In clinical laboratory medicine,measurement uncertainty (MU) is a fixed property of testing results in the measuring system.As an important part of ISO 15189,it is necessary for clinical laboratories to determine MU during the period of validation and verification for each measurement procedure and to review MU over time.Now,testing reports provided by clinical laboratories usually do not offer MU,but some clinical laboratories have already estimated MU in their routine work.Estimation andmonitoring of MU can help clinical laboratories offering more accurate results and provide objective tools for clinicians used in result intcrpretatinn.Generally,result interpretation can be achieved by the result comparison with three main comparators,including a previous result from the same patient,a population reference interval and a clinical decision point.The means of true value and the components contributing to the estimation of MU are both different when the com parison is conducted between testing results and different comparators,so the optimum estimation method of MU is accordingly different,which will subsequently affect the MU value and the determination of clinical decisions.Obviously,depending on the actual clinical uses,laboratories can choose appropriate comparators to the result interpretation and the determination of optimum estimation method of MU.For different clinical uses (diagnosis or monitoring) of the same mearurands,the adoption of different estimation methods should be used to acq uire reasonable MU.By interpreting the concept,characteristics,estimation,and uses of MU,as well as explaining how three main comparison methods of results exploit their own traceable chain to get MU,this paper intends to help clinical laboratories get further understanding of the importancc of MU and provide guidance for the MU estimation in routine work.

In the clinical laboratory medicine,the measurement uncertainty (MU)is a relatively new concept.Over the years, experts of clinical laboratory medicine from all over the world made a great number of further researches and promote the development of MU,which led clinical laboratories to pay more and more attention to the meanings and functions of MU at the same time.However,because of the habitual using of the total error (TE)in clinical laboratories and similarities between concepts of MU and TE which easily resulted in confusion,a lot of laboratories still cannot completely accept MU.By explai-ning concepts of TE and MU and analyzing the pros and cons of models of TE and MU as well as their functions,the obj ec-tive of this paper is to help clinical laboratories make further comprehensions of TE and MU and understand how to properly use them in practice.

Objective To analyze the reference intervals of serum total bilirubin (TBIL) and serum direct bilirubin (DBIL) by all Chinese clinical laboratories and make a comparison with the upcoming part 4 of Industry Standard WS/T 404.Methods Relevant information about reference intervals of all clinical laboratories participating in TBIL and DBIL testing items of 2014 national external quality assessment scheme of clinical routine chemistry was collected by a web-based external quality assessment software,including source,grouping,verification,upper and lower limits of reference intervals and instruments,reagents,methods and calibrators used.Microsoft Excel 2010 and SPSS 19.0 were applied to statistical analysis.The comparison between reference intervals used and the upcoming Industry Standard was conducted by the simple mean t test.Laboratories derived from the highest percentage of source distribution whose reagent and instrument were matching with each other were grouped according to the test systems used and the differences of reference intervals between three mainly used test systems and the upcoming Industry Standard were also compared with the single sample mean t test.Results The number of laboratories participated in the investigation about source distribution of reference intervals for TBIL and DBIL was 749 and 709 respectively.For these two items,the highest sources were both instructions of reagent(TBIL 58.08％,DBIL 58.67 ％),next were both National Clinical Laboratory Operation Rules (3rd Edition) (TBIL 29.64 ％,DBIL 28.91 ％),the percentages of other sources were all less than 10％.Besides,there were respectively 379 (50.60％) and 354 (49.93％) laboratories verifying their reference intervals for TBIL and DBIL.The difference of the comparison between reference intervals used and the upcoming Industry Standard had statistical significance (P＜0.05).The using reference intervals were narrower than the upcoming Industry Standard for both items.In all laboratories with reference intervals from instructions of reagent,themating laboratories respectively accounted for 41.88％ and 41.48％％ for item TBIL and DBIL.As the single sample mean t test showed,the comparison of the reference intervals between three mainly used test systems in these mating laboratories and the upcoming Industry Standard had statistical significance (P＜0.05),except for the lower limit of DBIL with Beckman test system (P value was 0.068) and the upper limit of DBIL with HITACHI test system (P value was 0.087).Conclusion Currently,the using situation of reference intervals about TBIL and DBIL by all Chinese laboratories was not scientific and rational enough and has significant difference with the upcoming Industry Standard.Should publish the part 4 of Industry Standard WS/T 404 as soon as possible,which would help clinical laboratories establishing suitable reference intervals and promote the standardization of its usage.

Objective To evaluate the effects of age factors on the pharmacokinetics of ropivacaine during combined lumbar plexus-sciatic nerve block in patients.Methods Twenty patients of both sexes,aged ≥ 18 yr,weighing 50-75 kg,of American Society of Anesthesiology physical status Ⅰ or Ⅱ,scheduled for elective lower extremity surgery,were divided into 2 groups (n=10 each) according to age:young and middle-aged group (18-59 yr) and elderly group (≥ 60 yr).Combined lumbar plexus-sciatic never block was performed using an ultrasonic instrument and a nerve stimulator.Lumbar plexus block was performed with 0.5％ ropivacaine 30 ml.Sciatic never block was performed with 2％ lidocaine 10 ml plus 0.75％ ropivacaine 10 ml.Before administration and at 5,10,15,20,30,45,60,120,180 and 360 min after administration,blood samples were collected from the radial artery for determination of the blood concentration of ropivacaine by high-performance liquid chromatography.The area under the concentrationtime curve,maximum concentration (Cmax),time to C terminal elimination half-life and clearance were calculated.Results Compared with young and middle-aged group,the blood concentration of ropivacaine was significantly decreased at 5-45 min after administration,the Cmax was significantly decreased,terminal elimination half-life was significantly prolonged (P＜0.05),and no significant change was found in area under the concentration-time curve,the time to C and clearance in elderly group (P＞ 0.05).Conclusion Age factors can affect the pharmacokinetics of ropivacaine during combined lumbar plexus-sciatic nerve block,and both absorption and metabolism of ropivacaine are slower in elderly patients than in young and middle-aged patients.

OBJECTIVE: To observe the effect of Qiang Jin exercises on the muscle strength and activity of lumbar spine in patients with lumbar disc herniation. METHODS: From March 2016 to September 2017, at the Department of Orthopaedics, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, a total of 110 subjects were enrolled, and 98 eligible subjects were screened. The subjects were randomized by stratified randomization and divided into experimental group and control group, 49 cases in each group, 25 males and 24 females in the experimental group, 25 males and 24 females in the control group. The experimental group exercised with Qiang Jin exercises, one time each morning and evening, each time10 sets were made;the control group used classic rehabilitation training, training twice a week, and three months was a course of treatment. After 12 weeks of training, the muscle strength and activity of the lumbar spine were evaluated and compared with the muscle strength and activity of the lumbar spine before training. RESULTS: The experimental group and the control group had different muscle strength and activity of the lumbar spine before and after treatment ( CONCLUSION Qiang Jin exercises can effectively improve the muscle strength and activity of the lumbar spine and improve the daily living ability of patients.
China ; Female ; Humans ; Intervertebral Disc Degeneration ; Intervertebral Disc Displacement ; Lumbar Vertebrae ; Lumbosacral Region ; Male ; Treatment Outcome

Objective To explore the efficacy, safety, and factors that might influence the efficacy of antiPD-1 antibody-based therapy in advanced hepatocellular carcinoma in the real world. Methods The clinical features, efficacy, and safety in patients with advanced hepatocellular carcinoma who received anti-PD-1 antibody-based therapy were retrospectively analyzed. The survival status was followed-up. Results The objective response and the disease control rate were 21.8% and 76.4%, respectively. The overall incidence of adverse events during treatment was 81.8%, of which the incidence of grade 3/4 adverse events was 14.5%. The incidence of immune-related adverse events was 58.2% and the incidence of grade 3/4 immune-related adverse events was 3.6%, and no treatment-related death was observed. The median PFS of the 55 patients was 5.0 (95%CI: 3.9-6.1) months, and the median OS was 11.4 (95%CI: 6.5-16.3) months. Univariate and multivariate analyses showed that liver function Child-Pugh scores and performance status ECOG score were the influencing factors of the objective response rate and survival. Conclusion In the real world anti-PD-1 antibody-based therapy is safe and effective in patients with advanced hepatocellular carcinoma, in which the performance status ECOG score and liver function Child-Pugh score before treatment are independent prognostic factors influencing survival.

Objective:To investigate the effects of genomic location of a foreign gene in Shanghai-191 strain measles virus (MV) vector on gene expression and virus replication.Methods:The nucleotide sequence encoding S1 protein of SARS-CoV-2 was inserted at different positions in MV antigenome (the upstream of the N gene, between P and M genes, between H and L genes), and co-transfected into 293T cells with helper plasmids coding T7 RNA polymerase and N, P, and L proteins, respectively. The transfected cells were lysed and the supernatants were used to infected Vero cells to harvest recombinant viruses. S1 proteins expressed by the recombinant viruses were identified by RT-PCR, indirect immunofluorescence assay, Western blot and ELISA. Growth kinetics of the recombinant viruses were analyzed.Results:Recombinant viruses were failed to be rescued when the S1 protein-coding sequence was cloned into the upstream of N gene. Two recombinant viruses, MV-M-S1 and MV-L-S1, were successfully rescued when cloning the S1 protein-coding sequence into the intergenic region between P and M genes, or H and L genes, and could express S1 protein. MV-M-S1 expressed more S1 protein than MV-L-S1, but the titer of MV-M-S1 was lower.Conclusions:Inserting a foreign gene at different positions in the MV genome might have different effects on gene expression and virus replication. This study provided reference for the subsequent construction of MV vector.

Objective To investigate the characteristics of multimodal MRI of breast cancer with different molecular subtypes and the correlation between each molecular type and MRI findings. Methods Multimodality MRI date of 87 patients with breast cancer confirmed by pathology were retrospectively analyzed. According to the expression of estrogen receptors(ER),progesterone receptors(PR)and human epidermal growth factor receptor-2 (HER-2),the tumors were classified into triple-negative breast cancer,HER-2 overexpression,Luminal A and Lu-minal B subtypes. The MRI features of breast cancers of different molecular subtypes were compared. Results Among the 87 cases of breast cancer,luminal type A accounted for 29.9%(26/87),luminal type B accounted for 36.8%(32/87),HER-2 type accounted for 19.5%(17/87),and triple-negative type accounted for 13.8%(12/87). The average ADC value is 0.97 × 10-3 mm2/s;those whose irregular or edge burr like mass were more often Lu-minal type MRI,triple-negative breast cancer showed the edge smooth,clear boundary,annular enhancement, more easily showed enhanced mode of TIC type Ⅲ. The mean ADC values of type Luminal and HER-2 over-expres-sion were lower than the mean ADC values of the triple-negative type. Conclusion The different molecular sub-types of breast cancer MRI morphologic and hemodynamic characteristics and the value of ADC has certain charac-teristics. The MRI features of breast cancer can be predicted to analyze the molecular typing,providing a reference for clinical treatment.

Objective:To construct a recombinant herpes simplex virus 2 (HSV-2) expressing enhanced green fluorescent protein (EGFP) using clustered, regularly interspaced, short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology.Methods:Four strategies for inserting exogenous EGFP gene into HSV-2 genome using CRISPR/Cas9 technology were designed: (1) conventional homology-directed repair: circular two homology arm donor-mediated gene knock-in; (2) linearized single homology arm donor-mediated gene knock-in; (3) homology-independent targeted integration; (4) conventional homology-directed repair-mediated by cell lines stably expressing Cas9 and sgRNA.Results:The recombinant virus HSV-2-EGFP was successfully constructed based on the second, the third and the fourth strategies. The second strategy was the most efficient, followed by the third and the fourth strategies. The purified recombinant virus could stably express green fluorescent protein in seven passages and shared similar growth characteristics in Vero cells to the parental virus.Conclusions:Linearized single homology arm donor could increase the efficiency of gene knock-in, and cell lines stably expressing Cas9 and sgRNA could increase the efficiency of gene knock-in mediated by homology-directed repair.