A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC-MS/MS methods for simultaneous determination of 19 main active components.

INTRODUCTION: Ginkgo biloba extract (GBE) is an effective substance from traditional Chinese medicine (TCM) G. biloba for treating ischaemic stroke (IS). However, its active ingredients and mechanism of action remain unclear. OBJECTIVES: This study aimed to reveal the potential active component group and possible anti-IS mechanism of GBE. MATERIALS AND METHODS: The network pharmacology method was used to reveal the possible anti-IS mechanism of these active ingredients in GBE. An ultra-high-performance liquid chromatography triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous detection of the active ingredients of GBE. RESULTS: The active components of GBE anti-IS were screened by literature integration. Network pharmacology results showed that the anti-IS effect of GBE is achieved through key active components such as protocatechuic acid, bilobalide, ginkgolide A, and so on. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the possible anti-IS mechanism of GBE is regulating the PI3K-Akt signalling pathway and other signal pathways closely related to inflammatory response and apoptosis regulation combined with AKT1, MAPK, TNF, ALB, CASP3, and other protein targets. Nineteen main constituents in seven batches of GBE were successfully analysed using the established UPLC-MS/MS method, and the results showed that the content of protocatechuic acid, gallic acid, ginkgolide A, and so forth was relatively high, which was consistent with network pharmacology results, indicating that these ingredients may be the key active anti-IS ingredients of GBE. CONCLUSION: This study revealed the key active components and the anti-IS mechanism of GBE. It also provided a simple and sensitive method for the quality control of related preparations.

A brain-tumor neural circuit controls breast cancer progression in mice.

Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.

Dioscin ameliorates doxorubicin-induced heart failure via inhibiting autophagy and apoptosis by controlling the PDK1-mediated Akt/mTOR signaling pathway.

Heart failure (HF) is a disease with high mortality and morbidity rate. Autophagy is critically implicated in HF progression. The current research was designed to investigate the function of Dioscin on oxidative stress, autophagy, and apoptosis in HF. In this study, doxorubicin (Dox) was employed to induce HF model and HL-1 cell damage model. Echocardiography implied that Dioscin could dramatically relieve heart function in vivo. Western blotting determined that Dioscin treatment reversed the promotive effect of autophagy caused by Dox through modulating levels of key autophagy-associated molecules, including Atg5 and Beclin1. Dioscin also impaired apoptosis by regulating apoptosis-related protein, including Bcl-2 and cleaved caspase-3 following Dox treatment in vivo and in vitro. Furthermore, the impacts of Dioscin were mediated by upregulation of PDK1-mediated Akt/mTOR signaling. The mTOR inhibitor (rapamycin) could counteract the therapeutic impact of Dioscin in vitro. Taken together, Dioscin could relieve cardiac function through blocking apoptosis and autophagy by activating the PDK1-elicited Akt/mTOR pathway.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

Quantitative Evaluation of the Normal Cervix, Cervical Cancer, and Cervical Precancerous Changes Via Real-Time Shear Wave Elastography.

OBJECTIVES: The present study aims to evaluate the clinical application values of ultrasound real-time shear wave elastography (SWE) in the diagnosis and differential diagnosis of cervical cancer (CC). METHODS: A total of 285 married female patients were screened and divided into three groups according to the results of the pathological examination and the cervical ThinPrep cytologic test: 1) the CC group (n = 94); 2) the cervical intraepithelial neoplasia (CIN) group (n = 91); and 3) the normal control group (n = 100). The maximum Young's modulus (Emax), mean Young's modulus (Emean), minimum Young's modulus (Emin), and Young's modulus stability (Esd) in each group were measured and statistically analyzed. RESULTS: There were no statistically significant differences in Emax, Emean, Emin, and Esd values between the anterior and posterior cervical walls, premenopausal and postmenopausal women, and nonparturient and parturient women in the normal control group. The Emax, Emean, Emin, and Esd values in the CIN group showed no statistically significant differences in different periods when compared with the control group. The differences between the normal control group and the CC group were statistically significant; the CC group showed no statistically significant differences in Emax, Emean, Emin, and Esd values at different clinical stages and in different pathological types. The cutoff value of Emax for CC diagnosis, which was of the highest accuracy (89.7%), was 43.48 kpa. CONCLUSION: Ultrasound real-time SWE can be applied to CC diagnosis.

Fabrication of anti-icing/de-icing surfaces by femtosecond laser.

In this minireview, we comprehensively reviewed recent progress on fabricating anti-icing/de-icing surfaces by femtosecond laser technologies. Typical bioinspired micro-/nano-structures fabrication strategies, superhydrophobic surfaces with anti-icing properties, and photothermal surfaces with de-icing properties are summarized. At last, we discussed challenges and prospects in anti-icing/de-icing surfaces fabricated by femtosecond laser technologies.

A new technique for performing interstitial implants for gynecologic malignancies using transvaginal ultrasound guidance.

Objectives: This study concerns a new technique that aims to achieve precise interstitial brachytherapy of pelvic recurrent tumors under transvaginal ultrasound (US) guidance, enhance the conformity index of the brachytherapy (BT), and improve the curative effect of radiotherapy for gynecological oncology patients with pelvic relapse. Methods: A real-time transvaginal US-guided interstitial implant device was developed to assist in implant BT. Prior to implant brachytherapy, the size and location of the tumor in the pelvis and the interrelationship with adjacent organs were first assessed with intracavitary ultrasound. The transvaginal US-guided interstitial implant device was then placed on the endoluminal ultrasound probe, the probe was oriented intravaginally to determine a safe needle path, the implant needle was placed into the needle passage of the device, and the implant needle was inserted into the tumor tissue in the direction guided by the ultrasound puncture guide line. After the implant needle was placed in place, the cover of the transvaginal US-guided interstitial implant device was opened perpendicular to the ultrasound probe, and the needle was separated from the ultrasound probe smoothly, and then the cover was re-covered for subsequent implantation. Results: In this study, 56 patients who underwent real-time transvaginal ultrasound-guided implantation for gynecologic oncology were enrolled, and insertion of 736 implant needles was completed. Among them, 13 patients had recurrent pelvic tumors after cervical cancer surgery and 6 patients had recurrent pelvic tumors after endometrial cancer surgery. Thirty-two patients who underwent radical radiation therapy for cervical cancer did not have adequate regression of parametrial invaded tissue after completion of standard EBRT treatment; and 5 patients had recurrent tumors in the radiation field after previous standard course of pelvic radiotherapy. The accuracy of the implant therapy was improved. The radiotherapy dose for recurrent pelvic masses was successfully increased, and the cumulative dose of external irradiation combined with BT was augmented to 80-100 Gy. The use of a new device for transvaginal implant for recurrent masses located in the lateral wall of the pelvic cavity was successful. Conclusion: This intravascular US-guided interstitial implant device can realize interstitial implant with the shortest path under transvaginal US guidance. With convenient operation, high precision, and good security, the device not only improves the accuracy of implant therapy, but it also reduces the risks of anesthesia and organ injury, so it is suitable for widespread promotion and use.

Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1­G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1­G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7­G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9­G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.

Concurrent lung adenocarcinoma and bladder diffuse large B-cell lymphoma: a case report and literature review.

Lung adenocarcinoma is one of the most common solid tumors, and diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of adult non-Hodgkin's lymphoma. Although extra-nodular lesions are frequently observed in patients with DLBCL, urinary bladder involvement is rare. We report the case of a 77-year-old woman with lung adenocarcinoma who was diagnosed with a second primary bladder DLBCL, 9 months after treatment with molecular targeted drugs. Simultaneous therapies for her lymphoma with lenalidomide and rituximab and a tyrosine kinase inhibitor therapy for her lung cancer were both effective. This result was consistent with previous reports suggesting that patients unable to tolerate intensive chemotherapy could benefit from targeted therapies. Current research into the use of lenalidomide for the treatment of lymphomas and solid tumors is promising in terms of exploring immunotherapy as an alternative option for patients with concurrent solid tumors and lymphomas who have poor tolerance to radiotherapy and chemotherapy.

[The Expression and Clinical Correlation of the CD68 Factor in Acute Myeloid Leukemia Patients].

OBJECTIVE: To analyze the expression and clinical characteristics of CD68 in bone marrow and peripheral blood of patients with acute myeloid leukemia (AML). METHODS: The expression of CD68 in bone marrow blast cells was detected by four-color flow cytometry in 50 newly diagnosed AML patients and 23 controls. The expression of CD68 in peripheral blood of 85 newly diagnosed AML patients, 29 remission AML patients and 24 controls was detected by ELISA. The correlation between the expression rate of non-M3 AML bone marrow CD68, peripheral blood CD68 concentration and white blood cell count and other clinical data was compared respectively. RESULTS: The median CD68 expression rate in myeloid leukemia cells of non-M3 AML patients was 19.7%, significantly higher than control (0.2%) (P<0.001). The median concentration of non-M3 CD68 in peripheral blood was 67.97 pg/ml, significantly higher than in control (29.94 pg/ml)（P<0.01）. There was no statistically significant difference in the plasma CD68 concentration of the peripheral blood between the newly diagnosed (45.72 pg/ml) and the remission stage (55.12 pg/ml) of non-M3 AML patients by paired analysis (P>0.05). The results showed that the higher the expression rate of CD68 in bone marrow, the higher the count of white blood cells in peripheral blood, and the lower the count of hemoglobin and platelet in peripheral blood. The higher the plasma concentration of CD68 in peripheral blood, the higher the white blood cell count and the lower the complete remission rate. CONCLUSION: The expression of CD68 both in bone marrow and peripheral blood of patients with non-M3 AML is higher than that of control group. Patients with high expression of CD68 show a low rate of complete remission, suggesting that the expression level of CD68 is correlated with treatment response.

Response of autoimmune and inflammatory disorders in myelodysplastic syndromes to 5-azacytidine: report of two cases and literature review.

Paraneoplastic autoimmune and inflammatory disorders are often associated with myelodysplastic syndromes (MDS). The etiopathogenesis of MDS-associated autoimmune and inflammatory disorders is still unclear and treatment options are limited. Patients with MDS are at high risk of infections, which can be increased by the use of steroids. In the present study, we report on two patients with MDS-related autoimmune and inflammatory disorders who were in remission and reduced the steroid dose with 5-azacytidine treatment. The first case was a 67-year-old patient diagnosed with MDS and the whole-body erythroderma was the chief complaint. When the patient was treated with decitabine, steroid treatment was needed to control the erythroderma. When we changed decitabine to 5-azacytidine, both his erythroderma and his dependency on the steroid treatment were resolved. The second patient was a 68-year-old man with MDS who presented with Sweet's syndrome. Sweet's syndrome was completely treated after the first cycle of 5-azacytidine. In addition, Sweet's syndrome can occur as an adverse reaction of 5-azacitidine, so we illustrate that it is important to distinguish whether Sweet's syndrome is MDS-related skin disorders or 5-azacitidine-related skin side-effects.

Transvaginal Real-Time Shear Wave Elastography in the Diagnosis of Endometrial Lesions.

BACKGROUND: To explore the value of transvaginal real-time shear wave elastography (SWE) in the diagnosis of endometrial lesions. METHODS: A total of 140 female patients with endometrial lesions, confirmed by pathological results, were divided into three groups: 45 cases of endometrial polyps, 29 cases of endometrial hyperplasia and 66 cases of endometrial cancer. A total of 100 cases of normal endometrium were used as the control group, including 52 cases in the proliferative stage and 48 cases in the secretory stage. Transvaginal real-time shear wave elastography was performed in all four groups. RESULTS: Emean, Emax and Esd were expressed as the average standard deviation. Among the control group, the results were 26.24±9.74, 38.09±9.18, and 4.25±2.73 kPa, respectively, in the proliferative endometrium cases and 12.51±7.46, 27.22±11.32, 4.40±2.52 kPa, respectively, in the secretory endometrium cases. Among the experimental group, the result was 15.68±8.18, 27.28±10.28 and 3.62±1.81 kPa respectively in the endometrial polyps cases; 21.20 ± 12.57, 36.32 ± 15.04, and 5.09 ±3.93 kPa in the endometrial hyperplasia cases; 49.36±25.51, 86.66±42.27 and 14.86±10.63 kPa in the endometrial cancer cases. The difference was statistically significant (P <0.05). When the truncation values of Emean, Emax and Esd were 28.50, 52.45 and 9.05 kPa, respectively, to distinguish between normal endometrium and endometrial cancer, Emax has the highest diagnostic value. CONCLUSION: Real-time SWE technology might be used as an auxiliary method in the diagnosis and differential diagnosis of endometrial cancer. More quantitative indicators are conducive to diagnosis.

A novel double target fluorescence probe for Al3+/Mg2+ detection with distinctively different responses and its applications in cell imaging.

The metal cations, Al3+ and Mg2+, could affect human health and cell biological processes. Their fast and selective detection using one probe remains a challenge. A novel fluorescence probe, N'-((1-hydroxynaphthalen-2-yl)methylene)isoquinoline-3-carbohydrazide (NHMI), was developed for selectively monitoring Al3+ and Mg2+. The probe NHMI showed a distinctive "turn-on" fluorescence signal towards Al3+ and Mg2+ (cyan for Al3+ with 2556-folds enhancement and yellow for Mg2+ with 88-folds enhancement), which is quite distinct from other metal cations and allows for naked-eye detection. This interesting response was attributed to the influence of PET, ESIPT process and CHEF effect, when Al3+ or Mg2+ chelated with NHMI. Furthermore, the fluorescence titration experiments manifested that the detection limit of probe NHMI for Al3+/Mg2+ was as low as 1.20 × 10-8 M and 7.69 × 10-8 M, respectively. The formed complexes NHMI-Al3+ and NHMI-Mg2+ were analyzed by Job's plot, ESI-MS, 1H NMR and FT-IR. The coordination pockets and fluorescence mechanisms of two metal complexes were explored by density functional theory calculation. Moreover, NHMI showed low cytotoxicity and good cell permeability. Fluorescence bioimaging of Al3+/Mg2+ in MCF-7 cells with NHMI indicated its potential application in biological diagnostic analysis.

Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Radix Kansui Stir-Fried with Vinegar Reduces Radix Kansui-Related Hepatotoxicity in Mice via Mitochondrial Pathway.

OBJECTIVE: To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice. METHODS: According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P<0.01). Compared with the RK group, VRK group induced significant increase on Bcl-2 protein expression, and decreased the caspase-3, NF- κ B and ICAM-1 protein expression (P<0.05 or P<0.01). CONCLUSION: The mechanism of reduced hepatotoxicity of VRK may be associated with the reduced inflammation, regulation of antiapoptotic and proapoptotic mediators in the mitochondrial pathway.

Application Value of Real-Time Shear Wave Elastography in Diagnosing the Depth of Infiltrating Muscular Layer of Endometrial Cancer.

OBJECTIVE: To explore the clinical value of real-time shear wave ultrasonic elastography in diagnosing the depth of infiltrating muscularis of endometrial cancer. METHODS: Seventy-one patients with stage I endometrial cancer infiltrating the myometrium and 37 patients with normal physical examination were enrolled and divided into three groups: endometrial cancer superficial muscle infiltration group, endometrial cancer deep muscle infiltration group, and normal control group. After completing 2-dimensional ultrasound examination, each patient switched to the real-time shear wave elastography mode to measure the elasticity values Emax, Emean, and Esd. RESULTS: For control group, comparison of elastic modulus values between superficial muscular layer near the intimal surface and the deep muscular layer near the serosa surface showed no difference (P > 0.05). For endometrial cancer superficial muscular infiltration group, significant difference was found regarding the elastic modulus values of infiltrated muscular layer and uninfiltrated muscular layer (Emax and Emean) without difference for Esd (P > 0.05). A significant difference of elastic modulus was observed between control group and deep myometrial infiltration group (P < 0.05) without difference of Emean or Emax but with difference of Esd. The accuracy in diagnosing muscular layer infiltration was 78.9% for Emax cutoff and 82.5% for Emean cutoff. The rate of using Emax ≥32.22 kPa or Emean ≥27.54 kPa as the ultrasound standard for diagnosing myometrium infiltration was 92.9%. The accuracy for the diagnosis of muscular layer infiltration was 96.1% for Emax cutoff, 94.1% for Emean cutoff and 86.3% for Esd cutoff. CONCLUSION: Real-time shear wave elastography is helpful to determine the depth of infiltrating myometrium of endometrial cancer.

A novel hydrazide Schiff base self-assembled nanoprobe for selective detection of human serum albumin and its applications in renal disease surveillance.

Human serum albumin (HSA) is considered as a biomarker for the early diagnosis of renal disease, therefore identifying and detecting HSA in biological fluids (especially urine) with an easy method is of great importance. Herein, we report a novel hydrazide Schiff base fluorescent probe N'-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)pyrazine-2-carbohydrazide (NPC), which self-assembled into nanoparticles in aqueous solution. Based on disassembly-induced emission and the site-specific recognition mechanism, the binding of NPC with HSA resulted in a fluorescence "turn-on" response. Probe NPC exhibited superior selectivity and sensitivity toward HSA with a detection limit of 0.59 mg L-1 in PBS and 0.56 mg L-1 in the urine sample. The site-binding mechanism of NPC with HSA was explored by fluorescence quenching study, Job's plot analysis, HSA destruction, site marker displacement and molecular docking. Fluorescence imaging of HSA in MCF-7 cells was achieved by using a non-toxic NPC probe, suggesting that NPC could be applied to visualize the level of HSA in vivo. More importantly, further practical applications of probe NPC in human urine samples were achieved with satisfactory results by using a fluorometer or test paper, which could provide extensive application in clinical diagnosis.