A signature based on neutrophil extracellular trap-related genes for the assessment of prognosis, immunoinfiltration, mutation and therapeutic response in hepatocellular carcinoma.

BACKGROUND: Liver cancer is a highly lethal and aggressive form of cancer that poses a significant threat to patient survival. Within this category, liver hepatocellular carcinoma (LIHC) represents the most common subtype of liver cancer. Despite decades of research and treatment, the overall survival rate for LIHC has not significantly improved. Improved models are necessary to differentiate high-risk cases and predict possible treatment options for LIHC patients. Recent studies have identified a set of genes associated with neutrophil extracellular traps (NETs) that may contribute to tumor growth and metastasis; however, their prognostic value in LIHC has yet to be established. This study aims to construct a prognostic signature based on a set of NET-related genes (NRGs) for patients diagnosed with LIHC. METHODS: The transcriptomic data and clinical information concerning LIHC patients were procured from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium LIHC (ICLIHC) databases, respectively. To determine the NRG subtypes, the k-means algorithm was employed, along with consensus clustering. The aforementioned analysis aided the construction of a prognostic signature utilizing the last absolute shrinkage and selection operator Cox analysis. To validate the prognostic model, an external dataset, receiver operating characteristic curve, and principal component analysis were utilized. Moreover, the immune microenvironment and the proportion of immune cells between high- and low-risk cases were scrutinized by ESTIMATE and CIBERSORT algorithms. Finally, gene set enrichment analysis was executed to investigate the potential mechanism of NRGs in the pathogenesis and prognosis of LIHC. RESULTS: Two molecular subtypes of LIHC were identified based on the expression patterns of differentially expressed NRGs (DE-NRGs). The two subtypes demonstrated significant differences in survival rates and immune cell expression levels. The study results demonstrated the role of NRGs in antigen presentation, which led to the promotion of tumor immune escape. A risk model was developed and validated with strong overall survival prediction ability. The model, comprising 34 NRGs, showed a strong ability to predict prognosis. CONCLUSION: We built a dependable prognostic signature based on NRGs for LIHC. We identified that NRGs could have a significant interaction in LIHC's immune microenvironment and therapeutic response. This finding offers insight into the molecular mechanisms and targeted therapy for LIHC.

The pharmacokinetics and safety of lidocaine in liver cancer patients undergoing hepatic resection.

PURPOSE: The purpose of this study was to explore the pharmacokinetics (PK) characteristics and safety of continuous lidocaine infusion during hepatectomy in liver cancer patients. METHODS: This study included thirty-five patients undergoing laparoscopic hepatectomy from January 2021 to December 2021. Patients received a short infusion of 1% lidocaine at a dose of 1.5 mg/kg based on ideal body weight, followed by a continuous infusion of 1 mg/kg/h during the operation. The plasma concentrations of lidocaine and its active metabolites were measured using validated ultra-performance liquid chromatography-tandem mass spectrometry. Safety was evaluated by monitoring and recording all adverse events (AEs). RESULTS: The concentrations of lidocaine were within the safe range, except one patient's concentration of lidocaine which reached the toxic range (> 5 µg/mL). The mean half-life (T1/2), the mean time to maximum observed concentration (Tmax), and the mean maximum observed concentration (Cmax) of lidocaine were 3.96 h, 2.85 h, and 2030 ng/mL, respectively; the mean T1/2, Tmax, and Cmax (n = 32) of MEGX were 6.59 h, 5.05 h, and 333.28 ng/mL, respectively; and the mean T1/2, Tmax, and Cmax of GX (n = 18) were 25.98 h, 7.33 h, and 75.81 ng/mL. Although eight subjects with AEs were reported, there were no serious AEs or deaths. No patients had serious postoperative complications. No deaths occurred within 30 days after the operation. CONCLUSIONS: Under the administration regimen of this study, intravenous infusion of lidocaine is safe and tolerable for liver cancer patients with laparoscopic hepatectomy. Fine safety and PK characteristics support the application of lidocaine in such patients and further clinical research. TRIAL REGISTRATION: China Clinical Trial Registration Center (ChiCTR2100042730), Registered 27 January 2021.

Association of novel rare coding variants with juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common type of arthritis among children, but a few studies have investigated the contribution of rare variants to JIA. In this study, we aimed to identify rare coding variants associated with JIA for the genome-wide landscape. METHODS: We established a rare variant calling and filtering pipeline and performed rare coding variant and gene-based association analyses on three RNA-seq datasets composed of 228 JIA patients in the Gene Expression Omnibus against different sets of controls, and further conducted replication in our whole-exome sequencing (WES) data of 56 JIA patients. Then we conducted differential gene expression analysis and assessed the impact of recurrent functional coding variants on gene expression and signalling pathway. RESULTS: By the RNA-seq data, we identified variants in two genes reported in literature as JIA causal variants, as well as additional 63 recurrent rare coding variants seen only in JIA patients. Among the 44 recurrent rare variants found in polyarticular patients, 10 were replicated by our WES of patients with the same JIA subtype. Several genes with recurrent functional rare coding variants have also common variants associated with autoimmune diseases. We observed immune pathways enriched for the genes with rare coding variants and differentially expressed genes. CONCLUSION: This study elucidated a novel landscape of recurrent rare coding variants in JIA patients and uncovered significant associations with JIA at the gene pathway level. The convergence of common variants and rare variants for autoimmune diseases is also highlighted in this study.

A preliminary evaluation study of applying a deep learning image reconstruction algorithm in low-kilovolt scanning of upper abdomen.

OBJECTIVE: To investigate feasibility of applying deep learning image reconstruction (DLIR) algorithm in a low-kilovolt enhanced scan of the upper abdomen. METHODS: A total of 64 patients (BMI<28) are selected for the enhanced upper abdomen scan and divided evenly into two groups. The tube voltages in Group A are 100kV in arterial phase and 80kV in venous phase, while tube voltages are 120kV during two phases in Group B. Image reconstruction algorithms used in Group A include the filtered back projection (FBP) algorithm, the adaptive statistical iterative reconstruction-Veo (ASIR-V 40% and 80%) algorithm, and the DLIR algorithm (DL-L, DL-M, DL-H). Image reconstruction algorithm used in Group B is ASIR-V40%. The different reconstruction algorithm images are used to measure the common hepatic artery, liver, renal cortex, erector spinae, and subcutaneous adipose in the arterial phase and the average CT value and standard deviation of the portal vein, liver, spleen, erector spinae, and subcutaneous adipose in the portal phase. The signal-to-noise ratio (SNR) is calculated, and the images are also scored subjectively. RESULTS: In Group A, noise in the aorta, liver, portal vein (the portal phase), spleen (the portal phase), renal cortex, retroperitoneal adipose, and muscle is significantly lower in both the DL-H and ASIR-V80% images, and the SNR is significantly higher than those in the remaining groups (P<0.05). The SNR of each tissue and organ in Group B is not significantly different from that in DL-M, DL-L, and ASIR-V40% in Group A (P>0.05). The subjective image quality scores in the DL-H and B groups are higher than those in the other groups, and the FBP group has significantly lower image quality than the remaining groups (P<0.05). CONCLUSION: For upper abdominal low-kilovolt enhanced scan data, the DLIR-H gear yields a more satisfactory image quality than the FBP and ASIR-V.

Xylanosomes produced by Cellulosimicrobium cellulans F16 were diverse in size, but resembled in subunit composition.

The hemicellulolytic enzyme system produced by Cellulosimicrobium cellulans strain F16 was resolved by ultracentrifugation and size exclusion chromatography. The particle size and molecular weight were determined by both dynamic light scattering and negative stain electron microscopy. The results showed that xylanosomes produced by strain F16 were found to have an apparent sedimentation coefficient of 28 S, were diverse in size (18-70 nm), molecular weight (11-78 MDa) and morphology, but resembled in subunit composition (SDS-PAGE and proteomic results). It is proposed that particles of 22 nm may be the basic unit, while 43 nm and 60 nm particles observed may be dimer and trimer of the basic unit, or xylanosomes with smaller size might be degradation products of larger size xylanosomes. Moreover, such xylanosomes are also found to have strong binding affinity toward water-insoluble substrates such as Avicel, birchwood xylan, and corn cob.

Detection of nitroaromatics in aqueous media based on luminescence resonance energy transfer using upconversion nanoparticles as energy donors.

Upconversion nanoparticle (UCNP)-based luminescence resonance energy transfer (LRET) systems are a powerful tool widely used to detect organic molecules or metal ions because of their simplicity and high sensitivity. The sandwich structure NaYF4:Er3+,Yb3+@NaYF4@NH2 UCNPs, as a highly selective and sensitive aqueous probe for detecting nitroaromatics, has been designed and prepared by a cothermolysis method and modified with polyetherimide to acquire amine groups on the surface of the core/shell UCNPs. The detection principle of nitroaromatics is based on LRET, which forms the Meisnheimer complex between the electron-deficient cyclobenzene of nitroaromatics and the electron-rich amino group on the surface of the sandwich structure UCNPs. As a consequence, nitroaromatics can be brought into close proximity to the sandwich structure UCNPs. With the increase of nitroaromatics (2,4,6-trinitrophenol and 2,4,6-trinitrotoluene) concentrations, the sandwich structure NaYF4:Er3+,Yb3+@NaYF4@NH2 UCNPs display a dramatic luminescent quenching effect at 407 nm and 540 nm under 980 nm excitation. The luminescent quenching intensity of the sandwich structure UCNPs is linearly correlated to the concentration of the nitroaromatics. The detection limit of 2,4,6-trinitrophenol (TNP) and 2,4,6-trinitrotoluene (TNT) are 0.78 and 0.77 ng ml-1, respectively. Therefore, the sandwich structure of NaYF4:Er3+,Yb3+@NaYF4@NH2 UCNPs can act as a valuable probe to detect nitroaromatics in public safety and security conditions.

Effects of Different Carbon Sources on Enzyme Production and Ultrastructure of Cellulosimicrobium cellulans.

The secretomes of the strain Cellulosimicrobium cellulans F16 grown on different carbon sources were analyzed by zymography, and the subcellular surface structures were extensively studied by electron microscope. The exo-cellulase and xylanase systems were sparse when cells were grown on soluble oligosaccharides, but were significantly increased when grown on complex and water-insoluble polysaccharides, such as Avicel, corn cob, and birchwood xylan. The cellulosome-like protuberant structures were clearly observed on the cell surfaces of strain F16 grown on cellulose, with diameters of 15-20 nm. Fibrous structures that connected the adjacent cells can be seen under microscope. Moreover, protuberances that adsorbed the cell to cellulose were also observed. As the adhesion of Cellulosimicrobium cellulans cells onto cellulose surfaces occurs via thick bacterial curdlan-type exopolysaccharides (EPS), such surface layer is potentially important in the digestion of insoluble substrates such as cellulose or hemicellulose, and the previously reported xylanosomes are part of such complex glycocalyx layer on the surface of the bacterial cell.

Antifungal activity change of Streptomyces rimosus MY02 mediated by confront culture with other microorganism.

Streptomyces rimosus can produce antibacterial and antifungal antibiotics, which have important applications in medicine and agriculture. Seventy-nine microbial strains were employed to assay interaction between S. rimosus MY02 and different fungi, actinomyces, and bacteria when confront cultured on solid media. The results showed that the presence of a microorganism might affect the activity of another one. When S. rimosus MY02 confront cultured with other microorganisms, the inductive effect might be positive or negative. In this study, fungi showed to be effective elicitors, with a highest inductivity rate of 90.1%, and all of fungi showed positive induction behavior. Followed by bacteria with 59.6% of the tested bacterial strains showing positive inductivity, and the highest inductivity was 54.9%. Only six actinomyces (counting for 40% of the tested actinomyces strains) showed positive inductivity, and the highest induction rate of the strain NK413 was 34.1%. We also found that growth of most of bacteria or actinomyces which showed negative inductivity were similar or better than that of the strain MY02. However, the growth status of the strains was not positive related to inducing ability directly.

Relationship between molecular weight, monosaccharide composition and immunobiologic activity of Astragalus polysaccharides.

Four Astragalus polysaccharides (APS1-APS4) were isolated from the water extract of Radix Astragali and purified through ethanol precipitation with 20 %, 40 %, 60 % and 80 % ethanol, respectively. The total sugar content was measured by sulfuric acid-phenol method. Their molecular weight was determined using high performance gel permeation chromatography (HPGPC) and their monosaccharide composition was analyzed by reversed-phase high performance liquid chromatography (HPLC) after pre-column derivatization. Then the immunobiologic activity of APS was evaluated by the experiment of spleen lymphocytes proliferation in vitro. The data suggested that precipitation by different concentration of ethanol will obtain different molecular weight APS, the higher concentration of ethanol the smaller molecular weight for APS. The molecular weights of four APS were 257.7 kDa, 40.1 kDa, 15.3 kDa and 3.2 kDa. Monosaccharide composition analysis indicated that APS1 consisted of glucose only, and APS2 all consisted of arabinose. APS3 consisted of rhamnose, glucose, galactose and arabinose and APS4 consisted of galactose and arabinose, in a molar ratio of 1:10.76:6.55:12 and 3.02:1. The result of immunobiologic activity assay showed that both APS2 and APS3 can effectively stimulate normal spleen lymphocyte proliferation in vitro. Apart from this, the effect of APS2 also showed dose dependent tendency from 6.25 µg/mL to 800 µg/mL. The result of this research indicated that Astragalus polysaccharides, which consist of arabinose and their molecular weight between 15.2 kDa to 40.1 kDa, neither too high nor too low, had significant immune activity.

[Qualitative Determination of Organic Vapour Using Violet and Visible Spectrum].

Vapours of organic matters were determined qualitatively employed with ultraviolet-visible absorption spectroscopy. Vapours of organic matters were detected using ultraviolet-visible spectrophotometer employing polyethylene film as medium, the ultraviolet and visible absorption spectra of vegetable oil vapours of soybean oil, sunflower seed oil, peanut oil, rapeseed oil, sesame oil, cotton seed oil, tung tree seed oil, and organic compound vapours of acetone, ethyl acetate, 95% ethanol, glacial acetic acid were obtained. Experimental results showed that spectra of the vegetable oil vapour and the organic compound vapour could be obtained commendably, since ultra violet and visible spectrum of polyethylene film could be deducted by spectrograph zero setting. Different kinds of vegetable oils could been distinguished commendably in the spectra since the λ(max), λ(min), number of absorption peak, position, inflection point in the ultra violet and visible spectra obtained from the vapours of the vegetable oils were all inconsistent, and the vapours of organic compounds were also determined perfectly. The method had a good reproducibility, the ultraviolet and visible absorption spectra of the vapours of sunflower seed oil in 10 times determination were absolutely the same. The experimental result indicated that polyethylene film as a kind of medium could be used for qualitative analysis of ultraviolet and visible absorption spectroscopy. The method for determination of the vapours of the vegetable oils and organic compounds had the peculiarities of fast speed analysis, well reproducibility, accuracy and reliability and low cost, and so on. Ultraviolet and visible absorption spectrum of organic vapour could provide feature information of material vapour and structural information of organic compound, and provide a novel test method for identifying vapour of compound and organic matter.

Neural network L1 adaptive control of MIMO systems with nonlinear uncertainty.

An indirect adaptive controller is developed for a class of multiple-input multiple-output (MIMO) nonlinear systems with unknown uncertainties. This control system is comprised of an L 1 adaptive controller and an auxiliary neural network (NN) compensation controller. The L 1 adaptive controller has guaranteed transient response in addition to stable tracking. In this architecture, a low-pass filter is adopted to guarantee fast adaptive rate without generating high-frequency oscillations in control signals. The auxiliary compensation controller is designed to approximate the unknown nonlinear functions by MIMO RBF neural networks to suppress the influence of uncertainties. NN weights are tuned on-line with no prior training and the project operator ensures the weights bounded. The global stability of the closed-system is derived based on the Lyapunov function. Numerical simulations of an MIMO system coupled with nonlinear uncertainties are used to illustrate the practical potential of our theoretical results.

Recent Advances in Vitamin D3 Intervention to Eradicate Helicobacter pylori Infection.

Helicobacter pylori (HP) infections affect approximately one-third of children worldwide. In China, the incidence of HP infection in children ranges from approximately 30% to 60%. In addition to damaging the gastrointestinal tract mucosa, HP infection in children can negatively affect their growth and development, hematology, respiratory and hepatobiliary system, skin, nutritional metabolism, and autoimmune system. However, the rate of HP eradication also fell considerably from the previous rate due to the presence of drug-resistant HP strains and the limited types of antibiotics that can be used in young patients. Vitamin D3 (VitD3) is a steroid hormone that can reduce inflammation in the stomach mucosa induced by HP and can alleviate and eradicate HP through a variety of pathways and mechanisms, including immune regulation and the stimulation of antimicrobial peptide (AMP) secretion and Ca2+ influx, to reestablish lysosomal acidification; thus, these results provide new strategies and ideas for the eradication of drug-resistant HP strains.

Adaptive Dosage Strategy of Levetiracetam in Chinese Epileptic Patients: Focus on Pregnant Women.

There is presently no efficient dose individualization strategy for the use of antiseizure medications in epileptic pregnant patients. This study aimed to develop a population pharmacokinetics model for levetiracetam and propose a tailored adaptive individualized dosage strategy for epileptic pregnant patients. A total of 322 levetiracetam plasma concentrations from 238 patients with epilepsy were included, including 216 women with epilepsy (20.83% of whom were pregnant). The levetiracetam plasma concentration was measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were modeled using a nonlinear mixed-effects model. The resultant model served as the basis for simulating the dosage adjustment strategy. A one-compartment model with first-order elimination best described the pharmacokinetic data of levetiracetam. The apparent clearance (CL/F) was 3.43 L/h (95% CI 3.30-3.56) and the apparent volume of distribution was 43.7 L (95% CI 40.4-47.0) for a typical individual of 57.2 kg. Pregnancy and body weight were found to be significant covariates of CL/F of levetiracetam. The recommended regimen of levetiracetam could be predicted by the population pharmacokinetic model based on body weight, gestational age, and the daily dose of levetiracetam taken before pregnancy.

Image quality assessment and feasibility of three-dimensional amide proton transfer-weighted imaging for hepatocellular carcinoma.

Background: With the continuous innovation of magnetic resonance imaging (MRI) hardware and software technology, amide proton transfer-weighted (APTw) imaging has been applied in liver cancer. However, to our knowledge, no study has evaluated the feasibility of a three-dimensional amide proton transfer-weighted (3D-APTw) imaging sequence for hepatocellular carcinoma (HCC). This study thus aimed to conduct an image quality assessment of 3D-APTw for HCC and to explore its feasibility. Methods: 3D-APTw MRI examinations were completed in 134 patients with clinically suspected HCC. According to the uniformity of APTw signal in the liver and within the lesion and the proportion of artifact and missing signal regions, APTw images were subjectively scored using a 5-point scale. The scanning success rate of liver APTw imaging was calculated as the ratio of the number of cases with a quality assurance measurement of more than 3 to the total number of HCC cases. The intra- and interobserver quality assurance measurements for APTw images were compared via the Kappa consistency test. Within the HCC cases with a minimum image quality threshold of 3 points, the APT values of HCC and the liver parenchyma, signal-to-noise ratio of APT-weighted images (SNRAPTw), and contrast-to-noise ratio of HCC (CNRHCC) were measured by two observers. The intra- and interobserver agreement was assessed using the intraclass correlation coefficient (ICC). The differences in APT values between HCC and liver parenchyma was determined using the Mann-Whitney test. Results: Sixty-six HCC cases with a quality assurance measurement of APTw imaging were included in the final analysis, and the calculated success rate was 70.21% (66/94). The subjective APT image quality scores of the two observers were consistent (3.66±1.18, 3.50±1.19, and 3.68±1.18), and no intergroup or intragroup statistical differences were found (P=0.594, and P=0.091), but the consistency of inter- and intraobserver was not as satisfactory (κ=0.594 and κ=0.580). The APT values in HCC lesion were significantly higher than those in liver parenchyma (2.73%±0.91% vs. 1.62%±0.55%; P<0.001). The APT values in HCC showed favorable intra- and interobserver consistency between the two observers (ICC =0.808 and ICC =0.853); the APT values in liver parenchyma, SNRAPTw, and CNRHCC values had moderate intraobserver consistency (ICC =0.578, ICC =0.568, and ICC =0.508) and interobserver consistency (ICC =0.599, ICC =0.199, and ICC =0.650). The coefficients of variation of the APTw values in the HCC lesion and in liver parenchyma were 33.4% and 34.4%, respectively. The SNRAPTw and CNRHCC were 30.75±18.74 and 3.56±3.19, with a coefficient of variation of 60.9% and 74.9%, respectively. Conclusions: Liver 3D-APTw imaging was preliminarily demonstrated to be clinically feasible for evaluating HCC.

Quantification of meropenem in serum and cerebrospinal fluid in children with bacterial meningitis with augmented renal clearance by UPLC-MS/MS.

Meropenem is an ultrabroad-spectrum antimicrobial agent that is often recommended for the treatment of bacterial meningitis (BM) in children. However, a subtherapeutic phenomenon occurred in BM children complicated with augmented renal clearance (ARC) at the recommended dose of meropenem. To support its pharmacokinetics, a sensitive, fast and robust ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to measure meropenem concentrations in serum and cerebrospinal fluid (CSF). The method involved protein precipitation, and samples were diluted with a large proportion of water to eliminate solvent effects. The separation of samples was performed on a Waters Acquity™ BEH C18 column (2.1 × 50 mm i.d., 1.7 µm) with a gradient profile. The mobile phases were formic acid-water (1:1000, v/v) and acetonitrile. The linear range was good, with a concentration range of 0.100-100 µg/mL for serum and 0.0400-20.0 µg/mL for CSF. The intra-day and inter-day precisions were less than 8.0%, and the intra-day and inter-day accuracies varied -6.6% from 6.5% for the both serum and CSF. The selectivity, carry-over, dilution integrity, matrix effect, recovery and stability were validated according to international guidelines. The developed UPLC-MS/MS method successfully determined the meropenem concentrations in the serum and CSF of children with BM complicated with ARC. The results indicated that under the recommended dosing regimen (40 mg/kg every 8 h), the time to reach the effective treatment target of 50%T > MIC was only approximately 3 h and lower CSF concentrations of meropenem were observed in children with BM with ARC.

JUNO high purity nitrogen plant.

The Jiangmen Underground Neutrino Observatory (JUNO) is a 20 kt low level radioactivity liquid scintillator detector in a laboratory 650 m underground. An excellent energy resolution and a large volume offer exciting opportunities for addressing many important topics in neutrino physics. High purity nitrogen is an important factor to ensure the low background of the JUNO detector. High Purity Nitrogen (HPN) is used for detector purging, pipe cleaning, and scintillator purification, among other things in JUNO. According to JUNO's requirements, the radon concentration in HPN should be less than 10 µBq/m3. To meet this requirement, A high-purity nitrogen plant with 100 Nm3/h maximum rate was designed and constructed. Low-temperature adsorption technology is used to remove radioactive impurities in nitrogen. High purification efficiency was ensured by using an activated carbon column with high column height-to-diameter ratio. Electrostatic collection and low-temperature enrichment methods are combined to measure radon in nitrogen. After ten days of continuous operation at 50 Nm3/h flux rate, the plant can to reduce the radon concentration in nitrogen from 37.4±1.8µBq/m3 to less than 1.33 µBq/m3. After HPN with flow rate of 50 Nm3/h passing through low-background pipeline (About 1.3 km), the radon concentration of HPN is 5.6±0.6µBq/m3.

Comparison of intravenous ibuprofen pharmacokinetics between Caucasian and Chinese populations using physiologically based pharmacokinetics modeling and simulation.

BACKGROUND: Intravenous ibuprofen, a nonsteroidal anti-inflammatory drug, is widely used as an antipyretic and analgesic in adults and children. This study was designed to evaluate ethnic differences by comparing the pharmacokinetics of intravenous ibuprofen in Caucasian and Chinese populations using physiologically based pharmacokinetics (PBPK) modeling and simulation. METHODS: A PBPK model for intravenous ibuprofen was developed in adults and children utilizing the Simcyp Simulator. The model was tested and verified against published literature and unpublished data obtained from the Caucasian adult population, Caucasian pediatric population and Chinese adult population. RESULTS: The developed PBPK model could adequately pilot the pharmacokinetics of intravenous ibuprofen, and the major observed values were within the 90% prediction interval in both adults and children. Both folding errors of the maximum peak concentration (Cmax) and area under the concentration-time curve (AUC) were 1.5-fold less in the Caucasian and Chinese populations. In addition, no significant differences in weight-normalized Cmax and AUC were observed between the Caucasian and Chinese adult populations. Moreover, there were no obvious pharmacokinetic differences between the Caucasian and Chinese pediatric populations with intravenous infusion (10 minutes) of 10 mg/kg by age group. CONCLUSION: This study indicates that the pharmacokinetic profile and the parameters of intravenous ibuprofen are analogous in Caucasian and Chinese populations, either adults or children. In addition, this study provides effective evidence that the dosing scheme of intravenous ibuprofen in Chinese children can remain the same as the regimen that the original company (Caldolor®) provided.

Computed tomography features of gastric leiomyoma versus gastric stromal tumor: a case-control study with propensity score matching.

OBJECTIVE: To differentiate gastric leiomyomas (GLs) and gastric stromal tumors (GSTs) based on preoperative enhanced computed tomography characteristics. METHODS: Twenty-six pathologically confirmed GLs were propensity score-matched to 26 GSTs in a 1:1 ratio based on sex, age, tumor site, and tumor size. Tumor shape and contour, mucosal ulceration, growth pattern, enhancement pattern and degree, longest diameter, and longest diameter/vertical diameter ratio were compared between the groups. Hemorrhage, calcification, peripheral invasion, and distant metastasis were also included in the regression analysis for differentiation of the two tumors. RESULTS: Mucosal ulceration was significantly more frequent in GSTs than GLs. The enhancement degree of GSTs was significantly higher than that of GLs in the arterial and portal venous phases. Using enhancement degrees of 18 HU and 23 HU in the arterial phase and venous phase as cutoff values, respectively, we found that an enhancement degree of <18 HU in the arterial phase was an independent influential factor for diagnosis of GLs. No significant differences were found in other morphological characteristics. GLs did not metastasize or invade adjacent tissues. CONCLUSION: A low enhancement degree in GLs is the most valuable quantitative feature for differentiating these two similar tumors.

Insulin use and gout risk among patients with type 2 diabetes mellitus: a real-world cohort study in Shanghai, China.

OBJECTIVES: The effect of insulin use on gout risk remains unknown. This study aimed to investigate the association between insulin use and gout risk among patients with type 2 diabetes mellitus (T2DM). METHODS: Based on the Shanghai Link Healthcare Database, patients with newly diagnosed T2DM, with or without insulin exposure, were identified from January 1, 2014 to December 31, 2020, and followed until December 31, 2021. Apart from the original cohort, we also established a 1:2 propensity score-matched cohort. A time-dependent Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for gout incidence associated with insulin exposure. RESULTS: A total of 414,258 patients with T2DM, including 142,505 insulin users and 271,753 insulin non-users, were enrolled in this study. After a median follow-up of 4.08 years (interquartile range, 2.46-5.90 years), the incidence of gout was significantly higher in insulin users than in insulin non-users (319.35 versus 302.20 cases per 100,000 person-years; HR 1.09, 95% CI 1.03-1.16). The results were robust in propensity score-matched cohort, sensitivity analyses, and stratified analysis of aspirin. In other stratified analyses, the association between insulin use and increased gout risk was found only in patients who were female, or aged 40-69 years, or without hypertension, dyslipidemia, ischemic heart disease, chronic lung disease, kidney disease, or not using diuretic. CONCLUSIONS: Insulin use is associated with a significantly increased risk of gout among patients with T2DM. Key Points • The first real-world study to investigate the effect of insulin use on gout risk. • Insulin use is associated with a significantly increased risk of gout among patients with type 2 diabetes mellitus.

Developing a prediction model for all-cause mortality risk among patients with type 2 diabetes mellitus in Shanghai, China.

BACKGROUND: All-cause mortality risk prediction models for patients with type 2 diabetes mellitus (T2DM) in mainland China have not been established. This study aimed to fill this gap. METHODS: Based on the Shanghai Link Healthcare Database, patients diagnosed with T2DM and aged 40-99 years were identified between January 1, 2013 and December 31, 2016 and followed until December 31, 2021. All the patients were randomly allocated into training and validation sets at a 2:1 ratio. Cox proportional hazards models were used to develop the all-cause mortality risk prediction model. The model performance was evaluated by discrimination (Harrell C-index) and calibration (calibration plots). RESULTS: A total of 399 784 patients with T2DM were eventually enrolled, with 68 318 deaths over a median follow-up of 6.93 years. The final prediction model included age, sex, heart failure, cerebrovascular disease, moderate or severe kidney disease, moderate or severe liver disease, cancer, insulin use, glycosylated hemoglobin, and high-density lipoprotein cholesterol. The model showed good discrimination and calibration in the validation sets: the mean C-index value was 0.8113 (range 0.8110-0.8115) and the predicted risks closely matched the observed risks in the calibration plots. CONCLUSIONS: This study constructed the first 5-year all-cause mortality risk prediction model for patients with T2DM in south China, with good predictive performance.