Detection of HER2 expression using 99mTc-NM-02 nanobody in patients with breast cancer: a non-randomized, non-blinded clinical trial.

BACKGROUND: 99mTc radiolabeled nanobody NM-02 (99mTc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99mTc-NM-02 uptake and HER2 expression in patients with breast cancer. METHODS: Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99mTc-NM-02 SPECT/computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group (n = 24) and the treated group (n = 6). The maximal standard uptake value (SUVmax) of 18F-FDG and SUVmax and mean SUV (SUVmean) of 99mTc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression. RESULTS: No meaningful relationship was observed between 18F-FDG uptake and HER2 expression in 30 patients with breast cancer. 99mTc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. 99mTc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. 99mTc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from 18F-FDG PET/CT. 99mTc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer. CONCLUSIONS: 99mTc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer. TRIAL REGISTRATION: NCT04674722, Date of registration: December 19, 2020.

Impact of ambient temperature, diurnal temperature range on hyperventilation syndrome emergency admission: a time-series analysis in Beijing, China.

OBJECTIVES: To assess the association between ambient temperature and diurnal temperature range (DTR) on emergency admissions for hyperventilation syndrome (HVS). DESIGN: Distributed lag non-linear model design was used with a lag time to 5 days. SETTING: Emergency admission data used were from the Beijing Red Cross Emergency Centre (2017-2018). PARTICIPANTS AND EXPOSURE: Cases were those with emergency visits to the Beijing Emergency Center during the period 2017-2018 and who were given the primary outcome indicator defined as HVS according to the International Classification of Diseases, 10th edition code F45.303. Ambient temperature and DTR were used as exposure factors with adjustments for relative humidity, wind speed, precipitation, seasonality long-term trend and day of the week. MAIN OUTCOME MEASURE: We used the minimum emergency visits temperature as a reference to indicate the relative risk with 95% CI of exposure-response for the risk of HVS visits at different temperatures. RESULTS: A u-shape was described between ambient temperature and HVS visits, with a minimum risk at 12°C. Moderate heat (23°C) at lag (0-3) days, extreme heat at lag 0 days, had greatest relative risks on HVS visits, with 2.021 (95% CI 1.101 to 3.71) and 1.995 (95% CI 1.016 to 3.915), respectively. A stronger association between HVS visits and temperature was found in women and aged ≤44 years. Notably, the relationship between DTR and HVS visits appeared a reverse u-shaped. Low DTR (4°C) effect appeared at lag (0-1) days with 0.589 (95% CI 0.395 to 0.878), lasting until lag (0-3) days with 0.535 (95% CI 0.319 to 0.897) and was associated with a reduced risk of HVS visits in women and those aged ≤44 years. CONCLUSIONS: Ambient temperature and DTR were associated with HVS visits, appearing a differentiation in gender and age groups. Timely prevention strategies during high temperatures and control mild changes in temperature might reduce the risk of HVS.

Structural characterization of a distinct fucan sulfate from Pattalus mollis through an oligosaccharide mapping approach.

The elucidation of the precise structure of fucan sulfate is essential for understanding the structure-activity relationship and promoting potential biomedical applications. In this work, the structure of a distinct fucan sulfate fraction V (PmFS in Ref 15 and FSV in Ref 16 → PFV) from Pattalus mollis was investigated using an oligosaccharide mapping approach. Six size-homogeneous fractions were purified from the mild acid hydrolyzed PFV and identified as fucitols, disaccharides and trisaccharides by 1D/2D NMR and MS analysis. Significantly, the sulfation pattern, glycosidic linkages, and sequences of all the oligosaccharides were unambiguously identified. The common 2-desulfation of the reducing end residue of the oligosaccharides was observed. Overall, the backbone of PFV was composed of L-Fuc2S (major) and L-Fuc3S (minor) linked by α1,4 glycosidic bonds. Importantly, the branches contain both monosaccharide and disaccharide linked to the backbone by α1,3 glycosidic linkages. Thus, the tentative structure of natural PFV was shown to be {-(R-α1,3)-L-Fuc2S-α1,4-(L-Fuc2S/3S-α1,4)x-}n, where R is L-Fuc(2S)4S-α1,3/4-L-Fuc4S(0S)- or L-Fuc(2S)4S-. Our results provide insight into the heterogeneous structure of the fucan sulfate found in sea cucumbers. Additionally, PFV and its fractions showed strong anticoagulant and anti-iXase activities, which may be related to the distinct structure of PFV.

Constructing "smart" chelators by using an activatable prochelator strategy for the treatment of Wilson's disease.

Wilson's disease (WD) is a genetic disorder that primarily leads to the pathological accumulation of copper (Cu) in the liver, causing an abnormal increase in reactive oxygen species (ROS). The prevailing clinical therapy for WD involves lifelong use of Cu chelation drugs to facilitate Cu excretion in patients. However, most available drugs exert severely side-effects due to their non-specific excretion of Cu, unsuitable for long-term use. In this study, we construct a prochelator that enables precise and controlled delivery of Cu chelator drugs to the liver in WD model, circumventing toxic side effects on other organs and normal tissues. This innovative prochelator rapidly releases the chelator and the fluorescent molecule methylene blue (MB) upon activation by ROS highly expressed in the liver of WD. The released chelator coordinates with Cu, efficiently aiding in Cu removal from the body and effectively inhibiting the pathological progression of WD.

Discovery and Bioinspired Synthesis of Salpratone A.

Salpratone A (1), a novel abietane diterpenoid containing a unique cis-fused A/B ring, was isolated from Salvia prattii. Bioactivity studies showed that 1 has potent activity in inhibiting platelet aggregation induced by multiple agonists as well as antithrombotic efficacy in the FeCl3-induced rat in vivo thrombosis model. Furthermore, a bioinspired synthesis of 1 from the abundant natural product ferruginol was achieved in 6 steps with a 22% overall yield. The key steps include a stereoselective allyl oxidation and a subsequent regioselective Meinwald rearrangement.

Duchenne muscular dystrophy treatment with lentiviral vector containing mini-dystrophin gene in vivo.

Duchenne muscular dystrophy (DMD) is an incurable X-linked recessive genetic disease caused by mutations in the dystrophin gene. Many researchers aim to restore truncated dystrophin via viral vectors. However, the low packaging capacity and immunogenicity of vectors have hampered their clinical application. Herein, we constructed four lentiviral vectors with truncated and sequence-optimized dystrophin genes driven by muscle-specific promoters. The four lentiviral vectors stably expressed mini-dystrophin in C2C12 muscle cells in vitro. To estimate the treatment effect in vivo, we transferred the lentiviral vectors into neonatal C57BL/10ScSn-Dmdmdx mice through local injection. The levels of modified dystrophin expression increased, and their distribution was also restored in treated mice. At the same time, they exhibited the restoration of pull force and a decrease in the number of mononuclear cells. The remissions lasted 3-6 months in vivo. Moreover, no integration sites of vectors were distributed into the oncogenes. In summary, this study preliminarily demonstrated the feasibility and safety of lentiviral vectors with mini-dystrophin for DMD gene therapy and provided a new strategy to restore truncated dystrophin.

Economic Evaluation of the Comprehensive AIDS Prevention and Control Program - Tianjin Municipality, China, 2011-2022.

What is already known about this topic?: Acquired immunodeficiency syndrome (AIDS) represents a significant public health challenge globally, not only inflicting harm on the health of individuals but also placing a considerable economic strain on society. What is added by this report?: This study represents the inaugural report on the potential reduction in economic burden attributable to human immunodeficiency virus (HIV) prevention strategies in Tianjin. Between 2011 and 2022, it is estimated that effective measures could prevent 2,965 new HIV infections and avert 658 deaths, resulting in an economic benefit of approximately 14.437 billion Chinese Yuan. What are the implications for public health practice?: The findings of this study offer valuable evidence to inform the development of localized HIV prevention and control strategies, as well as to guide public health policymaking.

Structural Characterization and Anticoagulant Activities of a Keratan Sulfate-like Polysaccharide from the Sea Cucumber Holothuria fuscopunctata.

A sulfated polysaccharide (AG) was extracted and isolated from the sea cucumber H. fuscopunctata, consisting of GlcNAc, GalNAc, Gal, Fuc and lacking any uronic acid residues. Importantly, several chemical depolymerization methods were used to elucidate the structure of the AG through a bottom-up strategy. A highly sulfated galactose (oAG-1) and two disaccharides labeled with 2,5-anhydro-D-mannose (oAG-2, oAG-3) were obtained from the deaminative depolymerized product along with the structures of the disaccharide derivatives (oAG-4~oAG-6) identified from the free radical depolymerized product, suggesting that the repeating building blocks in a natural AG should comprise the disaccharide ß-D-GalS-1,4-D-GlcNAc6S. The possible disaccharide side chains (bAG-1) were obtained with mild acid hydrolysis. Thus, a natural AG may consist of a keratan sulfate-like (KS-like) glycosaminoglycan with diverse modifications, including the sulfation types of the Gal residue and the possible disaccharide branches α-D-GalNAc4S6S-1,2-α/ß-L-Fuc3S linked to the KS-like chain. Additionally, the anticoagulant activities of the AG and its depolymerized products (dAG1-9) were evaluated in vitro using normal human plasma. The AG could prolong activated partial thromboplastin time (APTT) in a dose-dependent manner, and the activity potency was positively related to the chain length. The AG and dAG1-dAG3 could prolong thrombin time (TT), while they had little effect on prothrombin time (PT). The results indicate that the AG could inhibit the intrinsic and common coagulation pathways.

Comparative Assessment of APTT Reagents for Evaluating Anticoagulant Sensitivity of Fucosylated Glycosaminoglycans (FGs) Derived from Sea Cucumbers.

Fucosylated glycosaminoglycans (FGs) derived from sea cucumbers exhibit potent intrinsic Xase (iXase) inhibition, anticoagulation, and antithrombosis. Plasma activated partial thromboplastin time (APTT), a widely used screening test worldwide, is crucial for evaluating anticoagulant efficacy. However, the applicability of these commercially available APTT reagents for assessing anticoagulation of FGs remains unreported. In this study, we investigated the disparity between ellagic acid and colloidal silica APTT reagents in evaluating anticoagulation of dHG-5 and dHLFG-4, two depolymerized FGs, and elucidated the underlying rationale. The results demonstrated that dHG-5 and dHLFG-4 exhibited heightened sensitivity to the ellagic acid APTT reagent both in vitro and in vivo, and did not significantly affect the activation of APTT reagents for plasma. In addition, both ellagic acid and colloidal silica APTT reagents inhibited the anti-iXase of dHG-5 and dHLFG-4, and the inhibition of the ellagic acid APTT reagent was less pronounced compared to the colloidal silica APTT reagent. These findings suggest that the reduced impact of the ellagic acid APTT reagent on the anti-iXase activity of dHG-5 and dHLFG-4 is responsible for the increased sensitivity in plasma APTT analysis. This study offers valuable insights into the characteristics of two APTT reagents applied for assessing the anticoagulant activity of FG-related compounds.

Phosphorus core-shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters.

Nanoplatforms with amplified passive tumor targeting and enhanced protein resistance can evade unnecessary uptake by the reticuloendothelial system and achieve high tumor retention for accurate tumor theranostics. To achieve this goal, we here constructed phosphorus core-shell tecto dendrimers (CSTDs) with a rigid aromatic backbone core as a nanoplatform for enhanced fluorescence and single-photon emission computed tomography (SPECT) dual-mode imaging of tumors. In this study, the phosphorus P-G2.5/G3 CSTDs (G denotes generation) were partially conjugated with tetraazacyclododecane tetraacetic acid (DOTA), cyanine5.5 (Cy5.5) and 1,3-propane sulfonate (1,3-PS) and then labeled with 99mTc. The formed P-G2.5/G3-DOTA-Cy5.5-PS CSTDs possess good monodispersity with a particle size of 10.1 nm and desired protein resistance and cytocompatibility. Strikingly, compared to the counterpart material G3/G3-DOTA-Cy5.5-PS with both the core and shell components being soft poly(amidoamine) dendrimers, the developed P-G2.5/G3-DOTA-Cy5.5-PS complexes allow for more efficient cellular uptake and more significant penetration in 3-dimensional tumor spheroids in vitro, as well as more significant tumor retention and accumulation for enhanced dual-mode fluorescence and SPECT (after labelling with 99mTc) tumor imaging in vivo. Our studies suggest that the rigidity of the core for the constructed CSTDs matters in the amplification of the tumor enhanced permeability retention (EPR) effect for improved cancer nanomedicine development.

Branch distribution pattern and anticoagulant activity of a fucosylated chondroitin sulfate from Phyllophorella kohkutiensis.

Fucosylated chondroitin sulfate (FCS) extracted from Phyllophorella kohkutiensis (PkFCS) is composed of d-GalNAc, d-GlcA, l-Fuc and -SO42-. According to the defined structures revealed by NMR spectra of the branches released by mild acid hydrolysis and oligosaccharides generated by ß-eliminative depolymerization, the backbone of PkFCS is CS-E, and the branch types attached to C-3 of d-GlcA include l-Fuc2S4S, l-Fuc3S4S, l-Fuc4S, and the disaccharide α-d-GalNAc-1,2-α-l-Fuc3S4S with the ratio of 43:13:22:22. Notably, novel heptasaccharide and hendecasaccharide were identified that are branched with continuous distribution of the disaccharide. The structural sequences of the oligosaccharides indicate that three unique structural motifs are present in the entire PkFCS polymer, including a motif branched with randomly distributed different sulfated l-Fuc units, a motif containing regular l-Fuc2S4S branches and a motif enriched in α-d-GalNAc-1,2-α-l-Fuc3S4S. This is the first report about the distribution pattern of diverse branches in natural FCS. Natural PkFCS exhibited potent anticoagulant activity on APTT prolonging and anti-iXase activity. Regarding the structurally defined oligosaccharides with sulfated fucosyl side chains, octasaccharide (Pk4b) is the minimum fragment responsible for its anticoagulant activity correlated with anti-iXase. However, further glycosyl modification with a non-sulfated d-GalNAc at the C-2 position of l-Fuc3S4S could significantly decrease the anticoagulant and anti-iXase activity.

11,12-seco-Abietane-type diterpene lactones with potential antiplatelet activity from Salvia prattii.

Eleven new abietane-type diterpene lactones, salpratlactones D-N (1-11), including five 11,12-seco-11-nor-abietane diterpenes (1-5), four 11,12-seco-abietane diterpenes (6-9), two 20(10 â†’ 5)-abeo-4,5;11,12-bis-seco-abietane diterpenes (10-11), and two known analogues (12-13), were characterized from Salvia prattii. Notably, compounds 1-3 were characterized by a unique linear 6/6/6 tricyclic skeleton. The structures were established by spectroscopic data interpretation, calculated NMR-DP4+ and electronic circular dichroism analysis, as well as single-crystal X-ray diffraction. A bioactivity study showed that 1, 2, 5, 11, and 12 can potently inhibit platelet aggregation induced by arachidonic acid (AA), with IC50 values of 5.66-16.10 µg/ml, stronger than aspirin. In addition, the lactate dehydrogenase assay showed that they had no effect on platelet integrity. Structurally, the same 1,2-benzopyrone fragments of 1, 2, and 5 should be the important pharmacophore for antiplatelet activity.

Celastrol as an intestinal FXR inhibitor triggers tripolide-induced intestinal bleeding: Underlying mechanism of gastrointestinal injury induced by Tripterygium wilfordii.

BACKGROUND: Tripterygium wilfordii has been widely used for the treatment of rheumatoid arthritis, which is frequently accompanied by severe gastrointestinal damage. The molecular mechanism underlying the gastrointestinal injury of Tripterygium wilfordii are yet to be elucidated. METHODS: Transmission electron microscopy, and pathological and biochemical analyses were applied to assess intestinal bleeding. Metabolic changes in the serum and intestine were determined by metabolomics. In vivo (time-dependent effect and dose-response) and in vitro (double luciferase reporter gene system, DRATs, molecular docking, HepG2 cells and small intestinal organoids) studies were used to identify the inhibitory role of celastrol on intestinal farnesoid X receptor (FXR) signaling. Fxr-knockout mice and FXR inhibitors and agonists were used to evaluate the role of FXR in the intestinal bleeding induced by Tripterygium wilfordii. RESULTS: Co-treatment with triptolide + celastrol (from Tripterygium wilfordii) induced intestinal bleeding in mice. Metabolomic analysis indicated that celastrol suppressed intestinal FXR signaling, and further molecular studies revealed that celastrol was a novel intestinal FXR antagonist. In Fxr-knockout mice or the wild-type mice pre-treated with pharmacological inhibitors of FXR, triptolide alone could activate the duodenal JNK pathway and induce intestinal bleeding, which recapitulated the pathogenic features obtained by co-treatment with triptolide and celastrol. Lastly, intestinal bleeding induced by co-treatment with triptolide and celastrol could be effectively attenuated by the FXR or gut-restricted FXR agonist through downregulation of the duodenal JNK pathway. CONCLUSIONS: The synergistic effect between triptolide and celastrol contributed to the gastrointestinal injury induced by Tripterygium wilfordii via dysregulation of the FXR-JNK axis, suggesting that celastrol should be included in the quality standards system for evaluation of Tripterygium wilfordii preparations. Determining the mechanism of the FXR-JNK axis in intestinal bleeding could aid in the identification of additional therapeutic targets for the treatment of gastrointestinal hemorrhage diseases. This study also provides a new standard for the quality assessment of Tripterygium wilfordii used in the treatment of gastrointestinal disorders.

Microextraction of essential oils: A review.

Liquid phase microextraction (LPME) and solid phase microextraction (SPME) are popular extraction techniques for sample preparation due to their green and highly efficient single-step extraction efficiency. With the increasing attention to essential oils, their evaluation and analysis are significant in analytical sciences. In this review, starting from a brief description of the recent advances in the last decade, the attention has been focused on the up-to-date research works and applications based on liquid and solid phase microextraction for essential oil analyses. Particular attention has been given to the approaches using ionic liquids, eutectic solvents, gas flow assisted, and novel composite materials. In the end, the technological convergence of novel microextraction of essential oils in the future has been prospected.

[Diagnostic and Prognostic Value of 18F-FDG PET/CT in Bone Marrow Infiltration of Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the diagnostic value of 18F-FDG PET/CT in bone marrow infiltration (BMI) of newly diagnosed diffuse large B-cell lymphoma (DLBCL), compared with the results of bone marrow biopsy (BMB) and investigate whether the BMI diagnosed by 18F-FDG PET/CT and other factors have independent prognostic values. METHODS: Ninety-four newly diagnosed DLBCL patients who underwent PET/CT in Clinical Medical College of Shanghai General Hospital of Nanjing Medical University were included. BMB was performed within 2 weeks before or after PET/CT, and standardized treatment was performed after PET/CT. The manifestations of bone marrow (BM) FDG uptake were recorded. The diagnostic criteria of BMI were BMB positive or focal BM FDG uptake confirmed by imaging follow-up. The relationship between clinical features and BM FDG uptake and the values of PET/CT and BMB in the diagnosis of BMI was analyzed. The progression-free survival (PFS) was analyzed by Kaplan-Meier survival curves, log-rank test was used to compare PFS rate, and Cox regression model was used to analyze the independent risk factors affecting PFS. RESULTS: Among 94 DLBCL patients, 34 patients showed focal BM uptake (fPET), 7 patients showed super BM uptake (sBMU), 11 patients showed diffuse homogenous uptake higher than liver (dPET), and the other 42 patients had normal BM uptake (nPET) (lower than liver). BMB positive was found in all sBMU patients, in 20.6%(7/34) of fPET patients, and in 27.3% (3/11) of dPET patients. All nPET patients had negative BMB results. dPET patients were associated with lower hemoglobin level and leukocyte count compared with nPET group (P < 0.001, P =0.026). Compared with fPET patients, sBMU patients were more likely to have B symptoms and elevated lactate dehydrogenase (LDH). A total of 44 patients were diagnosed BMI, including 17 cases with BMB+. The sensitivity and specificity of BMB in the diagnosis of BMI was 38.6% (17/44) and 100% (50/50), respectively. Using fPET and sBMU as criteria of PET BMI, the diagnostic sensitivity and specificity of PET/CT was 93.2% (41/44) and 100% (50/50), respectively. Kaplan-Meier analysis showed that there was no significant difference in 2-year PFS rate between nPET and dPET patients (P >0.05), while sBMU patients had lower 2-year PFS rate compared with fPET patients (P < 0.001). Multivariate analysis showed that higher Ann Arbor stage (HR=9.010, P =0.04) and sBMU (HR=3.964, P =0.002) were independent risk factors affecting PFS. CONCLUSIONS: Increased BM FDG uptake of DLBCL can be manifested as dPET, fPET and sBMU. fPET and sBMU can replace BMB to diagnose BMI. Although dPET cannot completely exclude the possibility of BMI, it does not affect the prognosis, so it can be diagnosed as PET BMI negative. sBMU is an independent prognostic risk factor.

Effect of short-term exposure to ambient air pollutants on non-accidental mortality in emergency department visits: a time-series study.

Objectives: Exposure to air pollution has been linked to an increased risk of premature mortality. However, the acute effects of air pollution on the risk of non-accidental mortality have not been extensively researched in developing countries, and the findings thus far have been inconsistent. Therefore, this study aimed to examine the association between short-term exposure to six pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and non-accidental mortality in Beijing, China. Methods: Daily data on non-accidental deaths were gathered from 1 January 2017 to 31 December 2018. Air pollution data for the same period were collected from 35 fixed-site air quality monitoring stations in Beijing. Generalized additive models (GAM) based on Poisson regression were used to investigate the association between non-accidental mortality in emergency department visits and the daily average levels of air pollutants. Results: There were 8,676 non-accidental deaths recorded during 2017-2018. After sensitivity analysis, short-term exposure to air pollutants, particularly gaseous pollutants, was linked to non-accidental mortality. Specifically, for every 10 µg/m3 increase (5 µg/m3 in SO2, 0.5 mg/m3 in CO) of SO2 (lag 04), NO2 (lag 04), O3 (lag 05), and CO (lag 04), the relative risk (RR) values were 1.054 (95% CI: 1.009, 1.100), 1.038 (95% CI: 1.013, 1.063), 1.032 (95% CI: 1.011, 1.054), and 1.034 (95% CI: 1.004, 1.066), respectively. In terms of causes of death, short-term exposure to NO2, SO2, and O3 increased the risk of circulatory mortality. Further stratified analysis revealed that the stronger associations were presented in females for O3 while in males for CO. People aged 65 and over were strongly associated with ambient air pollution. Conclusions: Our study showed that ambient air pollutants were associated with non-accidental mortality. Our findings suggested that efforts to control gaseous pollution should be stepped up, and vulnerable groups should be the focus of health protection education.

Early Prediction of Epilepsy after Encephalitis in Childhood Based on EEG and Clinical Features.

Objective: The present study was designed to establish and evaluate an early prediction model of epilepsy after encephalitis in childhood based on electroencephalogram (ECG) and clinical features. Methods: 255 patients with encephalitis were randomly divided into training and verification sets and were divided into postencephalitic epilepsy (PE) and no postencephalitic epilepsy (no-PE) according to whether epilepsy occurred one year after discharge. Univariate and multivariate logistic regression analyses were used to screen the risk factors for PE. The identified risk factors were used to establish and verify a model. Results: This study included 255 patients with encephalitis, including 209 in the non-PE group and 46 in the PE group. Univariate and multiple logistic regression analysis showed that hemoglobin (OR = 0.968, 95% CI = 0.951-0.958), epilepsy frequency (OR = 0.968, 95% CI = 0.951-0.958), and ECG slow wave/fast wave frequency (S/F) in the occipital region were independent influencing factors for PE (P < 0.05).The prediction model is based on the above factors: -0.031 × hemoglobin -2.113 × epilepsy frequency + 7.836 × occipital region S/F + 1.595. In the training set and the validation set, the area under the ROC curve (AUC) of the model for the diagnosis of PE was 0.835 and 0.712, respectively. Conclusion: The peripheral blood hemoglobin, the number of epileptic seizures in the acute stage of encephalitis, and EEG slow wave/fast wave frequencies can be used as predictors of epilepsy after encephalitis.

The efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary lesions and metastasis in newly diagnosed prostate cancer.

Purpose: Compared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa). Methods: A retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3-4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression. Results: The SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS ≥8, and tPSA >20 ng/ml and GS≥8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P <0.05) in distant metastatic prediction. For both the guideline tPSA level (20 ng/ml) and the cut-off level (84.3 ng/ml), the difference in the distant metastasis detection rate between the low predicted tPSA group and the high predicted tPSA group was statistically significant (0% vs. 47.62%, P = 0.005; 9.09% vs. 88.89%, P = 0.000, respectively). Twenty patients with pathological 99mTc-PSMA avid only in the prostate beds underwent radical prostatectomy. Seven of them underwent lymph node dissection, a total of 35 lymph nodes were removed, and no lymph nodes were detected with metastasis, which was consistent with 99mTc-HYNIC-PSMA SPECT/CT. Conclusion: 99mTc-HYNIC-PSMA SPECT/CT is effective in the risk stratification and distant metastasis detection of primary PCa patients. It is of great value in guiding treatment strategies.

Oligomer-guided recognition of two fucan sulfate from Bohadschia argus and inhibition of P-selectin binding to its ligand.

Fucan sulfate (FS) from sea cucumber shows intriguing structure and extensive activities. Here, three homogeneous FS (BaFSI - III) were obtained from Bohadschia argus, followed with physicochemical properties analyses including monosaccharide composition, molecular weight, and sulfate content. BaFSI was proposed to carry a unique distribution pattern of sulfate groups as a novel sequence composed of domain A and domain B that formed by different FucS residues, markedly differing from FS reported before, according to the analyses of 12 oligosaccharides and a representative residual saccharide chain. BaFSII possessed a highly regular structure {4-L-Fuc3S-α1,}n according to its peroxide depolymerized product. BaFSIII was confirmed as a FS mixture bearing similar structural characteristics with BaFSI and BaFSII by means of mild acid hydrolysis and oligosaccharide analysis. Bioactivity assays showed that BaFSI and BaFSII could potently inhibit P-selectin binding to PSGL-1 and HL-60 cells. Structure-activity relationship analysis showed that molecular weight and sulfation pattern were the essential factors for the potent inhibition. Meanwhile, an acid hydrolysate of BaFSII with a molecular weight about 15 kDa exhibited a comparable inhibition with the native BaFSII. Given the potent activity and highly regular structure of BaFSII, it shows great potential for development as a P-selectin inhibitor.

Application of molecular dynamics simulation in self-assembled cancer nanomedicine.

Self-assembled nanomedicine holds great potential in cancer theragnostic. The structures and dynamics of nanomedicine can be affected by a variety of non-covalent interactions, so it is essential to ensure the self-assembly process at atomic level. Molecular dynamics (MD) simulation is a key technology to link microcosm and macroscale. Along with the rapid development of computational power and simulation methods, scientists could simulate the specific process of intermolecular interactions. Thus, some experimental observations could be explained at microscopic level and the nanomedicine synthesis process would have traces to follow. This review not only outlines the concept, basic principle, and the parameter setting of MD simulation, but also highlights the recent progress in MD simulation for self-assembled cancer nanomedicine. In addition, the physicochemical parameters of self-assembly structure and interaction between various assembled molecules under MD simulation are also discussed. Therefore, this review will help advanced and novice researchers to quickly zoom in on fundamental information and gather some thought-provoking ideas to advance this subfield of self-assembled cancer nanomedicine.