Accuracy of quantitative viral secondary standards: a re-examination.

Interlaboratory agreement of viral load assays depends on the accuracy and uniformity of quantitative calibrators. Previous work demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values in both log10 copies/mL and log10 international unit (IU)/mL, with bias from manufacturer-assigned nominal values of 0.0-0.9 log10 units (either copies or IU)/mL. Standards normalized to IU and those values assigned by dPCR rather than by real-time PCR (qPCR) showed better agreement with nominal values. The latter reinforces prior conclusions regarding the utility of using such methods for quantitative value assignment in reference materials. Quantitative standards have improved over the last several years, and the remaining bias from nominal values might be further reduced by universal implementation of dPCR methods for value assignment, normalized to IU. IMPORTANCE: Interlaboratory agreement of viral load assays depends on accuracy and uniformity of quantitative calibrators. Previous work, published in JCM several years ago, demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values, indicating a substantial improvement in the production of accurate secondary viral standards, while supporting the need for further work in this area and for the broad adaption of international unit (IU) as a reporting standard for quantitative viral load results.

New approaches in the diagnosis and prognosis of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common pregnancy metabolic disorder in which a person with no history of hyperglycemia exhibits any degree of impaired glucose tolerance during gestation. GDM can be resolved on its own after birth, but mothers with GDM are more at risk for future problems, such as type 2 diabetes, obesity, and cardiovascular disease. In addition, GDM can cause macrosomia in infants and obesity or even the risk of diabetes in childhood. Standard diagnostic tests for GDM are the oral glucose tolerance test (OGTT) and glucose challenge test (GCT), which is a mandatory test at 28-28 weeks of pregnancy in most countries. Disorders in various molecular mechanisms, such as hepatocyte growth factor (HGF), mechanistic target of rapamycin (mTOR), and nuclear factor-kappaB (NF-κB) signaling pathways are involved in GDM. Therefore, a better understanding of these mechanisms can help find new therapeutic and diagnostic strategies accordingly. In this review, we first deal with molecular mechanisms involved in GDM occurrence and then summarized the studies that hired this knowledge for early diagnosis and prognosis of GDM. Finally, we present the latest achievements in the diagnosis of GDM based on exosomes, microRNAs, glycosylated hemoglobin, and inflammatory factors detection in maternal circulation.

Successful percutaneous coronary intervention with extracorporeal membrane oxygenation for patient with acute coronary syndrome and cardiac arrest: a case report.

BACKGROUND: The incidence rate of acute coronary syndrome (ACS) in China is on the rise and is considered a leading cause of death. Emergency percutaneous coronary intervention (PCI) is the preferred treatment method for ACS. However, severe complications may hinder emergency PCI and lead to increased mortality. Extracorporeal membrane oxygenation (ECMO) redirects blood flow and oxygenates it before returning. Therefore, ECMO support during PCI may improve functional recovery and outcomes. This case report presents a successful case of extracorporeal membrane oxygenation (ECMO)-assisted emergency PCI treatment of an outpatient with ACS. CASE REPORT: Male, 43 years old, experienced sudden, severe, and persistent squeezing-like chest pains accompanied by profuse sweating. After half an hour, the patient suddenly lost consciousness and was unable to exhale. After ECMO-assisted PCI, the patient's blood pressure and blood oxygen status improved, and the autonomous rhythm was restored. Imaging results showed 100% occlusion of the middle to distal anterior descending branch. After undergoing distal thrombus aspiration, a stent was implanted in the proximal end of the anterior descending branch. Repeated angiography showed good stent adhesion and restored blood flow in the anterior descending branch. The postoperative patient was transferred to the coronary care unit (CCU) ward with ECMO and ventilator for monitoring. CONCLUSIONS: ECMO-assisted emergency PCI effectively improved the blood pressure and oxygen status of the ACS patient with cardiac arrest, and restored the autonomous rhythm, with a good rehabilitation effect.

[Value of C-peptide-based insulin resistance index for evaluating correlation between insulin resistance and serum uric acid level in individuals undergoing health examination].

OBJECTIVE: To investigate the value of C-peptide-based insulin resistance index in evaluating the correlation between insulin resistance and serum uric acid (Ua) level in subjects undergoing health examination. METHODS: The data of 46 017 subjects undergoing health examination were retrospectively collected from the Second Medical Center of PLA General Hospital from January, 2017 to December, 2021. The subjects were divided into Ua≤420 µmol/L group and Ua>420 µmol/L group for comparison of HOMA insulin resistance index (HOMA2-IR) and HOMA insulin resistance-C peptide (HOMA2 IR-CP). The correlations of HOMA2-IR and HOMA2 IR-CP with Ua level were analyzed using Pearson correlation analysis and linear regression analysis. Hierarchical interaction analysis was conducted to assess the differences in the association between insulin resistance index and Ua level in different subgroups. The ROC curve was used to evaluate the predictive ability of insulin resistance index for an increased Ua level. RESULTS: The levels of HOMA2-IR and HOMA2 IR-CP were significantly lower in Ua≤420 µmol/L group than in Ua>420 µmol/L group. Univariate Pearson correlation analysis showed a weak correlation of HOMA2-IR with Ua (r=0.262, P<0.001) and moderate correlation of HOMA2 IR-CP with Ua (r=0.409, P<0.001). Multivariate linear regression analysis, after adjustment for confounding factors, demonstrated that HOMA2-IR (R2=0.445, P<0.001) and HOMA2 IR-CP (R2=0.461, P<0.001) were both factors affecting Ua level. Hierarchical interaction analysis showed that the association of insulin resistance index with Ua level varied significantly with gender, age, and glucose metabolism (P<0.001). ROC curve showed that the areas under the curve predicted an increased Ua level by HOMA2-IR and HOMA2 IR-CP were 0.662 and 0.722, respectively. CONCLUSIONS: HOMA2 IR-CP is a more accurate indicator for assessing the correlation between insulin resistance and Ua level.

[Clinical value of arterial stiffness assessment on risk prediction of vascular stiffness in the octogenarian elderly].

Objective: This study aimed to analyze clinical factors related to arterial stiffening and establish a risk prediction nomogram of arterial stiffening in the octogenarian(≥80 years). Methods: This study was a retrospective cross-sectional study, which enrolled the octogenarian elderly who underwent physical examination and secondary prevention intervention in the outpatient department of Chinese People's Liberation Army General Hospital from April 2022 to August 2022. Clinical data including demographics, biochemical indicators and medical history were collected. Brachial-ankle pulse wave velocity (baPWV) was detected during the clinical visit. Participants were divided into the control group (baPWV≤1 800 cm/s) and vascular sclerosis group (baPWV>1 800 cm/s). The risk factors of arterial stiffness were analyzed by univariate and logistic regression analysis, and the nomogram model was constructed by R programming language. The predictive effect of the nomogram model was evaluated by the receiver operating characteristic curve (ROC). Results: The median age of the 525 participants was 87.0 (82.0, 92.0) years, 504 (96.0%) were male, 82 in the control group, 443 in the vascular sclerosis group. The baPWV, age, systolic blood pressure, mean arterial pressure and diastolic blood pressure were significantly lower in the control group than those in the vascular sclerosis group (all P<0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol, alanine aminotransferase and amylase were protective factors, and alkaline phosphatase and creatinine were risk factors of arterial stiffening (all P<0.05). The combined nomogram model scores including age, mean arterial pressure and the above five laboratory indicators indicated that mean arterial pressure and serum creatinine levels were strongly correlated with vascular sclerosis. The ROC curve suggested that the nomogram model had good prediction ability. Conclusions: Age, mean arterial pressure, high-density lipoprotein cholesterol, alanine aminotransferase, alkaline phosphatase, amylase and creatinine are independently determinants for increased vascular stiffness. The combined prediction model in this study can provide reference for individualized clinical risk prediction of vascular sclerosis in the octogenarian elderly.

[Comparison of risk factors for hemorrhagic stroke and ischemic stroke, a prospective long-term follow-up cohort study].

Objective: To analyze and compare the risk factors for hemorrhagic stroke and ischemic stroke and understand the exposure levels in population. Methods: A cohort study of risk factors of stroke was conducted in a rural community in Fengxian District of Shanghai in 2003, and the common risk factors of stroke were investigated at baseline survey, the cerebrovascular hemodynamics indexes were detected, the cerebrovascular function score was calculated according to the unified integral rule, and the incidence of stroke was observed in follow up. The risk factors for hemorrhagic stroke and ischemic stroke were analyzed by cohort study. The risk factors for two subtypes of stroke were compared. Result: A total of 10 565 participants were included in the study, with a mean follow-up period of (11.15±2.26) years, and 103 hemorrhagic stroke cases and 268 ischemic stroke cases were observed during follow-up period. The independent risk factors of hemorrhagic stroke included decreased cerebrovascular function score [hazard ratio (HR)=1.56, 95%CI: 1.23-1.98], history of alcohol consumption (HR=2.46, 95%CI: 1.39-4.34), hypertension (HR=1.75, 95%CI: 1.00-3.07) and older age (HR=1.07, 95%CI: 1.04-1.10). The independent risk factors of ischemic stroke included decreased cerebrovascular function score (HR=1.43, 95%CI: 1.25-1.65), smoking history (HR=1.52, 95%CI: 1.13-2.05), hypertension (HR=1.51, 95%CI: 1.10-2.07), family history of stroke (HR=1.89, 95%CI: 1.13-3.15), left ventricular hypertrophy (HR=1.74, 95%CI: 1.07-2.81) and older age (HR=1.07, 95%CI: 1.05-1.08). Conclusions: Decreased cerebrovascular function score, hypertension, and older age were common independent risk factors of both types of stroke, alcohol consumption history was an independent risk factor of hemorrhagic stroke, and smoking history, and family history of stroke and left ventricular hypertrophy were independent risk factors of ischemic stroke.

[Efficacy and safety of transcatheter aortic valve replacement in the treatment of severe aortic stenosis].

Objective: To investigate the efficacy and safety of transcatheter aortic valve replacement (TAVR) in the treatment of severe aortic stenosis. Methods: The clinical data of patients with severe aortic stenosis who underwent TAVR at the People's Hospital of Xinjiang Uygur Autonomous Region between September 2016 and September 2022 were retrospectively analyzed. Changes in aortic transvalvular pressure gradients, valve orifice area, and activity tolerance of patients before and after the surgery were compared. Moreover, postoperative complications and follow-up results from 30 days to 6 years after the surgery were recorded. Results: A total of 76 patients were included in the study (50 males and 26 females), with an average age of (71.3±7.6) years, including 16 rheumatic valvular diseases, 60 senile degenerative diseases, 46 bicuspid valves and 30 tricuspid valves. The success rate of the operation was 96.1% (73/76). Compared with that before the operation, the mean aortic transvalvular pressure gradients decreased [(8.5±2.8) mmHg vs (68.5±19.2) mmHg (1 mmHg=0.133 kPa),P<0.001], but the valve orifice area increased [(1.91±0.31) cm2 vs (0.65±0.21) cm2, P<0.001]. Likewise, six-minute walking test (6MWT) showed that walking distance was longer after the surgery [(430±13) m vs (201±28) m, P<0.001]. There were 1 case of retroperitoneal hematoma, 1 case of stricture balloon dilatation after femoral artery suture concomitant with postoperative puncture site infection, 1 case of femoral artery surgical incision, 2 cases of valve-in-valve (ViV) and 5 cases of perivalvular leakage (4 cases were mild and 1 case was moderate) after the surgery, respectively. Moreover, acute left main artery occlusion during operation occurred in 1 case, ventricular rupture during operation occurred in 1 case and the patient was transferred to valve replacement surgery and finally dead, delayed coronary artery occlusion and death happened in 1 case, and all of the above-mentioned 3 cases were due to surgical failure. Postoperative pacemaker implantation due to third-degree atrioventricular block was performed in 5 cases. There were 1 case of pulmonary embolism, 1 case of transient right limb disorder, 1 case of gastrointestinal bleeding and 1 case of urethral bleeding after the surgery, respectively. The patients were followed up for (1.0±0.1) years (30 days to 6 years), and the results showed that 2 cases died, including 1 case died suddenly at home (the cause of death was unknown) and 1 case died of acute heart failure 8 months after the surgery. Chronic heart failure occurred repeatedly in 6 cases. The quality of life of other patients improved significantly. Conclusion: TAVR is effective and safe for patients with severe aortic stenosis.

[Research progress of mouse model of hepatitis B virus infection].

Hepatitis B virus (HBV) infection is a global health problem. Animal models are important for the study of the HBV infection mechanism. In the study related to the mouse model of HBV infection, the researchers have established a variety of mouse models, including transgenic, plasmid hydrodynamic injection, virus vector transfection, cccDNA cycle simulation, human and mouse liver chimerism, and liver/immune dual humanization, according to the characteristics of HBV infection. Herein, the research progress of these models is summarized. Notably, the application of these models can further clarify the mechanism of HBV infection under the conditions of a specific immune response in vivo and lay the foundation for the development of new antiviral drugs and immunotherapy for HBV infection.

[Analyze of the correlation and corresponding value of serum C-peptide and insulin in adult population].

Objective: To investigate the correlation between serum C-peptide and in adult population, and establish the corresponding insulin values of serum C-peptide levels. Methods: Cross-sectional study. The clinical data of the adults who underwent physical examination in the Second Medical Center of PLA General Hospital from January 2017 to December 2021 were retrospectively included. The participants were divided into type 2 diabetes group, prediabetes group and normal plasma glucose group according to the diagnostic criteria for diabetes. The correlation between serum C-peptide and insulin was explored by Pearson correlation analysis, linear regression analysis, and nonlinear regression analysis, and the corresponding insulin values of serum C-peptide were established. Results: A total of 48 008 adults were enrolled, including 31 633 males (65.9%) and 16 375 females (34.1%), aged (50.1±9.9) years (18-89 years). There were 8 160 subjects (17.0%) with type 2 diabetes, 13 263 subjects (27.6%) with prediabetes, and 26 585 subjects (55.4%) with normal plasma glucose. The serum fasting C-peptide (FCP, M(Q1, Q3)] of the three groups were 2.76(2.18, 3.47), 2.54(1.99, 3.21) and 2.18(1.71, 2.79)µg/L, respectively. The fasting insulin [FINS, M(Q1,Q3)] of the three groups were 10.98(7.57, 16.09), 10.06(6.95, 14.47) and 8.43(5.86,12.12)mU/L, respectively. FCP was positively correlated with FINS (r=0.82), and 2 h postprandial C-peptide (2 h CP) was positively correlated with 2 h postprandial insulin (2 h INS) (r=0.84) (both P<0.001). FCP was linearly associated with FINS (R2=0.68), and 2 h CP was linearly associated with 2 h INS (R2=0.71) (both P<0.001). There was a power function correlation between FCP and FINS (R2=0.74), and 2 h CP and 2 h INS (R2=0.78) (both P<0.001). The results of the statistical analysis were similar in various glucose metabolism subgroups. Since the fitting degree of the power function model was higher than that of the linear model, the power function model was the best model. The power function equation was FINS=2.96×FCP1.32, and 2 h INS=1.64×(2 h CP)1.60, respectively. Multivariate linear regression analysis demonstrated that FCP was a related factor of FINS (R2=0.70, P<0.001) and 2 h CP was a related factor of 2 h INS (R2=0.73, P<0.001), after adjusting for related confounders. Conclusions: There was a power function correlation between FCP and FINS, 2 h CP and 2 h INS in adult population. The insulin values corresponding to C-peptide levels were established in the study.

[Relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status].

Objective: To investigate the relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status. Methods: The demographic data and biochemical indicators of the adult population who had received physical examination in the Second Medical Center of the PLA General Hospital from January 2018 to December 2021 were collected. The subjects were divided into two groups according to the level of serum uric acid: the normal uric acid group and the hyperuricemia group. The relationship between hemoglobin (stratified into four levels of Q1 to Q4 by the quartile) and serum uric acid was quantified by using Pearson correlation and logistic regression analysis. The effects of age and glucose metabolism status on the relationship between hemoglobin and serum uric acid were analyzed. Results: A total of 33 183 adults were enrolled with age (50.6±10.0) years. The level of hemoglobin in the normal uric acid group (142.61±14.24) g/L was significantly lower than that in the hyperuricemia group [(151.79±11.24) g/L, P<0.001]. Univariate Pearson correlation analysis showed that hemoglobin was positively associated with serum uric acid (r=0.444, P<0.001). After adjusting for related confounding factors, multivariate logistic regression analysis showed that hemoglobin was associated with serum uric acid, and the OR values (95%CI) of hemoglobin Q2 to Q4 group were 1.29 (1.13-1.48), 1.42 (1.24-1.62) and 1.51 (1.32-1.72), respectively (Ptrend<0.001) when compared with hemoglobin Q1 group. Subgroup analysis and hierarchical interaction analysis suggested that with the increase of hemoglobin, the serum uric acid in the age<60 years subgroup, normal glucose subgroup and prediabetes subgroup increased gradually (Ptrend<0.05 and Pinteraction<0.001). Conclusion: The association between hemoglobin and serum uric acid in adults is affected by age and glucose metabolism status.

Spatiotemporal characteristics of ozone and the formation sensitivity over the Fenwei Plain.

High surface ozone (O3) levels affect human and environmental health. The Fenwei Plain (FWP), one of the critical regions for China's "Blue Sky Protection Campaign", has reported severe O3 pollution. This study investigates the spatiotemporal properties and the causes of O3 pollution over the FWP using high-resolution data from the TROPOspheric Monitoring Instrument (TROPOMI) from 2019 to 2021. This study characterizes spatial and temporal variations in O3 concentration by linking O3 columns and surface monitoring using a trained deep forest machine learning model. O3 concentrations in summer were 2-3 times higher than those found in winter due to higher temperatures and greater solar irradiation. The spatial distributions of O3 correlate with the solar radiation showing decreased trends from the northeastern to the southwestern FWP, with the highest O3 values in Shanxi Province and the lowest in Shaanxi Province. For urban areas, croplands and grasslands, the O3 photochemistry in summer is NOx-limited or in the transitional regime, while it is VOC-limited in winter and other seasons. Reducing NOx emissions would be effective for decreasing O3 levels in summer, while VOC reductions are necessary for winter. The annual cycle in vegetated areas included both NOx-limited and transitional regimes, indicating the importance of NOx controls to protect ecosystems. The O3 response to limiting precursors shown here is of importance for optimizing control strategies and is illustrated by emission changes during the 2020 COVID-19 outbreak.

[Three-dimensional analysis of maxillary dentition during molar distalization with clear aligners under different movement designs: an in vitro experiment].

Objective: To investigate the three-dimensional force in the maxillary dentition under different movement designs for molar distalization with clear aligners Methods: Three groups were designed: simultaneous movement group (simultaneous distalization of maxillary first and second molars), second molar movement group (distalization of maxillary second molars) and first molar movement group (distalization of maxillary first molars). Ten clear aligners were made in each group, and the displacement was designed to be 0.2 mm. A force sensing device was established to measure the three-dimensional force on the upper dentition with the clear aligner. The device contained a model of the maxillary dentition consisting of 14 teeth, each tooth connected to an individual sensor. After the clear aligner was fitted, the data of 14 sensors were collected and analyzed using computer analysis software. The moving teeth were taken as the target teeth, and the rest of the teeth were anchorage. The data of the three-dimensional force in the three groups in each tooth position were measured and compared. Results: The sagittal forces on the first and second molars in the simultaneous movement group were (5.61±0.94) and (5.81±1.08) N, respectively, which were significantly smaller than those of the target teeth in the same position in other groups (P<0.05). The second molars in the first molar movement group received a sagittal reaction force, which was (-6.73±1.99) N. The anterior teeth in the three groups were all subjected to sagittal reaction force, and the force value was in a range of (-3.33 to 0.46) N. In the coronal direction, the second premolars of the simultaneous movement group received the reaction force in the palatal direction, and the force value was (-2.17±1.06) N. The first molars in the second molar movement group were also subjected to palatal reaction force of (-1.99±0.70) N. The second molars and second premolars in the first molar movement group were also subjected to palatal reaction force, which were (-2.85±0.57) and (-1.85±0.74) N, respectively. Compared with the sagittal and coronal forces, the target teeth and anchorage teeth in the three groups were less stressed in the vertical direction. Conclusions: The first and second molars distalized simultaneously, the correction force in the sagittal direction was relatively small. When first molar was moved distally alone, a greater reaction force in the sagittal direction was exerted on the second molar. Buccal displacement of the adjacent anchorage teeth should be designed to counteract the palatal reaction force on the anchorage teeth as the molars moved distally.

Favorable outcome in advanced pheochromocytoma and paraganglioma after hypofractionated intensity modulated radiotherapy.

PURPOSE: The purpose of this study was to review outcomes of patients with advanced/metastatic pheochromocytoma/paraganglioma (PPGL) treated at our institution with Intensity-modulated radiotherapy (IMRT), describe the treatment outcomes, and determine predictors. METHODS: A retrospective study on patients with advanced/metastatic PPGL who received IMRT at Peking Union Medical College Hospital between 2014 and 2019. A total of 14 patients with 17 lesions were included in this study. Ultra-hypofractionated radiation therapy was used for 7 lesions in 5 patients, while hypofractionated radiation therapy was used for 8 lesions in 7 patients. 2 patients got conventional fractionated radiotherapy. Patients who received external beam radiation therapy were given a median total radiation dose of 74.4/130 Gy (BED10/3) in a median of 13 fractions. RESULTS: OS at 2 years was 78% for all patients. For lesions evaluated by RECIST response, at least stable disease of the target lesion was achieved in 94% and distant progression in 28.5%, with an average time to progression of 5.2 months. Patients with locally advanced primary tumors or recurred in situ (n = 8) achieved 100% local control, and none of them got recurrence or distant metastasis after radiotherapy at last follow-up (median 29 months). Of patients with catecholamine-related syndromes (n = 12), 91% of symptomatic lesions improved following radiation therapy and a more than 50% decline in catecholamines. CONCLUSIONS: We have found hypofractionated IMRT effective as an additional therapy for patients with advanced primary tumors or recurrence in situ and not amenable to complete surgical resection.

Impact of COVID-19 on acute ischemic stroke presentation and prognosis in a county-level stroke center.

OBJECTIVE: The COVID-19 pandemic has influenced regular medical procedures and health-seeking behaviors. In this study, we aimed to investigate the influence of the COVID-19 pandemic on the presentation and prognosis of acute ischemic stroke (AIS) patients in county-level stroke centers. PATIENTS AND METHODS: We retrospectively collected AIS patients during the strict lockdown period (January 24, 2020, to March 27, 2020) and the corresponding "new normal" period (2021) of the COVID-19 pandemic. Patients seen during the same timeframe in 2019 were enrolled as controls. Statistical analysis was conducted to compare the clinical characteristics of AIS patients who presented during the lockdown and new normal periods and those who presented during the pre-COVID-19 pandemic period. RESULTS: A total of 134 AIS patients presented during the lockdown period (the 2020 group), 207 patients in the pre-COVID-19 period (the 2019 group) and 201 patients in the "new normal" period (the 2021 group). Compared to the 2019 group, there was approximately 1/3 reduction in the number of patients who presented during the lockdown period, while the number of patients who received IVT or EVT was similar between the two groups. The number of patients, baseline characteristics, workflow intervals and clinical outcomes presented during the "new normal" period were similar between the 2019 and 2021 groups. Logistic regression showed that lockdown or new normal status were not risk factors associated with a poor outcome at 90 days. CONCLUSIONS: In county-level city stroke centers, the COVID-19 lockdown resulted in a reduction in the number of patients with AIS admitted to the hospital but had no effect on patients treated with IVT or EVT. Lockdown or new normal status did not influence the prognosis of AIS patients.

Matrix Matters: Assessment of Commutability among BK Virus Assays and Standards.

Quantitative testing of BK virus (BKPyV) nucleic acid has become the standard of care in transplant patients. While the relationship between interassay harmonization and commutability has been well characterized for other transplant-related viruses, it has been less well studied for BKPyV, particularly regarding differences in commutability between matrices. Here, interassay agreement was evaluated among six real-time nucleic acid amplification tests (NAATs) and one digital PCR (dPCR) BKPyV assay. Differences in the commutability of three quantitative standards was examined across all assays using a variety of statistical approaches. Panels, including 40 samples each of plasma and urine samples previously positive for BKPyV, together with one previously negative plasma sample and four previously negative urine samples, were tested using all assays, with each real-time NAAT utilizing its usual quantitative calibrators. Serial dilutions of WHO, National Institute for Standards and Technology (NIST), and commercially produced (Exact/Bio-Rad) reference materials were also run by each assay as unknowns. The agreement of the clinical sample values was assessed as a group and in a pairwise manner. The commutability was estimated using both relativistic and quantitative means. The quantitative agreement across assays in the urine samples was within a single log10 unit across all assays, while the results from the plasma samples varied by 2 to 3 log10 IU/mL. The commutability showed a similar disparity between the matrices. Recalibration using international standards diminished the resulting discrepancies in some but not all cases. Differences in the sample matrix can affect the commutability and interassay agreement of quantitative BKPyV assays. Differences in commutability between matrices may largely be due to factors other than those such as amplicon size, previously described as important in the case of cytomegalovirus. Continued efforts to standardize viral load measurements must address multiple sources of variability and account for differences in assay systems, quantitative standards, and sample matrices.

Quasi-isentropic compression of LiH above 400 GPa using magnetocumulative generator.

The knowledge of high-pressure behavior of LiH is significant for the validation of fundamental theoretical models and applications in thermonuclear materials and potential energy supplies. The compressibility of 7LiH under isentropic compression at high pressure was investigated experimentally and theoretically. The experimental technique for quasi-isentropic compression with low-density materials was developed using the magnetocumulative generator CJ-100 and x-ray flash radiography. The x-ray images and extracted interface of the sample target in dynamic flash radiography experiments were obtained. According to each interface size of the target both before and after compression, the compression ratio of 7LiH and reference material aluminum was obtained. The density of the reference and using its known isentropic curve provide the pressure in the reference. The pressure in 7LiH was deduced from the pressure in the reference and using the calculated gradient correction factor. The quasi-isentropic data point at 438 GPa was obtained experimentally. A semiempirical three-term complete equation of state was constructed and validated for 7LiH using the theory of Mie-Grüneisen-Debye with experimental data from the literature. The quasi-isentrope data point is reasonably consistent with the theoretical results. The quasi-isentropic experimental techniques and results broaden the existing research scope and are practical and helpful to further validate theoretical models in the future.

[Extranuclear p53 suppresses autophagy through AMPK/mTOR signaling to promote heat stress-induced vascular endothelial cell damage].

OBJECTIVE: To explore the role of extranuclear p53-mediated autophagy suppression by regulating AMPK/mTOR signaling pathway in heat stress (HS)-induced injury of mouse aortic endothelial cells (MAECs). METHODS: Primary cultures of MAECs were pretreated with compound C (an AMPK inhibitor), rapamycin (a mTOR inhibitor) or pifithrin-α (PFT, a selective p53 inhibitor) for 1 h before exposure to HS (43 ℃) for 2 h. The changes in cell viability at different time points after HS were examined using CCK-8 assay, and the protein expressions of P53, LC3-II, Beclin-1, p62 and the AMPK/mTOR signaling proteins were detected using Western blotting. In the animal experiment, C57 mice were pretreated with compound C, rapamycin or PFT and exposed to a high temperature at 40 ℃ to induce HS. The pathological changes in the aorta of the mice were observed with HE staining, and cell apoptosis was detected using TUNEL staining. RESULTS: In cultured MAECs, the cell viability was significantly reduced (P < 0.05) and the mitochondrial fraction of p53 increased while its cytoplasmic fraction decreased progressively over time following HS. HS significantly lowered the expressions of LC3-II and Beclin-1, increased p62 level, suppressed AMPK phosphorylation, and increased mTOR phosphorylation and the expressions of its downstream proteins at 6 h after the exposure (P < 0.05). Pretreatment with compound C significantly inhibited LC3-II and Beclin- 1 expression, enhanced p62 expression, and aggravated HS-induced cell injury and apoptosis in MAECs; rapamycin treatment produced the opposite effects (P < 0.05). PFT treatment significantly enhanced the viability of MAECs and alleviated HSinduced injury and apoptosis; PFT also significantly promoted activation of AMPK phosphorylation, inhibited mTOR phosphorylation and its downstream proteins (P < 0.05), enhanced the expressions of LC3-II and Beclin 1, and inhibited p62 expression in the MAECs (P < 0.05). In C57 mice, HS resulted in swelling, shedding and apoptosis of aortic vascular endothelial cells. Pretreatment with compound C obviously aggravated HS-induced vascular injury and endothelial cell apoptosis, while pretreatment with either rapamycin or PFT significantly alleviated these injuries. CONCLUSION: Autophagy inhibition mediated by extranuclear p53 via inhibiting AMPK activity and activating mTOR signaling participates in HS-induced injury of MAECs.

[Analysis of Dimethyltryptamine in Captured Suspicious Substances：Three Case Reports].

ABSTRACT: Abstract.