The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

We present an unusual case of a patient with bilateral-lung transplantation due to severe coronavirus disease 2019 (COVID-19), who subsequently suffered complications with acute myocardial infarction and underwent primary percutaneous coronary intervention (PCI).
Aged ; Betacoronavirus ; China ; Coronavirus Infections ; complications ; Humans ; Lung Diseases ; surgery ; virology ; Lung Transplantation ; Male ; Pandemics ; Percutaneous Coronary Intervention ; Pneumonia, Viral ; complications ; ST Elevation Myocardial Infarction ; surgery ; virology

Background: Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC. Methods: RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development. Results: RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC. Conclusion RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

Objective To analyze the status of quality indicators(QI) on specimen acceptability and establish preliminary qual ity specification.Methods Web based External Quality Assessment system was used to collect data of laboratories partici pated in "Medical quality control indicators in clinical laboratory" from 2015 to 2017,including once in 2015 and 2017 and twice in 2016.Rate and sigma scales were used to evaluate incorrect sample type,incorrect sample container,incorrect fill level and anticoagulant sample clotted.The 25th percentile (P25) and 75th percentile (P75) of the distribution of each QI were employed to establish the high,medium and low specification.Results 5 346,7 593,5 950 and 6 874 laboratories sub mitted the survey results respectively.The P50 of biochemistry (except incorrect fill level),immunology and microbiology reach to 6σ.The P50 of clinical laboratory is 4 to 6σ except for incorrect sample container.There is no significant change of the continuous survey results.Based on results in 2017 to establish the quality specification,the P25 and P75 of the four QIs is 0 and 0.084 4 ％,0 and 0.047 6 ％,0 and 0.114 2 ％,0 and 0.078 4 ％,respectively.Conclusion According to the results of the survey,most laboratories had a faire performance in biochemistry,immunology and microbiology,and clinical laboratory needs to be strengthened.Laboratories should strengthen the laboratory information system construction to ensure the actual and reliable data collection,and make a long time monitoring to achieve a better quality.

BACKGROUNDThe diagnostic value of current prostate-specific antigen (PSA) tests is challenged by the poor detection rate of prostate cancer (PCa) in repeat prostate biopsy. In this study, we proposed a novel PSA-related parameter named PSA density variation rate (PSADVR) and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy.

METHODSData from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study. The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results. Prostate volume, PSA density (PSAD), free-total PSA ratio, and PSADVR were calculated according to corresponding formulas at the second biopsy. These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups, and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection.

RESULTSPCa was detected in 24 patients on the second biopsy. Mean values of PSA, PSAD, and PSADVR were greater in the PCa group than in the non-PCa group (8.39 μg/L vs. 7.16 μg/L, 0.20 vs. 0.16, 14.15% vs. -1.36%, respectively). PSADVR had the largest area under the curve, with 0.667 sensitivity and 0.824 specificity when the cutoff was 10%. The PCa detection rate was significantly greater in subjects with PSADVR >10% than PSADVR ≤10% (28.6% vs. 6.5%, P< 0.001). In addition, PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa (r = 0.63, P = 0.03).

CONCLUSIONSOur results demonstrated that PSADVR improved the PCa detection rate on second biopsies, especially for mid-to-high-risk cancers requiring prompt treatment.

Aged ; Biopsy ; methods ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Prostate ; metabolism ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; diagnosis ; ROC Curve

Objective To assess the clinical effectiveness and safety of relinqing pharmaceutical preparations for the treatment of uncomplicated urinary tract infection(UTI). Methods The genitourinary infection, urinary tract infection, pyelonephritis, cystitis, stranguria and urethritis were used as key words to search at CNKI,VIP,SinoMed,PubMed,Wan Fang and Cochrane Library Databases up to April 2015. Data of randomised controlled trials (RCTs) comparing treatments using relinqing were included in this study. The quality of the literature was evaluated by the method of Cochrane handbook 5.1.0. Data extraction was carried out independently by two authors. RevMan 5.2 software was used for Meta-analysis. Results Five RCTs were included that involved a total of 471 uncomplicated UTIs. Analysis of four studies showed a higher rates of effectiveness for uncomplicated UTI in the treatment with relinqing plus antibiotics than those of antibiotics alone [RR and 95%CI:1.15 (1.08-1.23), P<0.001]. Analysis of two studies showed a higher rates of bacterial clearance for uncomplicated UTI in the treatment with relinqing plus antibiotics than those of antibiotics alone [RR and 95% CI: 4.04 (1.78-9.16)]. Conclusion Data from five small studies suggest that relinqing as an independent intervention or in conjunction with antibiotics may be beneficial for treating uncomplicated UTIs. However, the small number and poor quality of the included studies meant that it is not possible to formulate robust conclusion on the use of relinqing for uncomplicated UTI either alone or as an adjunct to antibiotics.

Objective To analyze the relation between personality characteristics,coping styles and division management,so as to understand the relationship between mental health status,personality characteristics,and workplace of new nurses during the adapting period of department environment,and improve the quality of care.Methods Totals of 61 nurses who were assigned to a comprehensive hospital in 2010 as the experimental group,and other 65 nurses who were assigned to the hospital in 2009 as the control group.The experimental group adopted the management of department division by analyzing the personality traits,coping style assessment and nurse leadership style,while the control group was randomly division.Intervention effects were evaluated respectively in before division,6 months and 18 months after division.Results There were six nurses left in control group,the left rate was 9％,while no one left in experimental group.Hostility factor score of SCL-90 of experimental group was lower than that in control group after 6 months of division (t =3.12,P ＜0.01),as well as the scores of retreat of coping style and rationalization factor (t =3.75,3.35,respectively;P ＜ 0.01).Forcing factor score of SCL-90,and self-reproach factor score of coping in experimental group were lower than that in control group (t =2.02,2.68,respectively ; P ＜ 0.05),while EPQL factor score was significantly higher than that in control group(t =2.20,P ＜ 0.01) after 18 months of division.Conclusions According to the psychological characteristics and coping style of new nurses,and leadership style of head nurses to divide the department for new nurses can improve mental health of the new nurses,promote them to adopt mature and positive coping styles to the stress,and promote their loyalty for the nursing and the stability of nurses team.

BACKGROUND AND OBJECTIVEExpression of Skp2 was related with the prognosis of several tumors. However, there was no intensive study on the relationship between Skp2 and extranodal NK/T cell lymphoma. This study was to explore the role of Skp2 in extranodal NK/T cell lymphoma.

METHODSThe clinicopathological data of 39 patients with extranodal NK/T cell lymphoma were analyzed. The expression of Skp2 was examined by immunohistochemistry on formalin fixed, paraffin embedded tissue sections.

RESULTSAmong the patients with high expression of Skp2, complete remission (CR) rate was only 14.3% (2/14). However, CR rate among the patients with low expression of Skp2 was 68.0% (17/25). Significant difference was shown between these two groups (P < 0.001). In the group of low expression, the median overall survival (OS) was 85.59 months (95% CI: 35.83 135.34 months), the 1 and 2 year OS rates were 81% and 71%, respectively. However, in the group of high expression, the median OS was only 9.73 months (95% CI: 2.05-17.40 months), the 1 and 2 year OS rates were 42% and 14%, respectively. There was statistical difference between these two groups (P < 0.001). Multivariate analysis showed that Skp2 expression (P <0.001), LDH (P = 0.026) and ECOG PS (P = 0.003) were dependent prognostic factors of extranodal NK/T cell lymphoma.

CONCLUSIONHigh expression of Skp2 is an independent unfavorite adverse prognostic factor of extranodal NK/T cell lymphoma.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; L-Lactate Dehydrogenase ; blood ; Lymphoma, Extranodal NK-T-Cell ; drug therapy ; metabolism ; pathology ; radiotherapy ; Male ; Middle Aged ; Neoplasm Staging ; Remission Induction ; S-Phase Kinase-Associated Proteins ; metabolism ; Survival Rate ; Young Adult

BACKGROUND AND OBJECTIVECD133-positive colon cancer stem like cells (CSLCs) are resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU). Wnt signaling pathway plays important roles in colon cancer carcinogenesis and metastasis, and regulates the self-renewal capacity of CSLCs. In the present study, we explored the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and the relation between Wnt signaling pathway and drug resistance of CD133-positive colon CSLCs.

METHODSMagnetic activation cell separation was used to collect CD133-positive cells from colon cancer cell line DLD1, which was transfected with luciferase reporter for Wnt signaling activity. The activity of Wnt signaling pathway was compared between CD133-positive and CD133-negative cells. After the treatment with 1 μg/mL of 5-FU, the cell proliferation rates of DLD1 cells, CD133-positive cells, and CD133-negative cells were compared. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU for 48 h, Wnt activity was compared between CD133-positive and CD133-negative cells. The expression of CD133 and cell apoptosis of CD133-positive cells was detected after exposure to 50 ng/mL of dickkopf (DKK)-1, a Wnt pathway inhibitor.

RESULTSAfter the treatment with 5-FU, the cell proliferation rate of CD133-positive cells was higher than that of CD133-negative cells and the sensitivity of CD133-positive cells to 5-FU decreased. Wnt activity was higher in CD133-positive cells than in CD133-negative cells [(46.3 ± 0.3)% vs. (33.9 ± 2.7)%, P = 0.009]. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU, Wnt activity of CD133-positive cells was (90.1 ± 10.0)% (P = 0.012) and (52.9 ± 2.5)% (P = 0.047), respectively, whereas that of CD133-negative cells was (35.5 ± 3.3)% (P = 0.434) and (26.5 ± 0.4)% (P = 0.046), respectively. CD133 expression in CD133-positive cells decreased from (87.2 ± 5.3)% to (60.6 ± 3.1)% (P = 0.022) after treatment with DKK-1, whereas the cell apoptosis rate increased from (11.8 ± 0.2)% to (28.3 ± 0.6)% (P = 0.013).

CONCLUSIONSWnt activity is higher in CD133-positive DLD1 cells than in CD133-negative DLD1 cells. 5-FU can upregulate Wnt activity of CD133-positive colon CSLCs. Blocking Wnt activity may reverse drug sensitivity of CD133-positive cells to 5-FU.

AC133 Antigen ; Antigens, CD ; metabolism ; Antimetabolites, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; metabolism ; pathology ; Drug Resistance, Neoplasm ; Fluorouracil ; pharmacology ; Glycoproteins ; metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; pharmacology ; Neoplastic Stem Cells ; metabolism ; pathology ; Peptides ; metabolism ; Wnt Signaling Pathway ; drug effects

Objective To observe the state of endemic flurosis in Qinghai province in 2008 and to provide scientific basis for endemic flurosis control and prevention. Methods All the endemic fluorosis villages in Qinghai province was divided into slight,medium and heavy degree according to the water fluoride content before improving water,and 2,4,4 villages were collected from each degree,respectively. Water samples were collected from each direction of east,west,south,north and centre,and fluoride concentration were determined from each surveyed villages with unimproved-water. At the same time,3 copies of the peripheral water samples and a sample of source water were collected to determine fluoride concentration. In all the village children aged 8 to 12 were tested for dental fluorosis by Dean method. Six copies of the urinary fluoride were randomly sampled in different age groups. The fluorine content in urine was determined with F-ion selective electrode. The situation of clinical skeletal fluorosis of adults over 16 years of age was examined,and 20 adults in the villages of medium and heavy levels were filmed for skeletal fluorosis. Results The detectable rate of dental fluorosis of children aged 8-12 years old was 43.59% (245/562),that of skeletal flurosis of adults aged above 16 years was 50.32% (1582/3144) and detectable rate of X-ray was 29.45% (48/163). Fluoride content in urine was 1.52 mg/L. Conclusions Endemic fluorosis is still very serious in Qiaghai province in a rising trend,so the control measures need to be strengthen.