[The connotation of universal health management and its implementation in the context of Healthy China Strategy].

In the context of the implementation of Healthy China Strategy, universal health management is an effective approach to promote the construction of the chain of social health governance system of"prevention, treatment, and management". This paper composes the connotations and main characteristics of universal health management from five aspects: coverage, resource input, service content, management mode, and expected results, with a view to providing reference for the clarification of the connotation of universal health management and related practices.

[Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease].

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

[Associations between 24-hour urinary sodium excretion and all-cause mortality in adults living in north China].

Objective: To investigate the associations between 24-hour urinary sodium excretion (24hUNaE) and all-cause mortality in adult Northern Chinese population. Methods: Data from this study were derived from the prospective urban and rural epidemiology (PURE) study in north China. Baseline information of all participants were obtained by face to face interview through trained research staffs based on questionnaires, and morning fasting urine samples of participants were collected to estimate 24hUNaE and 24-hour potassium excretion (24hUKE). Multivariable frailty Cox regression models were used to explore the association between 24hUNaE (<3.00, 3.00-3.99, 4.00-4.99, 5.00-5.99 and ≥6 g/d) and all-cause death. Results: A total of 27 310 participants were included in this study. The mean 24hUNaE was (5.84±1.73) g/d. After a median follow-up of 8.8 years, 1 024 participants died (3.7%), including 390 cardiovascular related deaths and 591 non-cardiovascular related deaths. The cause of death of the remaining patients could not be determined. Using 24hUNaE level of 4.00-4.99 g/d as the reference group, after fully adjustment, 24hUNaE ≥6.00 g/d was associated with an increased risk of all-cause death (HR=1.24, 95%CI: 1.02-1.49) and cardiovascular related death (HR=1.39, 95%CI: 1.02-1.88). 24hUNaE<3.00 g/d was associated with increased risk of all-cause mortality (HR=1.38, 95%CI: 0.96-1.99). There was no significant association between 24hUNaE and non-cardiovascular related death. Furthermore, using the combination of 24hUNaE 4.00-4.99 g/d and 24hUKE≥2.11 g/d as the reference group, the highest risk occurred in participants with the combination of low sodium (<3.00 g/d) and low potassium (<2.11 g/d). Conclusion: 24hUNaE equal or higher than 6 g/d or lower than 3 g/d is associated with increased risk of all-cause mortality and cardiovascular related death in Northern Chinese population. Besides, moderate sodium intake in combination with increased potassium intake might reduce the risk of all-cause death.

Is there a shared genetic basis and causal relationship between polycystic ovary syndrome and psychiatric disorders: evidence from a comprehensive genetic analysis.

STUDY QUESTION: Is there a shared genetic basis or causal relationship between polycystic ovary syndrome (PCOS) and a range of psychiatric disorders? SUMMARY ANSWER: Genome-wide genetic correlation analysis and bidirectional Mendelian randomisation (MR) analysis suggest no shared genetic basis or causal relationship of PCOS with psychiatric disorders including depression, anxiety, schizophrenia and bipolar disorder. WHAT IS KNOWN ALREADY: The comorbidity of PCOS with a range of psychiatric disorders has been recognised by epidemiological investigations yet a causal relationship remains unclear. Understanding of how genetic variations contribute to the susceptibility to PCOS and psychiatry disorders could provide meaningful insights into disease mechanisms. STUDY DESIGN, SIZE, DURATION: We incorporated summary statistics from the hitherto largest genome-wide association studies (GWAS) conducted in subjects with PCOS (Ncase = 9322) or four common psychiatric disorders (depression, anxiety, schizophrenia and bipolar disorder) (Ncase ranges between 20 352 and 246 363), all of European ancestry. PARTICIPANTS/MATERIALS, SETTING, METHODS: We quantified pairwise genetic correlation to understand the shared genetic predisposition using genome-wide genetic variants. We performed a two-sample bidirectional Mendelian randomisation analysis to make causal inferences, using GWAS-identified 102 depression-associated genetic instruments, 6 anxiety-associated instruments, 179 schizophrenia-associated instruments, 30 bipolar disorder-associated instruments and 14 PCOS-associated instruments. We performed several important sensitivity analyses examining sex hormones and utilising different MR approaches. MAIN RESULTS AND THE ROLE OF CHANCE: We did not find significant genetic correlations (rg) for PCOS with psychiatric disorders (depression (rg = 0.09, P = 0.06), anxiety (rg = 0.15, P = 0.06), schizophrenia (rg = 0.02, P = 0.59), bipolar disorder (rg = 0.08, P = 0.19)). Genetic predisposition to PCOS was associated with depression in some of our MR approaches, without any evidence of pleiotropy (PMR-Egger intercept = 0.60). However, this weak PCOS-depression causal association attenuated to null after adjusting for BMI (1.00 (0.99-1.02), P = 0.28). On the contrary, we did not observe any statistically significant association between genetically instrumented PCOS with other psychiatric disorders (anxiety 1.01 (0.93-1.08), P = 0.89; schizophrenia 1.03 (0.97-1.10), P = 0.37; bipolar disorder 0.96 (0.90-1.03), P = 0.26). Bidirectional MR did not reveal an effect by which mental health conditions influenced PCOS risk. LIMITATIONS, REASONS FOR CAUTION: Despite our study being the largest in sample size of its kind, the overall negligible causal relationship between PCOS and psychiatric outcomes may reflect a true null association but may also be due to a true effect too modest to be detected. We were not able to investigate PCOS subtypes and used an overall heterogenous PCOS sample due to limited availability of data. WIDER IMPLICATIONS OF THE FINDINGS: Our comprehensive analysis does not identify a shared genetic basis of PCOS with psychiatric diseases. Although genetically instrumented PCOS appears to correlate with depression, such an effect is likely mediated by BMI, suggesting a role of non-genetic exposures underlying the observed comorbidity. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by the Swedish Medical Research Council 2018-02435 (to E.S.V.), Novo Nordisk Foundation NNF19OC0056647 (to E.S.V.), the Adlerbert Research Foundation (to E.S.V.), the SRP in Diabetes at Karolinska Institutet (to E.S.V.) and the Swedish Research Council VR 2018-02247 (to X.J.). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

[Activity comparison of humanized CD19 CAR-T cells with murine CD19 CAR-T on Nalm-6 cells and xenograft tumor model].

Objective: To compare the activity difference of the high affinity humanized CD19 chimeric antigen receptor (CAR)-T cells and murine CD19 CAR-T cells. Methods: Peripheral venous blood T cells from 8 healthy volunteers were collected and infected with humanized and murine CD19 CAR lentivirus. Human and murine CD19 CAR-T cells were prepared and cell proliferation was detected by cell counting kit-8 (CCK-8) method. The cytotoxicity of CD3(+) T cells, humanized and murine CD19 CAR-T cells to NALM-6 cells was detected by lactate dehydrogenase assay. Thirty BAL B/c nude mice transplanted with NALM-6 cells were randomly divided into 3 groups with 10 mice in each group and injected humanized CD19 CAR-T cells, mouse CD19 CAR-T cells and control CD3(+) T cell via tail vein, respectively. The proportion of NALM-6 cells in peripheral blood and the proportion of CD19 CAR-T cells in T cells from the vein of the inner canthus were detected by flow cytometry. The overall survival of BAL B/c nude mice was observed. Results: The proliferation of mouse and humanized CD19 CAR-T cells were (68.50±0.93)% and (80.63±1.41)%, respectively (t=20.353, P<0.001) after cultured in vitro for 24 hours, and were (91.38±1.41)% and (148.13±1.25)%, respectively (t=85.364, P<0.001) after cultured for 48 hours. When the effect to target ratio was 1∶1, there was no difference between the humanized and murine CD19 CAR-T cell group after co-culture for 24 hours (P=0.169), while the killing activity of humanized CD19 CAR-T cells against NALM-6 cells was higher than that of murine CD19 CAR-T cells (P<0.01) after 48 hours of co-culture. When the effect to target ratio was 4∶1, the cytotoxicity of humanized CD19 CAR-T cells against NALM-6 cells was higher than that of murine CD19 CAR-T cells in co-culture for 24 and 48 hours (P<0.01). On the seventh day of CD19 CAR-T cell therapy, the proportion of NALM-6 cells in the peripheral blood of BAL B/c nude mice decreased to the lowest level in the humanized CD19 CAR-T cell group and the murine CD19 CAR-T cell group. After 21 days, the proportion of NALM-6 cells in the murine CD19 CAR-T cell group was higher than that in the humanized CD19 CAR-T cell group (P(21 d)=0.001, P(28 d)<0.001, P(35 d)<0.001). The proportion of humanized and murine CD19 CAR-T cells in the peripheral blood reached the peaks after 7 days of therapy, and the proportion of humanized CD19 CAR-T cells was higher than that of murine CAR-T cells (P(7 d)=0.002). The CD19 CAR-T cells disappeared in the peripheral blood in the murine CD19 CAR-T cell group after 14 days of therapy, while in the humanized CD19 CAR-T cell group it disappeared after 21 days of therapy. The median survival of BAL B/c nude mice in the murine CD19 CAR-T cell group and the humanized CD19 CAR-T cell group was 42 days and 63 days, respectively (χ(2)=15.382, P<0.001). Conclusions: High affinity humanized CD19 CAR-T cells have stronger proliferation, higher cytotoxicity and longer survival time compared with those of murine CD19 CAR-T cells. The results indicate that the clinical efficacy of humanized CD19 CAR-T cells would be better than that of murine CD19 CAR-T cells.

[Effect of hemocoagulase agkistrodon on coagulation status in patients with traumatic brain injury in vitro].

Objective: To analyze the effects of hemocoagulase agkistrodon (HCA) on the coagulation status of healthy people and traumatic brain injury (TBI) patients in vitro. Methods: A total of 10 TBI patients were enrolled from December 2018 to June 2019,and 24 age and sex matched healthy controls were also enrolled. Clinical and pathological data, blood samples of all subjects were collected. Different gradient concentrations of HCA were added to the blood samples which were detected by thromboelastography, and the R value, K value, α angle and MA value of thromboelastography parameters between the two groups were analyzed to explore the effect of HCA on the coagulation status of patients with TBI. Results: With the increase of HCA concentration in blood samples, the R and K values gradually increased, and the α angles and MA values gradually decreased in both TBI patients group which included 7 males and 3 females, with an median age of 33 (28-39) years old and healthy control group which included 11 males and 13 females, with an median age of 33 (23-49) years old. The differences in the R values, K values, α angles, and MA values of different concentration gradients were statistically significant in both healthy control group and TBI patients group (χ2 were 109.80, 131.28, 185.47, 165.97 and 54.92, 75.60, 80.12, 59.25, respectively, all P<0.001). The differences between R values after adding HCA of 0-0.105 U/ml in the healthy group were statistically significant (P=0.025), but K values, α angles and MA values were not statistically significant (P values were 0.275, 0.206 and 0.330, respectively); the R values of the TBI patients group were not statistically significant after adding HCA of 0 to 0.105 U/ml (P=0.976), and the K values, α angles, and MA values were statistically significant (P values were 0.047, 0.041, and 0.034, respectively).The R values of the healthy control group, the TBI patients group, and the overall data were significantly positively correlated with the HCA dose (r values were 0.552、0.700、0.420, respectively, P<0.001), the K values were significantly positively correlated with the HCA dose (r values were 0.726、0.861、0.750, respectively, P<0.001), the α angles were significantly negatively correlated with the HCA dose (r values were -0.815、-0.876、-0.807, respectively, P<0.001) and the MA values were significantly negatively correlated with the HCA dose (r values were -0.757、-0.710、-0.729, respectively, P<0.001). Conclusions: HCA does not aggravate the procoagulant state of blood in healthy people and TBI patients, and with the increase of HCA concentration in blood, the blood samples of both groups show a tendency to decrease the coagulation ability.

[Analysis of families with fetal congenital abnormalities but negative prenatal diagnosis by whole exome sequencing].

Objective: To evaluate the value of whole exome sequencing (WES) in prenatal clinical application. Methods: A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed. Results: Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results. Conclusions: WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

[Identification of New Psychoactive Tryptamines 4-OH-MET and 4-AcO-DMT Using High Resolution Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy].

ABSTRACT: Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry （GC-QTOF-MS）, ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry （UPLC-LTQ-Orbitrap MS） and 1H-nuclear magnetic resonance spectroscopy （1H-NMR）. Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 （molecular ion peak）, 72.080 6 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation （CID） mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 （molecular ion peak）, 58.065 1 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and 1H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and 1H-NMR can be used together to identify unknown new psychoactive substances.

Determination of Azide Ions in Blood by Pentafluorobenzyl Derivation Followed by GC-MS.

ABSTRACT: Objective To establish a method for determination of the azide ions in blood by gas chromatography-mass spectrometry （GC-MS） following pentafluorobenzyl derivatization. Methods A blood sample of 0.2 mL was placed into a 10 mL glass test tube, and the internal standard sodium cyanide, derivatization reagent pentafluorobenzyl bromide and catalyst tetradecyl benzyl dimethyl ammonium chloride were added in turn. After vortex mixing, the mixture was heated with low-power microwave for 3 min. After centrifugation, the organic phase was taken for GC-MS analysis. Results The azide ions in blood had a good linear relationship in the mass concentration range of 0.5 to 20 µg/mL. The lowest detection limit was 0.25 µg/mL and the relative recovery was 91.36%-94.58%. The method was successfully applied to a case of death from sodium azide poisoning. The mass concentration of azide ions in the blood of the dead was 11.11 µg/mL. Conclusion The method developed in this paper has strong specificity and is easy to operate, which is suitable for the rapid detection of azide ions in blood.

Meta-analysis of preoperative high-sensitivity cardiac troponin measurement in non-cardiac surgical patients at risk of cardiovascular complications.

BACKGROUND: Patients undergoing major non-cardiac surgery are at risk of cardiovascular complications. Raised levels of high-sensitivity troponin are frequently detected before operation among these patients. However, the prognostic value of high-sensitivity troponin in predicting postoperative outcomes remains unclear. METHODS: A systematic search of PubMed, Embase and Science Citation Index Expanded was undertaken for observational studies published before March 2018 that reported associations between raised preoperative levels of high-sensitivity troponin and postoperative major adverse cardiac events and/or mortality after non-cardiac surgery. Meta-analyses were performed, where possible, using random-effects models. RESULTS: Seven cohort studies with a total of 4836 patients were included. A raised preoperative high-sensitivity troponin level was associated with a higher risk of short-term major adverse cardiac events (risk ratio (RR) 2·92, 95 per cent c.i. 1·96 to 4·37; I2  = 82·6 per cent), short-term mortality (RR 5·39, 3·21 to 9·06; I2  = 0 per cent) and long-term mortality (RR 2·90, 1·83 to 4·59, I2  = 74·2 per cent). The addition of preoperative high-sensitivity troponin measurement provided improvements in cardiovascular risk discrimination (increase in C-index ranged from 0·058 to 0·109) and classification (quantified by continuous net reclassification improvement) compared with Lee's Revised Cardiac Risk Index alone. There was substantial heterogeneity and inadequate risk stratification analysis in the included studies. CONCLUSION: Raised preoperative levels of high-sensitivity troponin appear to represent a risk for postoperative major adverse cardiac events and mortality. Further study is required before high-sensitivity troponin can be used to predict risk stratification in routine clinical practice.

ANTECEDENTES: Los pacientes a los que se realiza una cirugía mayor no cardíaca tienen riesgo de presentar complicaciones cardiovasculares. En estos pacientes se observan con frecuencia niveles preoperatorios elevados de troponina de alta sensibilidad (high-sensitivity troponin, hs-cTn). Sin embargo, el valor pronóstico de la hs-cTn para predecir los resultados postoperatorios no está bien definido. MÉTODOS: Se realizó una búsqueda sistemática en las bases de datos PubMed, EMBASE y Science Citation Index Expanded de estudios observacionales publicados antes de marzo de 2018 que analizasen la posible relación de los niveles elevados preoperatorios de hs-cTn y los efectos adversos graves de tipo cardíaco (major adverse cardiac events, MACE) postoperatorios y/o la mortalidad después de la cirugía no cardíaca. Se realizó el metaanálisis utilizando modelos de efectos aleatorios siempre que fuera posible. RESULTADOS: Se incluyeron siete estudios de cohortes con un total de 4.836 pacientes. La elevación preoperatoria de hs-cTn se asoció con un mayor riesgo de MACE a corto plazo (tasa de riesgo, risk ratio, RR 2,92, i.c. del 95% 1,96-4,37, I2 = 82,6%) y con la mortalidad a corto plazo (RR 5,39, i.c. del 95 % 3,21-9,06, I2 = 0%) y a largo plazo (RR 2,90, i.c. del 95% 1,83-4,59, I2 = 74,2%). Añadir la medición preoperatoria de hs-cTn mejoró la capacidad discriminativa para el riesgo cardiovascular (aumento de 5,8% a 10,9% en el índice C) y también la clasificación de los pacientes (cuantificada mediante el índice de reclasificación neta continua) en comparación con el uso de solo el índice de riesgo cardíaco revisado de Lee. En los estudios incluidos, hubo gran heterogeneidad y análisis inadecuado de la estratificación del riesgo. CONCLUSIÓN: Los niveles preoperatorios elevados de troponina de alta sensibilidad parecen ser un marcador de riesgo de efectos adversos graves de tipo cardíaco en el postoperatorio y de mortalidad. Se requieren más estudios antes de utilizar la troponina de alta sensibilidad para la estratificación del riesgo en la práctica clínica rutinaria.

MicroRNA-4443 regulates monocyte activation by targeting tumor necrosis factor receptor associated factor 4 in stroke-induced immunosuppression.

BACKGROUND AND PURPOSE: MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the early stage of acute ischaemic stroke (AIS). The purpose of this study was to investigate the expression patterns of miRNAs in peripheral blood mononuclear cells (PBMCs) from AIS patients and further explore related molecular mechanisms in stroke-induced immunodeficiency syndrome (SIDS). METHODS: The miRNA expression patterns of PBMCs were detected by miRNA microarray and validated by quantitative real-time polymerase chain reaction (qRT-PCR) in AIS patients and healthy controls. Bioinformatics methods and luciferase reporter assays were used to detect the downstream target genes. Following stimulation with lipopolysaccharide and interleukin-4, the expression of miR-4443, tumor necrosis factor receptor associated factor 4 (TRAF4) and the nuclear factor kappa B (NF-κB) pathway were evaluated. Furthermore, transfection with miR-4443 mimic or inhibitor in the monocytes was carried out to gain insight into the mechanisms in SIDS. RESULTS: Interleukin-10 in AIS patients was significantly higher than that of healthy controls. The miRNA microarray analysis and qRTPCR validation showed that only miR-4443 was upregulated expressed in PBMCs from AIS patients, especially in monocytes. miR-4443 was shown to directly interact with the 3' untranslated regions of TRAF4, resulting in suppression of TRAF4 protein expression. Furthermore, the expression of miR-4443 and TRAF4 was regulated by stimulation with lipopolysaccharide or interleukin-4. Additionally, overexpression of miR-4443 suppressed the TRAF4/Iκα/NF-κB signaling pathway to activate the expression of anti-inflammatory cytokines in monocytes. CONCLUSIONS: The increased expression of miR-4443 induced monocyte dysfunction by targeting TRAF4, which may function as a crucial mediator in SIDS.

Coronal root canal morphology of permanent two-rooted mandibular first molars with novel 3D measurements.

AIM: To measure the coronal root canal morphology of permanent mandibular first molars using 3D coordinates for more precise conservative endodontic cavity preparation. METHODOLOGY: In total, 57 cone beam computed tomography (CBCT) images of sound mandibular molars with fully formed apices without previous endodontic treatment were taken from 33 patients aged 16 to 75 years. The CBCT machine (MCT-1[EX-2F], J. Morita Manufacturing Corp, Kyoto, Japan) provided 14-bit greyscale images with the voxel size of 0.125 mm. All images were taken at 80 kV and 5.0 mA, with a 17-s exposure time, which were then reconstructed in 3D models and viewed by an endodontist. The gender of the patients and the tooth position, and number of root canals, were recorded. The landmarks of coronal root canals were determined, then the distribution of landmarks, maximum curvature in the axial direction and curvature directions in the horizontal direction of coronal root canals were measured. Distributions of landmarks were analysed using a spatial statistics method. Data about curvature were compared using a t test. RESULTS: Overall, the distribution of root canal orifices and the centre of the canal primary curve were more centralized than other landmarks. The landmarks were located more mesiobuccally to the centre of the occlusal plane of mandibular first molars. Specifically, the measurements of the maximum curvature of coronal root canals in the axial direction were as follows: in 3-canal teeth, the average angles of curvatures were 22°,23°,15° for mesiobuccal (MB), mesiolingual (ML) and distobuccal (DB) canals, respectively; in 4-canal teeth, the average angles of curvatures were 24°,26°,15°,22°for MB, ML, DB and distolingual (DL) canals, respectively. The degrees of coronal root canal curvatures in the horizontal direction were as follows: in 3-canal teeth, the average angles of curvatures were -8°,47°,-2° for MB, ML and DB canals, respectively; in 4-canals teeth, the average angles were -11°,50°,-28°,45° for MB, ML, DB and DL canals, respectively. Statistically, there was no reliable side or sex difference in any of the measurements (P > 0.05). CONCLUSIONS: In permanent two-rooted mandibular first molars, the coronal canals clustered in the direction of the mesiobuccal side of the occlusal surface of the teeth.

[The evaluation of modified cell infusion method to reduce febrile non-hemolytic transfusion reaction in CD(19) chimeric antigen receptor T cell threapy].

Objective: To retrospectively analyze the efficacy and safety of modified cell infusion method in reducing the incidence of febrile non-hemolytic transfusion reaction (FNHTR). Methods: A total of 69 patients were enrolled in the clinical trial of CD(19) chimeric antigen receptor T (CAR-T) cell treatment from February 2017 to October 2018. Study group received the modified cell infusion method, that 1×10(6) CAR-T cells were re-suspended in 2 mg human serum albumin with total volume of 20 ml and injected intravenously. The control group was intravenously administrated with CAR-T cell in 100 ml normal saline. The incidence of FNHTR, cytokine releasing syndrome (CRS) grade, cytokine level and efficacy were compared. Results: (1)The incidence of FNHTR in the study group was 21.1%, significantly lower than that in the control group (71%)(P=0.000). (2)There was no statistical difference in cell proliferation between the study group and the control group on day 4, 7, 14 and 21 after CAR-T cell infusion (P=10.223, 3.254, 5.551, 7.605). (3)There was no statistical difference in CRS grading between the study group and the control group (P=0.767). There was no statistical difference in the levels of interleukin 2 receptor (IL-2R), IL-6, tumor necrosis factor (TNF)-α between the two groups. (4)The C-reaction protein (CRP) level of the study group was lower than that of the control group on day 4 and 7 (P=0.026, 0.007). (5)There was no statistical difference of response rates in acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL) patients between the two groups (P(ALL)=0.842; P(NHL)=0.866). Conclusion: The modified cell infusion method in CD(19) CAR-T cell treatment reduces the incidence of treatment-related FNHTR. It does not affect the proliferation of CAR-T cells in vivo, the grading of CRS and the response rates.

[The association between plasma levels of 20 amino acids and risk of diabetes].

Objective: To investigate the association between the plasma levels of 20 amino acids and the risk of diabetes in middle-aged and elderly population. Methods: This study was a part of the Chinese multi-provincial cohort study conducted in communities of Shougang. In 2007 and 2012, the population was investigated for diabetes and other risk factors. Blood samples collected from 475 people were tested for various amino acid levels by liquid chromatography-tandem mass spectrometry. A multivariate logistic regression analysis was used to analyze the association between plasma amino acid levels and diabetes risk. Results: The age of the selected population at baseline was (58.7±6.3) years, and the blood glucose level at baseline was (5.68±1.34) mmol/L. Among them, 56 (11.79%) subjects were diabetes. Multivariate logistic regression analyses showed that after adjusting for age, gender, body mass index, systolic blood pressure and dyslipidemia, individuals with plasma branched-chain amino acid (valine, leucine and isoleucine) and cysteine in the highest tertile levels were at high risk of diabetes with the ORs of 3.61 (95% CI 1.48-8.80), 3.27 (95% CI 1.34-7.99), 2.46 (95% CI 1.04-5.84) and 2.09 (95% CI 1.02-4.27), respectively. After 5 years' followed up, 5.73% (24/419) subjects developed diabetes. Compared with those in the lowest tertile, individuals with plasma branched-chain amino acid (total concentration), phenylalanine, and tyrosine levels at baseline in the highest tertile had 3.69 times, 3.61 times and 4.14 times higher risk to develop new diabetes, respectively. In contrast, individuals with plasma glycine level in the highest tertile had only 76% (OR 0.24, 95% CI 0.06-0.91) risk for the development of diabetes compared with those with plasma glycine level in the lowest tertile. Conclusions: The increase in plasma branched-chain amino acid and cysteine levels is significantly associated with an increase in incident diabetes. Subjects with higher levels of branched-chain amino acids and aromatic amino acids (phenylalanine, tyrosine) had a significantly higher risk of developing new-onset diabetes, while those with higher glycine levels had a significantly lower risk of developing diabetes in 5 years.

Effects of lactic acid bacteria and smectite after aflatoxin B1 challenge on the growth performance, nutrient digestibility and blood parameters of broilers.

This study aimed to investigate the effect of lactic acid bacteria (LAB) and smectite on the growth performance, nutrient digestibility and blood parameters of broilers that were fed diets contaminated with aflatoxin B1 (AFB1 ). A total of 480 newly hatched male Arbor Acres broilers were randomly allocated into four groups with six replicates of 20 chicks each. The broilers were fed diets with the AFB1 (40 µg/kg) challenge or without (control) it and supplemented with smectite (3.0 g/kg) or LAB (4.0 × 1010  CFU/kg) based on the AFB1 diet. The trial lasted for 42 days. The results showed that during days 1-42 of AFB1 challenge, the feed intake (FI) and body weight gain (BWG) were depressed (p < .05). The inclusion of LAB and smectite increased (p < .05) the BWG by 71.58 and 41.89 g/bird, respectively, which reached the level of the control diet (p ≥ .05), but there were no differences (p ≥ .05) in performance between LAB and smectite. LAB and smectite also increased (p < .05) the apparent total tract digestibility of the crude protein. Regarding the blood parameters, AFB1 decreased (p < .05) the levels of red blood cell count, haematocrit, mean corpuscular volume, haemoglobin, albumin and total protein. In the meantime, the AFB1 increased (p < .05) leucocyte counts, urea nitrogen, cholesterol, total bilirubin, creatinine, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline phosphatase. By contrast, LAB and smectite affected (p < .05) these parameters in the opposite direction. It can be concluded that after the AFB1 challenge, LAB and smectite have similar effects on the growth and health of the broilers, suggesting that LAB could be an alternative against AFB1 in commercial animal feeds.

[Multilevel logistic regression analysis on hypercholesterolemia related risk factors among adults in China].

Objective: To investigate the prevalence of hypercholesterolemia among Chinese adults in different geographic areas, and to analyze the related factors. Methods: China Chronic and Non-Communicable Disease and Risk Factor Surveillance was conducted in 2013, based on 298 counties/districts in 31 provinces of Chinese mainland. The adults aged 18 years old were randomly selected using multi-stage stratified clustering sampling method. Information on chronic disease and risk factors was collected using face-to-face questionnaire interview and physical measurement. Blood samples were collected by local staffs. Serum total cholesterol (TC) was determined using standard method in a central laboratory. After excluding 565 participants missing key variables and 1 558 participants with abnormal TC values, a total of 174 976 participants were included. Weighted prevalence of hypercholesterolemia was calculated. Hypercholesterolemia related individual or geographic determinants were defined using multilevel logistic regression. Results: The prevalence of hypercholesterolemia in Chinese adults age 18 years old and above was 6.9% (95%CI: 6.4%-7.3%), ranged from 3.0% (95%CI: 2.5%-3.4%) in the northwest of China to 14.2% (95%CI: 12.9%-15.5%) in the south (χ(2)=183.42, P<0.001). The prevalence of hypercholesterolemia was higher in 6 provinces including Tianjin, Liaoning, Fujian, Guangdong, Guangxi, and Hainan (≥9.0%), but lower in 7 provinces including Shanxi, Shannxi, Gansu, Qinghai, Ningxia, Xinjiang, and Tibet (<3.9%). There was a 1.27 fold variation in hypercholesterolemia prevalence by provincial level, and 72.5% of the geographical variation in hypercholesterolemia prevalence was account for by area-level determinants. With multilevel logistic analysis, the individual risk factors associated with hypercholesterolemia included aging, higher education level or annual household income per capita, regular drinking, too much red meal intake, inactivity, overweight or obesity. For geographic factors, residents living at south China, counties/districts with higher urbanization rates, higher education level or lower standardized death rates were more likely to have hypercholesterolemia (all P<0.05). Conclusion: The prevalence of hypercholesterolemia was high in Chinese adults, it was different between regions and related with characteristics of population, individual behaviors and geographical regions.

[Geographical variation and related factors in prediabetes prevalence in Chinese adults in 2013].

Objective: To investigate the geographical variation of prediabetes in adults in different regions of China, and to analyze the related factors of prediabetes. Methods: Data was obtained from China Chronic Disease and Related Risk Factor Surveillance in 2013. The surveillance adopted multiple-stage stratified cluster random sampling method, which sampled 177 099 residents aged above 18 years old among 298 surveillance points in 31 provinces of Chinese Mainland. Questionnaire interview was used to obtain demographic variables, personal living style, and socio-economical information. Physical examination was conducted and fasting venous blood sample and (oral glucose tolerance test-2 hours, OGTT-2 h) venous blood sample were obtained from the participants. A total of 171 567 residents aged 18 and above were included in the analysis. The prevalence of prediabetes was analyzed by provinces and by China's geographical regions, after complex weighting. Multilevel logistic models were established to explore the related factors of prediabetes on the area level and individual level. Results: The prevalence of prediabetes among residents aged 18 and above was 16.6% (95%CI: 15.6%-17.6%) in China. The prevalence of prediabetes was the highest (18.3%) in the south China and lowest (13.1%) in the northwest area. The difference of the prevalence in different areas were not statistically significant (P=0.510). If categorized the prevalence of prediabetes into 5 groups by quintile, Hainan, Jilin, Shandong, Anhui, Hunan and Chongqing were in the highest group of prevalence of prediabetes (18.6%-22.7%), and Tibet, Qinghai, Gansu, Ningxia, Guizhou, and Jiangxi were in the lowest group (7.6%-12.6%). The variance of prevalence of prediabetes on the county level (MOR: 1.60 (95%CI:1.53-1.67)) was more diverse than the province level (MOR: 1.21(95%CI:1.08-1.29)) and higher than the street level (1.23 (95%CI:1.14-1.30)). Several factors increased risk of pre-diabetes, including smoking, hazardous drinking and harmful drinking, drinking in the past 30 days, overweight, obesity, central obesity, sugary drink intake, hypertension, high total cholesterol, high triglycerides, high blood low-density lipoprotein cholesterol, low blood high-density lipoprotein cholesterol (all P<0.05). After adjusted the above variables, 92.5% of variance of prediabetes prevalence conld be explained on the provincial level. Conclusion: The geographical distribution of prediabetes in adults in China differed by geographic areas, and it significantly varied on the county level. The related variables included demographic variables, personal behavior, and geographic related variables.

Triglyceride to high-density lipoprotein cholesterol ratio predicts worse outcomes after acute ischaemic stroke.

BACKGROUND AND PURPOSE: The effect of the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) on clinical outcomes of acute ischaemic stroke (AIS) patients is unclear. This study sought to determine whether the TG/HDL-C ratio in AIS patients is associated with worse outcomes at 3 months. METHODS: Acute ischaemic stroke patients who were admitted from 2011 to 2014 were enrolled in this study. TG, total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) were collected on admission. Three end-points were defined according to the modified Rankin scale (mRS) score at 3 months after symptom onset (excellent outcome, mRS 0-1; good outcome, mRS 0-2; and death, mRS 6). RESULTS: In all, 1006 patients were included (median age 68.5 years; 58.2% male). Higher TG, non-HDL-C and TG/HDL-C were strongly associated with the three end-points after adjustments: excellent [odds ratio (OR) = 1.39, OR 1.89 and OR 2.34, respectively] and good (OR 1.48, OR 2.90 and OR 4.12) outcomes, and death (OR 0.59, OR 0.29 and OR 0.26). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a TG/HDL-C ≥ 0.87 for excellent outcomes [area under the ROC curve (AUC) 0.596; sensitivity 73.3%; specificity 42.7%] and non-death (AUC 0.674; sensitivity 67.8%; specificity 60.6%) as well as a TG/HDL-C ≥ 1.01 for a good outcome (AUC 0.652; sensitivity 61.6%; specificity 63.2%). Patients with a TG/HDL-C < 0.87 had a 2.94-fold increased risk of death (95% confidence interval 1.89-4.55) compared with patients with a TG/HDL-C ≥ 0.87. CONCLUSIONS: A lower TG/HDL-C was independently associated with death and worse outcome at 3 months in AIS.

[Efficacy and safety of vertebrae pedicle subtraction osteotomy by posterior trans apical for correction of severe and rigid idiopathic scoIiosis].

Objective: To evaluate the efficacy and safety of pedicle subtraction osteotomy for correction of severe rigid idiopathic scoliosis. Methods: From January 2003 to December 2014, eighteen patients with severe rigid idiopathic scoliosis were treated by posterior wedge osteotomy in department of spinal surgery, the First Affiliated Hospital of Xinjiang Medical University. There were 5 males and 13 females, and the average age at was (16.9±9.1)years, and the average follow-up was 47.6 months. The coronal and sagittal Cobb's angles, sagittal trunk shifts, apical vertebral translation, height change and fusion segments were measured on standing AP and lateral radiographs before, after surgery and the final follow-up. Results: The Cobb's angle in the coronal plane was corrected from (94.3±13.3)°to (31.6±14.8)°, representing 64.8% correction rate. The Cobb's angle in the sagittal plane was corrected from (62.5±17.8)°to (27.1±11.7)°, representing 82.6% correction rate. Coronal trunk shift was obviously improved from -29.8 mm to -3.5 mm. the average fusion segments was 13.7±1.8 ranging from 11 to 17 segments. Perioperative complications consisted of pleura injury in 4 cases, cerebrospinal fluid leakage in 2 cases transient neurological damage in 2 cases and delayed infection in 1 case. Conclusion: Pedicle Subtraction Osteotomy correction by the single posterior approach is a reliable and safe surgical technique for correction of severe rigid idiopathic scoliosis.

[The coping styles and its relationship with quality of life among 1 968 female breast cancer patients in Shanghai in 2014].

Objective: To study the coping styles and its relationship with quality of life among part of the female breast cancer patients in Shanghai in 2014. Methods: In August of 2014, 1-3 block groups affiliated to Shanghai Cancer Rehabilitation Club were selected from each of the 17 districts of Shanghai by convenient sampling method. Respondents were recruited from these block groups via putting up posters in the community or top three hospitals nearby. The inclusion criteria were as follows: female, aged from 18 to 80 years old; the initial diagnosis or primary tumor was breast cancer, and active treatments including surgery, radiotherapy and chemotherapy were finished; capable of basic reading and comprehension, and there was no communication disorder; daily activities were not limited, and with no mental disorder or dysgnosia. Totally 2 205 respondents were included. Questionnaire survey was conducted to collect the information of demographic characteristics, disease characteristics, result of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and result of the Ways of Coping Inventory-Cancer Version (WOC-CA). 1 968 valid questionnaires were withdrawn. The results of respondent characteristics and WOC-CA were under descriptive analysis, and the differences of coping styles among groups of different demographic characteristics were compared using t test. In addition, we analyzed the correlation between respondents' coping styles and quality of life using partial correlation analysis. Results: The average age of the 1 968 respondents was (58.7±7.4) years old, and BMI was (24.4±5.4) kg/m(2). The score of positive coping styles was 2.04±0.41, and the score of negative coping styles was 1.79±0.33. The scores of Physical Functioning (PF), Role Functioning (RF), Cognitive Functioning (CF), Emotional Functioning (EF), Social Functioning (SF), and Global Health (GH) were 83.40±12.18, 90.80±15.92, 80.72±16.29, 84.67±15.19, 80.99±20.91, 65.27±21.21, respectively. Positive coping styles correlated with PF, EF, and GH positively, and the correlation coefficients were separately 0.581 (P=0.046), 0.593 (P=0.045), 0.770 (P<0.001). Negative coping styles correlated with RF, CF, EF, and SF negatively, and the correlation coefficients were separately-0.672 (P=0.021),-0.815 (P=0.005),-0.121 (P<0.001),-0.123 (P<0.001). Conclusion: Part of the female breast cancer patients in Shanghai in 2014 mainly adopted positive coping styles, and in general the positive coping styles correlated with quality of life positively and negative coping styles correlated with quality of life negatively.