Evaluation of Kidney Injury Using Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI: An Experimental Study in Rats With Carbon Tetrachloride-Induced Liver Cirrhosis.

BACKGROUND: Serum creatinine (Scr) may be not suited to timely and accurately reflect kidney injury related to chronic liver disease. Currently, the ability of arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) sequences to evaluate renal blood flow (RBF) and blood oxygen in chronic liver disease remains to be verified. PURPOSE: To investigate the value of ASL and BOLD imaging in evaluating hemodynamics and oxygenation changes during kidney injury in an animal model of chronic liver disease. STUDY TYPE: Prospective. ANIMAL MODEL: Chronic liver disease model was established by subcutaneous injection of carbon tetrachloride. Forty-three male Sprague-Dawley rats (8 weeks) were divided into a pathological group (0, 2, 4, 6, 8, 12 weeks, each group: N = 6) and a continuous-scanning group (N = 7). FIELD STRENGTH/SEQUENCE: 3-T, ASL, BOLD, and T2W. ASSESSMENT: Regions of interest in the cortex (CO), outer stripe of the outer medulla (OSOM), and inner stripe of the outer medulla (ISOM) are manually delineated. The RBF and T2* values at each time point (0, 2, 4, 6, 8, 12 weeks) are measured and compared. Hematoxylin-eosin score (HE Score, damage area scoring method), alpha-smooth muscle actin (α-SMA), hypoxia-inducible factor-1alpha (HIF-1α), peritubular capillar (PTC) density, Scr, and neutrophil gelatinase-associated lipocalin were harvested. STATISTICAL TESTS: Analysis of variance, Spearman correlation analysis, Kruskal-Wallis tests, and receiver operating characteristic analysis with the area under the curve (AUC). A P-value <0.05 was considered statistically significant. RESULTS: Renal RBF and T2* values of CO, OSOM, and ISOM were significantly different from baseline. Both RBF and T2* were significantly correlated with HE Score, α-SMA, HIF-1α, and PTC density (|r| = 0.406-0.853). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in this model of chronic liver disease (AUC = 0.964). DATA CONCLUSION: Imaging by ASL and BOLD may detect renal hemodynamics and oxygenation changes related to chronic liver disease early. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

[Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice].

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-ß1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-ß1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-ß1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

Circulating chemerin levels in preeclampsia: a systematic review and meta-analysis.

BACKGROUND: Preeclampsia (PE) is a new-onset pregnancy-specific disorder with a high prevalence that leads to over 70 000 maternal and 500 000 foetal fatalities worldwide each year. The level of chemerin, a newly identified adipokine, is increased in diabetic and obese patients. Currently, there are several studies describing the relationship between maternal circulating chemerin levels and PE. Therefore, this study aimed to assess their association in pooled samples. METHODS: Four databases were systematically searched to identify potential studies that reported circulating chemerin levels in PE and normal pregnancy groups. Standardized mean differences (SMDs), 95% confidence intervals (CIs), and 95% prediction intervals (PIs) were calculated using a random-effects meta-analysis. The probability of heterogeneity was also investigated by sensitivity analysis, subgroup analysis, and meta-regression. RESULTS: Thirteen studies in 11 articles with a total of 860 PE patients and 1309 women with normal pregnancies met the inclusion criteria. The results of the meta-analysis revealed that circulating chemerin, which levels in PE patients were considerably higher than those in controls (SMD = 1.39, 95% CI: 1.02, 1.77, 95% PI: -0.07, 2.86). Moreover, sensitivity analysis determined that the outcomes of the overall pooled results were not affected after the elimination of any study. Notably, subgroup analysis demonstrated a similar expression pattern irrespective of geographic location, severity, timing of sampling, and sample size. Last, there were no factors that significantly impacted the overall estimate, according to meta-regression. CONCLUSIONS: This meta-analysis is the first to assess circulating chemerin levels in PE patients. The findings indicate that circulating chemerin levels may be a potential marker to diagnose PE.

Added value of CE-CT radiomics to predict high Ki-67 expression in hepatocellular carcinoma.

BACKGROUND: This study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features. METHODS: A total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: HCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04-6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87-79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08-9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39-144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683-0.926] vs. 0.678 [95% CI: 0.536-0.839], P = 0.211; and 0.805 [95% CI: 0.657-0.953] vs. 0.667 [95% CI: 0.495-0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849-0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively). CONCLUSIONS: Preoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value.

Effect of Nasal Irrigation in Children With Omicron Variant of COVID-19 Infection.

Objective: To explore the effect of nasal irrigation on the disappearance of symptoms and nucleic acid conversion in children with Omicron variant. Methods: This quasi-experimental study included children diagnosed with asymptomatic, mild, and moderate Omicron variant infection during the isolation observation period in the Shandong Public Health Clinical Center between April 1, 2022 and May 1, 2022. The children were divided into a routine group (received Lianhua Qingwen (LhQw) Granules), isotonic saline group (received LhQw Granules combined with isotonic saline nasal irrigation), and hypertonic saline group (received LhQw Granules combined with 3% hypertonic saline nasal irrigation), respectively. The primary outcomes were the time of symptom disappearance and nucleic acid conversion time. The secondary outcomes were peripheral white blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), and C-reactive protein (CRP) levels. Results: A total of 60 children (7.26 ± 3.15 years old) were included (20 per group). The average time of nucleic acid conversion in the 2 saline nasal irrigation groups was significantly reduced compared with the routine group (all P < 0.001), while the fever time and cough duration among the 3 groups were comparable (all P > 0.05). LYM count in the 2 saline nasal irrigation groups was significantly increased after treatment compared to before treatment and was significantly higher than in the routine group (all P < 0.05). There was no significant difference in LYM count between the isotonic and hypertonic saline groups (P = 0.76). Additionally, all children in the saline group well tolerated the treatment, and no adverse events occurred in the isotonic saline group. Conclusions: Timely use of saline nasal irrigation may promote nucleic acid conversion in children with Omicron virus infection.

Radiomics nomogram for the prediction of microvascular invasion of HCC and patients' benefit from postoperative adjuvant TACE: a multi-center study.

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.

Epimedium sagittatum Maxim ameliorates adriamycin-induced nephropathy by restraining inflammation and apoptosis via the PI3K/AKT signaling pathway.

BACKGROUND: Modern pharmacological studies show that Epimedium sagittatum Maxim (EPI) has antioxidant, antiapoptotic, anti-inflammatory effects. However, the effects of EPI on adriamycin-induced nephropathy are unclear. AIM: The main purpose of this study is to investigate the effects of EPI on adriamycin-induced nephropathy in rats. METHODS: The chemical composition of EPI was detected by high performance liquid chromatography. Network pharmacology was used to collect the effects of EPI on adriamycin nephropathy; renal histological changes, podocyte injury, inflammatory factors, oxidative stress levels, apoptosis levels, and the PI3K/AKT signaling pathway were examined. Moreover, analyze the effects of icariin (the representative component of EPI) on adriamycin-induced apoptosis and PI3K/AKT signaling pathway of NRK-52e cells. RESULTS: Network pharmacological results suggested that EPI may ameliorate adriamycin-induced nephropathy by inhibiting inflammatory response and regulating the PI3K/AKT signaling pathway. The experimental results showed that EPI could improve pathological injury, renal function, podocyte injury, and inhibit inflammation, oxidative stress, apoptosis in adriamycin-induced nephropathy rats through the PI3K/AKT signaling pathway. Furthermore, icariin inhibited adriamycin-induced mitochondrial apoptosis in NRK-52e cells. CONCLUSION: This study suggested that EPI ameliorates adriamycin-induced nephropathy by reducing inflammation and apoptosis through the PI3K/AKT signaling pathway, icariin may be the pharmacodynamic substance basis for this effect.

[Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism]. / ç¯ç›èŠ±ç´ å¯¹å®«å† ç‚Žç—‡è‡´æ—©äº§å¤§é¼ è„‘æŸä¼¤çš„ä¿æŠ¤ä½œç”¨åŠå ¶æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism. METHODS: A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats. RESULTS: Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1ß, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1ß, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05). CONCLUSIONS: Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Recommendation of mHAP and ABCR scoring systems for the decision-making of the first and subsequent TACE session in HCC patients.

BACKGROUND: Due to the high heterogeneity among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE), the prognosis of patients varies significantly. Various predictive scoring systems have been developed to identify the patients who could benefit from TACE. However, there is no consensus on which is better. This study aims to validate and compare the predictive capabilities of scoring systems for first and subsequent TACE. MATERIALS: A total of 524 HCC patients were treated with TACE, and 222 patients who met the inclusion criteria were included. Log-rank test was used to verify the predictive value of six scoring systems for the first TACE and four TACE retreatment scoring systems. Harrell's concordance (C)-index, likelihood ratio and integrated Brier score (IBS) were used to compare the predictive performance. RESULTS: For the scoring systems of TACE, the overall survival (OS) of candidates screened by Hepatoma Arterial-embolization Prognostic (HAP), modified HAP (mHAP), mHAP3, alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response (ABCR), albumin-bilirubin grade (ALBI), tumor size, alpha-fetoprotein, first TACE response and pre-/post-TACE was significantly longer than that of the noncandidates (all P < 0.05), whereas the mHAP2 and assessment for retreatment with TACE did not distinguish the candidates from noncandidates (P = 0.206, 0.115, respectively). The predictive and calibration performances of mHAP and ABCR were the highest for the first TACE and TACE retreatment, respectively. CONCLUSION: mHAP identifies the patients who could benefit from the first TACE, whereas ABCR distinguishes patients who could benefit from subsequent TACE sessions.

Diagnostic markers of metabolic bone disease of prematurity in preterm infants.

Due to the higher birth rate of preterm infants and improvements in their management, metabolic bone disease of prematurity (MBDP) has a high incidence and is attracting attention. However, clear indicators for the early diagnosis of MBDP are lacking. We aimed to explore simple and feasible early warning indicators for diagnosing MBDP. Our study collected case data of premature infants from two medical centers in Chongqing from January 2020 to February 2022. According to the inclusion and exclusion criteria, data from 136 cases were collected. The correlation between 14 variables in each case and the occurrence of MBDP was analyzed. According to area under the receiver operating characteristic curve (AUROC) analysis, the best cutoff value for each variable was determined. Potential predictors were selected, and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to establish the association of two models with MBDP, whose results were used to develop a diagnostic nomogram. Furthermore, a model decision curve was analyzed. Four predictors were selected from 14 clinical variables by LASSO regression, and Model I was established, including the following characteristics: height (>36 cm), head circumference (≤29.49 cm), total serum calcium (Ca) (>2.13 mmol/L), and alkaline phosphatase (ALP) (>344 U/L) levels. A single predictor, the ALP level (>344 U/L), was used to establish Model II. The AUROC values of the two models were 0.959 for Model I and 0.929 for Model II. In conclusion, in this study, two diagnostic models of MBDP were developed using four combinations of predictors and ALP as a single predictor. Both models showed good sensitivity and specificity for the early diagnosis of metabolic bone disease (MBD), and an ALP level of 344 U/L was defined as a simple and effective diagnostic threshold. In future studies, using larger samples, diagnostic threshold values of ALP for premature infants of different ages should be established, and internal and external validations are needed to improve the adaptability of the current model.

Minor iridoid glycosides from the fruits of Cornus officinalis Sieb. et Zucc. and their anti-diabetic bioactivities.

Fifteen previously undescribed minor iridoid glycosides, including four monomers and eleven dimers, were isolated from the fruits of Cornus officinalis Sieb. et Zucc. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. All of the isolated compounds were evaluated for their effects of the glucose consumption on the insulin resistant HepG2 cells, and four compounds, named cornuofficinalisides F, H, L, and O, increased the glucose consumption significantly at 10 µM, the EC50 values of them were determined to be 0.898, 1.625, 0.923, and 8.589 µM, respectively. Moreover, the four compounds could improve the ability of glucose uptake significantly in insulin resistant HepG2 cells.

Multi-parametric magnetic resonance imaging of liver regeneration in a standardized partial hepatectomy rat model.

BACKGROUND: We aimed to evaluate the correlation between the pathological changes and multi-parameter MRI characteristics of liver regeneration (LR) in a standard partial hepatectomy (PH) rat model. METHODS: Seventy Sprague-Dawley rats were randomly divided into two groups: MR scan group (n = 14) and pathologic analysis (PA) group (n = 56). All 14 rats in the MR group underwent liver T1 mapping, T2 mapping, and diffusion kurtosis imaging before and the 1st, 2nd, 3rd, 5th, 7th, 14th, and 21st day after 70% hepatectomy. Seven rats in the PA group were euthanized at each time point to determine Ki-67 indices, hepatocyte size (HTS), steatosis grade, and inflammation score. RESULTS: Liver T1 and T2 values increased to maximum on day 2 (P < 0.001 vs. baseline), D and K values decreased to minimum on day 3 and 2, respectively (P < 0.001 vs. baseline), then all parameters returned to baseline gradually. Hepatocyte Ki-67, hepatocyte size, steatosis grade, and inflammation score initially increased after surgery (P < 0.05 vs. baseline), followed by a gradual decline over time. Both T2 and K values correlated well with Ki-67 indices (r = 0.765 and - 0.807, respectively; both P < 0.001), inflammation (r = 0.809 and - 0.724, respectively; both P < 0.001), steatosis grade (r = 0.814 and - 0.725, respectively; both P < 0.001), and HTS (r = 0.830 and - 0.615, respectively; both P < 0.001). CONCLUSIONS: PH induced liver changes that can be observed on MRI. The MRI parameters correlate with the LR activity and allow monitoring of LR process.

pcnaDeep: a fast and robust single-cell tracking method using deep-learning mediated cell cycle profiling.

SUMMARY: Computational methods that track single cells and quantify fluorescent biosensors in time-lapse microscopy images have revolutionized our approach in studying the molecular control of cellular decisions. One barrier that limits the adoption of single-cell analysis in biomedical research is the lack of efficient methods to robustly track single cells over cell division events. Here, we developed an application that automatically tracks and assigns mother-daughter relationships of single cells. By incorporating cell cycle information from a well-established fluorescent cell cycle reporter, we associate mitosis relationships enabling high fidelity long-term single-cell tracking. This was achieved by integrating a deep-learning-based fluorescent proliferative cell nuclear antigen signal instance segmentation module with a cell tracking and cell cycle resolving pipeline. The application offers a user-friendly interface and extensible APIs for customized cell cycle analysis and manual correction for various imaging configurations. AVAILABILITY AND IMPLEMENTATION: pcnaDeep is an open-source Python application under the Apache 2.0 licence. The source code, documentation and tutorials are available at https://github.com/chan-labsite/PCNAdeep. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Anti-Pulmonary Fibrosis Activities of Triterpenoids from Oenothera biennis.

Five new triterpenoids, oenotheralanosterols C-G (1-5), with seven known triterpenoidcompounds, namely 2α,3α,19α-trihydroxy-24-norurs4,12-dien-28-oic acid (6), 3ß,23-dihydroxy-1-oxo-olean-12-en-28-oic acid (7), remangilone C (8), knoxivalic acid A (9), termichebulolide (10), rosasecotriterpene A (11), androsanortriterpene C (12), were extracted and separated from the dichloromethane part of Oenothera biennis L. The anti-pulmonary fibrosis activities of all the compounds against TGF-ß1-induced damage tonormal human lung epithelial (BEAS-2B) cells were investigated in vitro. The results showed that compounds 1-2, 6, 8, and 11 exhibited significant anti-pulmonary fibrosis activities, with EC50 values ranging from 4.7 µM to 9.9 µM.

Epimesatines A-I, nine undescribed prenylated flavonoids with SPHK1 inhibitory activities from Epimedium sagittatum maxim.

Epimesatines A-I, nine undescribed prenylated flavonoids, along with ten known analogues, were isolated from the aerial parts of Epimedium sagittatum Maxim. The structures and absolute configurations of epimesatines A-I were determined using a combination of spectroscopic data, Rh2(OCOCF3)4-induced electronic circular dichroism (ECD) experiments, ECD comparisons, and X-ray crystallography analysis. Epimesatines A and I displayed notable activities on the viabilities of human non-small cell lung cancer (NSCLC) A549 cells with IC50 values of 1.77 and 9.97 µM, respectively. Furthermore, epimesatines A and I significantly inhibited the expression of sphingosine kinase 1 (SPHK1) in A549 cells. In addition, none of these compounds showed obvious toxicity on normal human lung bronchial epithelial BEAS-2B cells.

Series of Intravoxel Incoherent Motion and T2* Magnetic Resonance Imaging Mapping in Detection of Liver Perfusion Changes and Regeneration Among Partial Hepatectomy in Sprague-Dawley Rats.

RATIONALE AND OBJECTIVES: To evaluate liver perfusion changes and their effect on liver regeneration (LR) after partial hepatectomy (PH) using intravoxel incoherent motion (IVIM) and T2* mapping in a rat model. METHODS: One hundred and two rats underwent 30%, 50%, or 70% PH. Within each group (n = 34), rats in MR imaging subgroup (n = 10) underwent liver IVIM and T2* mapping before and within 2 h, 1, 2, 3, 5, 7, 14, and 21 days post-PH to measure D*, perfusion fraction (PF), and T2* values. Three rats from histologic subgroup (n = 24) sacrificed at each time point for hepatocyte Ki-67 indices and diameters measurement. RESULTS: Liver D* and PF values decreased immediately post-PH, then returned to original level as LR progressed in all groups. PF values in 70% PH group were significantly lower than in the other two groups (p < .05). D* and PF values correlated significantly with hepatocyte Ki-67 indices (r = -0.588 to -0.915; p < .05) and hepatocyte diameter (r = -0.555 to -0.792; p < .05). Liver T2* values decreased immediately within 2 h post-PH, then increased to a high level and followed with returning to original level gradually. The duration of the high T2* levels was consistent with Ki-67 indices. CONCLUSIONS: Liver perfusion decreased immediately followed with increasing gradually after PH. IVIM and T2* mapping are promising methods for monitoring changes of liver perfusion. IVIM-derived D* value is the best indicator in reflecting the process of LR noninvasively.

Preoperative determination of pathological grades of primary single HCC: development and validation of a scoring model.

PURPOSE: This study aimed to establish a reliable diagnostic score model for the preoperative determination of pathological grade in HCC based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI and biochemical indicators. METHODS: In this retrospective study, we analyzed 139 patients with HCC who underwent Gd-EOB-DTPA MRI between 2014 and 2020, including an establishment cohort of 76 patients and a validation cohort of 63 patients. Based on the imaging features demonstrated on Gd-EOB-DTPA MRI images and biochemical indicators of the establishment cohort, a scoring model based on logistic regression was developed, and compared with postoperative pathological findings in terms of effective determination of pathological grade. The validity of the scoring model was assessed by ROC curves and an independent external validation cohort. RESULTS: Three parameters related to pathological grades were identified, including maximum diameter of the tumor, peritumoral hypointensity in the hepatobiliary phase, and [alkaline phosphatase (U/L) + gamma glutamyl transpeptidase (U/L)]/ lymphocyte count (× 109/L) (AGLR) ratios. Based on these three parameters, a scoring model was developed. ROC curve showed that a score of > 5 was set as the threshold for determining pathological grades with accuracy, sensitivity, specificity, PPV, and NPV of 89.5%, 75.0%, 95.1%, 85.7%, and 90.7%, respectively. CONCLUSION: The study provided the groundwork for a promising and easily implementable scoring model for preoperative determination of HCC pathological grades, for which further validation should be pursued.

Efficacy of Bevacizumab Combined with Pemetrexed in the Treatment of Recurrent and Metastatic Cervical Cancer.

Background: To investigate the efficacy and safety of bevacizumab combined with pemetrexed in the treatment of recurrent and metastatic cervical cancer. Methods: Clinical data of 65 patients with recurrent and metastatic cervical cancer who were admitted to our hospital were collected for retrospective analysis. All patients were administered with bevacizumab combined with pemetrexed for 4-6 cycles (21 days as 1 cycle). The short-term clinical efficacy and adverse reactions were compared between the two groups. In addition, the survival status of patients was followed up and recorded. Results: At least 4 cycles of chemotherapy were given to the 65 patients. There were 0 cases of complete response (CR), 14 cases of partial response (PR), 36 cases of stable disease (SD) and 15 cases of progressive disease (PD). The objective response rate (ORR) and the disease control rate (DCR) were 21.5% (14/65) and 76.9% (50/65), respectively. DCR was superior in patients with squamous cell carcinoma to that in those with adenocarcinoma (p = 0.039), but no statistically significant difference was found in ORR. Patients with extra-pelvic metastatic lesions had a better efficacy than those with intra-pelvic metastatic lesions, but the difference was not statistically significant (p > 0.05). The post-treatment adverse reactions mainly involved fatigue, nausea and vomiting, bleeding, leukopenia, anemia, thrombocytopenia, transaminase elevation, hypertension, proteinuria and neurotoxicity, most of which were grade I-II that ameliorated after symptomatic therapy. Grade III adverse reactions mainly included pain in 5 cases (7.7%), leukopenia in 17 cases (26.2%), anemia in 22 cases (33.8%), thrombocytopenia in 6 cases (9.2%), hypertension in 5 cases (7.7%) and neurotoxicity in 7 cases (10.8%). The follow-up results manifested that median overall survival (OS) and median progression-free survival (PFS) were 10.6 months and 6.6 months, respectively. Conclusion: Bevacizumab combined with pemetrexed exhibits certain efficacy in the treatment of recurrent and metastatic cervical cancer, with tolerable adverse reactions. Therefore, this therapeutic option deserves clinical popularization and application.

Deep learning image reconstruction in pediatric abdominal and chest computed tomography: a comparison of image quality and radiation dose.

Background: Studies on the application of deep learning image reconstruction (DLIR) in pediatric computed tomography (CT) are limited and have so far been mostly based on phantom. The purpose of this study was to compare the image quality and radiation dose of DLIR with that of adaptive statistical iterative reconstruction-Veo (ASiR-V) during abdominal and chest CT for the pediatric population. Methods: A pediatric phantom was used for the pilot study, and 20 children were recruited for clinical verification. The preset scan parameter noise index (NI) was 5, 8, 11, 13, 15, and 18 for the phantom study, and 8 and 13 for the clinical pediatric study. We reconstructed CT images with ASiR-V 30%, ASiR-V 70%, DLIR-M (medium) and DLIR-H (high). The regions of interest (ROI) were marked on the organs of the abdomen (liver, kidney, and subcutaneous fat) and the chest (lung, mediastinum, and spine). The CT dose index volume (CTDIvol), CT value, image noise (N), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured and calculated. The subjective image quality was assessed by 3 radiologists blindly using a 5-point scale. The dose reduction efficiency of DLIR was estimated. Results: In the phantom study, the interobserver assessment of the data measurement demonstrated good agreement [intraclass correlation coefficient (ICC) =0.814 for abdomen, 0.801 for chest]. Within the same dose level, the N, SNR, and CNR were statistically different among reconstructions, while the CT value remained the same. The N increased and SNR decreased as the radiation dose decreased. The DLIR-H performed better than ASiR-V when the radiation dose was reduced, without sacrificing image quality. In the patient study, the interobserver assessment of the data measurement demonstrated good agreement (ICC =0.774 for abdomen, 0.751 for chest). DLIR-H had the highest subjective and objective scores in the abdomen. Conclusions: Application of DLIR could help to reduce radiation dose without sacrificing the image quality of pediatric CT scans. Further clinical validation is required.

IFI16 induces inflammation in hepatitis B virus-associated glomerulonephritis by regulating the Caspase-1/ IL-1 ß pathway.

AIMS AND BACKGROUND: IFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1ß. However, the role of IFI16 in regulating the immune response to viruses in Hepatitis B Virus-Associated Glomerulonephritis (HBV-GN), especially in sensing hepatitis B virus (HBV), has not been determined. In this study, we investigated the inflammatory role of IFI16 in HBV-GN. METHODS: A total 75 kidney tissue including 50 HBV-GN and 25 chronic glomerulonephritis (CCN) were collected to determine the expression of IFI16, Caspase-1 and IL-1ß using immunohistochemistry (IHC), then the correlation between them was analyzed. In vitro, the primary human glomerular mesangial (HGM) cells and HEK-293 T cell lines were used in this study. The cell lines were both co-transfected with HBVDNA and overexpression or silencing IFI16. Quantitative Real-time PCR and western blotting were used to determine the expression of IFI16, Caspase-1 and IL-1ß. RESULTS: IFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and positively correlated with HBVDNA,caspase-1 and IL-1ß expression in HBV-GN. Meanwhile, over expression of IFI16 increased caspase-1 and IL-1ß expression in HBV-infected HGM and HEK-293 T cell lines, knockdown of IFI16 mRNA by siRNA resulted in downregulation of the caspase-1 and IL-1ß expression in both cell lines. CONCLUSIONS: The elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for researching the pathogenesis of HBV-GN.