A comparative study of mono-exponential and advanced diffusion-weighted imaging in differentiating stage IA endometrial carcinoma from benign endometrial lesions.

PURPOSE: The purpose of the current investigation is to compare the efficacy of different diffusion models and diffusion kurtosis imaging (DKI) in differentiating stage IA endometrial carcinoma (IAEC) from benign endometrial lesions (BELs). METHODS: Patients with IAEC, endometrial hyperplasia (EH), or a thickened endometrium confirmed between May 2016 and August 2022 were retrospectively enrolled. All of the patients underwent a preoperative pelvic magnetic resonance imaging (MRI) examination. The apparent diffusion coefficient (ADC) from the mono-exponential model, pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) from the bi-exponential model, distributed diffusion coefficient (DDC), water molecular diffusion heterogeneity index from the stretched-exponential model, diffusion coefficient (Dk) and diffusion kurtosis (K) from the DKI model were calculated. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency. RESULTS: A total of 90 patients with IAEC and 91 patients with BELs were enrolled. The values of ADC, D, DDC and Dk were significantly lower and D* and K were significantly higher in cases of IAEC (p < 0.05). Multivariate analysis showed that K was the only predictor. The area under the ROC curve of K was 0.864, significantly higher compared with the ADC (0.601), D (0.811), D* (0.638), DDC (0.743) and Dk (0.675). The sensitivity, specificity and accuracy of K were 78.89%, 85.71% and 80.66%, respectively. CONCLUSION: Advanced diffusion-weighted imaging models have good performance for differentiating IAEC from EH and endometrial thickening. Among all of the diffusion parameters, K showed the best performance and was the only independent predictor. Diffusion kurtosis imaging was defined as the most valuable model in the current context.

Acute hepatic and kidney injury after ingestion of Lepiota brunneoincarnata: Report of 2 cases.

Lepiota brunneoincarnata is a highly toxic mushroom species known to cause acute liver failure. However, there are limited reports investigating L. brunneoincarnata causing acute hepatic and renal damage. The present article reports 2 cases of L. brunneoincarnata poisoning in a mother and son from Chuxiong City, Yunnan Province, China. Both patients presented with gastrointestinal symptoms approximately 8-9 h after ingesting the suspect mushrooms and sought medical attention 27-28 h post-ingestion, both exhibiting acute hepatic and kidney injuries. Morphological and molecular biology studies confirmed the species of the mushrooms as L. brunneoincarnata. Liquid chromatography-tandem mass spectrometry analysis revealed mean fresh-weight concentrations of 123.5 µg/g α-amanitin and 45.7 µg/g ß-amanitin in the mushrooms. The patients underwent standard treatments, including multiple-dose activated charcoal, oral silibinin capsules, N-acetylcysteine, penicillin G, hemoperfusion, and plasma exchange. One patient recovered completely and was discharged after 16 days of hospitalization. The other patient exhibited gradual improvement in liver and renal function; however, renal function deteriorated 9 days after ingestion, and the patient declined renal replacement therapy and returned home 14 days post-ingestion. The patient was then re-hospitalized due to oliguria and edema in both lower extremities. Renal biopsy revealed acute tubular necrosis, inflammatory cell infiltration, minor glomerular capsular fibrosis, loss of microvilli in the renal tubular epithelial cells, and interstitial edema. The patient underwent 2 rounds of continuous renal replacement therapy, which eventually resulted in improvement, and was discharged 31 days after mushroom consumption. It is noteworthy that this patient had already progressed to chronic kidney insufficiency 11 months after intoxication.

A CD326 monoclonal antibody modified core cross-linked curcumin-polyphosphoester prodrug for targeted delivery and cancer treatment.

Stimuli-responsive cross-linked micelles (SCMs) are ideal nanocarriers for anti-cancer drugs. Compared with non-cross-linked micelles, SCMs exhibit superior structural stability. At the same time, the introduction of an environmentally sensitive crosslinker into a drug delivery system allows SCMs to respond to single or multiple stimuli in the tumor microenvironment, which can minimize drug leakage during the blood circulation process. In this study, curcumin (CUR) was modified as the hydrophobic core crosslinker by utilizing the bisphenol structure, and redox sensitive disulfide bonds were introduced to prepare the glutathione (GSH) stimulated responsive core crosslinker (abbreviated as N3-ss-CUR-ss-N3). In addition, amphiphilic polymer APEG-b-PBYP was prepared through the ring opening reaction, and reacted with the crosslinker through the "click" reaction. After being dispersed in the aqueous phase, core cross-linked nanoparticles (CCL NPs) were obtained. Finally, monoclonal antibody CD326 (mAb-CD326) was reduced and coupled to the hydrophilic chain ends to obtain the nanoparticles with surface modified antibodies (R-mAb-CD326@CCL NPs) for further enhancing targeted drug delivery. The structures of the polymer and crosslinker were characterized by 1H NMR, UV-Vis, FT-IR, and GPC. The morphology, size and stability of CCL NPs and R-mAb-CD326@CCL NPs were investigated by DLS and TEM. The in vitro drug release behavior of CCL NPs was also studied. The results showed that the CCL NPs exhibited reduction-responsiveness and were able to release the original drug CUR under 10 mM GSH conditions. Additionally, the CCL NPs exhibited excellent stability in both the simulated body fluid environment and organic solvents. Especially, R-mAb-CD326@CCL NPs can actively target tumor cells and showed better therapeutic efficacy in in vivo experiments with a tumor suppression rate of 78.7%. This work provides a new idea for the design of nano-drugs targeting breast cancer.

CD163 Monoclonal Antibody Modified Polymer Prodrug Nanoparticles for Targeting Tumor-Associated Macrophages (TAMs) to Enhance Anti-Tumor Effects.

Tumor-associated macrophages (TAMs)-based immunotherapy is a promising strategy. Since TAMs are mainly composed of M2-type macrophages, they have a promoting effect on tumor growth, invasion, and metastasis. M2-type macrophages contain a specific receptor CD163 on their surface, providing a prerequisite for active targeting to TAMs. In this study, we prepared CD163 monoclonal antibody modified doxorubicin-polymer prodrug nanoparticles (abbreviated as mAb-CD163-PDNPs) with pH responsiveness and targeted delivery. First, DOX was bonded with the aldehyde group of a copolymer by Schiff base reaction to form an amphiphilic polymer prodrug, which could self-assemble into nanoparticles in the aqueous solution. Then, mAb-CD163-PDNPs were generated through a "Click" reaction between the azide group on the surface of the prodrug nanoparticles and dibenzocyclocytyl-coupled CD163 monoclonal antibody (mAb-CD163-DBCO). The structure and assembly morphology of the prodrug and nanoparticles were characterized by 1H NMR, MALDI-TOF MS, FT-IR UV-vis spectroscopy, and dynamic light scattering (DLS). In vitro drug release behavior, cytotoxicity, and cell uptake were also investigated. The results show that the prodrug nanoparticles have regular morphology and stable structure, especially mAb-CD163-PDNPs, which can actively target TAMs at tumor sites, respond to the acidic environment in tumor cells, and release drugs. While depleting TAMs, mAb-CD163-PDNPs can actively enrich drugs at the tumor site and have a strong inhibitory effect on TAMs and tumor cells. The result of the in vivo test also shows a good therapeutic effect, with a tumor inhibition rate of 81%. This strategy of delivering anticancer drugs in TAMs provides a new way to develop targeted drugs for immunotherapy of malignant tumors.

Morphology and phylogeny identify two new species and one new subspecies of Podoscypha from Yunnan Province, Southwest China.

In this study, Podoscypha was taxonomically and phylogenetically evaluated. In total, five specimens collected from the tropical areas of Yunnan Province in Southwest China were studied. In combination with morphological observations and phylogenetic analyses based on ITS and LSU loci, two new species and one new subspecies, Podoscypha subinvoluta, P. tropica, and P. petalodes subsp. cystidiata, respectively, were discovered. The illustrated descriptions of the new species and subspecies are provided. Moreover, the main morphological differences between related species are discussed.

Application of Three-Dimensional Technology in Evaluating the Lower Face Lifting by Regional Platysma Injection with Botulinum Toxin-A.

BACKGROUND: Botulinum toxin-A (BTX-A) injection of regional platysma has been utilized in the lower-part elevation and mandibular contour sculpture. However, the relative research, especially in quantitative assessment appears very spare. Our aim is to investigate the efficacy of three-dimensional (3D) technology as a method for regional platysma injection with BTX-A. MATERIALS AND METHODS: From October 2019 to September 2020, patients with mild or moderate degrees of facial sagging on the lower face were recruited to regional platysma BTX-A injection, and 3D scanning and measurement technology was used to evaluate the difference of curved distances and angels. Patients' improvement was assessed by the global aesthetic improvement scale (GAIS). RESULTS: A total of 57 patients underwent regional platysma BTX-A injection and 32 patients were followed up successfully. Compared with Pre-operative, postoperative facial reference curves distance and cervico-mental angles had statistical differences (p < 0.05). GAIS suggested that the 3D imaging measurement technology could improve satisfaction. CONCLUSION: 3D technology can evaluate the improvement of the lower face with BTX-A. It provides effective measurement methods and raises satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Deep learning model improves radiologists' performance in detection and classification of breast lesions.

OBJECTIVE: Computer-aided diagnosis using deep learning algorithms has been initially applied in the field of mammography, but there is no large-scale clinical application. METHODS: This study proposed to develop and verify an artificial intelligence model based on mammography. Firstly, mammograms retrospectively collected from six centers were randomized to a training dataset and a validation dataset for establishing the model. Secondly, the model was tested by comparing 12 radiologists' performance with and without it. Finally, prospectively enrolled women with mammograms from six centers were diagnosed by radiologists with the model. The detection and diagnostic capabilities were evaluated using the free-response receiver operating characteristic (FROC) curve and ROC curve. RESULTS: The sensitivity of model for detecting lesions after matching was 0.908 for false positive rate of 0.25 in unilateral images. The area under ROC curve (AUC) to distinguish the benign lesions from malignant lesions was 0.855 [95% confidence interval (95% CI): 0.830, 0.880]. The performance of 12 radiologists with the model was higher than that of radiologists alone (AUC: 0.852 vs. 0.805, P=0.005). The mean reading time of with the model was shorter than that of reading alone (80.18 s vs. 62.28 s, P=0.032). In prospective application, the sensitivity of detection reached 0.887 at false positive rate of 0.25; the AUC of radiologists with the model was 0.983 (95% CI: 0.978, 0.988), with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 94.36%, 98.07%, 87.76%, and 99.09%, respectively. CONCLUSIONS: The artificial intelligence model exhibits high accuracy for detecting and diagnosing breast lesions, improves diagnostic accuracy and saves time.

Association of Brain Iron Overload With Brain Edema and Brain Atrophy After Intracerebral Hemorrhage.

Objective: This study evaluated iron overload after intracerebral hemorrhage (ICH) using ESWAN sequences. Methods: This single-center prospective observational cohort study enrolled supratentorial ICH patients. MRI was obtained with a 3.0-T scanner at day 1, day 14, day 30, and follow-up (300 days or later). R2* mapping was generated based on the ESWAN. R2* value of the ipsilateral side represented iron deposition, and the R2* value of the contralateral side served as control. R2* value was adjusted by volume and used to assess total iron overload. Brain edema was measured on T2 FLAIR-weighted images. Brain atrophy was calculated as the contralateral hemisphere volume minus the injured hemisphere volume. Results: Twnety-seven patients with a spontaneous supratentorial ICH were included in this analysis. The ipsilateral R2* value was 40.27 ± 11.62, 41.92 ± 13.56, and 60.89 ± 14.09 at days 1, 14, and 30, respectively. The R2* value was significantly higher in the ICH side than the contralateral side (p < 0.01). Increased R2* value was seen on day 30 compared to day 14 (p < 0.01). The R2* value showed logistic decay with the distance to the hematoma margin (p < 0.01). Brain edema at day 14 and brain atrophy at follow-up correlated with R2* value adjusted by volume at day 14 (p < 0.01). Conclusions: After ICH, the iron deposition in the perihematomal region was progressively increased during the first month. R2* value adjusted by volume predicted acute brain edema and chronic brain atrophy.

Chemical Composition of Bawei Longzuan Granule and Its Anti-Arthritic Activity on Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses.

Bawei Longzuan granule (BLG) is a representative Zhuang medicine preparation. The present work aims to characterize the chemical constituents of BLG and evaluate its anti-arthritic activity. The major chemical constituents of BLG were tentatively identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), which revealed the presence of some alkaloids (e. g., magnoflorine, sinomenine and nitidine) and flavonoids (e. g., hesperidin, diosmin and sinensetin) that may be partly responsible for the anti-arthritic effect of BLG. In addition, the collagen-induced arthritis (CIA) model in rats was induced by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of tail. The CIA rats received oral administration of BLG (1.25, 2.5 and 5 g/kg) for 30 days. Then, various indicators were determined to evaluate its anti-arthritic activity, including paw swelling, arthritic score, body weight, knee joint pathology, thymus index and spleen index. Additionally, the serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1ß, IL-6, IL-4 and IL-10 were measured to determine the underlying mechanisms. The results showed that BLG efficiently ameliorated the severity of arthritis in CIA rats by decreasing paw swelling and arthritis score and improving the histological lesions of knee joint. Moreover, the serum levels of several pro-inflammatory cytokines (i. e., IL-1ß, TNF-α, IL-6 and IFN-γ) were downregulated, whereas two anti-inflammatory factors (i. e., IL-4 and IL-10) were upregulated after BLG administration. These results indicated that BLG possessed promising therapeutic effect on collagen-induced arthritis by inhibiting inflammatory responses. BLG can be used as a complementary or alternative traditional medicine to treat rheumatoid arthritis.

Early Hemolysis Within Human Intracerebral Hematomas: an MRI Study.

Early hemolysis occurs in the hematoma within 24 h in rat model of intracerebral hemorrhage (ICH). The present study investigated the prevalence of early hemolysis in ICH patients using MRI and the relationship between early hemolysis and perihematomal edema. Thirty ICH patients were prospectively enrolled within 24 h of onset. All patients had cranial CT on admission. Cranial MRI with T2 FLAIR-weighted imaging and T2*-weighted imaging were undertaken at days 1 and 14. The evolution of a non-hypointense lesion on T2*-weighted images and the relationship between the volume of that non-hypointense lesion and perihematomal edema volume were investigated. MRI images of 15 patients were analyzed. The median hematoma volume was 16.3 ml on admission. All patients underwent a baseline MRI within 24 h of ICH onset and showed a non-hypointense lesion within the hematoma on T2*-weighted images. The volume of non-hypointense lesion on T2*-weighted image was 6.0 (8.9) ml at day 1 and 8.6 (17.3) ml at day 14. The absolute perihematomal edema volume was 16.0 (17.9) ml and 24.8 (27.5) ml at days 1 and 14, respectively. There was a linear correlation between non-hypointense T2* lesion and perihematomal edema volume at day 1 and day 14 (p < 0.01). Early hemolysis in the hematoma occurs in humans and contributes to the development of perihematomal edema.

Lnc-PCDH9-13:1 Is a Hypersensitive and Specific Biomarker for Early Hepatocellular Carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) show great potential as diagnostic tools in many diseases. We aimed to develop sensitive and noninvasive biomarkers in saliva for detecting early hepatocellular carcinoma (HCC). METHODS: Candidate lncRNA biomarkers identified by Agilent microarray were subjected to validation using qPCR for the quantification of their expression levels in independent tissue, plasma and saliva sample sets, including healthy controls, HBsAg carriers, patients with chronic Hepatitis B, liver cirrhosis, early HCC, and advanced HCC. Levels of candidate biomarkers were also measured in totally 108 saliva samples from patients with any one of other nine leading causes of cancer death in men and women. FINDINGS: Lnc-PCDH9-13:1 was significantly elevated in HCC tissues, plasma and saliva of HCC patients compared with healthy controls and groups of several benign liver diseases and other leading cancers. Its level was significantly reduced after curative hepatectomy but significantly elevated again if HCC recurrence occurred. Salivary lnc-PCDH9-13:1 showed reasonable specificities and sensitivities for detecting HCC compared with several control groups. Furthermore, the overexpression of lnc-PCDH9-13:1 promotes cell proliferation and migration in vitro. INTERPRETATION: Salivary lnc-PCDH9-13:1 is a desirable biomarker for early HCC. It may help warrant prospective validation with larger sample sizes in multi-centers.

Effect of Biliary Drainage on the Toxicity and Toxicokinetics of Amanita exitialis in Beagles.

Amatoxin poisoning induces delayed-onset acute liver failure, which are responsible for more than 90% of deaths in mushroom poisoning. It has been postulated from animal and human studies that biliary drainage interrupting enterohepatic amatoxin circulation may affect amatoxin poisoning. Dogs were randomly divided into four groups of six animals each. In 20 mg/kg and 60 mg/kg with biliary drainage groups, after accepting bile drainage operation, beagles were fed Amanita exitialis powder (20 or 60 mg/kg) in starch capsules. In control and bile drainage groups, the beagle dogs were fed with empty capsules. They were assessed for toxicity signs, biochemical and pathological changes, and peptide toxins in plasma, urine and bile. The data were directly compared with those from our published studies on Amanita exitialis-exposed beagles without biliary drainage. Amatoxins were rapidly absorbed and eliminated from plasma after Amanita exitialis ingestion. Amatoxins in 0⁻1-day urine accounted for more than 90% of the total urine excretion, and amatoxins in bile accounted for less than 20% of the total urine and bile excretion. The dogs with biliary drainage showed less severe toxicity signs and biochemical and pathological changes and much lower internal exposure than dogs without biliary drainage. Biliary drainage caused a more than 70% reduction in intestinal amatoxin absorption and could reduce amatoxin absorption from the gastrointestinal tract.

Natural Medicines Used in the Traditional Tibetan Medical System for the Treatment of Liver Diseases.

Liver disease is one of the most risk factors threatening human health. It is of great significance to find drugs that can treat liver diseases, especially for acute and chronic hepatitis, non-alcoholic fatty liver disease, and liver cancer. The search for drugs with good efficacy from traditional natural medicines has attracted more and more attention. Tibetan medicine, one of the China's traditional medical systems, has been widely used by the Tibetan people for the prevention and treatment of liver diseases for hundreds of years. The present paper summarized the natural Tibetan medicines that have been used in Tibetan traditional system of medicine to treat liver diseases by bibliographic investigation of 22 Tibetan medicine monographs and drug standards. One hundred and ninety three species including 181 plants, 7 animals, and 5 minerals were found to treat liver diseases in traditional Tibetan medicine system. The most frequently used species are Carthamus tinctorius, Brag-zhun, Swertia chirayita, Swertia mussotii, Halenia elliptica, Herpetospermum pedunculosum, and Phyllanthus emblica. Their names, families, medicinal parts, traditional uses, phytochemicals information, and pharmacological activities were described in detail. These natural medicines might be a valuable gift from the old Tibetan medicine to the world, and would be potential drug candidates for the treatment of liver diseases. Further studies are needed to prove their medicinal values in liver diseases treatment, identify bioactive compounds, elucidate the underlying mechanism of action, and clarify their side effects or toxicity with the help of modern phytochemical, pharmacological, metabonomics, and/or clinical trial methods.

Salivary HOTAIR and PVT1 as novel biomarkers for early pancreatic cancer.

Sensitive and non-invasive biomarkers for pancreatic cancer (PC) are lacking. We aimed to identify salivary long non-coding RNAs (lncRNAs) as biomarkers in diagnosis of resectable PC. Five well-documented lncRNAs: H19, HOTAIR, HOTTIP, MALAT1, PVT1, which are most closely associated with pancreatic cancer from previous studies were selected as putative lncRNA biomarkers. Their expression in pancreatic tissues and saliva of cancer patients and healthy controls was measured by quantification polymerase chain reaction (qPCR). Compared with benign pancreatic tumour (BPT) and normal pancreatic tissues (NPT), HOTAIR, HOTTIP and PVT1 were significantly up-regulated in pancreatic cancer tissues (PCT). As compared to BPT or healthy groups, the salivary levels of HOTAIR and PVT1 were significantly higher in PC group. They were significantly reduced after the curative pancreatectomy. Both salivary lncRNAs distinguished PC patients from healthy controls and BPT patients with sensitivities and specificities ranging from 60-97%. The expression of salivary HOTAIR and PVT1 did not differ significantly between healthy controls and any one of eight leading cancers worldwide. Collectively, our findings indicate that salivary HOTAIR and PVT1 show potential as novel non-invasive biomarkers for detecting PC.

Disruption and molecular characterization of calpains-related (MoCAPN1, MoCAPN3 and MoCAPN4) genes in Magnaporthe oryzae.

Calpains are intracellular, cysteine proteases found in plants, animals and fungi functioning as signal transduction components in different cellular pathways including sporulation and alkaline adaptation in fungi. Calpains-related MoCAPN1 (MGG_14872), MoCAPN3 (MGG_15810) and MoCAPN4 (MGG_04818) genes from Magnaporthe oryzae genome which are 2604, 3513 and 771-bp in length and encoding identical proteins of 867, 1170 and 256 amino acids were functionally characterized for different phenotypes through gene disruption method. All the mutants except those for MoCAPN1 showed normal phenotypes. In pathogenicity test, the mutants did not lead to any visible changes in phenotypes causing similar blast lesions on blast susceptible rice and barley leaves as those of the Guy-11 strain suggesting no major role in pathogenicity. Germ tubes formation, appressorium formation, mycelium radial growth and mating with 2539 strain were indistinguishable among the mutants and Guy-11 strains. Cell wall integrity (congo red) test, stress response under chemical pressure (ZnSO4, CuSO4 and CdCl2), osmotic and oxidative (NaCl and H2O2) stress response, growth response on glucose and nitrogen deficient media resulted in similar results in the mutants and Guy-11 strains. However, mutants for ΔMoCAPN1 gene produced reduced (0.57±0.15B and 0.54±0.05B) conidia compared to that (1.69±0.13A) of the Guy-11 strain showing its involvement in conidiation.

Taxonomy and phylogeny of the genus Megasporoporia and its related genera.

Taxonomic and phylogenetic studies on Megasporoporia s.l. were carried out. Phylogenetic analysis based on ITS and nLSU sequences showed that Megasporoporia s.l. belonging to the core polyporoid clade, however, it is not monophyletic, and four clades were recognized. The Megasporoporia s.s. clade includes M. setulosa and two new species, M. bannaensis and M. minor spp. nov. Two monophyletic clades were segregated from Megasporoporia s.l., and two new genera were established. Megasporia gen. nov. is composed of M. cystidiolophora, M. ellipsoidea, M. hexagonoides, M. major, M. violacea, and two new species, M. guangdongensis and M. hengduanensis spp. nov. Megasporoporiella gen. nov. including M. cavernulosa, M. rhododendri, M. subcavernulosa, and two new species, M. lacerata and M. pseudocavernulosa spp. nov. Megasporoporia quercina grouped with Grammothele fuligo in the Grammothele clade, so it is transferred to Grammothele and a new combination, G. quercina, is proposed. The main morphological characters of Megasporoporia and the two new genera are discussed, and identification keys to the three genera are provided.