Association between Serum Ferritin Levels and Metabolic-associated Fatty Liver Disease in Adults: a Cross-sectional Study Based on the NHANES.

OBJECTIVE: Ferritin, initially acting as an iron-storage protein, was found to be associated with metabolic diseases. Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease (MAFLD) using data from the National Health and Nutrition Examination Survey (NHANES) of the United State of America. METHODS: A cross-sectional study was conducted, enrolling a total of 2145 participants from the NHANES in the 2017-2018 cycles. Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes. Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis. RESULTS: The analysis revealed that participants with higher serum ferritin levels (Q3 and Q4 groups) had a higher prevalence of MAFLD than those with the lowest serum ferritin levels [Q3 vs. Q1: OR=2.17 (1.33, 3.53), P<0.05 in fatty liver index (FLI); Q4 vs. Q1: OR=3.13 (1.91, 5.13), P<0.05 in FLI]. Additionally, participants with the highest serum ferritin levels (Q4 group) displayed a higher prevalence of liver fibrosis [Q4 vs. Q1: OR=2.59 (1.19, 5.62), P<0.05 in liver stiffness measurement; OR=5.06 (1.12, 22.94), P<0.05 in fibrosis-4 index], with significantly increased risk observed in participants with concomitant diabetes [OR=7.45 (1.55, 35.72), P=0.012]. CONCLUSION: Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients. Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.

Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma.

BACKGROUND: Drug resistance poses a significant challenge in cancer treatment, particularly as a leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, the development of resistance against cisplatin is a major obstacle. Therefore, identifying genes resistant to cisplatin and adopting personalized treatment could significantly improve patient outcomes. METHODS: By examining transcriptome data of cisplatin-resistant LUAD cells from the GEO database, 181 genes associated with cisplatin resistance were identified. Using univariate regression analysis, random forest and multivariate regression analyses, two prognostic genes, E2F7 and FAM83A, were identified. This study developed a prognostic model utilizing E2F7 and FAM83A as key indicators. The Cell Counting Kit 8 assay, Transwell assay, and flow cytometry were used to detect the effects of E2F7 on the proliferation, migration, invasiveness and apoptosis of A549/PC9 cells. Western blotting was used to determine the effect of E2F7 on AKT/mTOR signaling pathway. RESULTS: This study has pinpointed two crucial genes associated with cisplatin resistance, E2F7 and FAM83A, and developed a comprehensive model to assist in the diagnosis, prognosis, and evaluation of relapse risk in LUAD. Analysis revealed that patients at higher risk, according to these genetic markers, had elevated levels of immune checkpoints (PD-L1 and PD-L2). The prognostic and diagnosis values of E2F7 and FAM83A were further confirmed in clinical data. Furthermore, inhibiting E2F7 in lung cancer cells markedly reduced their proliferation, migration, invasion, and increased apoptosis. In vivo experiments corroborated these findings, showing reduced tumor growth and lung metastasis upon E2F7 suppression in lung cancer models. CONCLUSION: Our study affirms the prognostic value of a model based on two DEGs, offering a reliable method for predicting the success of tumor immunotherapy in patients with LUAD. The diagnostic and predictive model based on these genes demonstrates excellent performance. In vitro, reducing E2F7 levels shows antitumor effects by blocking LUAD growth and progression. Further investigation into the molecular mechanisms has highlighted E2F7's effect on the AKT/mTOR signaling pathway, underscoring its therapeutic potential. In the era of personalized medicine, this DEG-based model promises to guide clinical practice.

Laser-activable murine ferritin nanocage for chemo-photothermal therapy of colorectal cancer.

Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.

CRISPR/Cas-based CAR-T cells: production and application.

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment approach for cancer, autoimmune disease, and heart disease. The integration of CAR into T cells is typically facilitated by retroviral or lentiviral vectors. However, the random insertion of CARs can lead to issues like clonal expansion, oncogenic transformation, variegated transgene expression, and transcriptional silencing. The advent of precise gene editing technology, like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), allows for controlled and precise genome modification, facilitating the translation of CAR-T research to the clinical applications. This review aims to provide a comprehensive analysis of the application of CRISPR gene editing techniques in the context of precise deletion and insertion methodologies, with a specific focus on their potential for enhancing the development and utilization of CAR-T cell therapy.

Two pairs of bioactive cyclohexene alkaloid enantiomers from the roots of Piper nigrum.

Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.

Simulation Study of Polyethylene Terephthalate Hydrolase Adsorption on Self-Assembled Monolayers.

Polyethylene terephthalate (PET) hydrolase, discovered in Ideonella sakaiensis (IsPETase), is a promising agent for the biodegradation of PET under mild reaction conditions, yet the thermal stability is poor. The efficient immobilization and orientation of IsPETase on different solid substrates are essential for its application. In this work, the combined parallel tempering Monte Carlo simulation with the all-atom molecular dynamics simulation approach was adopted to reveal the adsorption mechanism, orientation, and conformational changes of IsPETase adsorbed on charged self-assembled monolayers (SAMs), including COOH-SAM and NH2-SAM with different surface charge densities (SCDs). The results show that the protein adsorption orientation was determined not only by attraction interactions but also by repulsion interactions. IsPETase is adsorbed on the COOH-SAM surface with an "end-on" orientation, which favors the exposure of the catalyzed triplet to the solution. In addition, the entrance to the catalytic active center is larger on the COOH-SAM surface with a low SCD. This work reveals the controlled orientation and conformational information on IsPETase on charged surfaces at the atomistic level. This study would certainly promote our understanding of the mechanism of IsPETase adsorption and provide theoretical support for the design of substrates for IsPETase immobilization.

Prevalence and associated factors of secondary traumatic stress in emergency nurses: a systematic review and meta-analysis.

Background: Nurses in emergency departments are at a high risk of experiencing secondary traumatic stress because of their frequent exposure to trauma patients and high-stress environments.Objective: This systematic review and meta-analysis aimed to determine the overall prevalence of secondary traumatic stress among emergency nurses and to identify the contributing factors.Method: We conducted a systematic search for cross-sectional studies in databases such as PubMed, Web of Science, Embase, CINAHL, Wanfang Database, and China National Knowledge Internet up to October 21, 2023. The Joanna Briggs Institute's appraisal checklists for prevalence and analytical cross-sectional studies were used for quality assessment. Heterogeneity among studies was assessed using Cochrane's Q test and the I2 statistic. A random effects model was applied to estimate the pooled prevalence of secondary traumatic stress, and subgroup analyses were performed to explore sources of heterogeneity. Descriptive analysis summarized the associated factors.Results: Out of 345 articles retrieved, 14 met the inclusion criteria, with 11 reporting secondary traumatic stress prevalence. The pooled prevalence of secondary traumatic stress among emergency nurses was 65% (95% CI: 58%-73%). Subgroup analyses indicated the highest prevalence in Asia (74%, 95% CI: 72%-77%), followed by North America (59%, 95% CI: 49%-72%) and Europe (53%, 95% CI: 29%-95%). Nine studies identified associated factors, including personal, work-related, and social factors. In the subgroup of divided by recruitment period, emergency department nurses in the COVID-19 outbreak period had a higher prevalence of secondary traumatic stress (70%, 95% CI: 62%-78%).Conclusions: Secondary traumatic stress prevalence is notably high among emergency department nurses, with significant regional variations and period differences. The factors affecting secondary traumatic stress also varied across studies. Future research should focus on improving research designs and sample sizes to pinpoint risk factors and develop prevention strategies.Registration: PROSPERO CRD42022301167.

Secondary traumatic stress is considered an occupational hazard for nurses. Emergency department nurses, in particular, face a greater risk of secondary traumatic stress compared to other professions.While various studies have investigated the prevalence of secondary traumatic stress among these nurses, findings have been inconsistent.The pooled prevalence of secondary traumatic stress among emergency nurses is 65%. Subgroup analysis by region shows that Asia experiences the highest combined prevalence at 74%, with North America at 59% and Europe at 53%. Emergency department nurses in the COVID-19 outbreak period had a higher prevalence of secondary traumatic stress (70%, 95% CI: 62%­78%).

The effect of ghrelin on bursa and cecal tonsils of chickens infected with an attenuated virus strain of infectious bursal disease virus.

Infectious bursal disease (IBD) significantly affects the poultry industry, causing substantial economic losses. This study aimed to investigate the effects of ghrelin on chicks infected with an attenuated virus strain of IBDV (aIBDV). Chicks were divided into 3 groups: a control group (group I), an aIBDV infection group (group II), and a ghrelin + aIBDV infection group (group III). Mice in groups II and III were fed until they reached 19 d of age and then inoculated with aIBDV to establish a subclinical infection model. Group III received an intraperitoneal injection of 0.5 nmol/100 g ghrelin from d 17 to 23. The present study utilized paraffin sectioning, H&E staining, and immunohistochemical staining to examine the effects of ghrelin on the bursa of fabricius and cecum tonsils in aIBDV-infected chicks. The results indicated that at 3 d postinfection (dpi), the average body weight of group III was significantly greater than that of group II (P < 0.05). At 3 and 7 dpi, the proportion of large lymphoid follicles in the bursa of fabricius in group III was notably greater than that in group II (P < 0.05). aIBDV infection resulted in bleeding, edema, and fibrosis in the cecal mucosal layer of chicks, but ghrelin administration mitigated these pathological changes. At 3 and 7 dpi, the thickness of the lamina propria in the cecal tonsils of group III was significantly lower than that in the cecal tonsils of group II (P < 0.05). Additionally, the percentage of large lymphoid follicles in the cecal tonsils of group III was significantly greater than that in group II at 3 and 5 dpi (P < 0.05). There were significantly fewer macrophages in the cecal tonsils of group III than in those of group II at 1, 3, and 5 dpi (P < 0.05). In conclusion, ghrelin supplementation improved performance and mitigated bursal atrophy in aIBDV-infected chicks. It also reduced histological lesions and immune responses in the cecum tonsil. Notably, the reduction in macrophages in the cecum tonsil following ghrelin administration may decrease the risk of aIBDV spread.

Predicting the error magnitude in patient-specific QA during radiotherapy based on ResNet.

BACKGROUND: The error magnitude is closely related to patient-specific dosimetry and plays an important role in evaluating the delivery of the radiotherapy plan in QA. No previous study has investigated the feasibility of deep learning to predict error magnitude. OBJECTIVE: The purpose of this study was to predict the error magnitude of different delivery error types in radiotherapy based on ResNet. METHODS: A total of 34 chest cancer plans (172 fields) of intensity-modulated radiation therapy (IMRT) from Eclipse were selected, of which 30 plans (151 fields) were used for model training and validation, and 4 plans including 21 fields were used for external testing. The collimator misalignment (COLL), monitor unit variation (MU), random multi-leaf collimator shift (MLCR), and systematic MLC shift (MLCS) were introduced. These dose distributions of portal dose predictions for the original plans were defined as the reference dose distribution (RDD), while those for the error-introduced plans were defined as the error-introduced dose distribution (EDD). Different inputs were used in the ResNet for predicting the error magnitude. RESULTS: In the test set, the accuracy of error type prediction based on the dose difference, gamma distribution, and RDD + EDD was 98.36%, 98.91%, and 100%, respectively; the root mean squared error (RMSE) was 1.45-1.54, 0.58-0.90, 0.32-0.36, and 0.15-0.24; the mean absolute error (MAE) was 1.06-1.18, 0.32-0.78, 0.25-0.27, and 0.11-0.18, respectively, for COLL, MU, MLCR and MLCS. CONCLUSIONS: In this study, error magnitude prediction models with dose difference, gamma distribution, and RDD + EDD are established based on ResNet. The accurate prediction of the error magnitude under different error types can provide reference for error analysis in patient-specific QA.

Effects of dietary supplementation of fermented Artemisia argyi on growth performance, slaughter performance, and meat quality in broilers.

Artemisia argyi (AA) is promising as a potential feed additive. Microbial fermentation is beneficial to the degradation of cell walls and the better release of bioactive compounds of AA. However, there are few reports on the application of fermented AA as a feed additive for broilers. The present study intended to evaluate the application value of fermented AA as a feed additive for broilers by examining the effects of the dietary supplementation of Aspergillus niger-fermented AA and unfermented AA on growth performance, slaughter performance, and meat quality of brokers. A total of 360 newly hatched (1-day-old) broilers with similar body weight were randomly divided into the following 5 groups: basal diet group as control (C) group, basal diet +3% unfermented AA (E1) group, basal diet + 1% fermented AA (E2) group, basal diet + 3% fermented AA (E3) group, basal diet + 5% fermented AA (E4) group. Each group included 6 replicates with 12 broilers per replicate, and the feeding trail lasted for 48 d. Body weight and feed intake were recorded every 2 wk, and the feed gain ratio was calculated to assess growth performance. At 42 d, 6 broilers from each group were slaughtered, and the carcass traits were calculated. The results showed that compared with the control group, Aspergillus Niger could effectively destroy AA fiber, which contributed to better release of AA bioactive compounds. Moreover, dietary supplementation with AA could improve the growth performance of broilers (P < 0.05), and the effect of fermented AA was better than unfermented AA, especially 3% fermented AA. From 28 to 42 d, compared with the control group, the average daily gain of broilers in the group supplementation with 3% fermented AA was significantly increased (P < 0.05), and the feed-to-gain ratio was decreased (P < 0.05). At 42 d, the dressing percentage, half-eviscerated carcass percentage, eviscerated carcass percentage, and breast muscle percentage of broilers in the groups of 1, 3, and 5% fermented AA diets were significantly improved (P < 0.05), and the thigh muscle percentage of broilers in the group with 3% fermented AA diets was significantly improved (P < 0.05). Meanwhile, the meat quality of broilers in the group with fermented AA diets was also significantly improved. Birds in AA groups had higher a* value and lower shear force of breast muscle, especially the group supplementation with 3% fermented AA (P < 0.05). In conclusion, fermented AA has good application value as a potential feed additive for broilers, dietary supplementation of fermented AA can improve the production performance and meat quality of broiler chickens, of which 3% fermented AA is more effective.

Improvement of Prediction Performance for Radiation Pneumonitis by Using 3-Dimensional Dosiomic Features.

INTRODUCTION: Patients with early non-small-cell lung cancer (NSCLC) have a relatively long survival time after stereotactic body radiation therapy (SBRT). Predicting radiation-induced pneumonia (RP) has important clinical and social implications for improving the quality of life of such patients. This study developed an RP prediction model by using 3-dimensional (3D) dosiomic features. The model can be used to guide radiation therapy to reduce toxicity. METHODS: Radiomic features were extracted from pre-treatment CT, dose-volume histogram (DVH) parameters and dosiomic features were extracted from the 3D dose distribution of 140 lung cancer patients. Four predictive models: (1) CT; (2) CT + DVH; (3) CT + Rtdose; and (4) Hybrid, CT + DVH + Rtdose, were trained to predict symptomatic RP by extremely randomized trees. Accuracy, sensitivity, specificity, and area under the receiver operator characteristic curve were evaluated. RESULT: Results showed that the fraction regimen was correlated with symptomatic RP (P < .001). The proposed model achieved promising prediction results. The performance metrics for CT, CT + DVH, CT + Rtdose, and Hybrid were as follows: accuracy: 0.786, 0.821, 0.821, and 0.857; sensitivity: 0.625, 1, 0.875, and 1; specificity: 0.8, 0.565, 0.5, and 0.875; and area under the receiver operator characteristic curve: 0.791, 0.809, 0.907, and 0.920, respectively. CONCLUSION: Dosiomic features can improve the performance of the predictive model for symptomatic RP compared with that obtained with the CT + DVH model. The model proposed in this study can help radiation oncologists individually predict the incidence rate of RP.

Molecular properties, structure and chiral resolution of secondary metabolites from the leaves of Viburnum chingii.

A chemical investigation of leaves of Viburnum chingii afforded eleven compounds, including one undescribed lignan (1), a pair of known phenylpropanoid enantiomers (2a/2b), and eight known lignans (3-10). Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. The absolute configurations of compounds 1 was determined by comparing the experimental ECD data with the calculated values. The compounds 2a/2b were separated successfully by a chiral chromatographic column. In addition, the acetylcholinesterase (AChE) inhibitory activities of described compounds were evaluated.

Computer Vision-Based Biomass Estimation for Invasive Plants.

We report on the detailed steps of a method to estimate the biomass of invasive plants based on UAV remote sensing and computer vision. To collect samples from the study area, we prepared a sample square assembly to randomize the sampling points. An unmanned aerial camera system was constructed using a drone and camera to acquire continuous RGB images of the study area through automated navigation. After completing the shooting, the aboveground biomass in the sample frame was collected, and all correspondences were labeled and packaged. The sample data was processed, and the aerial images were segmented into small images of 280 x 280 pixels to create an image dataset. A deep convolutional neural network was used to map the distribution of Mikania micrantha in the study area, and its vegetation index was obtained. The organisms collected were dried, and the dry weight was recorded as the ground truth biomass. The invasive plant biomass regression model was constructed using the K-nearest neighbor regression (KNNR) by extracting the vegetation index from the sample images as an independent variable and integrating it with the ground truth biomass as a dependent variable. The results showed that it was possible to predict the biomass of invasive plants accurately. An accurate spatial distribution map of invasive plant biomass was generated by image traversal, allowing precise identification of high-risk areas affected by invasive plants. In summary, this study demonstrates the potential of combining unmanned aerial vehicle remote sensing with machine learning techniques to estimate invasive plant biomass. It contributes significantly to the research of new technologies and methods for real-time monitoring of invasive plants and provides technical support for intelligent monitoring and hazard assessment at the regional scale.

Dosimetry and treatment efficiency of SBRT using TaiChiB radiotherapy system for two-lung lesions with one overlapping organs at risk.

Purpose: This study aims to assess the dosimetry and treatment efficiency of TaiChiB-based Stereotactic Body Radiotherapy (SBRT) plans applying to treat two-lung lesions with one overlapping organs at risk. Methods: For four retrospective patients diagnosed with two-lung lesions each patient, four treatment plans were designed including Plan Edge, TaiChiB linac-based, RGS-based, and a linac-RGS hybrid (Plan TCLinac, Plan TCRGS, and Plan TCHybrid). Dosimetric metrics and beam-on time were employed to evaluate and compare the TaiChiB-based plans against Plan Edge. Results: For Conformity Index (CI), Plan TCRGS outperformed all other plans with an average CI of 1.06, as opposed to Plan Edge's 1.33. Similarly, for R50 %, Plan TCRGS was superior with an average R50 % of 3.79, better than Plan Edge's 4.28. In terms of D2 cm, Plan TCRGS also led with an average of 48.48%, compared to Plan Edge's 56.25%. For organ at risk (OAR) sparing, Plan TCRGS often displayed the lowest dosimetric values, notably for the spinal cord (Dmax 5.92 Gy) and lungs (D1500cc 1.00 Gy, D1000cc 2.61 Gy, V10 Gy 15.14%). However, its high Dmax values for the heart and great vessels sometimes exceeded safety thresholds. Plan TCHybrid presented a balanced approach, showing doses comparable to or better than Plan Edge without crossing safety limits. In terms of beam-on time, Plan TCLinac emerged as the most efficient treatment option in three out of four cases, followed closely by Plan Edge in one case. Plan TCRGS, despite its dosimetric advantages, was the least efficient, recording notably longer beam-on times, with a peak at 33.28 minutes in Case 2. Conclusion: For patients with two-lung lesions treated by SBRT whose one lesion overlaps with OARs, the Plan TCHybrid delivered by TaiChiB digital radiotherapy system can be recommended as a clinical option.

ADP-ribosylation factor 6 promotes infectious bursal disease virus replication by affecting the internalization process via clathrin.

ADP-ribosylation factor 6 (ARF6) is a small G protein with extensive functions, including regulation of cellular membrane transport and viral infection. Infectious bursal disease (IBD) is caused by infectious bursal disease virus (IBDV), which mainly invades the bursa of Fabricius and causes low immunity in poultry. Our study demonstrated that IBDV infection could promote the expression of ARF6; however, the underlying mechanism remains unclear. Herein, the function of ARF6 in IBDV infection was explored, and it was revealed that viral replication was significantly promoted by ARF6 overexpression and hampered by siRNA-mediated inhibition of ARF6. Using two site mutants of ARF6 (ARF6-T27N and ARF6-Q67L), we found that IBDV replication was repressed by ARF6-T27N, indicating that ARF6 promotes IBDV replication. Further exploration of its mechanism revealed that ARF6 affects the copy number of IBDVs entering cells. A clathrin inhibitor (pitstop 2) impeded the early replication of IBDV, even when ARF6 was overexpressed. These results indicated that ARF6 promotes viral replication by affecting the internalization of IBDV, which may involve clathrin-dependent endocytosis. Our findings improve the understanding of the processes governing IBDV infection and provide insights into its prevention and control.

Carrier screening for spinal muscular atrophy in 22913 Chinese reproductive age women.

BACKGROUND: To determine the carrier frequency of, and evaluate a carrier screening program for, spinal muscular atrophy (SMA) in reproductive age women in Shenzhen area. METHODS: A staged screening procedure was used to perform carrier screening for SMA in 22,913 Chinese reproductive age women between 2019 and 2022 in Shenzhen area of China. First, the copy number of exon 7 in the SMN1 gene were detected in women of reproductive age using real-time quantitative polymerase chain reaction. If SMA carriers were detected, their spouses were then recommended to test. Prenatal diagnosis was carried out in couples who were both carriers. RESULTS: A total of 389 women were found to be SMA carriers (1.70%, 95% CI: 1.53%-1.87%), indicating the carrier prevalence was approximately 1:59. Despite the proportion of nonpregnant women increased from 37.96% in 2019 to 58.18% in 2022 (p < 0.05) among the 22,913 reproductive age women, the recall rate of spouses was still not high (62.21%, 95% CI: 57.39%-67.03%). Eight partners were found to be SMA carriers and two fetuses were determined to have SMA with no copies of the SMN1 gene. CONCLUSION: Although the acceptability and awareness of SMA carrier screening in Chinese population has increased in recent years, it still fails to reach the ideal expectation. Our experience may provide a basis for and facilitate the popularization of SMA carrier screening in Shenzhen area.

Safety assessment of Wuzhuyu decoction extract: acute and subacute oral toxicity studies in rats.

Wuzhuyu decoction (WZYD) is a well-known classic traditional Chinese medicine prescription and has been widely used to treat headache, nausea, vomiting, insomnia, etc. However, little published information is available about its safety. Our aim was to investigate the acute and subacute oral toxicity of WZYD extract in rats following the technical guidelines from China's National Medical Products Administration (NMPA) for single and repeated doses toxicity studies of drugs. Acute oral toxicity was assessed in rats via oral administration of WZYD extract at 4 g/kg three times within a day followed by a 14-day observation period. To evaluate the subacute toxicity, rats were orally administered with WZYD extract at doses of 0, 0.44, 1.33, and 4 g/kg for 28 days. The items examined included clinical signs, body weight, food consumption, hematological and biochemical parameters, bone marrow smear, organ index, and histopathology. After the rats were administered with 12 g/kg (3 × 4 g/kg) WZYD extract, no mortality and toxic effects were observed during the observation period. In the subacute toxicity study, WZYD extract did not cause any significant treatment-related abnormality in each examined item of rats, so the no observed adverse effect level (NOAEL) of WZYD extract for 28 days orally administered to rats is considered to be 4 g/kg, which is approximately 80-fold of its clinical proposed dosage.

Expanded Application of Piper nigrum: Guided Isolation of Alkaloids with Inhibitory Activities of AChE/BuChE and Aß Aggregation.

Piper nigrum is a popular crop that can be used as seasoning or as an additive but its active ingredients also have an effect on the nervous system. Nineteen new amide alkaloids (1a/1b, 2-5, 6a/6b, 7, 8a/8b, 9, 10a/10b, 11a-11b, 12-14) were isolated from P. nigrum, guided by inhibitory activity of AChE and LC-MS/MS based on GNPS. The configurations were determined by extensive spectral analysis, Bulkiness rule, and NMR calculations. The inhibitory activities of AChE/BuChE and Aß aggregation were tested, and the results showed compounds 2, 7, and 12 had significant inhibitory activities. These components were identified in the crude fraction and their relative quantities were tested, which suggested that compound 2 was the index component in the active site from P. nigrum.

Exposure frequency and radiation dose from CT examinations in Huaian.

This study quantified the exposure frequency and established the local diagnostic reference levels (DRLs) for the most common computed tomography (CT) examinations. A combined method census and sampling survey was used to quantify both frequency and radiation dose of CT examinations. Data were acquired through Picture Archiving and Communication System (PACS) or Radiology Information System (RIS). The annual frequency of CT examinations was 239.8 per 1000 inhabitants. The P75 of volume CT dose index (CTDIvol) to adult patients from CT scanning for head, chest, abdomen and lumbar spine examinations were 63.0, 12.4, 20.0 and 24.0 mGy, respectively. The P75 of dose-length product were 858.6, 416.0, 620.7 and 559.2 mGy·cm, respectively. This dose audit of CT practice can act as a starting point for establishing Huaian local DRLs and could be a reference for dose optimisation in China. This study compared DRLs in different countries and analysed some reasons for the rapid growth of CT examination frequency in Huaian.

Acute and chronic toxicity in Sprague-Dawley rats of orally-administered total lignans from Arctii Fructus, a potential therapeutic drug for diabetes.

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.