Validation is a documented process that provides a high degree of assurance. The computer system does exactly and consistently what it is designed to do in a controlled manner throughout the life. The validation process begins with the system proposal/requirements definition, and continues application and maintenance until system retirement and retention of the e-records based on regulatory rules. The objective to do so is to clearly specify that each application of information technology fulfills its purpose. The computer system validation (CSV) is essential in clinical studies according to the GCP standard, meeting product's pre-determined attributes of the specifications, quality, safety and traceability. This paper describes how to perform the validation process and determine relevant stakeholders within an organization in the light of validation SOPs. Although a specific accountability in the implementation of the validation process might be outsourced, the ultimate responsibility of the CSV remains on the shoulder of the business process owner-sponsor. In order to show that the compliance of the system validation has been properly attained, it is essential to set up comprehensive validation procedures and maintain adequate documentations as well as training records. Quality of the system validation should be controlled using both QC and QA means.
Clinical Trials as Topic ; Database Management Systems ; standards ; Information Storage and Retrieval ; standards ; Software Validation

Objective To assess the dietary risk of organophosphates pesticides residues in some vegetables in Shaanxi Province. Methods The monitoring data of organophosphorus pesticides in vegetables from 2012 to 2016 were derived from Shaanxi Province Food Contamination Monitoring Network. The exposure of organophosphorus to vegetables by using exposure risk index (ERI) , dietary exposure risk index (RI) and dietary exposure risk assessment. Results Exposed risk index (ERI) of organophosphorus in some vegetables in Shaanxi Province ranged from 1.25E-06 to 1.87E-01, and among them, the highest ERI of clozaptid in garlic was 1.87E-01, followed by onion. In some vegetables, the highest exposure to organophosphorus was isocarbophos of fresh beans with an exposure of 4.27E-02 μg / (kg body weight · day) and the lowest dietary exposure was bulbs, and stems and fresh beans were 2.00E-04μg / (kg body weight·day) . The exposure of organophosphorus to all kinds of vegetables was less than their respective daily allowable intake (ADI) . The risk of dietary exposure to organic- phosphorus in vegetables was 187％ and greater than 100％ for the risk index (RI) of lettuce, and RI for all other vegetables was <100％. Conclusion The dietary exposure and risk index of organophosphates pesticides in some vegetables in Shaanxi Province was safe, and more attention should be paid to dimethoate and isazofos.

OBJECTIVES(1) To evaluate the prevalence, phenotypes and suppressive function of CD4+CD25+ regulatory T cells (Tregs) among the in peripheral blood mononuclear cells (PBMCs) and tumor-infiltration lymphocytes (TILs) from hepatocellular carcinoma (HCC) patients and patients with chronic hepatitis B. (2) To investigate the correlation between the frequency of CD4+CD25+ Tregs and clinical characteristics of HCC patients.

METHODSPBMCs and TILs in 18 HCC patients, 10 chronic hepatitis B (CHB) patients and 15 healthy donors were evaluated for the phenotypes of CD4+CD25+ Tregs and the proportion of CD4+CD25+ Tregs as a percentage of the total CD4+ cells, by flow cytometric analysis with three or four color staining. The relationship between the frequency of CD4+CD25+ Tregs and tumor TNM stages was analyzed. The CD4+CD25+ Tregs and CD4+CD25- T cells were isolated from PBMC of HCC patients and donors. The suppressive function of CD4+CD25+ Tregs was analyzed.

RESULTSThe percentages of CD4+CD25+ Tregs of the HCC patients (6.38% +/- 6.30%) and CHB patients (4.29% +/- 1.82%) were significantly higher than those of the healthy donors (1.58% +/- 0.55%, P less than 0.01). Among the TILs, the percentage of CD4+CD25+ Tregs was higher (t = 4.39, P < 0.01). There were significant differences in the prevalence of CD4+CD25+ Tregs in early and advanced stage HCCs (stage II vs. III, P less than 0.05; stage II vs. IV P < 0.01). The proliferative capacity of CD4+CD25- T cells was inhibited by the presence of CD4+CD25+ T cells in a dose-dependent manner where the level of suppression was correlated to the ratio of the two-cell populations.

CONCLUSIONThese results suggest that the increase in frequency of CD4+CD25+ Tregs might play a role in the suppression of the immune response against HCC, which may contribute to the HCC cells that escaped from immunological surveillance.

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; Female ; Humans ; Interleukin-2 Receptor alpha Subunit ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; T-Lymphocytes, Regulatory ; immunology ; Young Adult

OBJECTIVETo explore the mechanism of tanshinol on alleviate the inflammatory injury of lung tissue in rat hepatopulmonary syndrome (HPS).

METHODSSD rats were randomly divided into normal control group (n = 8), hepatopulmonary syndrome (HPS) group (n = 11) and tanshinol intervention group (n = 9). HE staining was used to observe the histopathology changes of pulmonary and hepatic tissues, and to count the number of macrophages in lung tissues. The activity of alanine transferase (ALT) and concentrations of endotoxin, tumor necrosis factor-a (TNF-alpha) and homocystein (Hcy) in plasma were detected. The concentrations of TNF-alpha, nitric oxide (NO) and malondialdehyde (MDA) and the activity of inducible nitric oxide synthase (iNOS) in the lung tissues were measured, respectively.

RESULTSThickened alveolar septum and increased macrophages were observed in lungs in HPS rat. After administered with tanshinol, the pulmonary pathological changes were alleviated and the number of macrophages in lung tissue was decreased compared with HPS group. The activity of ALT and the concentrations of endotoxin, TNF-alpha and Hcy in plasma ,and TNF-alpha, iNOS, NO and MDA in lung tissue in HPS group were higher than those of normal control group; meanwhile, those tanshinol group were less those that of HPS group.

CONCLUSIONTanshinol may play an important role in delaying the development of HPS through protecting liver or directly antagonizing the effect of intestinal endotoxemia so as to alleviate the inflammatory reaction in lung tissue.

Alanine Transaminase ; metabolism ; Animals ; Caffeic Acids ; pharmacology ; Disease Models, Animal ; Endotoxins ; blood ; Hepatopulmonary Syndrome ; drug therapy ; pathology ; Homocysteine ; blood ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo explore the impact of 36-hour sleep deprivation (SD) on the brain electrophysiological indicators of visuo-motor coupling in young soldiers.

METHODSDuring the 36-hour SD, 10 healthy young soldiers were tested on visuospatial rotation tasks by event-related potentials system before and after SD. The incubation period and amplitude of P500 as well as their error number and reaction time were measured.

RESULTSCompared with subjects in SD 0-hour,subjects in SD 36-hour had significantly increased error rate [(9.7 ± 3.9)% vs. (18.3 ± 4.5)%, P<0.05] and significantly increased reaction time [(632.5 ± 53.6) ms vs. (693.6 ± 65.7) ms, P < 0.05]. Subjects in SD 36-hour showed significantly reduced amplitudes than those in SD 0-hour [(8.7 ± 2.3) ΜV vs. (5.2 ± 1.6) ΜV, P < 0.05]. Additionally, subjects in SD 36-hour showed significantly increased P500 latencies than did those in SD 0-hour [(489.6 ± 42.6) ms vs .(530.2 ± 51.9) ms, P < 0.05]. Compared with subjects in SD 0-hour, the deficit was an absence of a mental rotation function SD 36-hour in subjects.

CONCLUSIONSThe 36-hour SD in young soldiers can harm the processing mechanism of visuo-motor coupling in a certain extent. SD can affect the fixed position ability of visual space cognition in young soldiers.

Adolescent ; Adult ; Evoked Potentials ; Feedback, Sensory ; Female ; Humans ; Male ; Military Personnel ; Reaction Time ; Sleep Deprivation ; physiopathology ; Young Adult

ObjectiveThis study is aimed to investigate the association of human leukocyte antigen (HLA)-DRB1 with rheumatoid arthritis (RA) in Chinese Han population.MethodsA total of 281 Chinese Han patients with RA and 202 healthy controls were recruited.DNA was extracted from PBMC and HLA typing was performed by sequence based typing and PCR-Sequence Specific Primer.The frequency of HLADRB1 was compared between patients and controls using x2 test with continuity correction.ResultsThe susceptible HLA-DRB1 alleles were * 0101,* 0102,*0404,* 0405,and * 0410 which belonged to QRRAA.DRRAA and DERAA were protective alleles.At genotypic level,The association of S3P and S3D was detected.However,the protective effect of S3D was shown to be in a recessive mode.ConclusionOur results have shown that there are racial differences in RA susceptibility between Chinese Han population and Caucasians.

BACKGROUNDThe dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria are two major types. While clinical and histological presentations are similar in these two diseases, genetic diagnosis is critical in the differential diagnosis of these entities.

METHODSThree patients initially diagnosed with DUH were included. The gene test was carried out by targeted gene sequencing. All mutations detected on ADAR1 and ABCB6 genes were analyzed according to the frequency in control database, the mutation types, and the published evidence to determine the pathogenicity.

RESULTSFamily pedigree and clinical presentations were reported in 3 patients from two Chinese families. All patients have prominent cutaneous dyschromatoses involving the whole body without systemic complications. Different pathogenic genes in these patients with similar phenotype were identified: One novel mutation on ADAR1 (c. 1325C>G) and one recurrent mutation in ABCB6 (c. 1270T>C), which successfully distinguished two diseases with the similar phenotype.

CONCLUSIONTargeted gene sequencing is an effective tool for genetic diagnosis in pigmentary skin diseases.

ATP-Binding Cassette Transporters ; genetics ; Adenosine Deaminase ; genetics ; Adolescent ; Asian Continental Ancestry Group ; Child ; Diagnosis, Differential ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Pedigree ; Pigmentation Disorders ; congenital ; diagnosis ; genetics ; RNA-Binding Proteins ; genetics ; Skin Diseases, Genetic ; diagnosis ; genetics

OBJECTIVETo compared outcomes of robotic mitral valve repair with those of standard sternotomy, and right anterolateral thoracotomy.

METHODFrom August 2010 to July 2011, 70 patients with degenerative mitral valve disease and posterior leaflet prolapsed scheduled for elective isolated mitral valve repair were prospectively nonrandomized to undergo mitral valve operation by standard sternotomy (n = 30), right anterolateral thoracotomy (n = 30), or a robotic approach (n = 10). There were 49 male and 21 female patients, aging from 16 to 70 years with a mean of 53.4 years. Outcomes of the three groups were compared.

RESULTSMitral valve repair was achieved in all patients except 1 patient in the standard group. There were no in-hospital deaths. The median operation time [(300 ± 41) min, (184 ± 20) min and (169 ± 22) min, F = 112.5, P < 0.01], cardiopulmonary bypass time [(139 ± 26) min, (82 ± 20) min and (69 ± 23) min, F = 36.8, P < 0.01], aortic cross-clamping time [(93 ± 23) min, (47 ± 10) min and (38 ± 8) min, F = 75.0, P < 0.01] were longer for robotic than standard sternotomy and right anterolateral thoracotomy. The robotic group had shortest time of mechanical ventilation time [(4.9 ± 2.1) h, (5.3 ± 4.5) h and (14.1 ± 10.2) h, F = 13.2, P < 0.01], ICU time [(15.1 ± 2.1) h, (16.4 ± 5.4) h and (28.7 ± 16.1) h, F = 11.6, P < 0.01], postoperative hospital stay time [(4.6 ± 1.0) d, (5.7 ± 1.7) d and (8.8 ± 5.1) d, F = 8.0, P < 0.01] with the lowest of drainage [(192 ± 200) ml, (215 ± 163) ml and (405 ± 239) ml, F = 7.1, P < 0.01] and ratio of the patients needed blood transfusion (0, 20.0% and 66.7%, χ(2) = 22.7, P < 0.01). Patients were followed up 6 to 17 months, with 100% completed. No patients died during follow-ups, and no moderate or more mitral regurgitation was observed. The robotic group had the shortest time of return to normal activities compared with the other two groups [(2.4 ± 0.7) weeks, (4.2 ± 1.2) weeks and (8.2 ± 1.8) weeks, F = 83.0, P < 0.01].

CONCLUSIONThis study shows mitral valve repair via the right anterolateral thoracotomy and a robotic approach is safe and feasible, with good cosmetic results and rapid postoperative recovery, and is worthy of clinical selective application.

Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Mitral Valve ; surgery ; Mitral Valve Prolapse ; surgery ; Prospective Studies ; Robotics ; Thoracic Surgical Procedures ; methods ; Treatment Outcome ; Young Adult

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.
Consolidation Chemotherapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Remission Induction

OBJECTIVESTo investigate the possibilities of an association between the degrees of HBV suppression with nucleoside treatments at week 24 and week 52 in hepatitis B patients and to find a useful predictor for treatment efficacy.

METHODSIn this phase III, double-blind, multicenter trial, we compared the efficacy of telbivudine treatment with lamivudine treatment in 332 Chinese compensated chronic hepatitis B patients. The patients were randomly assigned to a daily 600 mg telbivudine treatment group or daily 100 mg lamivudine group for 24 weeks. They were then categorized into 4 groups according to their serum HBV DNA levels (copies/ml) at week 24: a PCR-undetectable group (< 300 copies/ml); a QL- < 10(3) copies/ml group; a 10(3)-<10(4) copies/ml group; and a > or = 10(4) copies/ml group. The treatments were continued as they previously had been for another 28 weeks and the patients serum HBV DNA levels were examined again.

RESULTSAt week 52, mean reductions of serum HBV DNA were significantly greater in the telbivudine-treated patients than in the lamivudine-treated group (6.2 log10 vs 5.4 log10, t = 3.6, P < 0.01). Viral resistance was twice as common in lamivudine-treated patients compared to those receiving telbivudine. Telbivudine was well-tolerated with an adverse event profile similar to that of lamivudine. The lower the HBV DNA level achieved at week 24, the higher HBV DNA non-detectable by PCR. ALT normalization and HBeAg seroconversion achieved at week 52, and viral resistance at week 48 decreased parallel to the degree of HBV DNA inhibition.

CONCLUSIONHBV DNA PCR-undetectable at week 24 in nucleoside-treated hepatitis B patients suggests a better efficacy at week 52 and lower viral resistance at week 48. The degree of suppression of HBV at week 24 may be used as a predictor of 1-year outcome.

Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Double-Blind Method ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Nucleosides ; therapeutic use ; Pyrimidinones ; therapeutic use ; Thymidine ; analogs & derivatives ; Treatment Outcome ; Young Adult