Analysis of the time consumption of clinical trials contract signing and its influencing factors / 中华医学科研管理杂志

Objective:To study the time consumption of clinical trial projects in each link of contract signing in medical institutions and its influencing factors, to provide a reference for further optimizing the clinical trial management process and improving the efficiency of contract signing.Methods:All of the review records of projects that signed clinical trial contracts at Peking Union Medical College Hospital from January 1st, 2018 to December 31st, 2021 were retrospectively analyzed by comparing the time consumption in each link before signing the contracts and the frequency of contract reviews. Multiple linear regressions were applied to multivariate analyze the influence of different factors on contract signing.Results:A total of 761 clinical trial contracts signed at Peking Union Medical College Hospital from 2018 to 2021 were included in this study, and the average time consumption of contract signing was 127.0 days, among which the consumption of contract review by the hospital was 10.5 days and by sponsors was 99.0 days. The time consumption of contract signing has been decreasing in recent 4 years, from 154.0 days in 2018 to 104.0 days in 2021. The phase of clinical trials, category of sponsors, frequency of contract reviews, and different policies of the institutions were the main influencing factors for contract signing time ( P<0.05). Conclusions:Clinical trial institutions should optimize the contract approval progress, provide agreement templates and targeted service, and strengthen propaganda and information system construction, to improve the efficiency of reviewing and signing clinical trial contracts.

Clinical Value of Autoantibody Prognostic Markers in Tumor Immune Checkpoint Inhibitor Therapy / 中国肺癌杂志

Serum autoantibody markers have the advantages of easy specimen acquisition, simple detection technology and dynamic real-time monitoring. With the wide application of immune checkpoint inhibitors in the treatment of malignant tumors, autoantibody markers in predicting tumor immune checkpoint inhibitors efficacy and forecasting irAEs (immune related adverse events) show good prediction of potential. This review mainly focused on the progress of autoantibody markers in the prediction of therapeutic effect and the monitoring of irAE in tumor immunotherapy.
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MUC16: The Novel Target for Tumor Therapy / 中国肺癌杂志

Mucin16 (MUC16), also known as carbohydrate antigen 125 (CA125), is a glycoprotein antigen that can be recognized by the monoclonal antibody OC125 detected from epithelial ovarian carcinoma antigen by Bast et al in 1981. CA125 is not present in normal ovarian tissue but is usually elevated in the serum of epithelial ovarian carcinoma patients. CA125 is the most commonly used serologic biomarker for the diagnosis and recurrence monitoring of epithelial ovarian carcinoma. MUC16 is highly expressed in varieties of tumors. MUC16 can interact with galectin-1/3, mesothelin, sialic acid-binding immunoglobulin-type lectins-9 (Siglec-9), and other ligands. MUC16 plays an important role in tumor genesis, proliferation, migration, invasion, and tumor immunity through various signaling pathways. Besides, therapies targeting MUC16 have some significant achievements. Related preclinical studies and clinical trials are in progress. MUC16 may be a potential novel target for tumor therapy. This article will review the mechanism of MUC16 in tumor genesis and progression, and focus on the research actuality of MUC16 in tumor therapy. This article also provides references for subsequent tumor therapy studies targeting MUC16.
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Tumor autoantibodies in the diagnosis and prognosis of prostate cancer / 中华检验医学杂志

Detection of prostate specific antigen (PSA) is the most commonly used screening method for prostate cancer. However, many studies have found that the false positive rate and false negative rate of PSA detection for prostate cancer screening are very high, which easily leads to the overuse of PSA detection. Autoantibodies appear at the early stage of cancer, accompany the occurrence and development of prostate cancer. Autoantibodies have a long half-life and are easy to detect. Existing studies have found that autoantibodies can be used in the diagnosis of prostate cancer, and correlated with some prognostic indicators such as Gleason grade and overall survival (OS) of prostate cancer patients. This paper summarized 8 studies on the role of single autoantibody in the diagnosis and prognosis of prostate cancer. Most of the reported single autoantibodies have better diagnostic performance than PSA, and combined application could improve the diagnostic performance. Some autoantibodies are related to a poor prognosis of prostate cancer.

Advances in Drug Resistance Mechanisms and Prognostic Markers of Targeted Therapy in ALK-positive Non-small Cell Lung Cancer / 中国肺癌杂志

Echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion accounts for 3%-5% of non-small cell lung cancer (NSCLC) patients. With the in-depth study of the EML4-ALK driver gene, ALK inhibitors represented by crizotinib have been gradually developed and applied in the clinic. However, the response to ALK-targeted therapy is heterogeneous among different patients. Most patients with ALK-targeted therapy will inevitably develop drug resistance, leading to tumor progression. Monitoring the efficacy of patients with prognostic markers to change the treatment in time, and selecting individualized follow-up treatment according to the mechanism of drug resistance, can effectively improve the prognosis of patients. This article will review the mechanism of ALK tyrosine kinase inhibitor (ALK-TKI) resistance and related prognostic markers to discuss the prediction for ALK-targeted therapy and the choice of subsequent treatment for drug-resistant patients.
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The diagnostic efficacy of FNA-Tg in detecting lymph node metastasis of differentiated thyroid cancer and its influencing factors / 中华检验医学杂志

Differentiated thyroid cancer (DTC) patients are prone to cervical lymph node metastasis, which affects patients′ quality of life. Accurate diagnosis of lymph node metastasis can guide surgical resection and dissection, and improve patient′s prognosis. Since the first use of fine-needle aspiration washout thyroglobulin (FNA-Tg) to diagnose lymph node metastasis in DTC patients, a large number of studies have shown that FNA-Tg has a good diagnostic performance. However, due to the various influencing factors of detection and the lack of uniform detection standards, the results of studies very largely. How to screen suitable patients and establish uniform standards to maximize the efficiency of FNA-Tg detection is an urgent problem to be solved. This article will systematically review and analyze the diagnostic efficacy of FNA-Tg and its influencing factors,and explore the subsequent clinical application and research direction of FNA-Tg.

Effects of behaviral activation on mental health and habitual behaviors among college students with depression and anxiety / 中国学校卫生

Objective@#To analyze the effects of behavioral activation on mental health status, self-efficacy and habitual among college students with depression and anxiety, and to provide reference for clarifying the application value of this therapy in the treatment of depression and anxiety.@*Methods@#A total of 2 000 depression and anxiety students from two colleges in Beijing from Sept. 2014 to Sept. 2018 were enrolled. They were divided into control group and observation group by simple random sampling, with 1 000 cases in each group. The control group was given cognitive behavioral theory, while observation group was given behavioral activation theory. Before and after intervention, depression and anxiety symptoms were assessed by Self-rating Depression Scale and Self-rating Anxiety Scale. Mental health status was assessed by Symptom Checklist 90. Self-efficacy scoring was performed by General Self-efficacy Scale. Behaviral activation and behavior evasion were assessed by Behavioral Activation for Depression Scale-short Form. Quality of life was assessed by Short Form 36 Health Survey.@*Results@#The proportion of depressive symptoms in the observation group after intervention was 51.80%, significantly lower than 56.20% in the control group (U=5.08, P<0.05), and the proportion of anxiety symptoms was 47.30%, significantly lower than 51.50% in the control group (U=4.91, P<0.05). After intervention, mental health level, self-efficacy, quality of life, behavioral activation scores and BADS-SF total scores in observation group were significantly higher than those of control group, and behavior evasion score was significantly lower than that of control group (P<0.05).@*Conclusion@#Behavioral activation can change habitual behavior among college students with depression or anxiety, improve their mental health and self-efficacy, and improve quality of life.

Progress of inflammatory cytokines as lymphoma biomarkers and molecular targets / 白血病·淋巴瘤

The inflammatory response is involved in the development of most diseases. In recent years, tumor associated inflammatory response in tumor microenvironment has been paid more attention. Inflammation promotes the progress of lymphoma, and the growth and proliferation of lymphoma cells also depend on the inflammatory tumor microenvironment. Inflammatory response plays an important role in the development and treatment of lymphoma. Inflammatory cytokines are main types of inflammatory mediators, their expression levels reflect the inflammatory response state of the body, and have potential to be biomarkers and molecular targets of lymphoma.

The clinical significance of HCV antibody S/CO values in the diagnosis of active HCV infection in cancer patients / 中华检验医学杂志

Objective To investigate the clinical significance of HCV antibody S /CO values in active HCV infection diagnosis in cancer patients .Methods 390 cancer patients were enrolled from Cancer Hospital Chinese Academy of Medical Sciences between January 2013 and April 2015.All of the cancer patients had pathological diagnosis , including 240 males and 150 females, aged from 25 to 83 years old. HCV antibody and HCV RNA levels were detected using the Abbott i 2000 immunity analyzer and Roche LC480 real-time fluorescent quantitative PCR machine , respectively.The relationship between HCV antibody S/CO value and RNA level was analyzed in the group of HCC and non-HCC patients.Results There were obvious statistical differences in age (P＝0.004), gender (P＜0.001) and HCV antibody levels (P＜0.001) between the group of HCC and non-HCC patients.There was no statistical difference in distribution of RNA positive rate between the two groups (P＝0.528).Using ROC curve analysis, the best cut-off value to diagnose active HCV infection in cancer patients is 10.0 with sensitivity 97.6%and specificity 81.3%. According to the results of the ROC curve , the cut-off was 11.4 and 10.4 in HCC and non-HCC patients respectively.Conclusion The best cut-off value to diagnose active HCV infection in cancer patients is 10.0, either in HCC or in non-HCC.

Correlation between Plasma-soluble Urokinase Plasminogen Activator Receptor(suPAR) Levels and Disease Severity in Psoriasis Patients / 现代检验医学杂志

Objective To investigate the correlation between plasma-soluble urokinase plasminogen activator receptor (suPAR) levels and disease severity in psoriasis patients.Method 60 psoriasis patients and 60 healthy controls were enrolled from Jan.2013 to Dec.2015 in the hospital.The plasma suPAR of all objects were measured by ELISA.Kruskal-Wallis and Mann-Whitney U test were used to compared plasma suPAR in the difference groups.Correlation between clinical data and plasma suPAR were analyzed by Spearmans's rho method.Result The plasma suPAR of psoriasis patients (3.92± 1.74 ng/ml) were higher than controls (3.03 ± 1.08 ng/ml,Z=13.05,P=0.009).The plasma suPAR of mild patients (PASI＜ 10) were lower than moderate patients (10≤ PASI≤ 20,3.90 ± 1.67 ng/ml,Z =8.00,P =0.035) and severity patients (PASI＞20,4.55 ± 1.88 ng/ml,Z=48.5,P=0.031).Positive correlation were found between plasma suPAR and psoriasis area and severity dndex (PASI) score (r=0.264,P=0.041).The plasma suPAR of the patients with disease duration＞10years (n=35,4.43 ± 1.98 ng/ml) were higher than the patients with disease duration＜10 years (n=25,3.41 ± 0.69 ng/ ml,Z=-2.064,P=0.035).Conclusion There was a positive correlation between the plasma suPAR and psoriasis disease severity.The Plasma suPAR can be the biomarker of psoriasis disease severity.It facilitate the clinical diagnosis of psoriasis.

Expression and significance of thyroid hormone receptors mRNA of residents exposed to arsenic via drinking water / 中华地方病学杂志

Objective To detect thyroid hormone receptors (TRs) mRNA expression of subjects exposed to different levels of arsenic,to further study the endocrine disturbing effect of arsenic.Methods Molecular epidemiological method was used,in drinking water type of endemic arsenic poisoning areas,which were divided into control (＜ 10 μg/L),low (10-＜ 100 μg/L),medium (100-＜ 200 μg/L) and high (≥200 μg/L) dose groups based on the drinking water arsenic concentrations.According to the gender stratification,a total of 273 (control,low,medium and high dose groups were 58,49,66,100,respectively) residents were chosen.To carry out the questionnaire,urine arsenic determination,electrocardiographic examination.Real-time PCR was used to detect blood TRs mRNA expression.Results TRα mRNA relative expression levels in the control,low,medium and high dose groups were (12.2 ± 5.7) × 10-4,(12.2 ± 5.0) × 10-4,(12.3 ± 5.4) × 10-4,(12.2 ± 4.3) × 10-4,respectively,the differences were not statistically significant (F =0.109,P ＞ 0.05).TRβ mRNA relative expression levels were all low,the control,low,medium and high dose groups were (5.7 ± 4.1) × 10-6,(8.6 ± 7.6) × 10-6,(6.3 ± 4.2) × 10-6 and (6.2 ± 3.8) ×10~,respectively,the differences were statistically significant (F =2.938,P ＜ 0.05).The levels of TRβ mRNA relative expression changed with increased content of arsenic in water and urine trends in inverse U-shaped curves (R2 =0.035,0.067,all P ＜ 0.05).TRβ mRNA relative expression in low dose group was higher than that in control group,the difference was statistically significant (P ＜ 0.05);TRβ mRNA relative expression in high dose group was lower than that in low dose group,the difference was statistically significant (P ＜ 0.05).Arsenic induced arrhythmia which most displayed sinus bradycardia;the prevalence of arrhythmia in the control,low,medium and high dose groups were 12.1％ (7/58),10.2％ (5/49),13.6％ (9/66),19.4％ (19/98),respectively,the differences were not statistically significant (x2 =2.877,P＞ 0.05).Heart rate was positively associated with the level of TRβ mRNA relative expression in lg value (r =0.218,P ＜ 0.05).Conclusion Chronic arsenic exposure can disturb TRβ mRNA expression;there is a possible relationship between TRβ mRNA abnormal expression and arrhythmia caused by arsenic.

Value of urine sediment analyzer in the screening of urinary tract infection in cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the value of urine sediment analyzer in the screening of clinically suspected urinary tract infection (UTI) in cancer patients.</p><p><b>METHODS</b>The results of bacterial count of 1 053 midstream urine samples by UF-1000i urine sediment analyzer (UF-1000i urine sediment analyzer, UF-1000i) were compared with the results of bacterial culture. Moreover, the results of distinguishing bacterial species by the bacterial scattergram were compared with the results of bacteria culture. At the same time, the sensitivity, specificity, positive predictive value and negative predictive value of UF-1000i analyzer for UTI screening were evaluated.</p><p><b>RESULTS</b>Of all the 1 053 samples, the top three bacteria were E. coli, Enterococci and P. aeruginosa. The top three malignant tumors of UTI were bladder, lung cancer and cervical cancers. The positive rate of UF-1000i analyzer was 20% (211/1 053), and that of bacteria culture was 17.9% (188/1 053). There was statistically no significant difference in the positive rates between the two methods (χ(2)=1.636, P>0.05), and the two methods had a considerable consistency (Kappa=0.756). Compared with the clinical diagnosis, UTI screening by UF-1000i analyzer showed a sensitivity of 79.6% (160/201), specificity of 95.5% (814/852), positive predictive value of 80.8% (160/198) and negative predictive value of 95.2%(814/855). The distribution of cocci and bacilli acquired by the bacterial scattergram was basically in accordance with the results of bacterial culture.</p><p><b>CONCLUSIONS</b>Bacterial count by UF-1000i analyzer plays an important role in early screening of UTI, and the bacterial scattergram may help to distinguish bacterial species, providing reference for the use of antibiotics in early medication.</p>

Duration of filgrastim prophylaxis for chemotherapy-induced neutropenia and its predictors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the duration of preventive filgrastim administration as support for chemotherapy and its affecting factors.</p><p><b>METHODS</b>Single institutional data from a phase Ⅱ clinical trial and a phase Ⅲ clinical trial of pegylated filgrastim were combined. In the two randomized cross-over trials, patients with previously untreated cancer received two cycles of chemotherapy of the same regimen. In the study group, the patients received a single subcutaneous injection of 100 μg/kg pegylated filgrastim, and in the control group, they received daily subcutaneous injections of 5 μg/kg filgrastim.</p><p><b>RESULTS</b>In 53 chemotherapy cycles, the median duration of filgrastim administration was (9.57±2.10)d. 83.0% (44/53) of them received filgrastim for 7-11 days. Patients with baseline absolute neutrophil count of <4×10(9)/L or body mass index less than 22 received a longer filgrastim prophylaxis(P<0.05). RESULTS of multivariate analysis showed that the baseline absolute neutrophil count is associated with the time of filgrastim administration(P=0.019). The most common adverse event of rhG-CSF was skeletal pain, generally mild and no treatment-related death occurred.</p><p><b>CONCLUSIONS</b>The median duration of filgrastim support for chemotherapy was 10 days. Patients with lower baseline neutrophil count require a longer filgrastim prophylaxis.</p><p><b>TRIAL REGISTRATION</b>: ClinicalTrials.gov identifier, NCT01285219.</p>

Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin's lymphoma / 癌症

<p><b>BACKGROUND</b>The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is an efficient treatment of non-Hodgkin's lymphoma (NHL). This study aimed to assess the efficacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab (R-CHOP) by examining the stem cell mobilization in NHL patients. Factors affecting the collection of CD34+ cells were also explored.</p><p><b>METHODS</b>Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were financially eligible received R-CHOP for autologous peripheral blood stem cell (APBSC) mobilization; the remaining 25 patients received CHOP.</p><p><b>RESULTS</b>The median CD34+ cell yield was 7.01×10(6) cells/kg body weight (range 1.49-28.39×10(6) cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ≥2.0×10(6) cells/kg body weight. The median number of apheresis procedures per patient was 1 (range 1-3). The APBSC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group (P=0.005), whereas the success rate was similar between groups. R-CHOP elevated the complete response (CR) rate in B cell lymphoma patients as compared with CHOP (P=0.01). No significant differences in toxicity or engraftment were observed between the two groups.</p><p><b>CONCLUSION</b>The present study demonstrated that dose-adjusted CHOP chemotherapy effectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.</p>

Efficacy analysis of pegylated filgrastim as prophylaxis for chemo-therapy-induced neutropenia / 中国肿瘤临床

Objective:To compare the efficacy of a single injection of pegylated filgrastim with daily doses of filgrastim as pro-phylaxis for chemotherapy-induced neutropenia in Chinese cancer patients. Methods:Single-institution data from a phase 2 study and a phase 3 trial on pegylated filgrastim were combined to analyze the efficacy and safety parameters. In the two randomized crossover tri-als, patients with previously untreated cancers received two cycles of chemotherapy with identical regimen. In the study cycle, the pa-tients received a single subcutaneous injection of pegylated filgrastim (100 μg/kg), whereas those in the control cycle received daily subcutaneous injections of filgrastim (5μg/kg). Results:Among the 56 patients enrolled, 53 were evaluable for efficacy. These patients received one cycle with pegylated filgrastim prophylaxis and one cycle with filgrastim support each. Results indicated that 94.3%(50/53) of the cycles with pegylated filgrastim or filgrastim support did not develop grade 4 neutropenia. Moreover, febrile neutropenia did not occur in the cycles. The incidence rates of antibiotic administration were 7.5%(4/53) and 3.8%(2/53) in the pegylated filgrastim and filgrastim cycles, respectively (P=0.678). The median duration of filgrastim administration was 10 days (3-14 days). Generally, the safety profile of pegylated filgrastim is similar to that of filgrastim, including skeletal pain, pain at the injection site, palpitation, fever, and fatigue. Conclusion:A single dose of pegylated filgrastim demonstrated comparable efficacy with 10 consecutive doses of filgras-tim as prophylaxis for chemotherapy-induced neutropenia.

Companion diagnosis for personalized targeted therapy in lung cancer / 中华检验医学杂志

As the precision medicine has been proposed , personalized therapy in cancer steps into a new stage.Since the development of gene molecular biology in lung cancer , numerous molecular targets were discovered.However, selecting patients who will be the most likely to benefit from the therapy is still a great challenge in clinical practice .Companion diagnosis could help evaluate the status of patients , which may provide better suggestions for health care professionals during treatment decision , in order to benefit the patients and decline the side effects risk together .Besides, high-throughput sequencing technics and diverse detection samples has provided a novel direction to understand the tumorigenesis and find more potential gene targets.

Clinical characteristics of drinking-water type endemic arsenism in population lived in the diseased areas before and after water improvement in Inner Mongolia / 中华地方病学杂志

Objectives To analyze the clinical characteristics of drinking-water type endemic arsenism in population lived in the diseased areas before and after water improvement in Inner Mongolia,so as to assess the natural development and the effects of human intervention measures.Methods Residents of four villages lived in Hangjinhouqi Bayinnaoer city Inner Mongolia were followed-up and their skin lesions were examined in 2004 (before water improvement),2010 (complete water improvement),2014 (after water improvement).Meanwhile,blood pressure and heart rate of the subjects were measured.The arsenic poisoning skin damage indexing was in accordance with endemic arsenic poisoning diagnostic criteria (WS/T 211-2001).Results Totally,229,122,161 people were investigation in 2004,2010,2014,respectively.The clinical grading of arsenic exposed population were mainly normal and suspicious cases in 2004,accounting for 61.6％ (141/229) and 22.7％ (52/229),respectively.The clinical grading of normal,suspicious,mild and severe cases were 20.5％ (25/122),31.1％ (38/122) and 48.4％ (59/ 122),respectively,in 2010,which were significantly different compared with those of 2004 (x2 =68.53,P ＜ 0.01).The clinical grading percentages of normal and suspicious of the subjects in 2014 were 46.6％ (75/161) and 39.8％ (64/161),respectively,which were significantly different compared with those of 2010 (x2 =45.22,P ＜ 0.01).Meanwhile,91 subjects examined in 2004 were re-examined in 2010 and 47 subjects examined in 2010 were reexamined in 2014.Totally,12 cases were migitation,accounting for 13.2％ (12/91),52 cases were aggravation,accounting for 57.1％ (52/91) in 2010,and 25 cases were migitation,accounting for 53.2％ (25/47),9 cases were aggravation,accounting for 19.1％ (9/47) in 2014.The differences of skin lesion transition between these two periods were significant (x2 =28.66,P ＜ 0.05).In addition,the systolic pressures and diastolic pressure of the subjects were (132.19 ± 21.21),(126.99 ± 18.32),(147.69 ± 22.65);(84.88 ± 14.13),(76.52 ± 10.08),(84.39 ± 13.89)mmHg in 2004,2010 and 2014,respectively,which declined in 2010 compared with them of 2004 (all P ＜ 0.05) and raised in 2014 compared with them of 2010 (all P ＜ 0.01).The heart rate of the subjects were (76.05 ± 12.56),(78.86 ± 11.69),(82.05 ± 11.26)times/min.The heart rate of the subjects raised in 2010 and 2014 compared with that of 2004 (all P ＜ 0.05).Conclusion The skin lesions induced by arsenism could be effectively alleviated through water improvement,but the late stage changes such as the cardiovascular system injury are still worthy of attention.

A standardized protocol for detection of ALK protein expression and gene fusion in lung adenocarcinoma cytologic specimens / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to establish a standardized protocol for detection of ALK protein expression and gene fusion in cytologic specimens.</p><p><b>METHODS</b>Lung adenocarcinoma cytologic specimens were collected from seven hospitals in Beijing city. A detection protocol for ALK protein expression and gene fusion was designed according to the results of comparative experiment. Ventana immunohistochemical (IHC) ALK(D5F3) detecting ALK protein expression was performed in 203 prepared formalin-fixed paraffin-embedded (FFPE) cell blocks. ALK gene fusion in 98 EGFR gene wild type cytologic specimens and in 4 bronchoalveolar lavage fluid (BL) samples was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). ALK gene fusion in the Ventana IHC ALK (D5F3) positive samples was further tested by fluorescence in situ hybridization (FISH). Six patients with ALK IHC-positive result were followed up to analyze the responses of crizotinib therapy. Comparative experiments: (1) Comparison of the results of 4% neutral buffered formalin fixed for different time (24 h, 48 h, 72 h) on the Ventana IHC ALK (D5F3) staining was conducted in two cases of IHC ALK positive FFPE cell blocks; (2) Comparing qRT-PCR results for ALK fusion in samples from FFPE cell blocks and cytospin prepared slides in 10 cases of lung adenocarcinoma cytologic specimens.</p><p><b>RESULTS</b>Among the specimens examined using the standardized protocol recommended by this study, 229 cases of cytologic specimens met the diagnostic criteria of lung adenocarcinoma. Among them, 207 cases obtained ALK gene test results (by at least one method), with an ALK test ratio of 90.4% (207/229). FFPE cell blocks were successfully prepared in 203 cases, Ventana IHC ALK (D5F3) were successfully performed in all the 203 FFPE cell blocks (100%), and the ALK protein positive detection rate was 10.3% (21/203). ALK fusion was tested in 98 FFPE cytologic samples of EGFR wild types by qRT-PCR, and 96 out of 98 (97.96%) cytologic samples were successfully performed.18 out of 19 IHC ALK-positive cases were verified to be of ALK fusion status by qRT-PCR. The concordance rate was 94.7% (Kappa=0.967, P<0.001) between Ventana IHC ALK (D5F3) and qRT-PCR, and the sensitivity of the Ventana IHC ALK (D5F3) assay compared with qRT-PCR was 100% and the specificity was 98.7%. FISH assay was used to verify the positive cases detected by Ventana IHC ALK (D5F3) staining. Two cases of low tumor cell content FFPE samples obtained indefinite results by FISH test. The six patients with positive ALK protein expression received crizotinib therapy, and 5 paitents got treated effectively. For two ALK IHC positive cases, which were 4% neutral buffered formalin fixed for 72 h, the result of Ventana IHC ALK (D5F3) staining became weakened obviously and uneven. In 10 cases of samples, total RNA was extracted from FFPE cytologic sections and cytospin prepared slides, and the results of qRT-PCR test and ALK gene fusion showed good concordance.</p><p><b>CONCLUSIONS</b>The standardized protocol recommended in this study expands the detection types and quantity of cytologic specimens for ALK protein expression and gene fusion and increased the detection rate. Ventana IHC ALK (D5F3) is a reliable method for detecting ALK protein expression in FFPE cell blocks. The pathologic quality control procedure prior to Ventana IHC ALK (D5F3) is crucial for the accuracy of testing the ALK gene status. When FFPE cell blocks could not be prepared or prepared unsuccessfully from the cytologic specimens, qRT-PCR may be an alternative option for the detection of ALK gene fusion.</p>

Effects of chronic arsenic exposure on mRNA expression of estrogen receptor-binding fragment-associated gene 9 and estrogen-responsive finger protein in female rat's uterus and ovary tissue / 中华地方病学杂志

Objective To observe the effects of chronic arsenic exposure on mRNA expression of estrogen receptor-binding fragment-associated gene 9 (Ebag9) and estrogen-responsive finger protein (efp) in uterus and ovary of female rats.Methods Fifty female Wistar rats were randomly divided into five groups according to arsenic (As2O3) concentrations given through drinking-water:0.00 (control),0.05,0.10,0.20,0.40 mg/L arsenic exposure groups and real-time RCR (RT-PCR) was used to detect the mRNA expression of Ebag9 and efp in uterus and ovary tissue at the 31 weeks of experiment.Results The mRNA expression levels of Ebag9 and efp of the 0.00,0.05,0.10,0.20,0.40 mg/L arsenic exposure groups were respectively as follows:0.761 ± 0.178,0.521 ± 0.130,0.544 ± 0.035,0.525 ± 0.198,0.498 ± 0.240 and 0.795 ± 0.171,0.874 ± 0.077,0.797 ± 0.066,0.796 ± 0.040,0.832 ± 0.096.Compared with control group,a decreased tendency was observed in Ebag9 mRNA level(with P value 0.055 in 0.40 mg/L arsenic exposure group) and increased tendency in efp mRNA level in experimental groups (all P ＞ 0.05).The mRNA expression levels of Ebag9 and efp in ovary of the five groups were by turns:0.702 ± 0.484,0.719 ± 0.336,0.693 ± 0.095,0.706 ± 0.055,0.728 ± 0.073 and 0.924 ± 0.061,1.009 ± 0.034,0.930 ± 0.085,0.929 ± 0.068,1.012 ± 0.101.Compared with control group,the expression level of Ebag9 mRNA showed a increased tendency in 0.05,0.20,0.40 mg/L arsenic exposure groups(all P ＞ 0.05).The efp mRNA level increased in experimental groups,with significant difference in 0.05,0.40 mg/L groups (all P ＜ 0.05).Conclusions The expression of efp mRNA has changed in ovary of female rats exposed to chronic arsenic.Arsenic may act as an environmental endocrine disruptor to exert its effect.

Clinical scheme design of in vitro tumor diagnostic reagents / 中华检验医学杂志

Cancer is a serious threat to human health with high morbidity and high mortality , using vitro tumor diagnostic reagents can improve the level of diagnosis and treatment.In order to develop the value of in vitro tumor diagnostic reagents in clinical use , this article would analyze “in vitro diagnostic reagents technical guidelines for clinical research” ,“in vitro diagnostic reagents registration” and other laws and regulations ,as well as the development of research in domestic and foreign.To discuss the clinical scheme design and development trend of in vitro tumor diagnostic reagents.