Nanocrystal technology changes the solubility and dissolution rate of insoluble drugs by reducing the particle size to the nanometer level.This technology is not limited by carrier materials and encapsulation rate.It is suitable for a variety of drug delivery routes and easy for industrial production.It has gradually become a cutting-edge hot technology in the international pharmaceutical field to improve the absorption of insoluble drugs and improve their bioavailability.This article introduces the influencing factors and challenges of nanocrystal drugs(NC)in parenteral,ocular,transdermal and pulmonary administration,and focuses on nanocrystal drugs that have been marketed or are still in the preclinical or clinical trial stages of these delivery systems,in order to provide some insight for the further development of poorly soluble drug nanocrystal preparations.

Objective:To summarize the clinical and EEG characteristics of children with self-limited epilepsy with centrotemporal spikes (SeLECTS), and explore the risk factors for comorbid attention-deficit hyperactivity disorder (ADHD).Methods:Demographic and medical history data, seizure characteristics, EEG data, and treatment information of 122 children with SeLECTS admitted to Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from July 2020 to March 2024 were collected. Based on Swanson, Nolan and Pelham-IV Rating Scale (SNAP-IV) results, these patients were divided into comorbid ADHD group ( n=64) and non-ADHD group ( n=58); the clinical data and EEG characteristics (location and lateralization of discharges, synchronicity of bilateral discharges, period of discharges, spike wave frequency and special waveforms) of the patients between the 2 groups were compared to analyze the risk factors for comorbid ADHD. Results:(1) In 122 SeLECTS children, 70 (57.38%) were males and 52 (42.62%) were females; onset age was (7.50±1.98) years (3-12 years); 72.95% (89/122) patients had seizures only within 1 h after falling asleep, 9.84% (12/122) had seizures only 1-2 h before awakening in the morning, 9.84% (12/122) had seizures both after falling asleep and before awakening in the morning; duration of a single episode was (116.60±89.68) seconds (10-600 seconds). (2) Background activity in EEG showed no obvious abnormalities; the discharges were located in the central temporal region in 93.20% (96/103) patients and in the central temporal region and other brain regions (including frontal region, anterior head, bilateral occipital midline and bilateral cerebral hemispheres) in 6.80% (7/103) patients; among 69 patients whose overnight EEG recording was obtained, the spike frequency was 35.00 (20.67, 55.00) times/min (0.33-86.33 times/min). (3) Among 120 patients who accepted drug treatment, 87 (72.50%) received monotherapy, including valproic acid ( n=30, 34.48%), oxcarbazepine ( n=21, 24.14%), lacosamide ( n=17, 19.54%), levetiracetam ( n=17, 19.54%), perampanel ( n=1, 1.15%), and lamotrigine ( n=1, 1.15%); 33 (27.50%) received combination therapy with two or more drugs. (4) The comorbid ADHD group had statistically younger age of onset, longer duration of a single episode, higher proportion of seizures both after falling asleep and before awakening, and higher spike wave frequency in EEG than the non-ADHD group ( P<0.05). Conclusions:SeLECTS patients generally have onset age of 3-12 years, seizures within 1 h after falling asleep or 1-2 h before awakening, normal EEG background activity, and epileptiform discharges mostly located in the centrotemporal area, which are different from other types of epilepsy. SeLECTS patients with young age of onset, long duration of a single episode, seizures both after falling asleep and before awakening and high spike wave frequency in EEG trend to develop ADHD comorbidity.

Objective:To develop a novel, flexible, dual-arm, master-slave digestive endoscopic minimally invasive surgical robot system named dual-arm robotic endoscopic assistant for minimally invasive surgery (DREAMS) and to evaluate its feasibility for endoscopic submucosal dissection (ESD) by using ex vivo porcine stomachs.Methods:A novel endoscopic robot (DREAMS) system was developed which was composed of a flexible two-channel endoscope, two flexible robotic manipulators, a master controller, a robotic arm, and a control system. A total of 10 artificial round-like lesions with diameters ranging from 15 to 25 mm were created (5 in gastric antrum and 5 in gastric body) by using fresh peeled stomach of healthy pigs as the model. Submucosal dissection was performed with the assistance of the DREAMS system by two operators. The main outcome was submucosal dissection speed, and the secondary outcomes included muscular injury rate, perforation rate, and grasping efficiency of the robot.Results:All 10 lesions were successfully dissected en bloc by using the DREAMS system. The diameter of the artificial lesions was 22.34±2.39 mm, dissection time was 15.00±8.90 min, submucosal dissection speed was 141.79±79.12 mm 2/min, and the number of tractions required by each ESD was 4.2 times. Muscular injury occurred in 4/10 cases of ESD. No perforation occurred. Conclusion:The initial animal experiment shows the DREAMS system is safe and effective.

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type Ⅰ interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.
Animals ; Swine ; African Swine Fever Virus/metabolism* ; Membrane Proteins/metabolism* ; Immunity, Innate ; Nucleotidyltransferases/metabolism* ; Signal Transduction/genetics*

In order to understand the prevalence and evolution of porcine reproductive and respiratory syndrome virus (PRRSV) in China and to develop subunit vaccine against the epidemic lineage, the genetic evolution analysis of PRRSV strains isolated in China from 2001 to 2021 was performed. The representative strains of the dominant epidemic lineage were selected to optimize the membrane protein GP5 and M nucleotide sequences, which were used, with the interferon and the Fc region of immunoglobulin, to construct the eukaryotic expression plasmids pCDNA3.4-IFNα-GP5-Fc and pCDNA3.4-IFNα-M-Fc. Subsequently, the recombinant proteins IFNα-GP5-Fc and IFNα-M-Fc were expressed by HEK293T eukaryotic expression system. The two recombinant proteins were mixed with ISA206VG adjuvant to immunize weaned piglets. The humoral immunity level was evaluated by ELISA and neutralization test, and the cellular immunity level was detected by ELISPOT test. The results showed that the NADC30-like lineage was the main epidemic lineage in China in recent years, and the combination of IFNα-GP5-Fc and IFNα-M-Fc could induce high levels of antibody and cellular immunity in piglets. This study may facilitate the preparation of a safer and more effective new PRRSV subunit vaccine.
Humans ; Animals ; Swine ; Porcine respiratory and reproductive syndrome virus/genetics* ; Porcine Reproductive and Respiratory Syndrome/prevention & control* ; HEK293 Cells ; Viral Envelope Proteins/genetics* ; Antibodies, Viral ; Viral Vaccines/genetics* ; Recombinant Proteins ; Vaccines, Subunit

Objective To investigate the effect of IFN-γ on the proliferation and migration of esophageal squamous cell carcinoma cell line Eca9706 and related mechanism. Methods Cells were cultured in vitro and treated with interferon-γ. Cell morphology changes were observed under microscope, cell proliferation ability was detected by CCK-8 experiment, and cell migration ability was detected by cell scratch experiment and Transwell experiment. Real-time PCR method was used to detect the expression efficiency of chemokine CXCL8 (interleukin 8), and the ELISA experiment was used to detect the change of CXCL8 secretion. Results Compared with the blank control group, Eca9706 cells treated with different concentrations of interferon-γ did not change significantly in cell morphology. CCK8 experiment confirmed that the proliferation ability of Eca9706 cells after IFN-γ treatment was significantly reduced (P < 0.01). Cell scratch experiment found that IFN-γ significantly decreased the migration ability of Eca9706 cells (P < 0.01). Transwell experiment showed that after IFN-γ treatment, the migration ability of Eca9706 cells was significantly inhibited (P < 0.01). CXCL8 gene expression level in Eca9706 cells treated with interferon-γ was significantly down-regulated (P < 0.01), and the amount of CXCL8 secretion significantly reduced (P < 0.05). Conclusion Interferon-γ can inhibit the proliferation and migration of esophageal cancer cell line Eca9706, which may be related to its inhibition of the expression and secretion of CXCL8.

Objective:To investigate the effectiveness and advantage of visual laryngoscope in the treatment of patients with sudden cardiac arrest who need spontaneous respiration tracheal intubation.Methods:Totally 60 patients who suffered from cardiac arrest and needed spontaneous respiration tracheal intubation were enrolled from June 2020 to February 2021 in the Affilicated Hospital of Chifeng University. Theywere randomlydivided into two groups-traditional laryngoscope (TL) group and visual laryngoscope (VL) group, with30 patients in each group. Then the success rate of glottis exposure, the operative time, success rate and complication rate of tracheal intubation were compared between the two groups. Subgroup assessment between the junior emergency resident doctor (A group) and the senior emergency resident doctor (B group) was conducted.Results:According to Cormack Lehan grades, the success rate of glottis exposure in VL group was higher than that in TL group ( P>0.05), and the success rate of Grade I in VL group was significant higer than that in TL group: 56.70%(17/30) vs. 30.00%(9/30), P<0.05. The trial times of successful intubation cases and the operative time of successful intubation cases were significantly less than those in TL group (1.30 vs 1.67, P = 0.049) and (56.37 s vs 67.12 s, P<0.05). In the subgroup, the one-time success rate of tracheal intubation in A-TL group was significantly lower than that in B-TL group (4/15 vs. 11/15, P<0.05), while the one-time success rate of tracheal intubation in A-VL group was 60.00%, which is lower than that in B-VL group ( P>0.05). The operative time consumed for successful intubation in A-TL group was significantly longer than that in B-TL group: 78.00 s vs. 55.57 s, P<0.05, while the operative time in A-VL group was a little longer than that in B-VL group ( P>0.05). Conclusions:Visual laryngoscope used in spontaneous respiration tracheal intubation can not only increase the success rate of glottis exposure, decrease trial times and shorten operative time of intubation, but also improve the success rate and decrease the complication rate of emergency tracheal intubation.

Objective:To investigate the functional imaging parameters that effectively distinguish isocitrate dehydrogenase (IDH) gene mutation status in clinical practice with long echo time (TE) point-resolved spectroscopy (PRESS) MRS.Methods:Totally 25 patients with suspected diagnosis of low grade gliomas(LGGs; Grade II) were recruited prospectively and divided into IDH mutation group and IDH wild group according to pathological results in the study. All patients were scanned with long TE PRESS MRS. In addition, IDH mutational status was determined by post-operation Sanger sequencing. The t test or Mann-Whitney U test was used to analyze the differences of 2-hydroxyglutarate (2HG), Glutamate (Glu), Glutamine (Gln) and 2HG/Glu+Gln between the IDH mutation group and the IDH wild group, then ROC curve was plotted with statistically significant indexes to obtain the efficacy of predicting IDH mutation status. Results:Of the 25 patients, 19 had IDH mutant gliomas and 6 had IDH wild-type gliomas. 2HG, Glu, Gln and 2HG/Glu+Gln in IDH mutated group were 1.42 (1.09, 1.93)mmol/L, (1.74±1.31)mmol/L, (1.68±0.66)mmol/L, 0.55 (0.28, 0.77), respectively; while the corresponding values were 0.00 (0.00, 1.30)mmol/L, (3.28±1.02)mmol/L, (2.55±1.47)mmol/L, 0.00 (0.00, 0.26) in IDH gene wild type group, respectively. The differences of 2HG, Glu, and 2HG/Glu+Gln between the two groups were statistically significant ( P values were 0.030, 0.016, 0.004, respectively). The area under the ROC curve of 2HG/Glu+Gln was the largest (0.877), and the sensitivity was the highest (84.2%). Conclusion:The integration of 2HG with Glu and Gln can effectively realize the noninvasive assessment of IDH mutation status.

Objective:To explore the application of psychological resilience intervention combined with prospective nursing in patients with free skin flap transplantation to repair skin and soft tissue defects of extremities.Methods:Using the convenient sampling method, a total of 65 patients with soft tissue injury in the skin of extremities after undergoing free skin flap transplantation who were admitted to Henan Provincial People's Hospital from October 2019 to October 2020 were selected. According to the admission time, they were divided into the observation group (34 cases) and the control group (31 cases) . Patients in the observation group received psychological resilience intervention combined with prospective nursing, while patients in the control group only received prospective nursing. The surgical success rate, flap necrosis rate, incidence of vascular crisis and complications were compared between the two groups. Symptom Checklist-90 (SCL-90) was used to evaluate treatment effects of patients in two groups before and after the intervention.Results:There was no statistically significant difference in the surgical success rate, flap necrosis rate and incidence of vascular crisis between the observation group (100.00%, 2.94%, 2.94%) and the control group (96.77%, 12.90%, 16.13%) ( P>0.05) . The observation group had 1 case of deep venous thrombosis (DVT) and 2 cases of other complications, and the control group had 3 cases of pressure injury, 1 case of infection, 2 cases of DVT and 3 cases of other complications. The complication rate in the observation group was 8.82%, which was lower than 29.03% in the control group, and the difference was statistically significant ( P<0.05) . After intervention, the scores of anxiety and paranoia in the observation group were lower than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Psychological resilience intervention combined with prospective nursing has a good application effect on patients with free skin flap transplantation to repair skin and soft tissue defects of extremities. The complication rate is reduced, and mental health of patients is good.

Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The and investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and nonspecific biodistribution.