Objective To compose and evaluate the measurement uncertainty of two kinds of chemiluminescence detection system using different methods.Methods The measurement uncertainty was composed by 4 different methods:(1) U 1％ was composed of within-run CV(CVw ％),between-run CV(CVB ％)and bias (CVBias ％);(2) U2％ was composed of CVB ％ and uncertainty of calibration (CVcal ％);(3) U3％ was composed of CVW％,CVs％ and CVcal％;(4) U4％ was composed of CVW％,CVB％,CVBias％ and CVcal％.The measurement uncertainty of Architect i2000SR system (Abbott,USA) and DXI800 system (Beckman,USA) was assessed.Pearson correlation analysis,Spearman correlation analysis,Paried t test and Mann-Whitney u test were performed to analyze the data.Results For Architect i2000SR system,U1％,U2％,U3％ and U4％ were significantly correlated (r=0.727-0.988,all P＜0.05),U3％ and U2％ were significantly different (t =6.88,P＜0.05),U4％ and U1％ were significantly different (t =6.21,P＜0.05).For DXI800 system,U1％,U2％,U3％ and U4％ were also significantly correlated (r =0.608-0.975,all P＜0.05),no significant difference was found between U3％ and U2％ (z=-1.33,P＞0.05),or between U4％ and U 1％ (z =-1.04,P＞ 0.05);the expanded measurement uncertainty was correlated with CVW％,CVB％,CVBias％(rs=0.653-0.912,all P＜0.05),but not with CVcal％(rs=0.548,P＞0.05).Conclusions For Architect i2000SR system,the fourth method is more proper to compose the measurement uncertainty (U4％).For DXI800 system,the first method is more appropriate (U1％).According to the contribution of different components to the measurement uncertainty,the measurement quality could be improved by reducing the imprecision and bias.

Objective To study the alteration of Th17 cells and related molecules in patients with Hashimoto's thyroiditis (HT).Methods Th17 cells were determined by flow cytometry.Real-time PCR method was applied to detect the expression of the orphan nuclear receptor RORγt and interleukin(IL) -17.Serum IL-6 and IL-23 were detected by ELISA method.Results ( 1 ) Compared with healthy controls,the frequency of Th17 cells [ (0.75± 0.79) ％ vs ( 0.28 ± 0.23 )％ ] and expression of RORγt ( 0.30 ± 0.38 vs 0.04 ± 0.02,both P ＜ 0.05 ) were significantly increased in HT patients.( 2 ) The levels of IL-6 and IL23 in HT patients were higher than those in healthy controls ( 3.66 ± 4.70 vs 0.47 ± 1.11,154.7 ± 75.81 vs 80.65 ± 61.41,both P＜0.05 ).( 3 ) A positive correlation between Th17 cells and serum TgAb was revealed in HT patients ( r =0.848 4,P =0.007 7 ).(4) The results of PCR showed that IL-17 and RORγt expressed in thyroid tissues of patients HT.Conclusion An increased frequency of Thl7 cells was found in HT patients,implying that this cell subset may play an important role in the pathogenesis of autoimmune thyroid disease.

Objective: To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD). Methods: From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up. Results: In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c. 1484T>C, c. 394-1G>T, c. 431T>C and c. 265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c. 1400C>G (42.3%), c. 760C>T (11.5%) and c. 51C>G (7.7%). During the 8 ~ 42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment. Conclusion The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c. 1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.

Migraine is a complex disorder of brain function. The hypothalamus has been identified to play a crucial role in attack generation and secretes various neuropeptides. The orexinergic system plays a role in energy metabolism, arousal, sleep, stress and pain modulation. These disorders are closely related to clinical symptoms of migraine. Therefore, the study of the mechanism of hypothalamic orexinergic system in migraine may provide a new perspective for treatment. This article discusses the relationship between hypothalamic orexin system and migraine premonitory symptoms, and briefly summarizes the possible role and mechanism of hypothalamic orexin system in migraine.

Objective:To explore the related factors for clinical prognoses of ruptured anterior communicating artery (ACoA) aneurysms.Methods:A retrospective study was performed on the clinical data of 309 patients with ruptured ACoA aneurysms admitted to our hospital from January 2014 to January 2020. The preoperative data included age, gender, smoking history, hypertension, Hunt-Hess grading, Fisher grading, sizes of aneurysms, and spasm of parent artery; and the postoperative data included pneumonia, intracranial infection, cerebral hernia, recurrence and re-hemorrhage of aneurysms, and delayed cerebral ischemia. Clinical prognoses were assessed by modified Rankin scale (mRS). Univariate analysis and multivariate Logistic regression analysis were used to determine the independent risk factors for clinical prognoses. Preoperative model (independent risk factors appeared before surgery) and postoperative model (independent risk factors appeared during the whole treatment process) were constructed; based on these Logistic models, the preoperative and postoperative independent risk factors were concluded. Independent risk factors presented in the preoperative and postoperative models were used as variables to analyze the predictive value of the models by receiver operating characteristic (ROC) curve.Results:Among 309 patients, 264 (85.4%) had good prognosis and 45 (14.6%) had poor prognosis. (1) Univariate analysis showed that significant differences were noted in proportion of smoking patients, and patients with hypertension, Hunt-Hess grading IV-V, Fisher grading IV, wide-necked aneurysm, re-hemorrhage of aneurysms, cerebral vasospasm, pneumonia, intracranial infection, cerebral hernia, delayed cerebral ischemia, and postoperative lumbar cistern drainage between good prognosis group and poor prognosis group ( P<0.05). (2) Multivariate Logistic regression analysis showed that Hunt-Hess grading Ⅳ-V ( OR=24.198, P=0.000, 95%CI: 4.288-136.559), Fisher grading Ⅳ ( OR=4.792, P=0.044, 95%CI: 1.040-22.079), spasm of parent artery ( OR=12.136, P=0.005, 95%CI: 2.121-69.426), pneumonia ( OR=8.177, P=0.018, 95%CI: 1.438-46.506), postoperative cerebral hernia ( OR=147.042, P=0.002, 95%CI: 6.386-3385.519) and delayed cerebral ischemia ( OR=606.720, P=0.000, 95%CI: 52.288-7040.088) were independent risk factors for prognoses; postoperative lumbar cister drainage ( OR=0.072, P=0.050, 95%CI: 0.005-1.000) was the independent protective factor. (3) ROC curve showed that the preoperative model (with Hunt-Hess grading IV-V, Fisher grading Ⅳ and cerebral vasospasm as variables) had excellent discrimination with an area under the curve (AUC) of 0.870 ( 95%CI: 0.82-0.93, P=0.000), and the postoperative model (with variables of preoperative model, pneumonia, delayed cerebral ischemia, and herniation as variables) had excellent discrimination (AUC=0.980, 95%CI: 0.97-0.99, P=0.000). Conclusion:Besides decreasing Hunt-Hess grading and Fisher grading, and relieving the arterial spasm, the management of lumbar subarachnoid continuous drainage and avoidance of postoperative complications, such as cerebral hernia, delayed cerebral ischemia and pneumonia, can also play important roles in improving the prognoses of ruptured ACoA aneurysms.

Malignant tumors are the second most important cause of death after cardiovascular and cerebrovascular diseases. Chemotherapeutic drugs for tumor treatment have strong toxic side effects. The common solution is to use nanoparticle as a carrier that can deliver drugs to tumor issues so as to kill the tumor cells. However, most of the current drug-carriers have a serious drug loss before reaching the tumor area, which makes the difficult control of drug release. Multi-stimulus responsive nano-carrier systems can overcome these drawbacks and make drug release controllable. pH/redox dual sensitive nano-carrier systems are currently hot research direction. In this paper, the research progress of pH/redox dual sensitive nano-carrier systems in recent years was reviewed in order to provide reference for relative researches.

In recent years, mesoporous silica nanoparticles (MSNs) have been widely used in the construction of various intelligent drug delivery systems due to their unique and excellent properties. The stimuli-responsive drug delivery system based on mesoporous silica nanoparticles can effectively load anticancer drugs and target them to tumor cells, and then responsively release anticancer drugs under the action of specific stimulation signals. The method of specifically delivering anticancer drugs to target sites not only can greatly improvethe drug efficacy, but also effectively reduce the side effects of anticancer drugs on normal tissues and organs. Thereby the advantages of anticancer drugs in tumor therapy are improved. In this paper, the applications and developments of stimuliresponsive mesoporous silica nano drug delivery systems in tumor therapy were summarized.

Objective:To explore the genetic basis for a child featuring tetrahydrobiopterin deficiency and global developmental delay.Methods:Clinical and laboratory examinations were carried out for the child. Genomic DNA of the patient was subjected to high-throughput sequencing to identify genetic variants associated with hyperphenylalaninemia. Candidate variants were verified by Sanger sequencing.Results:The result of blood tandem mass spectrometry showed that the Phenylalanine in the blood was 642.7 μmol/l, and the ratio of Phenylalanine/Tyrosine was 5.42. Analysis of urinary pterin: neopterin 0.09 mmol/mol Cr, biopterin 0.04 mmol/mol Cr, biopterin% 77%, which suggested tetrahydrobiopterin deficiency. The parents of the proband were first cousins. DNA sequencing revealed that the proband has harbored homozygous c. 353A>T variants in exon 2 of the GCH1 gene, for which his great grandmother, grandfather, mother, uncle, father and elder brother were heterozygous carriers with normal phenotype and no clinical symptoms associated with dopa responsive dystonia. Conclusion:The homozygous c. 353A>T variant of the GCH1 gene probably underlay the tetrahydrobiopterin deficiency in this pedigree of consanguineous marriage.

Objective:To observe the changes of peri-implant tissue around the individualized abutment that was grinded from zirconia provisional crown in one year.Methods:In this research, a prosthodontic-driven virtual implant planning and immediate provisionalization were conducted in computer assisted design software. And computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate the zirconia provisional crown and surgical guide template before surgery. The implant was accurately placed with the surgical guide, and the zirconia provisional crown was immediately delivered after surgery. Three months later, the implant osseointegration was completed, and zirconia provisional crown was prepared intraorally to generate customized zirconia abutment for final prosthesis. The study included 30 patients with single anterior tooth loss, including 18 males and 12 females, aged from 26 to 50 years old, and the mean age was (36.2±6.1) years old. The patients were from the Center of Oral Implantology, The First Affiliated Hospital of Zhejiang University Medical College from January 2017 to February 2018. After cementation of the final prosthesis, the cases were followed up at 6 and 12 months time intervals. Implant survival rate, probing depth, bleeding on probing, marginal bone level loss and papilla index score (PIS) were recorded in every appointment.Results:The survival rate of 30 implants was 100%, and the probing depths were less than 5 mm. The bone resorption at 6 and 12 months follow-up after the final delivery was 0 (0, 0) mm and 0 (-0.2, 0) mm, respectively, and the difference was not statistically significant ( P>0.05). The PIS was 3.0 (2.0, 4.0), 3.0 (2.8, 4.0) and 3.0 (3.0, 4.0) on the final delivery, 6 and 12 months after final delivery, respectively. Conclusions:Marginal bone level and bone loss were stable with this new implant clinical protocol at the one-year follow-up.

Objective:To explore the prognostic influencing factors of adult lymphoma-associated hemophagocytic syndrome (LAHS) based on multicenter data.Methods:The clinical data of 86 LAHS patients diagnosed in 9 medical centers of Huaihai Lymphoma Working Group from January 2015 to August 2020 were retrospectively analyzed. The optimal cut-off value of continuous variables was obtained based on MaxStat algorithm. Cox proportional hazard regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used for survival analysis, and log-rank test was performed.Results:Among the 86 adult LAHS patients, 50 (58.1%) were males and 36 (41.9%) were females, the median age of the patients was 57 years old (19-76 years old), and the median overall survival (OS) time was 1.67 months (95% CI 0.09- 3.24 months). The most common pathologic type was diffuse large B-cell lymphoma (58 cases, 67.44%). Based on MaxStat algorithm, the optimal cut-off values of age, albumin, serum creatinine, lactate dehydrogenase, fibrinogen and platelet count were 64 years old, 30.1 g/L, 67 μmol/L, 1 045 U/L, 4.58 g/L and 72×10 9/L, respectively. Multivariate analysis showed that patient's age, lactate dehydrogenase, albumin and fibrinogen levels were independent influencing factors for OS (all P < 0.05). Conclusions:LAHS is dangerous and progresses quickly. Patients with age ≥ 64 years old, lactate dehydrogenase ≥ 1 045 U/L, fibrinogen ≥ 4.58 g/L and albumin < 30.1 g/L have poor survival.