The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.

The Wnt signaling pathway includes both classical and non classical pathways,Wnt5a-Frizzled-2 pathway participates in the Wnt/Ca2+signaling pathway in the non-classical pathway,which is activated by the Wnt-related protein Wnt5a and its ligand Frizzled-2.It can regulate some key sites in cells to affect cell signal transduction,and is closely related to cell growth process.Activation of Wnt5a-Fizzled-2 pathway occurs in some tissues with abundant blood supply,such as heart and brain tissues,during ischemia-reperfusion.Activation of the Wnt5a-Frizzled-2 pathway causes these intracellular calcium overload,ultimately promoting apoptosis.This article reviews the abnormal activation of Wnt5a-Frizzled-2 signaling pathway in ischemia-reperfusion injury diseases and the induced calcium overload leading to apoptosis,in order to provide reference for the study of physiological mechanisms of ischemia-reperfusion injury.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective To evaluate the correlation between 3D morphological parameters of aneurysms based on the computer-assisted semi-automated measurement and the risk of aneurysm rupture.Methods From October 2019 to October 2022,patients with ruptured multiple aneurysms admitted to the Department of Neurosurgery of Xuanwu Hospital,Capital Medical University were retrospectively included.Aneurysmal morphological parameters(including aneurysmal diameter,maximum diameter,width,neck width,volume,flow angle,parental artery diameter,surface area,wave index and non-spherical index)were measured by computer-assisted semi-automated measurement methods.The length-to-width ratio,wide-to-neck ratio,aspect ratio and size ratio were calculated,and the aneurysm location information was recorded.The ruptured aneurysms in multiple aneurysms were included in the ruptured group,and the remaining aneurysms were included in the unruptured group.Uni variable analysis and binary Logistic analysis were used to evaluate the differences in morphological parameters and location information between the ruptured and unruptured groups.Results All 56 patients with multiple ruptured aneurysms and a total of 126aneurysms were included in the group for analysis.Concerning morphology,including diameter＞5 mm(51.8％[29/56]vs.15.7％[11/70],P＜0.01),maximum diameter＞6mm(57.1％[32/56]vs.25.7％[18/70],P＜0.01),flow angle＞107°(57.1％[32/56]vs.35.7％[25/70],P=0.016),wide-to-neck ratio＞1.1(50.0％[28/56]vs.30.0％[21/70],P=0.022),aspect ratio＞1.1(46.4％[26/56]vs.25.7％[18/70],P=0.015)and size ratio＞1.9(57.1％[32/56]vs.10.0％[7/70],P＜0.01),there was significant difference between the ruptured and unruptured group;Concerning locations,aneurysms are mainly located in the posterior communicating segment of the internal carotid artery(39.3％[22/56])and the middle cerebral artery(23.2％[13/56])in ruptured group,while in the middle cerebral artery(28.6％[20/70])and the non-posterior communicating segment of internal carotid artery(27.1％[19/70])in unruptured group,and there was significant difference in distribution of aneurysm locations(P=0.003).Multivariate Logistic regression analysis showed that size ratio＞1.9 was an independent risk factor for aneurysm rupture(OR,11.62,95％CI 2.40-56.15;P=0.002).Concerning locations,posterior communicating artery aneurysms had a significantly higher risk of rupture compared with the non-posterior communicating segment of internal carotid artery(OR,19.25,95％CI 2.19-169.51;P=0.008).Conclusion For multiple intracranial aneurysms,the size ratio of the three-dimensional morphological parameters of aneurysms＞1.9 is an independent risk factor for aneurysm rupture,and the rupture risk of posterior communicating artery aneurysms is significantly higher than that of non-posterior communicating segment of internal carotid artery.

Objective To create a semi-automatic technology based on convolutional neural networks for saccular aneurysm segmentation.Methods The single-center data of Xuanwu Hospital of Capital Medical University in the database of"China Intracranial Aneurysm Program"from July 2017 to July 2020 were retrospectively included,and all data were anonymized before analysis.Baseline data were collected from all patients,including sex,age(≥60 years and＜60 years),DSA model,number of DSA sequences,and aneurysm information,including the number of aneurysms,diameter(≥5 mm and＜5 mm),neck width(wide neck,narrow neck),and location(bifurcation,sidewall).According to the ratio of 8∶1∶1,the data were randomly divided into training set,test set and validation set by random number table method.The DSA 3D tomography data of all patients were completed in the contrast machine using the 3D rotary DSA mode,and the aneurysms shown in the DSA 3D tomography data were annotated by 3 experienced neurosurgeons,and the standard label of the aneurysm was finally generated.The proposed aneurysm segmentation method consisted of a training stage and a segmentation stage.In the training stage,the model was trained end-to-end by using the DSA 3D tomography image data of the training set,the segmentation label of the aneurysm and the vascular edge information extracted by the Marching Cubes algorithm,and the segmentation index of the model was monitored on the test set to retain the model with the highest segmentation index.In the segmentation stage,the physician selects a point inside the aneurysm on the DSA 3D tomography image of the aneurysm in the validation set,intercepts the volume of interest(VOI),inputs the trained optimal model of vascular and aneurysm segmentation,obtains the segmentation result of the aneurysm,and locates the segmented VOI back to the original DSA 3D tomography image to obtain the final aneurysm outline.The segmentation results of the segmentation network model were compared with standard labels to calculate the Dice similarity coefficient(DSC).The validation set data was stratified by aneurysm diameter,neck width,and location to compare the segmentation results in different datasets.We calculated the bounding boxes for the length,width,and height of the aneurysm segmentation mask,and used the maximum of these as the longest diameter of the aneurysm compared to the maximum diameter in the standard label.In the validation set,the standard label manual acquisition time was counted and compared with the segmentation network model acquisition time(from the time of locating the aneurysm to obtaining a satisfactory aneurysm neck segmentation).Results Finally,969 DSA sequences from 756 patients were included to show 3D tomographic data for 1 094 aneurysms.Among them,604 patients with 877 aneurysms with a total of 783 DSA sequences were included in the training set,117 aneurysms with a total of 100 DSA sequences in 77 patients were included in the test set,and 100 aneurysms with a total of 86 DSA sequences were included in 75 patients in the validation set.(1)The baseline comparison results of each dataset showed that there were statistically significant differences between the datasets of aneurysm diameter(P=0.003)and aneurysm location(P=0.003).There was no significant difference between the remaining baseline data sets(all P＞0.05).(2)The mean DSC of centralized aneurysm segmentation was 0.868±0.078.The mean DSC of aneurysm segmentation≥5 mm diameter was higher than that of aneurysms with＜5 mm diameter(0.891±0.041 vs.0.855±0.088,P=0.038).The DSC values of narrow-necked,wide-necked,bifurcated and lateral wall aneurysms were 0.882±0.065,0.859±0.085,0.876±0.072 and 0.863±0.080,respectively,and there was no significant difference between the groups(all P＞0.05).(3)The maximum diameter of the mask obtained by the aneurysm segmentation model in the validation set was in good agreement with the maximum diameter of the standard label obtained by manual segmentation([5.78±3.18]mm vs.[5.37±2.92]mm,r=0.97).In the validation set,the average time of manual segmentation and neural network segmentation of aneurysms was 2.5 min and 34 s,respectively.Conclusion In this study,a semi-automatic saccular aneurysm segmentation technique based on convolutional neural network can accurately segment aneurysms and is helpful to improve aneurysm morphology analysis.

Purpose: This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices. Materials and Methods: Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. Results: Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. Conclusion TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. About a quarter of the world's population were infected with Mycobacterium tuberculosis in 2020, and the majority of them were latently infected. Approximately 5%-10% of the population with latent tuberculosis infection may progress to active TB disease. Identifying latent TB infection from active TB by biomarkers and screening people with latent TB infection at high risk of progression for preventive treatment by biomarkers that can reliably predict the progression is one of the most effective strategies to control TB. This article reviews the progress of research on transcriptional and immunological biomarkers for identifying TB infection and predicting the progression from latent infection to active TB, with the aim of providing new ideas for tuberculosis control.
Humans ; Latent Tuberculosis/diagnosis* ; Tuberculosis/diagnosis* ; Mycobacterium tuberculosis/genetics* ; Biomarkers