Chronic Kidney Disease (CKD) has become one of the main diseases severally threatening human health, which has aroused global attention. Acute Kidney Injury (AKI) is the main cause of CKD. Early diagnosis of AKI is the most effective way to prevent CKD. More and more new biomarkers of renal injury will be found through genomics, proteomics, and metabolomics methodologies. The clinical application of a single marker in the real world will be subject to certain restrictions because of the etiological diversity and personal differences. Kidney damage monitoring models will be established by artificial intelligence method. However, standardizing the evaluation of its clinical application value is essential to screen out truly valuable kidney injury biomarkers or monitoring models, to promote the clinical application of kidney injury markers, and to effectively reduce the incidence of CKD.

Acute kidney injury is a common and severe clinical event, the morbidity and mortality of acute kidney injury are increasing steadily, which is related with heavy burden to the country and social economy. Early diagnosis and intervention could significantly reduce the occurrence and progression of acute kidney injury. Therefore, it is of particular importance to find sensitive, specific, and economic biomarkers for acute kidney injury. In recent years, efforts have been made on exploring proteins in blood and urine as biomarkers of acute kidney injury. Present review summarizes progress in this field based on results of recent basic and clinical research.

Objective:This study aimed to explore the feasibility and clinical value of monitoring the progression of early kidney injury in type 2 diabetic patients by assessment of the urinary C-terminal agrin fragment (uCAF) with enzymatic chemiluminescence immunoassay.Methods:A total of 251 patients with type 2 diabetes, who attended the Second Affiliated Hospital of Wenzhou Medical University from October 2018 to March 2020, were included in this retrospective analysis. One hundred and fifty-six participants undergoing health check-up at the Second Affiliated Hospital of Zhejiang University School of Medicine in February 2021 served as controls. Basic clinical information, glycosylated hemoglobin type A 1c and serum creatinine values were recorded, and urine specimens were collected for urinary creatinine, urinary α 1 microglobulin(uα 1M), urinary immunoglobulin G (uIgG), urinary albumin, urinary N-Acetyl-B-D-glycosaminidase (uNAG) and uCAF measurements. Based on the estimated glomerular filtration rate (eGFR), 251 patients were classified into G1~G5 stage groups with 116, 22, 28, 55 and 30 patients in each group. One hundred and sixty-six patients with early diabetic kidney disease (stage G1-G3) were divided into subgroups A1 (79), A2 (48) and A3 (39) according to the urinary albumin/creatinine ratio (UACR), the uα1M levels were divided into uα1M subgroup 1 (83 cases), uα1M subgroup 2 (42 cases), and uα1M subgroup 3 (41 cases), and uIgG subgroup 1 (83 cases), uIgG subgroup 2 (42 cases), and uIgG subgroup 3 (41 cases) according to uIgG levels. The Spearman method was used to analyze the correlation between uCAF levels and eGFR, UACR, uα1M and uIgG levels. Results:(1) The linear range of the uCAF detected by enzymatic chemiluminescence immunoassay was 3.97-2 000.00 ng/ml, with a detection limit of 2.28 ng/ml, intra-batch coefficients of variation of 1.15% and 1.57%, inter-batch coefficients of variation of 1.63% and 5.78%, and a biological reference interval of <95.35 μg/g Cr. (2) The uCAF level and positive rate (UACR≥30 mg/g) increased with the decrease of eGFR from G1-G3, uCAF level was negatively correlated with eGFR value ( r=-0.543, P<0.000 1), and the positive rate increased from 24.14% (28/116) to 85.71% (24/28) from G1-G3. The uCAF level and positivity rate decreased with the decrease of eGFR from G4 to G5. uCAF level was positively correlated with eGFR value ( r=0.495, P<0.001), and the positivity rate decreased from 30.91% (17/55) to 23.33% (7/30) from G4 to G5. (3) In patients with early diabetic kidney disease, uCAF levels and positivity rates increased gradually with the increase of UACR. uCAF levels were positively correlated with UACR values ( r=0.602, P<0.001), and the uCAF positivity rate reached 21.52% (17/79) in the A1 subgroup. (4) uCAF level was positively correlated with uα1M and uIgG levels in patients with early diabetic kidney disease ( r=0.757, 0.596, both P<0.001). Conclusion:Analytical performance of enzyme chemiluminescence immunoassay for the detection of CAF is satisfactory and could be used a biomarker for monitoring damage and progression of early diabetic kidney disease in patients with type 2 diabetes.

红石山地区金矿床位于东昆仑多金属成矿带中段,研究区通过1:5万水系沉积物测量圈出4处以As、Sb为主的综合异常;通过1:2.5万地球化学测量圈出4处以Au、As、Sb为主的综合异常.不同比例尺的化探异常位置基本吻合,而Au异常最为明显,且与断裂构造关系最为密切,为本区金矿找矿提供了依据.进一步对3处以Au、As、Sb为主的1∶2.5万综合异常实施地化剖面、槽探、浅钻工程,圈出含金构造破碎蚀变带4条,带内圈定8条金矿体、6条金矿化体.区内矿化主要赋存于中三叠统洪水川组和闹仓坚沟组地层之间的构造破碎蚀变带中,矿化受北西西向断裂构造控制明显,主要赋矿岩性为构造碎裂岩及强硅化蚀变岩.综上所述,研究区具有优越的成矿地质条件,地球化学异常发育,经检查发现了较好的金矿找矿信息,充分展示出本区具有较大的找矿潜力,通过进一步工作,有望取得较好的找矿成果.

2022年2月18日,国家卫生健康委员会、国家医疗保障局、国家中医药管理局、中央军委后勤保障部卫生局联合印发《关于印发医疗机构检查检验结果互认管理办法的通知》[1](下文简称《管理办法》),检查检验结果互认受到各界的广泛关注.《管理办法》提出,医疗机构开展检查检验结果互认工作的原则是以保障质量安全为底线,以质量控制合格为前提,以降低患者负担为导向,以满足诊疗需求为根本,以接诊医师判断为标准.对于医院和临床实验室管理者而言,检查检验结果互认面临着很多压力和挑战,但同样蕴藏着发展的机遇.本期主持人邀请国内相关政策研究专家和临床实验室管理者从不同的角度深度剖析检查检验结果互认及其对检验医学未来发展的影响,以期为广大同行提供参考.

Aims: The red blood cell distribution width-to-platelet ratio (RPR) has been reported to be an indicator of hepatic fibrosis in patients with chronic hepatitis B (HBV), nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (HCV). However, no research has explored the RPR in all patients with hepatic fibrosis. There is a recognized need to establish whether the RPR could assess hepatic fibrosis and reflect the severity of fibrosis, regardless of the patient's etiology. Methods: Quantitative data from 1282 patients who underwent liver biopsy between January 2010 and December 2014 at the Second Affiliated Hospital of Zhejiang University School of Medicine were included. The etiologies included HBV or HCV infection, NAFLD, schistosomiasis, granulomatous liver disease, and vascular abnormalities. Five noninvasive models were calculated for all patients based on laboratory parameters. The degrees of fibrosis severity were evaluated based on the Metavir scoring scale. Results: The RPR demonstrated the best accuracy of predicting hepatic fibrosis among the selected five models (0.75, p < .001) regardless of etiology. In addition, the RPR values increased with advanced hepatic fibrosis progression. Furthermore, combining the RPR with the white blood cell (WBC) count improved the accuracy of grading hepatic fibrosis as reflected by the likelihood ratio (LR + 9.03, LR - 0.49). Conclusion: The RPR is a useful indicator for hepatic fibrosis, regardless of etiology, and can reflect the severity of fibrosis. This study supports further clinical development of the RPR both in a stepwise manner or in combination with inflammatory parameters to improve the accuracy of scoring hepatic fibrosis.

目的 探讨围产期孕妇无乳链球菌定植与胎膜早破的关系及对抗生素耐药性.方法 选择围产期孕妇4963例,分别对其阴道分泌物与直肠拭子进行无乳链球菌培养.根据检测结果将受试者分为两组,将无乳链球菌培养呈阳性的围产期孕妇275例设为观察组,同期入院的无乳链球菌培养呈阴性的围产期孕妇4688例设为对照组.比较两组胎膜早破发生情况、不良妊娠结局以及新生儿感染情况;分析无乳链球菌对抗生素的耐药性.结果 观察组胎膜早破发生率为22.91％(63/275),对照组发生率为8.85％(415/4688),差异有显著性(χ2=58.97,P<0.01).观察组早产发生率为8.72％(24/275),对照组为6.35％(298/4688),差异无显著性(χ2=2.41,P>0.05).观察组宫内感染发生率为7.63％(21/275),对照组为4.48％(210/4688),差异有显著性(χ2=5.83,P<0.05).观察组娩出新生儿无乳链球菌感染发生率为6.90％(19/275),对照组为2.75％(129/4688),差异有显著性(χ2=15.52,P<0.01).观察组分离的无乳链球菌对四环素、克林霉素、环丙沙星与左氧氟沙星四种药物的耐药率分别为72.7％、50.5％、38.5％和37.8％;对青霉素G、氨苄西林、万古霉素、利奈唑胺、替加环素与奎奴普丁/达福普汀不耐药.结论 围产期孕妇无乳链球菌定植可增加胎膜早破发生风险;青霉素G与氨苄西林是无乳链球菌阳性孕妇首选抗菌药物.

目的:探讨血清降钙素原(PCT)检验在中枢神经系统病毒和细菌感染鉴别中的价值.方法:选取某院收治的100例中枢神经系统感染患者,根据诊断方法分为细菌感染组(n=40例)和病毒性感染组(n=60例),并选择同期住院伴有神经系统症状的非感染患者30例作为对照组,分析3组患者血清和脑脊液当中的PCT水平.结果:细菌感染组脑脊液PCT含量显著高于病毒感染组、正常对照组(P<0.05);细菌感染组血液PCT含量显著高于病毒感染组、正常对照组(P<0.05).结论:对于中枢神经系统病毒和细菌感染,采取PCT检验有助于协助临床诊断.

Through analysis of common nonconformities in the assessment of clinical immunology laboratory with ISO15189 medical laboratory accreditation, in more than one year′s implementation process of China National Accreditation Service for Conformity Assessment (CNAS)CL39:2012, we put forward reasonable corrective methods. The aim is to improve clinical immunology laboratory quality management system, ensure the laboratory results accuration, provide the high quality service for clinicians, and help to understand deeply the CNAS-CL02:2012 and CNAS-CL39:2012. Key words: Laboratory accreditation; Clinical immunology

肝纤维化是肝脏对各种病因所致的慢性、非自限性肝损伤的一种可逆的创伤修复反应.准确诊断肝纤维化、预测肝纤维化严重程度,对诊疗工作极为重要.肝脏活组织检查仍是肝纤维化的金标准,但其无法满足动态预测肝纤维化严重程度及动态监测疗效.临床迫切需要无创、可重复、快速检测的诊断指标.我国Chen等[1]提出基于乙肝的红细胞平均分布宽度-血小板比率(red cell volume distribution width-platelet ratio, RPR)模型.Chen等[1]研究发现该模型诊断乙肝性肝纤维化患者时的诊断效能优于纤维化4-指数(Fibrosis-4 index, FIB-4) 模型、 AST/血小板比值(AST/platelet ratio index, APRI)模型等其他模型;但未深入研究RPR对非乙肝性肝纤维化的诊断效能以及在肝纤维分级诊断中的临床价值.

AIM:To investigate the role of imperatorin in reversing the resistance of the PC 9 CD133+cell sub-sets to gefitinib.METHODS:MTT assay was performed to evaluate the viability of PC 9 cells treated with imperatorin and gefitinib.The expression of c-met, activation of caspases and phosphorylation of epidermal growth factor receptor (EGFR), PI3K and AKT in the PC9 cells treated with imperatorin and gefitinib were determined by Western blot .The percentage of CD133 +cell subsets population and the apoptotic rate of the PC 9 cells treated with imperatorin and gefitinib were analyzed by flow cytometry .RESULTS:The sensitivity of the PC 9 CD133 +cell subsets to gefitinib was significantly lower than that of the PC9 CD133 -cell subsets.Treatment with gefitinib alone significantly inhibited the protein levels of EGFR /PI3K/AKT in the PC9 CD133 -cell subsets but not the PC 9 CD133 +cell subsets .Treatment with gefitinib alone increased the percentage of CD133 +cell subsets population in the PC9 cells.However, combination of gefitinib with imperatorin signifi-cantly inhibited the enrichment of CD 133 +cell subsets population .Imperatorin down-regulated c-met expression , sugges-ting the c-met was the target of imperatorin in the PC9 CD133 +cell subsets.The results of MTT assay, Western blot analy-sis and flow cytometry indicated that imperatorin increased the gefitinib induced inhibition of PI 3K/AKT protein levels by down-regulating the expression of c-met, which subsequently induced the cleavage of caspases and apoptosis in the PC 9 CD133 +cell subsets.CONCLUSION:Imperatorin increases the sensitivity of lung cancer CD 133 +cell subsets to gefitinib&nbsp;by down-regulating the expression of c-met, and the synergistic anti-tumor effect exists between imperatorin and gefitinib .

Objective To study the expression of IFN-γby tuberculosis specific T cells ( TB-IGRA) and Human Leukocyte Antigen-G( HLA-G) in the peripheral blood of tuberculosis patients and its diagnostic value in tuberculosis.Methods This was a retrospective cohort study . Study cases were all from Resparation Department of Shaoxing Municipal Hospital from January 2015 to December 2015. These patients were devided into tuberculosis group (TB) (34 cases), lung cancer group (LCa) (25cases) and non tuberculous pneumonia group (Non-TB pneumonia) (25cases) according to diagnosis, meanwhile, health group (35 cases) was set.IFN-γand sHLA-G were detected by ELISA , and mHLA-G was detected by Flowcytometre.The receiver operating characteristic curve ( ROC) was used to evaluate the diagnostic efficacy of TB-IGRA, sHLA-G and mHLA-G.Results The expression of TB-IGRA, sHLA-G and mHLA-G were higher in the TB group ( with the median of 182.5 ng/L,99.44 U/ml and 13.63%) than in the LCa group (117.0 ng/L,82.3 U/ml and 9.12%), Non-TB pneumonia group (80.84 ng/L,34.2 U/ml and 10.92%) and health group ( 30.5 ng/L, 31.28 U/ml and 8.18%) ( P<0.05 ) .The AUC-ROC of TB-IGRA, sHLA-G and mHLA-G were 0.842(95%CI, 0.761-0.922), 0.746(95% CI, 0.652-0.840) and 0.706(95%CI,0.605-0.806).The sensitivity for TB-IGRA, sHLA-G and mHLA-G was 88.24%, 70.59% and 67.65%, and the specificity was 60%, 72.94%and 70.59%at the cutoff value of 35 ng/L, 60 U/ml and 10% respectively.The sensitivity and specificity of combination detection for TB-IGRA and HLA-G were 88.24%and 81.18%.Conclusions TB-IGRA, sHLA-G and mHLA-G were all increased in TB, while, the quantitative detection of TB-IGRA is more helpful for diagnosis .The combination detection of TB-IGRA, sHLA-G and mHLA-G can improve the sensitivity in the diagnosis of tuberculosis .

The incidence of prostate cancer ( PCa ) is rising steadily among males in many countries.Serum prostate-specific antigen ( PSA ) is widely applied in clinical diagnosis and screening of PCa.However, the grey area of PSA levels has a low specificity in PCa screening and may lead to a high rate of negative biopsy and overtreatment.The PCA3 gene is strongly and specifically overexpressed in PCa cells and malignant prostate tissue.The gene has been identified as a molecular biomarker for PCa detecting.The diagnostic significance of PCA3, however, is awaiting further researches.In this review, the progress of molecular biological characteristics of PCA3,and its applications in diagnosis and treatment of prostate cancer were discussed.

Affected by many factors such as environment and lifestyle change , prostate cancer has become common malignancy in older men . The introduction and widespread adoption of PSA has revolutionized the way prostate cancer is diagnosed and treated .However , the use of PSA has also led to over-diagnosis and overtreatment of prostate cancer resulting in controversy about its use for screening .PSA also has limited predictive accuracy for predicting outcomes after treatment and for making clinical decisions about adjuvant and salvage therapies .Hence, there is an urgent need for novel biomarkers to supplement PSA for detection and management of prostate cancer .In this review, we discuss the traditional and new relevant molecular markers of early diagnosis and prognosis of prostate cancer for clinical diagnosis and prognosis of prostate cancer providing a reference .

Microfluidics-based digital PCR depends on microfluidic chip to split PCR reaction mixture into many tiny equal-volume units.Quantitative assessment of target DNA template can be obtained by counting the number of fluorescence-positive units after thermocycling.Microfluidics-based digital PCR exhibits many advantages including absolute quantification, high sensitivity and accuracy, and shows great promise in a variety of applications, such as infectious diseases diagnose, early cancer detection and prenatal diagnose. There are already several microfludics-based digital PCR products produced from sereval companies.It is believed that as the technology improves, microfluidics-based digital PCR will find broader applications and become the next-generation tool for genetic tests.

Objective To investigate the effects of 5-Aza-2'-deoxycytidine (5-Aza-dc),a methylation inhibitor,on the proliferation of androgen-sensitive prostate cancer line (LNCaP),and on its regulation of methylation on glutathione s transferaseP1 (GSTP1) and retinoic acid receptorβ2 (RARβ2) gene.Methods LNCaP cells were treated with 5-Aza-dc in different concentration,CCK8 method was used to detect the growth of LNCaP cells.The methylation of GSTP1 and RARβ2 gene in LNCaP cell was detected by nested methylation specific polymerase chain reaction (nMSP).Results The proliferation of LNCaP cells was inhibited after exposed to 5-Aza-dc.The methylation of GSTP1 and RARβ2 gene was changed from hypermethylation to demethylation by the 5-Aza-dc.These effects were dose-and time-dependent within certain concentration of 5-Aza-dc,but LNCaP cells grew better after 72 h than within 48 h when exposed to 5 Aza dc below 1.0 μmol/L.Also the methylation of GSTP1 and RARβ2 gene changed from hypermethylation to demethylation by the 5-Aza-dc was not different when exposed to 5-Aza-dc below 1.0 μmol/L within 72 h and 48 h.Conclusions 5-Aza-dc may effectively inhibit the growth of LNCaP cells and reverse the DNA methylation damage in some tumor suppressor genes,but the continuity and stability of low dose 5-Aza-dc is changeable.The study will provide a research basis for clinical treatment.

Prostate cancer is one of the most common malignant tumor of male population in the West.Via binding to androgen response element in the genome and interacting with co-regulators,androgen receptor can participate in the development of prostate cancer and the convertion from androgen dependent prostate cancer to androgen independent prostate cancer.Chromatin immunoprecipitation ,coupled with PCR , chip,and high-throughput sequencing ,makes a huge progress in the study on the downstream target genes of androgen receptor and provide a new way to understand the molecular mechanisms of castration -resistant prostate cancer.

Objective:The research project was in the interest of establishing the reference intervals of 36 physicochemical indexes for healthy adults in the location of Hangzhou, Zhejiang province. Methods:The respondents of the study were healthy residents in Hangzhou (including its 8 districts and 5 countries), the number of which was 523 (including 257 male and 266 female samples). All the samples were divided into five different age groups (19-29, 30-39, 40-49, 50-64 and 65 or more) to analyze 36 physicochemical indexes in serum. Result:Statistical significance (P>0.05) was obtained among various age groups and genders in ALB, ALT, AST, CK, CL, GGT, HDL,LDL,LIP,NA,TG,UREA,FOL. Only gender-related difference in reference intervals were observed in ALP,CR,TBIL,TP,TRF,UA,Fe,AFP,FER,CEA,CA125,PSA. The levels of ALP, CR, TBIL, UA, Fe, AFP, PSA were higher in male samples than female ones. The levels of TP, TRF, CA125 were higher in female samples. Age-related difference of reference intervals was observed in Ca, GLU, LDH, Mg, P, TC, PTH. GLU, LDH, Mg, TC, PTH have positive correlation with age, while Ca and P have negative correlation. There is no statistical significance in AMY, K, VB12, INS among various age groups or genders. Conclusion:There is significant difference in Fe, TG, HDL, LDL, CR, UA, UREA, AFP, CEA, CA125, PSA, FER between genders, considering healthy residents in Hangzhou. Distinguishing reference interval of those indexes in the classification of sexes is recommended in clinical diagnosis. Levels of UA, UREA, TC, TG, LDL, GGT, ALB of healthy adults in Hangzhou show gaps with related studies in other locations. As a result, it’s necessary to modify native reference intervals in consideration of those indexes.

Liver cancer has a high morbidity and mortality in China.With new technologies and diagnostic instruments being developed,it is a common goal for researchers to discover some new diagnostic biomarkers of high sensitivity and specificity on liver cancer.The clinical laboratory is responsible to choose and understand the diagnosis value of these laboratory indicators and variation in the liver cancer progress.Then,these new biomarkers in screening for early malignancy,aiding cancer diagnosis,determining prognosis can be used effectively in the clinical laboratory to improve laboratory diagnostic capacity in order to serve the clinic more effectively and better.

ObjectiveTo unveil the causes of unqualiifed specimens and provide basis for improvement so as to make progress in the pre-testing quality by overall tracing of inpatients’ blood specimens and periodical analysis.MethodsThe entire process monitoring information system based on blood sample barocode was adopted to compare the rate of specimen loss overdue transportation and rejection between January to June 2012 and January to June 2013 in the Second Afifliated Hospital, Zhejiang University School of Medicine. The distribution of unqualiifed specimen and causes were futher analyzed.ResultsTotally 501 135 in patients blood samples were received with 0.006‰ (3/501 135 specimens) sample loss rate, 1.64% (8195/501 135 specimens) specimen transportation overtime rate, 3.676‰ (1842/501 135 specimens) specimen unqualified rate from January to June 2013; otherwise, 450 463 specimens with 0.053‰ (24/450 4630 specimens) loss rate, 6.50% (29 280 / 450 463 specimens) transportation overtime rate, 7.830‰ (3527/450 463 specimens) unqualiifed rate without control measures during the first half year of 2012 were received, differences were statistically significant (χ2=18.7, 14839.9, 729.7, P<0.01) between those two periods; the clotted, haemolysed and insufifcient volume were the three main rejection reasons which accounts for 28.3% (521/1842 specimens), 27.6% (508/1842 specimens) and 24.8% (456/1842specimens) respectively. Unqualiifed specimens are mainly distributed in six intensive care units (center ICU1/2, surgical ICU, neurology ICU, emergency ICU and heart ICU) ,which accounts for 32.6% (118/362 specimens), 39.3% (87/221 specimens), 35.0% (112/320 specimens), 32.7% (113/354 specimens), 32.2% (98/306 specimens) and 22.5% (63/27 specimens) of total reject ratio from January to June 2013.ConclusionsFull monitoring of specimens in the pre-analysis by Laboratory Information Systems can improve the timely rate of specimens transportation and reduce the rate of the lost and unqualified specimens. Analysis of the occurrence rate of unqualiifed specimens and effectively negotiating with relevant departments can make great progress in pre-analytical quality control of blood specimens.