Renal function test items mainly include creatinine, urea, uric acid, cystatin C, urine-alb, urine protein, α1-microglobulin, β2-macroglobulin and retinol binding protein, etc.The standardization and harmonization of these renal function test items will contribute to clinical diagnosis and treatment.Therefore, many scholars are committed to the standardization of renal function tests and part of these testshave been standardized.But some test items, due to the complexity of the determination, the process of achieving standardization are still facing some problems and challenges.

There are many types of serum tumor markers,and their structures and functions vary.The standardization and harmonization of serum tumor markers will contribute to clinical diagnosis and treatment.Therefore,many scholars are committed to the research of their standardization.However,there are only a few items have been standardized.Due to the complexity of determination,most tumor markers are still facing problems and challenges in the process of achieving standardization.

Objective:To develop a national secondary reference material of Urea and Creatinine in frozen human serum as a standard for metrological traceability.Methods:According to JJF1343-2012 "General and Statistical Principles for Characterization of Reference Materials" and JJF 1006-1994 " Technical Norm of Primary Reference Material ", the homogeneity, stability, and commutability were evaluated;Using the JCTLM recommended methods, the value of the reference materials was assigned through collaboration with 6 accredited reference laboratories from Guangdong Provincial Hospital of Chinese Medicine, Beijing Aerospace General Hospital, Shenzhen Mindray Bio-Medical Electronics, Maccura Biotechnology, Beijing Leadman Biochemistry, and Zhejiang MedicalSystem Biotechnology. Uncertainty components including inhomogeneity, stability and value assignment were evaluated.Results:The results of one-way analysis of variance of homogeneity for the reference materials showed P>0.05, and the stability evaluation was less than the critical value of the t-test. The measured values were in the 95% confidence interval in the four conventional detection systems for commutability, and the certified values and expanded uncertainties were urea:(14.7±0.3) mmol/L ( k=2),Cr:(313.9±14.5) μmol/L ( k=2). Conclusion:The prepared secondary reference materials of urea and creatinine had promising homogeneity, stability, and commutable, the values of urea and creatinine concentration in reference materials were accurate and reliable.

The concentration and accumulation rate of advanced glycation end products (AGEs) in the body are highly correlated with glycometabolic disorders. Therefore, the clinical detection of AGEs is of great value for the early diagnosis and prognostic evaluation of these diseases. However, due to the complexity of its structure, the diversity of glycosylation sites, and the limitations of existing detection methods, there is still a lack of widely available detection methods in clinical practice. Starting from the structure and classification of AGEs and the value of clinical testing, this article summarizes current status of various laboratory detection methods of AGEs, and the deficiencies and challenges of these testing methods, future directions are further prospected.

The performance of high sensitivity, specificity and throughput makes liquid chromatography-tandem mass spectrometry (LC-MS/MS) quickly developed and well applicated in clinical laboratories, such as quantitative detection of steroids, vitamins and metabolic small molecules, monitoring drug concertrations as well as the establishing reference methods or verifying reference materials. However, there were still some challenges for the widespread clinical application of LC-MS/MS.

Objective To investigate the prognostic value of American Joint Committee on Cancer-tumor regression grading ( AJCC-TRG) combined with ypTN stage in patients with locally advanced rectal cancer (LARC),who were treated with neoadjuvant chemoradiotherapy,and to identify the subgroups with the worst prognosis. Methods A total of 263 patients with LARC,including 176 males and 87 females,with a median age of 55 years,were admitted to Sun Yat-sen University Cancer Center from 2004 to 2012.All the patients received neoadjuvant chemoradiotherapy before surgery and underwent total mesorectal excision at 6 to 8 weeks after radiotherapy. All the surgical specimens were reevaluated according to the AJCC ( 7th edition)-TRG system and ypTN staging criteria. The prognostic prediction by TRG combined with ypTN was evaluated using survival analysis. The Kaplan-Meier method was used to calculate the rates of overall survival ( OS ) , disease-free survival ( DFS ) , local recurrence-free survival ( LRFS ) , and distant metastasis-free survival ( DMFS ) . The log-rank test was used for survival comparison and univariate prognostic analysis. Results The median follow-up was 601 months. The 5-year rates of OS, DFS, LRFS, and DMFS for all patients were 800%,750%,970%,and 810%,respectively. There were significant differences in OS, DFS,and DMFS between different ypT/TRG subgroups and different ypN/TRG subgroups (all P<005). ypT3-4/TRG 2-3 and ypN1-2/TRG 2-3 subgroups showed the worst prognosis. The 5-year rates of OS,DFS, and DMFS of the two subgroups were 669%/560%, 522%/414%, and 609%/460%, respectively. Conclusions A combination of AJCC-TRG system and ypTN staging can better predict the prognosis of LARC and identify the subgroups with the worst prognosis, which may provide a clinical guidance for postoperative individualized decision on adjuvant therapy for LARC.

Objective To investigate the feasibility of non-operative management (NOM) by comparing the therapeutic effects between NOM and total mesorectal excision (TME) for rectal cancer patients with clinical complete response (cCR) after neo-adjuvant chemoradiotherapy.Methods A total of 135 patients with stage Ⅱ/Ⅲ rectal cancer who obtained cCR after neo-adjuvant chemoradiotherapy in Sun Yat-sen University Cancer Center from 2006 to 2016 were recruited and assigned into the NOM (n =43) and standard operative management (SOM) groups (n=92).The local recurrence rate,accumulative local control (LC) rate after salvage therapy,disease-free survival (DFS),overall survival (OS) and sphincter preservation rate were statistically compared between two groups.Kaplan-Meier analysis and log-rank test were utilized to calculate the LC,OS and DFS.Chi-square test was performed to calculate the sphincter preservation rate.Results The mean follow-up duration was 39 months (range:10-127 months).Of 135 patients,the local recurrence rate and distant metastasis rate were 3.7％ and 11.1％,and the 3-year DFS and OS were 90.5％ and 97.0％.In the NOM and SOM groups,the 3-year DFS were 87％ and 93％,and the 5-year DFS were 73％ and 87％(P=0.089).The 3-year OS were 98％ and 99％,and the 5-year OS were 98％ and 97％ (P=0.578).In the NOM group,the local recurrence rate was 12％ (n =5),80％ of patients received salvage treatment and the accumulative LC rate was calculated as 98％.In the SOM group,the local recurrence rate was 0,which was significantly lower than that in the NOM group (P=0.O10).In the NOM group,the sphincter preservation rate was 93％,significantly higher compared with 70％ in the SOM group (P=0.030).Conclusions It is feasible for rectal cancer patients with cCR to receive NOM following neo-adjuvant chemoradiotherapy.Partial locally recurrent patients can be healed by timely salvage therapy,thereby averting TME and relevant complications and enhancing the quality of life of rectal cancer patients.

Objective:To establish a candidate reference method for serum progesterone using isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) in our laboratory, validate the analytic performance of five clinical routine detection systems to explore the comparability of serum progesterone detection by different detection systems.Methods:A candidate reference method for serum progesterone using ID-LC/MS/MS method was established. The sample was pretreated by liquid-liquid extraction method, and the reversed phase liquid phase separation in positive ion mass spectrometry mode was used to detect progesterone in human serum, and the detection time of a single sample was controlled within 5 minutes by gradient elution. In order to improve the accuracy of the method, the bracketing calibration method (BCM) was used to establish the standard curve. The sensitivity, accuracy, precision and specificity of BCM and classical calibration curve method were evaluated according to CLSI C62-A, EP15-A2, EP6-A2 and EP9-A3, and the analytical performance and comparability of five clinical routine progesterone detection systems were evaluated,compared with ID-LC/MS/MS method, the bias at medical decision level 2 and 25 ng/ml was evaluated to see if they were <1/2TEa (12.5%).Results:The limit of detection (LOD) of ID-LC/MS/MS was 0.005 ng/ml. The recoveries of BCM method and classical calibration curve method are 97.95%-101.58% and 96.88%-110.70%, respectively. The measurement results of BCM method for certified reference materials are within its declared uncertainty range. The intra-and inter-assay coefficient of variation ( CV) of BCM method was less than 3.0%, which was better than that of classical calibration curve method ( CV: 2.48%-9.33%). The precision and linear range of the five clinical routine detection systems can meet the detection requirements. The measurement bias of detection system 1, 3 and 5 at 25 ng/ml of medical decision level was less than 1/2TEa, and the measurement bias at 2 ng/ml of medical decision level was more than 1/2TEa. The measurement bias of detection system 2 and 4 at two medical decision levels was less than 1/2TEa. Conclusion:The candidate reference method for serum progesterone ID-LC/MS/MS established in our laboratory meets the requirements of the reference method. BCM has better detection performance than classical calibration curve method. The precision and linearity of the five progesterone clinical detection systems are satisfactory. The five clinical detection systems could meet the clinical requirements at the medical determination level of 25 ng/ml, however, only two of the five clinical detection systems meet the clinical requirements at the medical determination level of 2 ng/ml.

Objective:To compare long-term efficacy between watch and wait (W&W) strategy and total mesorectal excision (TME) in patients who were diagnosed with locally advanced rectal cancer (LARC) and attained clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT).Methods:A retrospective cohort study was carried out. A total of 238 patients with stage II-III LARC exhibiting cCR after nCRT in Sun Yat-sen University Cancer Center from September 16, 2010 to January 9, 2018 were enrolled. Patients who were diagnosed with other malignant tumor within 5 years, did not receive regular follow-up in our center for more than 1 year and had no complete examination items after nCRT were excluded. Of 238 patients, 151 were male and 87 were female with a median age of 57 (27-83) years old. According to TNM stage, 61 cases were cII, 177 cases were cIII. Concurrent chemoradiotherapy (CCRT) was performed in 20 patients. CCRT plus induction/consolidated chemotherapy was performed in 218 patients. Intensity-modulated radiotherapy (IMRT) was applied to radiotherapy. The median radiation dose was 50 Gy/25 Fr for both the primary tumor and clinical target volumes, and the total dose was 45.0 to 50.6 Gy for 227 patients. In 27 patients, single-agent fluorouracil or capecitabine was used as concurrent chemotherapy. But in the other 211 patients, a combined regimen of oxaliplatin and fluorouracil or capecitabine was used. After nCRT, 59 and 179 patients received W&W (W&W group) and TME 6-12 weeks later (TME group), respectively. After the ending of treatment, patient was interviewed one time every 3 months and after 3 years, one time every six months. Overall survival (OS) rate, distant-metastasis-free survival (DMFS) rate, and local-recurrence-free survival (LRFS) rate were compared between two groups. The salvage treatment and sphincter preservation rate were analyzed. The survival curve was drawn with Kaplan-Meier method and evaluated by log-rank method.Results:In the cases treated with TME, the median interval from nCRT to surgery was 59 days. The postoperative pCR rate was 63.1%(113/179). The median follow-up time of the whole cohort was 41.8 (12.0-99.0) months. The 3-year and 5-year OS rates were 98.4% and 96.5%; the 3-year and 5-year LRFS rates were 96.5% and 96.5%; the 3- and 5-year DMFS rates were 91.0% and 87.9%, respectively. The 3-year OS rates in the W&W group and the TME group were 100% and 97.9%; the 5-year OS rates in W&W group and the TME group were 90.6% and 97.9% ( P=0.339); The 3-year local recurrence rate (LRR) in the W&W group was 12.9% (7 cases recurred within 2 years), which was significanthy higher then that in the TME group (0.6%, P=0.003). Salvage surgery was successful in 5/6 cases. After salvage surgery, LRFS rate was not significantly different between the two groups ( P=0.137). The 3-year DMFS rate in the W&W group and the TME group were 88.4% and 81.1%, whose difference was not significant ( P=0.593). Recurrence with simultaneous metastasis was seen in 3/7 cases of the W&W group. The sphincter was preserved in 89.8% (53/59) of patients in the W&W group, which was significantly higher than 73.7% (132/179) in the TME group ( P<0.001). When distance of tumor from the anal verge was ≤ 5 cm, the sphincter preservation rate (SPR) in the W&W group was 88.0% (44/50), which was significantly higher than the 54.4% (56/103) in the TME group ( P<0.001). Conclusions:W&W is safe and feasible for patients with LARC and cCR after nCRT. The results should be verified by further clinical trials.

Objective:To compare long-term efficacy between watch and wait (W&W) strategy and total mesorectal excision (TME) in patients who were diagnosed with locally advanced rectal cancer (LARC) and attained clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT).Methods:A retrospective cohort study was carried out. A total of 238 patients with stage II-III LARC exhibiting cCR after nCRT in Sun Yat-sen University Cancer Center from September 16, 2010 to January 9, 2018 were enrolled. Patients who were diagnosed with other malignant tumor within 5 years, did not receive regular follow-up in our center for more than 1 year and had no complete examination items after nCRT were excluded. Of 238 patients, 151 were male and 87 were female with a median age of 57 (27-83) years old. According to TNM stage, 61 cases were cII, 177 cases were cIII. Concurrent chemoradiotherapy (CCRT) was performed in 20 patients. CCRT plus induction/consolidated chemotherapy was performed in 218 patients. Intensity-modulated radiotherapy (IMRT) was applied to radiotherapy. The median radiation dose was 50 Gy/25 Fr for both the primary tumor and clinical target volumes, and the total dose was 45.0 to 50.6 Gy for 227 patients. In 27 patients, single-agent fluorouracil or capecitabine was used as concurrent chemotherapy. But in the other 211 patients, a combined regimen of oxaliplatin and fluorouracil or capecitabine was used. After nCRT, 59 and 179 patients received W&W (W&W group) and TME 6-12 weeks later (TME group), respectively. After the ending of treatment, patient was interviewed one time every 3 months and after 3 years, one time every six months. Overall survival (OS) rate, distant-metastasis-free survival (DMFS) rate, and local-recurrence-free survival (LRFS) rate were compared between two groups. The salvage treatment and sphincter preservation rate were analyzed. The survival curve was drawn with Kaplan-Meier method and evaluated by log-rank method.Results:In the cases treated with TME, the median interval from nCRT to surgery was 59 days. The postoperative pCR rate was 63.1%(113/179). The median follow-up time of the whole cohort was 41.8 (12.0-99.0) months. The 3-year and 5-year OS rates were 98.4% and 96.5%; the 3-year and 5-year LRFS rates were 96.5% and 96.5%; the 3- and 5-year DMFS rates were 91.0% and 87.9%, respectively. The 3-year OS rates in the W&W group and the TME group were 100% and 97.9%; the 5-year OS rates in W&W group and the TME group were 90.6% and 97.9% ( P=0.339); The 3-year local recurrence rate (LRR) in the W&W group was 12.9% (7 cases recurred within 2 years), which was significanthy higher then that in the TME group (0.6%, P=0.003). Salvage surgery was successful in 5/6 cases. After salvage surgery, LRFS rate was not significantly different between the two groups ( P=0.137). The 3-year DMFS rate in the W&W group and the TME group were 88.4% and 81.1%, whose difference was not significant ( P=0.593). Recurrence with simultaneous metastasis was seen in 3/7 cases of the W&W group. The sphincter was preserved in 89.8% (53/59) of patients in the W&W group, which was significantly higher than 73.7% (132/179) in the TME group ( P<0.001). When distance of tumor from the anal verge was ≤ 5 cm, the sphincter preservation rate (SPR) in the W&W group was 88.0% (44/50), which was significantly higher than the 54.4% (56/103) in the TME group ( P<0.001). Conclusions:W&W is safe and feasible for patients with LARC and cCR after nCRT. The results should be verified by further clinical trials.