymph nodes were compared and analyzed in relationship with tissue differentiation degree. Results: The discordant rates of the expression and drug resistance between primary lesions and corresponding metastatic lymph nodes in LRP, P-gp, TS, TOPO-Ⅱ and GST-π were 63.0% and 26.9%, 42.6%and 22.2%, 48.1%and 25.9%, 50.0%and 29.6%, 18.5%and 1.9%respectively. The expression of LRP showed signiifcant difference between the primary tumors and lymph nodes (P=0.026). No signiifcant differences were found for the other four proteins, and GST-πwas expressed in all patients in both the primary tumors and lymph nodes. Protein expression was not associated with degree of differentiation. Conclusion:There is evident of heterogenous expression of MDR associated proteins in metastatic lymph nodes compared to the primary tumors of ESCC. The examination of expression levels of MDR associated proteins in metastatic lymph nodes is helpful to select the postoperative rational chemotherapy plan.

Multidrug resistance in primary tumors and metastases in patients with esophageal squamous cell carcinoma.

Studies have demonstrated that radical esophagectomy can significantly prolong disease-free survival and improve the survival rate of patients with T3 or T4 esophageal cancer and lymph node metastasis. Multidrug resistant cancer cells have active efflux mechanisms that prevent the accumulation of chemotherapeutic drugs in the cells. The purpose of this study was to compare the expression of five MDR related proteins between primary tumors in patients with thoracic esophageal squamous cell carcinoma (ESCC) and metastatic cancer in lymph nodes to explore the clinical significance of heterogeneity in MDR metastatic cancer cells. Fifty-four patients with ESCC and lymph node metastasis were included. All patients underwent subtotal esophagectomy and D2/D3 lymph node resection. The expression of lung resistance-related protein (LRP), P-glycoprotein, topoisomerase-II, thymidylate synthase, and glutathione S-transferase P1-1 (GST-π) were determined in the primary tumors and lymph nodes via immunohistochemistry. The expression of LRP was significantly different between the primary tumors and lymph nodes (P = 0.026). No significant differences were found for the other four proteins, and protein expression was not associated with either degree of differentiation or disease stage. It was also found that GST-π was expressed in all patients in both the primary tumors and lymph nodes, suggesting that the design and application of chemotherapeutic protocols capable of reducing GST-π expression may be beneficial for patients with ESCC. Additional research regarding the clinical utility of MDR protein expression in ESCC is warranted to design effective chemotherapeutic protocols.

The research progress of Aurora-B kinase and its inhibitors / 药学学报

Aurora-B as an important kinase to adjust the cell normal mitosis is a potent target for cancer treatment. Aurora-B is overexpressed in a broad range of tumor and tumor cells are more sensitive while Aurora-B is inhibited. Due to the key role of the Aurora-B in cell mitosis, the development of its inhibitors is becoming more and more important. Several small molecules inhibit with a similar efficacy both Aurora-A and Aurora-B, however, in most cases the effects resemble Aurora-B disruption by genetic methods, indicating that Aurora-B represents an effective therapeutic target. There were several Aurora-B kinase inhibitors which had entered the clinics and displayed good antitumor activity. In this review, we will outline the functions of Aurora kinase B in normal cell division and in malignancy. We will focus on recent preclinical and clinical studies that have explored the mechanism of action and clinical effect of Aurora-B inhibitors in cancer treatment.

Protamine sulfate downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF and its receptor binding in vitro.

OBJECTIVE: To investigate protamine sulfate inhibition of expression of the vascular endothelial growth factor (VEGF) and VEGF-VEGFR binding in vitro and to find a new drug that inhibits neovascularization, which can potentially be used to treat angiogenic eye diseases such as diabetic retinopathy and age-related macular degeneration (AMD). METHODS: Monkey retinal vascular endothelial cells (RF/6A) were cultured in vitro and different concentrations of protamine sulfate were added to the vascular endothelial cells after three passages. VEGF expression level was examined by ELISA and immunohistochemistry after the cells were treated with protamine sulfate. RESULTS: VEGF expression decreased in a dose-dependent pattern in 10-80 mug/ml of protamine sulfate. We also found that protamine sulfate could inhibit VEGF to bind to its receptor, VEGFR. CONCLUSION: Protamine sulfate could inhibit VEGF expression and VEGF-VEGFR binding in vitro. Protamine sulfate may be used for inhibiting neovascularization in angiogenic eye diseases. Angiogenic eye diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion are the main blindness-causing diseases. Previous studies indicated that VEGF and its receptor were involved in the pathogenesis, development and prognosis of these diseases. VEGF inhibition drugs have been used successfully in clinical treatment, but the cost is prohibitive.Protamine sulfate is a common, inexpensive anti-coagulation drug widely used for anti-coagulation in cases when heparin has been overused in the clinic. Recent studies suggest that protamine sulfate can inhibit tumor growth, probably through inhibiting vascular growth of the tumor. In this study we showed that protamine sulfate could inhibit VEGF and the binding of VEGF and its receptor, implying that protamine sulfate may inhibit blood vessel growth through inhibition of the VEGF pathway. This study further suggested that protamine sulfate may be potentially used to treat angiogenic eye diseases.

Action mechanism of narrow-band ultraviolet B on vascular regulatory factors in psoriasis vulgaris / 中华皮肤科杂志

Objective To evaluate the influence of narrow-band ultraviolet B on lesional microvessel density (MVD),vascular endothelial growth factor (VEGF),matrix metalloproteinases 2 (MMP-2)as well as on serum VEGF in patients with psoriasis vulgaris(PV).Methods Fifteen patients with PV were recruited into this study with 10 normal human controls.All patients received NB-UVB phototherapy thrice a week for 4-5 weeks.Prior and after the treatment,psoriasis area and severity index (PASI)was calculated,tissue specimens were taken from non-photoexposed lesions,and sera samples were obtained from these patients.Then,MvD and the expression level of VEGF and MMP-2 were measured by immunohistochemical labeled dextran polymer(LDP)method in the tissue specimens.Also,the serum level of VEGF was tested by enzyme-linked immunosorbent assay(ELISA).Results PASI score remarkably decreased in patients after the photothempy(t=13.35,P＜0.01).The MVDs were 20.52±5.02,7.33±1.24 and 4.26±0.79 capillaries per high power field(400 × amplification),in psoriatic lesions before treatment,after treatment,and normal control tissues,respectively,with a significant difference among the three groups (F=97.57,P＜0.05),and a significant increase was observed in the lesions before treatment compared with those after treatment and normal controls.The serum level of VEGF was 307.55±121.65 ng/L in psoriatic lesions before treatment,significantly higher than that after treatment(163.92±95.57 ng/L),and in normal control skin (139.78±79.06 ng/L),whereas there was no significant difference between the latter two groups(P＞0.05).The positivity rate of MMP-2 was similar among the three groups without statistical difference(P＞0.05).In psoriatic patients,a positive correlation was observed among PASI score,MVD,lesional and serum VEGF levels(P＜0.05),also among the MVD,VEGF and MMP-2 levels in lesions(P＜0.05).but lesional MMP-2 was unrelated to PASI score or sgrum VEGF(both P＞0.05).Conclusions NB-UVB may regulate superficial dermal microvascular proliferation by acting on the expression of VEGF in sera and lesions of psoriatic patients.VEGF and MMP-2 may bOth participate in the proliferation process of microvessels,while MMP-2 is unlikely to be involved in the therapeutic mechanism of NB-UVB.

Relationship between expression of apoptosis-related genes and multidrug resistance genes in lung cancer tissues and their clinical significance / 中国肺癌杂志

<p><b>BACKGROUND</b>Multidrug resistance (MDR) of lung cancer is a complex procedure involved in multiple genes and multiple pathways. Besides multidrug resistance genes, there is close relationship between expression of apoptosis-related genes and MDR in lung cancer. The aim of this study is to explore the relationship among the expression of apoptosis-related genes (p53, Bcl-2) and clinicopathological characteristics, and their correlation with multidrug resistance genes such as lung resistance protein (LRP), P-glycoprotein (P-gp), glutathione S-transferase π (GST-π), topoisomerase II (Topo II) and multidrug-resistance-associated protein (MRP) in lung cancer.</p><p><b>METHODS</b>The expression of P53, Bcl-2, LRP, P-gp, GST-π, Topo II and MRP was detected in 68 lung cancer patients (Bcl-2 for 51 patients) with immunohistochemical staining (Envision method).</p><p><b>RESULTS</b>The positive rate of P53 and Bcl-2 was 75.0% and 33.3% respectively. There was significant difference in P53 expression between non-small cell lung cancer and small cell lung cancer (P=0.001) and among various grades of cell differentiation (P=0.003). There was also significant difference in Bcl-2 expression between squamous cell carcinoma and adenocarcinoma (P=0.002). There was no relationship between the expression of P53 and Bcl-2 (P > 0.05). Spearman analysis showed that there was a positive correlation between the expression of P53 and P-gp (P=0.002), and between P53 and GST-π (P=0.017), and the coexpression rate was 70.6% and 47.1% respectively. There was no correlation between the expression of Bcl-2 and five multidrug resistance factors (P > 0.05).</p><p><b>CONCLUSIONS</b>The expression of apoptosis-related gene mutant p53 is significantly related to multidrug resistance factors P-gp and GST-π. It is important to detect both apoptosis-related genes and various multidrug resistance genes.</p>

Study on the relationship among multidrug resistance factor expression of lung cancer tissues and clinicopathological characteristics in patients with lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>Multidrug resistance (MDR) is not only the main reason of the failure of chemotherapy, but also the largest obstacle of the increase of survival rate in lung cancer. MDR of lung cancer is a complex procedure involved in multiple genes and mutiple pathways. Combined examination of resistance-related genes in lung cancer tissues has an important clinical significance. The aim of this study is to explore the relationship among the expression, coexpression of five multidrug resistance factors of lung cancer tissues and clinicopathological characteristics in patients with lung cancer.</p><p><b>METHODS</b>Immunohistochemical staining (EnVision method) was used to evaluated the expression of lung resistance protein (LRP), P-glycoprotein (P-gp), glutathione S-transferaseπ (GST-π), topoisomeraseII(TopoII), and multidrug-resistance-associated protein (MRP) in cancer tissues from 72 patients with lung cancer.</p><p><b>RESULTS</b>The positive rate of LRP, P-gp, GST-π, TopoII and MRP was 79.2%, 86.1%, 54.2%, 29.2% and 30.6% respectively. There was a significant difference of the expression of LRP and TopoII in different sex (Chi-square=11.460 and 4.877, P=0.001 and 0.027), of the expression of LRP, GST-π and TopoII in NSCLC and SCLC (Chi-square=15.104, 14.076 and 9.409, P=0.001, 0.001 and 0.009), of the expression of GST-π in various grade of cell differentiation (Chi-square=8.933,P=0.011), of the expression of TopoII in various T staging (Chi-square=3.963,P=0.049). Spearman analysis of rank relativity showed that there was a better relativity between the expression of LRP, TopoIIand sex (r=0.464 and -0.205, P=0.000 and 0.027), between the expression of LRP, GST-π, TopoII and histology. The expression of LRP and GST-π was significantly higher in NSCLC than in SCLC (r=-0.390 and -0.262, P=0.000 and 0.018), the expression of LRP was significantly higher in adenocarcinoma than in squamous cell carcinoma (r =0.604, P=0.000). The expression of GST-π and TopoII was significantly higher in squamous cell carcinoma than in adenocarcinoma (r =-0.257 and -0.264, P=0.015 and 0.012). There was a reverse relativity between the expression of GST-π and cell differentiation (r =-0.232, P= 0.012 ). There was a positive relativity between the expression of TopoII and T staging (r =0.200, P= 0.031 ) and a reverse relativity between the expression of GST-π and T staging (r =-0.182, P=0.050). Spearman analysis of rank relativity of five multidrug resistance factors' coexpression showed that there was a positive relativity beween LRP and P-gp, LRP and MRP, P-gp and GST-π, P-gp and MRP, GST-π and MRP (r = 0.283 , 0.234, 0.453, 0.204 and 0.323, P=0.002, 0.011, 0.000, 0.027 and 0.000), the coexpression rate was 70.8%, 27.8%, 52.8%, 29.2%, 23.6% respectively. There was a reverse relativity between LRP and TopoII (r =-0.183, P=0.048), and the coexpression rate was 19.4%.</p><p><b>CONCLUSIONS</b>The expression of partial multidrug resistance factors is relative significantly to sex, histology and cell differentiation, but not to T, N, M stage and clinical stage. The higher coexpression rate and positive relativity indicate MDR in lung cancer is affected by various multidrug resistance factors. It is important to detect coalescently various multidrug resistance factors.</p>